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diff --git a/old/62429-0.txt b/old/62429-0.txt deleted file mode 100644 index 0db37b0..0000000 --- a/old/62429-0.txt +++ /dev/null @@ -1,18059 +0,0 @@ -The Project Gutenberg EBook of Epidemic Respiratory Disease, by -Eugene Lindsay Opie and Francis G. Blake and James C. Small and Thomas M. Rivers - -This eBook is for the use of anyone anywhere in the United States and most -other parts of the world at no cost and with almost no restrictions -whatsoever. You may copy it, give it away or re-use it under the terms of -the Project Gutenberg License included with this eBook or online at -www.gutenberg.org. If you are not located in the United States, you'll have -to check the laws of the country where you are located before using this ebook. - -Title: Epidemic Respiratory Disease - The pneumonias and other infections of the repiratory tract - accompanying influenza and measles - -Author: Eugene Lindsay Opie - Francis G. Blake - James C. Small - Thomas M. Rivers - -Release Date: June 19, 2020 [EBook #62429] - -Language: English - -Character set encoding: UTF-8 - -*** START OF THIS PROJECT GUTENBERG EBOOK EPIDEMIC RESPIRATORY DISEASE *** - - - - -Produced by Richard Tonsing and the Online Distributed -Proofreading Team at https://www.pgdp.net (This file was -produced from images generously made available by The -Internet Archive) - - - - - - - - - - EPIDEMIC RESPIRATORY DISEASE - The Pneumonias and Other Infections of the Respiratory Tract - Accompanying Influenza and Measles - - - BY - - EUGENE L. OPIE, M.D. - - COLONEL, M. R. C., U. S. ARMY; PROFESSOR OF PATHOLOGY, WASHINGTON - UNIVERSITY SCHOOL OF MEDICINE - - FRANCIS G. BLAKE, M.D. - - MAJOR, M. R. C., U. S. ARMY; ASSOCIATE MEMBER OF THE ROCKEFELLER - INSTITUTE FOR MEDICAL RESEARCH - - JAMES C. SMALL, M.D. - - FORMERLY FIRST LIEUTENANT, M. C., U. S. ARMY; BACTERIOLOGIST, - PHILADELPHIA GENERAL HOSPITAL - - THOMAS M. RIVERS, M.D. - - FORMERLY FIRST LIEUTENANT, M. C., U. S. ARMY; ASSOCIATE IN BACTERIOLOGY, - JOHNS HOPKINS UNIVERSITY - - - _ILLUSTRATED_ - - - ST. LOUIS - C. V. MOSBY COMPANY - 1921 - - - - - COPYRIGHT, 1921, BY C. V. MOSBY COMPANY - - _Press of - C. V. Mosby Company - St. Louis, U. S. A._ - - - - - INTRODUCTION - - -Death from lobar pneumonia, bronchopneumonia and measles, fatal with few -exceptions in consequence of complicating pneumonia, constituted in 1916 -approximately one-sixth (16.8 per cent) of the mortality in the army,[1] -whereas in 1917 the same diseases were responsible for nearly two-thirds -(61.7 per cent) of all deaths. During the first half of 1918 the -incidence of pneumonia steadily increased and in some army camps there -were extensive outbreaks of unusually severe pneumonia. - -In July, 1918, the Surgeon General assigned a group of medical officers -to the study of the pneumonias prevalent in the army and stationed them -at Camp Funston, Kansas. At the base hospital of this camp all cases of -pneumonia occurring among troops assembled in the camp were studied, but -during the month of August there were few cases of pneumonia and these -were of mild type. - -Pneumonia which occurred at Camp Funston during August was almost wholly -limited to recently recruited colored troops from southern states -(Louisiana, Mississippi). There was a low rate of mortality, and few -complications. This pneumonia exhibited a noteworthy difference in -etiology from that usually seen in civil life, for it was associated -with a high incidence of those types of pneumococci which occur in the -mouths of healthy men, namely, Pneumococcus atypical II,[2] Type III, -and the group of microorganisms represented by Type IV. Pneumococcus -Type I was encountered in only a few instances and Type II was not -found, although these two microorganisms are responsible for two-thirds -of the lobar pneumonia which occurs in civil life. - -During the investigation at Camp Funston the Commission had the -courteous cooperation of Major Willard Stone, Director of Medical -Service, and received much valuable assistance from Lieutenant A. -McGlory, Registrar of the Base Hospital. - -A review of the accurately compiled records of the base hospital was -made in order to obtain a history of the pneumonias and other -respiratory diseases which had occurred throughout the existence of the -camp, established in September, 1917. It soon became evident that a -disease recognized as influenza had been prevalent throughout this -period and its incidence had shown a close parallel with that of acute -bronchitis. At the same time there had been much pneumonia and a high -death rate from this disease. The chart[3] which was constructed showed -that the disease which had been designated influenza assumed epidemic -proportions in March, 1918. Any doubt that may have been entertained -concerning the nature of the disease is dispelled by the characters of -this epidemic which, beginning at the end of February, reached its -height on March 12 and rapidly subsided; 1,127 men with influenza -entered the base hospital between March 4 and March 29 and many more -were treated in the infirmaries of the camp. In April there was a second -wave of influenza and in May a third, each in large part limited to -newly drafted men brought into the camp shortly before these outbreaks. -Corresponding to the epidemic of influenza there was a great increase of -pneumonia, reaching a maximum about one week after the height of the -incidence of influenza; subsequently the incidence of pneumonia -increased after each one of the secondary waves of influenza. Pneumonia -following measles occurred throughout the history of the camp; in -November and December, 1917, there was a severe outbreak of pneumonia -following measles and the mortality was high. Our conclusions in regard -to the pneumonias which occurred during the history of Camp Funston were -as follows: - -1. Pneumonia of a relatively stationary camp population, such as that -which occurred among white troops during the period of our -investigation, was in considerable part caused by Pneumococcus Types I -and II and resembled the pneumonia of civil life. - -2. Pneumonia of newly drafted colored troops from southern states during -the period of our investigation was caused in great part by pneumococci -of those types which occur in the mouths of healthy men, namely, Types -IV, III and atypical II. - -3. Pneumonia caused by influenza occurred after the epidemic of -influenza which we have described. The report states: “With the -information available it is not possible to draw a sharp line between -(1) the pneumonia of the stable camp population, (2) the pneumonia of -the newly drafted southern troops, and (3) the pneumonia following -influenza. It is possible that influenza, in greater or less degree, -also acts as a predisposing factor in the production of the first and -second varieties.” - -4. Pneumonia with measles was a frequent and unusually fatal type of the -disease. The most important causes of pneumonia during the history of -the camp were influenza and measles. - -Evidence is not lacking that influenza occurred in epidemic form in -other widely separated camps in the United States during the spring of -1918. Vaughan and Palmer[4] state that a disease strongly resembling -influenza became prevalent in the Oglethorpe camps about March 18, 1918, -and continued three weeks; during this time the number sent to hospital -or to quarters with this disease was 1,468 in a total strength of -28,586. Pneumonia does not appear to have followed this epidemic. - -Miller and Lusk[5] found the ordinary type of pneumonia prevalent at -Camp Dodge, Iowa, until March 18 to 20, 1918, when abruptly the -streptococcus type predominated and there was a great increase in the -rate of mortality. A mild tracheitis, they state, was widespread in the -camp during March. - -In March, 1918, one member of our commission saw an outbreak of -influenza at Fort Sam Houston which was identical in its clinical -characters with the disease which appeared as a pandemic in the fall of -1918. - -The report of the Surgeon General[6] for 1919 shows that there was a -sharp increase of the incidence of influenza in the army during March, -reaching a maximum in April. The rate of influenza for 1,000 troops fell -to its original level through May and June and finally rose to a great -height in September and October. - -Influenza in epidemic form made its appearance in the army camps of the -United States during March, 1918. The symptomatology of the disease -associated with its peculiar epidemiology as seen at Camp Funston make -its recognition unquestionable. The disease had doubtless been present -in this camp since its establishment in September, 1917, but did not -assume epidemic proportions until the spring of 1919. - -Pneumonia followed the epidemics of influenza which occurred in the -spring of 1918 and exhibited characters similar to those of the -pneumonias which followed the pandemic of September and October, 1918. -In both instances the height of the outbreak of pneumonia has been one -week after the maximum incidence of influenza. - -Influenza became epidemic in Spain about the middle of May and in other -countries received the name “Spanish influenza” which is not more -applicable than the designation “Russian influenza” often applied to the -disease during the pandemic of 1889–90. - -The studies of MacNeal[7] have shown that the first epidemic of -influenza in the American Expeditionary Force in France occurred about -April 15, 1918, at a rest camp near Bordeaux, reached its height on -April 22 and ceased May 5. The disease was of a mild character with few -complications. Localized epidemics were reported from various camps and -hospitals during May and June, when the disease, MacNeal states, had -become widespread in all sections of the American Expeditionary Force in -France and in the French and British armies as well. Influenza had -become epidemic in the Italian navy in the first two weeks of May. The -belief that the disease was introduced from America, the author thinks, -is “probably completely disproved by the fact that the epidemic was -subsequently introduced into America in August and September and found -there a most fertile soil for its spread.” This view is disproved by the -demonstration that influenza had appeared as scattered epidemics in the -army camps in March, 1918. There is little reason to doubt that -influenza in the American Expeditionary Force was brought from America. - -At the end of August our commission was transferred from Camp Funston to -Camp Pike, where throughout the history of the encampment pneumonia had -been so prevalent that it had given the camp the rank of third in death -rate from lobar pneumonia and fourth in death rate from bronchopneumonia -among 32 camps established in this country. We arrived at Camp Pike -September 5 and were stationed at the base hospital. Our work was -facilitated by the hearty cooperation of the commanding officer, Major -Morton R. Gibbons, who neglected no opportunity to promote the -investigation. Our work was cordially aided by Major Carl R. Comstock, -Director of the Medical Service, and by Major Henry H. Lissner, who -later occupied this position. Work in the laboratory of the hospital -received the valuable cooperation of Major Allen J. Smith, Director of -the Laboratory, who placed at our disposal every facility available. -Lieutenant James R. Davis, who was for a time in charge of the -laboratory, effectively assisted the work. - -The commission consisted of the following officers: E. L. Opie, Colonel, -M. R. C.; Allen W. Freeman, Major, M. C.; Francis G. Blake, Major, M. R. -C., James C. Small, Lieutenant, M. C. and Thomas M. Rivers, Lieutenant, -M. C. Major Freeman acted as epidemiologist and will publish a report -upon the epidemiology of influenza and pneumonia at Camp Pike. On -October 11 the laboratory car “Lister” in charge of Lieutenant Warren H. -Butz was assigned to the commission. Lieutenant Harry D. Bailey was -attached to the commission on October 14 and later assisted in its work. -Valuable technical assistance was given by Sergeant Charles Behre, by -Wm. E. Hoy, detailed from the Army Medical Museum, and by Thomas Payne. - -Study of the pathology of the lesions concerned was completed in the -Pathological Laboratory of Washington University School of Medicine. - -The existence of an epidemic of influenza at Camp Pike was recognized on -September 23, when 214 cases of influenza were admitted to the base -hospital. Preceding this date and beginning September 1 there had been a -gradual increase of the number of patients admitted with the diagnosis -of acute bronchitis. It is noteworthy that the demonstration of B. -influenzæ had been regarded as essential for a diagnosis of influenza -and since this microorganism had not been found, instances of acute -inflammation of the respiratory passages with the symptoms of influenza -were classified under a variety of names. - -After September 23 influenza was recognized by its symptoms. The number -of cases increased with great rapidity and on September 27 reached over -1,000 per day; this number was approximately maintained during one week -and after October 3 the epidemic gradually subsided. Among 52,551 men in -the camp, including those who arrived during October, 12,393 were -attacked by influenza; of these 1,499 suffered with pneumonia and 466 -died. The height of the outbreak of pneumonia followed approximately one -week after that of influenza. The statistics from September 20 to -October 14 collected by Major Freeman show that pneumonia following -influenza, like the pneumonia at Camp Funston during the interepidemic -period, has a conspicuous tendency to select men who have been in the -camp less than one month, designated in Table I as new recruits: - - TABLE I - - ════════════════════════════════╤══════════╤═════════════╤═════════════ - │POPULATION│ INFLUENZA │ PNEUMONIA - ────────────────────────────────┼──────────┼──────┬──────┼──────┬────── - „ │ „ │ No. │ Per │ No. │ Per - │ │ │cent. │ │cent. - ────────────────────────────────┼──────────┼──────┼──────┼──────┼────── - Men in camp more than one month │ 27,782│ 4,462│ 15.6│ 493│ 1.7 - New recruits │ 23,769│ 7,263│ 30.6│ 1006│ 4.2 - ────────────────────────────────┼──────────┼──────┼──────┼──────┼────── - Total │ 51,551│11,725│ 22.7│ 1499│ 2.9 - ────────────────────────────────┴──────────┴──────┴──────┴──────┴────── - -New recruits were nearly two and a half times as susceptible to -pneumonia as men who had been in camp more than one month. This -statement does not take into consideration differences in the -environment and mode of living of the new men. - -In view of the existing uncertainty concerning the bacteriology of -influenza and its associated pneumonias, the commission has availed -itself of the opportunity afforded by the epidemic of influenza to -determine what bacteria were present in the nasopharynx and sputum in -these diseases. The examinations have been necessarily limited to a -small proportion of the immense number of patients admitted to the -hospital with influenza and pneumonia. Autopsies on those who have died -with pneumonia have offered a more direct means of determining the -relation of bacteria to inflammation of the bronchi and lungs. An -attempt has been made to classify the pneumonias following influenza and -to determine their relation to the complex bacterial flora of the -injured respiratory passages. These studies have shown very early the -threatening prevalence of streptococcus pneumonia, and appropriate -measures have been taken to combat the spread of this infection. No -better illustration could be furnished to demonstrate the value of -routine performance of autopsies as a means for the recognition of -obscure epidemic disease. - -In view of the wide difference of opinion concerning the pathology of -influenzal pneumonia special study has been given to the lesions of the -disease, because the epidemic has furnished the unique opportunity of -examining all instances of pneumonia accurately referable to an epidemic -of influenza attacking a large but definitely defined group of -individuals (50,000 troops). In a civil hospital there is often great -difficulty in deciding, even in the presence of an epidemic, if death -from pneumonia is the result of influenza, but at Camp Pike the relation -of the heightened death rate to the epidemic has excluded all save a -trivial error in determining the relation of fatal pneumonia to -influenza. - -At the direction of Col. F. F. Russell, who has promoted the work of the -commission by unfailing aid, a special study has been made of the -relation of hemolytic streptococcus to the complications of measles. - -During the later period of the investigation at Camp Pike experiments -were performed on monkeys to determine the pathogenicity of B. influenzæ -and of microorganism isolated from the pneumonias following influenza. -Typical lobar pneumonia was produced in monkeys by intratracheal -injection of pneumococci. These experiments are described in an -appendix. - -The Surgeon General has approved the publication of this report but the -authors alone are responsible for the views expressed. - - EUGENE L. OPIE. - - Washington University - School of Medicine - - - - - CONTENTS - - - CHAPTER I - PAGE - THE ETIOLOGY OF INFLUENZA. (BY FRANCIS G. BLAKE, M.D.; THOMAS M. - RIVERS, M.D.; JAMES C. SMALL, M.D.) 25 - - Discussion, 43; Conclusions, 49. - - - CHAPTER II - - CLINICAL FEATURES AND BACTERIOLOGY OF INFLUENZA AND ITS ASSOCIATED - PURULENT BRONCHITIS AND PNEUMONIA. (BY FRANCIS G. BLAKE, M.D., - AND THOMAS M. RIVERS, M.D.) 51 - - Influenza, 52; Purulent Bronchitis, 56; Pneumonia, 59; - Hemolytic Streptococcus Pneumonia Following Influenza, 70; - Bacillus Influenzæ Pneumonia Following Influenza, 72; Summary, - 73; Discussion, 76. - - - CHAPTER III - - SECONDARY INFECTION IN THE WARD TREATMENT OF INFLUENZA AND - PNEUMONIA. (BY EUGENE L. OPIE, M.D.; FRANCIS G. BLAKE, M.D.; - JAMES C. SMALL, M.D.; AND THOMAS M. RIVERS, M.D.) 83 - - Secondary Infection with S. Hemolyticus in Pneumonia, 84; - Secondary Infection with Pneumococcus in Pneumonia, 91; - Secondary Contact Infection in Influenza, 95; Methods for the - Prevention of Secondary Contact Infection in Influenza and - Pneumonia, 98; Summary, 106. - - - CHAPTER IV - - THE PATHOLOGY AND BACTERIOLOGY OF PNEUMONIA FOLLOWING INFLUENZA. - (BY E. L. OPIE, M.D.; F. G. BLAKE, M.D.; AND T. M. RIVERS, M.D.) 107 - - Bronchitis, 142; Lobar Pneumonia, 154; Bronchopneumonia, 162; - Peribronchial Hemorrhage and Pneumonia, 189; Suppurative - Pneumonia with Necrosis and Abscess Formation, 199; - Interstitial Suppurative Pneumonia, 209; Suppurative Pneumonia - with Multiple Clustered Abscesses Caused by Staphylococci, - 225; Empyema, Pericarditis and Peritonitis, 232; - Bronchiectasis, 239; Unresolved Bronchopneumonia, 261. - - - CHAPTER V - - SECONDARY INFECTION IN THE WARD TREATMENT OF MEASLES. (BY JAMES C. - SMALL, M.D.) 282 - - Hemolytic Streptococci with Measles at Camp Pike, 297; - Complications of Measles, 303; The Dissemination of Hemolytic - Streptococci in Wards, 315; Carriers of Hemolytic - Streptococci, 321. - - - CHAPTER VI - - THE PATHOLOGY AND BACTERIOLOGY OF PNEUMONIA FOLLOWING MEASLES. (BY - EUGENE L. OPIE, M.D.; FRANCIS G. BLAKE, M.D.; JAMES C. SMALL, - M.D.; AND THOMAS M. RIVERS, M.D.) 334 - - Changes in Bronchi, 336; Lobar Pneumonia, 337; - Bronchopneumonia, 340; Suppurative Pneumonia, 347; Pneumonia - Associated with Acute Infectious Diseases other than Influenza - and Measles, 353. - - - CHAPTER VII - - SUMMARY OF THE INVESTIGATION AND CONCLUSIONS REACHED. (BY EUGENE - L. OPIE, M.D.) 359 - - Lobar Pneumonia, 362; Bronchopneumonia, 363; Streptococcus - Pneumonia, 365; Staphylococcus Pneumonia, 366; Empyema, 366; - Bronchiectasis, 367; Unresolved Bronchopneumonia, 368; B. - Influenzæ, 369; Pneumococcus, 372; S. Hemolyticus, 374; - Nonhemolytic Streptococci, 376; Staphylococci, 377; Pneumonia - of Measles, 378; The Transmission of Streptococcus Pneumonia, - 381; Transmission of Pneumococcus Pneumonia, 383; Prevention - of the Transmission of Pneumonia, 383. - - - APPENDIX - - EXPERIMENTAL INOCULATION OF MONKEYS WITH BACILLUS INFLUENZÆ AND - MICROORGANISMS ISOLATED FROM THE PNEUMONIAS OF INFLUENZA. (BY - EUGENE L. OPIE, M.D.; ALLEN W. FREEMAN, M.D.; FRANCIS G. BLAKE, - M.D.; JAMES C. SMALL, M.D.; AND THOMAS M. RIVERS, M.D.) 387 - - Inoculation of the Nose and Pharynx with B. Influenzæ, 389; - Introduction of Bacillus Influenzæ into the Trachea, 391; - Introduction of B. Influenzæ and S. Hemolyticus into the - Trachea, 392; Introduction of B. Influenzæ and of Pneumococcus - or of Pneumococcus Alone into the Trachea, 393. - - - - - ILLUSTRATIONS - - - CHARTS PAGE - 1. The onset of cases of pneumonia shown by autopsy to be - uncomplicated by secondary infection with hemolytic - streptococcus and of cases of streptococcus pneumonia 141 - - 2. The date of onset of cases in which autopsy demonstrated - lobar pneumonia 161 - - 3. Shows the relation of the epidemic of measles to that of - influenza at Camp Pike, and the relations of the - pneumonia following measles to both measles and influenza 293 - - 4. Shows the time interval between the onset of measles and - the onset of the subsequent pneumonia in the 56 cases of - pneumonia following measles at Camp Pike 306 - - 5. Shows the time relation between the identification of - hemolytic streptococci in the throats and the development - of otitis media in 27 cases shown to be due to hemolytic - streptococci 314 - - - FIG. - 1. Acute bronchitis showing engorgement of blood vessels of - mucosa and elevation of epithelium by serum and blood 146 - - 2. Acute bronchopneumonia with nodules of peribronchiolar - consolidation and purulent bronchitis 167 - - 3. Acute bronchopneumonia with peribronchiolar consolidation 169 - - 4. Acute bronchopneumonia with peribronchiolar consolidation 170 - - 5. Bronchopneumonia with hemorrhagic peribronchiolar - consolidation 174 - - 6. Acute bronchopneumonia with confluent gray lobular - consolidation in lower part of upper lobe and hemorrhagic - peribronchiolar pneumonia in lower lobe; purulent - bronchitis 180 - - 7. Bronchopneumonia with purulent bronchitis and peribronchial - hemorrhage 190 - - 8. Streptococcus pneumonia with massive necrosis 201 - - 9. Abscess below pleura with perforation caused by hemolytic - streptococci 202 - - 10. Interstitial suppurative pneumonia; interstitial septa are - the site of suppuration and lymphatics are distended with - purulent fluid; empyema 211 - - 11. Suppurative interstitial pneumonia 212 - - 12. Suppurative interstitial pneumonia 216 - - 13. Suppurative interstitial pneumonia showing a dilated - lymphatic 217 - - 14. Endophlebitis occurring in association with suppurative - pneumonia 219 - - 15. Abscesses in two clusters caused by S. aureus in upper part - of right upper lobe 227 - - 16. Abscesses in cluster caused by S. aureus at apex of right - lobe 228 - - 17. Acute bronchiectasis showing fissures penetrating into - bronchial wall and at one place entering alveolar tissue 246 - - 18. Acute bronchiectasis showing fissures in the bronchial wall - extending into neighboring alveoli which in zone about - are filled with fibrin 247 - - 19. Acute bronchiectasis; the bronchial wall indicated by - engorged mucosa shows a varying degree of destruction, - fissures extending into and through the bronchial wall 248 - - 20. Acute bronchiectasis with destruction of bronchial wall - exposing alveoli filled with fibrin 249 - - 21. Bronchiectasis with fissures extending through the - bronchial wall into alveolar tissue which is site of - fibrinous pneumonia 251 - - 22. Regeneration of epithelium over fissures which have been - formed in the wall of a bronchus 252 - - 23. Squamous epithelium growing over the defect in the - bronchial wall 253 - - 24. Acute bronchiectasis with fissures extending through - bronchial wall which is marked by great engorgement of - blood vessels 255 - - 25. Advanced bronchiectasis throughout lower left lobe 258 - - 26. Unresolved bronchopneumonia with tubercle-like nodules of - peribronchiolar consolidation best seen in lower lobe; - bronchiectasis 268 - - 27. Unresolved pneumonia with peribronchial formation of - fibrous tissue; bronchiectasis 270 - - 28. Unresolved pneumonia with bronchiectasis showing new - formation of fibrous tissue about a greatly dilated - bronchus of which the epithelial lining has been lost 271 - - 29. Lobar pneumonia following measles 338 - - 30. Unresolved bronchopneumonia with measles showing new - formation of fibrous tissue about a bronchus and in - immediately adjacent alveolar walls 342 - - 31. Unresolved bronchopneumonia with measles showing a nodule - of chronic fibrous pneumonia surrounding a respiratory - bronchiole 343 - - 32. Unresolved bronchopneumonia with measles showing chronic - pneumonia about a respiratory bronchiole and alveolar - duct 344 - - 33. Experimental lobar pneumonia in the stage of gray - hepatization produced by injection of Pneumococcus III - into the trachea of a monkey 395 - - - - - EPIDEMIC RESPIRATORY DISEASE - - THE PNEUMONIAS AND OTHER INFECTIONS OF THE RESPIRATORY TRACT - ACCOMPANYING INFLUENZA AND MEASLES - - - - - CHAPTER I - THE ETIOLOGY OF INFLUENZA - - FRANCIS G. BLAKE, M.D.; THOMAS M. RIVERS, M.D.; JAMES C. SMALL, M.D. - - -The bacteriologic investigation which will be described was made at Camp -Pike, Arkansas, during the period of the influenza epidemic from -September 6 to December 5, 1918. The data presented are limited to -observations made during life in uncomplicated cases of influenza and to -control studies in normal individuals, and in cases of measles. -Bacteriologic studies made at autopsy will be described in a subsequent -part of this report. - -Because of the wide variations in opinion concerning the relationship of -various bacteria to influenza that have arisen during the progress of -the recent pandemic, a brief review of the salient features of the -earlier literature seems advisable. In 1892 Pfeiffer[8] found a small, -Gram-negative, hemophilic bacillus in all cases of influenza, often in -almost pure culture, both during life and at autopsy. He stated that the -organism was found only in cases of influenza or in those convalescent -from the disease. Similar bacilli occasionally found in other conditions -he classified as pseudoinfluenza bacilli. He furthermore showed that -freshly isolated cultures were pathogenic for monkeys, producing a -disease not unlike influenza, though lacking in what he considered the -characteristic lung lesions. He therefore felt justified in claiming -that this bacillus, which he designated B. influenzæ, was the cause of -epidemic influenza. Pfeiffer’s work, though hailed by many as -unassailable, has failed to stand the test of time in two respects. It -has been definitely shown, by Wollstein[9] in particular, that there is -no justification for recognizing a group of pseudoinfluenza bacilli, -organisms so classified by Pfeiffer being indistinguishable from B. -influenzæ. Furthermore, numerous investigations have demonstrated that -B. influenzæ may frequently be found in a variety of diseases affecting -the respiratory tract and in a small proportion of normal individuals. -Kretz[10] found it 47 times in 950 examinations, usually associated with -disease of the respiratory tract. Süsswein,[11] Liebscher,[12] -Jehle,[13] Wollstein,[9] Davis[14] and many others have demonstrated its -presence in cases of measles. Lord[15] isolated B. influenzæ in 30 per -cent of 186 sputums from patients with acute and chronic infection of -the respiratory tract. Boggs[16] found it in frequent association with -chronic bronchiectasis. Wollstein[9][17] showed that it was often -present in the respiratory diseases of infants, and was not an -infrequent cause of meningitis. Rosenthal[18] found that one in six of -normal individuals harbors influenza bacilli and therefore considered it -purely a saprophyte, a position, of course, thoroughly untenable in the -face of indisputable evidence that it may be highly pathogenic. The -widely accepted statement that B. influenzæ is nonpathogenic for animals -has apparently served in considerable degree to shake belief in its -etiologic relationship to epidemic influenza. It would appear, however, -that this opinion is not founded upon fact. Reference is again made to -the work of Wollstein[19], who has shown that virulent strains of B. -influenzæ, when freshly isolated from the human host, are highly -pathogenic for rabbits and monkeys and that nearly all strains are more -or less pathogenic for mice and guinea-pigs. - -None of these modifications of Pfeiffer’s original work, however, would -seem to constitute any valid reason for abandoning the conception of the -etiologic importance of B. influenzæ. On the contrary, they are quite in -harmony with well-established facts concerning other bacteria which -cause infections of the respiratory tract. Such bacteria are frequently -found in normal individuals leading a saprophytic existence, are often -associated with other disease conditions, and tend to show marked -variations in virulence. - -Since the outbreak of scattered epidemics of influenza beginning in -1915–16, which finally culminated in the pandemic of 1918–19, a vast -amount of literature on the subject has appeared. No attempt has been -made thoroughly to analyze this, because much of it is not available, -much of it abounds in contradictions which it is difficult to harmonize -at the present time, and much of it has been written on the basis of -insufficient data gathered under the handicap of war conditions by men -without sufficient time to undertake special investigation, or it is -feared, in many instances, not sufficiently qualified by previous -bacteriologic training. - -The sum and substance of opinion in 1918 would seem to be best -summarized by quoting from the published report compiled by the British -Medical Research Commission:[20] “Although Pfeiffer may yet furnish -reasons why the verdict should not be pronounced, there is already -sufficient material to shake the orthodox conception out of its high -altar. Two facts stand out prominently: the generally acknowledged, or -by some reluctantly admitted, absence of B. influenzæ from organs on -postmortem examinations, and the universally recorded findings of -diplostreptococci, singly or in association with the Pfeiffer bacillus.” -Comment on this opinion will be made in the general discussion at the -end of this paper. - -In undertaking a study of the bacteriology of influenza, it seemed -essential to bear in mind certain clinical features of the disease which -will be discussed in greater detail in a subsequent paper. It suffices -to say for our present purpose that it is felt that influenza in itself -should be regarded as a self-limited disease of short duration (two to -five days in most instances), the most prominent local manifestation of -which is a rapidly progressing attack upon the mucous membranes of the -respiratory tract. Among the cases observed during the epidemic at Camp -Pike uncomplicated influenza never proved fatal and death invariably was -associated with a complicating pneumonia. In a large majority of cases -pneumococci, S. hemolyticus, or less frequently other bacteria in -addition to B. influenzæ were associated with the pneumonia. It is felt, -therefore, that in any attempt to determine the primary cause of -influenza bacteriologic studies made during life in early uncomplicated -cases of the disease are of primary importance and that the bacteriology -of the sputum of patients with complicating pneumonia and the -bacteriology of autopsies can only properly be used as valuable -supplements to data so obtained. - -Since cultures from the respiratory tract must often of necessity -contain many bacteria which play no part in the production of influenza, -it is essential to have a working knowledge of the bacteria that may be -encountered by the methods employed. It is also important that such -knowledge as may have been gained in interepidemic periods be amplified -by study of the bacterial flora present at various periods throughout -the course of an epidemic, both in normal individuals and in other -disease conditions. These points have been borne in mind throughout the -present study and such observations have formed an essential part of the -work. - -=Methods.=—In an investigation of this nature the culture methods -employed should be suitably directed to determine primarily what -bacteria are present and in what relative proportion they exist. The use -of culture or animal inoculation methods that are highly selective in -character, enhancing the growth of certain bacteria and retarding or -inhibiting the growth of others, are of great additional value, but can -only properly be used secondarily in order to augment the results -obtained by nonselective culture methods. As the most suitable medium -for the purpose in hand plain meat infusion agar, titrating 0.1+ to 0.3+ -to phenolphthalein, to which 5 per cent of sterile defibrinated horse -blood was added, was used. Since growth on freshly poured plates is -greatly superior to that on plates that have been stored, the agar was -melted as needed, the blood being added when the medium had cooled to -approximately 45° C. Cultures from the nose and throat were made by -swabbing the mucous membranes with a sterile applicator, touching the -applicator to a small area on the surface of a blood agar plate, and -spreading the inoculum over the surface of the medium with a platinum -needle, insuring as wide a separation as possible. Direct cultures of -selected and washed specimens of sputum were made when possible. In many -instances, of course, it was impossible to get sufficiently satisfactory -specimens to permit of washing, especially when cultures were made very -early in the disease. To supplement direct culture of the sputum the -mouse inoculation method as employed for the determination of -pneumococcus types was used. This is, of course, a highly selective -method, of particular value in the detection of pneumococcus and B. -influenzæ when they are present in relatively small numbers as compared -with other bacteria. Plates were examined after twenty to twenty-four -hours’ incubation and again at the end of thirty-six to forty-eight -hours when necessary. - -In the present study, attention has been centered upon B. influenzæ, S. -hemolyticus, and the various immunologic types of pneumococci, other -organisms encountered having played no significant part in the cases -studied except in rare instances. B. influenzæ was identified by its -morphologic, staining and cultural characteristics and conformed to the -classical description given by Pfeiffer. S. hemolyticus was identified -by its morphologic, staining, and cultural characteristics on blood -agar, supplemented by a confirmatory hemolytic test with washed sheep -corpuscles, and bile solubility test. Pneumococci were identified by -morphologic, staining and cultural characteristics, bile solubility -test, and agglutination with specific antipneumococcus immune sera. Note -was made in most instances of the presence of other organisms, such as -members of the Gram-negative diplococcus, staphylococcus, diphtheroid -and streptococcus viridans groups, but no attempt was made further to -isolate or identify them. - -=Bacillus Influenzæ in Cases of Influenza.=—On October 10, 1918, at the -height of the epidemic at Camp Pike, search for B. influenzæ was made in -a group of 23 consecutive cases of uncomplicated influenza from one to -six days after the onset of the disease. From each individual -simultaneous cultures on blood agar plates were made (a) from the nose, -(b) from the throat, and (c) from the sputum, and the sputum from each -case was injected into the peritoneal cavity of a white mouse. A similar -study of 5 consecutive cases was made on November 19. The results are -presented in Table II. - -By means of multiple cultures taken simultaneously from different -portions of the respiratory tract no difficulty was encountered in -demonstrating B. influenzæ in all these cases of uncomplicated -influenza. Not only was B. influenzæ found in all cases, but often in -very large numbers predominating over all other bacteria on at least one -of the plates from each patient, and in occasional instances occurring -in nearly pure culture. One culture made about two hours after onset of -the initial coryza is of interest. There was at the time a profuse -serous nasal discharge. One drop of this allowed to fall on the surface -of a blood agar plate gave a practically pure culture of B. influenzæ. - - TABLE II - - PRESENCE OF B. INFLUENZÆ IN 28 CASES OF INFLUENZA - - ═══════════╤═══════════╤═══════════╤═══════════╤═══════════╤═══════════ - NO. │ DAY OF │ NOSE │ THROAT │ SPUTUM │ SPUTUM - │ DISEASE │ │ │ CULTURE │ PASSED - │ │ │ │ │ THROUGH - │ │ │ │ │ MOUSE - ───────────┼───────────┼───────────┼───────────┼───────────┼─────────── - 1│ 1 │ + │ + │ + │ + - 2│ 4 │ − │ + │ + │ + - 3│ 5 │ − │ − │ + │ − - 4│ 4 │ − │ − │ + │ + - 5│ 3 │ − │ − │ + │ + - 6│ 4 │ − │ + │ + │ c - 7│ 2 │ − │ + │ − │ c - 8│ 4 │ + │ + │ + │ − - 9│ 5 │ − │ + │ + │ + - 10│ 2 │ + │ − │ − │ − - 11│ 2 │ − │ + │ c │ + - 12│ 3 │ c │ + │ + │ + - 13│ 3 │ − │ − │ − │ + - 14│ 2 │ − │ − │ + │ + - 15│ 3 │ c │ − │ − │ + - 16│ 1 │ − │ + │ + │ + - 17│ 3 │ − │ + │ − │ + - 18│ 4 │ + │ + │ c │ + - 19│ 6 │ − │ − │ + │ + - 20│ 1 │ − │ + │ + │ + - 21│ 2 │ − │ + │ − │ + - 22│ 4 │ + │ − │ + │ + - 23│ 3 │ c │ − │ − │ + - 24│ 2 │ + │ − │ − │ − - 25│ 1 │ − │ − │ + │ + - 26│ 5 │ − │ − │ + │ + - 27│ ? │ − │ + │ − │ + - 28│ 1 │ − │ − │ + │ + - ───────────┼───────────┼───────────┼───────────┼───────────┼─────────── - │ │ 6 │ 14 │ 17 │ 22 - ───────────┴───────────┴───────────┴───────────┴───────────┴─────────── - - c indicates that the plate was contaminated. - -During the latter part of November and in early December a small -secondary wave of influenza occurred at Camp Pike. In a series of 48 -consecutive cases, B. influenzæ was readily found in all by means of -combined throat cultures and mouse inoculation of the sputum, 33 times -(68.7 per cent) in the throat cultures, 39 times (81.3 per cent) in the -sputum. These cases were cultured on admission to the receiving ward of -the hospital within twenty-four to forty-eight hours after onset and -were all early cases of influenza without complications at the time the -cultures were made. In 90 more consecutive cases in this series 62 or -68.9 per cent showed B. influenzæ in a single throat culture taken on -admission. - -A summary of all cultures made in cases of uncomplicated influenza is -presented in Table III. - - TABLE III - - PRESENCE OF B. INFLUENZÆ IN CASES OF INFLUENZA - - ════════════════════════════════════════════╤════════╤═════════════════ - │ NUMBER │ - METHOD │OF CASES│ B. INFLUENZÆ - │CULTURED│ FOUND - ────────────────────────────────────────────┼────────┼────────┬──────── - „ │ „ │ NUMBER │PER CENT - ────────────────────────────────────────────┼────────┼────────┼──────── - Nose culture │ 28│ 6│ 21.4 - Throat culture │ 166│ 109│ 65.7 - Sputum culture │ 28│ 17│ 60.7 - Sputum (mouse passage) │ 76│ 61│ 80.3 - Combined nose, throat and sputum cultures │ │ │ - and sputum inoculation │ 28│ 28│ 100 - Combined throat cultures and sputum │ │ │ - inoculation │ 48│ 48│ 100 - ────────────────────────────────────────────┴────────┴────────┴──────── - -Of any single method used the intraperitoneal inoculation of a white -mouse with a specimen of the patient’s sputum proved the most efficient -in demonstrating the presence of B. influenzæ. No single method served -to demonstrate B. influenzæ in all cases, but by simultaneous cultures -from the nose, throat, and deeper air passages no difficulty was met in -showing that B. influenzæ was invariably present, usually in abundance -somewhere in the respiratory tract during the acute stage of the -disease. This result is not out of harmony with the rapidly progressive -character of the attack upon the mucous membranes of the respiratory -tract in influenza. - -Of interest in this connection are certain observations which suggest -that the presence of B. influenzæ in predominant numbers at least is in -many cases coincident with the acute stage of influenza and that the -organisms show a tendency rapidly to diminish in abundance with the -progress of the disease to recovery. In 82 cases of influenza cultured -on the day of admission to the hospital, B. influenzæ was present in 52 -(63.4 per cent) of the throat cultures. Repeated throat cultures in this -group of cases from the fourth to the eighth day after admission when -the temperature had fallen to normal, showed that B. influenzæ was still -present in demonstrable numbers in the throat of only 25 cases or 30.5 -per cent. Not only was there a material reduction in the number of -patients in whom B. influenzæ could be demonstrated by the throat -culture method, but the contrast in the predominance of B. influenzæ on -the plates made early in the disease with those made during -convalescence was often very striking. It is only fair to say, however, -that some cases continued to carry B. influenzæ in their throats in -large numbers throughout the period of observation. - -=Presence of Pneumococcus in Cases of Influenza.=—It seemed of some -importance to determine the prevalence of pneumococcus in cases of -influenza, not because of any possibility that pneumococci might bear an -etiologic relationship to the disease, but more by way of comparison -with the prevalence of B. influenzæ, since both organisms are found in -the mouths of normal individuals and are also frequently found together -in the pneumonias that complicate influenza. The results obtained in -cases of influenza early in the disease before the development of either -a purulent bronchitis or of pneumonia are presented. The presence of -pneumococcus was determined by the intraperitoneal inoculation of white -mice with the saliva or sputum. - -Twenty-four cases examined on September 27 and 28 gave the results shown -in Table IV. These patients had been in the hospital from two to five -days at the time the determinations were made. - - TABLE IV - - PNEUMOCOCCUS IN CASES OF INFLUENZA - - ═══════════════════════════════════╤═════════════════╤═════════════════ - │ NUMBER │ PER CENT - ───────────────────────────────────┼─────────────────┼───────────────── - Pneumococcus, Type I │ 0│ 0 - Pneumococcus, Type II │ 0│ 0 - Pneumococcus, Atypical II │ 0│ 0 - Pneumococcus, Type III │ 2│ 8.3 - Pneumococcus, Group IV │ 15│ 62.5 - No pneumococci found │ 7│ 29.2 - ───────────────────────────────────┴─────────────────┴───────────────── - -From November 27 to December 1, the pneumococci present in 47 -consecutive cases of influenza were determined. In this group specimens -of sputum were collected shortly after admission of the patients to the -receiving ward of the hospital. The results are shown in Table V. - - TABLE V - - PNEUMOCOCCI IN CASES OF INFLUENZA - - ═══════════════════════════════════╤═════════════════╤═════════════════ - │ NUMBER │ PER CENT - ───────────────────────────────────┼─────────────────┼───────────────── - Pneumococcus, Type I │ 0│ 0 - Pneumococcus, Type II │ 0│ 0 - Pneumococcus, Atypical II │ 2│ 4.3 - Pneumococcus, Type III │ 0│ 0 - Pneumococcus, Group IV │ 25│ 53.2 - No pneumococci found │ 20│ 42.5 - ───────────────────────────────────┴─────────────────┴───────────────── - -The results obtained show that pneumococci found in early uncomplicated -cases of influenza, both early and late in the course of the epidemic, -differ in no respect from those found in the mouths of normal -individuals at any time. - -Similar studies of the prevalence of S. hemolyticus as determined by -throat cultures in early cases of influenza are shown in Table VI. - -The only point of interest in these observations is the increased -prevalence of S. hemolyticus in cases examined late in the epidemic of -influenza as compared with that found early in the epidemic. The -significance of this will be discussed in other parts of this report. - - TABLE VI - - S. HEMOLYTICUS IN CASES OF INFLUENZA - - ══════════════╤══════════════╤═════════════╤═════════════╤═════════════ - │ │ S. │ S. │ PER CENT - DATE │ NUMBER OF │ HEMOLYTICUS │ HEMOLYTICUS │POSITIVE FOR - │CASES CULTURED│ FOUND │ NOT FOUND │ S. - │ │ │ │ HEMOLYTICUS - ──────────────┼──────────────┼─────────────┼─────────────┼───────────── - Sept. 25–26 │ 100│ 6│ 94│ 6 - Nov. 27–Dec. 5│ 138│ 39│ 99│ 28.3 - ──────────────┴──────────────┴─────────────┴─────────────┴───────────── - -=Presence of Bacillus Influenzæ in Normal Men.=—For comparison with the -results obtained in cases of influenza a fairly extensive study of the -prevalence of B. influenzæ in normal individuals has been made at -various times prior to and throughout the course of the epidemic. This -was deemed of special importance, since it was obvious that the results -obtained by previous workers during interepidemic periods would not in -all probability coincide with those obtained in the presence of a -widespread epidemic of influenza where the opportunity for the -dissemination of B. influenzæ was almost unlimited. - -From the results obtained in the multiple cultures in cases of influenza -it is obvious that only like methods can be compared. The results -obtained in normal individuals have, therefore, been tabulated in groups -dependent upon the culture method employed. These groups have been -subdivided according to the time and the place of the study, such -explanatory notes as seem necessary being added. (See Tables VII-IX.) - -The most striking feature of the figures presented in Table VII is the -wide variation in the incidence of B. influenzæ in different groups -varying all the way from 11.1 to 68 per cent. Analysis of these -differences brings out certain points of great interest. It is apparent -that the percentage of cases carrying B. influenzæ depended in large -part upon the prevalence of respiratory diseases in the group from which -the data were obtained. In the studies made at Camp Funston prior to the -fall outbreak of influenza in epidemic proportions, it is noteworthy -that “bronchitis” and pneumonia were prevalent throughout the summer in -those groups showing a relatively high incidence of B. influenzæ. At the -time these studies were made the presence of influenza in these -organizations was not recognized, but in view of knowledge gained -throughout the course of the epidemic at Camp Pike, it seems not -improbable that influenza in mild form was present throughout the summer -in certain organizations at Camp Funston. This would seem more likely in -view of the fact that this commission has clearly demonstrated that a -considerable epidemic of influenza swept through Camp Funston in March, -1918, and was followed by recurring smaller epidemics in April and -May.[21] In contrast with these groups showing a high incidence of B. -influenzæ is that of the 210th Engineers, an organization entirely free -from respiratory diseases during the period of our study. - - TABLE VII - - INCIDENCE OF B. INFLUENZÆ IN NORMAL MEN AS DETERMINED BY - INTRAPERITONEAL INOCULATION OF WHITE MICE WITH SALIVA OR SPUTUM - - ════╤═════════╤═════════════╤════════╤═════════╤═════════╤═════════════ - DATE│ PLACE │ORGANIZATION │ NUMBER │ B. │PER CENT │ REMARKS - │ │ │EXAMINED│INFLUENZÆ│POSITIVE │ - │ │ │ │ PRESENT │ FOR B. │ - │ │ │ │ │INFLUENZÆ│ - ────┼─────────┼─────────────┼────────┼─────────┼─────────┼───────────── - 1918│ │ │ │ │ │ - Aug.│Camp │22 Prov. │ 25│ 6│ 24│Bronchitis - 13│Funston, │Colored Co. │ │ │ │and pneumonia - │Kans. │164th Depot │ │ │ │were - │Detention│Brigade │ │ │ │prevalent in - │Camp, No.│ │ │ │ │this - │2 │ │ │ │ │organization - │ │ │ │ │ │of recently - │ │ │ │ │ │drafted - │ │ │ │ │ │negroes - │ │ │ │ │ │during July - │ │ │ │ │ │and August, - │ │ │ │ │ │1918 - ────┼─────────┼─────────────┼────────┼─────────┼─────────┼───────────── - Aug.│Camp │Co. D. 3rd │ 25│ 11│ 44│Recently - 18│Funston, │Dev. Bn. │ │ │ │drafted - │Kans. │ │ │ │ │southern - │Detention│ │ │ │ │negroes not - │Camp, No.│ │ │ │ │fit for full - │2 │ │ │ │ │military - │ │ │ │ │ │duty. - │ │ │ │ │ │Bronchitis - │ │ │ │ │ │and pneumonia - │ │ │ │ │ │were - │ │ │ │ │ │prevalent in - │ │ │ │ │ │this - │ │ │ │ │ │organization - │ │ │ │ │ │during July - │ │ │ │ │ │and August, - │ │ │ │ │ │1918 - ────┼─────────┼─────────────┼────────┼─────────┼─────────┼───────────── - Aug.│Camp │70th Inf. │ 25│ 11│ 44│25 men - 20│Funston, │ │ │ │ │presenting - │Kan. │ │ │ │ │themselves at - │ │ │ │ │ │sick call for - │ │ │ │ │ │various - │ │ │ │ │ │complaints; - │ │ │ │ │ │not strictly - │ │ │ │ │ │normal; - │ │ │ │ │ │respiratory - │ │ │ │ │ │diseases not - │ │ │ │ │ │prevalent - ────┼─────────┼─────────────┼────────┼─────────┼─────────┼───────────── - Aug.│Ft. │Quarters 4 M │ 32│ 16│ 50│Recently - 22│Riley, │M.O.T.C. │ │ │ │drafted white - │Kan. │ │ │ │ │men of 4 to 8 - │ │ │ │ │ │weeks’ - │ │ │ │ │ │service. - │ │ │ │ │ │Pneumonia - │ │ │ │ │ │fairly - │ │ │ │ │ │prevalent in - │ │ │ │ │ │this - │ │ │ │ │ │organization - ────┼─────────┼─────────────┼────────┼─────────┼─────────┼───────────── - Aug.│Camp │210th Eng. │ 27│ 3│ 11.1│About one - 26│Funston, │ │ │ │ │mile distant - │Kan. │ │ │ │ │from Camp - │ │ │ │ │ │Funston - │ │ │ │ │ │proper. No - │ │ │ │ │ │sickness in - │ │ │ │ │ │this - │ │ │ │ │ │organization - ────┼─────────┼─────────────┼────────┼─────────┼─────────┼───────────── - Nov.│Hot │Drafted men │ 50│ 11│ 22│50 men - 12│Springs, │assembled to │ │ │ │selected from - │Ark. │entrain for │ │ │ │isolated farm - │ │camp │ │ │ │communities; - │ │ │ │ │ │12 gave a - │ │ │ │ │ │history of - │ │ │ │ │ │“influenza” - │ │ │ │ │ │within the - │ │ │ │ │ │preceding 8 - │ │ │ │ │ │weeks - ────┼─────────┼─────────────┼────────┼─────────┼─────────┼───────────── - Nov.│Camp │Miscellaneous│ 26│ 13│ 50│12 of this - 25│Pike, │ │ │ │ │group had - │Ark. │ │ │ │ │influenza - │ │ │ │ │ │during the - │ │ │ │ │ │epidemic - ────┼─────────┼─────────────┼────────┼─────────┼─────────┼───────────── - Dec.│Camp │Miscellaneous│ 25│ 17│ 68│12 of this - 10│Pike, │ │ │ │ │group had - │Ark. │ │ │ │ │influenza - │ │ │ │ │ │during the - │ │ │ │ │ │epidemic - ────┼─────────┼─────────────┼────────┼─────────┼─────────┼───────────── - │Summary: │Normals │ 235│ 88│ 37.4│ - │ │Cases of │ 76│ 61│ 80.3│ - │ │influenza │ │ │ │ - │ │(for │ │ │ │ - │ │comparison) │ │ │ │ - ────┴─────────┴─────────────┴────────┴─────────┴─────────┴───────────── - -On November 12 search was made for B. influenzæ in 50 normal drafted men -who had assembled at Hot Springs, Ark., on that date preparatory to -entraining for Camp Pike. These men were all from isolated farming -communities where influenza was only moderately prevalent and where -there was little opportunity for the wide dissemination of B. influenzæ -such as occurs when large bodies of men are assembled in camps. Twelve -of the 50 gave a history of influenza within the preceding eight weeks. -The cultures were made by the same methods as those used at Camp Pike, -the laboratory car “Lister” being taken to Hot Springs for that purpose. -The incidence of B. influenzæ was only 22 per cent. In striking contrast -with this figure are the figures of 50 and 68 per cent obtained in the -last two groups studied at Camp Pike after the epidemic had swept -through the camp: 24 of the 51 men in these groups had influenza during -the epidemic. - -It is of interest to record that the incidence of pneumococcus in these -cases was approximately the same in all groups and bore no relation to -the prevalence of influenza, bronchitis, or pneumonia. - - TABLE VIII - - INCIDENCE OF B. INFLUENZÆ IN NORMAL MEN AS DETERMINED BY THROAT CULTURES - ON BLOOD AGAR PLATES - - ═══════╤════════╤═════════════╤════════╤═════════╤═════════╤════════════ - DATE │ PLACE │ORGANIZATION │ NUMBER │ B. │PER CENT │ REMARKS - │ │ │EXAMINED│INFLUENZÆ│POSITIVE │ - │ │ │ │ PRESENT │ FOR B. │ - │ │ │ │ │INFLUENZÆ│ - ───────┼────────┼─────────────┼────────┼─────────┼─────────┼──────────── - Sept. │Camp │Med. │ 82│ 14│ 17.1│82 throat - 14–Oct.│Pike, │Detachment, │ │ │ │cultures in - 5 │Ark. │Base Hos.; │ │ │ │42 - │ │personnel on │ │ │ │individuals - │ │measles wards│ │ │ │ - ───────┼────────┼─────────────┼────────┼─────────┼─────────┼──────────── - Nov. │Camp │Miscellaneous│ 296│ 71│ 23.9│Number among - 5–9 │Pike, │ │ │ │ │this group - │Ark. │ │ │ │ │who had had - │ │ │ │ │ │influenza - │ │ │ │ │ │not recorded - ───────┼────────┼─────────────┼────────┼─────────┼─────────┼──────────── - Nov. 12│Hot │Drafted men │ 64│ 0│ 0│Men, in - │Springs,│assembled to │ │ │ │large part - │Ark. │entrain for │ │ │ │from - │ │camp │ │ │ │isolated - │ │ │ │ │ │farm - │ │ │ │ │ │communities; - │ │ │ │ │ │13 gave a - │ │ │ │ │ │history of - │ │ │ │ │ │“influenza” - │ │ │ │ │ │within the - │ │ │ │ │ │preceding 8 - │ │ │ │ │ │weeks - ───────┼────────┼─────────────┼────────┼─────────┼─────────┼──────────── - Nov. 25│Camp │Miscellaneous│ 26│ 13│ 50│12 of this - │Pike │ │ │ │ │group had - │ │ │ │ │ │influenza - │ │ │ │ │ │during the - │ │ │ │ │ │epidemic - ───────┼────────┼─────────────┼────────┼─────────┼─────────┼──────────── - Dec. 10│Camp │Miscellaneous│ 25│ 13│ 52│12 of this - │Pike │ │ │ │ │group had - │ │ │ │ │ │influenza - │ │ │ │ │ │during the - │ │ │ │ │ │epidemic - ───────┼────────┼─────────────┼────────┼─────────┼─────────┼──────────── - │Summary │Normals │ 493│ 111│ 22.5│ - │ │Cases of │ 166│ 109│ 65.7│ - │ │influenza │ │ │ │ - │ │(for │ │ │ │ - │ │comparison) │ │ │ │ - ───────┴────────┴─────────────┴────────┴─────────┴─────────┴──────────── - -The results obtained by throat culture are quite similar to those -obtained by the mouse inoculation method. The entire absence of B. -influenzæ in the group of 64 throat cultures made in the draft men -assembled at Hot Springs as compared with the relatively high incidence -in the last two groups examined at Camp Pike is very striking. - -In consideration of the figures presented in Table IX it is important to -remember that the group of 50 men from Hot Springs were all from -isolated farm communities, had not previously been assembled and had not -been in continuous contact with a widespread epidemic of influenza. On -the other hand, the two groups of normal men at Camp Pike were studied -immediately after the epidemic had swept through the camp and had been -constantly in contact with epidemic influenza for a period of three -months, 24 of the 51 actually having had the disease during this period. -The fact that in the group of men from Hot Springs, B. influenzæ was -found only by the mouse inoculation method is noteworthy, since it -indicates that the organism was present in relatively small numbers and -could be detected only by a highly selective method. - - TABLE IX - - INCIDENCE OF B. INFLUENZÆ IN NORMAL MEN CONTRASTED WITH THAT IN EARLY CASES OF - INFLUENZA AS DETERMINED BY MULTIPLE CULTURES FROM NOSE, THROAT, AND SPUTUM - - ════╤════════╤═════════╤════════╤══════════════════════════════════════════════ - DATE│ PLACE │ GROUP │ NUMBER │ PER CENT SHOWING B. INFLUENZÆ - │ │ │EXAMINED│ - ────┼────────┼─────────┼────────┼────────┬────────┬───────┬───────────┬──────── - „ │ „ │ „ │ „ │ NOSE │ THROAT │SPUTUM │ SPUTUM │ BY - │ │ │ │ │ │DIRECT │ MOUSE │MULTIPLE - │ │ │ │ │ │CULTURE│INOCULATION│CULTURES - ────┼────────┼─────────┼────────┼────────┼────────┼───────┼───────────┼──────── - Nov.│Hot │Normal │ 50│ 0│ 0│ 0│ 22│ 22 - 12 │Springs,│draft men│ │ │ │ │ │ - │Ark. │assembled│ │ │ │ │ │ - │ │to │ │ │ │ │ │ - │ │entrain │ │ │ │ │ │ - │ │for camp │ │ │ │ │ │ - │ │ │ │ (4 │ (31 │ │ │ - │ │ │ │cultures│cultures│ │ │ - │ │ │ │ only) │ only) │ │ │ - ────┼────────┼─────────┼────────┼────────┼────────┼───────┼───────────┼──────── - Nov.│Camp │Normal │ 26│ 38.6│ 50│ 34.6│ 50│ 80.8 - 25 │Pike │men; 12 │ │ │ │ │ │ - │ │had │ │ │ │ │ │ - │ │influenza│ │ │ │ │ │ - │ │during │ │ │ │ │ │ - │ │the │ │ │ │ │ │ - │ │epidemic │ │ │ │ │ │ - ────┼────────┼─────────┼────────┼────────┼────────┼───────┼───────────┼──────── - Dec.│Camp │Normal │ 25│ 48│ 52│ 24│ 68│ 88 - 10 │Pike │men; 12 │ │ │ │ │ │ - │ │had │ │ │ │ │ │ - │ │influenza│ │ │ │ │ │ - │ │during │ │ │ │ │ │ - │ │the │ │ │ │ │ │ - │ │epidemic │ │ │ │ │ │ - ────┼────────┼─────────┼────────┼────────┼────────┼───────┼───────────┼──────── - Oct.│Camp │Patients │ 28│ 21.4│ 50│ 60.7│ 78.6│ 100 - 10 │Pike │with │ │ │ │ │ │ - and │ │influenza│ │ │ │ │ │ - Nov.│ │in Base │ │ │ │ │ │ - 19 │ │Hos. │ │ │ │ │ │ - ────┴────────┴─────────┴────────┴────────┴────────┴───────┴───────────┴──────── - -Summary of the results obtained in normal men shows that the incidence -of B. influenzæ in normal individuals from isolated communities or in -groups free from respiratory diseases prior to the occurrence of the -fall epidemic was relatively low, namely, 10 to 20 per cent; that in -observations made before the fall epidemic in groups in which -“bronchitis” and pneumonia were fairly prevalent, B. influenzæ was found -much more frequently, namely, in 25 to 50 per cent of the cases; and -that in groups studied at intervals during the epidemic the incidence of -B. influenzæ rapidly rose, reaching 85 per cent at the end of the -epidemic. In contrast with this, B. influenzæ was found in 100 per cent -of cases of influenza without reference to the time at which they -occurred during the epidemic. It is obvious that the high percentage of -normal men carrying B. influenzæ found at the end of the epidemic can -depend only on the wide dissemination of B. influenzæ that must occur -during epidemic times. - -=Bacillus Influenzæ in Measles.=—Since the presence of B. influenzæ in -other diseases than influenza has been advanced as an argument against -its causal relationship to influenza, an extensive study of the -incidence of B. influenzæ in the throats of measles patients was made -during the period of the epidemic of influenza at Camp Pike from -September 10 to October 20. In all a total of 830 throat cultures in 487 -cases of measles were made, many cases being cultured repeatedly at -weekly intervals. The results have been condensed as far as possible and -are presented in Tables X, XI, XII. - - TABLE X - - INCIDENCE OF B. INFLUENZÆ IN 400 CONSECUTIVE CASES OF MEASLES AS - DETERMINED BY THROAT CULTURE AT TIME OF ADMISSION TO THE BASE HOSPITAL - - ═════════════════╤═════════════════╤═══════════════════════════════════ - DATE │ NUMBER OF CASES │ B. INFLUENZA FOUND - ─────────────────┼─────────────────┼─────────────────┬───────────────── - „ │ „ │ NUMBER │ PER CENT - ─────────────────┼─────────────────┼─────────────────┼───────────────── - Sept. 16–Oct. 4 │ 100│ 27│ 27 - Oct. 4–Oct. 10 │ 100│ 32│ 32 - Oct. 10–Oct. 15 │ 100│ 32│ 32 - Oct. 15–Oct. 19 │ 100│ 48│ 48 - ─────────────────┴─────────────────┴─────────────────┴───────────────── - -The prevalence of B. influenzæ in cases of measles during the period of -the influenza epidemic corresponded very closely with that found in -normal individuals under similar circumstances. The increasing -proportion of cases carrying B. influenzæ as the epidemic of influenza -advanced is further evidence of the wide dissemination of the organism -during the epidemic. - - TABLE XI - - INCIDENCE OF B. INFLUENZÆ IN 830 THROAT CULTURES IN 487 CASES OF - MEASLES; CULTURES REPEATED AT WEEKLY INTERVALS - - ═════════════════╤═════════════════╤═══════════════════════════════════ - DATE │ NUMBER OF CASES │ B. INFLUENZA FOUND - ─────────────────┼─────────────────┼─────────────────┬───────────────── - „ │ „ │ NUMBER │ PER CENT - ─────────────────┼─────────────────┼─────────────────┼───────────────── - Sept. 10–15 │ 47│ 15│ 31.9 - Sept. 16–29 │ 106│ 33│ 31.1 - Sept. 30–Oct. 6 │ 122│ 38│ 31.1 - Oct. 7–13 │ 235│ 96│ 40.8 - Oct. 14–20 │ 320│ 157│ 49.1 - ─────────────────┼─────────────────┼─────────────────┼───────────────── - Total │ 830│ 339│ 40.8 - ─────────────────┴─────────────────┴─────────────────┴───────────────── - - TABLE XII - - TOTAL NUMBER OF B. INFLUENZÆ CARRIERS AMONG 223 CASES OF MEASLES AS - DETERMINED BY REPEATED THROAT CULTURES AT WEEKLY INTERVALS AFTER - ADMISSION TO HOSPITAL - - ══════════╤══════════╦═════════╤═══════════════════╦═══════════════════ - TIMES │NUMBER OF ║NUMBER OF│B. INFLUENZÆ FOUND ║ TOTAL CARRIERS IN - CULTURED │ CASES ║CULTURES │ ║ ONE OR MORE - │ ║ │ ║ CULTURES - ──────────┼──────────╫─────────┼─────────┬─────────╫─────────┬───────── - „ │ „ ║ „ │ NUMBER │PER CENT ║ NUMBER │PER CENT - ──────────┼──────────╫─────────┼─────────┼─────────╫─────────┼───────── - 2│ 129║ 1st│ 37│ 28.7║ 82│ 63.6 - │ ║ 2nd│ 63│ 48.8║ │ - ──────────┼──────────╫─────────┼─────────┼─────────╫─────────┼───────── - 3│ 69║ 1st│ 20│ 28.9║ 52│ 75.4 - │ ║ 2nd│ 31│ 44.9║ │ - │ ║ 3rd│ 33│ 47.8║ │ - ──────────┼──────────╫─────────┼─────────┼─────────╫─────────┼───────── - 4│ 25║ 1st│ 6│ 24║ 21│ 84.0 - │ ║ 2nd│ 10│ 40║ │ - │ ║ 3rd│ 13│ 52║ │ - │ ║ 4th│ 14│ 56║ │ - ──────────┴──────────╨─────────┴─────────┴─────────╨─────────┴───────── - -It is evident from the figures presented in Table XII that a large -percentage of the measles cases studied were at one time or another -carriers of B. influenzæ. In consideration of this fact, it must be -borne in mind that all these cases were cultured during the period when -the influenza epidemic was at its height and that many of these cases -had influenza while in the hospital for measles. No data are available -as to the exact number, since a definite diagnosis of influenza could -hardly be made during the acute stage of measles. It is probable that -approximately 25 per cent developed influenza, since that was the -incidence of influenza in the total population of Camp Pike. The -consistent increase in the percentage of influenza carriers clearly -demonstrates that this was due to wide dissemination of B. influenzæ -with the progress of the epidemic. Another point of exceeding interest -is that the percentage of measles cases carrying B. influenzæ in the -throat was lowest during the acute stage of the disease and increased -during convalescence. This is in direct contrast with the results found -in cases of influenza where the number of cases carrying B. influenzæ in -the throat was highest during the acute stage and rapidly diminished in -uncomplicated cases with the onset of convalescence. - -=Summary.=—Multiple cultures made simultaneously from the nose, throat -and lower respiratory tract showed that B. influenzæ was invariably -present in all cases of influenza from the onset of the disease. Not -only was B. influenzæ present in all cases, but it was frequently -present in predominant numbers, sometimes in nearly pure culture. In the -majority of cases that went on to rapid recovery without the development -of an extensive bronchitis or complicating pneumonia, the predominance -of B. influenzæ over other organisms rapidly diminished coincident with -onset of convalescence. Many cases, however, continued to carry B. -influenzæ in large numbers in the throat throughout convalescence. No -data on the possible duration of the carrier state have been obtained. -By the culture methods employed no other organism has been found that -would suggest any etiologic relationship to the disease. The two -organisms most frequently associated with B. influenzæ in postinfluenzal -pneumonias, pneumococcus and S. hemolyticus, have not differed in their -incidence in early uncomplicated cases of influenza from that found in -normal individuals. - -The incidence of B. influenzæ in normal men, in different groups -studied, has varied between 11.1 and 88 per cent. This wide variation -has depended upon the prevalence of respiratory diseases, more -particularly influenza, in the groups studied and the opportunity -thereby offered for the wide dissemination of B. influenza. With the -progress of the epidemic, the number of normal men carrying B. influenzæ -has steadily increased until it reached its maximum at the end of the -epidemic. - -The incidence of B. influenzæ in cases of measles studied during the -epidemic of influenza has been relatively high though never equaling -that found in cases of influenza. As in normal men, the incidence in -cases of measles has steadily increased during the period of the -epidemic. Repeated throat cultures at weekly intervals in cases of -measles have shown that approximately 80 per cent became temporary -carriers of B. influenzæ at one time or another during the period of the -epidemic. Many of these cases had influenza during the time that they -were in the hospital. The carrier state in cases of measles was found to -bear no relation to the acute stage of the disease since the number of -carriers at the time of admission to the hospital was considerably lower -than that found during convalescence as determined by repeated cultures -in the same cases. - - - Discussion - -The bacteriologic studies in cases of influenza described in this report -fully support Pfeiffer’s claim that B. influenzæ is invariably present -in the disease. It is particularly important to note that these results -were obtained in early uncomplicated cases of influenza and are not -dependent upon cultures made from cases complicated by pneumonia or -obtained at autopsy. In view of this fact the tendency so apparent in -much of the recent literature to relegate B. influenzæ to a place of -secondary or minor importance in the disease seems hardly justifiable. -It would seem that this tendency is largely dependent upon three -factors: first, the failure of many to find B. influenzæ either during -life or at autopsy in any considerable proportion of cases; second, the -frequent failure to draw a clear distinction between influenza itself -and the pneumonia to which it predisposes with a consequent overemphasis -upon autopsy bacteriology where a considerable variety of secondary -organisms have attracted particular attention; and third, an incorrect -interpretation of the undoubtedly large number of B. influenzæ carriers -found among normal individuals and those with other diseases during the -period of the epidemic and to less extent in interepidemic times. - -Since the majority of workers who are thoroughly familiar with the -technic of cultivating B. influenzæ have encountered little difficulty -in finding it in a large majority of cases, it is felt that the -considerable number of negative reports that have appeared can depend -only upon the unfamiliarity of those who have failed to find it with the -proper bacteriologic methods. This is quite apparent in many of the -reports that have been published, and is not surprising in the face of -the excessive demand for well-trained bacteriologists occasioned by the -war. - -One important feature in the successful isolation of B. influenzæ from -all cases that has been brought out in the course of the work here -reported, is the necessity of making simultaneous cultures from all -portions of the respiratory tract, since by no single culture method was -it found possible to find the organism in all cases. It has been pointed -out that one of the most characteristic local phenomena of the disease -is the rapidly progressing attack upon the mucous membranes of the -respiratory tract. It seems quite possible that B. influenzæ in -predominant numbers at least may be found in many cases only at the -crest of the wave, if we may speak of it as such. By way of analogy is -the well-recognized fact that the successful isolation of streptococcus -from cases of erysipelas often depends upon taking cultures from the -margin of the advancing lesion. While definite proof is lacking for this -opinion, it would seem to receive some support from the observation that -B. influenzæ rapidly disappears from the throat with the onset of -convalescence in a considerable proportion of cases. It is felt that -these observations, establishing the predominance of B. influenzæ in the -early acute stages of the disease, are of considerable significance, -especially when exactly the reverse condition was found in studying the -incidence of the organism in cases of measles. - -In consideration of the primary cause of influenza, attention has often -been focused upon the many different bacteria found in autopsy cultures. -The most prominent of these are the ill-defined diplostreptococci of the -European writers, the various immunologic types of pneumococci, and S. -hemolyticus. Other microorganisms less frequently found are -staphylococci, M. catarrhalis, nonhemolytic streptococci, and B. mucosus -capsulatus. It is not within the scope of this paper to discuss their -relation to the various types of pneumonia found at autopsy, but their -very multiplicity would seem sufficient _prima facie_ evidence that they -bear no etiologic relationship to influenza and must be regarded only as -secondary invaders. If any further support for this opinion were -necessary, it may be found in the studies upon the incidence of -pneumococcus and S. hemolyticus in early cases of influenza described in -this report. Both were found to occur in the same proportions in which -they may be found in normal individuals at any time. - -Although Pfeiffer maintained that B. influenzæ was found only in true -epidemic influenza, the incorrectness of this contention has been -thoroughly established by many reliable investigators and it has been -shown beyond question that influenza bacilli may always be found in a -small proportion of normal individuals and are not infrequently found in -other respiratory diseases. - -The fairly extensive study that has been made of the incidence of B. -influenzæ in normal men and in cases of measles has clearly demonstrated -that the proportion of carriers found in any group depends upon the -prevalence of influenza in the group studied and that with the progress -of the epidemic the percentage of carriers has steadily increased. When -one considers that the opportunity for the dissemination of B. influenzæ -by contact infection is almost unlimited during an epidemic of the -proportions of that which has swept over the country, this is not at all -surprising. That such a large number of normal individuals became -carriers of B. influenzæ during the epidemic would seem to be sufficient -evidence that actual dissemination does occur and to controvert the -theory that in actual cases of influenza, conditions are established in -the respiratory tract whereby B. influenzæ, always present in small -numbers, is enabled to “grow out” and become the predominant organism. -From a consideration of all the observations made as to the incidence of -B. influenzæ in various conditions it would appear that the carrier -condition is quite analogous to that found with many other bacteria, and -may be divided into three groups: (_a_) acute carriers, those having -influenza, (_b_) contact carriers, those who during epidemic times -become temporary carriers of the organism without contracting the -disease, and (_c_) chronic carriers, the relatively small number of -normal individuals or those with chronic respiratory conditions who -carry B. influenzæ over long periods of time. From the facts at hand -this would seem to be the most probable explanation of the conditions -found. It is certainly true that the established presence of -pneumococcus, B. diphtheriæ, meningococcus and many other organisms in a -varying proportion of normal individuals is not regarded as sufficient -evidence to exclude them as the etiologic agents of the diseases which -they cause. - -It is quite obvious that if B. influenzæ is to be regarded as the cause -of epidemic influenza, it must change quite rapidly under certain -circumstances from a relatively saprophytic organism to a relatively -virulent pathogenic organism, and conversely return to its avirulent -state following the passage of an epidemic. Animal experimentation has -taught us that virulence is acquired by the rapid passage of an organism -from host to host. That an opportunity for the rapid transference of B. -influenzæ from man to man was provided by the assembling of large groups -of individuals relatively susceptible to respiratory diseases in our -camps and cantonments is by no means impossible. It has been clearly -shown by Vaughn and Palmer[22] that men from rural districts are very -susceptible to respiratory diseases and that the camps in which such men -were assembled suffered most heavily in this respect during the winter -of 1917–18. This Commission has clearly demonstrated that an epidemic of -influenza swept through Camp Funston[21] in the spring of 1918 and that -a similar epidemic occurred at Camp Pike. Accumulating evidence will -undoubtedly show that like epidemics existed in many of our southern -camps (Vaughn and Palmer,[22] Soper[23]). It is of considerable interest -that B. influenzæ was found in almost one-half of the cases of -bronchopneumonia studied by Cole and MacCallum[24] at Fort Sam Houston -in February and March, 1918. This relation is especially noteworthy, -since an epidemic of influenza was seen by one of us (Blake) among the -troops at Kelly Field and Fort Sam Houston during these months. That -similar conditions existed in European armies as early as 1916–17 is -suggested by the reports of Hammond, Rolland, and Shore[25] and of -Abrahams, Hallows, Eyre, and French[26] on epidemics of “purulent -bronchitis” with bronchopneumonia in the British army. B. influenzæ was -found abundantly in these cases. - -Theoretically, under the conditions outlined above, ideal opportunities -have been provided for B. influenzæ to build up sufficient virulence to -enable it to produce the pandemic of 1918–19. While it is thoroughly -recognized that these considerations are in the main hypothetical, it is -felt that they are by no means beyond the bounds of possibility, and for -that reason are offered as suggestions worthy of further investigation. - -It is, of course, perfectly possible on the basis of the observations -presented still to regard B. influenzæ as a secondary invader which -makes its appearance in all cases of influenza simultaneously with the -onset of clinical symptoms. Final proof of its causal relationship to -the disease must depend upon the production of influenza by experimental -inoculation. Results hitherto obtained in attempts to produce the -disease experimentally have been contradictory. Pfeiffer[8] claimed to -have produced a disease in monkeys in some respects resembling influenza -by the intratracheal injection of freshly isolated cultures of B. -influenzæ. Wollstein,[19] in studies upon the pathogenicity of various -strains, has shown that B. influenzæ is generally pathogenic for mice -and guinea-pigs without respect to source or virulence for man. -Pathogenicity for rabbits and monkeys, on the other hand, was possessed -only by strains that were highly virulent for man. She furthermore -pointed out that for successful animal experimentation, it is imperative -that inoculations be carried out immediately after the isolation of the -bacilli because they rapidly lose virulence by subculture on artificial -media. It is felt that failure to appreciate these facts has been -responsible for the often repeated statement that B. influenzæ is not -pathogenic for animals. - -In a series of animal experiments carried out by this commission -recorded in an appendix to this report, sixteen-hour cultures of B. -influenzæ freshly isolated from early cases of influenza were -demonstrated to be pathogenic for monkeys, both by inoculation of the -nasal and pharyngeal mucosa and by intratracheal injection. Monkeys so -inoculated developed coryza, epistaxis, tracheitis, bronchitis, and -extreme prostration. Experiments with forty-eight-hour cultures of -strains preserved by subculture during from ten to fifteen days failed -to demonstrate pathogenicity for monkeys. Proof that these monkeys had -influenza can depend only upon the demonstration that they suffered with -a disease having the clinical character and pathologic lesions of -influenza. - -The reported failure to produce influenza in man by direct inoculation -with freshly isolated cultures of B. influenzæ in experiments conducted -on volunteers by the United States Public Health Service[27] at Gallops -Island, Boston, is interesting, but would seem to lack definite -significance since attempts to transmit the disease from man to man by -direct contact also failed. Since all the subjects of these experiments -had been previously exposed to influenza during the epidemic, 30 per -cent actually having contracted the disease, it would seem probable that -the remaining 70 per cent were only very slightly if at all susceptible. -It is noteworthy that the attack rate of influenza in most army groups -was approximately 20 to 30 per cent during the epidemic, the remaining -70 to 80 per cent failing to contract the disease though equally -exposed. No other explanation presents itself except that influenza is -no longer transmissible when clinical symptoms have appeared. - - - Conclusions - -1. Consideration of all the evidence available makes it seem highly -probable that B. influenzæ is the specific etiologic agent of epidemic -influenza, because (_a_) it is always present in early uncomplicated -cases of influenza; (_b_) it is predominantly so during the acute stage -of the disease in cases going on to rapid recovery without development -of complications; (_c_) its presence in varying numbers in normal -individuals and in other diseases of the respiratory tract is not valid -evidence against its etiologic relationship to influenza, but on the -contrary is quite in harmony with what should be expected from our -knowledge of other bacteria known to be the etiologic agents of various -respiratory diseases; (_d_) its rapidly increasing prevalence in normal -individuals simultaneously with the progress of the epidemic indicates -that actual dissemination of B. influenzæ readily occurs and is very -widespread during pandemic times; (_e_) cultures of B. influenzæ freshly -isolated from early acute cases of influenza are pathogenic for animals, -and may produce in monkeys a disease closely resembling influenza. - -2. Final proof of the exact relationship of B. influenzæ to influenza -must depend upon (_a_) more definite knowledge of the immunology both of -the organism and of the disease, and (_b_) knowledge of the pathologic -lesions of influenza and the production of these lesions in animals by -inoculation with B. influenzæ. - - - - - CHAPTER II - CLINICAL FEATURES AND BACTERIOLOGY OF INFLUENZA AND ITS ASSOCIATED - PURULENT BRONCHITIS AND PNEUMONIA - - FRANCIS G. BLAKE, M.D., AND THOMAS M. RIVERS, M.D. - - -The material presented in this section of the report consists of -clinical and bacteriologic observations made during the course of an -investigation of influenza and its associated bronchitis and pneumonia -at Camp Pike, Ark., between September 6 and December 15, 1918, -comprising part of a correlated study of the epidemiology, bacteriology, -pathology, and clinical features of these diseases. The bacteriologic -studies are in the main limited to those made during life, those made at -necropsy being reported in another section of this report. - -=Methods.=—All cases upon which the clinical and bacteriologic data -presented are based, were examined by the authors and our own clinical -histories and physical examinations were recorded. This was considered -of special importance, since in studying a group of diseases in which -secondary infection of the respiratory tract might supervene at any -time, it was essential to determine as far as possible the exact -clinical condition of the patient at the time when bacteriologic -examinations were made. The bacteriologic methods employed were the -direct culture of nose and throat swabbings and of selected and washed -specimens of sputum on the surface of 5 per cent defibrinated horse -blood agar plates, the intraperitoneal inoculation of white mice with -specimens of sputum according to the method described by Blake[28] for -the determination of pneumococcus types, and in some cases the method of -Avery.[29] B. influenzæ pneumococci and hemolytic streptococci were -identified by the methods described elsewhere. Note was made in most -instances of the presence of other organisms such as members of the -Gram-negative diplococcus group, staphylococci, diphtheroids, and -members of the streptococcus viridans group, but no attempt was made to -further isolate or identify them since they played no significant part -in the cases studied except in rare instances. - - - Influenza - -The fall epidemic of influenza at Camp Pike began about September 1, -1918, and reached epidemic proportions on September 23 when 214 cases -were admitted to the base hospital. The epidemic was at its height from -September 27 to October 3, during which period there were in the -neighborhood of 1,000 new cases daily. From this date until October 31 -the number of new cases occurring daily steadily decreased and by the -latter date the epidemic was over. Scattered cases continued to occur, -however, throughout November, and during the last week of this month and -the first week of December a second epidemic wave of relatively mild -character occurred. From September 1 to October 31 the total number of -cases of influenza reporting sick was 12,393. During the same period -there were 1,499 cases of pneumonia with 466 deaths. - -Influenza as observed at Camp Pike differed in no essential respects -from that occurring elsewhere. In brief, it presented itself as a highly -contagious, self-limited infectious disease of relatively short duration -in most instances, the principal manifestations of which were sudden -onset with high fever, profound prostration, severe aching pains in back -and extremities, conjunctival injection, flushing of the face, neck, and -upper thorax often amounting to a true erythema, and a rapidly -progressing attack upon the mucous membranes of the respiratory tract as -manifested by coryza, pharyngitis, tracheitis and bronchitis with a -marked tendency to hemorrhage; in itself it is rarely serious, but in -reality serious because of the large number of individuals attacked and -temporarily incapacitated and because it predisposed to widespread and -highly fatal secondary infection of the lungs. - -=Clinical Features.=—A clinical study of 100 consecutive cases of -influenza admitted during the height of the epidemic was made. - -The onset was sudden, in most instances being initiated with marked -sensations of chilliness in 82 cases. Although a severe chill was -probably relatively uncommon, 44 of these patients considered the -symptom of sufficient severity to describe it as such. This was -accompanied by extreme general malaise with severe aching pains -throughout the whole body. Intense backache was complained of in 40 -cases, headache in 54 cases. A varying degree of prostration, sometimes -leading to complete collapse, was almost universal; 5 patients -complained of extreme asthenia and 2 of marked dizziness. At time of -admission to the hospital the face, neck and upper chest exhibited a -uniform erythematous flush, never macular in appearance. The conjunctivæ -were deeply injected, but lacrimation was not noticeable and a true -exudative conjunctivitis was not encountered. Onset was accompanied by a -sharp elevation of temperature ranging from 100° F. to 106° F., in most -cases being between 102° F. and 105° F., at the time of admission. No -constant type of temperature curve was maintained. Excluding the 15 -cases in this group that developed pneumonia, the temperature was well -sustained throughout the course of the disease in 46, irregular in 33, -and definitely remittent in 6. The duration of the fever varied between -one and seven days, the temperature having returned to normal in all but -19 of the 85 cases by the end of four days. The duration of fever was -one day in 18 cases, two days in 12, three days in 19, four days in 17, -five days in 10, six days in 4, and seven days in 5. Of the 4 cases with -fever for six days, 2 had a fairly extensive bronchitis, 1 a laryngitis. -Of the 5 cases with fever of seven days’ duration, 3 had signs of an -extensive bronchitis, 2 of only a mild bronchitis. - -The pulse was relatively slow in rate as compared with the degree of -temperature elevation, running between 90 and 100 beats per minute in -the large majority of cases. At the height of the disease it was full -and easily compressed. No irregularities were noticed. With recovery it -fell promptly to normal. The respiratory rate showed only moderate -elevation, being between 20 and 26 in most cases. In a few instances a -rate as high as 32 was recorded at time of admission to the hospital, -but this promptly fell with rest in bed. A respiratory rate rising above -26 after the third or fourth day of the disease nearly always indicated -a beginning pneumonia. With recovery the rate promptly fell to normal. -Cyanosis did not occur in the absence of pneumonia. - -Aside from the manifestations of a profound toxemia, influenza was -preeminently characterized by symptoms of respiratory tract infection. -The appearance of respiratory symptoms occurred at varying intervals -after the onset of the disease, being well developed by the end of -twenty-four hours in most cases. A progressive attack upon the mucous -membranes of the respiratory tract was universal, beginning with coryza -and pharyngitis and progressing to tracheitis or _vice versa_. Further -extension of the infection to the bronchi, however, was by no means -universal, 49 cases in the group studied recovering without developing -evidence of bronchitis. Sore throat was rarely complained of, and -laryngitis, possibly due to secondary infection, occurred only once. The -progress of the infection was marked subjectively by sensations of -irritation, stinging, and a feeling of tightness. A profuse, thin, -mucoid exudate appeared; the pharyngeal walls and the soft palate showed -a characteristic deep red granular appearance. The onset of tracheitis -began with a sense of burning and tightness beneath the sternum -accompanied by a harassing cough, at first nonproductive, later with the -outpouring of an exudate becoming productive. The sputum varied in -character between a scanty, thin, mucoid sputum and a profuse, frankly -purulent sputum in cases subsequently developing an extensive -bronchitis. Hemorrhage from the mucous membranes was common. Epistaxis -occurred in 12 per cent of the cases and was often profuse. The sputum -contained fresh blood in varying amounts in 24 per cent of the cases; 51 -per cent of the cases developed signs of bronchitis. In 15 of these the -bronchitis was mild, probably limited to the larger bronchi, physical -examination showing only inconstant sibilant and musical râles. The -sputum in these cases was neither profuse nor frankly purulent; 36 cases -developed a fairly extensive purulent bronchitis as manifested by more -or less diffusely scattered moist râles and by moderately copious -mucopurulent or frankly purulent sputum. This bronchitis was not -accompanied by an increase in the respiratory rate or by cyanosis unless -pneumonia subsequently developed. - -Gastrointestinal symptoms were insignificant: 8 patients complained of -nausea early in the disease and 6 of them vomited. Diarrhea occurred in -only 1 case, constipation being the rule. The spleen was palpable in 21 -cases, but this is of doubtful significance, since nearly all the -patients came from malarial regions. Jaundice was not noted. Aside from -the profound depression, sometimes amounting to stupor, mental symptoms -were not noted except in 1 case which showed a mild delirium. - -Influenza, although _per se_ a self-limited disease of short duration, -frequently leads to the development of serious complications, the most -important of which are pneumonia and purulent bronchitis with a varying -degree of bronchiectasis. In the group of 100 cases of influenza -studied, purulent bronchitis developed in 36 instances, pneumonia in 15; -in 3 cases there was lobar pneumonia, in 12 bronchopneumonia. Further -discussion of these complications is reserved for the sections dealing -with them in detail. Other complications were relatively rare. Otitis -media occurred in one case and frontal sinusitis in one. No fatalities -were observed among cases of uncomplicated influenza, the deaths that -occurred being invariably associated with a secondary pneumonia due in -nearly all instances to secondary infection with pneumococci or -hemolytic streptococci. - - - Purulent Bronchitis - -It has been stated that a considerable number of cases of influenza -developed a more or less extensive purulent bronchitis. This term is -used as descriptive of a group of cases showing clinically evidence of a -diffuse bronchitis as manifested by numerous medium and fine moist râles -scattered throughout the chest and evidence of a definitely purulent -inflammatory reaction as indicated by the expectoration of fairly -copious amounts of mucopurulent or frankly purulent sputum. This -condition is regarded as quite distinct, on the one hand, from the -common type of mucoid bronchitis frequently associated with “common -colds” and a fairly common feature of uncomplicated cases of influenza, -in which physical examination of the chest reveals only transient -sibilant and musical râles without evidence of extension to finer -bronchi, and, on the other hand, from bronchopneumonia. - -=Bacteriology.=—Thirteen cases of purulent bronchitis following -influenza in none of which was there any evidence of pneumonia at the -time cultures of the sputum were made nor later were subjected to -careful bacteriologic study. Specimens of bronchial sputum were -collected in sterile Petri dishes and selected portions thoroughly -washed to remove surface contaminations before bacteriologic -examinations were made. The results are shown in Table XIII. - - TABLE XIII - - BACTERIOLOGY OF THE SPUTUM IN CASES OF PURULENT BRONCHITIS FOLLOWING - INFLUENZA - - ════╤══════════════════════════╤═════════════════════╤═════════════════ - CASE│ STAINED FILM OF SPUTUM │ DIRECT CULTURE ON │MOUSE INOCULATION - │ │ BLOOD AGAR PLATE │ - │ │ │ - ────┼──────────────────────────┼─────────────────────┼───────────────── - GJ │B. influenzæ + + + │B. influenzæ + + + + │B. influenzæ - │ │ │Pneumococcus - │Gram + diplococci + │Pneumococcus + │(type - │ │ │undetermined) - WAL │B. influenzæ + + │B. influenzæ + + + │ - │Gram + diplococci + + │Pneumococcus IV + + │ - TH │B. influenzæ + + + │B. influenzæ + + + + │ - │Gram + diplococci + + + │Pneumococcus IV + + │ - LH │B. influenzæ + │B. influenzæ + + │ - │Gram + diplococci + │Pneumococcus IV + + │ - FBD │Gram + diplococci + + + + │Pneumococcus IV + + +│Pneumococcus IV - │ │B. influenzæ + │B. influenzæ - Wa │B. influenzæ + + │B. influenzæ + + │ - │Gram + diplococci + + │Pneumococcus IV + + │ - Sh │B. influenzæ + + + │B. influenzæ + + │ - │Gram + diplococci + + │Pneumococcus IV + + +│ - Wal │Gram + diplostrep + + + │S. viridans + + │ - │B. influenzæ + │B. influenzæ + + │ - CLF │B. influenzæ + + + + + │ │B. influenzæ - │Gram + diplococci + │ │Pneumococcus IV - NCC │B. influenzæ + + │B. influenzæ + + + │B. influenzæ - │Gram − micrococcus + │M. catarrhalis + + │M. catarrhalis - │Gram + diplostrep. + │S. viridans + + │ - JCM │B. influenzæ + + + │B. influenzæ + + + + │B. influenzæ - │Gram + streptococcus + │S. hemolyticus + │S. hemolyticus - │Gram − micrococcus + │M. catarrhalis + │Pneumococcus IV - │Gram + diplococcus + │ │ - Bl │B. influenzæ + │ │B. influenzæ - │Gram + diplococcus + │ │Pneumococcus IIa - Bu │B. influenzæ + + + + │B. influenzæ + + + │B. influenzæ - │Gram + diplococcus + + + +│Pneumococcus IV + + +│Pneumococcus IV - ────┴──────────────────────────┴─────────────────────┴───────────────── - -From the data presented in Table XIII it is evident that a mixed -infection existed in all cases. The results obtained by stained sputum -films and by direct culture on blood agar plates are of special -significance. B. influenzæ was present in all cases, being the -predominant organism in 6 cases, abundantly present in others, and few -in number in 2. Of other organisms the pneumococcus was most frequently -found, occurring in 11 of the 13 cases, in all but 2 instances being -present in considerable numbers. S. viridans was encountered twice, once -in association with a Gram-negative micrococcus resembling M. -catarrhalis culturally. S. hemolyticus was found once, together with M. -catarrhalis and a few pneumococci, Type IV, coming through in the mouse -only and of doubtful significance. The stained sputum films and direct -cultures always showed these organisms present in sufficient abundance -to indicate that they were present in the bronchial sputum and were not -merely contaminants from the buccal mucosa. - -It seems quite probable from these results that purulent bronchitis -following influenza is, in most cases at least, due to mixed infection -of the bronchi and should be looked upon as a complication of influenza. -Whether the condition may be caused by infection with B. influenzæ alone -is difficult to say. No evidence that it may be caused by B. influenzæ -alone was obtained in the cases studied. It is not intended to enter -here into a discussion as to whether B. influenzæ should be regarded as -a secondary invader or not; the other organisms encountered certainly -are. It would seem most probable that purulent bronchitis is caused by -the mixed infection of B. influenzæ and various other organisms, -commonly the pneumococcus, but that the condition is initiated by the -invasion of the bronchi by these other organisms in the presence of a -preceding infection with B. influenzæ. - -=Clinical Features.=—Purulent bronchitis following influenza began -insidiously without any prominent symptoms to mark its onset. About the -third or fourth day of influenza, when recovery from the primary disease -might be looked for, the patient would begin to cough more frequently, -raising increasing amounts of mucopurulent sputum. This sputum was -yellowish green in color, copious in amount, and often somewhat nummular -in character, sometimes streaked with blood. These symptoms were -accompanied by the appearance of coarse, medium and fine moist râles -more or less diffusely scattered throughout the chest and usually most -numerous over the lower lobes. The percussion note, breath and voice -sounds, and vocal and tactile fremitus remained normal. There was no -increase in the respiratory rate or pulse rate, and cyanosis did not -develop in the absence of a beginning pneumonia. Many such cases, of -course, developed bronchopneumonia; in this event areas showing -diminished resonance, suppressed breath sounds, and fine crepitant râles -with the “close to the ear” quality would appear, the respiratory rate -would become increased and cyanosis would become evident. In those cases -of purulent bronchitis not developing pneumonia, a moderate elevation of -temperature, rarely above 101° F., and irregular in character usually -occurred and persisted for a few days or a week. - -Many cases maintained a persistent cough, raising considerable amounts -of sputum throughout the period of their convalescence in the hospital, -which was often considerably prolonged when this complication of -influenza occurred. Although no clinical data are available on such -cases over a prolonged period of observation, it seems probable that -some of them, at least, had developed some degree of bronchiectasis. -This would seem all the more probable, since many cases of pneumonia -following influenza showed at autopsy extensive purulent bronchitis with -well-developed bronchiectasis. Bronchiectasis will be discussed in -greater detail in another section of this report. It is this group of -cases with more or less permanent damage to the bronchial tree that -makes this type of bronchitis following influenza a serious complication -of the disease. - - - Pneumonia - -The opportunity presented for a correlated study of the clinical -features, bacteriology, and pathology of pneumonia following influenza -throughout the period of the epidemic at Camp Pike from September 6, -1918, to December 15, 1918, made it evident that this pneumonia could be -regarded as an entity in only one respect, namely, that influenza was -the predisposing cause. Clinically, bacteriologically, and -pathologically it presented a very diversified picture ranging all the -way from pneumococcus lobar pneumonia to hemolytic streptococcus -interstitial and suppurative pneumonia with the picture modified to a -varying extent by the preceding or concomitant influenzal infection. - -One hundred and eleven consecutive cases in which careful clinical and -bacteriologic studies were made form the basis of the material -presented. Of these cases, 38 came to necropsy so that ample opportunity -was presented to correlate the clinical and bacteriologic studies made -during life with the pathology and bacteriology at necropsy. It has -seemed advisable to group the cases primarily on an etiologic basis with -secondary division according to clinical features in so far as this can -be done. Bacteriologic studies showed that at the time of onset these -pneumonias were either pneumococcus pneumonias or mixed pneumococcus and -influenza bacillus pneumonias in nearly all instances. Certain of these -cases later became complicated by a superimposed hemolytic streptococcus -or a staphylococcus infection. In a few instances hemolytic -streptococcus pneumonia directly followed influenza without an -intervening pneumococcus infection. B. influenzæ was present in varying -numbers in nearly all cases. In only 2 instances however, was it found -unassociated with pneumococci or hemolytic streptococci, once alone and -once with S. viridans. - -Clinically the cases fell into four main groups: (1) Lobar pneumonia; -(2) lobar pneumonia with purulent bronchitis; (3) bronchopneumonia -(pneumococcus); (4) bronchopneumonia (streptococcus). It should be borne -in mind, however, that the picture was a complex one and that correct -clinical interpretation was not always possible, since many cases did -not conform sharply to any one type and superimposed infections during -the course of the disease often modified the picture. - -=Pneumococcus Pneumonia Following Influenza.=—Bacteriologic examination -of selected and washed specimens of sputum coughed from the lungs at -time of onset of pneumonia showed the various immunologic types of -pneumococcus to be present in 105 cases. The incidence of the different -types is shown in Table XIV. - - TABLE XIV - - TYPES OF PNEUMOCOCCUS IN 105 CASES OF PNEUMOCOCCUS PNEUMONIA FOLLOWING - INFLUENZA - - ═══════════════════════╤═════════╤═════════════════╤═════════╤═════════ - │ LOBAR │BRONCHOPNEUMONIA │ TOTAL │PER CENT - │PNEUMONIA│ │ │ - ───────────────────────┼─────────┼─────────────────┼─────────┼───────── - Pneumococcus, Type I │ 8│ 0│ 8│ 7.6 - Pneumococcus, Type II │ 3│ 1│ 4│ 3.8 - Pneumococcus, II atyp. │ 12│ 7│ 9│ 18.1 - Pneumococcus, Type III │ 3│ 3│ 6│ 5.7 - Pneumococcus, Group IV │ 32│ 36│ 68│ 64.8 - ───────────────────────┴─────────┴─────────────────┴─────────┴───────── - -The most noteworthy feature of the figures in Table XIV is the high -proportion of pneumonias due to types of pneumococci found in the mouths -of normal individuals, 93 cases or 88.6 per cent, being caused by -Pneumococcus Types II atypical, III, and IV. This is in harmony with the -results generally reported and is in all probability due to the fact -that in patients with influenza pneumococci, which under normal -conditions would fail to cause pneumonia, readily gain access to the -respiratory tract and produce the disease. It is also of interest that -with one exception the highly parasitic pneumococci of Types I and II -were associated with pneumonias clinically lobar in type. - -Superimposed infection of the lungs with other types of pneumococci than -those primarily responsible for the development of pneumonia occurred -not infrequently in this group of cases either during the course of the -disease or shortly after recovery from the first attack of pneumonia. -Pneumococcus Type II infection was superimposed upon or shortly followed -pneumonia caused by Group IV pneumococci in 4 instances, by Pneumococcus -II atypical in 1 instance. In 1 case pneumonia due to Pneumococcus II -atypical occurred three days after recovery from a Pneumococcus Type I -pneumonia, in another case Pneumococcus Type III infection was -superimposed upon a pneumonia originally due to a pneumococcus of Group -IV. These cases are presented in detail in another section of this -report, and in several instances were shown to be directly due to -contact infection from patients in neighboring beds. - -In a similar manner, superimposed infection with S. hemolyticus at some -time during the course of the pneumonia occurred in 13 cases in this -group, with fatal result in all but one. Streptococcus infection -occurred in pneumonia due to Pneumococcus II atypical once, to -Pneumococcus Type III once, and to pneumococci of Group IV eleven times. -Nine of these cases were free from hemolytic streptococci at the time of -onset of the pneumonia, 4 showed a very few colonies of hemolytic -streptococci in the first sputum culture made. - -B. influenzæ was found in the sputum coughed from the deeper air -passages in the majority of cases, being present in 80, or 76.2 per -cent, of the 105 cases. In the 58 cases of lobar pneumonia it was found -41 times, or 70.7 per cent, in the 47 cases of bronchopneumonia 39 -times, or 82.9 per cent. The abundance of B. influenzæ in the sputum -varied greatly in different cases. Microscopic examination of stained -sputum films and direct culture of the sputum on blood agar plates -showed that in general it was more abundant in the mucopurulent sputum -from cases of bronchopneumonia than in the mucoid rusty sputum from -cases of lobar pneumonia. This was by no means an invariable rule, -however, since in the former the bacilli were sometimes very few in -number, in the latter quite abundant. Whether B. influenzæ shared in the -production of the actual pneumonia in these cases is difficult to decide -and cannot be stated on the basis of the bacteriologic and clinical -observations which have been made. - -=Clinical Features.=—One of the most striking aspects of pneumococcus -pneumonia following influenza was the diversity of clinical pictures -presented. These varied all the way from the classical picture of lobar -pneumonia to that of bronchopneumonia of all grades of severity from the -rapidly fatal coalescing type to that of very mild character with very -slight signs of consolidation. For this reason it is questioned whether -there is any real justification for speaking of a typical influenzal -pneumonia, an opinion that seems well supported by the diversified -picture found at the necropsy table. - -For purposes of presentation, pneumococcus pneumonia following influenza -may be divided into three clinical groups: (1) Lobar pneumonia; (2) -lobar pneumonia with purulent bronchitis; (3) bronchopneumonia. No -accurate data are available as to the relative frequency with which -these three types occurred at Camp Pike. In the group of 105 cases -studied there were 58 cases of lobar pneumonia, 11 of which had purulent -bronchitis, and 47 cases of bronchopneumonia. The majority of these -cases, however, occurred during the early days of the epidemic of -influenza and probably show a considerably higher proportion of lobar -pneumonias than actually occurred in the total number of pneumonias -throughout the epidemic. This is indicated by the fact that of 100 -consecutive cases of influenza selected for observation at the height of -the epidemic, 3 developed clinical evidence of lobar pneumonia and 12 of -bronchopneumonia. - -(1) Lobar pneumonia presenting the typical clinical picture with sudden -onset, tenacious rusty sputum, sustained temperature, and physical signs -of complete consolidation of one or more lobes occurred in 47 cases; 36 -cases in this group definitely followed influenza. In 11 cases no -certain clinical evidence of a preceding influenza was obtained, and it -is probable that some of these represent cases of pneumonia occurring -independently of the epidemic of influenza. - -The onset of pneumonia in this group of cases occurred from four to nine -days after the onset of influenza and with few exceptions was ushered in -by a chill and pain in the chest. In several instances the patient had -apparently recovered from influenza as evidenced by fall of temperature -to normal. After twenty-four to seventy-two hours of normal temperature -the patient would have a chill and develop lobar pneumonia. In the -majority of cases, however, lobar pneumonia developed while the patient -was still sick with influenza. The course of the disease, symptomatology -and physical signs were quite characteristic of lobar pneumonia and -require no special comment. Recovery by crisis occurred in 21 cases, by -lysis in 8. Pneumococcus empyema developed in 3 cases, fibrinopurulent -pericarditis in 3 and all but 1 of these 6 cases terminating fatally. - -In Table XV 5 fatal cases of lobar pneumonia, which illustrate some of -the unusual features of the disease when it follows influenza, have been -summarized. The first 2 cases represent examples of recurring attacks of -pneumonia which developed shortly after recovery from the first attack, -in both instances being due to types of pneumococci different from those -causing the first attack. The third case represents an example of -superimposed infection of the lungs with hemolytic streptococci and -staphylococci during the course of a pneumonia due to Pneumococcus IV -and disappearance of the latter organism from the tissues so that it was -not found at time of necropsy. The last 2 cases are examples of -fulminating rapidly fatal cases of lobar pneumonia associated with mixed -infections of pneumococci and hemolytic streptococci, the streptococci -probably being secondary in both cases. Cases like the few examples -cited above, which occurred not infrequently throughout the epidemic of -influenza, serve to illustrate the difficulties which may be met in -attempting to correlate the clinical, bacteriologic and pathologic -features of pneumonia following influenza unless careful bacteriologic -examinations are made both during life and at the necropsy table in the -same group of cases. - - TABLE XV - - CASES OF LOBAR PNEUMONIA FOLLOWING INFLUENZA - - ════╤═════════╤══════════╤══════════════════╤════════════════════════════════ - CASE│ONSET OF │ ONSET OF │SPUTUM EXAMINATION│ COURSE OF PNEUMONIA - │INFLUENZA│PNEUMONIA │ │ - ────┼─────────┼──────────┼─────┬────────────┼──────────────────────────────── - │ │ │DATE │BACTERIOLOGY│ - ────┼─────────┼──────────┼─────┼────────────┼──────────────────────────────── - Pul │Sept. 7 │Sept. 9 │Sept.│Pn. IV ++++ │Recovery by crisis on Sept. 14. - │ │1st attack│10 │B. inf. +++ │On Sept. 21 developed lobar - │ │bronchopn.│ │ │pneumonia. Died Sept. 30 - │ │ │ │ │ - ────┼─────────┼──────────┼─────┼────────────┼──────────────────────────────── - Lew │Sept. 16 │Sept. 20 │Sept.│Pn. I +++ │Lobar pn., recovery by crisis - │ │chill │22 │B. inf. + │Sept. 29. Developed 2nd attack - │ │ │ │ │lobar pn. on Oct. 2. Died Oct. 8 - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ────┼─────────┼──────────┼─────┼────────────┼──────────────────────────────── - Col │Sept. 20 │Sept. 24 │Sept.│Pn. IV ++ │Severe lobar pneumonia. Died on - │ │ │27 │ │Sept. 30 - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ────┼─────────┼──────────┼─────┼────────────┼──────────────────────────────── - Gar │Sept. 23 │Sept. 28 │Sept.│Pn. IV ++ │Fulminating rapidly fatal lobar - │ │ │30 │S. hem. + │pneumonia. Died Sept. 30 - │ │ │ │B. inf. + │ - │ │ │ │ │ - ────┼─────────┼──────────┼─────┼────────────┼──────────────────────────────── - Hol │Sept. 25 │Sept. 30 │Sept.│Pn. III ++ │Fulminating rapidly fatal lobar - │ │ │30 │B. inf. ++ │pneumonia. Died Oct. 1. - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ────┴─────────┴──────────┴─────┴────────────┴──────────────────────────────── - - ════╤══════════════════════════════════════════════════ - CASE│ NECROPSY - │ - ────┼────────────────────────────────┬───────────────── - │ DIAGNOSIS │ BACTERIOLOGY - ────┼────────────────────────────────┼───────────────── - Pul │Lobar pneumonia. Gray │H.B. Pn. II - │hepatization L.L, L.U, R.L. │Br. Pn. II ++++ - │ │B. inf. +++ - │ │R.L. Pn. II + + - ────┼────────────────────────────────┼───────────────── - Lew │Lobar pneumonia. Gray │H.B. Pn. II atyp. - │hepatization R.U. │Br. B. inf. ++++ - │Fibrinopurulent pleurisy │Pn. IIa +++ - │ │S. hem. + - │ │Staph. + - │ │R.U. Pn. IIa ++++ - ────┼────────────────────────────────┼───────────────── - Col │Lobar pneumonia. Red │H.B. S. hem. - │hepatization all lobes. │Br. S. hem. ++++ - │Serofibrinous pl., rt. 125 c.c. │Staph. + - │ │L.L. S. hem. ++++ - │ │Staph. + - ────┼────────────────────────────────┼───────────────── - Gar │Lobar pneumonia. Engorgement and│H.B. S. hem. - │red hepatization L.U., R.U. │Br. S. hem. ++++ - │ │B. inf. +++ - │ │L.U. S. hem. ++++ - ────┼────────────────────────────────┼───────────────── - Hol │Lobar pneumonia. Engorgement all│H.B. sterile - │lobes │Br. B. inf. ++++ - │ │Pn. III ++ - │ │S. hem. + - │ │R.L. Pn. III ++++ - │ │B. inf. ++ - │ │S. hem. + - ────┴────────────────────────────────┴───────────────── - - L.L. R.L., etc., indicates lobes involved. H. B. = Heart’s blood. Br. = - bronchus. - -(2) There were 11 cases of lobar pneumonia with purulent bronchitis in -the group studied. Clinically, they closely resembled the cases in the -preceding group except in so far as the picture was modified by the -presence of the purulent bronchitis. All directly followed influenza. -The sputum, instead of being rusty and tenacious, was profuse and -mucopurulent, usually streaked with blood. Stained films and direct -culture on blood agar plates showed pneumococci in abundance and B. -influenzæ in varying numbers, in only two instances the predominant -organism. The physical signs were those of lobar pneumonia with, in -addition, those of a diffuse bronchitis as manifested by medium and -coarse moist râles throughout both chests. Five cases recovered by -crisis; 6 terminated fatally and in all of them the clinical diagnosis -of lobar pneumonia with purulent bronchitis was confirmed at necropsy. - -(3) Forty-seven cases in the group studied presented the clinical -picture of bronchopneumonia. The onset of pneumonia in these cases was -in most instances insidious and appeared to occur as a continuation of -the preceding influenza. The temperature, instead of falling to normal -after from three to four days, remained elevated or rose higher, the -respiratory rate began to rise, a moderate cyanosis appeared, the cough -increased, and the sputum became more profuse, usually being -mucopurulent and blood streaked, sometimes mucoid with fresh blood. The -pulse showed little change at first, being only moderately accelerated. -Pleural pain, so characteristic of the onset of lobar pneumonia, was -rarely complained of, but a certain amount of substernal pain was -common, probably due to the severe tracheobronchitis. Physical -examination at this time revealed small areas showing relative dullness, -diminished or nearly absent breath sounds, and fine crepitant râles. -These areas usually appeared first posteriorly over the lower lobes. - -The subsequent course of the disease showed the widest variation from -mild cases with limited pulmonary involvement going on to prompt -recovery in four or five days with defervescence by lysis or crisis to -those presenting the picture of a rapidly progressive and coalescing -pneumonia with fatal outcome. In the milder cases the diagnosis of -pneumonia depended in considerable part upon the general symptoms of -continued fever, increased respiratory rate, and slight cyanosis. -Definite pulmonary signs were always present if carefully looked for, -though sometimes not outspoken. Areas of bronchial breathing and -bronchophony often appeared late, sometimes not until the patient was -apparently recovering. In the severe cases cyanosis became intense and -an extreme toxemia dominated the picture. In certain of these cases -there was an intense pulmonary edema. The respiratory rate showed wide -variation, the breathing in some cases being rapid and gasping, in -others comparatively quiet. Progressive involvement of the lungs -occurred with the development of marked dullness, loud bronchial -breathing and bronchophony. Abundant medium and coarse moist râles were -heard throughout the chest, probably due in considerable part to the -extensive bronchitis almost universally present. An active delirium was -not uncommon. Signs of pleural involvement, even in the most severe and -extensive cases, rarely occurred, except in those cases in which a -hemolytic streptococcus infection supervened. - -Of the 47 cases in this group, 29 recovered; 14 by crisis, 15 by lysis. -The average duration of illness from the onset of influenza until -recovery from the pneumonia was ten days, the majority of these cases -being relatively mild in character with pneumonia of three to six days’ -duration. Empyema with ultimate recovery occurred in 1 of these cases, -Pneumococcus Type II being the causative organism. - -There were 18 fatal cases in the group. Nine of these are summarized in -Table XVI as illustrative of the frequently complex character of -bronchopneumonia following influenza and because of the interest -attaching to the bacteriologic examinations made during life and at -necropsy. Case 70 is a typical instance of the rapidly progressive type -of confluent lobular pneumonia with extensive purulent bronchitis, -intense cyanosis, and appearance of suffocation, with which pneumococci, -in this case Pneumococcus IV, and B. influenzæ are commonly associated. -Case 59 is illustrative of the small group of bronchopneumonias -following influenza which die, often unexpectedly, after a long drawn -out course, in this instance three weeks after onset. Examination of the -sputum at the time the pneumonia began, showed Pneumococcus Type IV and -B. influenzæ. At necropsy there was a lobular pneumonia with clustered -small abscesses, probably due to a superimposed infection with S. -aureus. There was a well-developed bronchiectasis in the left lower -lobe. Cultures taken at autopsy showed a sterile heart’s blood, which is -not infrequently the case in cases of pneumococcus lobular pneumonia -after influenza. Cultures from the consolidated portions of the lung -showed no growth, the pneumococcus having disappeared as might be -expected from the duration of the case. B. influenzæ together with -staphylococci were found in the bronchi. In Cases 50 and 56 a second -attack of pneumonia caused by a different type of pneumococcus from that -responsible for the first attack occurred, the second attack in both -instances being due to contact infection with Pneumococcus Type II from -a patient in a neighboring bed suffering with Pneumococcus Type II -pneumonia. Both cases showed at necropsy the type of confluent lobular -pneumonia so commonly found in pneumococcus pneumonias following -influenza. Case 107 illustrates well the extent to which mixed -infections may occur, especially when cases are treated in crowded -hospital wards. The sputum at time of onset showed Pneumococcus IV in -abundance and a few staphylococci. At necropsy there was a confluent -lobular pneumonia with clustered abscesses, purulent bronchitis, and -bronchiectasis in the left lower lobe. The heart’s blood was sterile, -the lungs showed Pneumococcus Type III and staphylococci. B. influenzæ -was not found, but through oversight, no cultures were taken from the -bronchi. Cases 92, 99, 102, and 104 are all examples of superimposed -hemolytic streptococcus infection occurring in the presence of a -Pneumococcus Type IV pneumonia, with the picture of interstitial -suppuration, abscess formation, and empyema due to S. hemolyticus on the -background of a pneumococcus lobular pneumonia found at necropsy. All -showed abundant pneumococci and B. influenzæ in the sputum and were free -from hemolytic streptococci at time of onset of pneumonia, except Case -92 which showed 2 colonies of S. hemolyticus in the first sputum culture -made. At time of death the pneumococci had disappeared in all cases and -were replaced by hemolytic streptococci. - - TABLE XVI - - CASES OF BRONCHOPNEUMONIA FOLLOWING INFLUENZA - - ════╤═════════╤═════════╤══════════════════╤═══════════════════════════ - CASE│ONSET OF │ONSET OF │SPUTUM EXAMINATION│ COURSE OF PNEUMONIA - │INFLUENZA│PNEUMONIA│ │ - ────┼─────────┼─────────┼─────┬────────────┼─────────────────────────── - │ │ │DATE │BACTERIOLOGY│ - ────┼─────────┼─────────┼─────┼────────────┼─────────────────────────── - 70│Sept. 18 │Sept. 21 │Sept.│B. inf. ++++│Diffuse bronchitis with - │ │ │22 │Pn. IV ++ │rapidly progressive - │ │ │ │ │confluent bronchopneumonia. - │ │ │ │ │Died Sept. 24 - │ │ │ │ │ - ────┼─────────┼─────────┼─────┼────────────┼─────────────────────────── - 59│Sept. 13 │Sept. 18 │Sept.│Pn. IV +++ │Bronchopneumonia with long - │ │ │19 │B. inf. + │drawn out course. Died Oct. - │ │ │ │ │4 - │ │ │ │ │ - ────┼─────────┼─────────┼─────┼────────────┼─────────────────────────── - 50│Sept. 14 │Sept. 17 │Sept.│Pn. IV +++ │Mild bronchopneumonia - │ │ │18 │ │improving on Sept. 24. On - │ │ │ │ │Sept. 26 became suddenly - │ │ │ │ │worse and died on Sept. 30 - │ │ │ │ │ - │ │ │ │ │ - ────┼─────────┼─────────┼─────┼────────────┼─────────────────────────── - 56│Sept. 10 │Sept. 17 │Sept.│Pn. IIa +++ │Bronchopneumonia with - │ │ │18 │ │recovery by crisis on Sept. - │ │ │ │ │19. Developed a second - │ │ │ │ │attack of pneumonia and - │ │ │ │ │died Sept. 29 - ────┼─────────┼─────────┼─────┼────────────┼─────────────────────────── - 107│Sept. 27 │Sept. 29 │Oct. │Pn. IV +++ │Diffuse bronchitis and - │ │ │1 │B. inf. + │severe bronchopneumonia. - │ │ │ │Staph. + │Died Oct. 5 - │ │ │ │ │ - ────┼─────────┼─────────┼─────┼────────────┼─────────────────────────── - 92│Sept. 23 │Sept. 28 │Oct. │B. inf. │Severe bronchopneumonia - │ │ │1 │+++++ │with empyema. Died Oct. 5 - │ │ │ │Pn. IV +++ │ - │ │ │ │S. hem. 2 │ - │ │ │ │col. │ - ────┼─────────┼─────────┼─────┼────────────┼─────────────────────────── - 99│Sept. 24 │Sept. 29 │Oct. │B. inf. ++++│Diffuse purulent bronchitis - │ │ │1 │Pn. IV ++ │with bronchopneumonia. Died - │ │ │ │S. vir. + │Oct. 7 - ────┼─────────┼─────────┼─────┼────────────┼─────────────────────────── - 102│Sept. 24 │Sept. 28 │Oct. │Pn. IIa +++ │Severe bronchopneumonia - │ │ │1 │B. inf. ++ │with empyema. Died Oct. 4 - │ │ │ │ │ - │ │ │ │ │ - ────┼─────────┼─────────┼─────┼────────────┼─────────────────────────── - 104│Sept. 26 │Oct. 1 │Oct. │B. inf. ++++│Diffuse purulent bronchitis - │ │ │1 │Pn. IV +++ │with severe - │ │ │ │ │bronchopneumonia. Developed - │ │ │ │ │streptococcus empyema. Died - │ │ │ │ │Oct. 11 - ────┴─────────┴─────────┴─────┴────────────┴─────────────────────────── - - ════╤══════════════════════════════════════════════════════════════════ - CASE│ NECROPSY - │ - ────┼─────────────────────────────────┬──────────────────────────────── - │ DIAGNOSIS │ BACTERIOLOGY - ────┼─────────────────────────────────┼──────────────────────────────── - 70│Nodular and diffuse confluent │H.B. sterile - │lobular pneumonia. Purulent │Br. B. inf. ++++ - │bronchitis. Bronchiectasis │Pn. IV ++ - │ │Lun. B.inf. +++ - │ │Pn. IV +++ - ────┼─────────────────────────────────┼──────────────────────────────── - 59│Lobular pneumonia, with clustered│H.B. sterile - │abscesses. Bronchiectasis │Br. B.inf. +++ - │ │Staph. ++ - │ │R.L. no growth. - ────┼─────────────────────────────────┼──────────────────────────────── - 50│Nodular and confluent lobular │H.B. sterile - │pneumonia. Purulent bronchitis │Br. B.inf. +++ - │ │Staph + - │ │R.L. Pn. II +++ - │ │B.inf. + - │ │L.U. Pn. II +++ - ────┼─────────────────────────────────┼──────────────────────────────── - 56│Confluent lobular pneumonia │H.B. Pn. II - │ │Br. Pn. II +++ - │ │B.inf. ++ - │ │L.L. Pn. II +++ - │ │B.inf. + - ────┼─────────────────────────────────┼──────────────────────────────── - 107│Confluent lobular pneumonia with │H.B. sterile - │clustered abscesses. Pur. │R.L. Pn. III ++ - │bronchitis and bronchiectasis │Staph. ++ - │ │L.L. Staph. ++ - ────┼─────────────────────────────────┼──────────────────────────────── - 92│Lobular pneumonia. Empyema. │H.B. S.hem. - │Purulent bronchitis │Br. B.inf. +++ - │ │S.hem. +++ - │ │R.L. S.hem. +++ - │ │B.inf. ++ Emp. S.hem. - ────┼─────────────────────────────────┼──────────────────────────────── - 99│Bronchopneumonia. Purulent │H.B. S.hem. - │bronchitis │Br. B.inf. +++ Lun. S.hem. +++ - │ │S.hem. ++ B. inf. + - ────┼─────────────────────────────────┼──────────────────────────────── - 102│Lobular pneumonia with │H.B. S.hem. - │interstitial suppuration. Pur. │Br. B.inf. +++ - │bronchitis. Empyema │S.hem. +++ - │ │R.L. S.hem. +++ - ────┼─────────────────────────────────┼──────────────────────────────── - 104│Nodular bronchopneumonia with │H.B. S.hem. - │interstitial suppuration. Pur. │R.L. S.hem. ++++ - │bronchitis and bronchiectasis. │Emp S.hem. - │Empyema. │ - │ │ - ────┴─────────────────────────────────┴──────────────────────────────── - -The cases cited in the preceding paragraph are illustrative examples -from a series of over 250 necropsies which are described in another -section of this report. They serve to indicate clearly the extent to -which mixed and superimposed infections of the lungs may occur in -pneumonia following influenza and leave little doubt that a considerable -proportion of the deaths from influenzal pneumonia are due to this -circumstance. - - - Hemolytic Streptococcus Pneumonia Following Influenza - -But 4 cases of hemolytic streptococcus pneumonia directly following -influenza without an intervening pneumococcus infection of the lungs -occurred in the group of cases studied clinically. Superimposed -infection with S. hemolyticus, however, occurred not infrequently during -the course of pneumococcus pneumonia following influenza, as has been -stated above. This occurred 3 times in lobar pneumonia and 10 times in -bronchopneumonia, with fatal outcome in all but 1 case. - -=Bacteriology.=—Bacteriologic examination of the sputum in the 4 cases -of streptococcus pneumonia directly following influenza showed S. -hemolyticus present in abundance. B. influenzæ was also present in large -numbers in 3 cases, but was not found in the fourth. In 1 case a -Gram-negative micrococcus resembling M. catarrhalis was also present in -large numbers in the sputum. Pneumococci were not found either by direct -culture on blood agar plates or by inoculation of the sputum -intraperitoneally in white mice. - -In the 13 cases of superimposed hemolytic streptococcus infection -occurring during the course of pneumococcus pneumonia, bacteriologic -examination of the sputum by direct culture and by mouse inoculation -shortly after onset of the pneumonia showed Pneumococci (atypical II -once, Type III once, Group IV eleven times) B. influenzæ present in -large numbers, and no hemolytic streptococci except in 4 instances in -which a very few organisms were present. Subsequent invasion of the -lower respiratory tract by S. hemolyticus was shown to occur by means of -cultures of empyema fluids or by cultures made at necropsy. - -=Clinical Features.=—The 4 cases of hemolytic streptococcus pneumonia -following influenza that occurred in this series resembled in all -respects the secondary streptococcus pneumonias of the winter and spring -of 1918 and presented no features requiring special comment. The onset -resembled that of pneumococcus bronchopneumonia, the disease appearing -to develop as a continuation of the preceding influenza. The sputum was -profuse and mucopurulent in 3 cases, mucoid and bloody in the other. Two -cases ran a severe and rapid course with the development of empyema -early in the disease and fatal outcome. The other 2 cases ran only -moderately severe courses without developing empyema and recovered by -lysis in twenty and fifteen days, respectively, after the onset of -influenza. Clinical differentiation between streptococcus and -pneumococcus bronchopneumonia following influenza did not seem possible -without bacteriologic examination of the sputum except in those cases of -the streptococcus group which developed an extensive pleural effusion -early in the disease. - -The advent of superimposed hemolytic streptococcus infection of the -lower respiratory tract during the course of pneumococcus pneumonia -following influenza presented no clinical features that made diagnosis -certain without bacteriologic examination. The sudden occurrence of a -pleural exudate during the course of the disease seemed of particular -significance, especially since empyema in the bronchopneumonias -following influenza was exceedingly rare in the absence of hemolytic -streptococcus infection. Other suggestive symptoms were a chill during -the course of the disease, a sudden turn for the worse in cases -apparently doing well, or the development of a cherry red cyanosis. None -of these features, however, was sufficiently constant or distinctive of -streptococcus invasion to be depended upon and when they occurred, were -merely indications for further bacteriologic examination. - - - Bacillus Influenzæ Pneumonia Following Influenza - -Bacteriologic evidence that cases of pneumonia following influenza might -be due to B. influenzæ alone was very meager in the group of cases -studied clinically at Camp Pike; in fact, no convincing evidence was -obtained that such cases occurred. In one case B. influenzæ alone was -found in the sputum coughed from the deeper air passages, and in another -case B. influenzæ with a few colonies of S. viridans was found. Both -were cases of bronchopneumonia, mild in character, and recovered -promptly. They presented no clinical features by which they could be -distinguished from cases of pneumococcus bronchopneumonia. - -It has been previously stated that B. influenzæ was found in all early -uncomplicated cases of influenza somewhere in the respiratory tract; -that it was present together with other organisms, notably pneumococcus -in the sputum from cases of purulent bronchitis following influenza; and -that it was found in the sputum coughed from the lung in approximately -80 per cent of cases of pneumonia complicating influenza. In 35 cases it -was very abundant, often being the predominating organism. In all these -cases, however, pneumococci or hemolytic streptococci were also present -in considerable numbers at the time of onset of the pneumonia. It is -impossible to say merely from the clinical and bacteriologic data under -consideration what part B. influenzæ played in the development of the -actual pneumonia in these cases. Discussion of this subject is therefore -reserved for the section of this report dealing with the pathology and -bacteriology of pneumonia following influenza. - - - Summary - -Influenza as observed at Camp Pike presented itself as a highly -contagious infectious disease, the principal clinical manifestations of -which were, sudden onset with high fever, profound prostration with -severe aching pains in the head, back and extremities, erythema of the -face, neck and upper chest with injection of the conjunctivæ, and a -rapidly progressive attack upon the mucous membranes of the respiratory -tract as evidenced by coryza, pharyngitis, tracheitis and bronchitis -with their accompanying symptoms. In the majority of cases it ran a -short self-limited course, rarely of more than four days’ duration, and -was never fatal in the absence of a complicating pneumonia. - -Bacteriologic examination in early uncomplicated cases of the disease -showed the B. influenzæ of Pfeiffer to be present in all cases, often in -predominating numbers. It was found more abundantly present during the -acute stage of the disease than during convalescence in uncomplicated -cases. No other organisms of significance were encountered by the -methods employed. - -Purulent bronchitis of varying extent developed in approximately 35 per -cent of the cases and often prolonged the course of the illness to a -considerable extent. Bacteriologic studies showed that it was invariably -associated with a mixed infection of the bronchi with B. influenzæ and -other bacteria, in most instances the pneumococcus, and indicated that -it should be regarded as a complication rather than as an essential part -of influenza. Its clinical features consisted of a mild febrile -reaction, frequent cough with the raising of considerable amounts of -purulent sputum, and the physical signs of a more or less diffuse -bronchitis. It led to a varying degree of bronchiectasis in at least -some instances. - -Pneumonia complicating influenza presented a very diversified picture -and appeared to have only one constant character, namely, that influenza -was the predisposing cause. It may be best classified on an etiologic -basis since the clinical features to some extent and the pathology to a -much greater extent depended upon the infecting bacteria in a given -case. - -Bacteriologic examination showed that a very large proportion of the -cases was due to infection with the different immunologic types of -pneumococci or to a mixed infection with B. influenzæ and pneumococci. -The types of pneumococci commonly found in normal mouths, namely, II -atypical, III, and IV, comprised approximately 88 per cent of these, the -highly parasitic Pneumococci Types I and II, but 12 per cent. A small -number of cases were due to hemolytic streptococci or to mixed infection -with B. influenzæ and S. hemolyticus. No certain evidence was obtained -that pneumonia was due to B. influenzæ alone. This organism was present -in varying numbers, however, in approximately 80 per cent of the sputums -examined, and it seems fairly certain that it must have played at least -a part in the development of the pneumonia in many of the cases in which -it was found. Superimposed infections with other types of pneumococci -than those primarily responsible for the development of pneumonia, with -hemolytic streptococci and with Staphylococcus aureus occurred -frequently in cases of pneumococcus or mixed pneumococcus and B. -influenzæ pneumonia and undoubtedly contributed to a considerable extent -in increasing the number of deaths. - -Three clinical types of pneumococcus pneumonia following influenza -occurred: lobar pneumonia, lobar pneumonia with purulent bronchitis, and -bronchopneumonia. Lobar pneumonia was usually sudden in onset and ran -the characteristic course of the primary disease. Lobar pneumonia with -purulent bronchitis similarly ran the characteristic course of the -primary disease but presented the unusual picture of lobar pneumonia -with mucopurulent rather than rusty, tenacious sputum and numerous moist -râles throughout the unconsolidated portions of the lungs. The cases of -bronchopneumonia ran a very variable course from mild cases of a few -days’ duration and meager signs of consolidation to rapidly progressive -cases with signs of extensive pulmonary involvement. Purulent bronchitis -was very frequently associated with bronchopneumonia. - -Hemolytic streptococcus pneumonia following influenza presented the -clinical picture of bronchopneumonia and was not readily distinguished -on clinical grounds from pneumococcus bronchopneumonia except in those -cases which developed a pleural exudate early in the disease. The advent -of tertiary infection of the lower respiratory tract with hemolytic -streptococci in cases of secondary pneumococcus pneumonia presented no -symptoms sufficiently constant or certain to make clinical diagnosis -easy. The development of empyema in pneumococcus bronchopneumonia -usually meant streptococcus infection. - -Pure B. influenzæ pneumonia, if such cases existed, presented no -diagnostic features by which it could be distinguished from pneumococcus -bronchopneumonia following influenza. It was impossible to determine on -clinical and bacteriologic grounds alone what part the prevalent -influenza bacilli played in the causation of the actual pneumonia. - - - Discussion - -That wide variations in the conception of influenza have arisen during -the recent pandemic, even a hasty review of the literature makes clear. -In its essence this divergence of opinion seems to depend upon whether -pneumonia is considered an essential part of influenza or a complication -due either to the primary cause of influenza or to secondary infection. -One extreme is expressed by Dunn[30] who says “the so-called -complication is the disease,” the other by Fantus[31] who finds -influenza a relatively mild disease with pneumonia a relatively -infrequent and largely preventable complication. - -A similar divergence of opinion prevails with respect to the -bacteriology of influenza. There is fairly general agreement that the -members of the pneumococcus and streptococcus groups and to a less -extent other organisms are responsible for a large proportion of the -secondary pneumonias, and but few observers hold that they possess any -etiologic relationship to influenza. No such uniformity of opinion -exists, however, with respect to the relation of B. influenzæ to -influenza and to the complicating pneumonia. By some it is considered -the primary cause of influenza, by others it is regarded as a secondary -invader responsible for a certain proportion of the secondary -pneumonias, and by still others it is not considered to bear any -relation either to influenza or its complications. - -A limited number of references to the extensive literature of the recent -pandemic will amply serve to illustrate the various points of view that -have developed. - -Keegan[32] regards pneumonia as a complication and considers that B. -influenzæ, the probable cause of influenza, is the primary cause of the -pneumonia which may or may not be still further complicated by -pneumococcus or streptococcus infection as a terminal event. -Christian[33] states that epidemic influenza causes a clinically -demonstrable bronchitis and bronchopneumonia in the larger proportion of -cases, and lays particular emphasis upon the fact that it is quite -incorrect to consider fatalities in the epidemic as due to influenza -uncomplicated by bronchopneumonia. Blanton and Irons[34] speak of -influenza as an “antecedent respiratory infection” of undetermined -etiology, and believe that pneumonia when it occurs is due to autogenous -infection by a variety of secondary invaders, principally of the -pneumococcus and streptococcus groups. Hall, Stone, and Simpson[35] -regard pneumonia strictly as a complication and quite distinct from -influenza itself. Synnott and Clark[36] believe that the infection is -characterized by a progressive intense exudative inflammation of the -respiratory tract often terminating in an aspiration pneumonia with a -variety of conditions found at autopsy and a multiplicity of secondary -organisms responsible for the fatal termination. B. influenzæ was -usually found but always with other organisms. Friedlander and his -collaborators[37] speak of a fulminating fatal type of influenza with -acute inflammatory pulmonary edema, but regard true bronchopneumonia as -secondary, due to infection with pneumococcus or S. hemolyticus. B. -influenzæ was not found more frequently than under normal conditions. -Brem[38] and his collaborators present a clear cut clinical picture both -of influenza and the secondary pneumonia to which it predisposes, -regarding the latter as definitely due to secondary infection with -pneumococcus, streptococcus or B. influenzæ, the virus of influenza -being unknown. Ely[39] and his collaborators make no distinction between -influenza and pneumonia, and apparently consider the epidemic due to a -hemolytic streptococcus of indefinite and inconstant characters. The -Camp Lewis Pneumonia Unit[40] states “the process [influenza], whether -mild or severe, is etiologically and pathologically the same; * * *.” B. -influenzæ was not found. In a report of The American Public Health -Association[41] it is stated that deaths resulting from influenza are -commonly due to pneumonias resulting from an invasion of the lungs by -one or more forms of streptococci, by one or more forms of pneumococci, -or by the so-called influenza bacillus. This invasion is apparently -secondary to the initial attack. Wolbach[42] found B. influenzæ in a -high proportion of cases, not infrequently in pure culture in the lung, -and believes that there is a true influenzal pneumonia whether B. -influenzæ is the cause of the primary disease or not. Spooner, Scott and -Heath[43] isolated B. influenzæ in a high percentage of cases and -consider it reasonable to suppose that it was the prime factor in the -epidemic. Kinsella[44] found B. influenzæ infrequently and regards it as -a secondary invader. MacCallum[45] regards B. influenzæ as a secondary -invader and believes that it is responsible for a form of purulent -bronchitis and bronchopneumonia following certain cases of influenza. -Pritchett and Stillman[46] found B. influenzæ in 93 per cent of cases of -influenza and bronchopneumonia. Hirsch and McKinney[47] state that B. -influenzæ played no rôle in the epidemic at Camp Grant and apparently -consider it due to a specially virulent pneumococcus. - -No further references to the extensive literature of the recent pandemic -seem necessary, since those cited above serve to illustrate the various -points of view that exist. A similar diversity of opinion may be found -in the reports from foreign sources. - -It would appear that much of the divergence of opinion that has been -formed has depended to a considerable extent upon the conditions under -which cases have been observed. This is clearly brought out by -contrasting the experience of Fantus[39] dealing with private cases in -civilian practice, where pneumonia was relatively uncommon, with that of -others dealing only with cases in large hospitals, where those admitted -have been in large part selected seriously ill patients with a high -incidence of pneumonia, the milder cases comprising from 60 to 90 per -cent of those attacked by influenza never reaching the hospital. -Variations in opinion with respect to the bacteriology of the epidemic, -especially in regard to B. influenzæ, would appear to be due for the -most part to differences in bacteriologic technic, in some degree to -differences in interpretation. Accumulating evidence can leave little -doubt that B. influenzæ was at least extraordinarily and universally -prevalent throughout the period of the epidemic and thereafter, and that -earlier reports of failure to find it were due to the use of methods -unsuitable for its detection and isolation. - -The opportunity afforded the commission at Camp Pike to devote their -full time to a systematic and correlated group study of the epidemic -simultaneously from many aspects throughout its whole course made it -apparent that influenza _per se_ is in the large majority of instances, -in spite of the initial picture of profound prostration, a relatively -mild disease which tends to rapid spontaneous recovery. This opinion is -supported by the fact that the disease during the first waves of the -epidemic in this country, which it is now recognized occurred pretty -generally in the army camps during the spring of 1918, was so mild that -it attracted only passing attention, since the disease at that time was -not sufficiently virulent to predispose to any alarming amount of -pneumonia. With the return of the epidemic in the late summer and early -fall, however, the disease had attained such a high degree of virulence -that it predisposed to an appalling amount of severe and often rapidly -fatal pneumonia, which often detracted attention from the real nature of -the preceding disease. Yet even during the fall epidemic from 60 to 90 -per cent of the cases of influenza proceeded to rapid recovery without -developing complications. On this ground alone it would seem only -logical to regard pneumonia strictly as a complication of influenza -rather than as an essential part of the disease, irrespective of whether -the pneumonia may be caused by the primary cause of influenza or not. -The complexity of the clinical features, the bacteriology and pathology -of the pneumonias following influenza lend further support to this -opinion. - -It seems better, therefore, to consider influenza first as a disease by -itself and subsequently to take up the question of pneumonia and the -relation of influenza to it. - -The most striking clinical features of influenza are its epidemic -character, its involvement of the respiratory tract, its extremely -prostrating effect, and the often surprising rapidity with which the -individual cures himself. These features strongly suggest that the -etiologic agent of the disease is an organism subject to rapid changes -in virulence; that it is confined to the respiratory tract where it -produces a superficial inflammatory reaction giving rise to the -characteristic symptoms of coryza, pharyngitis and tracheitis; that it -elaborates a poison, possibly a true toxin, readily absorbed by the -lymphatics, the effect of which is manifested in the profound -prostration, severe aching pains, erythema, and leucopenia; and that it -may either disappear promptly from the respiratory mucous membrane at -time of recovery or may persist, leading a relatively saprophytic -existence for an indefinite period of time, being no longer harmful to -the individual, at least more than locally, because of an acquired -immunity. Furthermore, in our opinion, the very brief incubation period -suggests that the disease is bacterial in origin, rather than that it is -analogous to the exanthemata, the majority of which present a -comparatively long, fairly constant, incubation period. - -B. influenzæ has characteristics in accord with the clinical features of -influenza. It is an organism of very labile virulence; it is always -present in our experience on the mucous membranes of the respiratory -tract in early uncomplicated cases of influenza, often in overwhelming -numbers; in only very exceptional instances, in adults at least, does it -invade the body producing a general infection, as the numerous reports -of negative blood cultures testify; recent investigations by Parker[48] -and others indicate that it is capable of producing a toxin quickly -fatal for rabbits; it is predominantly present in the respiratory tract -during the active stage of the disease and disappears in a considerable -proportion of cases at time of recovery, while in others, more -particularly those that develop an extensive secondary bronchitis and -bronchiectasis it may persist for an indefinite period of time. - -It is, of course, fully appreciated that the foregoing is in the main -merely argumentative reasoning and it is put forth only to suggest that -B. influenzæ merits a much closer scrutiny with respect to its etiologic -relationship to influenza than the trend of present opinion has awarded -it. - -Although there remains some difference of opinion as to the relation of -influenza to pneumonia, the majority of observers concur in regarding -pneumonia as a complication and this would seem to be the only logical -interpretation of the facts available. The same may be said with respect -to purulent bronchitis and bronchiectasis. It is of considerable -significance in this connection that pneumonia following influenza -presents no uniform clinical picture, no uniform bacteriology and no -uniform pathology. Whether the predisposition of patients with influenza -to contract pneumonia is preponderantly due to lowering of general -resistance to infection by the extremely prostrating effect of the -disease and the inhibition of leucocytic defense, or to a destruction of -local resistance against bacterial invasion by reason of profound injury -to the bronchial mucosa, or to a combination of both factors, is -difficult to say. It seems most probable that both are concerned. At any -rate it seems clear that in the presence of influenza a considerable -variety of organisms which under ordinary conditions do not find -lodgement in the lungs are able to gain access to the lower respiratory -tract and produce pneumonia. - - - - - CHAPTER III - SECONDARY INFECTION IN THE WARD TREATMENT OF INFLUENZA AND PNEUMONIA - - EUGENE L. OPIE, M.D.; FRANCIS G. BLAKE, M.D.; JAMES C. SMALL, M.D.; AND - THOMAS M. RIVERS, M.D. - - -One of the most pressing problems that presented itself in the care of -influenza and pneumonia patients in the army cantonments during the -recent epidemic was the danger of secondary contact infection because of -the overcrowding of the base hospitals, nearly all of which were taxed -far beyond the limits of their capacity. That this danger was very real -was fully demonstrated by certain studies in ward infection that this -commission was able to make at Camp Pike[49]. It is the purpose of the -present section of the report to present these studies and to discuss -the means whereby this danger may be most successfully met. - -It is perhaps well, first to define exactly what is meant by secondary -contact infection in influenza and pneumonia. In our experience at Camp -Pike it was found that a very large percentage of the pneumonias -following influenza were accompanied by secondary infection with -pneumococcus, some few being caused by hemolytic streptococcus. The -types of pneumococcus encountered were almost entirely those that are -found normally in the mouths of healthy men, approximately 85 per cent -being Types II atypical, III, and IV. It has been generally accepted -that infection with these types of pneumococci is usually -autogenous—that is, that under the proper conditions of lowered -resistance an individual becomes infected with the pneumococcus that he -carries in his own mouth. Many observations made during the course of -the present work have suggested that this is probably not so in many -instances and that the influenza patient may not be so much in danger -from the pneumococcus that he normally carries in his own mouth as he is -from that carried by his neighbor, in other words, he is in danger from -contact infection. The same considerations hold true with respect to -hemolytic streptococcus infection. Secondary contact infection in cases -of already existing pneumonia following influenza were found to occur -frequently. These were for the most part caused by hemolytic -streptococcus infection superimposed upon a pneumococcus pneumonia. Many -instances of double pneumococcus infection, however, either coincident -with or following one another were encountered. - - - Secondary Infection with S. Hemolyticus in Pneumonia - -Pneumonia caused by streptococci was repeatedly observed[50] during the -pandemic of influenza which occurred in 1889–90. With clearer -recognition of the characters which distinguish varieties of -streptococci several observers have shown that secondary infection with -hemolytic streptococci may occur during the course of pneumonia and -though definite evidence has been lacking have suggested that it may be -acquired within hospital wards. That a similar secondary infection with -S. hemolyticus in pneumococcus pneumonias following influenza occurred -not infrequently at Camp Pike during the epidemic was shown by -bacteriologic studies made during life and at autopsy in a considerable -series of cases. During the early days of the epidemic of influenza, -secondary streptococcus infection was almost entirely limited to certain -wards which were opened for the care of the rapidly increasing number of -patients with pneumonia. During this period these wards were -overcrowded, organization was incomplete, and the opportunities for -transfer of infection from patient to patient were almost unlimited. The -spread of streptococcus contagion and its fatal effect may be clearly -brought out by comparison of these wards with wards that had long been -organized for the care of patients with pneumonia. - -Ward 3 had been in use for the care of patients with pneumonia for some -time prior to the outbreak of influenza. It was provided with sheet -cubicles and conducted by medical officers, nurses and enlisted men -accustomed to the care of patients with pneumonia, ordinary precautions -being taken against transfer of infection from one patient to another. -The data in Table XVII show the average number of patients in the ward, -the number of new cases of pneumonia admitted, and the number of deaths -among patients admitted during the corresponding period, for three -periods of ten days each from September 6 to October 5. The types of -infection in fatal cases as determined by cultures taken at autopsy are -also shown. - - TABLE XVII - - PNEUMONIA IN WARD 3 - - ═════╤════════╤════════╤═════════════╤═════════════════════════════════════ - │AVERAGE │ NUMBER │TOTAL DEATHS │ CULTURES AT AUTOPSY - │ NUMBER │ OF │ AMONG │ - │ OF │PATIENTS│ PATIENTS │ - │PATIENTS│ADMITTED│ ADMITTED │ - │IN WARD │ │ DURING THE │ - │ │ │CORRESPONDING│ - │ │ │ PERIOD │ - ─────┼────────┼────────┼──────┬──────┼────────────┬───────────┬──────────── - „ │ „ │ „ │NUMBER│ PER│PNEUMOCOCCUS│ S.│UNDETERMINED - │ │ │ │ CENT│ │HEMOLYTICUS│(NO AUTOPSY) - ─────┼────────┼────────┼──────┼──────┼────────────┼───────────┼──────────── - Sept.│ 18.6│ 11│ 3│ 27.2│ 3│ 0│ 0 - 6–15 │ │ │ │ │ │ │ - Sept.│ 46.1│ 52│ 16│ 30.7│ 13│ 1│ 2 - 16–25│ │ │ │ │ │ │ - Sept.│ 58.6│ 23│ 8│ 34.7│ 5│ 1│ 2 - 26–Oct.│ │ │ │ │ │ │ - 5 │ │ │ │ │ │ │ - ─────┴────────┴────────┴──────┴──────┴────────────┴───────────┴──────────── - -During the period from September 6 to 15, just prior to the outbreak of -influenza in epidemic proportions, the ward had an average population of -18.6 patients. The total number of new patients admitted was 11, of whom -3 died, a mortality of 27.2 per cent. All these cases were pneumococcus -pneumonias as determined by bacteriologic examination of the sputum at -time of admission. The 3 fatal cases showed pneumococcus infection at -autopsy. During the second period, from September 16 to 25, with the -outbreak of the epidemic of influenza, the ward rapidly filled with new -cases of pneumonia, attaining an average population of 46.1 patients. Of -the 52 new cases admitted 16 died, a mortality of 30.7 per cent. Again -all the cases admitted during this period in which bacteriologic -examination of the sputum was made, were found to be pneumococcus -pneumonias with one exception. This case, admitted on September 21 and -dying two days later, had a hemolytic streptococcus pneumonia. -Fortunately, though quite by accident, he was placed in a bed at one end -of the porch and no transmission of streptococcus infection to other -cases in the ward took place. At autopsy 13 cases showed pneumococcus -infection; the foregoing case, hemolytic streptococcus. During the third -period from September 26 to October 5 the ward became even more crowded, -having an average of 58.6 patients; 23 new cases were admitted, 8 of -whom died, a mortality of 34.7 per cent. Autopsy showed that 5 of these -were pneumococcus pneumonias and 1 was caused by hemolytic streptococcus -infection. It is noteworthy that the death rate from pneumonia gradually -increased as the ward became more and more crowded. This may possibly be -attributed in part to the increasing severity of the pneumonia during -the early days of the influenza epidemic. That it was in part directly -due to secondary contact infection with pneumococcus will be shown when -the transmission of pneumococcus infection is discussed. In spite of the -overcrowding of the ward the introduction of 2 cases of streptococcus -pneumonia did not cause an outbreak of streptococcus infection. Whether -this was due to precautions taken against the transfer of infection or -was merely a matter of good luck is difficult to say, in view of the -fact that a considerable amount of transfer of pneumococcus infection -from one patient to another did occur. - -Ward 8 had long been used for the care of colored patients with -pneumonia. As in Ward 3 cubicles were in use and ordinary precautions -against the transfer of infection were used. The data are presented in -Table XVIII. - - TABLE XVIII - - PNEUMONIA IN WARD 8 - - ═══════╤════════╤════════╤═════════════╤═════════════════════════════════════ - │AVERAGE │ NUMBER │TOTAL DEATHS │ CULTURES AT AUTOPSY - │ NUMBER │ OF │ AMONG │ - │ OF │PATIENTS│ PATIENTS │ - │PATIENTS│ADMITTED│ ADMITTED │ - │IN WARD │ │ DURING THE │ - │ │ │CORRESPONDING│ - │ │ │ PERIOD │ - ───────┼────────┼────────┼──────┬──────┼────────────┬───────────┬──────────── - „ │ „ │ „ │NUMBER│ PER │PNEUMOCOCCUS│ S. │UNDETERMINED - │ │ │ │ CENT │ │HEMOLYTICUS│(NO AUTOPSY) - ───────┼────────┼────────┼──────┼──────┼────────────┼───────────┼──────────── - Sept. │ │ │ │ │ │ │ - 6–20 │ 25.5│ 18│ 2│ 11.1│ 2│ 0│ 0 - Sept. │ 46.1│ 59│ 20│ 33.9│ 10│ 1│ 9 - 21–Oct.│ │ │ │ │ │ │ - 5 │ │ │ │ │ │ │ - ───────┴────────┴────────┴──────┴──────┴────────────┴───────────┴──────────── - -During the period from September 6 to 20, prior to the outbreak of -influenza in epidemic proportions among the colored troops, the ward had -an average population of 25.5 patients; 18 new cases of pneumonia were -admitted during this period, all of whom were pneumococcus pneumonias as -determined by bacteriologic examination of the sputum at time of -admission to the ward. Only 2 died, a mortality of 11.1 per cent, -autopsy cultures showing pneumococcus in both cases. All these patients -were treated on the porch of the ward while they were acutely sick. -During the second period from September 21 to October 5, when the -influenza epidemic was at its height, the ward rapidly filled with -active cases of pneumonia and became distinctly crowded. It contained an -average of 46.1 patients, but had actually reached a population of 64 -patients at the end of the period. Of the 59 new cases admitted, 20 -died, a mortality of 33.9 per cent, 10 with pneumococcus pneumonia, one -with hemolytic streptococcus pneumonia. In 9 there was no autopsy. The -conditions in Ward 8 were quite analogous to those in Ward 3. In spite -of the overcrowding during the second period no outbreak of secondary -infection with S. hemolyticus occurred, but secondary pneumococcus -infection did occur as will be shown below. - -In contrast with these two wards are Wards 1 and 2 in which widespread -secondary contact infection with S. hemolyticus took place. Ward 2 was -opened September 26, at the beginning of the period when 20 new wards -for pneumonia were organized. From September 26 to October 1 the cubicle -system was not in use, the ward was crowded, organization was imperfect, -and few precautions were taken to prevent transfer of infection from one -patient to another. On October 2 the cubicle system was installed and -precautions against transfer of infection were instituted. The data are -shown in Table XIX. - - TABLE XIX - - PNEUMONIA IN WARD 2 - - ═════╤════════╤═════════╤═════════════╤═════════════════════════════════════ - │ │ │TOTAL DEATHS │ - │AVERAGE │ │ AMONG │ - │ NUMBER │NUMBER OF│ PATIENTS │ - │ OF │PATIENTS │ ADMITTED │ CULTURES AT AUTOPSY - │PATIENTS│ADMITTED │ DURING THE │ - │IN WARD │ │CORRESPONDING│ - │ │ │ PERIOD │ - ─────┼────────┼─────────┼──────┬──────┼────────────┬───────────┬──────────── - „ │ „ │ „ „ │NUMBER│ PER │PNEUMOCOCCUS│ S. │UNDETERMINED - │ │ │ │ CENT │ │HEMOLYTICUS│(NO AUTOPSY) - ─────┼────────┼─────────┼──────┼──────┼────────────┼───────────┼──────────── - Sept.│ 10│ 10 40│ 27│ 67.5│ 0│ 23│ 4 - 26 │ │ │ │ │ │ │ - Sept.│ 27│ 17 „ │ „ │ „ │ „ │ „ │ „ - 27 │ │ │ │ │ │ │ - Sept.│ 40│ 13 „ │ „ │ „ │ „ │ „ │ „ - 28 │ │ │ │ │ │ │ - ─────┼────────┼─────────┼──────┼──────┼────────────┼───────────┼──────────── - Sept.│ 51│ 12 17│ 6│ 35.3│ 2│ 2│ 2 - 29 │ │ │ │ │ │ │ - Sept.│ 49│ 1 „ │ „ │ „ │ „ │ „ │ „ - 30 │ │ │ │ │ │ │ - Oct. │ 43│ 4 „ │ „ │ „ │ „ │ „ │ „ - 1 │ │ │ │ │ │ │ - ─────┼────────┼─────────┼──────┼──────┼────────────┼───────────┼──────────── - Oct. │ 47│ 6 10│ 4│ 40.0│ 2│ 1│ 1 - 2 │ │ │ │ │ │ │ - Oct. │ 42│ 0 „ │ „ │ „ │ „ │ „ │ „ - 3 │ │ │ │ │ │ │ - Oct. │ 41│ 4 „ │ „ │ „ │ „ │ „ │ „ - 4 │ │ │ │ │ │ │ - ─────┴────────┴─────────┴──────┴──────┴────────────┴───────────┴──────────── - -During the first three days 40 patients with pneumonia were admitted to -the ward. Of these 40 patients, 27 died, a mortality of 67.5 per cent. -Cultures at autopsy showed that 23 of these died with hemolytic -streptococcus infection, none of pneumococcus infection. In four there -was no autopsy. To appreciate the full significance of these figures it -must be emphasized that these patients at time of admission to the ward -in no way differed from those admitted to Ward 3 during the -corresponding period and were not in any sense selected cases. The type -of infection in 9 of these patients had been determined by bacteriologic -examination of the sputum just prior to or immediately after admission -to the ward before opportunity for secondary contact infection in this -ward had occurred. All 9 were shown to have pneumococcus pneumonia free -from hemolytic streptococci at that time. All 9 died, 7 with secondary -streptococcus infection as shown by cultures taken at autopsy, 1 with a -secondarily acquired Pneumococcus Type III infection—sputum showed a -Pneumococcus Type IV on admission—and in 1 there was no autopsy. In view -of the fact that bacteriologic examination of the sputum in cases of -pneumonia following influenza had shown that the large majority of them -were due to pneumococcus infection, it is probable that most of the -other cases of pneumonia admitted to this ward were pneumococcus -pneumonias at time of admission, and that they acquired the -streptococcus infection after admission. - -During the next three days 17 new patients were admitted, of whom 6 -died, a mortality of 35.3 per cent. Cultures at autopsy showed -pneumococcus infection in 2, streptococcus in 2. It is noteworthy that -the porch was first put into use on September 29. Of the 12 patients -admitted on this date, 8 were treated throughout the acute stage of -their illness on the porch. Of these 8 patients but one died, of a -Pneumococcus Type IV infection and none became infected with S. -hemolyticus. From October 4 to October 6, 10 patients were admitted, of -whom 4 died. Cultures at autopsy showed pneumococcus infection in 2, -hemolytic streptococcus in 1. - -The widespread prevalence of hemolytic streptococcus infection in this -ward as compared with its almost entire absence in Wards 3 and 8 is very -striking. Cultures made during life and at autopsy have shewn clearly -that it was due to rapid spread of contagion throughout the ward. The -almost unlimited opportunities for transfer of infection from patient to -patient, during the first six days the ward was in use, undoubtedly -greatly facilitated this spread. From the data available it is -impossible to state exactly when and by which patients hemolytic -streptococcus infection was introduced into the ward, but it must have -been very early since the death rate was very high from the beginning, -and the first 23 cases coming to autopsy died with streptococcus -infection. - -Ward 1 was opened on September 24. From that date until October 2 no -cubicles were in use and few precautions were taken against transfer of -infection. On October 2 cubicles were installed and ordinary precautions -to prevent transfer of infection were instituted. On October 6 the ward -was closed to further admissions. The data presented in Table XX are -divided into two periods, because on September 29 and 30, 4 patients -with streptococcus pneumonia were admitted to the ward. - - TABLE XX - - PNEUMONIA IN WARD 1 - - ═══════╤════════╤════════╤═════════════╤═════════════════════════════════════ - │AVERAGE │ NUMBER │TOTAL DEATHS │ CULTURES AT AUTOPSY - │ NUMBER │ OF │ AMONG │ - │ OF │PATIENTS│ PATIENTS │ - │PATIENTS│ADMITTED│ ADMITTED │ - │IN WARD │ │ DURING THE │ - │ │ │CORRESPONDING│ - │ │ │ PERIOD │ - ───────┼────────┼────────┼──────┬──────┼────────────┬───────────┬──────────── - „ │ „ │ „ │NUMBER│ PER │PNEUMOCOCCUS│ S. │UNDETERMINED - │ │ │ │ CENT │ │HEMOLYTICUS│(NO AUTOPSY) - ───────┼────────┼────────┼──────┼──────┼────────────┼───────────┼──────────── - Sept. │ 35.8│ 34│ 11│ 32.3│ 5│ 3│ 3 - 24–29 │ │ │ │ │ │ │ - Sept. │ 55.3│ 40│ 24│ 60.0│ 6│ 14│ 4 - 30–Oct.│ │ │ │ │ │ │ - 5 │ │ │ │ │ │ │ - ───────┴────────┴────────┴──────┴──────┴────────────┴───────────┴──────────── - -During the first period from September 24 to 29 the ward contained an -average of 35.8 patients, being only moderately crowded; 34 cases of -pneumonia were admitted, of whom 11 died, a mortality of 32.3 per cent. -It is noteworthy that deaths among this group which occurred prior to -September 30 were due to pneumococcus infection with one exception, a -patient entering the ward on September 26 and dying the following day. -Of the other 2 patients in this group who died with hemolytic -streptococcus pneumonia, 1 was admitted to the ward on September 25, was -shown to be free from S. hemolyticus on September 30, and died on -October 12 with a secondarily acquired streptococcus pneumonia and -empyema; the other was admitted on September 29 with streptococcus -pneumonia and died the following day. - -During the second period from September 30 to October 5 the ward -contained an average of 55.3 patients, being very overcrowded; 40 new -cases of pneumonia were admitted of whom 24 died, a mortality of 60 per -cent. Cultures taken at autopsy showed that 6 died of pneumococcus -pneumonia, 14 with hemolytic streptococcus infection. As in Ward 2, -patients admitted to this ward were in no way selected and were -probably, as experience has shown, in large part pneumococcus pneumonias -at time of admission. The widespread dissemination of hemolytic -streptococcus and its fatal effect following the introduction of the -organism on September 29 and 30 is only too evident. - - TABLE XXI - - SECONDARY INFECTION WITH PNEUMOCOCCUS TYPE II - - ═════════════╤═════════╤═════════╤══════════════╤══════════════════════ - NAME │ BED │ADMITTED │PNEUMOCOCCUSIN│ SECONDARY INFECTION - │OCCUPIED │ │ SPUTUM ON │ - │ │ │ ADMISSION │ - ─────────────┼─────────┼─────────┼──────────────┼─────────┬──────────── - „ │ „ │ „ │ „ │ DATE │PNEUMOCOCCUS - │ │ │ │ │ AT AUTOPSY - ─────────────┼─────────┼─────────┼──────────────┼─────────┼──────────── - Pvt. Wolfe │No. 6 │Sept. 17 │IV │Sept. 23 │II[51] - Pvt. Pullam │No. 5 │Sept. 9 │IV │Sept. 24 │II - Pvt. Swain │No. 3 │Sept. 16 │II │ │ - ─────────────┴─────────┴─────────┴──────────────┴─────────┴──────────── - - - Secondary Infection with Pneumococcus in Pneumonia - -The foregoing studies have shown that hemolytic streptococcus infection -may spread by contagion throughout an entire ward with great rapidity. -Other observations have demonstrated that pneumococcus infection may be -transmitted in the same way. Only three instances of this nature will be -cited. The first occurred in Ward 3 (Table XXI). Between September 6 and -16 no cases of pneumonia caused by Pneumococcus Type II had been -admitted to the ward. On September 16 Pvt. Swain was admitted to the -ward and placed in Bed 3. Bacteriologic examination of his sputum showed -that his pneumonia was caused by Pneumococcus Type II. At this time Pvt. -Pullam, who had been admitted to the ward on September 9 with a -pneumococcus Type IV pneumonia, occupied Bed 5 separated from Bed 3 by -one intervening bed. He had had his crisis on September 14 and was doing -well, his temperature being normal. On September 24 he developed a -second attack of pneumonia and died on September 30. Cultures at autopsy -showed Pneumococcus Type II in heart’s blood and lung, Pneumococcus Type -II and B. influenzæ in the right bronchus. Pvt. Wolfe was admitted to -the ward with bronchopneumonia on September 17 and placed in Bed 6 next -to Pvt. Pullam. Pneumococcus Type IV and B. influenzæ were found in his -sputum. His temperature had fallen to normal by lysis on September 21 -and he was doing well. On September 23 his temperature suddenly rose and -he developed a second attack of pneumonia. Pneumococcus Type II was -isolated by blood culture on this date. He recovered. In both instances -Pneumococcus Type II was acquired after the admission of a patient with -a Pneumococcus Type II pneumonia, the opportunity for contact infection -having been favored by the association of these patients in adjoining -beds. - - TABLE XXII - - SECONDARY INFECTION WITH PNEUMOCOCCUS TYPE II - - ═════════════╤═════════╤══════════╤════════════╤═══════════════════════ - │ BED │ │PNEUMOCOCCUS│ - NAME │OCCUPIED │ ADMITTED │IN SPUTUM ON│ SECONDARY INFECTION - │ │ │ ADMISSION │ - ─────────────┼─────────┼──────────┼────────────┼──────────┬──────────── - „ │ „ │ „ │ „ │ DATE │PNEUMOCOCCUS - │ │ │ │ │ AT AUTOPSY - ─────────────┼─────────┼──────────┼────────────┼──────────┼──────────── - Pvt. Smith │No. 26 │Sept. 18 │II │ │II - Pvt. Thompson│No. 28 │Sept. 17 │Atyp. II │Sept. 21 │II - Pvt. Linehan │No. 30 │Sept. 16 │IV │Sept. 26 │II - ─────────────┴─────────┴──────────┴────────────┴──────────┴──────────── - -The second instance is almost identical and occurred on the opposite -side of Ward 3 at about the same time (Table XXII). Pvt. Linehan was -admitted on September 16 and placed in Bed 30. Pneumococcus Type IV was -found in his sputum. Pvt. Thompson was admitted the following day with a -Pneumococcus II atypical pneumonia and placed in Bed 28. The next day -Pvt. Smith was admitted and placed in Bed 26. Pneumococcus Type II was -found in his sputum. On September 19 Pvt. Thompson recovered by crisis -and was doing well. On September 21 he had a chill, his temperature rose -to 104.4° F. and he developed a second attack of pneumonia. He died on -September 29; cultures at autopsy showing Pneumococcus Type II in -heart’s blood and left pleural cavity, Pneumococcus Type II and B. -influenzæ in bronchus and lung. Pvt. Linehan had begun to improve on -September 24 and his temperature was falling by lysis. On September 26 -he became worse, developed signs of pericarditis and died on September -30. Cultures from lungs and bronchus at autopsy showed Pneumococcus Type -II and B. influenzæ. In both instances the fatal secondary infection -with Pneumococcus Type II was undoubtedly acquired from Pvt. Smith in -the nearby bed. - -The third instance occurred in Ward 8 (Table XXIII). Pvts. Lewis and -Scott were admitted on September 21 and were placed in adjoining beds, -50 and 51. Lewis showed Pneumococcus Type I in his sputum, Scott -Pneumococcus II atypical. The following day Pvts. Pighee, Jones, and -Columbus were admitted and given Beds 48, 49 and 53 respectively. All -showed Pneumococcus II atypical in the sputum. Pvt. Lewis with -Pneumococcus Type I pneumonia recovered by crisis on September 29. His -temperature remained normal until October 2 when it suddenly rose to -104.2° F. He developed a second attack of pneumonia and died on October -8. Cultures at autopsy from heart’s blood and lung showed Pneumococcus -II atypical, from the bronchus Pneumococcus II atypical and B. -influenzæ. It is, of course, impossible to say from which one of his -neighbors Pvt. Lewis acquired his second pneumococcus infection. - - TABLE XXIII - - SECONDARY INFECTION WITH PNEUMOCOCCUS II ATYPICAL - - ═════════════╤═════════╤══════════╤════════════╤═══════════════════════ - │ BED │ │PNEUMOCOCCUS│ - NAME │OCCUPIED │ ADMITTED │IN SPUTUM ON│ SECONDARY INFECTION - │ │ │ ADMISSION │ - ─────────────┼─────────┼──────────┼────────────┼──────────┬──────────── - „ │ „ │ „ │ „ │ DATE │PNEUMOCOCCUS - │ │ │ │ │ AT AUTOPSY - ─────────────┼─────────┼──────────┼────────────┼──────────┼──────────── - Pvt. Pighee │No. 48 │Sept. 22 │Atyp. II │ │ - Pvt. Jones │No. 49 │Sept. 22 │Atyp. II │ │ - Pvt. Lewis │No. 50 │Sept. 21 │I │Oct. 2 │Atyp. II - Pvt. Scott │No. 51 │Sept. 21 │Atyp. II │ │ - Pvt. Columbus│No. 53 │Sept. 22 │Atyp. II │ │ - ─────────────┴─────────┴──────────┴────────────┴──────────┴──────────── - -It is noteworthy that these instances of secondary contact infection -with pneumococci occurred in wards where every precaution was supposedly -taken to prevent transfer of infection from one patient to another. It -is true however that the wards were greatly overcrowded at the time. -Many other instances of secondary pneumococcus infection in cases of -pneumonia following influenza were encountered in which it was -impossible to trace the source of infection, many combinations of -different types of pneumococcus being found. There were two instances in -which Pneumococcus Type IV was found in the sputum by inoculation of -white mice shortly after onset of pneumonia, whereas secondary infection -with other types was found at autopsy, one with Pneumococcus Type II, -one with Pneumococcus Type III. In 2 cases by inoculation of white mice, -two types of pneumococcus were found simultaneously in the sputum -coughed from the lung, in one Pneumococcus Types III and IV, in the -other Pneumococcus Types I and IV. There were 5 cases in which two types -of pneumococcus were found in cultures at autopsy as shown in Table -XXIV. Combined pneumococcus infections of this nature are almost never -encountered in pneumonia occurring under normal conditions in the -absence of epidemic influenza. - - TABLE XXIV - - MIXED PNEUMOCOCCUS INFECTIONS IN PNEUMONIA - - ═════════════════╤═════════════════════════════════════════════════════ - NAME │ CULTURES AT AUTOPSY - ─────────────────┼─────────────────┬─────────────────┬───────────────── - „ │ HEART’S BLOOD │ BRONCHUS │ LUNGS - ─────────────────┼─────────────────┼─────────────────┼───────────────── - Pvt. Gal. │ │Pn. Type III │Pn. Type III - │ │B. influenzæ │Pn. Type IV - │ │Staphylococcus │B. influenzæ - ─────────────────┼─────────────────┼─────────────────┼───────────────── - Pvt. Sug. │Pn. Type III │Pn. Type III │Pn. Type III - │ │Pn. Type IV │Pn. Type IV - │ │B. influenzæ │B. influenzæ - │ │Staphylococcus │ - ─────────────────┼─────────────────┼─────────────────┼───────────────── - Pvt. Hig. │S. hemolyticus │ │Pn. Type II - │ │ │Pn. Type IV - │ │ │S. hemolyticus - │ │ │Staph. aureus - ─────────────────┼─────────────────┼─────────────────┼───────────────── - Pvt. Can. │Pn. Type I │ │Pn. Type III - │ │ │S. hemolyticus - ─────────────────┼─────────────────┼─────────────────┼───────────────── - Pvt. Fer. │Sterile │Pn. Type IV │Pn. Type I - │ │B. influenzæ │Pn. Type IV - │ │Staphylococcus │B. influenzæ - ─────────────────┴─────────────────┴─────────────────┴───────────────── - -The foregoing data show that infection with one type of pneumococcus may -readily be superimposed upon or closely follow infection with another -type. Cases have been cited in which it was clearly demonstrated that -this was due to contact infection. It is furthermore evident that -pneumonia caused by one type of pneumococcus affords no reliable -immunity against pneumonia caused by another type. The same conditions -that favored the spread of hemolytic streptococcus infection also -favored the transfer of pneumococcus infection from patient to patient. - - - Secondary Contact Infection in Influenza - -The material so far presented has dealt with contact infection in cases -of pneumonia following influenza. That a similar contact infection in -cases of influenza treated in crowded hospital wards is responsible in -considerable degree for the development of pneumonia in cases of -influenza seems quite probable. It has already been stated that this -pneumonia was found in large part to be caused by infection with types -of pneumococcus that are found in the mouths of normal individuals. It -has been fairly definitely established by Stillman[52] that lobar -pneumonia caused by pneumococcus Types I and II is in all probability -due to contact infection, and definite instances of such infection by -Pneumococcus Type II have been reported above. In a recent communication -Stillman[53] has furthermore shown that of the various groups of -Pneumococcus II atypical those most frequently associated with pneumonia -are rarely found in normal mouths, while those infrequently associated -with pneumonia are more commonly found. Whether similar considerations -will hold true for pneumococci of Group IV can only be determined by -further investigation. It has been stated that certain observations made -during the course of this work have suggested that cases of pneumonia -which complicate influenza may be due to contact rather than to -autogenous infection. The data available are far too limited to -establish this fact and it would require a very extensive study to -furnish conclusive evidence. - -Certain general observations have suggested this point of view. It is -well recognized that the incidence of pneumonia in patients with -influenza has been much higher where overcrowding has existed. It would -seem probable that this has been in large part due to the greater -opportunity for the dissemination of organisms capable of producing -pneumonia and the consequently increased opportunity for secondary -contact infection among patients treated under such conditions. The not -infrequent occurrence of influenzal pneumonia due to combined infections -of the different types of pneumococci, hemolytic streptococci, -staphylococci, and other bacteria, instances of which have been cited, -is in harmony with this view, especially since pneumonia under ordinary -conditions is rarely found to be associated with mixed infections of -this nature. It is true that healthy individuals occasionally carry more -than one type of pneumococcus simultaneously in the mouth, though this -is very infrequent, and autogenous infection occurring in such -individuals might account in some instances for the mixed pneumococcus -infections encountered. By way of analogy it has been clearly shown in -other studies by the Commission on the relation of hemolytic -streptococcus carriers to the complications of measles, that secondary -infection of the respiratory tract with S. hemolyticus is in very large -part due to contact infection, the chronic carrier rarely developing -complications due to this organism. - -To obtain further light on this question the type of pneumococcus -present in the mouths of 46 consecutive cases of early uncomplicated -influenza was determined by the mouse inoculation method at time of -admission to the receiving ward of the hospital before the patients had -been associated, with the purpose of determining if cases among this -group which subsequently developed pneumonia might be shown to have -acquired a pneumococcus which they did not carry at time of admission. -This group of patients was treated in a special ward set apart for the -purpose. The patients were assigned to beds in rotation and confined in -bed until thoroughly convalescent. Beds were well separated and -cubicles, masks and gowns were in use. Cultures were made from the ward -personnel. By these procedures an accurate record was kept of all -sources of pneumococcus infection. The types of pneumococcus found in -the mouths of these patients at time of admission are shown in Table -XXV. - - TABLE XXV - - TYPES OF PNEUMOCOCCI IN THE MOUTHS OF INFLUENZA PATIENTS - - ═══════════════════════════════════════════════════════════════════════ - PNEUMOCOCCUS NUMBER PER CENT - ─────────────────────────────────────────────────────────────────────── - Pneumococcus, Type I 0 0 - Pneumococcus, Type II 0 0 - Pneumococcus, II atypical 1 2.2 - Pneumococcus, Type III 0 0 - Pneumococcus, Group IV 25 54.3 - No pneumococci found 20 43.5 - ─────────────────────────────────────────────────────────────────────── - -Only 1 patient in this group developed pneumonia. At time of admission -he had no pneumococcus in his mouth as determined by inoculation of a -white mouse with his sputum. Examination of the sputum by the same -method at time of onset of pneumonia three days after admission showed -Pneumococcus Type III. The only ascertainable source of infection in -this case was one of the ward attendants who carried Pneumococcus Type -III in his throat in sufficiently large numbers to be demonstrable by -direct culture and who frequently came in contact with the patient. In -this instance the development of pneumonia was probably due to contact -infection. An extensive study of this nature would be necessary to -determine in what proportion of cases pneumonia following influenza is -caused by secondary contact infection and in what proportion to -autogenous infection. It is at least evident that contact infection with -a type of pneumococcus found in the mouth of normal individuals may -occur in influenza and be responsible for the development of pneumonia. -Therefore every precaution should be taken to prevent it. - - - Methods for the Prevention of Secondary Contact Infection in Influenza - and Pneumonia - -The methods at present in vogue for preventing the spread of contagion -in wards devoted to the care of patients with influenza and pneumonia -may be briefly enumerated: The separation of patients by means of sheet -or screen cubicles, the wearing of masks and gowns by the ward personnel -and to some extent by convalescent patients who are up and about the -ward, and in some hospitals the separation of streptococcus carriers -from noncarriers as determined by throat culture at time of admission. -That these methods are of some value in preventing spread of infection -cannot be denied, and it is probable that they are fairly effective -under ordinary conditions when conscientiously carried out. That they -inevitably break down in the presence of an overwhelming epidemic when -hospital wards become overcrowded is only too evident. Under such -conditions the sheets hung between the beds are constantly being -displaced and are slight proof against a patient’s curiosity as to the -identity and condition of the man in the adjoining bed; masks cannot be -worn by patients seriously ill with pneumonia, during the very time when -they are most dangerous and in greatest danger and those worn by the -ward personnel are very rarely sufficiently well made to prevent spread -of contagion by droplet infection as the studies of Haller and -Colwell[54] and Doust and Lyon[55] have shown; the separation of -streptococcus carriers from noncarriers as at present carried out cannot -keep pace with the ever increasing influx of patients nor with the -rapidity of the spread of the hemolytic streptococcus, in part because -of the time required to make the bacteriologic diagnosis, in part -because the amount of work involved cannot be accomplished by the -laboratory personnel available. That this is so will be shown in data -presented below. Not only do these methods break down in the face of an -epidemic, but they often provide a false sense of security. - -In searching for a solution of the problem it is essential to have the -following considerations clearly in mind. Every patient with influenza -must be considered a potential source of pneumococcus or hemolytic -streptococcus infection for his neighbor until he is proved otherwise by -bacteriologic examination. Every person engaged in the care of patients -with respiratory diseases must also be regarded as a potential source of -danger. Pneumonia cannot be regarded as one disease but must be looked -upon as a group of different diseases, with more or less similar -physical signs and symptoms, it is true, but caused by a considerable -variety of bacteria, infection with any one of which not only provides -no protection against infection with another, but may even render the -individual more susceptible to secondary infection. Therefore, every -patient with pneumonia must be regarded as an actual source of danger to -his neighbor, at least until it is established that he has the same type -of infection. All these considerations are especially true in the -presence of influenza, for it has become evident that many organisms -readily gain access to the lung and produce pneumonia in patients with -influenza which under ordinary circumstances fail to cause disease of -the respiratory organs. - -Since secondary infection in respiratory disease is undoubtedly spread -in large part by droplet and contact infection, the prevention of -secondary infection must depend upon the elimination of these methods of -transmission. Three solutions present themselves: (1) Ward treatment -with absolute elimination of overcrowding and much wider separation of -patients than has hitherto been deemed necessary; (2) segregation of -patients according to type of bacterial infection; (3) effective -individual isolation of every patient. - -It has been clearly shown that treatment of influenza and pneumonia in -overcrowded wards even with the use of such precautions to prevent -transfer of infection as cubicles, masking of attendants and patients, -etc., is attended by serious danger of contact infection and that such -infection will almost inevitably occur. This is not at all surprising -when it is remembered that we are treating in the same ward, in the case -of pneumonia, a group of what are in reality entirely different -diseases, all of which may be transmitted from one patient to another, -and in the case of influenza a group of individuals who carry a variety -of potentially pathogenic bacteria. No one would expect to treat cases -of scarlet fever, measles, and diphtheria together in a hospital ward -without having contact infection result. Among patients ill with -influenza and postinfluenzal pneumonia, certainly streptococcus -pneumonia and to some extent pneumococcus pneumonia may be transmitted -quite as readily as any of these diseases. In view of these -considerations it must be apparent if ward treatment of these diseases -is to be continued without respect to type of bacterial infection, not -only that overcrowding is absolutely contraindicated but also that much -wider separation of patients than has hitherto been regarded as -necessary is imperative. Furthermore, beds should be separated by -permanent cubicles that cannot readily be displaced. Patients should be -confined to their cubicles until thoroughly convalescent and when up and -about should not be allowed to enter cubicles occupied by patients still -sick. Medical officers, nurses and attendants who come into contact with -the patients should use the same rigid precautions that are used in the -care of patients with typhoid or erysipelas or meningitis with the -additional use of means to prevent droplet infection of the patients, -always bearing in mind that the respiratory tract in patients with -influenza or postinfluenzal pneumonia is as susceptible to secondary -infection as the postpartum uterus or an open surgical wound. In other -words, the most rigid aseptic technic should be maintained. The -recognition of a case of streptococcus pneumonia in a ward should be an -indication for immediate quarantine of the ward until it has been shown -by bacteriologic examination that there is no longer danger of spread of -streptococcus contagion. This is done in the case of meningitis or -diphtheria, neither of which diseases is comparable with streptococcus -pneumonia in rapidity of spread or in resulting fatality. - -Segregation of patients in wards according to type of bacterial -infection while theoretically an improvement over the indiscriminate -mixing of patients with many different types of infection presents many -practical difficulties which make it impossible to carry out in the -presence of an overwhelming epidemic. It is quite obvious that grouping -of influenzal patients on the basis of the types of pneumococci that -they carry in their mouths is impossible since the great majority of -mouth pneumococci belong to Group IV and comprise a heterologous -immunologic group. The separation of influenza patients who carry S. -hemolyticus from those who do not would appear to offer a more hopeful -field. Since we cannot make an immediate distinction between -streptococcus carriers and noncarriers by inspection of the patient, -this procedure requires the taking of throat cultures at time of -admission to the hospital, the holding of patients for eighteen to -twenty-four hours in receiving wards until the bacteriologic diagnosis -has been made, and their subsequent distribution to streptococcus and -nonstreptococcus wards. This is feasible when the admission rate is low -and the number of streptococcus carriers found at time of admission is -small. In the presence of an influenza epidemic it immediately becomes -impossible to carry out in base hospitals as now constituted, since the -demand for beds under such conditions at once converts a large part of -the hospital into a group of receiving wards with little room remaining -for subsequent separation of patients. The amount of bacteriologic work -involved at once becomes prohibitive and the time required to make the -bacteriologic diagnosis defeats its purpose since it allows the spread -of hemolytic streptococcus to occur in the receiving wards during the -interval. - -The foregoing statements are based on results obtained in an attempt to -separate streptococcus carriers from noncarriers in a limited group of -cases of influenza at Camp Pike, the investigation being conducted -during a secondary wave of influenza between November 27 and December 5. -A special group of five wards consisting of one receiving ward and four -distributing wards were set aside for the study. Cubicles, masks and -gowns were in use and the wards were not crowded. The personnel on these -wards did not carry S. hemolyticus in their throats. Patients entering -the receiving ward were assigned to beds in rotation. Throat cultures -were made on blood agar plates at time of admission. The plates were -examined promptly the next morning, the diagnosis of S. hemolyticus -being made by the characteristic hemolytic colonies and microscopic -examination of stained smears. By this method a report reached the -receiving ward at 9:30 a.m. and patients were promptly evacuated to the -streptococcus and nonstreptococcus wards, where they were again assigned -to beds in rotation, remaining confined in bed until convalescent. -Confirmation of all strains of hemolytic streptococcus was subsequently -carried out by isolation in pure culture, bile solubility test, and -hemolytic test with washed sheep corpuscles. All cases free from -hemolytic streptococci at time of admission who were sent to the “clean” -wards were recultured daily throughout the period of study, those -acquiring a hemolytic streptococcus being transferred to a streptococcus -ward as soon as the bacteriologic diagnosis was made. The results are -shown in Table XXVI. - - TABLE XXVI - - S. HEMOLYTICUS IN CASES OF INFLUENZA - - ══════════╤══════════╤═══════════════════╦═════════════════════════════ - DATE │ PATIENTS │THROAT CULTURES ON ║ “CLEAN” CASES ACQUIRING S. - │ ADMITTED │ ADMISSION. S. ║ HEMOLYTICUS IN THE HOSPITAL - │ TO │ HEMOLYTICUS: ║ - │RECEIVING │ ║ - │ WARD │ ║ - ──────────┼──────────┼─────────┬─────────╫─────────┬─────────┬───────── - „ │ „ │ + │ − ║WHILE IN │WHILE IN │ TOTAL - │ │ │ ║REC. WARD│ “CLEAN” │ - │ │ │ ║ │ WARD │ - ──────────┼──────────┼─────────┼─────────╫─────────┼─────────┼───────── - Nov. 27 │ 12│ 4│ 8║ 0│ 2│ 2 - Nov. 28 │ 8│ 2│ 6║ 0│ 1│ 1 - Nov. 29 │ 17[56]│ 8│ 9║ 1│ 2│ 3 - Nov. 30 │ 11│ 2│ 9║ 3│ 0│ 3 - Dec. 1 │ 10│ 5│ 5║ 0│ 0│ 0 - Dec. 2 │ 37│ 16│ 21║ 1│ 1│ 2 - Dec. 3 │ 21│ 8│ 13║ 0│ 2│ 2 - Dec. 4 │ 32[56]│ 11│ 21║ 4│ 2│ 6 - Dec. 5 │ 17│ 10│ 7║ 5│ 0│ 5 - ──────────┼──────────┼─────────┼─────────╫─────────┼─────────┼───────── - Totals │ 165│ 66│ 99║ 14│ 10│ 24 - ──────────┴──────────┴─────────┴─────────╨─────────┴─────────┴───────── - -One hundred and sixty-five cases were admitted to the receiving ward -during the period of study as cases of influenza. Of these, 137 had -influenza; 4 of those with influenza had pneumonia at time of admission, -23 had acute follicular tonsillitis, 3 epidemic cerebrospinal -meningitis, 1 scarlet fever, and 1 Vincent’s angina. Sixty-six cases (40 -per cent) showed hemolytic streptococcus in the throat at time of -admission and were sent to the streptococcus wards; 99 cases (60 per -cent) were negative for hemolytic streptococcus on admission, and of -these 91 were sent to the “clean” influenza wards. Twenty-four of these -clean cases subsequently became positive for S. hemolyticus. It is -especially noteworthy that 14 of them acquired a hemolytic streptococcus -during the short period that they were held in the receiving ward -awaiting the report of the culture taken at time of admission, the first -culture taken shortly after admission to the “clean” wards being -positive. This result was undoubtedly due to the fact that these cases -were unavoidably associated in the receiving ward with many carriers of -hemolytic streptococcus. It is evident that cases which were supposedly -free from streptococci but which in reality had picked up the organism -in the receiving ward were constantly being sent to the “clean” wards. -It is furthermore evident that if the precaution had not been taken of -reculturing all clean cases on day of admission to the “clean” wards and -daily thereafter these wards would soon have become saturated with -hemolytic streptococci. Even under these conditions, 10 cases, after -varying periods in the “clean” wards, acquired the organism in their -throats. When it is stated that it required the full time of two men -under very special conditions to carry out this work in a very limited -number of cases and that it failed to keep “clean” wards free from -hemolytic streptococci, it is only too apparent that the efficient -separation of carriers from noncarriers in the presence of an epidemic -of influenza is an impossible task. - -The segregation of pneumococcus pneumonias following influenza according -to type of infection is obviously impossible, since they are caused by -an almost unlimited variety of immunologic types as far as present -knowledge goes. - -Even the efficient separation of streptococcus pneumonias from -pneumococcus pneumonias would require a considerable team of workers and -the closest cooperation between laboratory and ward staffs, so that no -case of pneumonia would be sent to a pneumonia ward until the -bacteriologic diagnosis had been made. In our experience this is rarely -considered feasible even under ordinary conditions, and in the presence -of an epidemic is nearly impossible because of the volume of work -involved and the delay necessitated by bacteriologic methods. It is, -nevertheless, absolutely essential if highly fatal ward epidemics of -streptococcus pneumonia are to be prevented. - -In view of the considerations discussed above, it is believed that the -clear and most fundamental indication for the management of epidemic -respiratory diseases in the army is to scatter patients as widely as -possible instead of following the time-honored custom of concentrating -them. In brief, abandon open ward treatment and adopt effective -individual isolation of every case, maintaining as strict a quarantine -as is demanded in other highly contagious and infectious diseases. The -adoption of a strict aseptic technic in the handling of these patients -is an evident corollary. Only by this means can the serious and highly -fatal secondary hospital infections, which occur in influenza and -pneumonia when these diseases are present in epidemic form, be -prevented. - -The prevention of secondary infection, prior to admission to the -hospital, is another and more difficult problem. That opportunity for -secondary contact infection in cases of influenza before patients reach -the hospital is great seems unquestionable, since many cases have -already developed these infections at time of admission. During the -epidemic patients were crowded in regimental infirmaries, in ambulances, -and in the receiving office of the hospital with every opportunity for -droplet infection present. No study has been made of this question, but -it seems reasonable that the same methods of prevention should apply, -namely, effective separation of patients. - -It is not within the scope of this paper to discuss details of method, -but anything that is possible becomes feasible as soon as sufficient -evidence can be brought to bear that it is a necessity. In the present -instance it would seem that any means that can be used to reduce -materially the terrific toll taken by respiratory diseases is an -absolute necessity. - - - Summary - -1. Secondary contact infection with pneumococci not infrequently occurs -in patients with pneumonia following influenza when they are treated in -hospital wards. - -2. Secondary contact infection with S. hemolyticus readily occurs in -patients with pneumonia and may spread rapidly throughout an entire ward -with highly fatal results. - -3. Secondary contact infection may be responsible for the development of -pneumonia in patients with influenza. - -4. Ward treatment of these diseases is fraught with serious danger which -is greatly increased by overcrowding, by imperfect separation of -patients by cubicles, and by imperfect aseptic technic of medical -officers, nurses, and attendants. - -5. It is probable that secondary contact infection can be effectively -prevented only by individual isolation and strict quarantine of every -patient. - - - - - CHAPTER IV - THE PATHOLOGY AND BACTERIOLOGY OF PNEUMONIA FOLLOWING INFLUENZA - - E. L. OPIE, M.D.; F. G. BLAKE, M.D.; AND T.M. RIVERS, M.D. - - -Many observers have described isolated phases of the recent epidemic and -of past epidemics of influenza. Few have had an opportunity to follow -the pathology of influenza from the onset of an epidemic through a -period of several months and to observe the succession of acute and -chronic changes which occur in the lungs. Our commission arrived on -September 5, 1918, at Camp Pike two weeks before the outbreak of -influenza. The commission had previously made a careful study of the -clinical course, the bacteriology and to a limited extent the pathology -of pneumonia occurring at Camp Funston where there was little if any -influenza. Study of the records preserved at the base hospital at Camp -Funston had convinced us that this camp had passed through an epidemic -of influenza during the spring of 1918, this epidemic being followed by -a very severe outbreak of pneumonia. Our investigation at Camp Funston -had brought to our attention those phases of pneumonia which with the -facilities of a base hospital laboratory could be most profitably -studied with a view to determining the causation, the epidemiology and -the prevention of the pneumonias prevalent in the American army. - -Study of pneumonia after death offers the only opportunity of -determining the relation of pulmonary lesions to the considerable -variety of microorganism associated with them. Clinical diagnosis -furnishes no certain criterion for distinguishing lobar and -bronchopneumonia; suppurative pneumonia is rarely recognizable during -life. The relation of pneumococci, streptococci, staphylococci or B. -influenzæ to one or other type of pneumonia can be determined with -accuracy only after death; for the demonstration of one or more of these -microorganisms in material obtained from the upper respiratory passages -in life, though of value, furnishes us no definite evidence that the -organism which has been identified has entered the lung and passed from -the bronchi to produce pneumonia. - -Study of autopsies following examination of the sputum during life has -shown that an individual primarily attacked by influenza may suffer with -a succession of pneumonias, one microorganism having prepared the way -for another. The complexity of the subject is much increased by the -truth that pyogenic microorganisms, like the tubercle bacilli, are -capable of producing a considerable variety of pulmonary lesions. - -Examination of the lungs of a large number of individuals who have died -as the result of pneumonia following influenza has disclosed a -succession of acute and chronic diseases. Immediately succeeding the -height of the epidemic of influenza, death occurred with acute lobar -pneumonia or with diffusely distributed hemorrhagic bronchopneumonia -caused in the majority of instances by Pneumococcus IV in association -with B. influenzæ. Superimposed infection with hemolytic streptococci -increased in frequency and in individuals who had occupied certain wards -was almost invariable. At a later period, from one to two months -following the maximum incidence of influenza chronic lesions, namely, -bronchiectasis, unresolved pneumonia, and chronic empyema were common -and often occurred as the result of influenza which had had its onset at -the height of the epidemic. - -When influenza attacked the encampment, about 50,000 troops were -quartered in it, and for a considerable period no more troops were -brought into the camp and none left it. All cases of pneumonia occurring -among these troops were brought to the base hospital so that the -autopsies which were studied were representative of all the pneumonias -following influenza in this limited group of men. It is noteworthy that -autopsy disclosed no instance of fatal influenza unaccompanied by -pneumonia. - -=Pneumonia of Influenza.=—Knowledge concerning the bacteriology of the -pneumonia of influenza dates from the study of the epidemic of 1889–90. -The frequency with which Diplococcus lanceolatus occurred in association -with influenzal pneumonia was well recognized, although several -observers, notably Finkler[57] and Ribbert,[58] found Streptococcus -pyogenes so often that they attributed the pneumonia of influenza to -this microorganism. - -During a subsidiary outbreak of influenza occurring in 1891–92 -Pfeiffer[59] discovered the microorganism which he believed was the -cause of the disease. Pneumonia, he believed, was caused by the invasion -of this microorganism into the lung, and the pneumonia of influenza, if -death occurred at the height of the disease, was characterized not only -by the presence of the bacillus of influenza, but was recognizable by -its anatomic peculiarities. He described lobular patches of -consolidation which were separated from one another by air containing -tissue or were confluent, so that, although the lobular character was -still recognizable, whole lobes might be affected. The consolidated -tissue was dark red and within each lobular area were small, yellowish -gray spots varying in size from that of a pinhead to a pea. In the mucus -of the larynx and trachea were numerous microorganisms, including -diplococci and streptococci, among which influenza bacilli were -predominant; in the larger bronchi, bacteria other than influenza -bacilli were less abundant, whereas in the finer bronchi filled with -purulent fluid and in the lung tissue influenza bacilli had undivided -sway. Pfeiffer stated that the changes described were found when death -occurred at the height of the disease, whereas other pulmonary lesions -might be sequelæ of this typical influenzal pneumonia. - -Observations upon the pathology of influenzal pneumonia made during the -epidemic of 1889–92 have been collected in the monograph of -Leichtenstern[60] published in 1896. He combats the opinion held by some -observers that pneumonia with influenza is always catarrhal and cites -many writers to prove that lobar pneumonia not infrequently accompanies -the disease. Indeed, some have found “croupous” pneumonia more often -than “catarrhal.” Krannhals[61] at Riga found typical fibrinous -pneumonia in 53 instances, doubtful forms in 22 and bronchopneumonia in -37. Cruickshank[62] in England found croupous forms predominant. Among -43 autopsies performed upon individuals dead with influenza -Birch-Hirschfeld[63] found 11 instances of croupous lobar pneumonia, 8 -instances of croupous lobular pneumonia and 24 instances of catarrhal -pneumonia. Leichtenstern thinks that the atypical symptomatology of -lobar pneumonia with influenza—for example, the purulent character of -the sputum—has led many physicians to believe that lobar pneumonia -rarely occurs. It is equally true that many instances of confluent -lobular pneumonia are mistaken for lobar. - -There appears to be no comprehensive description of the pneumonias of -influenza based upon the epidemics of 1889–92. Descriptions dating from -this period are much obscured by attempts to separate croupous or -fibrinous from catarrhal pneumonias. Croupous lobular pneumonia has been -recognized, for example, by Birch-Hirschfeld. Leichtenstern describes a -form of pneumonia which he regards as neither lobar nor lobular although -it implicates whole lobes; the consolidated tissue is homogeneous and -varies in color from fleshy red to bluish red; it is tough and elastic -in consistency. The author thinks that it is an error to regard this -lesion as a confluent lobular pneumonia. - -Kuskow[64], who has discussed the pathology of influenza in considerable -detail, has seldom seen lobar pneumonia but has almost invariably found, -even when there is lobar distribution of the lesion, lobular patches of -consolidation involving groups of lobules, single lobules or only parts -of lobules; the lung tissue has been hyperemic and in places edematous. - -Opinions concerning the pathology and bacteriology of the pneumonias of -influenza, published since the recent epidemic, have varied almost as -much as those just cited. Few observers have had the opportunity of -making a considerable number of observations under conditions which -determine the relation of the pulmonary lesions to the primary disease. - -Keegan[65] has found with influenza a massive and confluent -bronchopneumonia, frequently resembling lobar pneumonia but -distinguishable particularly in its early stages when the cut section of -the consolidated lung has a finely granular character and each -bronchiole stands out as a grayish area with intervening dark red -alveolar tissue. - -Symmers[66] states that the pneumonia of influenza is a confluent -lobular exudative and hemorrhagic pneumonia which bears a close -resemblance to the pneumonic variety of bubonic plague. - -Our commission[67] published a preliminary report on pneumonia following -influenza observed at Camp Pike. The occurrence of purulent bronchitis, -distention of lungs, peribronchial hemorrhage and bronchiectasis were -described. B. influenzæ was isolated from the bronchi in approximately -85 per cent of instances of influenzal pneumonia but from the -consolidated lung in less than half this number of autopsies. Lobar -pneumonia was present in a large proportion of autopsies but was less -frequent than bronchopneumonia. Bronchopneumonic consolidation is in -part red, lobular and confluent, in part nodular; pneumococci have a -predominant part in the production of these lesions. Three types of -suppurative pneumonia are described: (_a_) Abscess caused by hemolytic -streptococci usually in contact with the pleura and accompanied by -empyema; (_b_) Suppuration of interstitial tissue of the lung caused by -hemolytic streptococci and accompanied by empyema; (_c_) multiple foci -of suppuration clustered about a bronchus of medium size and caused by -staphylococci. We have expressed the opinion that B. influenzæ descends -into the bronchi; pneumococci, usually Type IV, may enter the lung and -produce either lobar or bronchopneumonia. Hemolytic streptococci may -descend and infect the pneumonic lung causing death often before -suppuration has occurred. Epidemics of such superimposed streptococcus -pneumonia in wards of the hospital were described. - -LeCount[68] says: “The pneumonia of influenza is commonly referred to as -bronchopneumonia. It may be so designated, but it differs from other -bronchopneumonias in its predilection for the periphery of the lungs and -in the extent to which the inflammation is hemorrhagic.” - -MacCallum[69] states that the following types of pneumonia following -influenza may be recognized. 1. Pneumococcus pneumonia. The lobular -character of the consolidation is in these cases well marked, although -it tends to lose its definiteness through the confluence of adjacent -areas. The cut surface of the lung shows in the more acute cases a -peculiar lobular or confluent consolidation which corresponds well with -what is commonly written of the stage of engorgement in the description -of lobar pneumonia. Later stages in the pneumonia show within these -areas patches of rough gray consolidated tissue from which definite -plugs of exudate project. 2. Staphylococcal pneumonia. 3. Streptococcal -pneumonia. There is lobular pneumonia, the interlobular septa are -edematous and, microscopically, bronchi and alveoli are loaded with -streptococci. Whole areas of lung, though retaining their form, are -entirely necrotic. Lymphatics are distended with exudate containing -streptococci in great numbers, but in none of these cases is -interstitial bronchopneumonia found. 4. Pneumonia produced by B. -influenzæ of Pfeiffer. The lung is studded with palpable shot-like -grayish yellow nodules; the bronchi exude thick yellow pus, which -contains influenza bacilli. Microscopically, the walls of the bronchi -are found to be thickened by mononuclear infiltration and new formation -of connective tissue. The walls of the alveoli are thickened and -indurated and the alveoli often contain fibrin in process of -organization. Absence of conspicuous changes in lymphatics, absence of -intense pleural infection and relatively scant numbers of polynuclear -leucocytes in the exudate within the alveoli and bronchial walls are, -MacCallum states, all that distinguish this pulmonary change from the -interstitial bronchopneumonia caused by the hemolytic streptococcus and -described by him in previous papers. - -Lyon[70] designates the pulmonary lesion following influenza, -hemorrhagic pneumonitis, the lung tissue containing serous fluid loaded -with red blood corpuscles; in many instances there was such scant -consolidation that the process could not be regarded as a true -pneumonia. In 35 instances the lesion was lobular in distribution and in -16 instances was sufficiently extensive to be designated lobar, but it -was not typical lobar pneumonia, and, often associated with lobular -patches of consolidation, appeared to be a confluent lobular pneumonia. - -Goodpasture and Burnett[71] say: “The difficulties of analyzing the -pulmonary lesions in any group of influenza pneumonias as they have -appeared in this epidemic, are very apparent to anyone who has had an -opportunity to observe the bacteriology and pathology of this -accompaniment of the disease.” There is an acute outflow of the fluid -elements of the blood and of hemorrhage into the lung tissue filling the -alveoli in lobular areas and not infrequently in an entire lobe. By a -special method of staining these authors have studied the distribution -of Gram-negative bacilli with the morphology of B. influenzæ. The fact -that in certain very early cases demonstrable bacteria of any kind are -scarce or not found at all, has lead them to believe “notwithstanding -the demonstration of influenza bacilli in pure culture in the lung in -all but one instance, that at this stage organisms are comparatively few -within the alveoli, and the primary injury is due to a very potent toxic -agent elaborated in and disseminated through the larger air passages. In -the later stages or from the beginning, if the injury be slight, the -infection focalizes about the bronchi or their terminations, so that the -bronchial and lobular distribution becomes very conspicuous.” Typical -lobar pneumonia with “croupous” exudate within the alveoli occurs in -cases complicated by secondary pneumococcus infection. - -Wolbach[72] has found that two types of pneumonia are characteristic of -influenza. In cases in which death has occurred within a few days after -onset of pulmonary signs, the lung tissue is dark red and “meaty in -consistency” and contains abundant blood-tinged serous fluid which drips -from the cut surface. The other type of lesion is found in patients who -have lived for ten days or more after onset of the disease; there is -extensive bronchitis, bronchopneumonia, discrete or confluent, and -peribronchitis. The lungs are voluminous and the smaller bronchi are -distended. Microscopically, there is peribronchitis with extensive -infiltration of the interlobular septa and organization in alveoli and -bronchioles. This lesion is that designated by MacCallum as -“interstitial bronchopneumonia.” Wolbach thinks that the two types of -lesion represent different stages of the same process. He regards as -distinctive of the pneumonias of influenza the presence of hyalin fibrin -lining distended air spaces. With the two types of lesion which have -been described, B. influenzæ was the only organism which could be -cultivated, and the author associates these distinctive conditions with -that microorganism. - -=Streptococcus Pneumonia.=—Finkler emphasized the importance of -streptococcus pneumonia as a complication of influenza. In 1888 he -described instances of acute primary streptococcus pneumonia observed in -1887 and 1889. This form of pneumonia, Finkler thought, occurred in Bonn -in epidemic form before the influenza epidemic of 1889–90 and, he -states, exhibited an astonishing similarity to the pneumonia of -influenza. He thought that later there was in Bonn a mixed infection of -influenza and primary streptococcus pneumonia. In one type of -streptococcus pneumonia, described by Finkler, there was lobular -consolidation which in multiple patches produced “pseudolobar” -consolidation; the consolidated lung was smooth and red, and similar to -spleen, rather than hepatized. In another group of instances the lesion -merited the name “erysipelas of the lung.” The lesion was an acute -interstitial pneumonia in some places, a cellular or occasionally -fibrinous pneumonia with involvement of the interstitial tissue in other -places. There was edematous swelling and accumulation of leucocytes in -the interstices between the alveoli and about the blood vessels and -bronchi. Finkler stated that the similarity to erysipelas might suggest -that the lymphatics contain streptococci, but this relation did not -exist although large lymphatic channels were occasionally filled with -coagulum. He asserted that the disease was contagious and cited cases -which he believed had their origin in hospital wards. - -The widespread occurrence of streptococcus pneumonia in the army camps -in this country attracted attention during the first months of 1918. -Cummings, Spruit and Lynch[73] at Fort Sam Houston, Texas, recognized -the prevalence of streptococcus pneumonia, both as a complication of -measles and in association with lobar pneumonia, and showed that the -microorganism concerned was a hemolytic streptococcus. In 7 autopsies -upon individuals with lobar pneumonia, they found pneumococcus alone in -2 instances and pneumococcus and hemolytic streptococcus or hemolytic -streptococcus alone in 5 instances. Hemolytic streptococcus was found in -all of 24 instances of bronchopneumonia, three-fourths of which followed -measles. They recommend the bacteriologic examination of the throat of -patients with measles and the segregation of those who harbor hemolytic -streptococci. - -Cole and MacCallum[74] have published almost simultaneously, with that -just cited, a report upon the pneumonia which has occurred at Fort Sam -Houston and have shown the importance of hemolytic streptococci in its -causation. They have found two varieties of pneumonia, namely, acute -lobar pneumonia which does not differ essentially from that which occurs -elsewhere and bronchopneumonia which in most cases has followed measles -and is caused by S. hemolyticus. They think this infection is usually -acquired in the hospital. They believe that the pulmonary lesions are -characteristic. In this publication and elsewhere MacCallum has -designated the lesion “interstitial bronchopneumonia.” - -The epidemic of streptococcus pneumonia and empyema occurring at Camp -Dodge, Iowa, from March 20 to May 10 is described by Miller and -Lusk[75]. During this period there were 400 cases of pneumonia, whereas -from September 20, 1917, to March 20 there had been only 276 instances -of lobar pneumonia. The type of pneumonia changed, there was more severe -intoxication and empyema became very frequent; in 85 of 95 exudates -streptococci were found. The outbreak of pneumonia bore no relation to -measles. The authors state that a mild tracheitis was prevalent in the -cantonment during March, and whenever a large group of soldiers -congregated coughing was noticeable. - -MacCallum[76] studied the pneumonia at Camp Dodge during May and found -17 instances of the lesion which he had designated interstitial -bronchopneumonia; of these, 9 followed measles, although in the earlier -part of the epidemic there appear to have been, he states, few such -cases. Cultures made at autopsy, except in a few fatal cases of -uncomplicated lobar pneumonia caused by the pneumococcus, showed the -hemolytic streptococcus in every situation throughout the respiratory -tract and pleura. - -The pneumonia which occurred at Camp Funston is of special interest to -our commission because we were for a time stationed at this camp and had -the opportunity of following in the excellent records of the hospital -the history of the occurrence of pneumonia during the year following the -establishment of the camp in September, 1917. Stone, Phillips and -Bliss[77] have described the outbreak of pneumonia which occurred in -March, 1918. At this time there was, the authors state, severe pneumonia -with frequent empyemas due to hemolytic streptococci. This condition -which did not follow measles was responsible for the greatly increased -death rate in March; 9 deaths occurred in February, 45 in March, 25 in -April and 14 in May. They found during March 26 instances of multiple -pulmonary abscess. In 29 autopsies they found a pleural lesion which -they designate “subcostosternal pus pockets”; it occurs only in -association with empyema caused by hemolytic streptococci. - -Our commission[78] has shown that an epidemic of influenza, well -characterized by its epidemiology and symptoms, preceded and accompanied -the outbreak of pneumonia just described. Between March 4 and 29 1,127 -men from Camp Funston, which then contained 29,000 men, were sent to the -base hospital with influenza and many more were treated in the -infirmaries of the camp; on March 11 107 patients with influenza were -admitted to the hospital. The greatest incidence of pneumonia in the -history of the encampment up to this time occurred between March 9 and -29, immediately following the outbreak of influenza, the maximum -incidence of pneumonia occurring five days after the maximum for -influenza. - -The foregoing observations are cited to prove that streptococcus -pneumonia, which occurred during the spring of 1918 at Camp Funston and -doubtless at other camps, had its origin in influenza and did not differ -in character from that which occurred on a much larger scale in the fall -of 1918. - -=Table of Autopsies.=—In order to present as briefly as possible the -data upon which the present study has been based, autopsies have been -assembled in tabular form in the order of their performance (Table -XXVII). During the early period of the epidemic autopsies were performed -on all who died with pneumonia, but later, with increase in the number -of deaths, this became impossible and autopsies were performed on all -those who died in certain wards. - -Comparison of charts representing incidence of influenza and of deaths -from pneumonia furnishes evidence that fatal pneumonia during the period -of investigation was with few exceptions referable to influenza. During -two weeks, namely, from September 1 to 14, before the presence of the -epidemic was evident, there were only 2 fatal cases of pneumonia. In -most instances the relation of pneumonia to influenza is established by -a definite history of influenza having its onset during the epidemic. -Bronchopneumonia usually develops gradually as a sequence of influenza -in which purulent bronchitis has occurred. Lobar pneumonia may develop -in cases of influenza complicated by purulent bronchitis. In some -instances there is apparent recovery from influenza indicated by return -of temperature to normal; after from one to three days of normal -temperature there is typical lobar pneumonia with rusty sputum. In many -instances of pneumonia having their onset at the height of the epidemic -of influenza, the history indicates that pneumonia was present -immediately after the onset of symptoms, so that the onset resembled -that of pneumonia rather than of influenza. - -Cases of pneumonia following measles have been excluded from the table -in order that they may be studied separately and compared with the -pneumonias of influenza. It is noteworthy that the lesions of pneumonia -following measles have shown a very close resemblance to the pneumonias -of influenza, with regard both to pathologic characters and to -bacteriology. - -Five instances of pneumonia following typhoid fever (Autopsies 245 and -329), scarlet fever (Autopsy 311) or mumps (Autopsies 403 and 417) have -been excluded from the table. These secondary pneumonias are grouped as -an appendix to the section on pneumonia following measles. It is not -improbable that individuals with the diseases named are just as -susceptible as others to influenza. Included in the table is an instance -(Autopsy 487) in which a definite attack of influenza preceded scarlet -fever. - - TABLE XXVII - - ═══════╤════╤════════╤════════╤═════════╤═════════╤══════════╤═════════ - NO. OF │RACE│ LENGTH │DURATION│DURATION │CLINICAL │ PURULENT │ LOBAR - AUTOPSY│ │ OF │ OF │ OF │DIAGNOSIS│BRONCHITIS│PNEUMONIA - │ │MILITARY│ILLNESS │PNEUMONIA│ │ │ - │ │SERVICE │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 229 │ W │ 1m │ 12+ │ 12+ │ L │ P │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 231 │ W │ 2m │ 13 │ 4 │ B │ P │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 232 │ W │ 14d │ 9 │ 6? │ B │ │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 233 │ C │ 11m │ 5 │ 2 │ L │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 236 │ W │ 3w │ 8 │ 7+ │ L │ │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 237 │ W │ 10d │ 8 │ 2 │ L │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 238 │ W │ 2d │ 8 │ 5 │ L │ │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 239 │ W │ 11d │ 9 │ 5 │ L │ │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 240 │ W │ 13d │ 8 │ 4 │ L │ │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 241 │ W │ 14d │ 5 │ 5 │ L │ │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 242 │ C │ 14d │ 7 │ 4 │ L │ P │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 243 │ W │ 15d │ 5 │ 5 │ L │ │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 244 │ C │ 1m │ 6 │ 3 │ B │ P │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 246 │ C │ 2m │ 6 │ 3 │ L │ P │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 247 │ W │ 10d │ 10 │ 5 │ L │ P │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 248 │ W │ 1m │ 4 │ 2+ │ I │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 249 │ W │ 15d │ 12 │ 6+ │ L │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 250 │ W │ 14d │ 11 │ 7 │ L │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 251 │ W │ 25d │ 7 │ 1 │ B │ P │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 252 │ W │ 21d │ 14 │ 12 │ B │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 253 │ W │ 12d │ 19 │ 12+ │ B │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 254 │ W │ 21d │ 7 │ 6+ │ B │ P │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 255 │ W │ 12d │ 5 │ 4? │ B │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 256 │ W │ 17d │ 8 │ 4 │ B │ P │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 257 │ C │ 21d │ 10 │ 7+ │ L │ P │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 258 │ W │ 1m │ 6 │ 2+ │ B │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 259 │ W │ 3m │ 4 │ 1 │ B │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 260 │ W │ 1m │ 2 │ 1 │ L │ │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 261 │ W │ 2m │ 7 │ 5+ │ B │ P │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 262 │ W │ 12d │ 5 │ 4? │ B │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 263 │ W │ 21d │ 7 │ 5 │ L │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 264 │ W │ 21d │ 10 │ 7 │ L │ │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 265 │ W │ 14d │ 7 │ 6+ │ L │ │ + - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 266 │ W │ 1m │ 7 │ 2 │ L │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 267 │ W │ 2m │ 22 │ 10 │ B │ │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 268 │ W │ 2m │ 6 │ 4? │ L │ │ + - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 269 │ W │ 25d │ 8 │ 2 │ L │ │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 270 │ W │ 17d │ 18 │ 3 │ L │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 271 │ W │ 2d │ 12 │ 5 │ L │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 272 │ W │ 3m │ 7 │ 2 │ L │ │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 273 │ W │ 1m │ 8 │ 4+ │ L │ │ + - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 274 │ W │ 2w │ 9 │ 5 │ B │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 275 │ W │ 4m │ 9 │ 4 │ L │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 276 │ W │ 1m │ 6 │ 4+ │ L │ │ + - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 277 │ W │ 21d │ 10 │ 3 │ L │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 278 │ W │ 2m │ 16 │ 6+ │ L │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 279 │ W │ │ │ │ L │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 280 │ W │ 21d │ 8 │ 8 │ L │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 281 │ W │ 21d │ 9 │ 5 │ L │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 282 │ W │ 1m │ 10 │ ? │ B │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 283 │ W │ 7d │ 19 │ 8 │ B │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 284 │ W │ 21d │ 11 │ ? │ B │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 285 │ W │ │ 11 │ 9? │ B │ P │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 286 │ W │ 20d │ 9 │ 4+ │ L │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 287 │ W │ 3m │ 12 │ 4 │ L │ P │ + - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 288 │ W │ 1m │ 10 │ 5 │ B │ P │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 289 │ W │ 19d │ 12 │ 7 │ B │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 290 │ W │ 1m │ 3+ │ 3+ │ B │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 291 │ W │ 2w │ 18 │ 11 │ B │ P │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 292 │ W │ 3m │ 5 │ 5 │ L │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 293 │ W │ 2m │ 3+ │ 3+ │ L │ P │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 295 │ W │ 1m │ 12 │ 5 │ L │ P │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 296 │ W │ 16d │ 18 │ 3 │ L │ P │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 297 │ W │ 1m │ 5 │ ? │ I │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 298 │ C │ 21d │ 13 │ 10 │ B │ P │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 299 │ W │ 28d │ 9 │ 3 │ L │ P │ + - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 300 │ C │ 22d │ 16 │ 12+ │ L │ P │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 301 │ W │ 1m │ 7 │ 5 │ B │ │ + - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 302 │ C │ 5d │ 6 │ 3+ │ B │ │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 303 │ W │ 1m │ 7 │ 3+ │ L │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 304 │ W │ 4m │ 10 │ 2? │ L │ │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 305 │ W │ 5m │ 3+ │ 3+ │ L │ │ + - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 306 │ W │ 1y │ 6+ │ 3 │ B │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 308 │ W │ 1m │ 6 │ 6 │ L │ │ + - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 309 │ W │ 1m │ 4 │ 2? │ L │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 310 │ W │ 21d │ ? │ 3? │ L │ │ + - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 312 │ W │ 1m │ 17 │ 7 │ L │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 313 │ W │ 1y │ 5 │ 2 │ B │ │ + - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 314 │ W │ 1m │ 3+ │ 3+ │ L │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 315 │ W │ 1m │ 9 │ 2 │ B │ │ + - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 316 │ W │ 1m │ 11 │ 4 │ L │ │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 317 │ W │ 13d │ 9 │ 2 │ L │ │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 318 │ W │ 2m │ 8 │ 3 │ L │ │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 319 │ W │ 1m │ 4+ │ 4+ │ B │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 320 │ C │ 5m │ 1+ │ 1+ │ L │ │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 321 │ W │ 28d │ 4+ │ 4+ │ L │ │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 322 │ W │ 10d │ 8 │ 6 │ L │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 323 │ W │ 2m │ 12 │ 4 │ B │ │ + - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 324 │ W │ 22d │ 9 │ 6 │ B │ │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 325 │ W │ 1m │ 8 │ 8 │ B │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 326 │ W │ 1m │ 5+ │ 2 │ B │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 327 │ W │ 1m │ 4 │ ? │ B │ │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 328 │ W │ 5m │ 13 │ 3+ │ L │ P │ + - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 330 │ W │ 1m │ 10 │ 3 │ L │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 331 │ W │ 1m │ 12 │ 11+ │ B │ P │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 332 │ W │ 1m │ 17 │ 3 │ L │ P │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 333 │ W │ 19d │ 15 │ 7 │ L │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 334 │ W │ 14d │ 16 │ 5 │ B │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 335 │ W │ 1m │ 7 │ ? │ ? │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 336 │ W │ 2m │ 12 │ 6 │ B │ P │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 337 │ W │ 1m │ 9 │ 2? │ L │ │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 338 │ W │ 1m │ 7 │ 5+ │ B │ │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 339 │ W │ 2m │ 9 │ 6? │ L │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 340 │ W │ 35d │ 8 │ 3 │ L │ P │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 341 │ W │ 3m │ 6 │ 4+ │ │ │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 342 │ W │ 2m │ 9 │ 3? │ L │ P │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 343 │ W │ 1m │ 11 │ 1? │ L │ │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 344 │ W │ 4m │ 13 │ 6 │ L │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 345 │ W │ 1d │ ? │ 7 │ L │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 346 │ W │ 26d │ 16 │ 10 │ B │ P │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 347 │ C │ 3d │ 10 │ 3 │ L │ P │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 348 │ C │ 4d │ 8 │ 8 │ B │ P │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 349 │ W │ 2d │ 12 │ 6 │ L │ P │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 350 │ W │ 2m │ 6 │ 2? │ B │ │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 351 │ C │ 4m │ 4 │ 3+ │ L │ P │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 352 │ C │ 2m │ 8 │ 4 │ L │ P │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 353 │ C │ 6m │ 18 │ 18 │ L │ P │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 354 │ W │ 15d │ 2+ │ 2 │ L │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 355 │ W │ 21d │ 7 │ 7 │ B │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 356 │ C │ 5d │ 8 │ 4 │ L │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 357 │ W │ 1m │ 10 │ 6+ │ L │ │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 358 │ W │ 1m │ 15 │ 6? │ L │ │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 359 │ W │ 1m │ 7+ │ ? │ L │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 360 │ W │ 36d │ 10 │ 3 │ L │ P │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 361 │ W │ 3m │ 8 │ 2 │ L │ │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 362 │ W │ 4m │ 15 │ 13+ │ L │ │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 363 │ W │ 3m │ 8 │ 1+ │ L │ P │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 364 │ W │ 6d │ 9 │ 5+ │ B │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 365 │ W │ 2m │ 11 │ 2 │ B │ │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 366 │ W │ 6d │ 8 │ 1+ │ B │ │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 367 │ W │ 22d │ 15 │ 8+ │ L │ │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 368 │ C │ 4d │ 15 │ 11+ │ L │ P │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 369 │ W │ 68d │ 7+ │ 4 │ B │ P │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 370 │ W │ 17d │ 17 │ 14 │ L │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 372 │ W │ 1m │ 17 │ 5 │ L │ P │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 373 │ W │ 4d │ 11 │ 1? │ B │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 374 │ C │ 4d │ 10 │ 5 │ L │ P │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 375 │ C │ 4d │ 12 │ 6 │ L │ P │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 376 │ W │ 1m │ 10 │ 7+ │ B │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 377 │ W │ 1m │ 7 │ 4? │ B │ P │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 378 │ W │ 1m │ 28 │ 7 │ B │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 379 │ W │ 11m │ 7 │ 1 │ B │ │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 380 │ W │ 3m │ 11 │ ? │ B │ P │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 381 │ W │ 21d │ 13 │ 9? │ L │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 382 │ W │ 1m │ 9 │ 6+ │ L │ P │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 383 │ W │ 2m │ 9 │ 2 │ L │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 384 │ W │ 1m │ 13 │ 5 │ L │ │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 385a │ W │ 3w │ 12 │ 6? │ B │ P │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 385b │ W │ 2m │ 11 │ 4 │ L │ │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 385c │ W │ 24d │ 17 │ 10 │ B │ P │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 386 │ W │ 1m │ ? │ 5 │ L │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 387 │ W │ 3w │ 19 │ 9 │ B │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 388 │ W │ 3m │ 11 │ 7 │ L │ P │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 389 │ W │ 1m │ 15 │ 15 │ L │ P │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 391 │ W │ 25d │ 13 │ 13 │ L │ P │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 392 │ W │ 1m │ 12 │ 8+ │ L │ P │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 393 │ W │ 1m │ 20 │ 4 │ L │ │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 394 │ W │ 21d │ ? │ ? │ L │ P │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 395a │ W │ 1m │ 19 │ 11? │ L │ P │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 395b │ W │ 3m │ 12 │ 3? │ B │ P │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 396 │ W │ 2m │ 7 │ 1+ │ B │ │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 397 │ W │ 21d │ 22 │ 14 │ B │ P │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 398 │ W │ 1m │ 16 │ 6? │ B │ P │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 399 │ W │ 1m │ 18 │ 4 │ L │ │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 400 │ W │ 1m │ 15 │ 11+ │ L │ │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 401 │ W │ 1m │ 13+ │ 9 │ B │ P │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 402 │ W │ 1m │ 14 │ 8 │ B │ P │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 404 │ │ │ │ │ B │ P │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 405 │ W │ 21d │ 13 │ 11+ │ B │ │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 406 │ C │ 2d │ 18 │ 15? │ L │ P │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 408 │ C │ 1m │ 13 │ ? │ L │ P │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 409 │ C │ 6d │ 12 │ 9+ │ L │ P │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 410 │ W │ 35d │ 13+ │ 13+ │ L │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 411 │ W │ 3m │ 16 │ 2 │ B │ P │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 412 │ W │ 1m │ 15 │ 13? │ L │ │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 413 │ C │ 2m │ 13 │ 8+ │ L │ P │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 414 │ C │ 7d │ 18 │ 4 │ L │ P │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 415 │ C │ 16d │ 8 │ 6+ │ L │ P │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 416 │ C │ 7d │ 14 │ 6? │ L │ P │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 418 │ W │ 2m │ 19 │ 4 │ B │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 419 │ W │ 4m │ 20 │ ? │ L │ P │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 420 │ W │ 1m │ 11 │ 3 │ B │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 421 │ W │ 21d │ 19 │ 15? │ B │ P │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 422 │ W │ 3m │ 11+ │ 11+ │ B │ P │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 423 │ W │ 1m │ 16 │ 12? │ B │ P │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 424 │ W │ 5y │ 14 │ 6 │ L │ P │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 425 │ W │ 1m │ 29 │ 14 │ B │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 426 │ W │ 4m │ 20 │ 13 │ ? │ │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 427 │ W │ 1m │ 16 │ ? │ L │ P │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 428 │ W │ 3w │ 25 │ 21 │ L │ P │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 429 │ C │ 2m │ 7+ │ 5 │ L │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 430 │ W │ 2m │ 16+ │ 7 │ L │ P │ + - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 431 │ W │ 21d │ 23 │ 18 │ L │ P │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 432 │ W │ 42d │ 19 │ 12+? │ L │ P │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 433 │ W │ 1m │ 19 │ 17 │ B │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 434 │ W │ 4m │ 14+ │ 10 │ L │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 435 │ W │ 1m │ 16+ │ 2? │ B │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 436 │ C │ 11m │ 5 │ 3+? │ B │ │ + - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 437 │ C │ 5m │ 11 │ 7? │ L │ P │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 440 │ W │ 1m │ 19 │ 12? │ L │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 445 │ W │ 1m │ 27 │ 16? │ │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 446 │ W │ 8d │ 13 │ ? │ │ P │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 447 │ W │ 8d │ 10 │ 2 │ B │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 448 │ W │ 70d │ 17 │ 14+ │ L │ P │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 449 │ W │ 2m │ 27 │ 13+ │ B │ P │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 452 │ W │ 4m │ 14 │ 9 │ B │ P │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 451 │ C │ 2m │ 7 │ 3+ │ B │ │ + - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 455 │ C │ │ 26 │ 22+ │ B │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 456 │ W │ 1m │ 23+ │ 20+ │ L │ P │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 457 │ W │ 17m │ 17+ │ 17+ │ B │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 458 │ W │ 11m │ 10 │ 8+? │ L │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 459 │ C │ 10d │ 6 │ 3 │ B │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 460 │ W │ 1m │ 17 │ 17 │ L │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 461 │ C │ 5d │ 14 │ 8+ │ L │ P │ + - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 462 │ C │ 5d │ 15+ │ 12 │ B │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 463 │ W │ 3m │ 20 │ 12 │ B │ P │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 464 │ C │ 21d │ 24 │ 17? │ L │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 465 │ W │ 1m │ 24+ │ 11 │ LB │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 466 │ W │ 2d │ 13 │ 3 │ B │ │ + - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 467 │ W │ 3m │ 30 │ 25? │ B │ P │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 468 │ W │ 1m │ 22+ │ 6 │ L │ P │ + - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 469 │ W │ 1m │ 25 │ 12 │ B │ P │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 471 │ C │ │ 6+? │ 4 │ L │ P │ + - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 472 │ W │ 1m │ 37 │ 21 │ B │ P │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 473 │ W │ 2w │ 28+ │ 24 │ B │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 474 │ W │ 1m │ 36 │ 31+ │ L │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 476 │ W │ 7d │ 6 │ 2 │ B │ P │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 477 │ W │ 5d │ 9 │ 5 │ B │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 478 │ W │ 2m │ 9 │ 3 │ L │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 479 │ C │ 8d │ 29 │ 15 │ L │ P │ + - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 480 │ W │ 4m │ 31+ │ 29 │ B │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 482 │ W │ 2m │ 11 │ 5+ │ B │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 485 │ W │ 3d │ 9+ │ 3+ │ B │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 487 │ W │ 21d │ 55 │ 40 │ B │ P │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 488 │ W │ 4d │ 16 │ 8 │ L │ P │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 489 │ C │ 8d │ 11 │ 4 │ B │ P │ + - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 494 │ W │ 2m │ 11 │ 3 │ L │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 498 │ W │ 1y │ 6 │ 1? │ L │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 499 │ W │ 5m │ 36 │ 5 │ B │ P │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 504 │ W │ 3m │ 6 │ 3 │ L │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 506 │ W │ 8m │ 7+ │ 2? │ B │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┴────┴────────┴────────┴─────────┴─────────┴──────────┴───────── - - ═══════╤═══════════════╤═══════════════╤═════════════╤═════════════ - NO. OF │PERIBRONCHIOLAR│ HEMORRHAGIC │ LOBULAR │PERIBRONCHIAL - AUTOPSY│ CONSOLIDATION │PERIBRONCHIOLAR│CONSOLIDATION│CONSOLIDATION - │ │ CONSOLIDATION │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 229 │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 231 │ │ │ + │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 232 │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 233 │ │ │ + │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 236 │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 237 │ │ + │ + │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 238 │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 239 │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 240 │ M │ │ + │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 241 │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 242 │ │ + │ + │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 243 │ M │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 244 │ M │ + │ + │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 246 │ M │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 247 │ M │ + │ + │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 248 │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 249 │ M │ │ + │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 250 │ M │ │ + │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 251 │ │ + │ + │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 252 │ M │ │ + │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 253 │ M │ │ + │ + - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 254 │ M │ │ + │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 255 │ M │ + │ + │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 256 │ M │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 257 │ │ │ + │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 258 │ M │ │ + │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 259 │ │ │ + │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 260 │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 261 │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 262 │ │ │ + │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 263 │ │ │ + │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 264 │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 265 │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 266 │ │ + │ + │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 267 │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 268 │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 269 │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 270 │ │ │ + │ h - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 271 │ │ │ + │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 272 │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 273 │ + │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 274 │ │ │ + │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 275 │ M │ + │ + │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 276 │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 277 │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 278 │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 279 │ │ + │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 280 │ │ + │ + │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 281 │ │ + │ + │ h - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 282 │ │ │ + │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 283 │ + │ + │ + │ M - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 284 │ │ + │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 285 │ M │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 286 │ M │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 287 │ + │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 288 │ M │ │ + │ h - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 289 │ M │ │ + │ M - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 290 │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 291 │ + │ │ + │ M - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 292 │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 293 │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 295 │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 296 │ + │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 297 │ │ │ + │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 298 │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 299 │ │ │ │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 300 │ M │ │ │ h - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 301 │ │ │ │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 302 │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 303 │ │ │ + │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 304 │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 305 │ │ │ │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 306 │ │ │ + │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 308 │ │ │ + │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 309 │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 310 │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 312 │ M │ │ + │ h - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 313 │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 314 │ │ │ + │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 315 │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 316 │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 317 │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 318 │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 319 │ │ │ + │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 320 │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 321 │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 322 │ │ │ + │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 323 │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 324 │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 325 │ M │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 326 │ │ │ + │ h - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 327 │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 328 │ │ │ │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 330 │ M │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 331 │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 332 │ M │ │ │ h - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 333 │ M │ │ + │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 334 │ M │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 335 │ │ │ + │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 336 │ M │ │ + │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 337 │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 338 │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 339 │ │ │ + │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 340 │ │ + │ + │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 341 │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 342 │ │ + │ + │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 343 │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 344 │ │ │ + │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 345 │ + │ + │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 346 │ M │ + │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 347 │ │ │ + │ h - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 348 │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 349 │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 350 │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 351 │ │ │ + │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 352 │ │ + │ + │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 353 │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 354 │ M │ │ │ h - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 355 │ │ + │ │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 356 │ │ │ + │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 357 │ │ + │ + │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 358 │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 359 │ M │ │ │ h - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 360 │ + │ │ + │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 361 │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 362 │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 363 │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 364 │ │ │ + │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 365 │ │ + │ + │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 366 │ M │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 367 │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 368 │ M │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 369 │ │ + │ + │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 370 │ + │ │ + │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 372 │ │ + │ + │ Mh - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 373 │ │ │ + │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 374 │ │ │ │ + - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 375 │ + │ │ + │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 376 │ │ + │ + │ M - │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 377 │ │ │ + │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 378 │ + │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 379 │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 380 │ + │ │ + │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 381 │ │ │ + │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 382 │ + │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 383 │ │ │ + │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 384 │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 385a │ │ │ + │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 385b │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 385c │ M │ + │ + │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 386 │ │ + │ + │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 387 │ │ + │ + │ + - │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 388 │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 389 │ │ + │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 391 │ + │ │ + │ h - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 392 │ M │ │ │ + - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 393 │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 394 │ │ + │ + │ h - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 395a │ M │ │ + │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 395b │ │ │ + │ h - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 396 │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 397 │ M │ │ + │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 398 │ + │ │ │ M - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 399 │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 400 │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 401 │ M │ │ │ h - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 402 │ M │ │ + │ + - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 404 │ + │ + │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 405 │ M │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 406 │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 408 │ │ + │ + │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 409 │ │ + │ + │ M - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 410 │ + │ │ + │ M - │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 411 │ │ + │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 412 │ │ │ │ M - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 413 │ │ + │ + │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 414 │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 415 │ │ │ + │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 416 │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 418 │ │ │ + │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 419 │ + │ │ + │ M - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 420 │ │ + │ │ M - │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 421 │ │ │ + │ M - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 422 │ │ + │ │ M - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 423 │ + │ │ │ M - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 424 │ │ │ + │ + - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 425 │ + │ │ + │ M - │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 426 │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 427 │ │ + │ + │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 428 │ M │ │ + │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 429 │ + │ │ + │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 430 │ │ + │ │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 431 │ + │ │ + │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 432 │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 433 │ M │ + │ │ M - │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 434 │ │ │ + │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 435 │ │ + │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 436 │ │ │ │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 437 │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 440 │ + │ + │ + │ M - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 445 │ M │ │ │ h - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 446 │ │ + │ + │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 447 │ │ │ + │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 448 │ + │ │ + │ Mh - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 449 │ + │ + │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 452 │ M │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 451 │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 455 │ │ + │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 456 │ │ + │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 457 │ + │ + │ + │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 458 │ │ + │ + │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 459 │ │ + │ + │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 460 │ + │ │ + │ M - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 461 │ M │ + │ │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 462 │ │ │ + │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 463 │ + │ │ + │ Mh - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 464 │ │ │ + │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 465 │ M │ │ │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 466 │ │ │ + │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 467 │ │ + │ + │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 468 │ │ │ + │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 469 │ + │ │ + │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 471 │ │ │ │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 472 │ + │ + │ + │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 473 │ + │ │ + │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 474 │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 476 │ M │ │ + │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 477 │ │ + │ + │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 478 │ │ │ + │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 479 │ M │ │ │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 480 │ │ │ + │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 482 │ + │ + │ + │ M - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 485 │ M │ │ │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 487 │ + │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 488 │ M │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 489 │ │ + │ │ M - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 494 │ │ │ + │ h - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 498 │ │ │ + │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 499 │ M │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 504 │ M │ │ │ - │ │ │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 506 │ │ │ + │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┴───────────────┴───────────────┴─────────────┴───────────── - - ═══════╤═══════╤════════════╤═════════╤═══════╤══════════════ - NO. OF │ABSCESS│INTERSTITIAL│MULTIPLE │EMPYEMA│BRONCHIECTASIS - AUTOPSY│ │SUPPURATIVE │ABSCESSES│ │ - │ │ PNEUMONIA │ IN │ │ - │ │ │CLUSTERS │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 229 │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 231 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 232 │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 233 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 236 │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 237 │ N │ │ │ E │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 238 │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 239 │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 240 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 241 │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 242 │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 243 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 244 │ │ │ │ │ + - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 246 │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 247 │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 248 │ + │ │ │ E │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 249 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 250 │ │ │ │ E │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 251 │ + │ + │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 252 │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 253 │ │ │ │ E │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 254 │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 255 │ + │ │ │ E │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 256 │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 257 │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 258 │ + │ │ │ E │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 259 │ + │ + │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 260 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 261 │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 262 │ + │ │ │ E │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 263 │ + │ │ │ E │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 264 │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 265 │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 266 │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 267 │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 268 │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 269 │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 270 │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 271 │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 272 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 273 │ N │ │ │ E │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 274 │ N │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 275 │ N │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 276 │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 277 │ + │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 278 │ + │ │ │ E │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 279 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 280 │ │ │ + │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 281 │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 282 │ + │ │ │ E │ - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 283 │ │ │ │ │ + - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 284 │ + │ │ │ E │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 285 │ │ + │ │ E │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 286 │ │ │ + │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 287 │ │ │ │ │ + - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 288 │ + │ │ │ E │ + - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 289 │ │ │ │ │ + - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 290 │ + │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 291 │ │ │ │ │ + - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 292 │ + │ │ │ E │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 293 │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 295 │ + │ + │ │ E │ + - │ │ │ │ │ - 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328 │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 330 │ N │ + │ │ E │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 331 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 332 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 333 │ │ │ + │ │ + - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 334 │ N │ + │ │ E │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 335 │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 336 │ │ │ │ │ + - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 337 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 338 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 339 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 340 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 341 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 342 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 343 │ │ │ │ E │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 344 │ + │ │ │ E │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 345 │ + │ │ │ E │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 346 │ N │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 347 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 348 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 349 │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 350 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 351 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 352 │ │ │ │ │ + - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 353 │ │ │ │ E │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 354 │ + │ │ │ E │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 355 │ + │ │ │ E │ - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 356 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 357 │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 358 │ │ │ │ E │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 359 │ │ │ │ │ + - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 360 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 361 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 362 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 363 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 364 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 365 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 366 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 367 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 368 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 369 │ N │ + │ │ E │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 370 │ │ │ + │ │ - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 372 │ │ │ │ │ + - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 373 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 374 │ │ │ │ │ + - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 375 │ │ │ │ │ + - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 376 │ + │ │ │ E │ + - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 377 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 378 │ + │ │ │ E │ + - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 379 │ │ + │ │ E │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 380 │ + │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 381 │ + │ │ │ E │ + - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 382 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 383 │ + │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 384 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 385a │ + │ │ │ E │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 385b │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 385c │ │ + │ │ │ + - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 386 │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 387 │ + │ │ │ E │ + - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 388 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 389 │ │ + │ │ E │ + - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 391 │ │ │ │ │ + - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 392 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 393 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 394 │ │ │ │ │ + - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 395a │ + │ │ │ E │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 395b │ │ │ │ E │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 396 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 397 │ │ + │ │ E │ - 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411 │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 412 │ │ │ │ │ + - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 413 │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 414 │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 415 │ │ + │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 416 │ + │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 418 │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 419 │ │ │ │ │ + - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 420 │ │ + │ │ E │ - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 421 │ │ │ │ │ + - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 422 │ │ │ │ │ + - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 423 │ │ │ │ E │ + - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 424 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 425 │ │ │ + │ │ + - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 426 │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 427 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 428 │ │ + │ │ E │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 429 │ │ │ │ │ + - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 430 │ N │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 431 │ │ │ │ │ + - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 432 │ │ │ │ E │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 433 │ │ + │ │ E │ - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 434 │ │ + │ │ E │ - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 435 │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 436 │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 437 │ │ │ │ │ + - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 440 │ │ │ │ │ + - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 445 │ │ │ │ │ + - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 446 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 447 │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 448 │ │ │ │ │ + - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 449 │ + │ │ │ E │ + - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 452 │ │ + │ │ E │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 451 │ │ │ │ E │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 455 │ + │ │ │ E │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 456 │ │ │ │ E │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 457 │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 458 │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 459 │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 460 │ + │ │ │ E │ + - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 461 │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 462 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 463 │ │ │ │ │ + - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 464 │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 465 │ + │ │ │ E │ + - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 466 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 467 │ + │ │ │ E │ + - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 468 │ │ │ │ │ + - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 469 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 471 │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 472 │ + │ │ │ E │ + - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 473 │ │ │ │ E │ + - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 474 │ + │ + │ │ E │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 476 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 477 │ N │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 478 │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 479 │ N │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 480 │ + │ │ │ E │ - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 482 │ │ │ │ │ + - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 485 │ │ + │ │ E │ - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 487 │ + │ │ │ E │ + - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 488 │ + │ │ │ E │ + - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 489 │ │ │ │ │ + - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 494 │ + │ │ │ E │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 498 │ N │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 499 │ │ │ │ E │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 504 │ │ + │ │ E │ - │ │ │ │ │ - │ │ │ │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 506 │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┴───────┴────────────┴─────────┴───────┴────────────── - - ═══════╤════════════════╤══════════╤════════╤════════╤════════╤════════ - NO. OF │ UNRESOLVED │ORGANIZING│BACTERIA│BACTERIA│BACTERIA│BACTERIA - AUTOPSY│BRONCHOPNEUMONIA│BRONCHITIS│ IN │ IN │IN LUNG │IN BLOOD - │ │ │ SPUTUM │BRONCHUS│ │OF HEART - │ │ │ │ │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 229 │ │ │ Pn. I. │ │ │ 0 - │ │ │B. inf. │ │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 231 │ │ │ │ │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 232 │ │ │Pn. IIa.│ │Pn. IIa.│Pn. IIa. - │ │ │B. inf. │ │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 233 │ │ │Pn. IIa.│ │ │ Pn. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 236 │ │ │Pn. IV. │ │B. inf. │ 0 - │ │ │B. inf. │ │ Staph. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 237 │ │ │ St. h. │ │ │ St. h. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 238 │ │ │Pn. IV. │ │ │ Pn. IV - │ │ │B. inf. │ │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 239 │ │ │Pn. II. │ │Pn. II. │Pn. II. - │ │ │ │ │B. inf. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 240 │ │ │Pn. IV. │B. inf. │ │Pn. IV. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 241 │ │ │Pn. IV. │ │ │Pn. IV. - │ │ │B. inf. │ │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 242 │ │ │Pn. IIa.│ │ │Pn. IIa. - │ │ │B. inf. │ │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 243 │ │ │ │ │ │Pn. IV. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 244 │ │ │ │Pn. IV. │Pn. IV. │ 0 - │ │ │ │B. inf. │B. inf. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 246 │ │ │Pn. IIa.│ │ │ 0 - │ │ │B. inf. │ │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 247 │ │ │Pn. IV. │ │ │Pn. IV. - │ │ │B. inf. │ │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 248 │ │ │ │ St. h. │ St. h. │ St. h. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 249 │ │ │ │ │ │Pn. III. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 250 │ │ │Pn. IIa.│ │ │Pn. IIa. - │ │ │B. inf. │ │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 251 │ │ │ │ │ St. h. │ St. h. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 252 │ │ │ │Pn. II. │Pn. II. │ 0 - │ │ │ │B. inf. │B. inf. │ - │ │ │ │ St. v. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 253 │ │ │Pn. Ia. │Pn. II. │Pn. II. │Pn. II. - │ │ │ │B. inf. │B. inf. │ - │ │ │ │ Staph. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 254 │ │ │ │ Pn. I. │ Pn. I. │ 0 - │ │ │ │B. inf. │ Staph │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 255 │ │ │ │ St. h. │ St. h. │ St. h. - │ │ │ │Pn. IIa.│ │ - │ │ │ │ Staph. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 256 │ │ │ │ Pn. │Pn. IIa.│Pn. IIa. - │ │ │ │ Staph. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 257 │ │ │ │B. inf. │ │ Pn. I. - │ │ │ │ Staph │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 258 │ │ │ │ │ St. h. │ St. h. - │ │ │ │ │Pn. IV. │ - │ │ │ │ │B. inf. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 259 │ │ │ │ │ St. h. │ St. h. - │ │ │ │ │Pn. III.│ - │ │ │ │ │ Staph. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 260 │ │ │ │ │ │ 0 - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 261 │ │ │ │B. inf. │ │ 0 - │ │ │ │Pn. IV. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 262 │ │ │ │ St. h. │ St. h. │ St. h. - │ │ │ │B. inf. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 263 │ │ │ │ │ St. h. │ St. h. - │ │ │ │ │B. inf. │ Staph. - │ │ │ │ │ Staph. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 264 │ │ │Pn. IV. │ St. h. │ St. h. │ St. h. - │ │ │ Staph. │ Staph. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 265 │ │ │ │ St. h. │Pn. IV. │ St. h. - │ │ │ │ Staph. │B. inf. │ - │ │ │ │ inf. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 266 │ │ │ St. h. │ St. h. │ St. h. │ St. h. - │ │ │ │B. inf. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 267 │ │ │Pn. IV. │Pn. II. │Pn. II. │Pn. II. - │ │ │ │B. inf. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 268 │ │ │Pn. III.│Pn. III.│Pn. III.│ 0 - │ │ │ B. │B. inf. │B. inf. │ - │ │ │ │ St. h. │ St. h. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 269 │ │ │Pn. IV. │Pn. IV. │Pn. IV. │ 0 - │ │ │ B. │ Staph. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 270 │ │ │ │ St. h. │ St. h. │ St. h. - │ │ │ │B. inf. │ Staph. │ - │ │ │ │ Staph. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 271 │ │ │ │ St. h. │ St. h. │ St. h. - │ │ │ │Pn. IV. │ │ - │ │ │ │B. inf. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 272 │ │ │ │ │ │ St. h. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 273 │ │ │ │ St. h. │ St. h. │ St. h. - │ │ │ │B. inf. │Pn. IV. │ - │ │ │ │ Staph. │ Staph. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 274 │ │ │Pn. IV. │ St. h. │ St. h. │ St. h. - │ │ │ │ Staph. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 275 │ │ │ │ St. h. │ St. h. │ St. h. - │ │ │ │B. inf. │B. inf. │Pn. IV. - │ │ │ │ Staph. │ Staph. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 276 │ │ │ │ St. h. │ St. h. │ St. h. - │ │ │ │Staph B.│Pn. IV. │ - │ │ │ │ inf. │B. inf. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 277 │ │ │ │ St. h. │ St. h. │ St. h. - │ │ │ │ Staph │ Staph │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 278 │ │ │ │ St. h. │ St. h. │ St. h. - │ │ │ │B. inf. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 279 │ │ │ │ │ Pn. IV │Pn. IV. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 280 │ │ │ │ St. h. │ St. h. │ St. h. - │ │ │ │B. inf. │ │ - │ │ │ │ Staph. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 281 │ │ │ │ │ St. h. │ St. h. - │ │ │ │ │B. inf. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 282 │ │ │Pn. IV. │ St. h. │ St. h. │ St. h. - │ │ │B. inf. │B. inf. │Pn. II. │Pn. II. - │ │ │ │ Pn. II │ │ - │ │ │ │ Staph. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 283 │ │ │ │B. inf. │ Staph. │Pn. IV. - │ │ │ │Pn. IV. │B. inf. │ - │ │ │ │ Staph. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 284 │ │ │ │ St. h. │ St. h. │ St. h. - │ │ │ │B. inf. │ │ - │ │ │ │ Staph. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 285 │ │ │Pn. IIa.│ St. h. │ St. h. │ St. h. - │ │ │B. inf. │B. inf. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 286 │ │ │ │Pn. IV. │ 0 │Pn. IV. - │ │ │ │B. inf. │ │ - │ │ │ │ Staph. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 287 │ │ │ │Pn. IV. │Pn. IV. │Pn. IV. - │ │ │ │B. inf. │ B inf. │ - │ │ │ │ Staph. │ Staph. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 288 │ │ │ St. h. │ St. h. │ St. h. │ St. h. - │ │ │B. inf. │B. inf. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 289 │ │ │ │Pn. IV. │Pn. IV. │Pn. IV. - │ │ │ │B. inf. │ │ - │ │ │ │ Staph. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 290 │ │ │ │ St. h. │ St. h. │ St. h. - │ │ │ │B. inf. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 291 │ │ │Pn. IV. │B. inf. │ 0 │ 0 - │ │ │B. inf. │ Staph. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 292 │ │ │ │ │ St. h. │ St. h. - │ │ │ │ │B. inf. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 293 │ │ │ │Pn. III.│Pn. III.│Pn. III. - │ │ │ │B. inf. │B. inf. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 295 │ │ │Pn. IV. │ St. h. │ │ St. h. - │ │ │ St. h. │B. inf. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 296 │ │ │ │ St. h. │ St. h. │ St. h. - │ │ │ │B. inf. │B. inf. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 297 │ │ │ │B. inf. │Pn. IV. │ 0 - │ │ │ │Pn. IV. │B. inf. │ - │ │ │ │ St. h. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 298 │ │ │ │Pn. IIa.│Pn. IIa.│ - │ │ │ │B. inf. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 299 │ │ │ │B. inf. │ │ - │ │ │ │Pn. IV. │ │ - │ │ │ │ Staph. │ │ - │ │ │ │ St. h. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 300 │ │ │Pn. IIa.│Pn. IIa.│Pn. IIa.│ - │ │ │B. inf. │B. inf. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 301 │ │ │ │Pn. IV. │Pn. IV. │ - │ │ │ │B. inf. │ │ - │ │ │ │ Staph. │ │ - │ │ │ │ St. h. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 302 │ │ │ │Pn. IV. │Pn. IV. │ - │ │ │ │B. inf. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 303 │ │ │ │ Staph. │Pn. IV. │ - │ │ │ │Pn. IV. │B. inf. │ - │ │ │ │B. inf. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 304 │ │ │ │ St. h. │ St. h. │ - │ │ │ │B. inf. │B. inf. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 305 │ │ │ │B. inf. │B. inf. │ - │ │ │ │ St. h. │ St. h │ - │ │ │ │Pn. IV. │Pn. IV. │ - │ │ │ │ Staph. │ Staph. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 306 │ │ │ │B. inf. │ 0 │ 0 - │ │ │ │Pn. IV. │ │ - │ │ │ │ Staph. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 308 │ │ │ │Pn. IV. │ St. h. │Pn. IV. - │ │ │ │B. inf. │ │ - │ │ │ │ St. h. │ │ - │ │ │ │ Staph. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 309 │ │ │ │ │ St. h. │ St. h. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 310 │ │ │ │Pn. III.│Pn. III.│ - │ │ │ │B. inf. │Pn. IV. │ - │ │ │ │ Staph. │B. inf. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 312 │ │ │Pn. IV. │ St. h. │ St. h. │ St. - │ │ │B. inf. │B. inf. │B. inf. │ - │ │ │ St. h. │ Staph. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 313 │ │ │ │ St. h. │ St. h. │ St. h. - │ │ │ │B. inf. │ │ - │ │ │ │ Staph. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 314 │ │ │ │Pn. IV. │Pn. IV. │Pn. IV. - │ │ │ │B. inf. │ │ - │ │ │ │ Staph. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 315 │ │ │ │ │Pn. IV. │Pn. IV. - │ │ │ │ │B. inf. │ - │ │ │ │ │ Staph. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 316 │ │ │ │B. inf. │Pn. III.│Pn. III. - │ │ │ │ │B. inf. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 317 │ │ │ │Pn. IV. │Pn. IV. │ - │ │ │ │B. inf. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 318 │ │ │ │Pn. IV. │Pn. IV. │ - │ │ │ │B. inf. │B. inf. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 319 │ │ │ │ St. h. │ St. h. │ St. h. - │ │ │ │ Staph. │B. inf. │ - │ │ │ │ │ Staph. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 320 │ │ │ │Pn. IIa.│Pn. IIa.│Pn. IIa. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 321 │ │ │ │B. inf. │Pn. IV. │Pn. IV. - │ │ │ │ │B. inf. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 322 │ │ │Pn. IV. │ │Pn. III.│ 0 - │ │ │ │ │ Staph. │ - │ │ │ │ │ aur. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 323 │ │ │ │Pn. IV. │ │ 0 - │ │ │ │B. inf. │ │ - │ │ │ │ Staph. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 324 │ │ │ │ Pn. I. │ 0 │ Pn. I. - │ │ │ │B. inf. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 325 │ │ │ │ St. h. │ St. h. │ St. h. - │ │ │ │B. inf. │ │ - │ │ │ │ Staph. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 326 │ │ │ │ St. h. │ St. h. │ St. h. - │ │ │ │B. inf. │B. inf. │ - │ │ │ │ Staph. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 327 │ │ │ │ │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 328 │ │ │ │Pn. III.│Pn. III.│ Pn. - │ │ │ │Pn. IV. │Pn. IV. │ III. - │ │ │ │B. inf. │B. inf. │ - │ │ │ │ Staph. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 330 │ │ │ │ │Pn. IV. │Pn. IV. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 331 │ │ │ │ │ │Pn. IV. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 332 │ │ │ │ │ │ 0 - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 333 │ │ │ │ Staph. │ Staph. │Pn. IIa. - │ │ │ │aur. B. │aur. Pn.│ - │ │ │ │inf. St.│IIa. St.│ - │ │ │ │ h. │ h. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 334 │ │ │ │ │ St. h. │ St. h. - │ │ │ │ │ Staph │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 335 │ │ │ │ │ St. v. │Pn. IV. - │ │ │ │ │B. inf. │ - │ │ │ │ │ Staph. │ - │ │ │ │ │Pn. IV. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 336 │ │ │ │ │ │ 0 - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 337 │ │ │ │ │ │Pn. IV. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 338 │ │ │ │ │ │Pn. IV. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 339 │ │ │ │ │ │Pn. IV. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 340 │ │ │ │ │ │ 0 - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 341 │ │ │ │ │ │ 0 - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 342 │ │ │ │ │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 343 │ │ │ │ │Pn. IV. │Pn. IV. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 344 │ │ │ │ │ │ St. h. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 345 │ │ │ │ │Pn. III.│ - │ │ │ │ │ St. h │ - │ │ │ │ │ Staph. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 346 │ │ │B. inf. │ St. h. │ St. h. │ St. h. - │ │ │Pn. IV. │B. inf. │B. inf. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 347 │ │ │ │ │ │ St. h. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 348 │ │ │ │ │ │Pn. IIa. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 349 │ │ │ │ │Pn. III │ Pn. I. - │ │ │ │ │ St. h │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 350 │ │ │ │ │ │ St. h. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 351 │ │ │ │ │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 352 │ │ │ │ │ │Pn. IIa. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 353 │ │ │ Pn. I. │B. inf. │Pn. IIa.│Pn. IIa. - │ │ │B. inf. │ Pn. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 354 │ │ │ │ St. h. │ St. h. │ St. h. - │ │ │ │B. inf. │ │ - │ │ │ │ Staph. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 355 │ │ │ │ St. h. │ St. h. │ 0 - │ │ │ │B. inf. │B. inf. │ - │ │ │ │Pn. IV. │ Staph. │ - │ │ │ │ Staph. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 356 │ │ │ │ │ │Pn. IV. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 357 │ │ │ │ │Pn. IV. │Pn. IV. - │ │ │ │ │B. inf. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 358 │ │ │ │ │ │Pn. IIa. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 359 │ │ │ │ │ │Pn. IV. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 360 │ │ │ │ │ │ 0 - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 361 │ │ │ │ │ │Pn. IV. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 362 │ │ │ │ │ │ St. h. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 363 │ │ │ │ │ │Pn. IV. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 364 │ │ │ │ │ │ St. h. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 365 │ │ │ │ │Pn. IV. │Pn. IV. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 366 │ │ │ │ │ │Pn. IV. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 367 │ │ │ │ │ │Pn. IV. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 368 │ │ │ │ │ │ Pn. I. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 369 │ │ │ St. h. │ │ St. h. │ St. h. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 370 │ + │ + │[No. St.│ Staph. │ Staph. │ 0 - │ │ │ h.] │aur. Pn.│ aur │ - │ │ │ │ IV. B. │ │ - │ │ │ │ inf. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 372 │ │ │ │ │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 373 │ │ │ │ │ │ St. h. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 374 │ │ │ │ │ │Pn. IV. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 375 │ │ │ │ │ │ 0 - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 376 │ │ │[No. St │ St. h. │ St. h. │ St. h. - │ │ │ h.] │B. inf. │ │ - │ │ │ │ Staph. │ │ - │ │ │ │ aur. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 377 │ │ │ │ │ │Pn. IV. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 378 │ │ │ │ St. h. │ St. h. │Pn. IIa. - │ │ │ │B. inf. │B. inf. │ - │ │ │ │Pn. IIa.│Pn. IIa.│ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 379 │ │ │ │B. inf. │ ? │Pn. IIa. - │ │ │ │ + │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 380 │ │ │ │ │Pn. III.│Pn. III. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 381 │ │ │ │ │ St. h. │ St. h. - │ │ │ │ │Pn. II. │ - │ │ │ │ │Pn. IV. │ - │ │ │ │ │ Staph. │ - │ │ │ │ │ aur. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 382 │ │ │ │ │ │ 0 - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 383 │ │ │ │ │B. inf. │Pn. III. - │ │ │ │ │Pn. III.│ - │ │ │ │ │ St. h. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 384 │ │ │ │ │ │Pn. IV. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 385a │ │ │ │ │ St. h. │ St. h. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 385b │ │ │ │ │ │Pn. IV. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 385c │ │ │ │ │ St. h. │ St. h. - │ │ │ │ │B. inf. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 386 │ │ │ │ │Pn. III.│Pn. III. - │ │ │ │ │B. inf. │ - │ │ │ │ │ Staph. │ - │ │ │ │ │ aur. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 387 │ │ │ │ St. h. │ Staph. │ St. h. - │ │ │ │B. inf. │alb Pn. │ - │ │ │ │ Staph. │ II. B. │ - │ │ │ │aur. Pn.│ inf. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 388 │ │ │ │ │ │Pn. IV. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 389 │ │ │ │ │ St. h. │ St. h. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 391 │ │ │ │ │Pn. IV. │Pn. IV. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 392 │ │ │ │ │ │Pn. II. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 393 │ │ │ │ │ │Pn. IV. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 394 │ │ │ │ │ │ St. h. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 395a │ + │ │ │ │ St. h. │ St. h. - │ │ │ │ │B. inf. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 395b │ │ │ │ │Pn. IIa.│Pn. IIa. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 396 │ │ │ │ │ │ 0 - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 397 │ │ │ │ │ St. h. │ St. h. - │ │ │ │ │B. inf. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 398 │ + │ │ │ │ │ 0 - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 399 │ │ │ │ │ │Pn. IIa. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 400 │ │ │ │ │ │Pn. IV. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 401 │ │ │ │ │ │Pn. IV. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 402 │ + │ + │ │ │ │Pn. IV. - │ │ │ │ │ │ St. h. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 404 │ │ │ │ │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 405 │ │ │ │ │ │ Pn. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 406 │ │ │ │ │ │Pn. IV. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 408 │ │ │ │ │ │ 0 - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 409 │ │ │ │ │ │ 0 - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 410 │ │ │ │ │ St. h. │ - │ │ │ │ │B. inf. │ - │ │ │ │ │ Staph. │ - │ │ │ │ │ aur. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 411 │ │ │ │ │Pn. IIa.│Pn. IIa. - │ │ │ │ │B. inf. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 412 │ │ │ │Pn. II. │ │Pn. II. - │ │ │ │B. inf. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 413 │ │ │ │ │Pn. III.│Pn. III. - │ │ │ │ │B. inf. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 414 │ │ │ │ │Pn. IIa.│Pn. IIa. - │ │ │ │ │B. inf. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 415 │ │ │ │ │ St. h. │ 0 - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 416 │ │ │ │Pn. IV. │Pn. IV. │Pn. IV. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 418 │ │ │ │ │Pn. IIa.│Pn. IIa. - │ │ │ │ │ St. v. │ - │ │ │ │ │B. inf. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 419 │ │ │ │Pn. II. │Pn. II. │ 0 - │ │ │ │B. inf. │B. inf. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 420 │ + │ + │ │ │ St. h. │ St. h. - │ │ │ │ │B. inf. │ - │ │ │ │ │ Staph. │ - │ │ │ │ │ aur. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 421 │ + │ + │ │ │Pn. IV. │ St. h. - │ │ │ │ │ St. h. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 422 │ + │ │ │ │Pn. IIa.│ 0 - │ │ │ │ │B. inf. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 423 │ + │ │ │ │ St. h. │ St. h. - │ │ │ │ │B. inf. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 424 │ │ │ │ │Pn. IV. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 425 │ + │ │ │ │ St. h. │ St. h. - │ │ │ │ │B. inf. │ - │ │ │ │ │ Staph. │ - │ │ │ │ │ alb. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 426 │ │ │ │ │Pn. IIa.│Pn. IIa. - │ │ │ │ │B. inf. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 427 │ │ │ │ │ St. h. │ St. h. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 428 │ + │ │ │ St. h. │ St. h. │ St. h. - │ │ │ │B. inf. │B. inf. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 429 │ │ │ │ │B. inf. │ 0 - │ │ │ │ │ Staph. │ - │ │ │ │ │ alb │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 430 │ │ │ │ │ St. h. │ St. h. - │ │ │ │ │B. inf. │ - │ │ │ │ │ Staph. │ - │ │ │ │ │ aur. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 431 │ + │ │ │ │ 0 │ 0 - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 432 │ │ │ │ │B. inf. │Pn. IIa. - │ │ │ │ │Pn. IIa.│ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 433 │ + │ │ │ │ St. h. │ 0 - │ │ │ │ │B. inf. │ - │ │ │ │ │ Staph. │ - │ │ │ │ │ aur. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 434 │ │ │ │ St. h. │ St. h. │ St. h. - │ │ │ │B. inf. │ Staph. │ - │ │ │ │ Staph. │ aur. │ - │ │ │ │ aur. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 435 │ │ │ │ St. h. │B. inf. │ St. h. - │ │ │ │B. inf. │ + │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 436 │ │ │ │Pn. IIa.│Pn. IIa.│Pn. IIa. - │ │ │ │B. inf. │ │ - │ │ │ │ Staph. │ │ - │ │ │ │ aur. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 437 │ │ │ │ │ │ 0 - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 440 │ + │ │ │B. inf. │B. inf. │ 0 - │ │ │ │ Staph. │ Staph. │ - │ │ │ │ aur. │ aur. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 445 │ │ + │ │ Staph. │ Staph. │ St. h. - │ │ │ │ aur. │aur. Pn.│ - │ │ │ │ │ IV. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 446 │ │ │ │ │ 0 │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 447 │ │ │ │ Staph. │B. coli.│ 0 - │ │ │ │ aur. │ Staph. │ - │ │ │ │ │ aur. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 448 │ │ │ │ 0 │ 0 │ 0 - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 449 │ + │ │ │ St. h. │ St. h. │ St. h. - │ │ │ │B. coli.│B. coli.│ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 452 │ │ │ │ St. h. │ St. h. │ St. h. - │ │ │ │B. inf. │B. inf. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 451 │ │ │ │B. coli.│Pn. IIa.│Pn. IIa. - │ │ │ │ Staph. │B. inf. │ - │ │ │ │ St. v. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 455 │ │ │ │ St. h. │ St. h. │ St. h. - │ │ │ │B. inf. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 456 │ │ │ │B. coli.│ │ St. h. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 457 │ + │ + │ │Pn. IV. │ │ - │ │ │ │B. inf. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 458 │ │ │ │Pn. IV. │ │ 0 - │ │ │ │B. inf. │ │ - │ │ │ │ St. v. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 459 │ │ │ │ Staph. │ │ 0 - │ │ │ │aur. Pn.│ │ - │ │ │ │ IV. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 460 │ │ │ │ St. h. │ St. h. │ St. h. - │ │ │ │B. inf. │B. inf. │ - │ │ │ │ Staph. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 461 │ │ │ │ Staph. │ │ Pn. I. - │ │ │ │aur. Pn.│ │ - │ │ │ │ I. St. │ │ - │ │ │ │ h. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 462 │ │ │ │ │ │ 0 - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 463 │ + │ │ │B. inf. │B. inf. │ 0 - │ │ │ │ Staph. │ Staph. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 464 │ │ │ │B. inf. │B. inf. │ 0 - │ │ │ │ Pn. I. │ Pn. I. │ - │ │ │ │ Staph. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 465 │ │ │ │ St. h. │ St. h. │ St. h. - │ │ │ │B. inf. │ │ - │ │ │ │ Staph. │ │ - │ │ │ │ St. v. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 466 │ │ │ │Pn. IIa.│Pn. IIa.│Pn. IIa. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 467 │ │ │ │ St. h. │ 0 │ St. h. - │ │ │ │B. inf. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 468 │ │ │ │ Staph. │B. inf. │ 0 - │ │ │ │aur. B. │ St. v. │ - │ │ │ │inf. St.│ │ - │ │ │ │ v. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 469 │ + │ │ │ │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 471 │ │ │ │Pn. IV. │ Pn. I. │ 0 - │ │ │ │B. inf. │Pn. IV. │ - │ │ │ │ Staph. │B. inf. │ - │ │ │ │ aur. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 472 │ + │ │ │B. coli.│ St. h. │ St. h. - │ │ │ │ │B. coli.│ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 473 │ + │ + │ │B. inf. │ St. v. │Pn. III. - │ │ │ │ St. v. │ │ - │ │ │ │ Staph. │ │ - │ │ │ │M. cat. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 474 │ │ │ │ St. v. │ St. h. │ St. h. - │ │ │ │B. inf. │ │B. inf. - │ │ │ │M. cat. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 476 │ │ │ │ │ │ 0 - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 477 │ │ │ │ St. h. │ St. h. │ St. h. - │ │ │ │B. coli.│B. coli.│ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 478 │ │ │ │ │ St. h. │ St. h. - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 479 │ │ │ │B. inf. │ St. h. │ St. h. - │ │ │ │ St. h. │ Staph. │ - │ │ │ │ Staph. │ aur. │ - │ │ │ │M. cat. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 480 │ │ │ │ Staph. │ Staph. │B. coli. - │ │ │ │aur. St.│aur. B. │ St. - │ │ │ │ v. │inf. St.│ - │ │ │ │ │ v. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 482 │ │ │ │B. inf. │B. inf. │ 0 - │ │ │ │Pn. IV. │Pn. IV. │ - │ │ │ │ St. h. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 485 │ │ │ │ St. h. │ St. h. │ St. h. - │ │ │ │B. inf. │ │ - │ │ │ │ Staph. │ │ - │ │ │ │aur. B. │ │ - │ │ │ │ coli. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 487 │ + │ │ │B. inf. │B. inf. │ St. h. - │ │ │ │ St. h. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 488 │ │ │ │ St. h. │ St. h. │ St. h. - │ │ │ │Pn. IIa.│ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 489 │ │ │ │B. inf. │Pn. IV. │ 0 - │ │ │ │Pn. IV. │B. inf. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 494 │ │ │ │ St. h. │ St. h. │ St. h. - │ │ │ │B. inf. │B. inf. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 498 │ │ │ │ St. v. │ St. v. │ St. v. - │ │ │ │ │ Staph. │ - │ │ │ │ │ aur. │ - │ │ │ │ │ Staph. │ - │ │ │ │ │ alb. │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 499 │ │ + │ │ St. h. │ 0 │ St. h. - │ │ │ │B. inf. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 504 │ │ │ │ St. h. │ St. h. │ St. h. - │ │ │ │B. inf. │ │ - │ │ │ │ Staph. │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 506 │ │ │ │Pn. IV. │Pn. IV. │Pn. IV. - │ │ │ │B. inf. │ Staph. │ - │ │ │ │ Staph. │ aur. │ - │ │ │ │aur. M. │ │ - │ │ │ │ cat. │ │ - ───────┴────────────────┴──────────┴────────┴────────┴────────┴──────── - -In successive columns the table gives the autopsy number, race, and -length of military service. These factors have had an important -influence upon the incidence of influenza and pneumonia and have been -discussed in a preliminary report.[79] The duration of illness (4th -column of table), counted from the date of onset of symptoms of -influenza or in some instances, when the earliest symptoms were those of -pneumonia, from onset of pneumonia, can usually be determined -accurately. The duration of pneumonia (5th column of table) is much more -uncertain, because its determination dates from the first recognition of -the physical signs of pneumonia. - -=Clinical Diagnosis.=—The clinical diagnosis recorded upon the clinical -history of the patient is given in column 6. Many clinicians have been -impressed with the difficulty of determining during life the type of -pneumonia associated with influenza. The occurrence of purulent -bronchitis, the frequent coexistence of lobar and bronchopneumonia and -an atypical onset often make the recognition of lobar pneumonia more -difficult than usual. The diffuse consolidation of confluent lobular -pneumonia increases the difficulty of recognizing bronchopneumonia. In -the table (column 6) lobar pneumonia is indicated by L., -bronchopneumonia by B. Among 227 autopsies the clinical diagnosis agreed -with the condition found at autopsy in 109 instances (48 per cent); in -35 instances (15.4 per cent) both lobar and bronchopneumonia were found -at autopsy and a diagnosis of one or other was made during life. In 83 -instances (36.6 per cent) the diagnosis made during life was incorrect. -Cases admitted to the base hospital at Camp Pike were as carefully -studied as the conditions in a base hospital during an epidemic -permitted and diagnosis of pneumonia was doubtless as accurate as in -other base hospitals. Statistics from military and other hospitals based -upon clinical diagnosis of the pneumonias of influenza are probably -subject to an error of at least 1 in 3 cases, and conclusions based upon -them are almost valueless. - -The inaccuracy of clinical diagnosis of the pneumonia of influenza is -further illustrated by a consideration of lobar pneumonia. This -diagnosis on the one hand was made 136 times and was correct 67 times -and incorrect 69 times; on the other hand, lobar pneumonia was found at -autopsy 98 times and had been diagnosed in only 67 of these cases (68.4 -per cent). - -=Classification of the Pulmonary Lesions of Influenza.=— Influenzal -pneumonia exhibits the following noteworthy characters: - -1. Acute bronchitis with injury or destruction of lining epithelium and -accumulation of inflammatory exudate within the lumen. - -2. Hemorrhagic pneumonia with accumulation of blood within the alveoli -and within and about the bronchi. - -3. Susceptibility of bronchi and pulmonary tissue to secondary pyogenic -infection with necrosis and suppuration. - -4. Bronchiectasis. - -5. Tendency to the occurrence of chronic pneumonia following failure of -pneumonia to undergo resolution. - -All these changes are doubtless referable to the severity of the primary -injury to the lower air passages. - -In the presence of destructive changes in the bronchi many bacterial -species, including B. influenzæ, pneumococci of various types, -streptococci (notably hemolytic streptococci) and staphylococci may -invade the lungs and produce acute inflammation. The anatomic characters -of the pneumonic lesions following influenza are equally varied. - -In order to obtain insight into the pathogenesis of these lesions, it is -desirable to imitate the historical development of knowledge concerning -the characters and causes of disease, namely, first to define accurately -the lesions concerned and later to determine with what microorganisms -these lesions are associated. The difficulties of this undertaking are -increased by the multiplicity of the microorganisms concerned and by the -well-known truth that the same microorganism, _e. g._, the tubercle -bacillus, may produce widely different anatomic lesions. - -In the table of autopsies the following lesions are listed: - - =Column 7. Purulent bronchitis.=—“P” indicates that the small - bronchi contain mucopurulent fluid. - - =Column 8. Lobar pneumonia.=—The occurrence of the lesion is - indicated by the plus sign (+). - - =Column 9. Peribronchiolar consolidation.=—The presence of nodular - patches of consolidation about respiratory bronchioles is indicated - by the plus sign (+) when the lesion has been recognized at the time - of autopsy. When the lesion has been first recognized by microscopic - examination the letter “M” is used. - - =Column 10. Hemorrhagic peribronchiolar consolidation.=—The - occurrence of this lesion which represents the preceding on a - background of hemorrhage is indicated by the plus sign (+). - - =Column 11. Lobular consolidation.=—The presence of the lesion is - indicated by the plus sign (+). - - =Column 12. Peribronchial consolidation.=—Peribronchial pneumonia - recognized at the time of autopsy is indicated by the plus sign (+). - Peribronchial pneumonia recognized microscopically is indicated by - “M.” The presence of peribronchial hemorrhage without consolidation - is indicated by “h.” - - =Column 13. Abscess formation with pneumonia.=—Suppuration with - abscess formation almost invariably just below the pleura is - indicated by the plus sign (+). Necrosis of lung tissue recognized - microscopically and unaccompanied by suppuration is indicated by - “N.” - - =Column 14. Suppurative interstitial pneumonia.=—This lesion - invariably associated with suppurative lymphangitis is indicated by - the plus sign (+). - - =Column 15. Multiple abscess in clusters.=—Abscesses in clusters - about a bronchus of medium size are indicated by the plus sign (+). - - =Column 16. Empyema.=—The presence of the lesion is indicated by - “E.” - - =Column 17. Bronchiectasis.=—“B” indicates the lesion. - - =Column 18. Unresolved bronchopneumonia.=—Presence of the lesion is - indicated by the plus sign (+). - - =Column 19. Organizing bronchitis and bronchiolitis.=—“O” indicates - the lesion. - -The lesions of columns 7 to 12 are acute inflammatory processes, columns -9 to 12 represent different types of bronchopneumonia. Columns 13 to 15 -represent suppurative lesions. Columns 17 to 19 represent chronic -lesions. A survey of the table shows the predominance of acute lesions -in the early period of the study and the gradual increase of chronic -lesions. - -The last four columns of the table of autopsies give the bacteriology of -the sputum during life and the bacteria found in the bronchi, in the -lungs, and in the blood of the heart after death. - -=Mortality of Pneumonia Following Influenza.=—From September 6 to -December 15, 250 autopsies were performed on patients who had died with -pneumonia at the base hospital at Camp Pike, and with few exceptions -bacteriologic cultures were made from them. Although it was not possible -to perform autopsies on all who died, those which were performed afford -a fair index of all deaths, for throughout the epidemic of influenza and -its outbreak of pneumonia approximately one half of all who died were -examined after death. The relation of autopsies to deaths is shown by a -comparison by weeks of the number of deaths and number of autopsies -during the months of September and October. - - ═══════════════════════╤═══════════════════════╤═══════════════════════ - WEEK │ DEATHS │ AUTOPSIES - ───────────────────────┼───────────────────────┼─────────────────────── - Sept. 1–7 │ 1│ 1 - Sept. 8–14 │ 1│ 1 - Sept. 15–21 │ 4│ 3 - Sept. 22–28 │ 15│ 14 - Sept. 29–Oct. 5 │ 121│ 67 - Oct. 6–12 │ 191│ 78 - Oct. 13–19 │ 78│ 43 - Oct. 20–27 │ 22│ 15 - Oct. 28–31 │ 8│ 6 - │ ———│ ——— - │ 441│ 228 - ───────────────────────┴───────────────────────┴─────────────────────── - -For most of these autopsies there is a record of the date of onset of -the illness, namely, influenza, which finally resulted in pneumonia and -death. Comparison of the number of cases of influenza which developed on -any day with the number of fatal cases which had their onset on the same -day will determine the mortality of influenza at different periods of -the epidemic. Chart 1 shows the number of cases of influenza which had -their onset on each day from September 1 to October 31 and the number of -fatal cases with autopsy which had their origin on corresponding days. -The comparison by weeks between autopsies and total number of deaths -shows that the autopsies represent with considerable accuracy the -deaths. If there is any error it occurs at the height of the outbreak of -pneumonia from September 29th to October 5th and not at its beginning, -or end. The chart shows that the highest mortality occurred among cases -of influenza which had their origin at the beginning of the epidemic -from September 21 to October 1, whereas after October 1, though the -maximum number of cases of influenza occurred on October 3, very few -developed fatal pneumonia. - -=Mortality from Pneumococcus and Streptococcus Pneumonias.=—By referring -fatal cases of streptococcus pneumonia back to their date of origin it -is possible to determine what proportion of the cases of influenza, -which developed on any day, died with infection by hemolytic -streptococcus. The accompanying chart (Chart 1) shows that infection -with hemolytic streptococci has been very frequent at the beginning of -the epidemic of influenza (shown by area with double hatch in chart) -that is, from September 20 to 30 and subsequently has gradually -diminished so that few cases have had their onset in the second half of -the epidemic from September 30 to October 15. - -Pneumococcus pneumonia uncomplicated by streptococcus infection (shown -by area with single hatch in chart) pursued a course which more closely -conformed to the curve representing influenza. The cases of influenza -which resulted fatally bore a fairly constant ratio to the total number -of cases of influenza from the onset of the epidemic until October 1, -but subsequently few cases of influenza developed fatal pneumococcus -pneumonia. - -These charts arranged with reference to the onset of fatal pneumonias -dissociate very clearly the outbreak of streptococcus pneumonia, which -reached its height at the beginning of the influenza epidemic, from the -uncomplicated pneumococcus pneumonia which reached its maximum at the -midpart of the influenza epidemic and then abruptly abated. - -[Illustration: - - Chart 1—Showing the relation of (_a_) onset of cases of pneumonia - shown by autopsy to be uncomplicated by secondary infection with - hemolytic streptococcus, indicated by upper continuous line with - single hatch, and of (_b_) onset of fatal cases of streptococcus - pneumonia, indicated by the lower continuous line with double hatch, - to (_c_) the occurrence of influenza, indicated by the broken line. - The onset of each case of fatal pneumonia is represented by a single - square. -] - -Our study of ward infection in pneumonia furnishes an explanation of the -outbreak of fatal streptococcus pneumonia coincident with the initial -stage of the influenza epidemic. This outbreak is a true epidemic of -streptococcus infection superimposed, in many instances at least, upon -preexisting pneumococcus pneumonia, but in some instances, doubtless, a -primary streptococcus pneumonia, following the bronchitis of influenza. -In the absence of secondary streptococcus infection a very large -proportion of these individuals would have recovered. This epidemic of -streptococcus pneumonia, it has been shown, was the result of -unfavorable conditions produced by great overcrowding of the hospital -and in the early part of the epidemic by inadequate separation of those -with streptococcus infection from those with none. With control of these -conditions, streptococcus pneumonia rapidly diminished. - -Greater susceptibility to pneumococcus pneumonia in the early than in -the late period of the epidemic is perhaps explained by differences in -the severity of influenza; the more susceptible individuals were -attacked by influenza in the early period, whereas the less susceptible -did not acquire the disease until they had been exposed to an immensely -increased number of infected individuals. A better explanation is -furnished by the greater opportunity at the beginning of the epidemic -for the transmission of microorganisms causing pneumonia, for at this -time patients with influenza were crowded together and methods to -prevent the transmission of infection were little used. - - - Bronchitis - -Clinical study has shown that purulent bronchitis (see Fig. 2) occurs in -about one-third of the cases of influenza. In a large proportion of -cases of bronchitis there is no clinical evidence of pneumonia. The -bronchial lesions found in association with the pneumonia of influenza -are an index of the ability of the agent, which causes influenza, to -injure the bronchi. - -In those who have died with pneumonia following influenza the large -bronchi (with cartilage) are intensely injected, so that the mucosa has -a deep red color which on cross section contrasts very sharply with the -pearly white of the cartilage. Superficial injury to the bronchi is not -infrequently evident in the larger bronchial branches; superficial loss -of epithelium is indicated by erosion of the surface, whereas somewhat -deeper destructive changes are occasionally evident. Microscopic -examination accurately determines the degree of destructive change. - -Purulent bronchitis was noted in 134 autopsies (55.6 per cent of -autopsies). From the small bronchi, in many instances, purulent fluid -welled up upon the cut surface of the lung, whereas in other instances -tenacious mucopurulent fluid could be squeezed from small, cut bronchi -by pressure upon lung tissue. The consistency of the material within the -bronchi varied greatly, ranging from a viscid and tenacious mucus of -creamy, yellow color to a thin, turbid, gray fluid. The coexistence of -local inflammatory or of general edema of the lungs modifies the -character of the material found in the bronchi at autopsy; with edema -the purulent exudate is in some instances diluted so that a thin cloudy -fluid flows from the small bronchi. In the presence of advanced edema of -the lungs the bronchi rarely if ever contain purulent exudate. The -underlying changes in the bronchi are more significant than the -character of the exudate found at autopsy. Nevertheless, the group of -cases in which the diagnosis of purulent bronchitis has been made, -because small and medium sized bronchi have contained purulent or -mucopurulent exudate, represents instances of readily recognizable -bronchitis of considerable severity. - -With few exceptions, purulent bronchitis was diffusely distributed in -the lungs; occasionally it was observed in one lung alone, and in -several instances was limited to the bronchi at the base of a lung, -usually of the left lung. - -In a considerable proportion of instances of purulent bronchitis -abnormal distention of the lungs was noted. On removal from the chest -the lungs fail to collapse and retain the size and shape of the thorax. -Even after section is made through the organ, parts of the lung fail to -collapse and have a resistant cushion-like consistency. This condition -is present where the lung tissue is air containing and dry, and occurs -when very small bronchi contain tenacious mucous exudate which becomes -apparent upon the cut surface after the sectioned lung is squeezed. -Microscopic examination shows that the alveolar ducts and infundibula -are distended with air, though the respiratory bronchioles contain -inflammatory exudate. Complete obstruction of the bronchi is followed by -absorption of air from the tributary pulmonary tissue with atelectasis. -It is not improbable that partial obstruction, permitting the -penetration of air with inspiration, produces distention of air -containing tissue. - -It is furthermore probable that cyanosis, which is a conspicuous feature -of many instances of pneumonia following influenza, is referable, in -part at least, to obstruction of the bronchi by mucopurulent exudate. - -The term pneumonia will refer to those inflammatory changes in the lung -which are found within the alveoli; it will include inflammatory changes -in the alveoli surrounding the respiratory bronchioles, in the alveolar -ducts and infundibula and in their tributary alveoli. Bronchitis will be -described by defining the changes which occur (a) in the small bronchi -with no cartilage or mucous glands, and (b) in the large bronchi -including the primary branches of the trachea. - -For convenience of description those bronchi may be designated small, -which have no cartilaginous plates in their wall. Larger bronchi have -cartilage and mucous glands, the latter situated in considerable part -outside the cartilaginous plates. These bronchi, of which the largest -are the right and left bronchi formed by bifurcation of the trachea, -diminish with repeated branching to a caliber of about 1 mm. Small -bronchi are lined by columnar ciliated epithelium; their wall consists -of very vascular connective tissue containing a layer of smooth muscle -and their caliber varies approximately from 1 to 0.5 mm. It is -convenient to designate as respiratory bronchioles[80] the terminal -ramifications of the bronchi; they are lined by a single layer of -columnar ciliated cells passing over into cuboidal nonciliated -epithelium and are beset with small air sacs lined by flat cells or -epithelial plates similar to those of the alveoli elsewhere. Not -infrequently these alveoli occur along only one side of the bronchiole, -the remainder of the circumference being covered by a continuous layer -of cubical epithelium. The respiratory bronchiole by branching along its -course or at its end is continued into several alveolar ducts which -unlike the respiratory bronchioles have no cubical or columnar -epithelium but are closely beset by alveoli lined by flat epithelial -plates. The alveolar duct is recognized by the absence of cubical -epithelium and the presence of bundles of smooth muscle which occur in -the wall. The infundibula or alveolar sacs arise as branches from the -alveolar ducts and like them are beset with alveoli, but smooth muscle -does not occur in their walls. The base of the infundibulum is wider -than its orifice, which Miller states is surrounded by a sphincter-like -bundle of smooth muscle. - -Changes in the main bronchi and their primary branches are usually less -severe than those in bronchi of smaller size. The epithelium is often -intact, the superficial cells being columnar and ciliated, but not -infrequently desquamation of superficial cells has occurred and the -lower layers alone remain. Occasionally (Autopsy 471) there is necrosis -of epithelium with which, although the architecture of cells is -preserved, nuclei have disappeared. Accumulation of blood or serum may -separate epithelium from the underlying basement membrane (Fig. 1). -Complete loss of epithelium occurs, usually in small patches. - -Polynuclear leucocytes are numerous upon the surface of the epithelium -and are sometimes fixed in process of migration through epithelium and -basement membrane. - -[Illustration: - - Fig. 1.—Acute bronchitis showing engorgement of blood vessels of - mucosa and elevation of epithelium by serum and blood. Autopsy 352. -] - -The blood vessels of the mucosa are engorged. There is sometimes edema -or hemorrhage, and in the superficial part of the mucosa polynuclear -leucocytes are often fairly abundant. When superficial epithelium has -been lost, polynuclears are numerous immediately below the surface of -the exposed tissue. Fibrin is often present upon the denuded surface and -extends for a short distance into the tissue below. In the deeper part -of the mucosa, about the muscularis and especially about and between the -acini of the mucous glands, the tissue is infiltrated with lymphoid and -plasma cells. - -Changes in the mucous glands are invariably present. These changes are -distention of ducts and acini with mucous, degenerative changes -occasionally ending in necrosis of cells, disappearance of acini, dense -infiltration of interstitial tissue with lymphoid and plasma cells and -finally proliferation of this interstitial tissue. The duct of a mucous -gland, dilated and filled with mucus, may be surrounded by lymphoid and -plasma cells in great number. Acini, similarly dilated, contain mucus -and are composed of cubical cells which have discharged their mucous -content. In some instances (_e. g._, Autopsy 257) the cells of the acini -have undergone necrosis; the cytoplasm stains homogeneously and the -nuclei have disappeared. Where necrosis has occurred, polynuclear -leucocytes may penetrate into the dead cells. In association with -degenerative changes in the acini there is abundant infiltration of the -interstitial tissue within and about the glands with lymphoid and plasma -cells. When the acini have disappeared there is proliferation of -fibroblasts and new formation of fibrous tissue, and mucous glands are -found in which a few atrophied acini are separated by newly formed -fibrous tissue. - -With the bronchitis of influenza the small bronchi (with no cartilage or -mucous glands) show every stage of transition from early acute -inflammation characterized by accumulation of polynuclear leucocytes -within the lumen, engorgement of blood vessels, and infiltration of the -wall with polynuclear leucocytes, through various stages of destructive -changes to complete disappearance of the bronchial wall and formation of -an abscess cavity at the site of the bronchus. In the early stages of -acute bronchitis, hemorrhage is frequently associated with the lesion. -Blood may be abundant within the lumen of the bronchus, and in the -mucosa red blood corpuscles often infiltrate the tissue around greatly -distended blood vessels, or accumulating below the epithelium, separate -it from its basement membrane. Hemorrhage is not limited to the wall of -the bronchus, but frequently occurs into the alveoli in a zone -encircling the bronchus. - -With acute bronchitis there may be desquamation of epithelial cells with -partial or complete loss of epithelial lining. In the smallest bronchi -the single layer of columnar cells may be separated in places from the -underlying tissue, so that intact rows of cells are found within the -lumen. In somewhat larger bronchi, lined by epithelium in multiple -layers, superficial columnar ciliated cells may be lost. In some -instances superficial epithelial cells appear to have lost their -cohesion and are separated by narrow spaces; in these instances, -polynuclear leucocytes are often numerous between epithelial cells. -Epithelium is occasionally separated from its basement membrane by small -accumulations of serum or blood. Occasionally necrosis of epithelial -cells with disappearance of nuclei is seen and is doubtless caused by -the action of bacteria; the affected cells may be raised from the -underlying tissue by accumulated serum (Autopsy 253). The changes which -have been described bring about partial or complete loss of the ciliated -lining of the bronchial tube. - -The severity of changes in the bronchial wall is in direct relation to -the extent of destruction of the lining epithelium: when the epithelium -remains intact polynuclear leucocytes may be found in considerable -number immediately below it, but as the lesion progresses, cells in -great part mononuclear, namely, lymphoid and plasma cells, accumulate in -large number throughout the wall of the bronchus. There is often -abundant cellular infiltration within and about the bundles of the -muscular coat. The changes assume the character of chronic inflammation. - -When the lining epithelium of the bronchus is lost, fibrin tends to -accumulate over the surface of the defect, to which it is firmly -attached. It remains separated by a conspicuous space from adjacent -intact epithelium over which it may project. This superficial network of -fibrin merges with a similar network, extending to a variable depth -within the tissue. What may well be described as coagulative necrosis -has often occurred, and structures, such as white fibrous bundles or -wall of blood vessels, are marked out by hyaline material which merges -with fibrin. When the walls of the blood vessels which are invariably -engorged are involved, the lumen is plugged by a fibrinous thrombus. - -Little patches of fibrin adherent to the inner surface of the bronchus -may occur in spots where epithelium has been lost; with uniform loss of -epithelium the entire circumference may be lined with fibrin forming a -circular zone occasionally quite uniform in thickness. - -Accumulations of polynuclear leucocytes doubtless bring about conditions -which cause solution of fibrin or prevent its formation (when -disintegration of leucocytes sets free leucoprotease in abundance). The -activity of the infecting microorganisms, usually hemolytic streptococci -or staphylococci, may cause complete necrosis of a part or all of the -bronchial wall. The cavity which is formed may penetrate into lung -tissue that has previously undergone pneumonic consolidation. - -Further changes caused by the bronchitis of influenza will be considered -under peribronchial hemorrhage and edema, peribronchial pneumonia and -bronchiogenic abscess. Purulent bronchitis is almost invariably -associated with dilatation of the bronchi, the affected bronchi being -distended with pus. With increasing dilatation bronchiectasis becomes -evident upon gross examination of the tissue, and is much more advanced -in the small bronchi than in the larger cartilaginous passages. This -subject will be further considered under bronchiectasis. - -In association with the acute bronchitis of influenza the epithelium of -bronchi not infrequently looses its superficial columnar ciliated cells -and assumes some of the characters of a squamous epithelium being -covered by polygonal or flat cells (Figs. 17 and 18). The condition is -often described a “squamous metaplasia,” although it doubtless -represents a stage of regeneration following injury rather than a true -metaplasia. The basal cells of the epithelium have a cubical or columnar -form; above them the cells become polygonal and as the surface is -approached, cells are flat and even scale-like. The nuclei of these -superficial cells are often lost. There is no close resemblance to the -squamous epithelium of the skin, for intercellular bridges are not seen. - -This change may occur within six days after onset of influenza, though -in most instances the duration of illness has been two weeks or more. It -may affect either large or small bronchi, but it is more frequently -found in the latter. Whenever ciliated columnar cells are lost, -superficial cells tend to become flat. Epithelium on one side of a -bronchus may have a squamous character, whereas that elsewhere is -columnar and ciliated. The flat epithelium may undergo thickening so -that it is 0.1 mm. or more in thickness. It is noteworthy that -regenerating epithelium growing over a denuded surface has the squamous -character which has been described (Plate XIV, Fig. 22). - -=Bacteriology of the Bronchitis of Influenza.=—With the pneumonia of -influenza, bronchitis is invariably present. Cultures have been made -from the right or left main bronchus or from the very small bronchi -which contained purulent exudate. A routine method of making the culture -has been adopted. The right main bronchus, exposed by drawing the right -lung out of the chest and toward the midline, was widely seared with a -hot knife; the bronchus was partially cut across through the seared -surface with a heated knife and a platinum needle inserted into the -lumen. The bacteria obtained named in the approximate order of their -relative frequency have been: B. influenzæ, pneumococci, hemolytic -streptococci, staphylococci (aureus and albus), B. coli, S. viridans, M. -catarrhalis, and diphthoid bacilli which have not been identified. Mixed -infections occurred in most instances. The following list arranged by -grouping bacteria in the order cited above, shows how varied have been -the combinations which occur: - - B. influenzæ 3 - Pneumococci 5 - S. hemolyticus 3 - Staphylococci 3 - B. coli 3 - S. viridans 1 - B. influenzæ, pneumococci 17 - B. influenzæ, S. hemolyticus 18 - B. influenzæ, staphylococci 4 - Pneumococci, S. hemolyticus 1 - Pneumococci, staphylococci 3 - S. hemolyticus, staphylococci 4 - S. hemolyticus, B. coli 2 - Staphylococci, S. viridans 1 - B. influenzæ, pneumococci, S. hemolyticus 6 - B. influenzæ, pneumococci, staphylococci 15 - B. influenzæ, pneumococci, S. viridans 2 - B. influenzæ, S. hemolyticus, staphylococci 16 - B. influenzæ, S. hemolyticus, M. catarrhalis 1 - B. influenzæ, staphylococci, S. viridans 1 - Pneumococci, S. hemolyticus, staphylococci 3 - Staphylococci, B. coli, S. viridans 1 - B. influenzæ, pneumococci, S. hemolyticus, staphylococci 7 - B. influenzæ, pneumococci, staphylococci, M. catarrhalis 1 - B. influenzæ, S. hemolyticus, staphylococci, B. coli 1 - B. influenzæ, S. hemolyticus, staphylococci, S. viridans 1 - B. influenzæ, S. hemolyticus, staphylococci, M. catarrhalis 1 - B. influenzæ, staphylococci, S. viridans, M. catarrhalis 1 - -B. influenzæ has been present in the bronchi in 79.3 per cent of -instances of pneumonia referable to influenza. Combinations which have -been found most frequently are B. influenzæ and pneumococci (17 -instances), B. influenzæ and hemolytic streptococci (18 instances), or -the same combinations with staphylococci, namely, B. influenzæ, -pneumococci and staphylococci (15 instances), and B. influenzæ, -hemolytic streptococci and staphylococci (16 instances). There is little -doubt that B. influenzæ was not identified in some instances in which it -was present; when other microorganisms are very numerous its -inconspicuous colonies may be overgrown even though the presence of -pneumococci, streptococci or staphylococci tends to increase the size of -its colonies. Moreover, it is not improbable that the microorganism may -disappear from the bronchi. Comparison with observations made upon -influenza suggests that multiple methods of examination might have -demonstrated a much higher incidence of B. influenzæ. Throat cultures -alone made during life demonstrated the presence of B. influenzæ in only -65.7 per cent of patients with acute influenza, whereas when cultures -were made from the nose, throat and sputum, and a mouse was inoculated -with sputum from each patient, B. influenzæ was found in every instance. -After the acute stage of the disease had passed, the number of -microorganisms diminished, and in many instances B. influenzæ -disappeared from the upper air passages. In some of our autopsies B. -influenzæ doubtless present during life has similarly disappeared before -death due to pneumonia caused by pneumococci or streptococci. In view of -these considerations it is not improbable that B. influenzæ demonstrated -by a single culture in 80 per cent of instances has been constantly -present. - -Table XXVIII represents the incidence of pneumococci, hemolytic -streptococci, staphylococci, and B. influenzæ in the bronchi, lungs and -blood of those individuals with pneumonia in whom bacteriologic -examination has been made at autopsy. The number of cultures made from -the bronchi, lungs or blood of the heart is given in the second column -of the table and in other columns are given the incidence in number and -percentage of the microorganisms which have been mentioned. - - TABLE XXVIII - - ════════╤════════╤═════════════════╤═════════════════ - │ NO. OF │ │ HEMOLYTIC - │CULTURES│ PNEUMOCOCCI │ STREPTOCOCCI - ────────┼────────┼────────┬────────┼────────┬──────── - │ │ NO. │PER CENT│ NO. │PER CENT - │ │POSITIVE│POSITIVE│POSITIVE│POSITIVE - ────────┼────────┼────────┼────────┼────────┼──────── - Bronchus│ 121│ 56│ 46.3│ 58│ 47.9 - Lung │ 153│ 68│ 44.4│ 77│ 50.3 - Blood │ 218│ 87│ 39.9│ 85│ 39.0 - ────────┴────────┴────────┴────────┴────────┴──────── - - ════════╤═════════════════╤═════════════════ - │ │ - │ STAPHYLOCOCCI │ B. INFLUENZÆ - ────────┼────────┬────────┼────────┬──────── - │ NO. │PER CENT│ NO. │PER CENT - │POSITIVE│POSITIVE│POSITIVE│POSITIVE - ────────┼────────┼────────┼────────┼──────── - Bronchus│ 61│ 50.4│ 96│ 79.3 - Lung │ 37│ 24.2│ 70│ 45.7 - Blood │ 1│ 0.5│ 1│ 0.5 - ────────┴────────┴────────┴────────┴──────── - -Cultures from the bronchus represent the bacteriology of the bronchitis -of influenza. Infection of the lung following influenza doubtless occurs -by way of the bronchi, so that the bacteria which cause pneumonia are -present in the bronchi before they enter the lung tissue. The figures in -Table XXVIII, similar to those previously cited, show the high incidence -of B. influenzæ, and the occurrence of pneumococci, hemolytic -streptococci and staphylococci each present in approximately half of all -autopsies. - -The figures in Table XXVIII are an index of the capacity of the -microorganisms which enter the bronchi to invade the lungs and finally -the blood. Pneumococci were present in the bronchi in 46.3 per cent of -instances, in the lungs in only slightly less, and in approximately 40 -per cent of autopsies they had penetrated into the blood. Hemolytic -streptococci enter the bronchi with the same frequency and exhibit an -equal ability to penetrate into the lungs and blood. Staphylococci enter -the bronchi in half of these individuals, but penetrate into the lungs -in only a fourth of the instances. They have entered the blood only once -(Autopsy 263) in this instance in association with hemolytic -streptococci. B. influenzæ has been present in the bronchi in -approximately 80 per cent of autopsies. It is noteworthy that it has -been found in the lung in little more than half this percentage of -instances and has entered the blood only once (Autopsy 474), in this -instance in association with hemolytic streptococci. - -In a limited number of autopsies there was purulent bronchitis -recognized by the presence of mucopurulent exudate in small bronchi. It -has been stated that this group of cases is not sharply separable from -other instances of bronchitis, because in some cases death has occurred -before a purulent exudate has accumulated or in other instances a -purulent exudate has been displaced by edema. Table XXIX shows the -bacteriology of instances of purulent bronchitis: - - TABLE XXIX - - ════════╤════════╤═════════════════╤═════════════════ - │ NO. OF │ │ HEMOLYTIC - │CULTURES│ PNEUMOCOCCI │ STREPTOCOCCI - ────────┼────────┼────────┬────────┼────────┬──────── - │ │ NO. │PER CENT│ NO. │PER CENT - │ │POSITIVE│POSITIVE│POSITIVE│POSITIVE - ────────┼────────┼────────┼────────┼────────┼──────── - Bronchus│ 66│ 33│ 50.0│ 32│ 48.5 - ────────┴────────┴────────┴────────┴────────┴──────── - - ════════╤═════════════════╤═════════════════ - │ │ - │ STAPHYLOCOCCI │ B. INFLUENZÆ - ────────┼────────┬────────┼────────┬──────── - │ NO. │PER CENT│ NO. │PER CENT - │POSITIVE│POSITIVE│POSITIVE│POSITIVE - ────────┼────────┼────────┼────────┼──────── - Bronchus│ 36│ 54.5│ 53│ 80.3 - ────────┴────────┴────────┴────────┴──────── - -The percentages of various bacteria with purulent bronchitis do not -differ essentially from those obtained from all autopsies with -pneumonia. B. influenzæ is found in approximately 80 per cent of -autopsies. In 16 instances cultures were made from the purulent fluid -contained in a small bronchus and the incidence of B. influenzæ (namely, -81.4 per cent) has not differed from that in the main bronchus. In 7 of -8 instances in which cultures were made, both from the right main -bronchus and from the purulent fluid in a small bronchus, B. influenzæ -was found in one or other in all but one autopsy (87.5 per cent); in -this instance (Autopsy 472) respiratory disease began thirty-seven days -before death and cultures from large and small bronchi at autopsy were -overgrown by B. coli. Since observations upon influenza made during life -have shown that B. influenzæ is constantly demonstrable when multiple -methods are employed for its detection, the figures just cited give -support to the suggestion that B. influenzæ is constantly present in the -bronchi with the bronchitis of influenza. - - - Lobar Pneumonia - -The frequency with which the confluent lobular consolidation of -bronchopneumonia involving whole lobes or parts of lobes follows -influenza has emphasized the desirability of distinguishing carefully -between lobar and confluent lobular pneumonia. The pulmonary lesion has -been designated lobar pneumonia when it exhibited the well-known -characters of this lesion, namely, firm consolidation of large parts of -lobes, coarse granulation of the cut surface, fibrinous plugs in the -bronchi and, on microscopic examination, homogeneous consolidation and -fibrinous plugs within the alveoli. With confluent lobular consolidation -of bronchopneumonia the consolidated area is in most cases obviously -limited by lobule boundaries, and well-defined lobules of consolidation -occur elsewhere in the lungs. - -Lobar pneumonia occurred in 98 among 241 instances of pneumonia -following influenza, namely, in 40.7 per cent of autopsies. - -The difficulty of separating lobar and bronchopneumonia following -influenza has been increased by the frequent combination of the two -lesions in the same individual. There were 34 instances in which lobar -and bronchopneumonia occurred together. The anatomic diagnosis of lobar -pneumonia was made only when lobes or parts of lobes were firmly -consolidated and exhibited the characters of the lesion enumerated -above; in several instances, in which there was some doubt concerning -the nature of the lesion, microscopic examination was decisive. The -associated bronchopneumonic lesions represented all the types which have -been associated with influenza. In the group of 34 cases of coexisting -lobar and bronchopneumonia, lobular consolidation occurred 10 times, -peribronchiolar consolidation 14 times (recognized in all but 4 -instances by microscopic examination), hemorrhagic peribronchiolar -consolidation 9 times, peribronchial pneumonia 4 times. The intimate -relation of these lesions to changes in the bronchi is well shown by the -frequent presence of purulent bronchitis. The associated lesions of the -bronchi in these cases were as follows: purulent bronchitis in 23 -instances; peribronchial hemorrhage in 6; bronchiectasis in 11. The -frequency of purulent bronchitis and other bronchial lesions in -association with coexisting lobar and bronchopneumonia is in sharp -contrast with the occurrence of these lesions in association with lobar -pneumonia alone; with 69 instances of lobar pneumonia alone purulent -bronchitis occurred 17 times and bronchiectasis once. - -Lobar pneumonia following influenza passes through the usual stages of -red and gray hepatization. Red hepatization was found 16 times, combined -red and gray hepatization 28 times, and gray hepatization 20 times. The -average duration of pneumonia with red hepatization was 3.7 days, with -combined red and gray hepatization 5.1 days and with gray hepatization -7.5 days. These figures, it will be shown later, have some importance in -relation to the stage at which hemolytic streptococcus infects lungs the -site of lobar pneumonia. - -=Bacteriology of Lobar Pneumonia.=—Table XXX is compiled with the -purpose of determining the bacteriology of the bronchi, lungs and -heart’s blood in autopsies performed on individuals with lobar -pneumonia. In some instances bacteriologic examination of one or other -of these organs was omitted; the percentage incidence is an index of the -presence of pneumococci, hemolytic streptococci, staphylococci or B. -influenzæ in the bronchi, lungs or heart’s blood and measures the -invasive power of these microorganisms during the course of lobar -pneumonia following influenza. - - TABLE XXX - - ════════╤════════╤═════════════════╤═════════════════ - │ NO. OF │ │ HEMOLYTIC - │CULTURES│ PNEUMOCOCCI │ STREPTOCOCCI - ────────┼────────┼────────┬────────┼────────┬──────── - │ │ NO. │PER CENT│ NO. │PER CENT - │ │POSITIVE│POSITIVE│POSITIVE│POSITIVE - ────────┼────────┼────────┼────────┼────────┼──────── - Bronchus│ 44│ 56.9│ 14│ 31.8│ 22 - Lung │ 53│ 77.3│ 13│ 24.5│ 8 - Blood │ 87│ 65.5│ 11│ 12.6│ - ────────┴────────┴────────┴────────┴────────┴──────── - - ════════╤═════════════════╤═════════════════ - │ │ - │ STAPHYLOCOCCI │ B. INFLUENZÆ - ────────┼────────┬────────┼────────┬──────── - │ NO. │PER CENT│ NO. │PER CENT - │POSITIVE│POSITIVE│POSITIVE│POSITIVE - ────────┼────────┼────────┼────────┼──────── - Bronchus│ 37│ 84.1│ 96│ 79.3 - Lung │ 26│ 49.1│ 70│ 45.7 - Blood │ │ │ 1│ 0.5 - ────────┴────────┴────────┴────────┴──────── - - -Pneumococci, the recognized cause of lobar pneumonia, were found in the -lungs in 73.3 per cent of autopsies; failure to find the microorganism -in all instances is doubtless the result of its disappearance from the -lung, which, it is well known, occurs not infrequently particularly -during the later stages of the disease. In 65.5 per cent of instances of -fatal lobar pneumonia pneumococci have entered the heart’s blood. - -Hemolytic streptococci unlike pneumococci were found more frequently in -the bronchi than in the lungs; this microorganism which exhibits little -tendency to disappear, once it has established itself within the body, -found entrance into the bronchi in 31.8 per cent of instances of lobar -pneumonia and in 24.5 per cent entered the lungs. Its invasive power is -further illustrated by its penetration into the heart’s blood -approximately in half this proportion of autopsies. - -Staphylococci enter the bronchi in many instances (50 per cent), but -relatively seldom (15.1 per cent) invade the lung and rarely if ever -penetrate into the blood. - -The high incidence, namely, 84.1 per cent, of B. influenzæ in the -bronchi is particularly noteworthy; it exceeds that of pneumococci, the -well-recognized cause of lobar pneumonia, within the lung. It is found -much less frequently within consolidated lung tissue and shows no -tendency to invade the heart’s blood. B. influenzæ finds the most -favorable conditions for its multiplication within the bronchi. - -In view of the frequent occurrence of coexisting lobar and -bronchopneumonia it has appeared desirable to determine how far the -existence of obvious bronchopneumonia modifies the bacteriology of lobar -pneumonia. In Table XXXI the incidence of pneumococci, hemolytic -streptococci, staphylococci and B. influenzæ after death with lobar -pneumonia on the one hand is compared with their incidence after -combined lobar and bronchopneumonia on the other. - -Pneumococci are found in the lung more frequently with lobar than with -combined lobar and bronchopneumonia. The incidence of hemolytic -streptococci and of staphylococci in the lung is on the contrary higher -when bronchopneumonia is associated with lobar pneumonia. It is not -improbable that these microorganisms have a part in the production of -associated bronchopneumonia. The frequency with which microorganisms -invade the blood is almost identical in the two groups. - - TABLE XXXI - - WITH LOBAR PNEUMONIA ALONE - - ════════╤════════╤═════════════════╤═════════════════ - │ NO. OF │ │ HEMOLYTIC - │CULTURES│ PNEUMOCOCCI │ STREPTOCOCCI - ────────┼────────┼────────┬────────┼────────┬──────── - │ │ NO. │PER CENT│ NO. │PER CENT - │ │POSITIVE│POSITIVE│POSITIVE│POSITIVE - ────────┼────────┼────────┼────────┼────────┼──────── - Bronchus│ 30│ 20│ 66.6│ 9│ 30 - Lung │ 34│ 29│ 85.2│ 7│ 20.6 - Blood │ 54│ 36│ 66.7│ 7│ 13 - ────────┴────────┴────────┴────────┴────────┴──────── - - ════════╤═════════════════╤═════════════════ - │ │ - │ STAPHYLOCOCCI │ B. INFLUENZÆ - ────────┼────────┬────────┼────────┬──────── - │ NO. │PER CENT│ NO. │PER CENT - │POSITIVE│POSITIVE│POSITIVE│POSITIVE - ────────┼────────┼────────┼────────┼──────── - Bronchus│ 15│ 50│ 26│ 86.7 - Lung │ 3│ 8.8│ 18│ 52.9 - Blood │ │ │ │ - ────────┴────────┴────────┴────────┴──────── - - WITH COMBINED LOBAR AND BRONCHOPNEUMONIA - - ════════╤════════╤═════════════════╤═════════════════ - │ NO. OF │ │ HEMOLYTIC - │CULTURES│ PNEUMOCOCCI │ STREPTOCOCCI - ────────┼────────┼────────┬────────┼────────┬──────── - │ │ NO. │PER CENT│ NO. │PER CENT - │ │POSITIVE│POSITIVE│POSITIVE│POSITIVE - ────────┼────────┼────────┼────────┼────────┼──────── - Bronchus│ 14│ 9│ 64.3│ 5│ 34.3 - Lung │ 19│ 12│ 63.2│ 6│ 31.6 - Blood │ 33│ 21│ 63.1│ 4│ 12.1 - ────────┴────────┴────────┴────────┴────────┴──────── - - ════════╤═════════════════╤═════════════════ - │ │ - │ STAPHYLOCOCCI │ B. INFLUENZÆ - ────────┼────────┬────────┼────────┬──────── - │ NO. │PER CENT│ NO. │PER CENT - │POSITIVE│POSITIVE│POSITIVE│POSITIVE - ────────┼────────┼────────┼────────┼──────── - Bronchus│ 7│ 50│ 11│ 78.6 - Lung │ 5│ 26.3│ 8│ 42.1 - Blood │ │ │ │ - ────────┴────────┴────────┴────────┴──────── - -The relative frequency with which different types of pneumococci produce -lobar pneumonia under the conditions existing when Camp Pike was -attacked by an epidemic of influenza is indicated by Table XXXII in -which instances of lobar pneumonia alone and of combined lobar and -bronchopneumonia are listed separately. - -Pneumococcus I and II, which are found approximately in two-thirds of -instances of lobar pneumonia occurring in cities, have an insignificant -part in the production of these lesions. Pneumococcus IV and atypical -Pneumococcus II, which are commonly found in the mouth, are the -predominant cause of these lesions, and with Pneumococcus III, also an -inhabitant of the mouths of normal individuals, have been the cause of -two-thirds of all instances of lobar pneumonia observed in this camp. - - TABLE XXXII - - WITH LOBAR PNEUMONIA - - ════════╤════════╤═════════════════╤═════════════════╤═════════════════ - │ NO. OF │ │ │ PNEUMOCOCCUS II - │CULTURES│ PNEUMOCOCCUS I │ PNEUMOCOCCUS II │ (Atyp.) - ────────┼────────┼────────┬────────┼────────┬────────┼────────┬──────── - │ │ NO. │PER CENT│ NO. │PER CENT│ NO. │PER CENT - │ │POSITIVE│POSITIVE│POSITIVE│POSITIVE│POSITIVE│POSITIVE - ────────┼────────┼────────┼────────┼────────┼────────┼────────┼──────── - Bronchus│ 30│ 1│ 3.3│ 1│ 3.3│ 4│ 13.3 - Lung │ 34│ 1│ 2.9│ 2│ 5.9│ 9│ 26.5 - Blood │ 54│ 2│ 3.7│ 2│ 3.7│ 12│ 22.2 - ────────┴────────┴────────┴────────┴────────┴────────┴────────┴──────── - - ════════╤═════════════════╤═════════════════ - │ │ - │PNEUMOCOCCUS III │ PNEUMOCOCCUS IV - ────────┼────────┬────────┼────────┬──────── - │ NO. │PER CENT│ NO. │PER CENT - │POSITIVE│POSITIVE│POSITIVE│POSITIVE - ────────┼────────┼────────┼────────┼──────── - Bronchus│ 4│ 13.3│ 10│ 33.3 - Lung │ 6│ 17.6│ 11│ 32.4 - Blood │ 3│ 5.6│ 17│ 31.5 - ────────┴────────┴────────┴────────┴──────── - - WITH COMBINED LOBAR AND BRONCHOPNEUMONIA - - ════════╤════════╤═════════════════╤═════════════════╤═════════════════ - │ NO. OF │ │ │ PNEUMOCOCCUS II - │CULTURES│ PNEUMOCOCCUS I │ PNEUMOCOCCUS II │ (Atyp.) - ────────┼────────┼────────┬────────┼────────┬────────┼────────┬──────── - │ │ NO. │PER CENT│ NO. │PER CENT│ NO. │PER CENT - │ │POSITIVE│POSITIVE│POSITIVE│POSITIVE│POSITIVE│POSITIVE - ────────┼────────┼────────┼────────┼────────┼────────┼────────┼──────── - Bronchus│ 14│ 2│ 14.3│ 1│ 7.1│ 3│ 21.4 - Lung │ 19│ 1│ 5.3│ │ │ 5│ 26.3 - Blood │ 33│ 2│ 6.1│ 3│ 9.1│ 4│ 12.1 - ────────┴────────┴────────┴────────┴────────┴────────┴────────┴──────── - - ════════╤═════════════════╤═════════════════ - │ │ - │PNEUMOCOCCUS III │ PNEUMOCOCCUS IV - ────────┼────────┬────────┼────────┬──────── - │ NO. │PER CENT│ NO. │PER CENT - │POSITIVE│POSITIVE│POSITIVE│POSITIVE - ────────┼────────┼────────┼────────┼──────── - Bronchus│ │ │ 3│ 21.4 - Lung │ │ │ 6│ 31.6 - Blood │ │ │ 12│ 36.4 - ────────┴────────┴────────┴────────┴──────── - -There is no noteworthy difference in the occurrence of these types of -pneumococci among instances of lobar pneumonia, on the one hand, and of -combined lobar and bronchopneumonia, on the other. Different types -exhibit no noteworthy differences in their ability to penetrate into -lungs and blood. - -=Hemolytic Streptococcus with Lobar Pneumonia.=—There can be no doubt -that the concurrent infection with microorganisms other than -pneumococcus modifies the progress of lobar pneumonia. With lobar -pneumonia alone hemolytic streptococci have entered the bronchi in 30 -per cent of instances and have penetrated into the lungs in 20.6 per -cent; with associated lobar and bronchopneumonia the same microorganism -has entered the bronchi in 34.3 per cent of instances and invaded the -lung in 31.6 per cent. Hemolytic streptococci are the only -microorganisms other than pneumococci which, in association with lobar -pneumonia, have found their way from the lungs to the blood stream; more -than one-third of all instances of lobar pneumonia in which hemolytic -streptococci find entrance into the bronchi die with streptococcus -septicemia. - -Separation of instances of lobar pneumonia into groups on the basis of -the occurrence of red or gray hepatization shows that infection with -hemolytic streptococcus is more likely to occur during the early stages -of the disease. The average duration of lobar pneumonia with red -hepatization has been 3.7 days, with red and gray hepatization, 5.1 -days, and with gray hepatization, 7.5 days. Infection with hemolytic -streptococcus has occurred in association with red or gray hepatization -as shown in Table XXXIII. - - TABLE XXXIII - - ═════════════════════════════╤═════════════╤═════════════╤═════════════ - │ │ NO. WITH │PER CENT WITH - │ NO. OF │ HEMOLYTIC │ HEMOLYTIC - │ AUTOPSIES │STREPTOCOCCUS│STREPTOCOCCUS - ─────────────────────────────┼─────────────┼─────────────┼───────────── - Lobar pneumonia with red │ │ │ - hepatization │ 16│ 6│ 37.5 - Lobar pneumonia with red and │ │ │ - gray hepatization │ 28│ 6│ 21.4 - Lobar pneumonia with gray │ │ │ - hepatization │ 20│ 1│ 5.0 - ─────────────────────────────┴─────────────┴─────────────┴───────────── - -Notwithstanding the longer duration of the disease and consequent -prolongation of exposure to infection, lobar pneumonia, which has -reached the stage of gray hepatization, has shown the smallest incidence -of infection with hemolytic streptococci. In the stage of gray -hepatization there is diminished susceptibility to secondary infection -with this microorganism. - -Characteristic histologic changes have been found in the lungs of those -who have died with lobar pneumonia followed by invasion of lungs and -blood by hemolytic streptococci (_e. g._, Autopsies 273, 430), but with -no evidence of suppuration found at autopsy. Within the pneumonic lung -occur patches of necrosis implicating both exuded cells and alveolar -walls; in some places nuclei have disappeared; elsewhere nuclear -fragments are abundant. In these patches of necrosis Gram-positive -streptococci in short chains occur in immense number. In some instances -(_e. g._, Autopsies 273, 346, 479) interlobular septa are very edematous -and often contain a network of fibrin; lymphatics are dilated and -contain polynuclear leucocytes in abundance. Streptococci are found -within these lymphatics. The histologic changes which have been -described represent the earliest stages of abscess formation and -interstitial suppuration, lesions almost invariably caused by hemolytic -streptococci. - -[Illustration: - - Chart 2.—Showing the relation of (_a_) date of onset of cases in which - autopsy demonstrated lobar pneumonia, indicated by upper continuous - line with single hatch, and of (_b_) date of death of these cases, - indicated by lower continuous line with double hatch to (_c_) the - occurrence of influenza, indicated by the broken line, and to (_d_) - the total number of fatal cases of pneumonia, indicated by the - broken dotted line. Each case of fatal pneumonia is indicated by one - division of the scale as numbered on the left of the chart; cases of - influenza are indicated by the numbers on the right of the chart. -] - -=Relation of Lobar Pneumonia to Influenza.=—Some writers have suggested -that lobar pneumonia, heretofore observed during the course of epidemics -of influenza, is an independent disease with no relation to influenza, -both diseases being referable perhaps to similar meteorologic or other -conditions. Chart 2, which shows by weeks from September 1 to October 31 -the relation of deaths from lobar pneumonia (indicated by double hatch) -to deaths from all forms of pneumonia, disproves this suggestion. The -two curves follow parallel courses; that representing lobar pneumonia -reaches a maximum approximately one week after the outbreak of influenza -had reached its height. Lobar pneumonia, like other forms of pneumonia, -was secondary to influenza. When a chart is plotted to represent the -dates of onset of fatal cases of lobar pneumonia (indicated by single -hatch in Chart 2), it becomes evident that the greatest number of these -cases of pneumonia had their onset at the beginning of the influenza -epidemic, approximately one week before it reached its height. Fatal -lobar pneumonia developed less frequently in the latter part of the -epidemic; to obtain an explanation of this relation it is necessary to -chart separately cases of lobar pneumonia with secondary streptococcus -infection, for we have already learned that streptococcus infection was -the predominant cause of death in the early period of the influenza -epidemic. Exclusion of these instances of secondary streptococcus -infection makes no noteworthy change in the character of the chart. -Fatal lobar pneumonia, like all forms of fatal pneumonia (p. 140), was -more frequent in the first half than in the second half of the epidemic. -This difference is referable either to greater virulence of the virus of -influenza or to the greater susceptibility of those first selected by -the disease or, as more probable, to conditions such as crowding -together of patients with influenza, favoring the transmission of -microorganisms which cause pneumonia. - - - Bronchopneumonia - -For the purpose of the present study it is convenient to group together -instances of bronchopneumonia which have been unaccompanied, on the one -hand, by lobar pneumonia (p. 155) or, on the other hand, by suppuration, -which with few exceptions is caused by hemolytic streptococci or by -staphylococci. A group of cases in which lobar and bronchopneumonia have -occurred in the same individual have already been considered. In many -instances, bronchopneumonia is accompanied by abscess formation or by -some other form of suppuration; these lesions will be discussed -elsewhere. - -Bronchopneumonia unaccompanied by lobar pneumonia or by suppuration -occurred in 80 autopsies. - -Pneumonic consolidation distributed with relation to the bronchi -exhibits considerable variety, and an attempt to define a type of -bronchopneumonia characteristic of influenza would be futile. -Nevertheless, the bronchopneumonia of influenza has in many instances -distinctive characters. - -Lesions of bronchopneumonia which are frequently found in the autopsies -under consideration may be conveniently designated by descriptive terms, -indicative of their location in the lung tissue. These lesions, of which -two or more often occur in the same lung, are: - -1. Peribronchiolar consolidation with which the inflammatory exudate is -limited to the alveoli in the immediate neighborhood of the bronchioles. - -2. Hemorrhagic peribronchiolar consolidation in which gray patches of -peribronchiolar pneumonia occur upon a deep red background produced by -hemorrhage into alveoli. Pfeiffer believed that this lesion was -characteristic of influenza. - -3. Lobular consolidation with which consolidation is limited to lobules -or groups of lobules. - -4. Peribronchial pneumonia with which small bronchi are encircled by -pneumonic consolidation. - -Each one of these lesions will be discussed separately. - -Following is a list of the bacteria which have been isolated from the -consolidated lung of individuals with bronchopneumonia unaccompanied by -lobar pneumonia or by suppuration: - - B. influenzæ 1 - Pneumococci 5 - S. hemolyticus 5 - S. viridans 1 - B. influenzæ, pneumococci 9 - B. influenzæ, S. hemolyticus 4 - B. influenzæ, staphylococci 4 - Pneumococci, S. hemolyticus 1 - Pneumococci, staphylococci 2 - S. hemolyticus, staphylococci 1 - S. hemolyticus, B. coli 1 - Staphylococci, S. viridans 1 - Staphylococci, B. coli 1 - B. influenzæ, pneumococci, staphylococci 1 - B. influenzæ, pneumococci, S. viridans 1 - B. influenzæ, S. hemolyticus, staphylococci 2 - B. influenzæ, pneumococci, staphylococci, S. viridans 1 - No microorganisms found 6 - —— - 47 - -The similarity of this list to that representing the bacteriology of -bronchitis is evident; there is the same multiplicity of microorganisms -and the frequent occurrence of mixed infections. B. influenzæ is much -less frequently found in the lung. The relative pathogenicity of the -large group of microorganisms enumerated above is better indicated by -the following list which shows what microorganisms have penetrated into -the blood in autopsies performed on individuals with bronchopneumonia: - - Pneumococci 20 - S. hemolyticus 23 - S. viridans 1 - Pneumococci, S. hemolyticus 2 - No bacteria found 25 - —— - Total 71 - -Table XXXIV shows the percentage incidence of pneumococcus, hemolytic -streptococcus, staphylococcus and B. influenzæ in the bronchi, lungs and -blood and is inserted for comparison with the similar table (Table XXX) -showing the incidence of these bacteria in lobar pneumonia. - - TABLE XXXIV - - ════════╤════════╤═════════════════╤═════════════════ - │ NO. OF │ │ HEMOLYTIC - │CULTURES│ PNEUMOCOCCI │ STREPTOCOCCI - ────────┼────────┼────────┬────────┼────────┬──────── - │ │ NO. │PER CENT│ NO. │PER CENT - │ │POSITIVE│POSITIVE│POSITIVE│POSITIVE - ────────┼────────┼────────┼────────┼────────┼──────── - Bronchus│ 37│ 19│ 48.6│ 13│ 35.1 - Lung │ 47│ 20│ 42.6│ 14│ 29.8 - Blood │ 70│ 22│ 31.4│ 24│ 34.3 - ────────┴────────┴────────┴────────┴────────┴──────── - - ════════╤═════════════════╤═════════════════ - │ │ - │ STAPHYLOCOCCI │ B. INFLUENZÆ - ────────┼────────┬────────┼────────┬──────── - │ NO. │PER CENT│ NO. │PER CENT - │POSITIVE│POSITIVE│POSITIVE│POSITIVE - ────────┼────────┼────────┼────────┼──────── - Bronchus│ 22│ 59.5│ 28│ 75.7 - Lung │ 13│ 27.7│ 23│ 48.9 - Blood │ │ │ │ - ────────┴────────┴────────┴────────┴──────── - -Table XXXIV shows that pneumococci have a less important part in the -production of broncho than of lobar pneumonia; with lobar pneumonia this -microorganism was found in the lungs in 77.3 per cent of instances and -in the blood, in 65.5 per cent, whereas with bronchopneumonia it was -found in the lungs in 42.6 per cent and in the blood in 31.4 per cent. -Hemolytic streptococci (in lungs and blood) and staphylococci (in -lungs), on the contrary, were more common with bronchopneumonia, and -doubtless have a part in the production of the lesion. Streptococcus -viridans, B. coli and M. catarrhalis, which are not infrequently found -in the bronchi (p. 151), occasionally enter the lungs with -bronchopneumonia but are rarely found with lobar pneumonia. B. influenzæ -has been found in less than 80 per cent of instances in the bronchi and -in about half of the lungs, maintaining an incidence approximately the -same as that with lobar pneumonia. - -Table XXXV shows the types of pneumococci found in association with -bronchopneumonia and is inserted for comparison with the similar table -(Table XXXII) showing types of pneumococci with lobar pneumonia. - -With broncho as with lobar pneumonia pneumococci commonly found in the -mouth, namely, atypical II, and Types III and IV, have a more important -part in production of the lesion than the so-called fixed types, I and -II. Atypical Pneumococcus II has been less frequently encountered with -broncho than with lobar pneumonia. - - TABLE XXXV - - ════════╤════════╤═════════════════╤═════════════════╤═════════════════ - │ NO. OF │ │ │ PNEUMOCOCCUS II - │CULTURES│ PNEUMOCOCCUS I │ PNEUMOCOCCUS II │ (Atyp.) - ────────┼────────┼────────┬────────┼────────┬────────┼────────┬──────── - │ │ NO. │PER CENT│ NO. │PER CENT│ NO. │PER CENT - │ │POSITIVE│POSITIVE│POSITIVE│POSITIVE│POSITIVE│POSITIVE - ────────┼────────┼────────┼────────┼────────┼────────┼────────┼──────── - Bronchus│ 37│ 1│ 2.7│ 3│ 8.1│ │ - Lung │ 47│ 2│ 4.3│ 2│ 4.3│ 2│ 4.3 - Blood │ 70│ 1│ 1.4│ 1│ 1.4│ 5│ 7.1 - ────────┴────────┴────────┴────────┴────────┴────────┴────────┴──────── - - ════════╤═════════════════╤═════════════════ - │ │ - │PNEUMOCOCCUS III │ PNEUMOCOCCUS IV - ────────┼────────┬────────┼────────┬──────── - │ NO. │PER CENT│ NO. │PER CENT - │POSITIVE│POSITIVE│POSITIVE│POSITIVE - ────────┼────────┼────────┼────────┼──────── - Bronchus│ │ │ 14│ 37.8 - Lung │ 2│ 4.3│ 12│ 25.2 - Blood │ 4│ 5.7│ 11│ 15.9 - ────────┴────────┴────────┴────────┴──────── - - -=Peribronchiolar Consolidation.=—In many instances of bronchopneumonia, -usually in association with lobular or confluent consolidation, small -firm nodules of consolidation are clustered about the bronchioles (Fig. -2). These nodular foci of consolidation are usually 1.5 to 2 mm. in -diameter, being sometimes slightly smaller or slightly larger. They are -usually gray and occasionally surrounded by a red halo; sometimes they -are yellowish gray. They are clustered about the smallest bronchial -tubes to form groups which are from 0.5 to 1 cm. across. A group of -nodular foci of consolidation occupies the central part of a lobule of -lung tissue. When pneumonia has been of short duration these foci are -fairly soft and not sharply defined, and in many instances this form of -bronchopneumonia is first recognized by microscopic examination. When -the disease has lasted from ten days to two weeks, the consolidated -nodules are very firm and sharply circumscribed, closely resembling -tubercles. When they have assumed this character, microscopic -examination shows that chronic changes indicated by new formation of -interstitial tissue have occurred. - -The lesion may be designated peribronchiolar consolidation. It has -occurred usually in association with other types of pneumonic lesion in -61 instances, being recognized at autopsy in 18 and by microscopic -examination in 43. - -[Illustration: - - Fig. 2.—Acute bronchopneumonia with nodules of peribronchiolar - consolidation and purulent bronchitis. Autopsy 429. -] - -In association with this lesion there are almost invariably severe -lesions of the bronchi. Purulent bronchitis was noted in 47 of the 61 -instances, in which this nodular bronchopneumonia was found at autopsy. -An index of the severity of the bronchial injury is the frequency with -which bronchiectasis has occurred; dilatation of small bronchi was -observed in 24 instances. In 10 instances the bronchi were encircled by -conspicuous zones of hemorrhage. - -In association with this peribronchiolar lesion the lung is often -voluminous and fails to collapse on removal from the chest. Pressure -upon the lung squeezes from the smallest bronchi, both in the -neighborhood of the nodular consolidation and elsewhere, a droplet of -viscid, semifluid mucopurulent material. The presence of this tenacious -material throughout the small bronchi doubtless explains the failure of -the lung tissue to collapse. Interstitial emphysema has been present in -some of these lungs. - -A red zone of hemorrhage has occasionally been observed about the foci -of peribronchiolar pneumonia. A further stage in the same process is -represented by hemorrhage into all of the alveoli separating these -patches of consolidation. This hemorrhagic lesion, which will be -described in more detail later, has been found repeatedly in the same -lung with peribronchiolar pneumonia, being present in 8 among the 61 -autopsies cited. Lobular bronchopneumonia accompanied the -peribronchiolar lesion 27 times and lobar pneumonia accompanied it 20 -times. - -When an abscess caused by hemolytic streptococcus is associated with -peribronchiolar pneumonia, empyema is present, but otherwise pleurisy is -absent or limited to a scant fibrinous exudate. - -[Illustration: - - Fig. 3.—Acute bronchopneumonia with peribronchiolar consolidation; a - respiratory bronchiole partially lined by columnar epithelium passes - into alveolar duct and the adjacent alveoli are filled by - polynuclear leucocytes. Autopsy 333. -] - -Histologic examination demonstrates very clearly the relation of this -lesion to the bronchioles (Fig. 3). These passages are filled and -distended with an inflammatory exudate consisting almost entirely of -polynuclear leucocytes. The respiratory bronchioles are beset with -alveoli often limited to one side of the tubule and these alveoli are -filled with leucocytes. The alveolar ducts, distinguishable from the -bronchioles by the absence of columnar or cubical epithelium and by -possession of smooth muscle, are similarly filled with leucocytes; the -numerous alveoli which form the walls of the alveolar ducts are -distended by an inflammatory exudate. In sections which pass through an -alveolar duct and one or more of its infundibula, the further extension -of the lesion may be determined (Fig. 4). The infundibulum in proximity -with the alveolar duct contains polynuclear leucocytes and the same -cells are seen in the alveoli which here form its wall, but the -intensity of the inflammatory reaction diminishes toward the periphery, -so that the distal part of the infundibulum, which is much distended and -in consequence more readily definable than usual, is free from -inflammatory exudate. - -[Illustration: - - Fig. 4.—Acute bronchopneumonia with peribronchiolar consolidation; a - respiratory bronchiole is in continuity with an alveolar duct and - two distended infundibula; alveoli about bronchiole, alveolar duct - and proximal part of infundibula contain polynuclear leucocytes, the - distal part of the infundibula showing no evidence of inflammation. - Autopsy 333. -] - -Occasionally there is irregularly distributed hemorrhage and perhaps -some edema in the alveoli immediately adjacent to those which form the -peribronchiolar focus of inflammation. In such instances small bronchi, -that is, air passages, lined by columnar epithelium and devoid of -tributary alveoli, may be surrounded by a zone of hemorrhage; -immediately surrounding the bronchus, the wall of which shows intense -inflammation, alveoli, in a zone of which the radius represents several -alveoli, are filled with blood. This hemorrhagic zone is continued from -the bronchus over the focus of inflammation which surrounds the -bronchiole. - -Another variation in the character of the lesion is doubtless referable -to variation in the severity of primary bronchial injury. Alveoli -immediately surrounding small bronchi are filled with dense plugs of -fibrin. The alveoli which besot the walls of the bronchioles contain -fibrin, but the alveolar duct and its tributary alveoli are filled with -polynuclear leucocytes. - -The bacteria which have been cultivated from the lung in autopsies with -peribronchiolar pneumonia are as follows: - - Pneumococcus 5 - S. hemolyticus 8 - B. influenzæ, pneumococcus 5 - B influenzæ, S. hemolyticus 7 - B. influenzæ, staphylococcus 1 - Pneumococcus, staphylococcus 2 - S. hemolyticus, staphylococcus 2 - B. influenzæ, pneumococcus, S. hemolyticus 2 - B. influenzæ, pneumococcus, staphylococcus 1 - B. influenzæ, S. hemolyticus, staphylococcus 2 - Pneumococcus, S. hemolyticus, staphylococcus 3 - No organism 3 - —— - Total 41 - -The following list which shows the bacteria found in the blood is an -index to the pathogenicity of pneumococci and hemolytic streptococci: - - Pneumococcus 22 - S. hemolyticus 20 - Pneumococcus, S. hemolyticus 1 - No organism 14 - —— - Total 57 - -The percentage incidence of pneumococcus, hemolytic streptococcus, -staphylococcus and B. influenzæ in bronchus, lung and blood, given in -Table XXXVI, is inserted to indicate with what readiness each one of -these microorganisms passes from the bronchus through the lung into the -circulating blood. - - TABLE XXXVI - - ══════════════╤═════════════╤═════════════╤══════════════╤═════════════ - │PNEUMOCOCCUS │ HEMOLYTIC │STAPHYLOCOCCUS│B. INFLUENZA - │ │STREPTOCOCCUS│ │ - ──────────────┼─────────────┼─────────────┼──────────────┼───────────── - Bronchus │ 39.4%│ 57.7%│ 60.6%│ 84.8% - Lung │ 43.9%│ 61.0%│ 21.9%│ 43.9% - Blood │ 40.3%│ 36.8%│ 0. %│ 0. % - ──────────────┴─────────────┴─────────────┴──────────────┴───────────── - -B. influenzæ is present in the bronchi in a very large proportion (84.8 -per cent) of those in whom this type of bronchopneumonia has been found -at autopsy; it is much less frequently recovered from the lungs. -Staphylococci, in part S. albus and in part S. aureus, are less -frequently found in the bronchi and are recovered from the lungs in a -relatively small proportion of autopsies. The percentage incidence of -pneumococci and streptococci in lungs and blood demonstrates the -pathogenicity of these microorganisms, for whereas pneumococci and -hemolytic streptococci are found in the consolidated lungs in 43.9 and -61.0 per cent of instances of the lesion respectively, they make their -way into the blood in 40.3 and 36.8 per cent of instances. - -Coexisting infection with pneumococci and hemolytic streptococci has -been not uncommon e. g., Autopsy 275 in which both were in the blood; in -2 instances (Autopsies 333 and 378) in which pneumococci were obtained -from the blood, hemolytic streptococci were found in the lungs and -bronchi; in 3 instances (Autopsies 258, 273 and 445) in which hemolytic -streptococci were present in the blood, pneumococci were obtained from -the lungs. - -In the group of autopsies under consideration, examination of the sputum -was made during life and after onset of pneumonia in 11 instances. The -microorganisms found in the sputum and at autopsy were as follows: - - SPUTUM IN BLOOD, LUNGS OR BRONCHUS - AT AUTOPSY - Autopsy 240 Pneum. IV Pneum. IV - 246 Pneum. atyp. II, B. inf. - 247 Pneum. IV, B. inf. Pneum. IV - 250 Pneum. atyp. II, B. inf. Pneum. atyp. II - 253 Pneum. atyp. II Pneum. II - 285 Pneum. atyp. II, B. Inf. S. hem., B. inf. - 288 S. hem., B. inf. S. hem., B. inf. - 291 Pneum. IV, B. inf. Staph., B. inf. - 300 Pneum. atyp. II, B. inf. Pneum. atyp. II, B. inf. - 312 Pneum. IV, S. hem., B. inf. S. hem., B. inf. - 346 Pneum. IV, B. inf. S. hem., B. inf. - -In 2 instances (Autopsies 285 and 346) among this small group of cases, -pneumococci but no hemolytic streptococci were found in the sputum -several days before death, whereas death occurred as the result of -secondary invasion with hemolytic streptococci and no pneumococci were -found at autopsy. It is probable that this sequence of events is not -uncommon. B. influenzæ finds its way into the bronchi and pneumococci -follow it; pneumonia limited to peribronchiolar alveoli may occur in -consequence of this invasion. Later hemolytic streptococci may follow -the same path and cause death with bacteremia. - -=Hemorrhagic Peribronchiolar Consolidation.=—Peribronchiolar pneumonia -accompanied by diffuse accumulation of blood within the alveoli is one -of the most frequent complications of influenza. The lung tissue is -laxly consolidated, and on section there is a homogeneous dull deep red -background upon which are seen small gray spots (1.5 to 2 mm. in -diameter) grouped in clusters about the smallest bronchi (Fig. 5). Wide -areas of lung tissue are implicated and the lesion is more common in the -dependent parts of the lung than elsewhere. In common with other forms -of bronchopneumonia the lesion is in most instances associated with -changes in the bronchi; in 55 instances of hemorrhagic bronchiolar -pneumonia purulent bronchitis was found in 43 instances; it is -noteworthy that purulent bronchitis often is not evident in the presence -of pulmonary edema and edema is not infrequent with this pneumonic -lesion. - -Microscopic examination demonstrates the presence of acute bronchitis; -the lumina of the small bronchi contain polynuclear leucocytes and red -blood corpuscles. Accumulation of blood may separate the epithelium from -the basement membrane. The mucosa immediately below the epithelium -contains polynuclear leucocytes in fair abundance and the blood vessels -of the bronchial wall are much engorged. Respiratory bronchioles are -distended with polynuclear leucocytes and red blood corpuscles. In a -zone about each bronchiole, in areas corresponding to the small gray -spots seen upon the cut surface of the lung, the alveoli are filled with -polynuclear leucocytes. In the lung tissue intervening between these -spots of leucocytic pneumonia the alveoli are distended with red blood -corpuscles. - -[Illustration: - - Fig. 5.—Bronchopneumonia with hemorrhagic peribronchiolar - consolidation. -] - -In favorable sections it is occasionally possible to follow the -bronchiole and alveolar duct, both filled with leucocytes, into an -infundibulum. The proximal part of the infundibulum contains polynuclear -leucocytes, whereas the distal part and its tributary alveoli are filled -with serum and red blood corpuscles. - -When the lesion has persisted for a short time there is evidence of -beginning migration of polynuclear leucocytes from the blood vessels -into the alveoli which are filled with blood. The alveolar walls contain -numerous polynuclear leucocytes and leucocytes which have entered the -intraalveolar blood are numerous in contact with the wall but occur in -scant number in the center of the alveolar lumen. - -Alveolar epithelium in contact with the blood in the lumen is usually -swollen and often uniformly nucleated. - -The inflammatory process is evidently transmitted from the bronchioles -and to a less degree from the small bronchi to the adjacent alveoli. -Polynuclear leucocytes fill the lumen of the bronchiole and the alveoli -immediately adjacent; at the periphery of the focus of pneumonia, the -alveoli may contain fibrin. In such instances small bronchi (lined by a -continuous layer of columnar epithelial cells) may be surrounded by -alveoli containing fibrin. - -In sections from one part of the lung, the alveoli between the -peribronchiolar foci of pneumonia may be uniformly filled with red blood -corpuscles, whereas in sections from another part pneumonic foci may be -surrounded by a zone of intraalveolar hemorrhage or of hemorrhage and -edema outside of which some air-containing tissue occurs. There are -transitions between this halo of intraalveolar hemorrhage and edema -surrounding each bronchiolar focus and complete hemorrhagic infiltration -of all intervening alveoli. - -Large mononuclear cells are occasionally fairly numerous within the -alveoli containing blood. These cells act as phagocytes ingesting red -corpuscles, so that at times they are filled with corpuscles. -Disintegration of red corpuscles occurs and brown pigment remains within -the cell. It is not uncommon to find numerous mononuclear pigment -containing cells which resemble those found with chronic passive -congestion of the lungs. - -Lungs, the site of hemorrhagic peribronchiolar pneumonia, may undergo -chronic changes which will be described elsewhere. - -The lesion which has been designated hemorrhagic peribronchiolar -pneumonia is that which Pfeiffer regarded as the characteristic type of -influenzal pneumonia. In the small bronchi containing pus and in lung -tissue, Pfeiffer states, influenza bacilli are predominant and present -in astonishing number in smear preparations. The demonstration of B. -influenzæ by cultures from pneumonic lung is mentioned by him but its -association with other microorganisms in such cultures is not discussed. - -Microorganisms which we have isolated from the lungs of individuals with -hemorrhagic peribronchiolar pneumonia are as follows: - - B. influenzæ 1 - Pneumococcus 2 - S. hemolyticus 10 - B. influenzæ, pneumococcus 7 - B. influenzæ, S. hemolyticus 3 - B. influenzæ, staphylococcus 2 - S. hemolyticus, B. coli 3 - B. influenzæ, pneumococcus, staphylococcus 2 - B. influenzæ, S. hemolyticus, staphylococcus 5 - Pneumococcus, S. hemolyticus, staphylococcus 1 - No organisms 2 - —— - Total 38 - -With this type of pneumonia B. influenzæ has not been isolated in pure -culture; B. influenzæ alone is recorded only once (Autopsy 435), but in -this instance the culture has been so obscured by contamination that the -occurrence of pneumococci or streptococci cannot be excluded; S. -hemolyticus has doubtless been present in this lung, for it has been -found in the heart’s blood, in the bronchus, and in the peritoneal -exudate of the same individual. - -The incidence of pneumococci and hemolytic streptococci in this list -does not differ materially from that with peribronchiolar pneumonia -unaccompanied by extensive intraalveolar hemorrhage, though hemolytic -streptococci are somewhat more frequent with the hemorrhagic lesion. The -following table shows the frequency with which pneumococci and hemolytic -streptococci have penetrated into the blood: - - Pneumococcus 11 - S. hemolyticus 24 - Pneumococcus, S. hemolyticus 1 - No organism 12 - —— - Total 48 - -Table XXXVII showing the percentage incidence of pneumococci, hemolytic -streptococci, staphylococci and B. influenzæ further emphasizes the -similarity between the bacteriology of peribronchiolar pneumonia (Table -XXXVI) and the closely related hemorrhagic lesion: - - TABLE XXXVII - - ══════════════╤═════════════╤═════════════╤══════════════╤═════════════ - │ │ HEMOLYTIC │ │ - │PNEUMOCOCCUS │STREPTOCOCCUS│STAPHYLOCOCCUS│B. INFLUENZÆ - ──────────────┼─────────────┼─────────────┼──────────────┼───────────── - Bronchus │ 44.0%│ 64.0%│ 44.0%│ 72.0% - Lung │ 31.6%│ 57.9%│ 26.8%│ 52.6% - Blood of heart│ 25.0%│ 52.1%│ 0%│ 0% - ──────────────┴─────────────┴─────────────┴──────────────┴───────────── - -Pneumococci have been found in the lungs (31.6 per cent) and blood (25 -per cent), somewhat less frequently than with peribronchiolar pneumonia -(43.9 and 40.3 per cent respectively), and hemolytic streptococci have -been found in the blood more frequently (52.1 per cent) than with the -latter (36.8 per cent) but otherwise the bacteriology of the two lesions -corresponds closely. The low incidence of B. influenzæ in the bronchi -(72 per cent) with hemorrhagic peribronchiolar pneumonia is perhaps -incorrect as the result of the relatively small number of bacteriologic -examinations (namely, 25), but the incidence of the same microorganism -in the lung has been higher (52.6 per cent) than with nonhemorrhagic -peribronchiolar lesion (43.9 per cent). - -In some instances infection with hemolytic streptococci has occurred -after the onset of pneumonia. The following list compares the results of -bacteriologic examination of the sputum made after the onset of -pneumonia with that of blood, lungs or bronchus after death: - - SPUTUM IN BLOOD, LUNGS OR BRONCHUS - AT AUTOPSY - Autopsy 237 S. hem. S. hem. - 242 Pneum. atyp. II, B. inf. Pneum. atyp. II - 247 Pneum. IV, B. inf. Pneum. IV - 266 S. hem. S. hem., B. inf. - 346 Pneum. IV, B. inf. S. hem., B. inf. - 376 (No. S. hem.) S. hem., staph., B. inf. - -Instances of secondary infection with hemolytic streptococcus occur in -the list, namely, Autopsies 346 and 376. - -From the foregoing studies of the bacteriology of peribronchiolar and -hemorrhagic peribronchiolar pneumonia the following conclusions may be -drawn: (_a_) B. influenzæ is found in most instances of these lesions in -the bronchi and in about half of all instances in the lungs, but does -not occur unaccompanied by other microorganisms. (_b_) In a considerable -number of autopsies pneumococcus is the only microorganism that -accompanies B. influenzæ; from the lungs it penetrates into the blood -from which it is obtained in pure culture. (_c_) In a considerable -number of instances S. hemolyticus accompanies B. influenzæ, and in some -of these instances (representing a large proportion of the relatively -small number of cases examined during life), examination of the sputum -has demonstrated that infection has been secondary to a pneumonia with -which no hemolytic streptococci have been found in the sputum. - -=Lobular Consolidation.=—Consolidation of scattered lobules or groups of -lobules has occurred in nearly all instances, namely, 71 of 80 autopsies -with bronchopneumonia unaccompanied by lobar pneumonia or by -suppuration. When death follows shortly after the onset of pneumonia, -patches of consolidation have a dull deep red color; blood-tinged fluid -escapes from the cut surface which is almost homogeneous or finely -granular. The consolidated tissue seen through the pleura, which is -raised above the general level, has a bluish red color. Isolated lobules -or groups of lobules which have undergone consolidation may be scattered -throughout the lungs, but not infrequently there is confluent -consolidation of the greater part of lobes, of whole lobes or of almost -an entire lung. Such lungs are very heavy and may weigh 1,400 or 1,500 -grams; bloody serous fluid exudes from the cut surface. The lesion -resembles the red hepatization of lobar pneumonia, but confluent patches -of pneumonia are usually well defined by lobule boundaries. The tissue -is soft and the granulation of lobar pneumonia is absent. In many -instances the lobular or confluent areas of consolidation are reddish -gray; in some instances consolidated tissue is in places red and -elsewhere gray, and in a smaller group of autopsies there is gray -consolidation only (Fig. 6). Red lobular consolidation is often seen in -those who have died within the first four days following the onset of -pneumonia, but is almost equally frequent after from five to ten days; -the average duration of pneumonia in these cases was 5.5 days. Combined -red and gray consolidation was more frequently found when pneumonia had -lasted more than five days, the average duration of pneumonia being 7.3 -days. The greater number of instances of gray consolidation were found -after seven days of pneumonia, the average duration of the disease being -10.0 days. These figures are cited to show that lobular, like lobar, -consolidation passes gradually from a stage of red to gray hepatization, -but the change occurs more slowly and is often long delayed. - -Lobular pneumonia, which occurred 71 times among 80 cases classified as -bronchopneumonia, may be regarded as an almost constant lesion of the -disease. It is found not only in association with other lesions of -bronchopneumonia, but with lobar pneumonia of influenza as well. - -The bacteriology of this lesion shows no deviation from that of the -slightly larger group of bronchopneumonia (p. 163). All types of -pneumococcus have been found in association with the lesion, -Pneumococcus I in 2 instances, Pneumococcus II in 1 instance; atypical -Pneumococcus II and Pneumococcus IV have been found much more -frequently. Pneumococci have been found in more than a third of these -autopsies (42.9 per cent in the lungs, 33.3 per cent in the blood); -hemolytic streptococci in less than one-third (28.5 per cent in the -lungs, 30.2 per cent in the blood). - -[Illustration: - - Fig. 6.—Acute bronchopneumonia with confluent gray lobular - consolidation in lower part of upper lobe and hemorrhagic - peribronchiolar pneumonia in lower lobe; purulent bronchitis. -] - -The following list shows the bacteriology of a small group of autopsies -in which the sputum was examined after onset of pneumonia: - - SPUTUM BLOOD, LUNGS OR BRONCHUS AT - AUTOPSY - Autopsy 233 Pneum. atyp. II Pneum. - 237 S. hem. S. hem. - 242 Pneum. atyp. II, B. inf. Pneum. atyp. II - 250 Pneum. atyp. II, B. inf. Pneum. atyp. II - 253 Pneum. atyp. II Pneum. atyp. II, staph., B. - inf. - 266 S. hem. S. hem., B. inf. - 274 Pneum. IV S. hem. - 291 Pneum. IV, B. inf. Staph., B. inf. - 312 Pneum. IV, S. hem., B. inf. S. hem., staph., B. inf. - -In one instance of streptococcus pneumonia (Autopsy 274) infection with -streptococci occurred subsequent to the examination of the sputum made -five days before death; pneumococcus was found in the washed sputum. - -With lobar pneumonia there was evidence that superimposed infection -occurred more frequently during the stage of red than of gray -hepatization. With the lobular consolidation of bronchopneumonia this -relation has not been found. Among 27 instances of red lobular -consolidation, hemolytic streptococcus has occurred 6 times, namely in -22.2 per cent; among 26 instances of red and gray consolidation, 8 -times, namely, in 30.7 per cent; among 13 instances of gray -consolidation, 5 times, namely, in 38.5 per cent. Infection with -hemolytic streptococci is more frequent when the lesion has persisted to -the stage of gray hepatization. This difference between lobar and -bronchopneumonia is probably dependent in part at least upon the more -severe and persistent lesions of the bronchi with bronchopneumonia. - -The histology of consolidation which is definitely limited to secondary -lobules or groups of lobules varies considerably. When death occurs in -the early stage of the lesion, consolidated patches are deep red and -somewhat edematous, so that bloody serous fluid escapes from the cut -surface of the lung and red blood corpuscles are present in the alveoli -in great abundance together with polynuclear leucocytes, fibrin and -serum in varying quantity. It is not uncommon to find evidence that the -lesion has had its origin in the bronchioles and extended from them to -other parts of the lobule. Polynuclear leucocytes may be relatively -abundant within and immediately about the bronchioles and alveolar -ducts, whereas the intervening alveoli and infundibula are filled with -red blood corpuscles among which are polynuclear leucocytes and perhaps -some fibrin. It may be evident that bronchiolar pneumonia with -hemorrhage into intervening alveoli is in process of transformation into -a more diffuse leucocytic pneumonia, for polynuclear leucocytes are -making their way from the alveolar wall into the blood-filled lumen and, -as the result of the presence of blood, remain for a time close to the -lining of the alveolus. - -When the consolidated lobules have assumed a gray or reddish gray color, -polynuclear leucocytes are more abundant and often almost homogeneously -pack every alveolus within the boundaries of the lobule. In some -instances there is fibrin partially obscured by the presence of -leucocytes in great number. - -Although fibrin is less abundant with bronchopneumonia than with lobar -pneumonia, nevertheless in a considerable proportion of instances it is -a very conspicuous element of the inflammatory exudate within the -bronchioles, alveolar ducts and alveoli. It is unusual to find the -alveolar ducts and alveoli uniformly plugged with fibrin containing -leucocytes; there is a variegated distribution of exudate which has -little resemblance to that of lobar pneumonia. Occasionally (Autopsies -242 and 247) polynuclear leucocytes fill the bronchioles, alveolar ducts -and infundibula, whereas the surrounding tributary alveoli contain -fibrin and polynuclear leucocytes in moderate number; red blood -corpuscles may be present in sufficient number to give a homogeneously -red color to the lobular consolidation. - -In association with lobular pneumonia, fibrin within the lung tissue -undergoes certain changes which outline very sharply the alveolar ducts -and the other structures usually ill defined in preparations of the -lung. A remarkable appearance is produced by the deposit of hyalin -fibrin upon the surface of the alveolar ducts and infundibula. This -lesion has been described by LeCount. - -Within the alveolar tissue of the lung, spaces are seen lined by a layer -of fibrin which stains homogeneously and very brightly with eosin. They -are recognized as alveolar ducts by the presence of scattered bundles of -smooth muscle in their wall. The layer of hyaline fibrin overlying the -surface of the alveolar duct usually forms a continuous lining and -covers over the orifices of the alveoli which surround the alveolar -duct. These ducts are rendered still more conspicuous by the character -of their contents which exhibits a sharp contrast with that of the -surrounding alveoli. The alveoli duct occasionally contains a bubble of -air, but more frequently it is filled with serum in which red blood -corpuscles are sometimes numerous. There is within the lumen scant -fibrin and very few cells, among which polynuclear leucocytes are -predominant. In the surrounding alveoli on the contrary leucocytes and -fibrin are abundant. A similar change is found in the infundibula very -clearly defined by their conical form, which is especially well outlined -below the pleura or in contact with interlobular septa. The infundibulum -is outlined by hyaline fibrin which passes over the orifices of the -tributary alveoli and separates the serous contents of the infundibulum -from the cellular fibrinous contents of the alveoli about. - -The lesion which has been described is often associated with acute -bronchitis and bronchiolitis, and the alveoli immediately about the -respiratory bronchioles may be filled with polynuclear leucocytes. It is -very common to find large bubbles of air sharply defined within the -purulent contents of the bronchiole. In some lobules the alveolar ducts, -infundibula and alveoli intervening between these foci of leucocytic -pneumonia are almost uniformly filled with fibrin and polynuclear -leucocytes, but in other places the formation of complete layers of -hyaline fibrin is in process. Bubbles of air are often seen within the -alveolar ducts, and about them is an irregular layer of fibrin formed by -the penetration of air into a channel previously filled with a loose -network of fibrin containing serum in its meshes. The fibrin compressed -against the walls of alveolar duct and infundibulum remains as a compact -layer separating these structures from the alveoli which project from -their walls. The bubble of air is doubtless later absorbed and replaced -by serum, so that many alveolar ducts are filled with serum almost -wholly free from cells, whereas alveoli outside the fibrinous membrane -contain a network of fibrin with leucocytes in greater or less -abundance. - -In association with this fibrinous pneumonia, which has been described, -hyaline thrombosis of the capillaries is not uncommon. This hyalin -material within the capillaries gives reactions of fibrin, and in -sections stained by the Gram-Weigert method for demonstration of fibrin, -these thrombosed vessels have the appearance of capillaries irregularly -injected with a blue material. - -The interstitial tissue surrounding consolidated lobules is often -edematous; the lymphatics are distended with serum and contain a -moderate number of lymphocytes and polynuclear leucocytes. - -Among the lungs which have been studied histologically, pneumococcus has -been almost invariably associated with the lobular lesions which have -just been described, whether hemorrhagic, leucocytic or fibrinous; the -histologic changes accompanying infection of the lung with streptococcus -will be described later. Pneumococcus has been cultivated from the -consolidated lung and is found in section of the lung. B. influenzæ is -found in cultures made from the bronchi. Table XXXVIII includes those -instances in which the histology of the consolidated lung accords with -the description given above. - - TABLE XXXVIII - - ══════════╤═════════════╤════════════╤═══════════╤══════════╤══════════ - NO. OF │CHARACTER OF │PREDOMINANT │ CULTURE │ CULTURE │ CULTURE - AUTOPSY │ LOBULAR │ TYPE OF │ FROM │FROM LUNG │ FROM - │CONSOLIDATION│INFLAMMATORY│ HEART’S │ │ BRONCHUS - │ │ EXUDATE │ BLOOD │ │ - ──────────┼─────────────┼────────────┼───────────┼──────────┼────────── - 242 │ Red │ Fibrinous │ Pneum. │ │ - │ │ │ atyp. II │ │ - 244 │ Red │ Leucocytic │ │Pneum. IV │Pneum. IV, - │ │ and │ │ B. inf. │ B. inf. - │ │hemorrhagic │ │ │ - 247 │Red and gray │ Fibrinous │ Pneum. IV │ │ - 249 │Red and gray │ Fibrinous │Pneum. III │ │ - 252 │Red and gray │ Fibrinous │ │Pneum. II │Pneum. II, - │ │ │ │ B. inf. │ B. inf., - │ │ │ │ │ S. vir. - 257 │Red and gray │ Leucocytic │ Pneum. I │ │ B. inf., - │ │ │ │ │ staph. - 303 │ Red │ Fibrinous │ │Pneum. IV │Pneum. IV, - │ │ │ │ B. inf. │ B. inf., - │ │ │ │ │ staph. - 314 │ ? │ Fibrinous │ Pneum. IV │Pneum. IV │Pneum. IV, - │ │ │ │ │ B. inf., - │ │ │ │ │ staph. - 336 │ Red │ Fibrinous │ │ │ - 395 │Red and gray │ Leucocytic │ Pneum. │ Pneum. │ - │ │ │ atyp. II │ atyp. II │ - 464 │ Red │ Leucocytic │ │ Pneum. I │Pneum. I, - │ │ and │ │ B. inf. │ B. inf., - │ │hemorrhagic │ │ │ staph. - 476 │ Red │ Leucocytic │ │ │ - │ │ and │ │ │ - │ │hemorrhagic │ │ │ - 498 │Red and gray │ Fibrinous │ │ S. aur. │ - 506 │ Red │ Fibrinous │ Pneum. IV │Pneum. IV │Pneum. IV, - │ │ │ │ S. aur. │ B. inf., - │ │ │ │ │ S. aur., - │ │ │ │ │M. catarrh - ──────────┴─────────────┴────────────┴───────────┴──────────┴────────── - -Pneumococcus was found in all but 2 instances, and in one of these -(Autopsy 336) the only culture was from the heart’s blood and in the -other (Autopsy 498) cultures were unsatisfactory because proper media -were not obtainable. Pneumococci of Types I, II, II atypical, III and IV -are represented in the list. B. influenzæ has been found in a -considerable number of instances in which cultures have been made from -the lung and in every instance in which cultures have been made from the -bronchi. Staphylococci are often found in the bronchi, but in most -instances they do not penetrate into the lung. - -Another group of cases of lobular pneumonia are important because in -association with necrosis of lung tissue recognized by the microscope -hemolytic streptococci have been found in the lungs. In such instances -serum is abundant and polynuclear leucocytes are relatively scant though -their distribution varies considerably; in some places leucocytes are -fairly abundant though elsewhere almost absent, but this distribution -bears no obvious relation to the bronchioles. In some instances -(Autopsies 274 and 487) red blood corpuscles are numerous but in others -(Autopsies 275 and 312) they are inconspicuous. The characteristic -feature of the lesion is the occurrence of patches of necrosis within -which the nuclei both of exudate and of alveolar walls have partially or -completely disappeared. In these areas of necrosis short chains of -streptococci are found in immense number whereas in living tissue they -are present in moderate number. There has been a relatively inactive -inflammatory reaction, great proliferation of streptococci and necrosis -of invaded tissue. The bacteriology of instances of lobular pneumonia -with necrosis is shown in Table XXXIX. - - TABLE XXXIX - - ══════════╤═════════════╤════════════╤═══════════╤══════════╤══════════ - NO. OF │CHARACTER OF │PREDOMINANT │ CULTURE │ CULTURE │ CULTURE - AUTOPSY │ LOBULAR │ TYPE OF │ FROM │FROM LUNG │ FROM - │CONSOLIDATION│INFLAMMATORY│ HEART’S │ │ BRONCHUS - │ │ EXUDATE │ BLOOD │ │ - ──────────┼─────────────┼────────────┼───────────┼──────────┼────────── - 274 │ Red │ Leucocytic │ S. hem. │ S. hem. │ S. hem., - │ │ and │ │ │ staph. - │ │hemorrhagic │ │ │ - 275 │Red and gray │ Leucocytic │ Pneum. IV │ S. hem., │ S. hem., - │ │ │ S. hem. │ B. inf., │ B. inf., - │ │ │ │ staph. │ staph. - 312 │Red and gray │ Leucocytic │ S. hem. │ S. hem., │ S. hem., - │ │ │ │ B. inf. │ B. inf., - │ │ │ │ │ staph. - 478 │ Red │ Leucocytic │ S. hem. │ S. hem. │ - │ │ and │ │ │ - │ │hemorrhagic │ │ │ - ──────────┴─────────────┴────────────┴───────────┴──────────┴────────── - -Lobular pneumonia, in some of these instances at least, has been caused -primarily by pneumococci; necrosis has been the result of secondary -invasion by streptococci. In Autopsy 275 Pneumococcus IV has been -obtained from the blood, but in the presence of streptococci has -presumably disappeared from the lung and bronchus. In the case -represented by Autopsy 274, Pneumococcus IV has been found in the sputum -five days before death at the onset of pneumonia, but at this time no -hemolytic streptococci have been found. In the case represented by -Autopsy 312, Pneumococcus IV, B. influenzæ and a few colonies of -hemolytic streptococci have been obtained from the sputum two days after -recognition of pneumonia and five days before death. - -The hemorrhagic and edematous consolidation of the early pulmonary -lesions of influenzal pneumonia is their most distinctive feature. Red -confluent lobular pneumonia is frequently found in those who have died -within the first week following the onset of influenza. The lungs are -voluminous and heavy and may weigh as much as 1,500 grams; the pleura -which overlies the consolidated area is blue or plum colored and usually -shows scant if any evidence of pleurisy. Scattered patches of -consolidation are accurately limited to lobules, but in addition there -are large areas often involving the greater part of the lobes and not -infrequently situated in the lowermost part of the lower lobes. This -confluent consolidation may be obviously limited by lobule boundaries. -The consolidated tissue is deep red and laxly consolidated; red serous -fluid escapes from the cut surface. The lesion not infrequently occurs -in association with hemorrhagic peribronchiolar pneumonia. - -The histology of this confluent lesion has been studied in Autopsies -242, 244, 303, 336, 464, 474 and 506. The histology varies, because, in -some instances, leucocytes, in other instances, fibrin, is abundant, but -the presence of red blood corpuscles in large number within the alveoli -gives a red color to the consolidated tissue. In these cases -pneumococci, associated in the lungs or in the bronchi with B. -influenzæ, have been the cause of pneumonia. In two autopsies studied -histologically (Autopsies 274 and 478) there was red lobular and -confluent pneumonia and the blood and lungs contain hemolytic -streptococci demonstrated by cultures; microscopic examination showed -the presence of a widespread necrosis of the lung tissue. - -In the group of autopsies in Table XL there was red confluent lobular -pneumonia. These autopsies are separated from those just cited because -there was no histologic examination of the tissue. - - TABLE XL - - ═════════════════╤═════════════════╤═════════════════╤═════════════════ - NO. OF AUTOPSY │ BACTERIOLOGY OF │ BACTERIOLOGY OF │ BACTERIOLOGY OF - │ HEART’S BLOOD │ LUNGS │ BRONCHUS - ─────────────────┼─────────────────┼─────────────────┼───────────────── - 289 │ Pneum. IV │ Pneum. IV │ Pneum. IV, B. - │ │ │ inf., staph. - 297 │ │ Pneum. IV, B. │ Pneum. IV, B. - │ │ inf. │inf., S. hem. (a - │ │ │ few) - 306 │ │ │ - 339 │ Pneum. IV │ │ - 364 │ S. hem. │ │ - 418 │ Pneum. atyp. II │Pneum. atyp. II, │ - │ │B. inf., S. vir. │ - 424 │ │ Pneum. IV. │ - ─────────────────┴─────────────────┴─────────────────┴───────────────── - -This group of autopsies confirms the view that the red confluent lobular -pneumonia is caused by pneumococci in association with B. influenzæ. -Hemolytic streptococci may invade secondarily. In Autopsy 297 a few -hemolytic streptococci were found in the bronchus but apparently had not -entered the lungs. In the absence of histologic examination it is not -possible to determine if the invasion of hemolytic streptococcus (in -Autopsy 364) has caused necrosis of the pneumonic tissue. - -[Illustration: - - Fig. 7.—Bronchopneumonia with purulent bronchitis and peribronchial - hemorrhage. -] - - - Peribronchial Hemorrhage and Pneumonia - -In a considerable number of instances, namely, in 19 autopsies, -hemorrhage about the small bronchi has been recognizable upon gross -examination of the lung. A conspicuous zone of hemorrhage 2 or 3 mm. in -thickness surrounds small (with no cartilage) often dilated bronchi and -on longitudinal section may be tracted for a considerable distance along -the bronchus (Fig. 7). In many additional instances peribronchial -hemorrhage has been found by microscopic examination. In some instances -the peribronchial zone of hemorrhage is firmer than the tissue elsewhere -and it is occasionally difficult to determine whether the lesion is -hemorrhage or pneumonia. In 7 instances frank red consolidation of -peribronchial tissue was recognized at autopsy; this lesion will be -considered later under peribronchial pneumonia. Hemorrhage about -bronchi, like other evidences of severe injury to bronchi following -influenza, is more frequently found in the lowermost parts of the lungs -than elsewhere. It is invariably associated with severe bronchitis; the -bronchi have contained purulent fluid in 15 of 19 instances of -peribronchial hemorrhage and in 10 instances the lesion has been -associated with dilatation of the bronchi. - -Microscopic examination furnishes further evidence of the severity of -the bronchial changes which have brought about hemorrhage into the -surrounding alveoli. The lumen of the bronchus contains blood and -leucocytes; the epithelium is sometimes raised in places from the -underlying basement membrane by blood; blood vessels of the bronchial -wall are engorged, and there is hemorrhage into the tissue of the -bronchus. More frequently the bronchial epithelium is completely lost -and the denuded surface is often covered by a layer of fibrin intimately -adherent to the inflamed mucosa. Transitions between simple hemorrhage -and pneumonia are found, polynuclear leucocytes being mingled with red -blood corpuscles. In several instances the alveoli in immediate contact -with the bronchial wall have contained fibrin, whereas those in the -surrounding zone have contained blood. - -Bacteria found in the bronchi in 10 instances of peribronchial -hemorrhage have been as follows: - - Staphylococci 1 - B. influenzæ, pneumococci 1 - B. influenzæ, S. hemolyticus 2 - B. influenzæ, pneumococci, staphylococci 1 - B. influenzæ, S. hemolyticus, staphylococci 4 - No organism found 1 - -The high incidence of B. influenzæ and the frequent association of B. -influenzæ and hemolytic streptococci are noteworthy. The instance in -which no organisms were found is probably due to a defect in media and -should perhaps be excluded from the list. - -The percentage incidence of pneumococci, hemolytic streptococci, -staphylococci and B. influenzæ in the bronchus, lungs and blood of the -heart is an index of the facility with which these microorganisms -penetrate internal organs when the bronchi are the site of this -hemorrhagic lesion. - - TABLE XLI - - ════════╤════════╤═════════════════╤═════════════════ - │ NO. OF │ │ HEMOLYTIC - │CULTURES│ PNEUMOCOCCI │ STREPTOCOCCI - ────────┼────────┼────────┬────────┼────────┬──────── - │ │ NO. │PER CENT│ NO. │PER CENT - │ │POSITIVE│POSITIVE│POSITIVE│POSITIVE - ────────┼────────┼────────┼────────┼────────┼──────── - Bronchus│ 10│ 2│ 20.0│ 6│ 60.0 - Lung │ 13│ 4│ 30.8│ 7│ 53.8 - Blood │ 17│ 4│ 23.5│ 9│ 52.9 - ────────┴────────┴────────┴────────┴────────┴──────── - - ════════╤═════════════════╤═════════════════ - │ │ - │ STAPHYLOCOCCI │ B. INFLUENZÆ - ────────┼────────┬────────┼────────┬──────── - │ NO. │PER CENT│ NO. │PER CENT - │POSITIVE│POSITIVE│POSITIVE│POSITIVE - ────────┼────────┼────────┼────────┼──────── - Bronchus│ 6│ 60.0│ 8│ 80.0 - Lung │ 3│ 23.1│ 5│ 38.5 - Blood │ │ │ │ - ────────┴────────┴────────┴────────┴──────── - -When these figures are compared with those for all forms of bronchitis -no very noteworthy differences are found; the incidence of pneumococci -here is less and that of hemolytic streptococci greater. In association -with the severe changes present in the bronchi, hemolytic streptococci -which enter the lungs almost invariably find their way into the blood. - -In 6 instances there has been frank pneumonic consolidation limited to a -zone encircling small and medium-sized bronchi which have often been -obviously dilated. On cross section these patches of pneumonia are -circular, from 1 to 2 cm. in diameter and each contains a bronchus at -its center. When the bronchus is cut longitudinally it is evident that -pneumonic consolidation forms a cylindrical sheath about the tube. The -consolidation varies in color from red to grayish red. In one instance -(Autopsy 253) the consolidated tissue has formed a gray zone in contact -with the bronchus and is red in a peripheral zone; microscopic -examination shows that the alveoli about the bronchus contain fibrin, -whereas those at a greater distance contain red blood corpuscles. In -this instance, the associated pneumonia in another part of the lung has -been somewhat anomalous and has had characters both of lobar and -bronchopneumonia, for scattered in the left lung there have been patches -of firm consolidation not more than 2 cm. across. The smaller of these -patches are deep red, but the larger are coarsely granular and gray in -the center. The patchy character of the lesion has suggested -bronchopneumonia, but the coarse granulation on section and the presence -of fibrinous plugs within the small bronchi have presented a close -resemblance to lobar pneumonia. This autopsy is one of the few instances -in which Pneumococcus II has been found, Pneumococcus II being present -in blood and lungs, B. influenzæ, in lungs and bronchi. In 2 additional -instances (Autopsies 374 and 392) peribronchial pneumonia, recognizable -at autopsy, has been associated with consolidation having the characters -of lobar pneumonia. In one instance, Autopsy 374, the right lung has -contained two patches of firm, mottled red and pinkish red coarsely -granular consolidation each about 6 cm. across, one situated in the -upper lobe and the other in the lower lobe. Elsewhere in the lung, in -definite relation to dilated bronchi, occur patches of firm, red, -coarsely granular consolidation from 1 to 1.5 cm. in diameter when cut -transversely. The bronchus in the center has contained purulent fluid. -In the opposite lung similar consolidation has been limited to zones -about dilated bronchi which contain purulent fluid. Pneumococcus IV has -been obtained from the blood of the heart. - -The peribronchial pneumonia which has been described occurs in -association with evidence of profound injury to the bronchial wall. In 5 -of 6 instances purulent bronchitis has been found at autopsy; in half of -these instances bronchiectasis has been noted. The epithelium of the -bronchus has been found separated from the underlying tissue by serous -exudate, blood and leucocytes; epithelial cells undergo necrosis and -disappear, the denuded surface being covered by fibrin. Necrosis extends -a varying depth into the wall of the bronchus; blood vessels are -engorged, and there is in some instances hemorrhage throughout the wall -of the bronchus. - -The character of the exudate in the alveoli surrounding the bronchus -differs considerably in different instances. In some instances -(Autopsies 374 and 392) red blood corpuscles are predominant in the -alveoli in contact with the bronchial wall, whereas in a peripheral zone -polynuclear leucocytes are more abundant. In other instances (Autopsies -253 and 402) alveoli next the bronchial wall contain abundant fibrin and -these are surrounded by a zone in which the alveoli are filled with -blood. - -Peribronchial pneumonia is the result of the direct extension of the -inflammatory process through the wall of the bronchus; it occurs when -the epithelium of the bronchus is destroyed and the underlying tissues -are injured, but may be present in a wide encircling zone even when the -lesion has not penetrated the bronchial wall. The distribution of the -pneumonia demonstrates very clearly that the inflammatory process does -not reach the affected peribronchial alveoli by way of the bronchioles -tributary to the bronchus. - -The bacteriology of these instances of peribronchial pneumonia is -noteworthy. (Table XLII.) - - TABLE XLII - - ═════════════════╤═════════════════╤═════════════════╤═════════════════ - AUTOPSY │ BLOOD │ LUNG │ BRONCHUS - ─────────────────┼─────────────────┼─────────────────┼───────────────── - 253 │Pneum. II │Pneum. II, B. │Staph., B. inf. - │ │ inf. │ - 374 │Pneum. IV │ │ - 387 │Pneum. II, S. │Pneum. II, │Pneum. II, S. - │ hem. │ staph., B. inf.│ hem., staph., - │ │ │ B. inf. - 392 │Pneum. II │ │ - 402 │Pneum. IV, S. │ │ - │ hem. │ │ - 424 │? │Pneum. IV │ - ─────────────────┴─────────────────┴─────────────────┴───────────────── - -Pneumococcus has been found in every instance either in the lungs or -blood. Pneumococcus II, which has been uncommon with the pneumonia -following influenza at Camp Pike and has occurred only ten times in more -than 200 autopsies, has been present in one-half of these cases. The -constant association of the lesion with pneumococcus is particularly -significant when a comparison is made between the incidence of -pneumococcus with peribronchial hemorrhage, on the one hand, and -peribronchial pneumonia on the other; pneumococcus has been present in -less than a third of the instances of hemorrhage but in all instances of -pneumonia. - -In addition to the instances in which gross peribronchial consolidation -has been noted at autopsy, microscopic examination has demonstrated the -presence of fibrinous pneumonia surrounding bronchi in a considerable -number of autopsies. In a zone encircling small bronchi (with no -cartilage) alveoli are filled by plugs of dense fibrin (Fig. 20) -containing in variable number polynuclear leucocytes and mononuclear -cells. The width of the zone is often equal or greater than the diameter -of the bronchus. Alveoli outside the zone of fibrinous inflammation may -contain red blood corpuscles or serum, and desquamated epithelial cells -are often abundant. - -Of 21 instances of peribronchial fibrinous pneumonia 20 were associated -with purulent bronchitis. Further evidence of the relation of the lesion -to profound injury to the bronchi is its association with bronchiectasis -in 17 instances. - -Peribronchial fibrinous pneumonia, like other lesions encircling the -small bronchi, bears a direct relation to the severity of microscopic -changes in the bronchus. The epithelium of the bronchus is either -partially or completely lost. Occasionally epithelium is raised by -hemorrhage or leucocytes from the underlying tissue but more frequently -it is wholly lost and the surface is covered by a layer of fibrin. In -the early stages of the lesion, polynuclear leucocytes may be numerous -throughout the bronchial wall, indicating that the inflammatory irritant -within the lumen is affecting the entire wall and extending its -influence to the surrounding pulmonary tissue. Later lymphoid and plasma -cells are more abundant than polynuclear leucocytes. Coagulative -necrosis and disintegration of the bronchial wall, proceeding from the -inner surface outward, may extend more or less deeply, and fibrinous -inflammation of adjacent alveoli is often more extensive about that -segment of the bronchus which shows the greatest change. In some -instances segments of the bronchial wall or even the entire wall has -disappeared, so that alveoli containing fibrin form part of the wall of -the cavity thus formed. When bronchiectasis has occurred, there are -often fissures from the lumen through the entire wall extending into the -surrounding lung tissue: here fibrinous pneumonia is particularly -conspicuous, occurring in a zone about the edges of the defect. This -deposition of fibrin within the alveoli adjacent to the injury doubtless -has a part in limiting the distribution of bacterial infection. -Nevertheless breaks in the continuity of the bronchial wall are not -essential to the production of the lesion and the irritant, which is -responsible for the lesion, may penetrate through the bronchial wall to -surrounding alveoli and from alveoli to other alveoli immediately -adjacent. - -With this peribronchial pneumonia the smallest bronchi are distended -with pus and their walls are infiltrated with polynuclear leucocytes, -lymphoid and plasma cells. In a broad zone encircling the bronchus the -alveoli are filled with plugs of fibrin. Bronchioles are similarly -distended with polynuclear leucocytes; the alveoli which occur upon the -wall of the bronchiole are often limited to one side of the wall and are -filled with fibrin. This fibrin occasionally projects into the lumen of -the bronchiole and forms a continuous layer in contact with the wall on -the same side. The alveolar duct and infundibulum are distended with -polynuclear leucocytes. The alveoli upon the wall of the alveolar duct -and upon the proximal part of the infundibulum are filled with fibrin. -The bronchus, bronchiole, alveolar duct and part of the infundibulum are -thus surrounded by a continuous zone of alveoli containing fibrin. The -alveoli about the distal part of the infundibulum may be filled with -polynuclear leucocytes. Lung tissue between adjacent zones of fibrinous -pneumonia may contain serum and desquamated epithelial cells. - -Organization of peribronchial fibrin was found in 10 of the 22 autopsies -in which peribronchial fibrinous pneumonia had been found. Fibroblasts -have invaded the fibrin and newly formed capillaries have penetrated -into it. In some instances the interalveolar septa are thickened and -infiltrated with lymphoid and plasma cells, and in 7 instances there was -chronic pneumonia with thickening and mononuclear infiltration of the -interstitial tissue about the bronchi and blood vessels, and elsewhere. -The duration of the fatal illness in 12 instances with no organization -was usually from ten days to two weeks, though in 3 instances there was -no organization although the respiratory disease had lasted from -seventeen to nineteen days (average duration with no organization, 13.5 -days). The duration of illness in 10 instances with organization of -fibrin was slightly less than three weeks (average 18.9 days). These -figures do not accurately represent the duration of pneumonia which -usually develops after a period of several days following onset of -influenza. - -This group of instances of peribronchial fibrinous pneumonia has offered -an opportunity to study the bacteriology of pneumonia with organization -and to determine if it presents any unusual characters. The bacteriology -of autopsies with peribronchial fibrinous pneumonia with no organization -is shown in Table XLIII: - - TABLE XLIII - - ═════════════════╤═════════════════╤═════════════════╤═════════════════ - AUTOPSY │ BLOOD │ LUNG │ BRONCHUS - ─────────────────┼─────────────────┼─────────────────┼───────────────── - 289 │Pneum. IV │Pneum. IV │Pneum. IV, B. - │ │ │ inf., staph. - 372 │ │ │ - 376 │S. hem. │S. hem. │S. hem., B. inf., - │ │ │ S. aur. - 409 │0 │ │ - 410 │ │S. hem., B. inf. │ - │ │ S. aur. │ - 412 │Pneum. II │ │Pneum. II, B. - │ │ │ inf. - 420 │S. hem. │S. hem., B. inf. │ - │ │ S. aur. │ - 423 │S. hem. │S. hem., B. inf. │ - 440 │0 │B. inf., S. aur. │B. inf., S. aur. - 448 │0 │0 │0 - 482 │0 │B. inf., Pneum. │B. inf., Pneum. - │ │ IV │ IV, S. hem. - 489 │0 │Pneum. IV, B. │Pneum. IV, B. - │ │ inf. │ inf. - ─────────────────┴─────────────────┴─────────────────┴───────────────── - -The bacteriology of instances of peribronchial fibrinous pneumonia with -organization of the intraalveolar fibrin is shown in Table XLIV: - - TABLE XLIV - - ═════════════════╤═════════════════╤═════════════════╤═════════════════ - AUTOPSY │ BLOOD │ LUNG │ BRONCHUS - ─────────────────┼─────────────────┼─────────────────┼───────────────── - 283 │Pneum. IV │Staph., B. inf. │B. inf., Pneum. - │ │ │ IV, staph. - 291 │0 │0 │B. inf., staph. - 398 │0 │ │ - 419 │0 │Pneum. II, B. │Pneum. II, B. - │ │ inf. │ inf. - 421 │S. hem. │Pneum. IV, S. │ - │ │ hem. │ - 422 │0 │Pneum. II atyp., │ - │ │ B. inf. │ - 425 │S. hem. │S. hem., B. inf.,│ - │ │ S. alb. │ - 433 │0 │S. hem., B. inf.,│ - │ │ S. aur. │ - 460 │S. hem. │S. hem., B. inf. │S. hem., B. inf., - │ │ │ staph. - 463 │0 │B. inf., staph. │B. inf., staph., - │ │ │ Pneum. IV - ─────────────────┴─────────────────┴─────────────────┴───────────────── - -B. influenzæ has been present in the bronchi in every instance save one -in which cultures have been made, and it is probable that in this -exceptional instance cultures have remained sterile because the media -employed have been defective. The incidence of B. influenzæ in the lung -has been unusually high both with and without organization (66.7 per -cent with no organization; 77.8 per cent with organization). -Streptococci and staphylococci have been found in a considerable -proportion of all instances of peribronchial fibrinous pneumonia, but -there has been no notable preponderance of these microorganisms when -organization has occurred. Organization has been present in instances in -which pneumonia is referable to pneumococcus associated with B. -influenzæ and unaccompanied by either streptococci or staphylococci -(Autopsies 419 and 422). Wadsworth[81] found no organization after -inoculation of the lungs of dogs with pneumococcus or with -staphylococcus alone, but produced organization when he inoculated -animals with both microorganisms. - -Injury to bronchi produced in part at least by B. influenzæ exposes the -bronchi and lung tissue to repeated infection with a variety of -microorganisms; absorption of fibrin and regeneration of alveolar -epithelium are prevented, resolution fails to occur and organization of -fibrin follows. - - - Suppurative Pneumonia With Necrosis and Abscess Formation - -Three varieties of suppurative pneumonia have occurred in association -with influenza. - -A. Necrosis and suppuration with formation of one or several abscesses -usually below the pleura and almost invariably caused by hemolytic -streptococci. - -B. Interstitial suppurative pneumonia caused by hemolytic streptococcus. - -C. Multiple abscesses in clusters caused by staphylococci. - -Suppurative pneumonia with necrosis and abscess formation will be -discussed in this section. Pulmonary abscesses which occurred in 43 -autopsies may be included in this group; in 4 of these autopsies abscess -and interstitial suppurative pneumonia occurred in the same individual. -These abscesses were much more frequently situated in the lower than in -the upper lobes and more often in the right than in the left lung. In -most instances there was one or several abscesses situated below the -pleura of one lobe; occasionally abscesses occurred in two lobes of the -same lung or in both lungs. The distribution was as follows: Abscess in -only one lung occurred in right upper lobe in 6 autopsies; middle lobe, -3; lower lobe, 15; left upper lobe, 2; lower lobe, 16. Abscesses -occurred in both right and left lower lobes, twice. The usual situation -was at the lower and posterior part of the lower lobe at or near the -basal edge, less frequently below the posterior border or upon the basal -surface of the lobe. These abscesses in almost every instance were found -immediately below the pleural surface, so that they appeared upon the -pleura as opaque yellow spots usually surrounded by narrow zones of -hemorrhage. In one instance (Autopsy 376) the abscess cavity was -separated from the pleural cavity by remains of the pleura which was as -thin as tissue paper and in other instances perforation had occurred -(Fig. 9). In Autopsy 480 the abscess cavity which had perforated the -pleura was in free communication with a bronchus of medium size. - -In most instances of suppurative pneumonia there have been associated -lesions of bronchopneumonia which have been peribronchiolar, hemorrhagic -or lobular and have exhibited no unusual characters. The abscess or -abscesses are situated within an area of pneumonic consolidation which -is not limited by lobule boundaries and has not the characters of -bronchopneumonic consolidation. In some instances this consolidation is -limited to a zone immediately about the abscess, but often it involves -the greater part of a lobe. The tissue is laxly consolidated and flabby; -on section it has a dull, conspicuously cloudy appearance and is grayish -red, pinkish gray or gray; it is homogeneous or very finely granular. -Turbid gray fluid, which sometimes resembles thin pus, oozes from the -cut surface. - -Widespread necrosis of tissue is not infrequently a conspicuous feature -of this pyogenic pneumonia (Fig. 8). Upon a cloudy gray background of -consolidation are numerous opaque yellowish gray or yellow patches, -occasionally 2 or 3 cm. across, giving a mottled character to the cut -surface. Upon the pleura these necrotic patches appear as dull opaque -yellow spots. They may be surrounded by a zone of hemorrhage. The opaque -material is at first firm but may undergo softening, becoming semisolid -and finally purulent. Necrotic patches may be scattered throughout a -lobe, but fully formed abscesses are with few exceptions immediately -below the pleura (Fig. 9). - -[Illustration: - - Fig. 8.—Streptococcus pneumonia with massive necrosis. Autopsy 354. -] - -[Illustration: - - Fig. 9.—Abscess below pleura with perforation caused by hemolytic - streptococci. Healing suppurative interstitial pneumonia indicated - by yellowish gray lines marking interlobular septa at base of lower - lobe. Autopsy 474; right lung. (See left lung, Fig. 10.) -] - -The duration of illness in cases of pneumonia with abscess varied from a -week or less (11 instances) to more than four weeks. The duration of the -greater number of cases (17 instances) was between one and two weeks. In -one instance onset occurred with symptoms of influenza, pneumonia was -recognized two days later, and death occurred only four days after the -onset of illness. When the duration of the illness was less than a week -the symptoms of onset were in some instances those of pneumonia. - -Table XLV shows the incidence of pneumococcus, S. hemolyticus, -staphylococcus and B. influenzæ in instances of suppurative pneumonia -with abscess formation, 4 instances of abscess with interstitial -suppurative pneumonia being excluded: - - TABLE XLV - - ════════╤════════╤═════════════════╤═════════════════ - │ NO. OF │ │ HEMOLYTIC - │CULTURES│ PNEUMOCOCCI │ STREPTOCOCCI - ────────┼────────┼────────┬────────┼────────┬──────── - │ │ NO. │PER CENT│ NO. │PER CENT - │ │POSITIVE│POSITIVE│POSITIVE│POSITIVE - ────────┼────────┼────────┼────────┼────────┼──────── - Bronchus│ 24│ 5│ 20.8│ 22│ 91.6 - Lung │ 36│ 9│ 25.0│ 30│ 83.3 - Blood │ 37│ 6│ 16.2│ 31│ 83.8 - ────────┴────────┴────────┴────────┴────────┴──────── - - ════════╤═════════════════╤═════════════════ - │ │ - │ STAPHYLOCOCCI │ B. INFLUENZÆ - ────────┼────────┬────────┼────────┬──────── - │ NO. │PER CENT│ NO. │PER CENT - │POSITIVE│POSITIVE│POSITIVE│POSITIVE - ────────┼────────┼────────┼────────┼──────── - Bronchus│ 12│ 50.0│ 18│ 75.0 - Lung │ 14│ 35.6│ 8│ 22.2 - Blood │ │ │ │ - ────────┴────────┴────────┴────────┴──────── - -In over 80 per cent of instances of pulmonary abscess hemolytic -streptococcus has been found in blood, lungs and bronchus and, when -cultures have been made, in the inflamed pleural cavity as well. -Streptococci have been found in immense number in sections from the -necrotic lung tissue and the abscesses which have been formed. It is -evident that hemolytic streptococci have caused suppurative pneumonia -and death, being found in the blood of the heart just as frequently as -in the lungs (83 per cent). The relative unimportance of pneumococci is -indicated by their low incidence in the blood (16.2 per cent) when -compared with that of lobar pneumonia (65.5 per cent) or of -bronchopneumonia (31.4 per cent). B. influenzæ has been found in -three-fourths of these autopsies in the bronchus, but its incidence in -the lungs has been much smaller. - -In 3 instances of suppurative pneumonia with abscess formation no -hemolytic streptococci were found; they are as follows: - - =Autopsy 380.=—Bronchopneumonia with gray and red lobular - consolidation in right upper and lower lobes; peribronchiolar - nodules of consolidation in left lower lobe; abscess, 1.5 cm. - across, below the pleura of the posterior border of the left lower - lobe near its base; fibrinopurulent pleurisy (300 c.c.) on right - side; serous pleurisy (200 c.c.) on left. Pneumococcus III was found - in cultures from the blood of the heart from the right lung and with - B. influenzæ from the right pleural cavity. No culture was made from - the left lung which contained the abscess. In sections of the - abscess gram-positive streptococci in chains of 4 to 8 cocci were - numerous. - - =Autopsy 406.=—Acute lobar pneumonia with red hepatization of - greater part of right lung; patch of consolidation in lower lobe of - left lung containing an abscess cavity 2.5 x 1.5 cm.; localized - seropurulent pleurisy (375 c.c.) on left side. Pneumococcus IV was - obtained from the blood of the heart; a culture from the lung was - contaminated. Tissue from the abscess was not saved for histologic - examination. - - =Autopsy 416.=—Suppurative pneumonia with necrosis and abscess - formation in right lower lobe; fibrinous pleurisy on right side. - Pneumococcus IV was obtained from the blood, right lung and right - main bronchus. No streptococci were found in sections from the - abscess in the right lung. - -The foregoing observations demonstrate that suppurative pneumonia with -abscess formation following influenza is with few exceptions caused by -S. hemolyticus. - -The autopsies (Table XLVI) in which pneumococci have been found in -association with hemolytic streptococci in the blood or lungs indicate -that pneumococci have had a part in the production of fatal pneumonia. - - TABLE XLVI - - ═════════════════╤═════════════════╤═════════════════╤═════════════════ - AUTOPSY │ CULTURE FROM │ CULTURE FROM │ CULTURE FROM - │ BLOOD │ LUNGS │ BRONCHUS - ─────────────────┼─────────────────┼─────────────────┼───────────────── - 258 │S. hem. │S. hem., Pneum. │ - │ │ IV B. inf. │ - 282 │S. hem., Pneum. │S. hem., Pneum. │S. hem., B. inf. - │ II │ II │ Pneum. II, - │ │ │ staph. - 345 │ │S. hem., Pneum. │ - │ │ II, staph. │ - 378 │Pneum. atyp. II │S. hem., Pneum. │S. hem., B. inf., - │ │ atyp. II │ Pneum. atyp. II - 381 │S. hem. │S. hem., Pneum. │ - │ │ II Pneum. IV, │ - │ │ staph. │ - 383 │Pneum. III │S. hem., Pneum. │ - │ │ III B. inf. │ - 387 │S. hem. │Pneum. II, │S. hem., pneum., - │ │ staph., B. inf.│ staph., B. inf. - ─────────────────┴─────────────────┴─────────────────┴───────────────── - -These autopsies, notably those in which pneumococci have been found in -the blood, suggest that infection with pneumococci has preceded -suppurative pneumonia caused by hemolytic streptococci. In a small -number of instances the sputum was examined in life after onset of -pneumonia. - - TABLE XLVII - - ═══════╤═══════════════════════════════╤═══════════════════════════════ - AUTOPSY│ SPUTUM │CULTURES FROM BLOOD, LUNGS AND - │ │ BRONCHUS - ───────┼───────────────────────────────┼─────────────────────────────── - 282 │Pneum. IV. B. inf. │S. hem., Pneum. II, staph., B. - │ │ inf. - 288 │S. hem., B. inf. │S. hem., B. inf. - 376 │(No S. hem., Oct. 8) │S. hem., staph., B. inf. (Oct. - │ │ 11) - ───────┴───────────────────────────────┴─────────────────────────────── - -In 2 of these 3 cases infection with hemolytic streptococcus occurred -subsequent to the onset of pneumonia. - -Several observations help to explain the occurrence of abscess in -association with the pneumonia of influenza. The fissures which will be -described in association with bronchiectasis represent traumatic -ruptures of the bronchial wall consequent upon weakening by necrosis and -over distention. They expose the injured bronchial wall and the alveolar -tissue adjacent to it to infection by the microorganisms contained -within the lumen of the inflamed bronchus. Occasionally a favorable -microscopic section demonstrates the relation of pulmonary necrosis and -consequent suppuration to injuries of the bronchial wall. Peribronchial -fibrinous pneumonia occurs about the bronchi of which the epithelial -lining has been destroyed, and when a fissure penetrates the bronchial -wall fibrinous pneumonia is almost invariably found in a zone about the -tear; it doubtless tends to limit the extension of the process. -Occasionally, wide areas of necrosis occur within consolidated tissue -near the site of the fissure (Autopsy 312 with S. hemolyticus and B. -influenzæ, p. 254). Accumulation of polynuclear leucocytes between -living and dead tissue may form a line of demarcation (Autopsy 387); -finally, fairly large, irregularly formed, abscess cavities are found. - -Necrosis and beginning suppuration in contact with the lumen of the -bronchus will be described in association with bronchiectasis (Autopsies -312, Fig. 24, and 423, p. 256). In the following autopsies upon -individuals who have died with pulmonary abscesses, favorable -microscopic sections have demonstrated abscess formation in contact with -lesions which have penetrated the walls of small bronchi. They help to -explain the pathogenesis of abscess in association with influenza. - - =Autopsy 376.=—H. M., white, aged twenty-four, a fireman, resident - of Oklahoma, had been in military service one month. Onset of - illness occurred October 1, ten days before his death; he was - admitted to the base hospital on the fourth day of his illness with - the diagnosis of bronchopneumonia. - - =Anatomic Diagnosis.=—Acute bronchopneumonia with patches of lobular - and confluent lobular consolidation in both lungs and hemorrhagic - peribronchiolar consolidation in right upper lobe; abscess in right - upper lobe below pleura; fibrinopurulent pleurisy on right side; - purulent bronchitis; bronchiectasis at base of left lobe. - - An irregular abscess, 2 x 1 cm., filled with creamy purulent fluid - is separated from the interlobular surface of the right upper lobe - by a thin membrane representing the pleura. The right pleural cavity - contains 200 c.c. of turbid yellow fluid in which is soft fibrin. - The bronchi contain purulent fluid in great abundance. The bronchi - at the base of the left lower lobe are widely dilated, so that many - small bronchi with no cartilage in their wall measure from 3 to 5 - mm. in diameter. - - Cultures show the presence of hemolytic streptococci in the blood of - the heart and in three plates from the lung; B. influenzæ and S. - aureus were found in the left bronchus. - - The bronchi have wholly or partially lost their epithelium and there - is deep erosion of the walls. Cavities containing polynuclear - leucocytes occur within the alveolar tissue; in some instances pus - containing cavities are surrounded by alveolar tissue, but in other - places it is evident, that they have had their origin in bronchi. In - a short segment of the circumference the wall of the preexisting - bronchus is preserved and consists of squamous epithelium, vascular - connective tissue and smooth muscle. The remainder of the bronchus - has disappeared and a cavity is produced. The very irregular wall of - the cavity is formed by partially destroyed alveoli filled with - fibrin and leucocytes. - - =Autopsy 387.=—C. M., white, aged twenty-one, laborer, resident of - Mississippi, had been in military service twenty-one days. Illness - began on September 22, nineteen days before death, and the patient - was admitted to the hospital on the same day with a diagnosis of - bronchitis; a diagnosis of bronchopneumonia was made on October 2, - nine days before death. The leucocytes on October 3 numbered 8000 - (small mononuclear, 36 per cent; large mononuclear, 5 per cent; - polynuclear, 59 per cent). - - =Anatomic Diagnosis.=—Acute bronchopneumonia with consolidation in - right upper lobe and hemorrhagic peribronchiolar consolidation in - left lower lobe; abscess below pleura in left lower lobe; purulent - pleurisy on both sides; edema of mediastinum; purulent bronchitis; - bronchiectasis. - - There is advanced bronchiectasis, and bronchi with no visible - cartilage are dilated to from 4 to 8 mm. in diameter; they contain - purulent fluid which wells up from the cut surface. About dilated - bronchi there is in places dull red or grayish red consolidation - forming an encircling zone. Situated below the pleural surface - within an area of consolidation at the posterior border of the left - lower lobe there is a spot 3 cm. across where the tissue is yellow - and has in places undergone purulent softening. Several smaller - abscesses occur nearby. - - Cultures from the blood of the heart and from the edematous - mediastinum contain hemolytic streptococci. From the abscess are - grown S. albus, Pneumococcus II and B. influenzæ. The purulent - contents of a small bronchus contains S. hemolyticus, B. influenzæ, - S. aureus and a few pneumococci. - - Microscopic examination shows that the epithelium of dilated bronchi - has disappeared and the denuded surface is covered by fibrin and - polynuclear leucocytes; fissures extend from the lumen through the - bronchial wall into the surrounding alveolar tissue. A zone of - fibrinous pneumonia surrounds these bronchi and fissures in the - bronchial wall penetrate into this zone. One dilated bronchus 2.4 - mm. in diameter with no cartilage in its wall has vascular - connective tissue covered by epithelium on one side, whereas the - remainder of the circumference is formed by exposed alveoli filled - with fibrin, the bronchial wall having disappeared. A section - through a part of the abscess which has been mentioned shows a very - irregularly formed cavity approximately 1 x 0.7 cm. Remains of - bronchial wall, consisting of very vascular tissue covered by flat - epithelium in several layers, indicate the origin of the cavity. - Between these remnants of bronchi deep pockets extend into the - pulmonary tissue which in the margin of the cavity is the site of - fibrinous pneumonia. In one place, in contact with the cavity, a - wide area of consolidated tissue has undergone necrosis and both - alveolar walls and their contents have lost their nuclei. Leucocytes - which are accumulating at the margin of the necrotic patch form a - line of demarcation between living and dead tissue. - -Abscess may be the result of the profound changes which occur in the -bronchi as the result of influenza. Necrosis caused by bacteria within -the bronchi weakens and in places destroys the wall. Bacteria penetrate -into the surrounding tissue and hemolytic streptococci (or -staphylococci) may produce localized abscesses. These abscesses are -usually situated near the pleural surface of the lung, because -destructive changes causing rupture of the bronchial wall occur more -frequently in the smaller peripheral bronchi than in the larger bronchi -containing cartilage. Abscesses occur more frequently at the bases of -the lungs, because the most severe changes in the bronchi occur in the -dependent part. (See “Bronchiectasis,” p. 240.) - -=Healing of Abscess.=—The following autopsy is of interest in relation -to the treatment of pulmonary abscess and associated empyema. - - =Autopsy 467.=—P. C., white, aged twenty-five, a farmer from - Missouri, had been in military service three months. Illness began - September 27, thirty days before death, and the patient was admitted - the day following onset with headache, backache and cough. Pneumonia - with consolidation in the right lower lobe was recognized on the - sixth day of illness. On the ninth day 500 c.c. of fluid were - withdrawn from the right pleural cavity; there were cyanosis and - dyspnea. On the eleventh day 700 c.c. of fluid were withdrawn. On - the twelfth day thoracotomy was performed and 100 c.c. of greenish - fluid were removed. The patient’s condition improved for a time, but - on the twenty-sixth day 1,000 c.c. of straw colored fluid were - aspirated from the left pleural cavity and on the twenty-eighth day - the same amount of seropurulent fluid was withdrawn. - - =Anatomic Diagnosis.=—Healing abscess of right lower lobe - communicating with the pleural cavity; acute purulent pleurisy with - closed thoracotomy wound on the right side; purulent pleurisy on the - left side; acute bronchopneumonia with lobular consolidation in the - left lung; purulent bronchitis; bronchiectasis with formation of - spherical bronchiectatic cavities; acute splenic tumor. - - At the base of the right chest is a closed thoracotomy wound 2 cm. - in length; the right pleural cavity contains 200 c.c. of thick - creamy pus and the cavity is lined by a thick tough membrane. The - left pleural cavity contains 800 c.c. of white purulent fluid - thinner than that on the right side. The right lung is compressed - into the posterior and inner part of the chest. The upper lobe is - pink and air containing; the posterior and lower part of the lower - lobe is red and atelectatic, and fibrous septa are more conspicuous - than elsewhere. The pleura of the external surface near the basal - edge, in an area 2 cm. across, is depressed and yellowish gray in - color. In the center of this area is a small opening communicating - with a pocket 0.5 cm. across within the substance of the lung. - - In the lower lobe beneath the interlobular surface are two spherical - bronchiectatic cavities, each about 1.5 cm. across, with smooth - lining in continuity with two branches of the same bronchus of - medium size. - - Bacteriologic examination showed the presence of S. hemolyticus in - the blood of the heart. No growth was obtained from the left lung; - the left pleural cavity contained hemolytic streptococci and S. - aureus, the latter in small number. S. hemolyticus and B. influenzæ - were grown from the left main bronchus. - - A microscopic section through the abscess and its communication with - the pleura shows that its cavity contains polynuclear leucocytes and - the wall is formed by granulation tissue covered by fibrin. Some - alveoli outside the abscess contain compact balls of fibrin - containing a few fibroblasts; this fibrin stains deeply with - hematoxylin as if it contained calcium. The surface of the lung is - covered by fibrin in process of organization. - -In the foregoing instance a pulmonary abscess on the right side has -ruptured into the pleura and, completely separated from the adjacent -lung by a wall of newly formed tissue, is in process of healing. It -shows that these pulmonary abscesses below the pleura may heal provided -drainage is established by rupture into the pleural cavity and -subsequent evacuation of pleural exudate. It is noteworthy that in this -instance empyema extended from the right to the left pleural cavity, -both S. hemolyticus and S. aureus were found at autopsy. The thoracotomy -wound on the right side was closed at autopsy. - - - Interstitial Suppurative Pneumonia - -A second type of suppurative pneumonia is characterized by acute -inflammation of interstitial tissue between the secondary lobules of the -lung and by acute lymphangitis; suppuration involves the interstitial -septa and the walls of the lymphatics. The lesion is designated by -Kaufmann,[82] Beitzke[83] and others acute interstitial pneumonia. -_Pneumonia dissecans_ in which solution of interstitial tissue isolates -sections of lung tissue is said to be a consequence of the lesion. Many -text books of pathology, overlooking the occurrence of this lesion, -limit the consideration of interstitial pneumonia to chronic processes -in which the interlobular and interalveolar fibrous tissue is increased. - -Acute inflammation and edema of the interlobular septa of the lung with -no suppuration is often found with both lobar and bronchopneumonia and -is occasionally so far advanced that it can be recognized on gross -examination of the lungs. In a small area interlobular septa are -conspicuous as yellowish lines of edematous appearance which may be 1 to -1.5 mm. in thickness and sometimes form a network with rectangular or -polygonal meshes. The gelatinous appearance of the edematous fibrous -tissue does not suggest suppuration. Microscopic examination shows that -the tissue is distended by edema and contains fibrin and polynuclear -leucocytes; the lymphatics are distended and contain a network of fibrin -within which leucocytes are numerous. Inflammatory edema of the -interstitial tissue has been recognized at autopsy four times in -association with bronchopneumonia (Autopsy 253 with Pneumococcus II; -Autopsy 335, with Pneumococcus IV and S. viridans; Autopsy 477 with S. -hemolyticus and Autopsy 498 with S. viridans); twice with lobar -pneumonia (Autopsy 343 with Pneumococcus IV and Autopsy 353 with -atypical Pneumococcus II); twice with combined lobar and broncopneumonia -(Autopsy 273 with S. hemolyticus and Pneumococcus IV and Autopsy 357 -with Pneumococcus IV). Edema of interstitial septa was recognized at -autopsy in the immediate neighborhood of an abscess three times -(Autopsies 277 and 278 with hemolytic streptococci and Autopsy 282 with -hemolytic streptococci and Pneumococcus II). In these instances of -inflammation and edema the lymphatics are found distended by fibrinous -thrombi, and it is probable that occlusion of lymphatics determines the -occurrence of inflammatory edema within the surrounding tissue. -Inflammation has not proceeded to suppuration. - -With interstitial suppurative pneumonia, interlobular connective tissue -is marked by conspicuous yellow lines, 1 to 3 or even 5 mm. in -thickness, forming a network with polygonal meshes which represent -secondary lobules (Figs. 10 and 11). The distended septa not -infrequently have bead-like enlargements at intervals and from the cut -surface it is often possible to scrape away creamy yellow pus. These -lines of suppuration invariably extend up to the pleura and are often -broadest immediately below it. Adjacent septa which have not undergone -suppuration are much thickened and have the yellowish gray appearance -produced by edema. - -[Illustration: - - Fig. 10.—Interstitial suppurative pneumonia; interstitial septa are - the site of suppuration and lymphatics are distended with purulent - fluid; empyema. Autopsy 474, left lung. (See right lung) Fig. 9. -] - -[Illustration: - - Fig 11.—Suppurative interstitial pneumonia; the left lower lobe is the - site of almost uniform consolidation and here interstitial septa and - their lymphatics are distended with pus. There is more extensive - interstitial suppuration in the upper lobe where consolidation is - absent. The cloudy appearance of the consolidated lung is well - shown. Autopsy 452. -] - -Suppurative interstitial pneumonia frequently occurs in association with -bronchopneumonic consolidation which may be peribronchiolar, hemorrhagic -or lobular, but there is in addition consolidation of the pulmonary -tissue between the inflamed septa which may affect part of a lobe, an -entire lobe, or parts of several lobes; it does not exhibit the -characters of confluent lobular pneumonia. - -In approximately half of the cases consolidation, associated with -interstitial suppuration, has been lobar in distribution (Fig. 11). The -tissue is laxly consolidated, finely granular, and has a cloudy red or -gray appearance. The coarsely granular surface of lobar pneumonia is -absent. The affected lung may weigh 1,500 or 1,650 grams. Occasionally, -interstitial septa of air containing lung tissue is the site of -suppurative inflammation or edema. In Autopsy 452 the lower lobe, save a -small part at the base, is laxly consolidated; interstitial septa in the -consolidated area are yellow, 1.5 to 2 mm. in thickness, beaded and -exude purulent fluid on pressure. In the adjacent part of the upper lobe -there is a patch of consolidation, and a network of yellow thickened -septa extends from it far into the surrounding air containing tissue. -The weight of the right lung is 635 grams; of the left, 1,650 grams. - -The distribution of interstitial suppuration in 21 instances, including -4 in which the lesion has occurred in the same lungs with abscess -formation, has been as follows: right upper lobe, 9 instances; middle -lobe, 4; lower lobe, 5; left upper lobe, 7; left lower lobe, 6. In 6 of -these autopsies more than one lobe of the same lung has been affected by -the lesion; in 2 autopsies parts of both lungs have been affected. -Localized abscess of the lung is more common in the lower than in the -upper lobes, but suppuration of the interstitial tissue is more often -found in the upper lobes. - -The duration of illness with interstitial suppurative pneumonia has -varied from six days to five weeks. In over half of the cases death has -occurred during the second week of illness. - -The bacteriology of these cases is shown in Table XLVIII. - - TABLE XLVIII - - ════════╤════════╤═════════════════╤═════════════════ - │ NO. OF │ │ HEMOLYTIC - │CULTURES│ PNEUMOCOCCI │ STREPTOCOCCI - ────────┼────────┼────────┬────────┼────────┬──────── - │ │ NO. │PER CENT│ NO. │PER CENT - │ │POSITIVE│POSITIVE│POSITIVE│POSITIVE - ────────┼────────┼────────┼────────┼────────┼──────── - Bronchus│ 10│ │ │ 9│ 90.0 - Lung │ 20│ 1│ 5.0│ 17│ 85.0 - Blood │ 21│ 2│ 9.5│ 17│ 81.0 - ────────┴────────┴────────┴────────┴────────┴──────── - - ════════╤═════════════════╤═════════════════ - │ │ - │ STAPHYLOCOCCI │ B. INFLUENZÆ - ────────┼────────┬────────┼────────┬──────── - │ NO. │PER CENT│ NO. │PER CENT - │POSITIVE│POSITIVE│POSITIVE│POSITIVE - ────────┼────────┼────────┼────────┼──────── - Bronchus│ 5│ 50.0│ 10│ 100.0 - Lung │ 5│ 25.0│ 7│ 35.0 - Blood │ │ │ │ - ────────┴────────┴────────┴────────┴──────── - -S. hemolyticus has been almost invariably present in lungs, heart’s -blood and bronchi. In 16 of 21 autopsies hemolytic streptococci have -been obtained from the blood in pure cultures, in one instance -associated with pneumococcus. With associated empyema, pericarditis or -peritonitis, the same microorganism has been found in the pleural -cavities, pericardium or peritoneum. Furthermore, microscopic -examination has demonstrated the presence of chains of streptococci in -the affected interlobular tissue and in much greater abundance in the -distended lymphatics. - -Nevertheless in 2 instances no streptococci have been found. These cases -are as follows: - - =Autopsy 330.=—Illness began with symptoms of influenza ten days - before death; signs of pneumonia were recognized three days before - death. There is firm, gray red consolidation of the entire left - upper lobe; the interlobular septa are here indicated by yellow - lines of obvious suppuration and thick puslike fluid exudes from the - cut surface of the consolidated tissue. The upper half of the left - lower lobe has undergone gray hepatization, but here there is no - distention of the interlobular septa. There is fibrinopurulent - pleurisy on the left side with accumulation of 400 c.c. of fluid. - Pneumococcus IV is obtained from the blood of the heart and from the - lung. In the suppurating tissue diplococci which stain by Gram’s - method are present in large number; there are a few short chains. - - =Autopsy 379.=—Illness began seven days before death with influenza; - signs of pneumonia were first recognized the day before death. The - middle lobe of the right lung is firmly consolidated; on section - there is mottling of deep red and pinkish red and the cut surface is - coarsely granular. The interstitial septa are distended by fluid and - are grayish yellow. There is fibrinopurulent pleurisy on the right - side with accumulation of 600 c.c. of fluid. Pneumococcus atypical - II is obtained from the blood of the heart. A large bacillus - unstained by Gram’s method is obtained from the right lung and from - the right main bronchus. In the bronchus are a few influenza - bacilli. In the suppurating and necrotic tissue of the interstitial - septa are found diplococci and chains of 4 to 6 cocci in great - number; a few large Gram-negative bacilli are found. - -In both these autopsies consolidation had the characters of lobar -pneumonia, and pneumococci were obtained from the blood of the heart. It -is possible that streptococci failed to grow or while present elsewhere -were absent at the spot where cultures were made. - -It is noteworthy that B. influenzæ was found in the bronchi in every -instance (10) in which cultures were made, but was obtained much less -frequently from the lung. In one instance (Autopsy 474) this -microorganism was found in the blood in association with hemolytic -streptococci. There was suppurative interstitial pneumonia in the left -lung and abscess in the right lower lobe with rupture into the cavity -and empyema. Hemolytic streptococci and B. influenzæ were found in the -bronchus, right pleural cavity and blood of the heart. - -In 4 instances (Autopsies 251, 259, 295 and 474) interstitial -suppurative pneumonia has been associated with abscess formation. In one -instance (Autopsy 251) the right middle lobe has been the site of -interstitial suppuration and abscess formation; in another (Autopsy 295) -the left lower lobe has been the site of both lesions, but in the other -2 instances suppurative interstitial pneumonia and abscess formation -have occurred in opposite lungs. In all 4 autopsies hemolytic -streptococci have been found in the blood of the heart and in lungs or -bronchi. - -Empyema has been present in all but 3 of 21 instances of interstitial -suppurative pneumonia. - -[Illustration: - - Fig. 12.—Suppurative interstitial pneumonia, showing an immensely - dilated lymphatic containing purulent exudate, a short distance - below the pleura. Autopsy 474. -] - -Histologic examination of lungs with interstitial suppuration shows that -the interlobular septa are distended by serum and contain a conspicuous -network of fibrin. Polynuclear leucocytes are present in varying number, -and at times densely infiltrate the distended tissue; it is not uncommon -to find a zone of densely crowded polynuclear leucocytes along each edge -of the septum, whereas the central part contains comparatively few. -Occasionally, there is hemorrhage into the distended connective tissue. - -Within the distended septa occur greatly dilated lymphatics filled with -polynuclear leucocytes (Figs. 12 and 13). Thrombosis of the distended -lymphatics has usually occurred, and a conspicuous network of fibrin in -which are polynuclear leucocytes plugs the lumen. Streptococci in chains -of variable length are found in the inflamed interstitial tissue, but -are present in far greater number within the distended lymphatics. - -[Illustration: - - Fig. 13.—Suppurative interstitial pneumonia showing a dilated - lymphatic. Autopsy 428. -] - -Necrosis of the cells which fill the lymphatics occurs in spots, usually -in the center of the thrombus, and occasionally affects the entire -contents of the lymphatic; polynuclear leucocytes have lost their nuclei -or in some the nucleus has undergone fragmentation. In these spots the -network of fibrin has disappeared. Not infrequently the wall of the -lymphatic in a small sector or throughout the circumference has -undergone necrosis, and spots of necrosis may occur in the interlobular -septa distended by inflammatory exudate. Wherever necrosis has occurred, -chains of streptococci are present in immense number. - -Accumulation of polynuclear leucocytes, necrosis of these cells, -solution of fibrin at first in the centers of the lymphatic thrombus and -later throughout, occasionally with necrosis of the wall of the vessel, -result in the formation of an abscess at the site of the distended -lymphatic. These lymphatics, dilated by purulent fluid, may have a -diameter from 2 to 3 mm. and may cause considerable compression and -collapse of immediately adjacent alveoli. Lymphangitis, distention of -lymphatics, thrombosis and finally suppuration may occur in the -lymphatic vessels encircling the blood vessels and in those situated in -the adventitia of the bronchi of medium size. - -The alveoli adjacent to the distended septa are filled by inflammatory -products; edema is almost invariably present and the alveoli may contain -serum and desquamated epithelial cells; fibrin is often present, but -more frequently polynuclear leucocytes are predominant. Not -infrequently, abscess formation, recognized microscopically, has -occurred in contact with septa most often immediately below the pleura. -Polynuclear leucocytes are present in immense number and alveolar septa -have disappeared; occasionally, with abscess formation there is more or -less widespread necrosis of tissue, cells both of the exudate and of the -alveolar walls having lost their nuclei. - -Lymphatics in many places are distended and plugged by fibrinous -thrombi, whereas elsewhere softening of the thrombus has been brought -about by suppuration. Suppuration, both within the lymphatic and in -adjacent alveoli, appears to be secondary to lymphatic obstruction. In -some instances the lymphatic appears to have undergone distention after -the thrombus has formed, for between the thrombus and the wall of the -lymphatic a channel is occasionally found containing uncoagulated lymph. - -[Illustration: - - Fig. 14.—Endophlebitis occurring in association with suppurative - pneumonia; the intima contains lymphoid cells in great number; at - one spot there is a small thrombus adherent to the intima. Autopsy - 325. -] - -Acute endophlebitis has been repeatedly observed in association with -interstitial suppurative pneumonia (Fig. 14). The lesion usually occurs -in veins situated within the septa which are the site of intensely acute -inflammation associated with necrosis. The wall of the vein appears to -be so injured by the surrounding changes that polynuclear leucocytes and -small mononuclear cells accumulate below the endothelium. Throughout the -circumference of the veins, often 0.5 to 1 mm. in diameter, the -endothelium is separated from the underlying media by polynuclear -leucocytes which form a conspicuous zone encircling the lumen. Some -cells of lymphoid type are usually present among the polynuclear -leucocytes. Polynuclear leucocytes are often adherent to the endothelial -lining of the vessel and are not infrequently fixed in the process of -passing through the endothelium. The lesion may be more severe (Autopsy -325), so that the endothelium has disappeared, and upon the exposed -surface fibrin is deposited; within this fibrin polynuclear leucocytes -are numerous and nuclear fragmentation has occurred. The middle coat of -the vessel usually contains few cells; some polynuclear leucocytes -within it may be stretched out as if in process of wandering through the -wall. - -In other instances the accumulation of cells below the endothelium is -almost wholly mononuclear. Cells of the type of lymphocytes occur, but -more abundant are slightly larger cells with more abundant cytoplasm. -These cells may form a thick zone below the intima throughout the entire -circumference of the lesion. It seems probable that these cells, like -the polynuclear leucocytes, are derived from circulating blood within -the lumen of the vessel, for small cells of the type of lymphocytes are -not infrequently found adherent to the lumen and occasionally one is -fixed in process of passing through the endothelium. - -This endophlebitis appears to be the result of changes outside the -vessel; there is usually necrosis of the adjacent tissue and the -production of the lesion is favored by lymph stasis; as the result of -injury to the vessel wall, polynuclear leucocytes in response to -chemotaxis, or with milder irritation, mononuclear cells, wander through -the endothelium and accumulate below it perhaps on account of the -greater impermeability of the middle coat to the passage of cells. - -The lesion described does not occur exclusively with interstitial -suppurative pneumonia caused by hemolytic streptococci, but has been -found in association with abscess formation (Autopsies 354 and 383) -caused by hemolytic streptococci or (Autopsy 322) caused by -staphylococci. In 1 instance it has been found with lobar pneumonia -(Autopsy 320) caused by atypical Pneumococcus II and in 2 instances with -combined lobar and bronchopneumonia (Autopsy 357 with Pneumococcus IV; -Autopsy 392 with Pneumococcus II). In these 3 instances there has been -interstitial inflammation, edema and lymphangitis without suppuration. - -Interstitial suppurative pneumonia of long standing may occasionally be -accompanied by chronic changes which bring about thickening of the -interlobular tissue. In the following autopsy acute suppurative -inflammation in the left lung has been associated with conspicuous -thickening of interlobular septa in the right lung. - - =Autopsy 474.=—I. H., white, aged twenty-one, was a native of - Oklahoma and had been in military service one month. His illness - began with influenza thirty-six days before death; he was admitted - to the base hospital thirty-one days before his death with signs of - pneumonic consolidation of the right lower lobe. Evidence of fluid - in the right pleural cavity was obtained two weeks before death, and - from 100 to 700 c.c. of thick purulent fluid were aspirated on five - occasions. Hemolytic streptococci were found in the aspirated fluid. - - =Anatomic Diagnosis.=—Interstitial suppurative pneumonia in left - lung; abscess of right lower lobe with rupture into pleural cavity; - thickening of interlobular septa of right lower lobe; double - purulent pleurisy with thoracotomy on right side; serofibrinous - pericarditis. - -The right pleural cavity contains 85 c.c. of thick purulent fluid; the -right lung (Fig. 9) is collapsed and pushed to the median line, being -bound by firm adhesions to the pericardium. Over the external and basal -surfaces is a localized cavity walled off by adhesions. An abscess -cavity in the lower part of the lower lobe communicates through a -perforation in the basal surface of the lung with the pleural cavity and -is in free communication with a small bronchus. About the abscess the -lung is red and laxly consolidated, but elsewhere air containing; -throughout the lower half of the lower lobe, the interlobular septa are -marked by conspicuous yellowish gray lines about 1 mm. in thickness. -Between these thickened septa the lung tissue contains air. The lung -weighs 600 grams. The left lung (Fig. 10) is voluminous and heavy, -weighing 1,320 grams. The surface is everywhere covered by thickened -pleura and fibrin, the pleural cavity containing 150 c.c. of thick -purulent fluid. The lung is consolidated varying in color from a fleshy -red to yellowish gray. The surface is very conspicuously marked by -yellow lines 2 or 3 mm. thick, corresponding to the interlobular septa -which have undergone suppuration. The septa have bead-like swellings -along their course, and when pus escapes from the cut surface small -cavities remain at the site of these swellings. - -Bacteriologic examination has shown hemolytic streptococci in the blood, -left lung, right and left pleural cavities, and right bronchus. B. -influenzæ has been found in the bronchus, in the right pleura and in the -heart’s blood. A few colonies of S. aureus have been found on the plate -from the right pleural cavity (site of thoracotomy). - -Microscopic examination of the right lower lobe shows that the -interstitial septa are much thickened by young fibrous tissue -infiltrated with lymphoid and a few plasma cells. Large mononuclear -cells with granular cytoplasm are very numerous. A lymphatic is much -distended and contains a few polynuclear leucocytes and many lymphoid -and large mononuclear cells. There is no suppuration. Sections from the -right lung show suppurative lymphangitis with suppurative inflammation -of interstitial tissue. - -The right lung is the site of a healing lesion of the interstitial -tissue which has developed simultaneously with acute interstitial -suppurative pneumonia in the left lung. Both lesions are doubtless -caused by S. hemolyticus. This healing lesion exhibits little similarity -to the interstitial bronchopneumonia described by several observers with -both measles and influenza. - -The following autopsy furnishes further evidence that interstitial -suppurative pneumonia exhibits a tendency to heal. Proliferation of -endothelial cells lining the inflamed lymphatics gives rise to -phagocytic cells which aid in removing the accumulated leucocytes. - - =Autopsy 397.=—N. P., white, aged twenty-one, farmer, a native of - Oklahoma, had been in military service twenty-one days. Illness - began twenty-two days before death, the patient being admitted on - the day following onset with influenza, pharyngitis and bronchitis. - A diagnosis of lobar pneumonia was made fourteen days before death. - The left pleural cavity was aspirated twelve days later and 800 c.c. - of thick yellow pus were withdrawn. Hemolytic streptococci were - found in the sputum five days before death. - - =Anatomic Diagnosis.=—Interstitial suppurative pneumonia in left - upper lobe; acute bronchopneumonia with lobular consolidation in - right upper lobe; localized purulent pleurisy on left side with - compression and atelectasis of left lung; compensatory emphysema of - right lung; purulent bronchitis; beginning serofibrinous - pericarditis; chronic passive congestion of liver, spleen and - kidneys. - - The right lung is very voluminous, free from coal pigment and bright - pink save over lobular patches of consolidation which have a bluish - red color; the bronchi contain mucopurulent material. The anterior - surface of the left lung is bound to the chest wall by firm - adhesions, but over the external and posterior surfaces of the lung - there is a localized cavity containing 1,100 c.c. of turbid fluid. - The left lung is collapsed and airless with deep fleshy red color. - In the upper lobe there are scattered patches of consolidation 1.5 - to 2.5 cm. across where the tissue is grayish red and coarsely - granular. In the adjacent tissue interstitial septa are thickened to - 1 or 2 mm. and are conspicuous as gray bands. Along their course - occur bead-like swellings from which purulent fluid can be scraped. - These septa at one point reach the anterior surface of the lung - where the pleural cavity is in large part obliterated by adhesions; - here there is an encapsulated pocket 4 x 1.5 cm. containing thick - creamy pus. - - Bacteriologic examination of the blood shows the presence of - hemolytic streptococci; cultures from the lungs contain hemolytic - streptococci and B. influenzæ. - - Microscopic examination shows that interlobular septa are thickened - and infiltrated with plasma cells in large number. Leucocytes in the - center of much dilated lymphatics have undergone necrosis and have - lost their nuclear stain. About the periphery of the lumen and - evidently derived from the swollen endothelial cells which surround - it, are numerous large mononuclear cells. They act as phagocytes and - ingest polynuclear leucocytes. Multinucleated giant cells, derived - from these cells, occur. In several places thrombosed lymphatics in - process of organization occur; the lumen is filled with compact - fibrin which is invaded by fibroblasts and newly formed capillaries. - -The process just described is analogous to that which occurs whenever an -unopened abscess heals; mononuclear cells accumulate and act as -phagocytes ingesting polynuclear leucocytes. - -The following instance of streptococcus empyema is noteworthy because no -suppurative pneumonia has been found in association with it. -Nevertheless the character of the changes present in the lung indicate -that the organ has been the site of an interlobular inflammation which -has healed. - - =Autopsy 499.=—J. H. M., white, aged twenty-four, a farmer from - Arkansas, had been in military service five months. Onset of illness - began two weeks before his admission to the hospital on November 15 - with cough, fever, headache and malaise; on admission there was - acute bronchitis. Thirteen days after admission the patient - developed parotitis (mumps?); five days later and five days before - death pleurisy was recognized on the right side and pneumonia was - suspected. Death occurred thirty-six days after onset. The - temperature on admission was 103.2° F. and remained elevated during - one week falling by lysis; from this time until the pleurisy was - recognized it was normal and later it remained approximately 103° F. - - =Anatomic Diagnosis.=—Fibrinopurulent pleurisy on right side; - fibrinous pleurisy on left side; fibrinopurulent pericarditis; - chronic interstitial (interlobular) pneumonia in process of healing; - purulent bronchitis; acute splenic tumor; parenchymatous - degeneration of kidneys. - - The right pleural cavity contains 1,650 c.c. of grayish yellow fluid - containing an abundant sediment of softened fibrin. Part of this - fluid, more opaque than the remainder is confined in a localized - pocket between the inner surface of the lung and the pericardium. - The apex and anterior surface of the right upper lobe, over an area - about 7 cm. across, is held by fibrinous adhesions to the chest - wall; when this adhesion is broken a pocket is exposed 6.5 x 2.5 cm. - containing fibrin and fluid. The pericardial cavity is distended by - 350 c.c. of turbid yellow seropurulent fluid. The pericardial - surfaces are covered by shaggy, tough gray fibrin. - - The right lung is collapsed; the lower and posterior part of the - upper lobe is deep red and atelectatic. Throughout the upper lobe - the interlobular septa are thickened, often 1 mm. across and very - conspicuous; in the lower and anterior tip of the lobe is an area - where tissue is firm grayish red and heavier than water. The lower - and posterior half of the right lower lobe is firm and airless, and - the tissue is reddish gray or gray and in places finely granular on - section; interlobular septa are conspicuous. Although the lung is - cut into thin sections, no abscesses are found. Bronchi throughout - the lung contain mucopurulent fluid. - - The left lung over its lower half is covered by a thin layer of - fibrin. The tissue is crepitant throughout and moderately edematous. - Bronchi contain mucopurulent fluid. - - Hemolytic streptococci in pure culture are obtained from the blood - of the heart, right pleural cavity and pericardium. No growth is - obtained on a plate inoculated with material from the right lower - lobe. The right bronchus contains hemolytic streptococci and B. - influenzæ. - - The pleural surface of the right lung is covered by a thick layer of - fibrin which has undergone advanced organization. Fibrous septa - within the lung are much thickened by the presence of newly formed - fibrous tissue; the interstices of the tissue are distended and - contain fibrin into which fibroblasts and new blood vessels have - penetrated. Some lymphatics are plugged with fibrin and contain - polynuclear leucocytes, lymphoid and large mononuclear cells. In - several places organization of these thrombi is beginning. About the - blood vessels are thrombosed lymphatics in which polynuclear - leucocytes and mononuclear cells are equally abundant. Alveoli - immediately adjacent to blood vessels and to fibrous septa often - contain fibrin, and alveoli elsewhere contain desquamated cells in - abundance. - -In association with hemolytic streptococci in the blood, pleura and -pericardium, there has been inflammation of the interlobular septa of -the lungs with acute lymphangitis; there has been no suppuration and the -lesion is in process of healing with new formation of fibrous tissue. It -is evident that this lesion, as well as pleurisy with advanced -organization, preceded the exacerbation of the patient’s illness which -occurred five days before death. The advanced chronic changes found at -autopsy indicate that the pulmonary and pleural lesions had their origin -during the illness which was present at the time of admission to the -hospital. Interstitial pneumonia caused by hemolytic streptococci was of -mild character and did not produce suppuration within the lung; -nevertheless, hemolytic streptococci which reached the pleura caused -empyema. - - - Suppurative Pneumonia with Multiple Clustered Abscesses Caused by - Staphylococci - -In the preliminary report of this commission published in _The Journal -of the American Medical Association_, _loc. cit._, pg. 111, we described -suppurative pneumonia with multiple abscesses caused by staphylococci -and cited 4 instances of the lesion which followed influenza. Chickering -and Park[84] published in a subsequent number of the same journal an -account of staphylococcus pneumonia, a lesion which has heretofore -attracted very little attention. - -In a small group of cases abscesses in the lungs have had characters -which serve to distinguish them from the abscesses previously described. -Small, sharply circumscribed yellow nodules, which in their centers have -undergone suppurative softening, form a cluster upon a red, airless -background (Figs. 15 and 16). One or more of these groups several -centimeters across, occur in the lungs. It is usually evident that the -abscesses are clustered about a medium-sized bronchus, but occasionally -with increase in the size of the small cavities the lung tissue assumes -a honey-combed appearance. - -These clustered abscesses occur in association with bronchopneumonia and -have been in all instances associated with purulent bronchitis. The -mucosa of the small bronchi may be destroyed so that the surface is -eroded. These small clustered abscesses are seen as conspicuous yellow -spots immediately below the pleura, but there has been no associated -empyema. In 2 instances these abscesses were accompanied by fibrinous -pleurisy, but in the remaining autopsies the pleura has been normal. The -infrequency of empyema is in contrast with its almost invariable -presence when a streptococcus abscess is found below the pleura. - - =Autopsy 280.=—Onset of illness with malaise, headache, cough and - fever was on September 24, eight days before death. At autopsy there - were hemorrhagic peribronchiolar and lobular bronchopneumonia, - clustered foci of suppuration in right lung, purulent bronchitis and - fibrinous pleurisy. Hemolytic streptococci were obtained from the - consolidated lung and from a bronchus. A culture from the right lung - was contaminated. In the bronchus were found B. influenzæ and a few - staphylococci. Microscopic examination of the abscesses shows that - they contain Gram-staining cocci grouped into staphylococcus-like - colonies. - - =Autopsy 286.=—Duration of illness, which began September 25 with - symptoms of influenza, was nine days. At autopsy there were lobular - and confluent patches of bronchopneumonia, clustered abscesses in - the right lung below the pleura, purulent bronchitis, and - serofibrinous pleurisy localized in the neighborhood of the - abscesses. Pneumococcus IV was obtained from the blood of the heart, - and Pneumococcus IV, staphylococci and B. influenzæ from the right - main bronchus; growth failed to occur on plates from right and left - lungs. Microscopic examination shows the presence of clumps of cocci - with staphylococcus grouping in the centers of the small abscesses. - Section through one abscess shows its continuity with the wall of a - bronchus; along one side of the abscess is epithelium composed of - flattened epithelial cells in multiple layers continuous with that - of the bronchus; the remainder of the abscess wall is formed by - disintegrated lung tissue. - -[Illustration: - - Fig. 15.—Abscesses in two clusters caused by S. aureus in upper part - of right upper lobe; confluent lobular consolidation in lower part - of lobe. Autopsy 333. -] - -[Illustration: - - Fig. 16.—Abscesses in cluster caused by S. aureus at apex of right - upper lobe. Autopsy 322. -] - - =Autopsy 322.=—The patient was admitted with influenza eight days - before death; signs of pneumonia appeared two days later, and on the - following day Pneumococcus IV was obtained from the sputum. At - autopsy there were bronchopneumonia with lobar consolidation, - abscesses clustered about a bronchus in the right upper lobe and - purulent bronchitis. The blood was sterile; S. aureus was obtained - from the consolidated part of the left lung; S. aureus and - Pneumococcus III from the abscesses of the right lung. Microscopic - examination of sections of abscesses showed the presence of - Gram-staining cocci in staphylococcus-like colonies, surrounded by - necrotic material and polynuclear leucocytes; Gram-negative bacilli - resembling B. influenzæ were seen. (See Fig. 16.) - - =Autopsy 333.=—The onset of influenza was fifteen days before death; - a diagnosis of pneumonia was made seven days before death. At - autopsy there were confluent bronchopneumonia, clustered abscesses - in the right lung and purulent bronchitis (no pleurisy). The blood - contained Pneumococcus II atypical. S. aureus and Pneumococcus II - atypical were obtained from the abscesses; S. hemolyticus, from the - consolidated left lung; S. aureus, B. influenzæ and a few hemolytic - streptococci, from the bronchus. (See Fig. 15.) - - =Autopsy 370.=—The patient was admitted seventeen days before death - and signs of pneumonia were noted three days after admission. At - autopsy there were lobular and confluent bronchopneumonia and small - abscesses clustered about bronchi and situated within the gray - consolidated lung; purulent bronchitis and patches of atelectasis, - with distention of the lungs, so that they failed to collapse on - removal. No growth was obtained from the heart’s blood; S. aureus in - pure culture was obtained from the abscesses of the right lung; S. - aureus, Pneumococcus IV and B. influenzæ were obtained from a small - bronchus on the left side. - - =Autopsy 425.=—Illness began with influenza twenty-nine days before - death; a diagnosis of pneumonia was made fourteen days before death. - At autopsy there were chronic bronchopneumonia with tubercle-like - nodules of consolidation with some large patches of consolidation, - multiple small abscesses giving a honey-combed appearance to part of - the right middle lobe, purulent bronchitis and bronchiectasis. S. - hemolyticus was grown from the heart’s blood; S. hemolyticus, B. - influenzæ and S. albus from the lung. Sections of an abscess contain - clumps of cocci. An abscess cavity has along one side remains of a - bronchial wall covered by squamous epithelium; a dilated bronchus, - cut longitudinally, terminates in this irregular abscess cavity. - -Table XLIX shows the incidence of pneumococci, hemolytic streptococci, -staphylococci and B. influenzæ in the foregoing autopsies with abscesses -clustered about bronchi: - - TABLE XLIX - - ════════╤════════╤═════════════════╤═════════════════ - │ NO. OF │ │ HEMOLYTIC - │CULTURES│ PNEUMOCOCCI │ STREPTOCOCCI - ────────┼────────┼────────┬────────┼────────┬──────── - │ │ NO. │PER CENT│ NO. │PER CENT - │ │POSITIVE│POSITIVE│POSITIVE│POSITIVE - ────────┼────────┼────────┼────────┼────────┼──────── - Bronchus│ 4│ 2│ 50.0│ 2│ 50.0 - Lung │ 6│ 2│ 33.3│ 3│ 50.0 - Blood │ 6│ 2│ 33.3│ 2│ 33.3 - ────────┴────────┴────────┴────────┴────────┴──────── - - ════════╤═════════════════╤═════════════════ - │ │ - │ STAPHYLOCOCCI │ B. INFLUENZÆ - ────────┼────────┬────────┼────────┬──────── - │ NO. │PER CENT│ NO. │PER CENT - │POSITIVE│POSITIVE│POSITIVE│POSITIVE - ────────┼────────┼────────┼────────┼──────── - Bronchus│ 4│ 100.0│ 4│ 100. - Lung │ 4│ 66.7│ 2│ 33.3 - Blood │ │ │ │ - ────────┴────────┴────────┴────────┴──────── - -Staphylococcus shows in the lung the same tendency to produce localized -abscesses which it exhibits in other tissues of the body; it invades the -lung by way of the bronchi, but shows no ability to invade lymphatics, -and in the cases we have examined rarely enters the pleura or the blood. -In all of these cases B. influenzæ has been found in the bronchi and -perhaps precedes the staphylococcus as an invader of the lower -respiratory passages. Pneumococci atypical II, Types III and IV have -been found in over half of these cases. The significance of this -organism is emphasized by the 2 cases in which it has been found in the -heart’s blood at autopsy. It appears not improbable that S. aureus has -invaded the lung already the site of bronchopneumonia caused by -pneumococci. - -Notwithstanding the small number of autopsies, the figures in Table -XLIX, showing the incidence of pneumococci, streptococci, staphylococci -and B. influenzæ, are cited so that they may be compared with the -corresponding figures for the usual type of streptococcus abscess (p. -203). The incidence of hemolytic streptococci is relatively low, whereas -that of staphylococci approximates 100 per cent. S. aureus was present -in great number in the lung of Autopsies 322 and 333 and in pure culture -in the abscess of Autopsy 370. Microscopic examination of sections from -the abscesses which have been described, demonstrated the presence of -Gram-staining cocci in characteristic staphylococcus-like clumps within -the exudate of the abscesses; scattered chains of streptococci were not -found. In those instances (Autopsies 280 and 286) in which cultures -failed to demonstrate staphylococci, microscopic examination -demonstrated staphylococcus-like clumps of bacteria within the abscess -cavity. Cultures were usually made from the consolidated lung near the -abscess where the pleural surface could be seared, rather than from the -pus, so that in some instances the microorganism has doubtless escaped -detection although present. - -In association with the multiple abscesses which have been described, -injury to the bronchi and bronchopneumonia have been invariably present. -Purulent bronchitis has been present in all instances of this lesion; in -2 instances there has been dilatation of the bronchi, and in 1 instance -in which the onset of influenza was twenty-nine days before death, there -has been advanced bronchiectasis. - -Microscopic examination shows that the epithelium of the bronchi is -partially or completely destroyed and that destruction of the underlying -tissue, with acute suppurative inflammation, penetrates to a greater or -less depth into the wall. When the epithelium of the bronchus is wholly -destroyed and the lumen is filled and distended with polynuclear -leucocytes, a cross section of the tube has the appearance of a small -abscess; but more careful examination often shows that the engorged -mucosa is still intact. Occasionally, a network of fibrin forms a layer -covering the denuded mucosa. Disintegration of the superficial tissue -may extend to the muscularis or through it, and may penetrate the wall -of the bronchus. The tissue in contact with the exposed surface contains -many polynuclear leucocytes and blood vessels plugged with fibrinous -thrombi, but deeper in the tissue lymphoid and plasma cells are more -numerous. In 2 instances (Autopsies 286 and 425) favorable sections have -demonstrated that the wall of an abscess on one side consists of the -remains of a bronchus, covered by epithelium composed of squamous cells, -Whereas the remainder of the wall, here very irregular, is formed by -partially destroyed alveoli plugged with fibrin. The suppurative process -has penetrated the wall of the bronchus on one side and extended into -the surrounding alveolar tissue. In other instances, abscess cavities -occur within the alveolar tissue of the lung and their relationship to -bronchi is not evident. In the mass of polynuclear leucocytes which fill -the abscess cavity, are clumps of staphylococci in great abundance, -usually forming characteristic colonies which are conspicuous with the -low power of the microscope. - - - Empyema, Pericarditis and Peritonitis - -No sharp line can be drawn between nonpurulent and purulent pleurisy. A -diagnosis of empyema has been made when the fluid in the chest has -become opaque and fibrin has undergone softening or solution. The lesion -has been designated seropurulent when there has been abundant thin, -opaque, gray fluid. Pleurisy has been designated fibrinopurulent when -the cavity has contained opaque fluid and ragged soft white or yellowish -fibrin adherent to the chest wall; this fibrin is evidently in process -of disintegration and there may be numerous shreds and flakes of fibrin -which subside to the bottom of the fluid. The amount of fluid in the -cavity may occasionally exceed 1,700 c.c.; that in both pleural cavities -may exceed 2,500 c.c. The lesion has been designated purulent when -fibrin has almost wholly disappeared and the cavity contains thick -yellowish white fluid. In 4 of 5 instances in which thoracotomy had been -performed, empyema has assumed this otherwise uncommon type. - -Some inflammation of the pleura is almost constantly found in -association with all forms of pneumonia, but in many instances is so -slight that it has no noteworthy significance. Table L shows the -incidence of various types of pleurisy. - - TABLE L - - ═══════════════════╤═════════╤════════════════╤═══════════╤════════════ - │ LOBAR │BRONCHOPNEUMONIA│SUPPURATIVE│INTERSTITIAL - │PNEUMONIA│ │ PNEUMONIA │SUPPURATIVE - │ │ │ WITH │ PNEUMONIA - │ │ │ ABSCESS │ - ───────────────────┼────┬────┼────────┬───────┼─────┬─────┼──────┬───── - „ │No. │ % │ No. │ % │ No. │ % │ No. │ % - ───────────────────┼────┼────┼────────┼───────┼─────┼─────┼──────┼───── - No pleurisy noted │ 30│46.9│ 44│ 55│ 1│ 2.6│ 1│ 5.9 - Serous pleurisy │ 5│ 7.8│ 9│ 11.2│ │ │ │ - Fibrinous pleurisy │ 10│15.6│ 5│ 6.2│ 1│ 2.6│ │ - Serofibrinous │ 12│18.2│ 14│ 17.5│ 3│ 7.7│ │ - pleurisy │ │ │ │ │ │ │ │ - Seropurulent │ │ │ │ │ 9│ 23.1│ 1│ 5.9 - pleurisy │ │ │ │ │ │ │ │ - Fibrinopurulent │ 7│10.9│ 5│ 6.2│ 17│ 43.6│ 12│ 70.6 - pleurisy │ │ │ │ │ │ │ │ - Purulent pleurisy │ │ │ 3│ 3.7│ 8│ 20.5│ 3│ 17.6 - ───────────────────┼────┼────┼────────┼───────┼─────┼─────┼──────┼───── - Total │ 64│ │ 80│ │ 39│ │ 17│ - ───────────────────┴────┴────┴────────┴───────┴─────┴─────┴──────┴───── - -Empyema has occurred, on the one hand, in 12.4 per cent of instances of -lobar pneumonia and in 9.9 per cent of instances of bronchopneumonia -alone. It has occurred, on the other hand, in 87.2 per cent of instances -of suppurative pneumonia with abscess formation and in 94.1 per cent -instances of interstitial suppurative pneumonia. These suppurative -lesions are caused by hemolytic streptococci, and when cultures are made -from the pleural exudate this microorganism is isolated. - -Of 16 instances in which empyema has occurred in association with lobar -pneumonia or bronchopneumonia unaccompanied by suppuration in 6 there -has been infection with hemolytic streptococci. Empyema has occurred in -the absence of hemolytic streptococci only 10 times. - -=Empyema Caused by Hemolytic Streptococci.=—When necrosis preceding -abscess formation has occurred in the lung, streptococci are found in -immense numbers in the dead tissue. The pleura overlying the abscess -undergoes necrosis and occasionally streptococci are particularly -numerous upon the pleural surface of the necrotic tissue. In Autopsy 376 -a membrane thin as tissue paper, representing the pleura, separated an -abscess containing thick pus from the pleural cavity which was the site -of empyema. The abscess may rupture into the pleural cavity and at the -same time may be in free communication with a bronchus (Autopsy 480). In -one (Autopsy 467) instance an abscess which had ruptured into the -pleural cavity had completely discharged its contents and was in process -of healing, newly formed fibrous tissue being abundant in its wall. - -With few exceptions empyema has accompanied subpleural abscess caused by -hemolytic streptococci, being found on the side corresponding to the -abscess. Among 39 instances of pulmonary abscess, empyema has been -limited to the side of the abscess in 23; it has been present on the -opposite side as well in 10 instances. In 2 instances there have been -abscesses in both lungs; in one (Autopsy 385 A) there has been double -empyema, and in the other (Autopsy 487) empyema only on the left side. -In one instance abscess has been recognized by microscopic examination -and its location is not recorded. In 5 instances of abscess formation -there has been no empyema. In Autopsy 383 there has been no pleurisy -noted; in Autopsy 416 there has been fibrinous pleurisy and in Autopsies -277, 290 and 380, serofibrinous pleurisy. - -Empyema has been almost invariably found in association with -interstitial suppurative pneumonia. This lesion extends by way of the -lymphatics up to the pleural surface and is often more conspicuous just -below the pleura than elsewhere. Empyema has been absent in only 3 of 21 -examples of the lesion and in one of these there has been serous -effusion. In 12 instances interstitial suppuration has occurred only on -one side and empyema has been limited to this side; in 5 instances with -interstitial suppuration on one side there has been empyema on both -sides; in 2 instances with interstitial suppuration in both lungs there -has been double empyema. - -The amount of fluid in the pleural cavity has varied from less than 100 -to 1,500 c.c. The fluid has occasionally been seropurulent or yellow, -thick and purulent, but in most instances the exudate is best described -as fibrinopurulent. There is yellow or yellowish gray purulent fluid -containing flakes of soft ragged fibrin. - -The foregoing study has shown, on the one hand, that empyema is a -frequent complication of streptococcus pneumonia and, on the other hand, -that empyema following influenza with relatively few exceptions is -caused by hemolytic streptococci. Empyema caused by this microorganism -exhibits in some instances characters not seen with other varieties of -pleural inflammation. The tissue between sternum and pericardium is -often edematous and the adjacent fat has a firm brawny consistence. In -some instances the exudate contains blood, and hemolysis has occurred so -that the fluid has a diffuse red color. The occurrence of multiple -pocketed collections of purulent fluid within the pleural cavity is -peculiar to streptococcus empyema. These pockets have been found 6 times -in association with abscess and 5 times with interstitial suppurative -pneumonia. In the presence of an exudate within the pleural cavity, some -part of the lung, usually the anterior surface behind the sternum and -costal cartilages, is glued by fibrinous adhesions to the parietal -pleura. Here occur pockets containing thin purulent fluid and softened -fibrin or thicker creamy pus walled off by fibrin about the edges of the -pocket. At the site of the lesion the lung, after it is separated from -the chest wall, is marked by a shallow depression surrounded by the -fibrin which has walled in the pocket. The little cavity thus formed, -varying much in size, is usually oval, the long diameter being from 1 to -3 cm. These pleural pockets may occur over the external surface of the -lung (Autopsies 452, 455, and 472) or between the internal surface and -pericardium (Autopsy 452). Occasionally with partial fibrinous adhesion -between the pleural surfaces there are both scattered pockets containing -purulent fluid and a larger encapsulated collection of fluid; in Autopsy -455 the pleural surfaces were adherent and there was 100 c.c. of -purulent fluid encapsulated in a space over the external surface of the -lung, 12 × 8 cm. In Autopsy 452 the lower part of the pleural cavity was -encapsulated and contained 650 c.c. of fluid. This tendency of empyema -caused by S. hemolyticus to form encapsulated pockets is doubtless of -considerable importance in the treatment of the condition. - -Stone, Bliss and Phillips[85] have described these encapsulated pockets -as “subcostosternal pus pockets” and have maintained that they are -formed about the sternal lymphatic nodes. We have found them so widely -scattered that this relation seems improbable. - -=Pneumococcus Empyema.=—Empyema occurred in association with pneumonia -referable to pneumococci 10 times, once with Pneumococcus II; 6 times -with Pneumococcus atypical II; once with Pneumococcus III and twice with -Pneumococcus IV. The lesion was seropurulent once; fibrinopurulent 8 -times and purulent once. Fibrin in several instances was somewhat -voluminous. In the following instance voluminous masses of fibrin had an -important influence upon the attempted treatment. - - =Autopsy 473.=—A. D. P., white, aged twenty-one, a student from - Missouri, had been in military service two weeks. He was admitted to - the hospital with influenza twenty-eight days before his death, and - four days after admission there were signs of pneumonia. - Paracentesis was performed on the right side on the eleventh day - after admission; 4 c.c. of cloudy fluid which contained Pneumococcus - III were obtained at this time and later in the day 800 c.c. were - withdrawn. On the thirteenth day attempted withdrawal of fluid from - both pleural cavities failed. On the eighteenth day aspiration of - the right pleural cavity yielded only 30 c.c. of fluid. On the - nineteenth day 400 c.c. of purulent fluid were withdrawn from the - right pleural cavity. On the twenty-fifth day there was cyanosis and - delirium. Shortly before death aspiration of the right pleural - cavity was attempted, but only 4 c.c. of fluid were obtained. - - =Anatomic Diagnosis.=—Chronic bronchopneumonia with lobular and - peribronchiolar consolidation in left lung; fibrinopurulent pleurisy - on both sides; purulent bronchitis and bronchiectasis. - - On removal of the sternum, encysted purulent pleurisy is found - between the inner surface of the right lung and the pericardium; - there is here 450 c.c. of very thick creamy, greenish yellow pus - entirely separated from the remainder of pleural cavity. The - external part of the cavity contains 1,450 c.c. of fluid and - voluminous masses of firm fibrin which placed in a measuring - cylinder occupy 450 c.c. The left pleural cavity contains 400 c.c. - of seropurulent fluid in which there is abundant sediment of - fibrinous particles. - - The right lung is compressed; the bronchi exude purulent fluid. The - left lung is voluminous; in the upper and lower lobes there are - small yellowish gray nodules of consolidation, grouped in clusters, - and gray patches of lobular consolidation occur. Bronchi are dilated - and filled with purulent fluid. - - Bacteriologic examination shows the presence of Pneumococcus III - obtained in pure culture from the blood of the heart and from the - right pleural cavity. S. viridans is grown from the left lung; a - plate from the right bronchus contained B. influenzæ, S. viridans - and a few colonies of staphylococcus and M. catarrhalis. - -The foregoing case is particularly noteworthy because aspiration failed -repeatedly to yield more than a few cubic centimeters of fluid, -doubtless because the voluminous masses of fibrin present in the cavity -prevented escape of fluid. Aspiration was attempted shortly before -death, but only 4 c. c. of fluid were obtained; nevertheless, at autopsy -the right pleural cavity contained 2,350 c.c. of exudate. Another factor -of much importance in relation to treatment is the encapsulation of 450 -c.c. of purulent fluid between the inner surface of the right lung and -the pericardium. It is possible that free drainage might have emptied -the main cavity and perhaps even freed the encapsulated fluid. - -=Pericarditis.=—Among 241 autopsies on individuals with pneumonia -following influenza, pericarditis occurred 23 times; these lesions were -classified as follows: Serous pericarditis, 1; serofibrinous -pericarditis, 9; seropurulent pericarditis, 1; fibrinopurulent -pericarditis, 10; purulent pericarditis, 2. - -It is noteworthy that in 12 of 23 instances of pericarditis the lesion -was associated with S. hemolyticus infection of the lung and whenever in -these instances cultures were made (Autopsies 434, 485, 499 and 504) -hemolytic streptococci were obtained from the pericardial exudate in -pure culture. - -The tendency of interstitial suppurative pneumonia to produce -pericarditis is especially evident. Among 21 instances of interstitial -suppurative pneumonia pericarditis occurred 6 times (28.6 per cent); -among 39 instances of suppurative pneumonia with abscess formation, -pericarditis occurred twice (5.1 per cent); whereas among all other -autopsies, namely, 181, the lesion occurred 15 times (8.3 per cent). - -Pericarditis occurred in association with pneumonia referable to -Pneumococcus I, once, (Pneumococcus I isolated from the pericardium); to -Pneumococcus II, once; to atypical Pneumococcus II, 5 times (twice -isolated from the pericardium); and to Pneumococcus IV, twice (once -isolated from the pericardium). - -=Peritonitis.=—Purulent peritonitis occurred only twice, in both -instances in association with pneumonia caused by hemolytic -streptococci. Purulent peritonitis was part of a general serositis -involving both pleural cavities, pericardium and peritoneum in 2 -noteworthy instances: - - =Autopsy 465.=—J. K., white, aged twenty-two, farmer from Oklahoma, - had been in military service one month. He was admitted to the - hospital with influenza, sore throat and bronchitis twenty-four days - before his death. Signs of pneumonia were recognized thirteen days - later and at the same time there was otitis media on the right side. - Empyema and pericarditis were found three days before death and two - days later 1000 c.c. of cloudy fluid were withdrawn from the chest. - - =Anatomic Diagnosis.=—Suppurative pneumonia with consolidation and - abscess in right lower lobe below pleura; purulent pleurisy on - right, seropurulent pleurisy on left side; beginning serofibrinous - pericarditis; fibrinopurulent peritonitis; purulent bronchitis. - - The body is emaciated. The right pleural cavity contains 350 c.c. of - thick, creamy yellow pus in which are flakes of fibrin; the right - lung is collapsed and lies at the back and inner side of the cavity. - The left pleural cavity contains 500 c.c. of turbid, yellow, - seropurulent fluid in which is soft fibrin. The lower lobe of the - right lung is consolidated throughout, flabby, gray red and finely - granular on section. Below the pleura of the posterior border is a - wedge-shaped cavity with its base 1.5 cm. across, in contact with - the pleural surface. About the cavity consolidated tissue has an - opaque, yellow color. Bronchi in both lungs contain mucopurulent - fluid. The pericardial cavity contains 20 c.c. of turbid fluid; the - left auricular appendage is bound by a thin layer of fibrin to the - parietal pericardium. - - The peritoneal cavity contains 100 c.c. of thick, creamy, yellow, - purulent fluid. Between the diaphragm and liver is a layer of - fibrin, in places 1.5 cm. in thickness; fibrin is present upon the - peritoneum overlying the kidneys and base of mesentery. - - Bacteriologic examination shows the presence of hemolytic - streptococci, obtained in pure culture from the blood of the heart, - right pleural cavity and peritoneum. From the right bronchus are - grown S. hemolyticus, B. influenzæ and a few colonies of S. viridans - and staphylococcus. - - =Autopsy 504.=—G. R. C., white, aged twenty-eight, farmer from - Alabama, had been in military service three months. Onset of illness - occurred six days before death, and two days later he entered the - hospital with fever (103.4° F.), pains in the abdomen and vomiting. - Consolidation at the bases of the lung was recognized on the day - following admission and on the day before death 900 c.c. of greenish - brown fluid were aspirated from the left pleural cavity. - - =Anatomic Diagnosis.=—Interstitial suppurative pneumonia with - consolidation in left lower lobe; purulent pleurisy on both sides; - purulent pericarditis; purulent peritonitis; parenchymatous - degeneration of kidneys; acute splenic tumor. - - The body is that of a large well-nourished man. The left pleural - cavity contains 975 c.c. of creamy, yellow fluid; right pleural - cavity contains 425 c.c. of purulent fluid thinner than that on the - left side. The left lung is collapsed; the posterior and lower half - of the lower lobe is consolidated, flabby, deep red and fleshy in - appearance. The interstitial septa are yellow, thickened with - bead-like enlargements and contains creamy purulent fluid which - flows away and leaves small cavities. This interstitial suppuration - is more advanced below the outer surface of the lobe than elsewhere. - - The pericardial cavity contains 25 c.c. of creamy, yellow, purulent, - fluid; the epicardium is dull, covered in a few places by a small - amount of fibrin and below it are ecchymoses. - - The peritoneal cavity contains 100 c.c. of thick, yellow pus; the - peritoneal surfaces are injected and between the liver and diaphragm - is fibrin. - - Bacteriologic examination shows the presence of S. hemolyticus in - pure culture from the blood of the heart, the lower lobe of the left - lung, pericardium and peritoneum. The right main bronchus contains - the same microorganism, B. influenzæ and a few staphylococci. - -General serositis has been caused by hemolytic streptococci which in one -instance have entered the pleura from a subpleural abscess, and in the -other from the suppurating interstitial tissue of the lung. In one of -these cases the patient entered the hospital with symptoms suggestive of -acute peritonitis. - - - Bronchiectasis - -Acute dilatation of the bronchi is a common result of the bronchitis of -influenza, and its frequent occurrence is an index of the severity of -the changes in the bronchial wall. In some instances the smaller bronchi -in well-localized areas are uniformly dilated; in other instances, large -cavities, several centimeters in diameter, are formed and all -transitions between the two extremes occur. - -The occurrence of bronchiectasis following influenza is mentioned by -Leichtenstern[86]. He states that evidence of bronchiectasis can persist -for weeks or months and nevertheless end with complete restitution of -the lungs to normal. Lord[87] has described instances of bronchiectasis -occurring in association with infection by B. influenzæ and Boggs[88] -has recorded similar observations. - -We have had abundant opportunity to observe early stages in the -production of bronchiectasis and to study the much discussed -pathogenesis of the condition. - -The following figures show the predilection of bronchiectasis for the -left lung and for the lower lobes: Bronchiectasis occurred 30 times in -the left lung alone, 9 times in the right lung alone and 13 times in -both lungs, the total being 52. Among 30 instances in which the lesion -occurred only in the left lung, in 24 it was limited to the lower lobe, -and in 15 of these 24 instances to the base of the lower lobe. Among 9 -instances in which dilatation of bronchi occurred only in the right -lung, it was limited to the lower lobe in 4 instances and to the base of -the lower lobe in 2 of these 4 instances. - -When the lesion is limited to the base of the lower lobes small bronchi -with no recognizable cartilage in their wall are dilated to a diameter -of from 3 to 6 cm. and are distended with thick mucopurulent fluid. The -tenacious character of the bronchial contents and the action of gravity -doubtless have a part in the production of the dilatation. In several -instances dilatation of the bronchi was limited to the basal parts of -both upper and lower lobes. - -When bronchiectasis occurs throughout a whole lung, usually the left, or -in both lungs, the lesion is more advanced and conspicuous (Fig. 26). -There is diffuse dilatation of small and medium-sized bronchi. Dilated -bronchi with deeply injected mucosa and filled with yellow mucopurulent -fluid, are seen throughout the sectioned lung. A bronchus cut -longitudinally may have a nearly uniform diameter of from 5 to 9 mm. for -a distance of 5 or 6 cm., maintaining this diameter to within 1 cm. of -the pleural surface, where normally only small bronchi occur. - -More advanced bronchiectasis is represented by the occurrence of -spherical bronchiectatic cavities, having a diameter from 1 to 2.5 cm. -In some instances there have been two or three of these cavities but -occasionally there may be many. Cylindrical dilatation of the bronchi -usually occurs widely distributed in the lungs. In Autopsy 440 a small -bronchus, cut longitudinally, was dilated to a diameter of 5 mm. for a -distance of 5 cm. and terminated in a spherical cavity 2 cm. in -diameter; there was another smaller spherical cavity nearby and dilated -bronchi occurred elsewhere. In Autopsy 467, in the upper part of the -lower lobe, two spherical cavities 1 and 1.5 cm. in diameter -communicated with a bronchus of medium size. - -Autopsies with bronchiectasis are listed in the order of the duration of -illness to show the parallel increase in the severity of the lesion -(Table LI). In 2 instances (Autopsies 244 and 314) bronchiectatic -cavities surrounded by firm fibrous tissue have evidently existed before -the onset of the fatal illness, which has lasted in one instance -approximately four and in the other six days; these autopsies have been -omitted from the table. - -The table shows that bronchiectasis observed within twelve days after -onset of illness with symptoms of influenza is moderately advanced and -almost invariably limited to the left lower lobe and usually to the base -of the lobe. Advanced dilatation, indicated by the formation of -spherical or cylindrical cavities, occurs with increasing frequency as -the duration of the respiratory disease increases. - -Bronchiectasis has been almost invariably associated with purulent -bronchitis. The dilated bronchi contain mucopurulent material and -throughout the lungs the same condition is usually widespread. Among 137 -instances of purulent bronchitis bronchiectasis consequent upon -influenza has been present in 50. - - TABLE LI - - ═══════╤════════╤═════════════╤══════════════╤══════════════╤═══════════ - NO. OF │DURATION│ TYPE OF │ LOCATION OF │ CHARACTER OF │BACTERIA IN - AUTOPSY│ OF │ PNEUMONIA │BRONCHIECTASIS│BRONCHIECTASIS│ BRONCHUS - │ILLNESS │ │ │ │ - │IN DAYS │ │ │ │ - ───────┼────────┼─────────────┼──────────────┼──────────────┼─────────── - 394│ 5 ?│Broncho │Rt. base │Dilatation │ - 359│ 7 +│Lobar and │Lt. lower lobe│Dilatation │ - │ │ broncho │ │ │ - 322│ 8│Abscess │Lt. base │Dilatation │ - │ │ (staph.) │ │ │ - 325│ 8│Interst. │Lt. base │Dilatation │S. hem., B. - │ │ suppuration│ │ │ inf., - │ │ │ │ │ staph. - 352│ 8│Lobar and │Lt. lower lobe│Advanced │ - │ │ broncho │ │ dilatation │ - 429│ 8 ?│Broncho │Rt. base │Dilatation │ - 288│ 10│Abscess │Lt. base │Dilatation │S. hem., B. - │ │ │ │ │ inf. - 374│ 10│Lobar and │Rt. and lt. │Advanced │ - │ │ broncho │ lungs │ dilatation │ - 376│ 10│Abscess │Lt. base │Dilatation │S. hem. - 437│ 11│Lobar │Rt. lower lobe│Advanced │ - │ │ │ │ dilatation │ - 482│ 11│Broncho │Lt. base │Dilatation │B. inf., - │ │ │ │ │ Pneum. - │ │ │ │ │ IV, S. - │ │ │ │ │ hem. - 489│ 11│Lobar and │Lt. lung │Dilatation │B. inf., - │ │ broncho │ │ │ Pneum. - │ │ │ │ │ IV. - 287│ 12│Lobar and │Lt. lower lobe│Advanced │Pneum. IV., - │ │ broncho │ │ dilatation │ B. inf., - │ │ │ │ │ staph. - 289│ 12│Broncho │Lt. lower lobe│Advanced │Pneum. IV., - │ │ │ │ │ B. inf. - │ │ │ │ │ staph. - 295│ 12│Interst. sup.│Rt. lung │Advanced │S. hem., B. - │ │ and abscess│ │ dilatation │ inf. - 336│ 12│Broncho │Lt. base │Dilatation │ - 375│ 12│Broncho │Rt. and lt. │Dilatation │ - │ │ │ bases │ │ - 422│ 12 ?│Lobar and │Lt. base │Dilatation │ - │ │ broncho │ │ │ - 381│ 13│Abscess │Lt. base │Spherical │ - 391│ 13│Lobar and │Lt. lung │Dilatation │ - │ │ broncho │ │ │ - 401│ 14 ?│Lobar and │Rt. and lt. │Spherical │ - │ │ broncho │ lungs │ │ - 402│ 14│Chronic │Rt. lower lobe│Dilatation │ - │ │ broncho │ │ │ - 410│ 14 ?│Abscess │Rt. upper lobe│Dilatation │ - 333│ 15│Abscess │Lt. upper lobe│Dilatation │S aur., B. - │ │ (staph.) │ │ │ inf. S. - │ │ │ │ │ hem. - 389│ 15│Interst. │Lt. lung │Advanced │ - │ │ suppuration│ │ dilation │ - 412│ 15│Lobar and │Lt. lower lobe│Cylindrical │ - │ │ broncho │ │ │ - 398│ 16│Broncho │Rt. and lt. │Advanced │ - │ │ │ lungs │ dilatation │ - 423│ 16│Broncho │Lt. base │Dilation │ - 488│ 16│Abscess │Lt. lower lobe│Dilatation │S. hem., - │ │ │ │ │ Pneum. - │ │ │ │ │ atyp. II. - 312│ 17│Broncho │Rt. and lt. │Dilatation │S. hem., B. - │ │ │ lungs │ │ inf. - │ │ │ │ │ staph. - 372│ 17│Broncho │Rt. lung │Dilatation │ - 385 C│ 17│Interst. │Lt. base │Dilatation │ - │ │ suppuration│ │ │ - 448│ 17│Broncho │Lt. lung │Dilatation │ - 460│ 17│Abscess │Lt. lower lobe│Spherical │S. hem., B. - │ │ │ │ │ inf., - │ │ │ │ │ staph. - 291│ 18│Broncho │Lt. base │Advanced │B. inf., - │ │ │ │ dilatation │ staph. - 296│ 18│Abscess │Lt. base │Dilatation │S. hem., B. - │ │ │ │ │ inf., - 387│ 19│Abscess │Rt. and lt. │Advanced │S. hem., B. - │ │ │ lungs │ dilatation │ inf., S. - │ │ │ │ │ aur. - │ │ │ │ │ Pneum. - │ │ │ │ │ II. - 421│ 19│Chronic │Rt. lung │Advanced │ - │ │ broncho │ │ dilatation │ - 440│ 19│Chronic │Rt. and lt. │Spherical │B. inf., S. - │ │ broncho │ lungs │ │ aur. - 419│ 20│Broncho │Rt. lung │Dilatation │Pneum. II, - │ │ │ │ │ B. inf. - 463│ 20│Chronic │Rt. and lt. │Spherical │B. inf., - │ │ broncho │ lungs │ │ staph., - │ │ │ │ │ Pneum. IV - 431│ 23│Chronic │Lt. base │Dilatation │ - │ │ broncho │ │ │ - 468│ 23 ?│Lobar and │Lt. lung │Dilatation │S. aur., B. - │ │ broncho │ │ │ inf., S. - │ │ │ │ │ vir. - 465│ 25 ?│Broncho │Lt. base │Dilatation │S. hem., B. - │ │ │ │ │ inf., - │ │ │ │ │ staph., - │ │ │ │ │ S. vir. - 445│ 27│Broncho │Lt. lower lobe│Spherical │S. aur. - 449│ 27│Abscess │Rt. and lt. │Spherical │S. hem., B. - │ │ │ lungs │ │ coli. - 378│ 28│Abscess │Lt. base │Cylindrical │S. hem., B. - │ │ │ │ │ inf., - │ │ │ │ │ Pneum. - │ │ │ │ │ atyp. II. - 473│ 28│Chronic │Lt. lung │Advanced │B. inf., S. - │ │ broncho │ │ dilatation │ vir., - │ │ │ │ │ staph., - │ │ │ │ │ M. - │ │ │ │ │ catarr. - 425│ 29│Abscess │Rt. and lt. │Cylindrical │ - │ │ (staph.) │ lungs │ │ - 467│ 30│Abscess │Rt. lower lobe│Spherical │S. hem., B. - │ │ │ │ │ inf. - 472│ 37│Chronic │Rt. and lt. │Advanced │B. coli - │ │ broncho │ lungs │ dilatation │ - 487│ 55│Abscess │Rt. and lt. │Cylindrical │B. inf. S. - │ │ │ lungs │ │ hem. - ───────┴────────┴─────────────┴──────────────┴──────────────┴─────────── - -The bacteriology of autopsies with bronchiectasis is shown in Table LII. - - TABLE LII - - ════════╤════════╤═════════════════╤═════════════════ - │ NO. │ │ - │EXAMINED│ PNEUMOCOCCUS │ S. HEMOLYTICUS - ────────┼────────┼────────┬────────┼────────┬──────── - │ │ NO. │PER CENT│ NO. │PER CENT - │ │POSITIVE│POSITIVE│POSITIVE│POSITIVE - ────────┼────────┼────────┼────────┼────────┼──────── - Bronchus│ 29│ 9│ 31.0│ 15│ 51.7 - Lung │ 37│ 16│ 43.2│ 18│ 48.6 - Blood │ 50│ 12│ 24.0│ 22│ 44.0 - ────────┴────────┴────────┴────────┴────────┴──────── - - ════════╤═════════════════╤═════════════════ - │ │ - │ STAPHYLOCOCCUS │ B. INFLUENZÆ - ────────┼────────┬────────┼────────┬──────── - │ NO. │PER CENT│ NO. │PER CENT - │POSITIVE│POSITIVE│POSITIVE│POSITIVE - ────────┼────────┼────────┼────────┼──────── - Bronchus│ 16│ 55.2│ 23│ 79.3 - Lung │ 10│ 27.0│ 19│ 51.4 - Blood │ │ │ │ - ────────┴────────┴────────┴────────┴──────── - -Comparison of the percentage incidence of the organisms which have to be -found associated with bronchiectasis and with purulent bronchitis -unaccompanied by bronchiectasis shows that there is no noteworthy -difference in the occurrence of pneumococci, hemolytic streptococci or -B. influenzæ within the bronchi. When allowance is made for the -difficulty of demonstrating B. influenzæ in the presence of a large -number of other microorganisms, it is not improbable that this organism -has been constantly present in the purulent contents of the bronchi with -purulent bronchitis, with and without bronchiectasis. Pneumococci, -streptococci and staphylococci are each present in the bronchi in about -one-half of the instances of bronchiectasis and mixed infections are -very common, S. viridans, B. coli and M. catarrhalis being occasionally -found in the bronchi. The table shows that pneumococci, streptococci and -staphylococci show no greater tendency to enter the lungs and blood when -bronchiectasis and purulent bronchitis coexist than with purulent -bronchitis alone. - -Moderate dilatation of the small bronchi at the base of the left lung -was found in several instances eight days after onset of symptoms -referable to the respiratory passages. Advanced, diffuse dilatation of -the bronchi was seldom seen before the lapse of two weeks, and -bronchiectasis with formation of spherical or cylindrical cavities was -found with few exceptions three weeks after onset of the fatal illness. -Long continued, purulent bronchitis does not necessarily produce -dilatation of the bronchi. It is noteworthy that the average duration of -the fatal illness in 137 instances of pneumonia and purulent bronchitis -with no bronchiectasis was 12.5 days, whereas the average duration of 49 -instances of pneumonia with purulent bronchitis and bronchiectasis was -only 16.5 days. - -Bronchiectasis is almost invariably associated with purulent bronchitis -in which tenacious mucopurulent fluid accumulates in the bronchi. It -begins at the bases of the lower lobes and is usually more advanced here -than elsewhere. Mechanical distention of the small bronchi by viscid -fluid, expelled with difficulty, brings about their dilatation and -gravity appears to have a part in accentuating the process. Histologic -examination of the changes accompanying bronchitis show that lesions -which penetrate into the muscular layer and presumably weaken the -bronchial wall are not uncommon and partial or complete destruction of -the wall may result. To what extent infiltration of the muscular wall by -polynuclear leucocytes or by lymphoid and plasma cells is accompanied by -changes which weaken the wall may be questioned. When the epithelial -lining of the bronchus is destroyed coagulative necrosis of the -underlying tissue occurs and may extend a variable distance into the -bronchial wall, not infrequently penetrating into or entirely through -the muscular layer. These changes furnish an explanation of the -occurrence of bronchiectasis following influenza. - -[Illustration: - - Fig. 17.—Acute bronchiectasis showing fissures penetrating into - bronchial wall and at one place entering surrounding alveolar - tissue; the surrounding alveoli are filled with fibrin. Autopsy 425. -] - -Acute bronchiectasis may be found following influenza after the illness -has lasted eight or ten days. There is no increase of fibrous tissue. -Small bronchi with no cartilage, which in normal lungs have a diameter -approximating 1 mm., are dilated to 3 mm. or more. The surface -epithelium is wholly or partially lost. Necrosis occurs in places and -extends deep into the tissue, destroying muscle and often penetrating -the entire thickness of the wall which in these small bronchi consists -in large part of fibrous tissue containing greatly engorged blood -vessels. In this necrotic material nuclei are absent and the tissue -containing fibrin stains deeply with eosin. In it occur fissures or -tears which extend from the lumen a variable distance, very frequently -penetrating the entire thickness of the wall and entering adjacent -alveoli (Figs. 17 and 19). Alveoli thus exposed almost invariably -contain plugs of dense fibrin. Where these rents have occurred, adjacent -edges of the bronchial wall, held together by underlying lung tissue, -have separated from one another, so that the circumference of the -bronchus has been increased (Fig. 18). These breaks in the continuity of -the wall may occur in several places, so that a fourth or a third of the -circumference may be formed by exposed alveolar tissue which has become -the site of fibrinous pneumonia (Fig. 20). During life, though the -inflamed bronchus is filled by mucopurulent exudate, distention of loose -alveolar tissue, uniting the interrupted bronchial wall, is doubtless -greater than it appears in the lung fixed by hardening fluids. - -[Illustration: - - Fig. 18.—Acute bronchiectasis showing fissures in the bronchial wall - extending into neighboring alveoli which in zone about are filled - with fibrin; one fissure has separated widely; peribronchial - fibrinous pneumonia (fibrin is black). Autopsy 425. -] - -Recently dilated bronchi have an irregularly stellate lumen as the -result of clefts penetrating at intervals into or through the bronchial -wall (Fig. 26). Longitudinal fissures mark the lining of these dilated -bronchial tubes. - -When the fatal illness has lasted more than two weeks, abundant new -formation of fibrous tissue occurs in a zone surrounding the dilated -bronchus. Adjacent alveolar walls are thickened by young fibrous tissue. -Alveoli, much diminished in size, are filled by hyaline fibrin into -which fibroblasts and newly formed blood vessels have penetrated. These -changes are limited to a wide zone in immediate contact with the dilated -bronchus, whereas at a greater distance alveolar walls have undergone no -thickening and alveoli contain no fibrin. - -[Illustration: - - Fig. 19.—Acute bronchiectasis; the bronchial wall indicated by - engorged mucosa shows a varying degree of destruction, fissures - extending into and through the bronchial wall. Autopsy 352. -] - -[Illustration: - - Fig. 20.—Acute bronchiectasis; with destruction of bronchial wall - exposing alveoli filled with fibrin; peribronchial fibrinous - pneumonia is seen about several bronchi present in the section; Gram - Weigert fibrin stain. Autopsy 425. -] - -This stage is well represented by Autopsy 421 after an illness of -nineteen days. Bronchiectatic cavities, from 3 to 6 mm. in diameter, are -numerous in sections of the lung; their lumina are irregular in outline -and often irregularly stellate. Microscopic examination shows the -presence of clefts which interrupt the bronchial wall at intervals -throughout its entire circumference. The original wall is well indicated -by the very richly vascularized connective tissue containing scattered -muscle bundles and is infiltrated with lymphoid and plasma cells in -great number. Where fissures have occurred the adjacent edges of the -interrupted wall have separated from one another, leaving a wide -interval where underlying alveolar tissue is exposed. Two changes tend -eventually to render the fissures inconspicuous, namely, regeneration of -epithelium and new formation of fibrous tissue. Exposed alveoli filled -with fibrin are in process of organization and epithelium which has -assumed a squamous type has grown down over the exposed surfaces of the -interrupted bronchial wall. It has begun to cover or in some instances -has completely covered the surface of rents entering alveoli plugged -with fibrin (Fig. 21). In the periphery of the bronchus alveolar walls -are thickened and infiltrated with lymphoid and plasma cells. The same -changes affect bronchi containing cartilage which is undergoing atrophy. - -The reinforcement of the fissured bronchial wall by new formation of -fibrous tissue, by thickening of the interalveolar walls and by -organization of fibrin within the alveoli is well shown after four weeks -(Autopsy 425; Fig. 28). There are spherical bronchiectatic cavities more -than a centimeter in diameter surrounded by a dense fibrous wall in -which are atrophied alveoli lined by epithelium of cubical form. -Occasionally, the fibrous wall is interrupted and alveoli, plugged with -organizing fibrin, are in immediate contact with the lumen. When these -plugs of fibrin which are slowly absorbed disappear, evidence of -preexisting rents in the bronchial wall are lost, and there are in this -lung bronchiectatic cavities of which the wall is a continuous circle of -dense fibrous tissue. - -[Illustration: - - Fig. 21.—Bronchiectasis with fissures extending through the bronchial - wall into alveolar tissue which is the site of fibrinous pneumonia; - epithelium has grown down into these fissures and has covered the - exposed surfaces. Autopsy 463. -] - -[Illustration: - - Fig. 22.—Regeneration of epithelium over fissures which have been - formed in the wall of a bronchus; the epithelium in the neighborhood - of and within the fissure is squamous. -] - -Epithelium lining the dilated bronchi is at times completely destroyed -(Fig. 28), but more frequently it persists in part. That which remains -has almost constantly the character of squamous epithelium (Figs. 22 and -23). The lowermost cells are cubical; those above them are polygonal, -tending to become flatter as the surface is approached; upon the surface -are cells often much flattened and occasionally they have lost their -nuclei and stain deeply with eosin as the result of superficial -necrosis. The change should not be regarded as metaplasia, for the -epithelium assumes this squamous type when the superficial columnar -cells have been lost. Actual necrosis of superficial ciliated columnar -cells is occasionally seen (Autopsy 352); injured cells have separated -from one another and desquamated into the lumen of the bronchus. The -epithelium which remains after the superficial cells are lost consists -of cells which become flatter from base to surface, but the -intercellular bridges characteristic of the epithelium of the skin are -not found. When epithelium is in process of regeneration, a layer -gradually diminishing in thickness extends over the denuded surface, the -advancing edge being formed by very flat cells in a single layer. The -epithelium growing into fissures which have penetrated the bronchial -wall may completely cover the exposed alveolar tissue. The newly formed -epithelium may follow a fissure into an alveolus which has been opened -and come into contact with the fibrin which fills the alveolus. - -[Illustration: - - Fig. 23.—Squamous epithelium growing over the defect in the bronchial - wall shown in Fig. 22 more highly magnified; squamous epithelium is - present above and columnar epithelium below. -] - -Bronchiectasis usually affects the small bronchi with no cartilage. It -is not uncommon to find greatly dilated bronchi with no cartilage in -close proximity to cartilage containing bronchi of smaller caliber. In -one instance (Autopsy 421) a bronchus of medium size with cartilage -measured 3 mm. in diameter, whereas two bronchi with no cartilage were -dilated to 4 and 6 mm., respectively. Nevertheless, larger bronchi are -occasionally the site of superficial loss of epithelium, necrosis -extending into the bronchial wall, formation of fissures and stretching -of the wall at the spot which is weakened. In association with these -changes atrophy of the cartilage may occur (Autopsies 421, 425, 440, -463). Plates of cartilage in process of atrophy are readily recognized -by their irregularly indented outline and often by their small size. The -fibrous tissue surrounding the cartilage is the site of chronic -inflammation and is densely infiltrated with lymphoid and plasma cells -among which polynuclear leucocytes are scant. Nevertheless, polynuclear -leucocytes are abundant in immediate contact with the cartilage and -appear to have an important part in the solution of its matrix, for -about them occur indentations of the edge. Leucocytes penetrate into the -cartilage. - -The necrosis and tears which occur in the wall of the bronchus are not -always limited to the bronchus, but may extend deeply into the -surrounding tissue. In Autopsies 312 (Fig. 21) and 423 wide areas of -necrosis have penetrated deeply into the tissue about the bronchi. - - =Autopsy 312.=—Illness began with influenza on September 26, - seventeen days before death; a diagnosis of lobar pneumonia with - consolidation of the right lower lobe was made ten days after onset - and Pneumococcus IV, B. influenzæ and S. hemolyticus were found in - the sputum. At autopsy there was bronchopneumonia with red and gray - lobular and confluent lobular patches of consolidation and right and - left serofibrinous pleurisy; there was purulent bronchitis; no - abscesses were seen. Small bronchi throughout both lungs were - dilated and often surrounded by a zone of hemorrhage. - - Hemolytic streptococci were found in the heart’s blood, in the - pleural exudate, consolidated lung and bronchus; B. influenzæ was - found in the lung and in a small bronchus, and staphylococci in the - contents of a small bronchus. - -[Illustration: - - Fig. 24.—Acute bronchiectasis with fissures extending through - bronchial wall which is marked by great engorgement of blood - vessels; at one point a fissure has penetrated deep into the - alveolar tissue and formed a small cavity containing purulent - exudate and surrounded by fibrinous pneumonia. Autopsy 312. -] - - Bronchi which are the site of acute inflammation have lost their - epithelium wholly or in part, and deep fissures penetrate the entire - thickness of the bronchial wall, extending into the surrounding lung - tissue which is the site of fibrinous pneumonia. In some instances - plugs of fibrin within the alveoli are bisected by these tears. - There is some superficial necrosis along the edge of each fissure, - in several places extending outward from defects in the walls of - small bronchi dilated to approximately 1.5 mm. There are wide - patches of necrosis affecting both alveolar walls and contents of - alveoli and extending 2 mm. into the lung tissue. When a fissure has - penetrated from the lumen of the bronchus into necrotic tissue (Fig. - 21), polynuclear leucocytes have accumulated within the necrotic - tissue, disintegration of tissue occurs, and a small cavity - communicating with the bronchus is formed. - - =Autopsy 423.=—C. H., white, aged twenty-five, resident of Oklahoma, - had been in military service one month. Death occurred sixteen days - after onset of influenza. - - =Anatomical Diagnosis.=—Chronic bronchopneumonia with - peribronchiolar consolidation throughout right lung and in left - lower lobe; right purulent pleurisy; purulent bronchitis; - bronchiectasis at base of left lung. - - The right lung weighs 1,260 grams; in the upper lobe are yellowish - gray nodules having the appearance of tubercles clustered about - small bronchi; in places similar nodules occur upon a background of - pinkish gray consolidation occupying the greater part of the lower - lobe. Bronchi contain purulent fluid. The left lung weighs 760 - grams; it is edematous and small, yellowish gray nodules of - consolidation in the lower lobe are clustered about terminal - bronchi. Bronchi at the base of the lower lobe are dilated. - - Bacteriologic examination shows the presence of hemolytic - streptococci in the blood of the heart; hemolytic streptococci and - B. influenzæ in the lung. - - Microscopic examination shows that the walls of the bronchi are - infiltrated with lymphoid and plasma cells; these cells are very - numerous in peribronchiolar patches of consolidation. A small - bronchus 1 mm. in diameter has squamous epithelium along one side; - on the opposite side, the wall is completely absent and there is - superficial necrosis of exposed alveoli filled with fibrin. A deep - fissure passes from the bronchus into the consolidated tissue; its - edges are necrotic and it is filled with polynuclear leucocytes. A - small cavity in contact with the bronchus has been formed. In - another part of the lung a distended bronchus has lost its - epithelium on one side, and here alveoli filled with fibrin form the - wall of the bronchus which is filled with leucocytes. Extending - outward from the eroded wall is a focus of necrosis where both - alveolar walls and contained exudate have lost their nuclei. - -The necrosis which has had its origin in the bronchi is soon followed by -accumulation of polynuclear leucocytes, softening and disintegration of -tissue. Discharge of the disintegrated tissue through the bronchi -results in the formation of a small cavity continuous with the bronchus. -These changes are well illustrated by the bronchiogenic abscesses which -have been described elsewhere (Autopsies 376, p. 206, and 387, p. 206). -When disintegrated tissue is discharged by way of the bronchi no -accumulation of pus occurs, but cavities will be formed, in part by -dilation of bronchi, in part by erosion of the adjacent lung tissue. -Histologic examination shows that these changes have produced the -advanced bronchiectasis found in Autopsy 445 (Fig. 25). - - =Autopsy 445.=—W. F., white, aged twenty-three, from Mississippi, - had been in military service one month. His illness began September - 22, twenty-seven days before death, with severe coryza, weakness, - nausea and vomiting; great pain in bones, cough and sore throat. He - was admitted to the base hospital one week later with diagnosis of - influenza and bronchitis. On October 3, sixteen days before death, - signs of consolidation were found on the left side over the back and - a diagnosis of lobar pneumonia was made. On October 18 there was - severe headache, pupils were dilated, and there was rigidity of - neck; lumbar puncture was made and pneumococci were found in the - fluid obtained. Death occurred on the following day. - - =Anatomic Diagnosis.=—Bronchiectasis with unresolved pneumonia - limited to the left lower lobe; acute bronchopneumonia with - peribronchiolar consolidation in right lung; purulent bronchitis, - peribronchial hemorrhage and organizing bronchiolitis in right lung; - adherent pleura on left side; purulent meningitis. - - The left upper lobe is crepitant throughout. The outer and posterior - two-thirds of the left lower lobe is riddled with cavities often - rounded and varying in diameter from 0.5 to 3 cm. but not - infrequently irregular in shape and in communication with adjacent - cavities (Fig. 25). In places cavities pass in a tortuous course - from pleura to the midpart of lung. The lining of these cavities is - usually smooth, but in places is covered by gray necrotic material. - Communication between the cavities and medium-sized bronchi is - occasionally found. The lung tissue between the cavities is in part - grayish red and consolidated, in part pink and air containing. The - right lung is edematous throughout; the bronchi in the lower part of - the right lung contain purulent fluid and are in places surrounded - by zones of hemorrhage. - - The spleen is very large (14 × 11 × 5 cm.) and firm. - - The spinal fluid is cloudy and blood vessels over the lumbar - enlargement and lower thoracic region are congested; in the upper - thoracic region the cord is covered by purulent exudate. - - Bacteriologic examination demonstrates the presence of hemolytic - streptococci in the blood of the heart; plates from the left lung - contain a few colonies of S. aureus and Pneumococcus IV; plates from - the right main bronchus contain S. aureus and a large bacillus which - does not stain by Gram’s method. Three plates from the spinal - meninges contain Pneumococcus IV. - -[Illustration: - - Fig. 25.—Advanced bronchiectasis throughout lower left lobe. Autopsy - 445. -] - - Microscopic examination shows that the cavities which have been - described are lined by very vascular connective tissue containing - many cells; there is no epithelial lining and the surface is in - places covered by fibrin. On the surface polynuclear leucocytes are - numerous, but immediately below, large mononuclear cells occur and - frequently contain one or several ingested polynuclear leucocytes. - None of the structures peculiar to the bronchi can be identified in - the wall of these cavities, and in many places it is evident that - lung tissue has undergone destruction, for in places the lining of - vascular connective tissue is interrupted and an extension of the - cavity penetrating into the lung substance is surrounded by alveoli - filled with fibrin; in contact with the cavity there is some - necrosis. - -The cavities communicate with the bronchi and are lined in part by -vascular connective tissue which may in part represent preexisting -bronchial walls, but no epithelium is present and the relation to the -bronchi cannot be established with certainty. These cavities have -extended by necrosis which has broken the vascular connective tissue of -their wall and penetrated into adjacent lung tissue. Death has been the -result of purulent meningitis caused by pneumococcus, and the histologic -changes in the walls of the cavities suggest that the activity of the -inflammatory reaction here is subsiding, for large mononuclear cells are -numerous and are ingesting polynuclear leucocytes. The changes described -would, if continued, result in the formation of cavities lined by -fibrous tissue and resembling many of those formed as the result of -dilatation of the bronchi. - -A study of the progress of the changes which result in the formation of -bronchiectatic cavities has shown how the inflammatory irritant within -the bronchus destroys the epithelium of the bronchus, penetrates into -the deeper tissues and produces fissures which extend through the entire -thickness of the bronchial wall at one or usually several places. These -longitudinal fissures, which at first often give a stellate outline in -cross section to the cavity of the affected bronchus, permit the -separation of the edges of the fissure, so that an increase in the -circumference occurs. The base of the fissure is formed by surrounding -alveolar tissue and its edges are the site of necrosis. Tears may extend -into the surrounding alveolar tissue, thus permitting further stretching -of the bronchial wall. The consequences of rupture of the small bronchi -into the adjacent alveoli are to some extent overcome by the -inflammatory reaction which plugs the adjacent alveoli with fibrin. - -Compression of the lungs by forced expiration, even though the glottis -were closed as in coughing, would not dilate the bronchi, because -pressure outside and within the bronchi would be equally elevated -(Thornton and Pratt[89]). The pressure within the bronchi does not -differ greatly from atmospheric pressure, whereas the negative pressure -within the pleural cavity may vary from approximately 6 mm. of mercury -during quiet inspiration to 30 mm. with forced inspiration. Excess of -pressure upon the inner surface of the bronchial walls will vary with -coughing and other respiratory efforts, between these limits depending -upon the readiness with which pressure is equalized within and without -the bronchi by penetration of air into the alveoli. The presence of -viscid mucopurulent fluid within bronchioles will obstruct these tubules -and retard the entrance of air into alveoli. - -Weakening of the bronchial wall by the changes which have been described -will cause lasting dilatation of the bronchi. Whatever increases -pressure within the bronchi will increase the tendency to dilatation; -the bronchi being filled with mucopurulent exudate dilatation usually -appears first at the bases of the lung, since gravity increases -intrabronchial pressure here. New formation of fibrous tissue within the -wall of the bronchus, thickening of adjacent alveolar walls, and -organization of fibrin reinforce the weakened bronchial wall and limit -the dilatation which follows injury to the wall. Regeneration of -epithelium covering the dilated tube will further obscure the early -changes which have made dilatation possible. The changes which weaken -the bronchial wall permit dilatation at a time when there is no new -formation of fibrous tissue. When the bronchial lesion has persisted -several weeks, chronic pneumonia is associated with it. It has been -suggested that the contraction of newly formed fibrous tissue within the -substance of the lung might cause bronchi to be enlarged by traction -upon their walls. Newly formed connective tissue is most abundant in the -wall of the bronchiectatic cavity, and here contraction would tend to -diminish the size of the cavity. - - - Unresolved Bronchopneumonia - -Chronic bronchopneumonia is characterized by changes similar to those -associated with chronic inflammation in other parts of the body, namely, -by thickening of the interstitial tissue of the lung, by accumulation of -mononuclear cells, by proliferation of fibrous tissue and by -organization of exuded fibrin. In a few instances these changes have -begun at the end of two weeks after onset of influenza, but they have -been little advanced until three weeks has elapsed; advanced chronic -inflammation has occurred after from four to eight weeks. Chronic -inflammation primarily affects those structures which are most severely -injured by the acute lesion and is most conspicuous in immediate -proximity to the small bronchi and bronchioles; the perivascular and -interlobular connective tissue are secondarily involved. Corresponding -to each of the lesions of the alveolar tissue which have been found with -bronchopneumonia, namely, peribronchiolar, hemorrhagic peribronchiolar, -lobular and peribronchial consolidation, there is a chronic lesion which -develops when pneumonia has failed to resolve. - -The term interstitial bronchopneumonia has been used by MacCallum to -designate a lesion which he has found in association with measles at -Fort Sam Houston. This name he states does not describe accurately the -early stage of the lesion, for its interstitial character is not evident -at first. In his monograph on “Epidemic Pneumonia in the Army Camp,” -published in 1919, MacCallum describes and pictures instances of the -lesion which we have designated interstitial suppurative pneumonia and -classifies them as interstitial bronchopneumonia. We have shown that -this lesion, which is the result of infection of the lymphatics with S. -hemolyticus, bears no necessary relation to the lesion which is -characterized in its early stage by peribronchiolar pneumonia and in its -later stages by chronic inflammation with mononuclear infiltration and -proliferation of the peribronchial, perivascular and interalveolar -tissue. At Fort Sam Houston, nearly every patient with measles was -infected with hemolytic streptococci; we observed, following influenza, -similar prevalence of hemolytic streptococci in certain wards in the -base hospital at Camp Pike. Among the cases at Fort Sam Houston there -were doubtless instances both of interstitial suppurative pneumonia -caused by hemolytic streptococcus and of chronic bronchopneumonia not -referable to this microorganism. - -Studying pneumonia following influenza at Camp Lee, Va., and later at -Camp Dix, N. J., during the fall of 1918, MacCallum reached the -conclusion that “interstitial bronchopneumonia” following influenza was -caused by B. influenzæ of Pfeiffer. This lesion attributed to B. -influenzæ differed from that previously referred to hemolytic -streptococcus in the following characters: the lymphatic channels in the -bronchial walls and widened interlobular septa are inconspicuous and -none are found distended with exudate; there is no intense infection of -the pleura, and polynuclear leucocytes are inconspicuous in the alveolar -exudate and in the walls of the bronchi. It seems probable these -differences are explained by the absence of hemolytic streptococci which -tend to invade lymphatics and produce severe inflammatory changes in the -pleura. - -=Chronic Bronchitis.=—The earliest changes in the bronchial wall with -bronchitis of influenza are hyperemia, leucocytic infiltration and -hemorrhage, and they may occur even though the lining epithelium remains -intact. Epithelium frequently undergoes partial or complete destruction, -and with this severe injury the influence of the inflammatory irritant -may extend directly through the wall of the bronchus, for in some -instances there is hemorrhage into all the alveoli in a zone encircling -the bronchus. Since these alveoli have only indirect communication with -the affected bronchus through alveolar tissue not involved in the -inflammatory process, it is evident that the surrounding hemorrhage is -secondary to the lesion of the bronchus. Fibrinous inflammation in other -instances, similarly localized in a zone of alveoli encircling a -bronchus, is doubtless the result of direct extension of the -inflammatory process through the bronchial wall. After the disease has -existed during two or three weeks inflammation is still active -immediately below the inner surface of the bronchus; here polynuclear -leucocytes are numerous whereas in the deeper parts of the mucosa and -about the muscularis leucocytes are scant but lymphoid and plasma cells -are very numerous. The severity of the inflammatory reaction may be -judged by the abundance and extent of this cellular reaction and is in -close relation to the intensity of the changes affecting the mucous -membrane of the bronchus. Infiltration of the entire bronchial wall with -lymphoid and plasma cells is almost invariable when the primary injury -to the bronchus has destroyed the epithelial lining, and this -infiltration is not limited to the bronchial wall but extends outward -into the contiguous alveolar septa which are thickened by it. The sheath -of the pulmonary artery which accompanies the bronchus exhibits a -similar change, and the alveolar septa, as a fringe about it, are -thickened and infiltrated with mononuclear cells. Interlobular septa -continuous with the bronchus often show some infiltration. - -A later phase in this series of changes is represented by new formation -of fibrous tissue. The bronchial walls and interalveolar septa are -thickened by proliferating fibrous tissue, young fibroblasts and newly -formed collagen fibrils being abundant (Fig. 28; also Fig. 30). This -increase of fibrous tissue is especially noteworthy immediately -surrounding the walls of the small bronchi, which are often considerably -dilated, and about the smaller of those bronchi which have cartilage; -with thickening of alveolar walls immediately adjacent to the bronchus -every stage in the obliteration of the alveoli may be found. Their walls -are thickened and their lumina are diminished in size and often -flattened in a direction concentric with the bronchus. Such atrophied -alveoli lined by cubical epithelial cells occurring within the thickened -peribronchial fibrous tissue give evidence that this tissue has replaced -alveoli. Alveoli surrounding and within the new fibrous tissue are -frequently filled with fibrin, and organization indicated by penetration -of fibroblasts and capillaries into the fibrin may be far advanced. -There is some increase of perivascular and interlobular tissue. The -bronchiectasis which is almost invariably found with unresolved -bronchopneumonia has been described. Squamous transformation of -epithelium (page 251) is frequently found in association with the -chronic bronchitis of unresolved pneumonia. - -=Organizing Bronchitis and Bronchiolitis.=—When the bronchial epithelium -is destroyed, fibrin is deposited upon the denuded surface and may -partly or completely fill the lumen of the bronchial tube. The plug of -fibrin is adherent to the underlying tissue wherever epithelium is lost -but is separated from the bronchial wall by a well-defined space where -epithelial lining is still intact. Fibroblasts promptly migrate from the -wall of the bronchiole into this fibrin, and fibroblasts, fixed during -ameboid movement, are irregularly elongated in a direction toward the -fibrin. - -Organization of fibrin occurs within the smallest bronchi (diameter 0.3 -to 0.5 mm.) or within respiratory bronchioles. It has been found in 8 -autopsies. In one instance it has been present eleven days after the -onset of influenza, but usually it is seen three or four weeks after -onset of symptoms of respiratory disease. In the early stages of the -lesion a plug of fibrin within the lumen of the bronchus or bronchiole -is invaded by fibroblasts, plasma cells and newly formed capillaries. -These capillaries have their origin in the wall of the tube and enter -the fibrin at points where in consequence of loss of epithelium fibrin -is continuous with the connective tissue. When the bronchiole is cut -longitudinally, partially or completely organized fibrin may be found -adherent at several places with intact epithelium, sometimes beautifully -ciliated, between the sites of attachment. The fibrin is finally -replaced completely and the lumen of the bronchiole contains a mass of -organized fibrous tissue in which young fibroblasts and plasma cells are -numerous. - -The lesion has been associated with chronic bronchopneumonia in 6 of 8 -instances. In Autopsy 445, p. 257, organizing bronchitis and -bronchiolitis occurred in the right lung unassociated with other chronic -lesion, although there was advanced bronchiectasis with fibrous -induration in the left lung. In Autopsy 499 (p. 224) organizing -bronchiolitis occurred in association with chronic changes which appear -to have followed interstitial suppurative pneumonia caused by S. -hemolyticus. Other severe lesions of the bronchi have accompanied -organizing bronchitis and bronchiolitis. Purulent bronchitis has been -present in 7 of 8 instances; bronchiectasis in 5 of 8 instances. - -The bacteriology of autopsies with organizing bronchitis and -bronchiolitis is shown in Table LIII. - -The bacteriology of these cases presents no constant feature. Invasion -of the blood by S. hemolyticus has been present in a large proportion of -cultures, namely, in 5 of 7 (71.4 per cent). In one of the 2 instances -in which hemolytic streptococci have been found, neither in the blood -nor lungs, Pneumococcus III has been found in the blood and S. viridans -in the lungs and bronchus; in the other, S. aureus has been found in the -lung and bronchus. Staphylococci have been found frequently in the -bronchi (60 per cent) and in the lungs (50 per cent). B. influenzæ has -been present in the bronchi in the usual proportion of instances (80 per -cent). The lesion has occurred in the presence of B. influenzæ combined -with streptococci or staphylococci. - - TABLE LIII - - ═══════════╤══════════════╤══════════════╤══════════════╤══════════════ - AUTOPSY │ DURATION OF │ BLOOD │ LUNGS │ BRONCHUS - │ ILLNESS │ │ │ - ───────────┼──────────────┼──────────────┼──────────────┼────────────── - 420 │11 days │S. hem. │S. hem., B. │ - │ │ │ inf., S. │ - │ │ │ aur. │ - 402 │14 days │Pneum. IV, │ │ - │ │ S.hem. │ │ - 370 │17 days │ │S. aur. │S. aur., - │ │ │ │ Pneum. IV, - │ │ │ │ B. inf. - 457 │17+ days │ │ │Pneum. IV, B. - │ │ │ │ inf. - 421 │19 days │S. hem. │Pneum. IV, S. │ - │ │ │ hem. │ - 445 │27 days │S. hem. │Pneum. IV, S. │S. aur. - │ │ │ aur. │ - 473 │28+ days │Pneum. III │S. vir. │B. inf., S. - │ │ │ │ vir., - │ │ │ │ staph., M. - │ │ │ │ catarr. - 499 │36 days │S. hem. │ │S. hem. B. - │ │ │ │ inf. - ───────────┴──────────────┴──────────────┴──────────────┴────────────── - -Thrombosis of lymphatics in the wall of bronchi adjacent to blood -vessels and in interlobular septa occurs, and occasionally organization -of the fibrinous plug within the lymphatic is in progress (Autopsies -283, 425 and 463). Fibroblasts and capillaries penetrate from the wall -of the lymphatic into a mass of hyaline fibrin which fills the lumen. - -=Unresolved Bronchopneumonia.=—The most common type of pneumonic lesion -following influenza is characterized by acute inflammation of the -alveoli immediately adjacent to the bronchioles and the lesion is -associated in many instances with hemorrhage or edema. If this lesion -persists unresolved during several weeks, evidences of chronic -inflammation are found. Peribronchial, perivascular and interlobular -connective tissue is thickened and richly infiltrated with lymphoid and -plasma cells, large mononuclear cells and many young fibroblasts. -Interalveolar septa adjacent to the walls of bronchi and between alveoli -surrounding inflamed bronchioles are implicated in the process. -Interstitial changes characterize the lesion only in its late stage. It -appears undesirable to give the name “interstitial pneumonia” to the -early stage of a lesion which begins and in most instances terminates as -an acute relatively superficial inflammation of the bronchi, bronchioles -and peribronchiolar alveoli. - -Chronic bronchopneumonia is often overlooked at autopsy because newly -formed connective tissue is not present in sufficient quantity to -attract attention (Fig. 26). When the lesion is advanced conspicuous -gray white patches of fibrous tissue may be seen about the bronchi -(Autopsy 487; Fig. 27) and interlobular septa may be obviously thickened -(Autopsy 472). The most distinctive feature of the lungs is the presence -of small, firm, gray or yellowish gray nodules of consolidation which -resemble miliary tubercles. They represent the peribronchiolar patches -of bronchopneumonia present during the acute stage and have assumed the -well-defined outline and firm consistence of tubercles because -polynuclear leucocytes and red blood corpuscles have in large part -disappeared, interstitial tissue is increased, and exudate is in process -of organization. These nodules are grouped in clusters about the small -bronchi. - -With unresolved bronchopneumonia the lungs are very voluminous and fail -to collapse after they are removed from the chest and in some instances -even after incision. The air containing tissue is usually dry. In our -autopsies the lungs have been pink in color and often free from coal -pigment, because those suffering with pneumonia have been in -considerable part men from rural districts. Thick mucopurulent material -exudes from the small bronchi which have been cut across; purulent -bronchitis has been present in 20 of 21 instances of chronic -bronchopneumonia. Bronchiectasis has been present in 13 instances; -dilatation is often advanced, so that throughout the lungs are found -bronchi with no cartilage distended to a diameter of 0.5 cm. In addition -to the firm peribronchiolar tubercle-like nodules of consolidation there -are scattered patches of gray lobular or confluent lobular -consolidation. Yellowish nodules, grouped about bronchi and resembling -those found elsewhere in air containing tissue, are occasionally seen -scattered upon the cut surface of a patch of gray, confluent lobular -consolidation (Autopsies 421, 423, 431). - -[Illustration: - - Fig. 26.—Unresolved bronchopneumonia with tubercle-like nodules of - peribronchiolar consolidation best seen in lower lobe; - bronchiectasis. Autopsy 425. -] - -Microscopic examination demonstrates the presence of those changes which -have been described in association with chronic bronchitis and -bronchiectasis. There is abundant new formation of fibrous tissue about -the bronchi of small and medium size, thickening of adjacent -interalveolar walls and incorporation of alveoli into the thickened -bronchial wall (Figs. 27, 28, 30, and 31). In half of the instances of -chronic bronchopneumonia there has been peribronchial fibrinous -pneumonia, and organization of fibrin within the alveoli is usually well -advanced. In one instance (Autopsy 487; Figs. 27 and 28) after an -illness of fifty-five days this process has resulted in the formation of -conspicuous patches of firm, grayish white fibrous tissue surrounding -dilated bronchi. Organization of fibrinous exudate within the lung has -not been limited to the alveoli but has occurred in the bronchioles as -well. Organizing bronchiolitis has been present in 5 instances -(Autopsies 370, 402, 457 and 473). - -Increase of fibrous tissue occurs about the blood vessels and in the -septa between the lobules, which are infiltrated with mononuclear -wandering cells and fibroblasts. Dilatation and thrombosis of the -lymphatic vessels have occurred in both situations, and in 3 instances -(Autopsies 283, 425 and 463) organization of these fibrinous thrombi has -occurred. - -[Illustration: - - Fig. 27.—Unresolved pneumonia with peribronchial formation of fibrous - tissue; bronchiectasis. Autopsy 487. -] - -[Illustration: - - Fig. 28.—Unresolved pneumonia with bronchiectasis showing new - formation of fibrous tissue about a greatly dilated bronchus of - which the epithelial lining has been lost. Autopsy 487. -] - -Thickening, cellular infiltration and fibrosis of the bronchial walls -with interstitial inflammation and fibrosis of immediately adjacent -alveolar septa are found about the ramifications of the bronchial tree -and may be followed to the smallest bronchi. When the respiratory -bronchioles are reached it will be found that the alveoli which stud -their walls are implicated in the change. The fibrin which they contain -is infiltrated with lymphoid and plasma cells, and with progress of the -lesion is invaded by fibroblasts and capillaries. Infiltration and -fibroid thickening extends from the bronchiolar wall to the alveolar -septa continuous with it (Fig. 31 with measles). Similar changes occur -about the alveolar ducts, and about the orifices of the tributary -infundibula (Fig. 32), peribronchiolar foci of acute inflammation having -assumed the characters of a chronic inflammatory process. Fibrin within -the alveoli contains round cells and fibroblasts. With thickening of -alveolar walls the alveolar lumina may be much diminished in size and -often persist as spaces lined by cubical cells. Polynuclear leucocytes -are usually numerous within the alveolar duct and in a few alveoli -immediately adjacent to it, but elsewhere throughout the focus of -inflammation round cells are predominant. The changes which have been -described correspond with the transformation of ill-defined, gray or -reddish gray spots of consolidation grouped about the terminal bronchi -into firm sharply defined grayish white nodules having the consistence -and appearance of miliary tubercles. - -One of the most constant characters of pneumonia following influenza is -its hemorrhagic character. In the earlier stages of pneumonia -phagocytosis of red blood corpuscles by large mononuclear cells is -frequently seen. In association with the chronic changes which have been -described, large mononuclear cells filled with brown pigment, doubtless -formed from red corpuscles, are often found within the alveoli. These -pigment containing cells are similar to those commonly associated with -chronic passive congestion of the lungs. - -In one instance (Autopsy 457) hemorrhagic peribronchiolar pneumonia has -been found in process of organization. The bronchioles and alveoli -adjacent to them contain polynuclear leucocytes, but intervening alveoli -almost uniformly contain blood and are the site of new formation of -connective tissue. Interalveolar septa are thickened and alveoli which -are lined by cubical epithelium are often diminished in size. In many -places fibroblasts have penetrated in considerable number into the blood -within the alveoli and occasionally newly formed capillaries are found -within them. - -Lobular patches of pneumonia are often found in process of organization -(Autopsies 370, 421, 423, 433, 463, 472 and 473). Microscopic -examination shows that whole lobules well defined by thickened septa are -the site of chronic interalveolar inflammation and intraalveolar -organization of exudate, whereas adjacent lobules are air containing and -relatively normal. In the earlier stages of the process fibrin present -within the alveoli is invaded by fibroblasts, mononuclear wandering -cells and blood vessels but in the later stages fibrin has disappeared; -the lumina of the alveoli are occupied by cellular fibrous tissue and in -places the thickened alveolar walls and intraalveolar fibrous tissue -have been fused to form wide patches of new tissue. - -With chronic bronchopneumonia confluent lobular consolidation -occasionally has a gray ground upon which are scattered small yellow -spots clustered about the small bronchi (Autopsies 421, 423 and 431). -Microscopic examination has shown that the yellowish spots correspond to -dilated bronchioles filled with purulent exudate and surrounded with -alveoli containing many polynuclear leucocytes. In the interstitial -tissue about the bronchiole and between adjacent alveoli plasma cells -are often present in great number. Between these spots of subacute -bronchiolar inflammation lung tissue is the site of interalveolar -proliferation of fibrous tissue and intraalveolar organization of -exudate. - -In all instances of chronic bronchopneumonia there has been -peribronchial pneumonia in a zone encircling small bronchi with no -cartilage and the smallest of the bronchi which have cartilage in their -wall; thickening of interalveolar septa, organization of peribronchial -fibrinous pneumonia and partial disappearance of alveoli have been -described. In the following autopsy peribronchial fibroid pneumonia has -been so advanced that conspicuous patches of gray white tissue -surrounding bronchi have replaced in some parts of the lung a -considerable part of the lung substance. - - =Autopsy 487.=—W. C., white, aged twenty-seven years, a farmer from - Mississippi had been in military service twenty-one days. Illness - began on September 17, fifty-five days before death, with chill, - fever, cough, backache, pain in the chest and coryza. The patient - was admitted two weeks after onset with the diagnosis of influenza. - Eight days later his sputum was blood tinged and there were signs of - bronchopneumonia. One month after admission the patient developed a - rash and a diagnosis of scarlet fever was made. - - =Anatomic Diagnosis.=—Chronic bronchopneumonia with peribronchial - fibroid induration; bronchiectasis; purulent bronchitis; abscesses - at the bases of both lungs; seropurulent pleurisy on the left side. - - The body is much emaciated. The left pleural cavity contains 650 - c.c. of opaque, dull yellow, thin, purulent fluid. The surface of - the left lung is covered in spots by white partially organized - fibrin. - - On section of the right lung (Fig. 27) the tissue is found in great - part air containing but there are numerous firm, gray patches, - irregular in shape and from 1 to 2 cm. across. In these spots the - tissue is tough and resembles fibrous tissue; within them are much - dilated bronchi. In the central part of the upper lobe is a group of - cavities with smooth wall, the largest of these cavities being 12 - mm. in diameter; immediately adjacent are dilated bronchi. Between - and surrounding these cavities is gray tissue, like that described - above. Below the outer surface of the upper lobe is an extensive - area 7 cm. from above downward, thickly studded with bronchiectatic - cavities, in the walls of which there is tough fibrous tissue. In - the middle lobe are several dilated bronchi, the largest of which is - 7 mm. in diameter, and elsewhere occur dilated bronchi with - thickened walls. At the base of the lung below the pleura are two - abscesses, which are yellow in the center and surrounded by - hemorrhagic tissue. At the posterior part of the lower lobe there - are numerous firm, nodular, yellowish spots grouped in clusters upon - a background of red, air containing tissue. The bronchi throughout - the lung contain mucopurulent fluid. - - In the left lung patches of fibrous tissue are more numerous than on - the right side and are irregular in shape, from 1 to 2 cm. across - and most abundant in the center of the upper lobe. This fibrous - tissue is in great part gray but in places it has a yellowish tinge. - The bronchi everywhere are moderately dilated. At the base of the - lung below the pleura is an abscess. - - The other organs show no noteworthy change. - - =Bacteriologic Examination.=—The fluid in the left pleura and right - main bronchus contain S. hemolyticus. B. influenzæ is found in the - right lung and right main bronchus. - - Microscopic examination shows that the patches of dense fibrous - tissue seen at autopsy almost invariably surround dilated bronchi - with no cartilage in their walls (Fig. 28) and with a diameter of - from 1 to 2 or more millimeters. These bronchi have lost their - epithelial lining; they contain polynuclear leucocytes, and their - wall in contact with the lumen is infiltrated to a varying distance - with the same cells. Their inner surface is very irregular, and - superficial necrosis occurs. The limits of the preexisting bronchial - wall is no longer recognizable in the dense surrounding fibrous - tissue richly infiltrated with lymphoid and plasma cells. In contact - with the bronchus, often in a wide zone, all traces of alveoli have - been destroyed, but further outward alveoli are represented by - spaces lined by cubical epithelium. At the periphery of the zone of - fibroid induration alveolar walls are much thickened and richly - infiltrated with mononuclear wandering cells; the lumina of the - alveoli contain plugs of organized fibrous tissue often covered by - flat or cubical epithelium. In the surrounding tissue a few small - bronchi are lined by columnar epithelium; there is scant new - formation of fibrous tissue but the alveolar walls are thickened and - infiltrated with cells. Epithelium of the larger bronchi with - cartilage in their walls is usually intact and there is about them - little peribronchial inflammation. - -Advanced induration about the bronchioles represents a late stage of -chronic peribronchiolar pneumonia. A bronchiole cut transversely is -found in the center of a focus of induration situated within relatively -normal air containing lung tissue. Next the bronchiole which in some -instances has wholly or partly lost its epithelium there is very -cellular fibrous tissue; further from the bronchiole alveoli are much -diminished in size, lined by flat or cubical epithelium and separated by -thick cellular walls. Plugs of cellular fibrous tissue sometimes fill -the alveolar duct. In favorable sections, cut in a plane which shows the -alveolar duct opening out into infundibula, it is found that newly -formed fibrous tissue surrounds the alveolar duct and extends into the -walls of its tributary alveoli; alveoli may be obliterated by this -fibrous tissue. Induration of alveolar walls is evident along the -proximal part of the infundibula which are readily demonstrable because -they are much dilated. (See Fig. 32.) The distal parts of the -infundibula are surrounded by alveoli with delicate walls. - -One bronchus retains along one side part of its epithelium which has -assumed a squamous form. In other places the wall has undergone necrosis -which at one spot extends deeply into the surrounding tissue. Necrotic -tissue in another part of the circumference is infiltrated with -polynuclear leucocytes and separated from the surrounding tissue by a -space filled with leucocytes. An abscess communicating with the bronchus -is thus formed. - -The foregoing instance is an example of the chronic fibroid pneumonias -with bronchiectasis which occur as sequelæ of the epidemic of influenza. -It is not improbable that a considerable number of those who suffer with -chronic bronchitis and bronchiectasis following influenza have less -extensive lesions similar to those which have been described. - -=Bacteriology of Unresolved Bronchopneumonia.=—Bacteria found in the -bronchi in 10 instances of chronic bronchopneumonia have been as -follows: - - BACTERIA IN BRONCHI WITH CHRONIC BRONCHOPNEUMONIA - - B. coli 1 - B. influenzæ and pneumococcus 1 - B. influenzæ and S. hemolyticus 2 - B. influenzæ and staphylococcus 1 - S. hemolyticus and B. coli 1 - B. influenzæ, pneumococcus and staphylococcus 3 - B. influenzæ, S. viridans and M. catarrhalis 1 - -Bacteria found in the lungs in 17 instances of chronic bronchopneumonia -were as follows: - - BACTERIA IN LUNGS WITH CHRONIC BRONCHOPNEUMONIA - - B. influenzæ 1 - Staphylococcus 1 - S. viridans 1 - B. influenzæ and pneumococcus 1 - B. influenzæ and S. hemolyticus 3 - B. influenzæ and staphylococcus 3 - Pneumococcus and S. hemolyticus 1 - S. hemolyticus and B. coli 2 - B. influenzæ, S. hemolyticus and staphylococcus 3 - No organism found 1 - -A noteworthy feature of these lists is the multiplicity of microorganism -found, namely, B. influenzæ, S. hemolyticus, pneumococcus, -staphylococcus, S. viridans, B. coli, and M. catarrhalis. More than one -microorganism is usually found in both bronchus and lung. In the one -instance (Autopsy 472) in which B. coli alone has been found in the -bronchus, B. coli and S. hemolyticus have been found in the lung and -hemolytic streptococcus in the blood; it is evident that B. coli alone -has not been responsible for the lesion. In one instance (Autopsy 487) -B. influenzæ alone has been found in the lung but hemolytic streptococci -have been found in the bronchus, pleura and blood of heart; with S. -aureus alone in the lung (Autopsy 370), S. aureus, Pneumococcus IV and -B. influenzæ have been found in the bronchus. With S. viridans alone in -the lung (Autopsy 473), Pneumococcus III has been found in the pleura -and in the blood of the heart and has doubtless had an important part in -the production of pneumonia; S. viridans, M. catarrhalis and B. -influenzæ have been found in the bronchus in this instance. - -No single microorganism is associated with the lesions but combinations -of B. influenzæ with hemolytic streptococci or staphylococci are common -(over 50 per cent). In Autopsy 422 B. influenzæ and Pneumococcus -atypical II have been present in the lungs. Among 10 instances in which -cultures have been obtained from the bronchus B. influenzæ is found 8 -times, and in the 2 instances in which it has not been identified B. -coli has been present. B. influenzæ has seldom been found (Table XXVII) -in the presence of B. coli, and it is not improbable that B. coli -outgrows and obscures the presence of B. influenzæ. - -Table LIV shows the per cent incidence of pneumococci, hemolytic -streptococci, staphylococci and B. influenzæ in the bronchus, lung and -heart’s blood with chronic bronchopneumonia and serves as an index of -the readiness with which each of these microorganisms passes from -bronchus to lung and from lung to the blood in this disease. - - TABLE LIV - - ═══════════╤══════════════╤══════════════╤══════════════╤══════════════ - │ PNEUMOCOCCUS │ HEMOLYTIC │STAPHYLOCOCCUS│ B. INFLUENZÆ - │ PER CENT │STREPTOCOCCUS │ PER CENT │ PER CENT - │ POSITIVE │ PER CENT │ POSITIVE │ POSITIVE - │ │ POSITIVE │ │ - ───────────┼──────────────┼──────────────┼──────────────┼────────────── - Bronchus │ 40.0│ 30.0│ 50.0│ 80.0 - Lung │ 12.5│ 56.2│ 37.5│ 68.7 - Blood │ 16.6│ 55.6│ 0│ 0 - ───────────┴──────────────┴──────────────┴──────────────┴────────────── - -Comparison of Table LIV with the analogous figures for acute -bronchopneumonia shows little noteworthy difference. Pneumococci are -less frequently found in the lung (12.5 per cent) and in the blood (16.6 -per cent) with chronic bronchopneumonia than with acute bronchopneumonia -(lung 43.9 per cent; blood, 40.3 per cent). Hemolytic streptococci and -staphylococci are not more frequently found with unresolved than with -acute bronchopneumonia and failure to resolve cannot be referred to -either or to both microorganisms, for bronchopneumonia not infrequently -remains unresolved in their absence. B. influenzæ is present in the -bronchi in at least 80 per cent of instances and perhaps in all; it is -usually combined both in the lungs and in the bronchi with one of the -pyogenic cocci. - -The severity of the injury to the walls of bronchi resulting in -continued infection with a variety of bacteria, appears to be the factor -determining failure of resolution and the persistence of -bronchopneumonia. - -=The Relation of Unresolved Bronchopneumonia to Interstitial Suppurative -Pneumonia Caused by Hemolytic Streptococci.=—Hemolytic streptococci have -been present in a considerable proportion of those who have had -unresolved bronchopneumonia and its occurrence in the bronchi, lung and -blood of the heart indicates that it has had an important part in -causing death. Unresolved bronchopneumonia, following measles, -designated by MacCallum “interstitial bronchopneumonia” in a series of -autopsies at Fort Sam Houston in the spring of 1918, was constantly -associated with hemolytic streptococci. Among the lesions described as -interstitial bronchopneumonia was at least one which was evidently what -we have designated interstitial suppurative pneumonia. Lymphangitis was -not infrequently found with “interstitial bronchopneumonia” following -measles. At Camp Lee and Camp Dix, following the epidemic of influenza, -MacCallum found “interstitial bronchopneumonia” with no hemolytic -streptococci and noted that lymphatics in the interstitial septa were -inconspicuous and that none was found distended with exudate; empyema -was not present. - -We have shown that interstitial suppurative pneumonia is an acute lesion -caused by hemolytic streptococci. Unresolved bronchopneumonia is -accompanied by chronic pneumonia and has no necessary relation to this -microorganism. - -In a foregoing section we have described instances of interstitial -suppurative pneumonia unaccompanied by chronic changes, and in the -present section we have described instances of unresolved -bronchopneumonia with no infection by hemolytic streptococci. We have -pointed out that the incidence of streptococcus infection with -unresolved bronchopneumonia does not materially differ from that with -acute bronchopneumonia even though the greater duration of the disease -gives more opportunity for infection. In some of the autopsies made by -MacCallum at Fort Sam Houston, lesions of streptococcus infection -doubtless coexisted with unresolved bronchopneumonia. - -In the 3 autopsies described below, interstitial suppurative pneumonia -with empyema caused by hemolytic streptococcus occurs in association -with unresolved bronchopneumonia. - - =Autopsy 420.=—J. E. S., white, aged thirty-two years, born in - England and resident of Los Angeles, Cal., had been in military - service one month. Onset of illness began on October 3, eleven days - before his death. He was admitted to the hospital on the following - day with the diagnosis of influenza and acute bronchitis. Pneumonia - believed to be lobar was recognized eight days after admission. - - =Anatomic Diagnosis.=—Unresolved bronchopneumonia with hemorrhagic - peribronchiolar consolidation in right lung; interstitial - suppurative pneumonia with consolidation in left upper lobe; - fibrinopurulent pleurisy; purulent bronchitis. - - The left pleural cavity contains 200 c.c. of turbid yellow fluid in - which are flakes of fibrin. In the inner and upper part of the left - upper lobe there is an area of consolidation where the tissue has a - cloudy, pinkish gray color and is finely granular on section. Here - the interstitial septa are distended by edema, so that they are in - places 0.5 c.c. across; in some spots they have a bright yellow - color. In the posterior parts of the middle and lower lobes there is - flabby consolidation where the tissue has a cloudy, red color with - scattered ill-defined yellow spots. - - Bacteriologic examination shows the presence of hemolytic - streptococci in the blood of the heart; hemolytic streptococci with - B. influenzæ and S. aureus in the left lung and S. hemolyticus with - S. aureus in the right lung. - - Microscopic examination shows that bronchi, bronchioles, alveolar - ducts and the greater part of the infundibula are filled with - polynuclear leucocytes, whereas the alveoli surrounding these - structures contain fibrin. The walls of the small bronchi are - thickened and contain mononuclear cells; the adjacent alveolar walls - are similarly infiltrated and thickened and the fibrin within them - is undergoing organization, being invaded by plasma cells, - fibroblasts and newly formed blood vessels. In some sections - interstitial septa are distended by edema and contain fibrin in - abundance; in places the tissue contains polynuclear leucocytes - closely packed together. There are lymphatics greatly distended by - polynuclear leucocytes with some fibrin, lymphocytes and red blood - corpuscles. - - =Autopsy 428.=—D. B., white, aged twenty-five, a farmer from - Oklahoma, had been in military service three weeks. Onset of illness - was on September 21, twenty-five days before death, with fever, - cough and mucopurulent expectoration. The patient was admitted with - the diagnosis of acute bilateral bronchitis. Four days later - bronchopneumonia was recognized, and subsequently there was otitis - media and empyema; 600 c.c. of thin, purulent fluid were aspirated - from the right chest three days before death. - - =Anatomic Diagnosis.=—Unresolved bronchopneumonia; suppuration of - interstitial tissue of upper right and lower left lobes; purulent - bronchitis; fibrinopurulent pleurisy; thoracotomy wound at the base - of the right chest; collapse of both lungs; serofibrinous - pericarditis. - - The left pleural cavity contains 550 c.c. of turbid seropurulent - fluid in which are numerous flakes of soft fibrin. The right pleural - cavity contains 150 c.c. of similar fluid. The mediastinum is - edematous. The pericardial cavity contains 50 c.c. of yellow fluid. - - The right lung is moderately collapsed. In the upper and lower lobes - are small patches of red, lobular consolidation. The upper third of - the upper lobe is laxly consolidated and near its inner surface the - interstitial septa are thickened to from 1 to 1.5 mm. in width, and - at intervals occur bead-like swellings from which creamy purulent - fluid exudes upon the cut surface. In the left lung small patches of - gray consolidation occur throughout the lower lobe and here the - interstitial septa are thickened, beaded and contain purulent fluid. - - Bacteriologic examination shows that the blood contains S. - hemolyticus; from the right lung and from the right main bronchus - hemolytic streptococci and B. influenzæ are grown. - - Microscopic examination shows that the epithelium of the bronchi has - undergone hypertrophy; the wall is infiltrated with lymphoid and - plasma cells and thickened by new formation of fibrous tissue; there - is similar thickening of adjacent alveolar septa and alveoli, often - lined by cubical cells, are diminished in size. Connective tissue - about the blood vessels and the interstitial septa are thickened and - infiltrated with mononuclear cells. In parts of the lung the - interstitial septa are edematous and contain polynuclear leucocytes, - in some places in great number. Lymphatics are greatly dilated and - filled with polynuclear leucocytes which in the center of some - lymphatics have undergone necrosis. In one place a small abscess is - in contact with a distended lymphatic. Lymphatics contain - Gram-staining cocci in pairs and short chains, present in immense - number where necrosis has occurred. - - =Autopsy 433.=—B. J., white, aged twenty-seven, from Arkansas, has - been in military service one month. Onset of illness was on - September 28, nineteen days before death, with cough and - expectoration. Pneumonic consolidation was recognized two days later - and 20 c.c. of cloudy fluid were aspirated from the left chest on - the same day. Hemolytic streptococci were found in a culture from - the throat nine days before death. - - =Anatomic Diagnosis.=—Unresolved bronchopneumonia with - peribronchiolar and confluent lobular consolidation; interstitial - suppuration of the right lower lobe; purulent bronchitis; - fibrinopurulent pleurisy. - - The right pleural cavity contains 700 c.c. of yellowish gray - purulent fluid containing flakes of fibrin. The left pleural cavity - contains seropurulent fluid localized over the external part of the - lung. - - The right lung is voluminous and free from consolidation save at the - lower and posterior part of the lower lobe where the tissue is deep - red and studded with firmer spots of yellow color clustered about - the bronchi. In places the interstitial septa are thickened and - yellow. Surrounding some of the bronchi near the apex of the left - lung are red patches of consolidation. - - Culture from heart’s blood remained sterile. S. hemolyticus was - grown from right pleural cavity, and S. hemolyticus and B. influenzæ - were grown from the right lung. Culture from the left lung contained - S. aureus and contaminating microorganisms. - - Microscopic examination shows the presence of peribronchiolar - patches of pneumonia in which there are few polynuclear leucocytes - and many lymphoid and plasma cells; the alveolar walls are thickened - and infiltrated with mononuclear cells. In some sections the tissue - is wholly consolidated and the site of advanced organizing - pneumonia. Interlobular septa and connective tissue about blood - vessels are thickened and cellular. Small bronchi have lost their - epithelial lining, their walls are thickened and there is - peribronchial organizing pneumonia. In some sections the lymphatics - are immensely dilated and distended with polynuclear leucocytes. - There is necrosis of the walls of the lymphatics and of the - polynuclear leucocytes within the lumen. - -In the discussion of acute bronchopneumonia it has been shown that S. -hemolyticus is not infrequently a secondary invader of a pneumonic -lesion perhaps caused by pneumococci. With progress of the disease -hemolytic streptococci persist. In the autopsies with unresolved -pneumonia just described, hemolytic streptococci have found their way -into the lymphatics and produced suppurative lymphangitis with -inflammation of the interstitial septa of the lung. - - - - - CHAPTER V - SECONDARY INFECTION IN THE WARD TREATMENT OF MEASLES - - JAMES C. SMALL, M.D. - - -A study of 979 cases of measles was made in the base hospitals of Camps -Funston and Pike from July to December, 1918, with the purpose of -establishing any existing relation between the prevalence of the -hemolytic streptococci and the incidence of the graver complications of -measles, especially the pneumonia following measles. The greater number -of these cases occurred at Camp Pike coincidently with the influenza -epidemic, so that the picture is modified during this period by a -summation of the after effects of the two diseases. - -The work undertaken includes: - -(a) Routine throat cultures on admission of all patients with measles. - -(b) Separation and treatment in separate wards of the patients harboring -hemolytic streptococci and those free from such streptococci. - -(c) Investigation of the bacteriology of all cases under treatment, by -weekly throat cultures during the period in the hospital. - -(d) Bacteriologic study of the complications of measles during life and -at autopsy. - -(e) Study of the throat bacteriology of men on duty in the camp, to -establish the prevalence of hemolytic streptococci and of B. influenzæ -in normal individuals. - -The work is further divided into that done at Camp Funston during the -latter part of July and throughout August, and that done at Camp Pike -during September, October, November and December, 1918. - -=Studies at Camp Funston.=—The work done at Camp Funston is limited -strictly to the identification of hemolytic streptococci in the throats -of all patients with measles coming into the base hospital at Ft. Riley -and to the same study of a group of normal men on duty. During the -period of study hemolytic streptococci were identified by throat culture -in about 1 in 5 of all the normal men examined. Two instances of otitis -media represent the only complications developing in the 112 cases of -measles. Cultures from both patients showed staphylococci. The entire -absence of streptococcus complications appears the more surprising in -view of the fact that the prevalence of hemolytic streptococci among -patients under treatment in the ward was for a time as great as that -among the normal men. No special hospital management was instituted on -the basis of the findings in throat culture. S. hemolyticus carriers -remained in the wards and were treated alongside the “clean” cases. The -sheet cubicle system was used for bed patients. Face masks were not -worn. Convalescent patients were not segregated, and they assisted in -the care of the bed patients and in the ward kitchen. After the initial -throat culture on admission, the throats were gargled with argyrol and -afterwards sprayed with the same solution three times a day. This -solution was also employed to relieve the discomfort caused by the -conjunctivitis during the acute stage of the disease. - -=Throat Culture and Identification of Hemolytic Streptococci.=—In -general the methods for the isolation and identification of hemolytic -streptococci as adopted by the Medical Department of the Army were used. -All organisms were isolated in pure culture, grown in broth, examined -microscopically and subjected to tests for hemolysis, (a 5 per cent -suspension of sheep corpuscles being employed), and for bile solubility. - -Beef infusion broth and beef infusion agar constituted the two basic -media used. They were prepared so that the finished product titrated -about 0.3 per cent acid to phenolphthalein. - -Broth tubes were carried to the bedside. In swabbing, the attempt was -made to produce gagging. This causes the tonsils to protrude from behind -the anterior pharyngeal pillars and places a slight tension on the -capsule which tends to squeeze material from the crypts. The surfaces of -the tonsils thus protruding toward the midline were brushed quickly with -a small cotton swab which was lastly touched to the posterior pharyngeal -wall and withdrawn so as to avoid touching any other parts. The swab was -immediately introduced into a tube of broth, twirled freely under the -surface of the liquid and discarded. The material thus washed into the -broth was carried to the laboratory and kept in the ice box until -plating, which was accomplished with as little delay as possible. - -Tubes of melted agar containing 12 c.c. cooled below 45° C., after -receiving 0.6 c.c. of sterile defibrinated horse blood, were inoculated -with a loopful of this broth. Thorough mixing and pouring into Petri -dishes (10 cm. diameter) followed. After cooling, a second loopful was -streaked over the surface of one half of the plate. Deep and superficial -planting were thus effected on the same plate. - -This method was found to be very useful. It can be used with advantage -provided one is not called upon to make a great number of cultures when -its time consuming factor is a great inconvenience. Another disadvantage -is the difficulty of picking single colonies for subculture. In spite of -the most careful selection and fishing of a deep colony, subcultures are -less likely to be pure than when surface colonies are chosen. By careful -regulation of the amount of agar in the tubes, the addition of a -measured amount of blood to each enabled one to pour standard blood agar -plates. Uniform thorough mixing of the blood is essential so that the -plate may present the desired “silky” rather than a “curdled” appearance -when viewed by transmitted light. - -The plates were incubated eighteen to twenty-four hours when subcultures -in broth were made from the hemolytic colonies. After growing these for -a similar period the additional tests were carried out as indicated -above. - -=Hemolytic Streptococci with Measles.=—The incidence of hemolytic -streptococci in the throats of patients with measles admitted to the -base hospital at Ft. Riley was found to be remarkably small. - - TABLE LV - - HEMOLYTIC STREPTOCOCCI WITH MEASLES IN ALL PATIENTS ADMITTED TO THE - WARDS AT CAMP FUNSTON - - ═══════════════╤════════╤═══════════╤════════╤════════════╤════════════ - │ │APPROXIMATE│ NO. OF │ NO. WITH │ PER CENT - │DAYS IN │ DAY OF │PATIENTS│ HEMOLYTIC │ WITH - │HOSPITAL│ DISEASE │CULTURED│STREPTOCOCCI│ HEMOLYTIC - │ │ │ │ │STREPTOCOCCI - ───────────────┼────────┼───────────┼────────┼────────────┼──────────── - First Culture │ 0 to 1│ 1 to 8│ 112│ 3│ 2.67 - Second Culture │ 3 to 10│ 4 to 16│ 86│ 11│ 12.79 - Third Culture │ 8 to 23│ 12 to 26│ 58│ 14│ 24.14 - ───────────────┴────────┴───────────┴────────┴────────────┴──────────── - - The first culture represents the findings on admission, in a series of - 112 cases; 86 patients being cultured twice; 58 patients three times. - -Of the 112 cases examined on admission only 3, or 2.67 per cent were -found to carry hemolytic streptococci. Those patients who were -recultured after from three to ten days in the hospital showed an -incidence of 12.8 per cent. A third culture including patients from -eight to twenty-three days in the hospital, showed an incidence of 24.1 -per cent. - -=Hemolytic Streptococci in the Throats of Normal Men.=—A total of 274 -throat cultures from normal men on duty at Camp Funston (Table LVI) -shows that 21.9 per cent carried hemolytic streptococci at a time when -there were few upper respiratory infections in the camp. A small group -of men resident in the hospital shows a slightly higher prevalence of -hemolytic streptococci (29.3 per cent). - -The figures in Table LVI are in sharp contrast with those for measles -patients on admission to the hospital. - - TABLE LVI - - INCIDENCE OF HEMOLYTIC STREPTOCOCCI, CAMP FUNSTON. - - ════════════════════════════════════╤════════╤════════════╤════════════ - │ │ │ PER CENT - │ │ HEMOLYTIC │ WITH - │ NUMBER │STREPTOCOCCI│ HEMOLYTIC - │EXAMINED│ PRESENT │STREPTOCOCCI - ────────────────────────────────────┼────────┼────────────┼──────────── - (_a_) White Men: │ │ │ - 70th Infantry │ 24│ 4│ 16.7 - 210th Engineers, Co. C │ 26│ 6│ 23.1 - 164th Depot Brigade, Co. 15 │ 50│ 10│ 20.0 - 164th Depot Brigade, Co. 18 │ 51│ 13│ 25.5 - 164th Depot Brigade, Co. 28 │ 50│ 13│ 26.0 - ────────────────────────────────────┼────────┼────────────┼──────────── - Total │ 201│ 46│ 22.9 - │ │ │ - (_b_) Colored Men, Detention Camp │ │ │ - No. 2: │ │ │ - 164th Depot Brigade, Prov. Co. 22 │ 25│ 6│ 24.0 - 3d Development Battalion, Co. A │ 24│ 3│ 12.5 - 3d Development Battalion, Co. D │ 24│ 5│ 20.8 - ────────────────────────────────────┼────────┼────────────┼──────────── - Total │ 73│ 14│ 19.2 - │ │ │ - (_c_) Men resident in the hospital: │ │ │ - Laboratory workers │ 10│ 3│ 30.0 - Patients in surgical ward │ 14│ 4│ 28.6 - ────────────────────────────────────┼────────┼────────────┼──────────── - Total │ 24│ 7│ 29.3 - ────────────────────────────────────┴────────┴────────────┴──────────── - -Two organizations from which normal men were chosen for examination -furnished a considerable number of cases of measles and offer data -(Table LVII, A and B) for further comparison. - - TABLE LVII - - A. HEMOLYTIC STREPTOCOCCI WITH MEASLES IN 164TH DEPOT BRIGADE, COMPANY - 28. - - ═══════════════════════════╤════════╤════════╤════════════╤════════════ - │ │ │ │ PER CENT - │ │ NO. OF │ NO. WITH │ WITH - │DAYS IN │PATIENTS│ HEMOLYTIC │ HEMOLYTIC - │HOSPITAL│CULTURED│STREPTOCOCCI│STREPTOCOCCI - ───────────────────────────┼────────┼────────┼────────────┼──────────── - First Culture │ 0 to 1│ 23│ 0│ 0 - Second Culture │ 3 to 9│ 23│ 4[90]│ 17.4 - Third Culture │10 to 21│ 21│ 4│ 19.05 - Normal men of Co. 28 │ │ 50│ 13│ 26.00 - ───────────────────────────┴────────┴────────┴────────────┴──────────── - - B. HEMOLYTIC STREPTOCOCCI WITH MEASLES IN SEVENTIETH INFANTRY - - ───────────────────────────┬────────┬────────┬────────────┬──────────── - First Culture │ 0 to 1│ 38│ 0│ 0 - Second Culture │ 5 to 9│ 25│ 1│ 4.0 - Third Culture │ 8 to 17│ 12│ 2│ 16.7 - Normal men on duty with │ │ │ │ - 70th Infantry │ │ 24│ 4│ 16.7 - ───────────────────────────┴────────┴────────┴────────────┴──────────── - -No one of the 61 cases of measles from the two organizations was found -to be positive on admission to the hospital. Yet among normal men in one -of these organizations the incidence of hemolytic streptococci was 26 -per cent and in the other, 16.7 per cent. In both organizations the -incidence among normal individuals compares closely with that of the -patients after a period in the measles wards of the hospital. - -=Discussion.=—Three features of the data collected at Camp Funston are -noteworthy. First, the small percentage of S. hemolyticus carriers among -the men admitted to the hospital with measles as compared with the -percentage found in normal men in the camp. Second, the increase in the -number of S. hemolyticus carriers among patients during their stay in -the hospital, the increase continuing until it approaches that of the -normal men on the outside. Third, the prevalence of hemolytic -streptococci in normal throats. - -In comparing men arriving at the hospital acutely ill with measles with -normal men in the organization from which they came, only one variable -can be found on which to base the differences observed in the two -groups. This is the advent of the acute disease. The figures seem to -suggest a temporary disappearance of hemolytic streptococci from the -throats of patients acutely ill with measles, at least, to such an -extent that the same cultural methods fail to identify the organisms. - -The increase in the S. hemolyticus carriers among patients with measles -after a period in the hospital might depend upon two factors: First, the -exposure to contact infections in the hospital ward, depending on the -length of time in the ward as well as on the character of the ward -management; second, the passing of the acute stage of measles with a -return of the bacterial flora of the throat to the condition existing -before the onset of the acute disease. The first appears the more -probable. The second has only the support of the observation that the -streptococci were absent from the throat during the acute stage of -measles or were much less frequently found in patients with measles than -in normal men and later their incidence approached that in normal -individuals. The rather high incidence of hemolytic streptococci in -normal men at Camp Funston may have been due to the very recent -assembling of the 10th Division which now occupied the camp. It is -probable that the housing of large numbers of men in barracks is -attended by the same contact dissemination of mouth organisms that -occurs in hospital wards. - -=Measles at Camp Pike.=—All cases of measles coming into the base -hospital at Camp Pike between September 15 and December 15, 1918, a -total of 867 cases, are included in the report. Upon the arrival of the -commission at Camp Pike early in September, a plan for the separation of -cases carrying hemolytic streptococci and those free from these -organisms was put into operation. The preliminary arrangements included -the allotment of suitable wards for treatment of the different classes -of cases; a throat culture survey of all patients with measles under -treatment at the time; their separation in accordance with the results -of bacteriologic examination, and the transfer of each group of patients -to its designated ward. By September 15 these preliminary arrangements -had been completed. Cases of measles admitted on this date and -afterwards were held in an observation ward pending the report upon a -throat culture before they were transferred to the treatment wards. - -Beginning September 15 the following system of handling measles cases -was maintained in the wards of the base hospital. - -All patients were received in an observation ward where they remained -until the results of a throat culture for hemolytic streptococci could -be reported back to the ward. Cases reported positive or negative were -immediately transferred to their respective treatment wards. All -patients in the treatment wards were cultured at intervals of one week -and cases found positive were transferred from the “clean” treatment -wards to a treatment ward for cases carrying hemolytic streptococci. The -ward personnel attending patients in the “clean” treatment wards was -examined by throat cultures from time to time with the purpose of -eliminating S. hemolyticus carriers. Patients segregated in the -streptococcus wards remained there, if uncomplicated, throughout their -hospital treatment even though subsequent repeated throat cultures -showed that the carrier condition had disappeared. Two wards were -provided to care for the pneumonia following measles. One received only -patients whose throat cultures were negative for hemolytic streptococci; -the other, those positive. It is essential that the throat culture on -which this differentiation is made be taken as soon as the complication -is reported and that transfer be made promptly on receipt of the report -of the culture. To facilitate this transfer, cases of pneumonia -complicating measles were reported to the laboratory as soon as -diagnosed and cultures were taken at once. The case remained in the -measles ward during twenty-four hours, isolated as well as possible, -awaiting report of culture before transfer. Within the positive ward for -measles pneumonias, distinction was made between streptococcus -pneumonias and nonstreptococcus pneumonias harboring hemolytic -streptococci in their throats. The two classes of cases were treated in -separate sections of the ward. - -Ear complications were seen and treated by medical officers from the -otological service. These patients remained in the measles wards while -in the acute stage of measles, but later were transferred to the service -of otology whenever further surgical treatment became necessary. - -Within the individual wards for treatment of measles and measles -pneumonias, precautions for minimizing the dangers of contact infections -were carried out as well as possible. Throughout the study we had the -hearty cooperation of the base hospital authorities and earnest, -well-directed effort to perfect ward management on the part of the ward -surgeons and their staffs. Difficulties encountered during the emergency -created by the sudden explosion of the influenza epidemic, in spite of -the best efforts of all, did much to disrupt the plan which had been -instituted for the control and study of the complications of measles. -Scarcely had wards been designated and all measles patients on hand -differentially allotted to them, when the influenza epidemic appeared -and quickly filled the hospital beyond its capacity. Measles wards were -taken over for the care of influenza patients. Measles patients, of -which there were not a great number at the time, were necessarily -crowded together, so that compartments of wards instead of separate -wards had to be used in maintaining our separation of the two groups of -patients. While the base hospital was yet filled with patients with -influenza and influenza pneumonia, admission of patients with measles -increased, so that one ward after another was reclaimed for the care of -this disease. During this period the measles wards were at times -overcrowded and the strictest ward technic could not be practiced. Again -new wards were, on occasions, partly filled by admission and transfer -before they were properly equipped to receive patients. This -disorganization was directly due to the necessity of treating a rapidly -increasing number of measles patients before the hospital was cleared of -patients with influenza and pneumonia. After this emergency, the system -of ward management was rapidly readjusted, and admissions were limited -to the normal capacities of the wards. - -The cubicle system was used in all wards. Bed patients were not required -to wear masks, but the mask was strictly enforced upon all patients -leaving the cubicle. All attendants were required to wear gowns, caps -and masks while in the wards. An attempt was made to prevent the -congregating of convalescents. Guards were posted at the latrine doors -to limit admission to the capacity of the latrine. Borrowing and lending -of any materials between patients were strictly forbidden. Paper sputum -cups were provided, kept clean and covered. In the measles pneumonia -wards hand disinfectant solutions were provided for use by attendants -when they passed from one patient to another. The ward floors were -scrubbed at intervals with lysol in water. Dry sweeping of the wards in -the morning is regrettable. - -=Bacteriologic Methods Used in the Study.=—The methods used for the -identification of hemolytic streptococci here were essentially the same -as those used at Camp Funston and described above, the one exception -being the use of surface cultures on blood agar instead of the combined -surface and deep culture. Blood agar plates containing 5 per cent -defibrinated horse blood were poured and used while fresh. The throat -swabs were carried to the laboratory in sterile test tubes. The plates -were inoculated by touching the swab lightly to the surface of the agar -plate at two places, one near either extremity of a given diameter of -the plate. On touching the swab to the agar, the swab stick was rolled -between the fingers so as to turn it through one revolution and thereby -bring all points of the circumference of the cotton swab in contact with -the agar surface. - -The material thus inoculated on the plates was spread by means of a -platinum wire slightly turned over at the end in “hockey stick” fashion. -The wire was passed back and forth several times over the point of -inoculation and then multiple streaks and cross streaks were made over -the agar surface. The initial contact of the wire with the point of -inoculation was not repeated. The cross streaking serves to spread and -distribute this material evenly over the surface. Well seeded plates by -this multiple streak method are the rule and the uniform distribution of -well separated colonies over the surface makes it very easy to pick pure -cultures, and renders plate reading easy. - -Very early in the course of our study of throat cultures at Camp Pike, -the great frequency of abundant growths of B. influenzæ was observed. -Consequently, the throat cultures of all measles patients examined from -September 15 to October 20 were studied for the identification of B. -influenzæ. In all cases identification was based on the cultural, -staining and morphologic characteristics. Tests for growth on hemoglobin -free media were not made as a routine. - -=Relation of Measles and Pneumonia Following Measles to the Influenza -Epidemic.=—The influenza epidemic at Camp Pike was recognized on -September 23 because of an alarming increase of hospital admissions. It -ran its brief course, and ten days later, October 3, the decline began. -The first four days of October rank highest in admissions of patients -with pneumonia following influenza. The onset of 20 scattered cases of -measles occurred before September 25, and later the number slowly -increased reaching its height about the middle of October; after this -time a gradual decline began, and continued during about three weeks -before the preepidemic level was reached. During this period of six -weeks following September 25, 709 cases of measles occurred. - - TABLE LVIII - - ONSET OF MEASLES AND OF PNEUMONIA FOLLOWING MEASLES BY WEEKS FROM - SEPTEMBER 11 TO DECEMBER 11, 1918 - - ═══════════════════════╤═══════════════════════╤═══════════════════════ - DATES │ MEASLES │ PNEUMONIA FOLLOWING - │ │ MEASLES - ───────────────────────┼───────────────────────┼─────────────────────── - Sept. 11 to 17 │ 18│ 0 - Sept. 18 to 24 │ 20│ 0 - Sept. 25 to Oct. 1 │ 74│ 0 - Oct. 2 to 8 │ 143│ 13 - Oct. 9 to 15 │ 178│ 9 - Oct. 16 to 22 │ 158│ 16 - Oct. 28 to 29 │ 100│ 6 - Oct. 30 to Nov. 5 │ 56│ 3 - Nov. 6 to 12 │ 38│ 4 - Nov. 13 to 19 │ 23│ 1 - Nov. 20 to 26 │ 29│ 1 - Nov. 27 to Dec. 3 │ 22│ 1 - Dec. 4 to 10 │ 8│ 1 - Dec. 11 │ 0│ 1 - ───────────────────────┴───────────────────────┴─────────────────────── - -Pneumonia following measles began to appear on October 5, and within the -week following 16 cases occurred. An equal number of cases appeared each -week during about three weeks and fewer scattered cases occurred -throughout November and December. Table LVIII shows date of onset of -measles and measles pneumonia cases. - -Chart 3 presents the occurrence of measles and of the pneumonia -following measles by weeks of onset compared with that of epidemic -influenza. - -[Illustration: - - Chart 3.—Shows the relation of the epidemic of measles to that of - influenza at Camp Pike, and the relations of the pneumonia following - measles to both measles and influenza. The large incomplete curve - represents influenza; the intermediate curve, measles; the small - curve, pneumonia following measles. -] - -It will be noted from the overlapping of the two curves in Chart 3 that -a considerable portion of the measles cases appeared before the -influenza had subsided in Camp Pike. This occurrence of the two -epidemics at the same time makes it impossible to separate the parts -played by each disease in producing the pneumonias and other -complications following measles. Analysis of the chart, however, shows -that the pneumonia with measles occurred in large part during the first -half of the measles epidemic. This is of particular significance since -it was during this period that the effects of the influenza wave were -felt most severely. - -In Table LIX the cases of measles are grouped into fifteen day periods -according to their dates of onset and the pneumonias arising from each -group are tabulated. This tabulation shows very clearly that the -pneumonia complications developed in large part in patients with measles -entering the hospital during the influenza period, that is, late in -September and during the first half of October. - - TABLE LIX - - PATIENTS WITH MEASLES AND WITH SUBSEQUENT PNEUMONIA - - ═════════════════╤═════════════════╤═════════════════╤═════════════════ - DATES │ TOTAL CASES OF │ TOTAL CASES │ OF PER CENT - │ MEASLES DURING │ PNEUMONIA FROM │ INCIDENCE OF - │ INTERVALS OF 15 │ SAME │ PNEUMONIAS - │ DAYS │ │ - ─────────────────┼────────┬────────┼────────┬────────┼────────┬──────── - Sept. 11 to 30 │ 86│ 433│ 14│ 42│ 16.28│ 9.7% - Oct. 1 to 15 │ 347│ „ │ 28│ „ │ 8.07│ „ - ─────────────────┼────────┼────────┼────────┼────────┼────────┼──────── - Oct. 16 to 31 │ 270│ 434│ 8│ 14│ 2.96│ 3.2% - Nov. 1 to 15 │ 91│ „ │ 2│ „ │ 2.2│ „ - Nov. 16 to 30 │ 56│ „ │ 4│ „ │ 7.15│ „ - Dec. 1 to 15 │ 17│ „ │ 0│ „ │ - ─────────────────┴────────┴────────┴────────┴────────┴───────────────── - -The high incidence of pneumonia among measles patients coming into the -hospital prior to, with, or immediately following the height of the -influenza epidemic is very striking. It so happens that half of the -total number of measles cases considered, date their onsets prior to -October 15. From the 433 cases included in this first half, 42 cases of -pneumonia arose, while from the 434 cases arising during the two months -following October 15, only 14 or one-third as many cases of pneumonia -developed. These figures very strongly suggest that influenza played a -large part in the production of the pneumonia with measles in this group -of cases. - -Again the 9.7 per cent incidence of pneumonia in the first half of cases -considered, approaches the 12 per cent incidence of pneumonia following -influenza observed in the epidemic at Camp Pike, while the incidence of -3.2 per cent in the second half of the cases conforms more nearly to -figures for pneumonia following measles in the army prior to the -pandemic of influenza. - -It has been shown that the prevalence of B. influenzæ at Camp Pike -increased with the passing of the wave of influenza (p. 40) and that -this increase applied to the measles admissions. For a time the -separation of measles patients carrying B. influenzæ as identified by -throat culture on admission, from those free from it, was practiced. All -cases were then followed up by weekly throat cultures, and cases in -negative wards on being identified as positives were transferred. - -This practice was discontinued as impractical when it became apparent -that about 80 per cent of patients with measles would be found positive -for B. influenzæ when repeated throat cultures were made during their -hospital treatment. The dissemination of B. influenzæ through the wards -from which we were attempting to exclude it took place much faster than -we could follow its spread by cultural methods. When this became -evident, the practice of separating the two groups of patients with -reference to B. influenzæ was discontinued and the great inconvenience -of repeated transfer of patients was largely eliminated. - -Table LX gives the findings in 426 cases of measles cultured for B. -influenzæ during the period when the practice of separating measles -patients carrying B. influenzæ from those not carrying the organisms was -followed. - - TABLE LX - - RESULTS OF REPEATED THROAT CULTURES FOR B. INFLUENZÆ ON 426 CASES OF - MEASLES, CAMP PIKE, SEPT. 15 TO OCT. 20, 1918. - - ═══════════╤════════╤═════════╤═════════════════════════════════════ - │ │ │ - │ │ │ - │ │GROUP NO.│ - │ TOTAL │NEGATIVE │ - GROUPS │ NUMBER │ FOR B. │ RESULTS OF CULTURES TO DATE - │CULTURED│INFLUENZÆ│ - │IN GROUP│ ON │ - │ │ADMISSION│ - │ │ │ - │ │ │ - ───────────┼────────┼─────────┼───────┬───────┬───────┬───────┬───── - │ │ │ │ │ │ │ NO. - „ │ „ │ „ │ 1ST │ 2ND │ 3RD │ 4TH │ IN - │ │ │CULTURE│CULTURE│CULTURE│CULTURE│EACH - │ │ │ │ │ │ │CLASS - ───────────┼────────┼─────────┼───────┼───────┼───────┼───────┼───── - I │ │ │ │ │ │ │ - 1st culture│ │ │ │ │ │ │ - on │ 426│ ——│ − │ │ │ │ 274 - admission│ │ │ │ │ │ │ - „ │ „ │ „ │ + │ │ │ │ 152 - ───────────┼────────┼─────────┼───────┼───────┼───────┼───────┼───── - II │ │ │ │ │ │ │ - 1st and 2nd│ │ │ │ │ │ │ - culture, │ │ │ │ │ │ │ - after one│ 201│ 143│ − │ − │ │ │ 75 - week in │ │ │ │ │ │ │ - hospital │ │ │ │ │ │ │ - „ │ „ │ „ │ − │ + │ │ │ 68 - „ │ „ │ „ │ + │ + │ │ │ 29 - „ │ „ │ „ │ + │ − │ │ │ 29 - ───────────┼────────┼─────────┼───────┼───────┼───────┼───────┼───── - III │ │ │ │ │ │ │ - 1st, 2nd │ │ │ │ │ │ │ - and 3rd │ │ │ │ │ │ │ - cultures │ 94│ 69│ − │ − │ − │ │ 22 - after two│ │ │ │ │ │ │ - weeks in │ │ │ │ │ │ │ - hospital │ │ │ │ │ │ │ - „ │ „ │ „ │ − │ − │ + │ │ 18 - „ │ „ │ „ │ − │ + │ − │ │ 13 - „ │ „ │ „ │ − │ + │ + │ │ 16 - „ │ „ │ „ │ + │ + │ + │ │ 8 - „ │ „ │ „ │ + │ − │ + │ │ 6 - „ │ „ │ „ │ + │ + │ − │ │ 4 - „ │ „ │ „ │ + │ − │ − │ │ 7 - ───────────┼────────┼─────────┼───────┼───────┼───────┼───────┼───── - IV │ │ │ │ │ │ │ - 1st, 2nd, │ │ │ │ │ │ │ - 3rd and │ │ │ │ │ │ │ - 4th │ │ │ │ │ │ │ - cultures │ 25│ 19│ − │ − │ − │ − │ 4 - after │ │ │ │ │ │ │ - three │ │ │ │ │ │ │ - weeks in │ │ │ │ │ │ │ - hospital │ │ │ │ │ │ │ - „ │ „ │ „ │ − │ − │ − │ + │ 3 - „ │ „ │ „ │ − │ − │ + │ + │ 3 - „ │ „ │ „ │ − │ − │ + │ − │ 2 - „ │ „ │ „ │ − │ + │ + │ + │ 2 - „ │ „ │ „ │ − │ + │ − │ + │ 2 - „ │ „ │ „ │ − │ + │ + │ − │ 2 - „ │ „ │ „ │ − │ + │ − │ − │ 1 - „ │ „ │ „ │ + │ + │ + │ + │ 2 - „ │ „ │ „ │ + │ − │ − │ + │ 1 - „ │ „ │ „ │ + │ − │ + │ + │ 1 - „ │ „ │ „ │ + │ + │ + │ − │ 1 - „ │ „ │ „ │ + │ − │ − │ − │ 1 - ───────────┴────────┴─────────┴───────┴───────┴───────┴───────┴───── - - ═══════════╤════════╤══════════╤════════╤═════════ - │ │ GROUP OF │ │GROUP PER - │ │POSITIVES │ │ CENT OF - │ GROUP │DEVELOPING│PER CENT│POSITIVES - │ NO. │TO DATE IN│OF GROUP│ TO DATE - GROUPS │POSITIVE│ CASES │POSITIVE│ AMONG - │ FOR B. │ NEGATIVE │ FOR B. │ CASES - │INF. TO │ FOR B. │INF. TO │NEGATIVE - │ DATE │ INF. ON │ DATE │ FOR B. - │ │ADMISSION │ │ INF. ON - │ │ │ │ADMISSION - ───────────┼────────┼──────────┼────────┼───────── - │ │ │ │ - „ │ „ │ „ │ „ │ „ - │ │ │ │ - │ │ │ │ - ───────────┼────────┼──────────┼────────┼───────── - I │ │ │ │ - 1st culture│ │ │ │ - on │ 152│ ————│ 35.6│ ———— - admission│ │ │ │ - „ │ „ │ „ │ „ │ „ - ───────────┼────────┼──────────┼────────┼───────── - II │ │ │ │ - 1st and 2nd│ │ │ │ - culture, │ │ │ │ - after one│ 126│ 68│ 62.7│ 47.5 - week in │ │ │ │ - hospital │ │ │ │ - „ │ „ │ „ │ „ │ „ - „ │ „ │ „ │ „ │ „ - „ │ „ │ „ │ „ │ „ - ───────────┼────────┼──────────┼────────┼───────── - III │ │ │ │ - 1st, 2nd │ │ │ │ - and 3rd │ │ │ │ - cultures │ 72│ 47│ 77.7│ 68.1 - after two│ │ │ │ - weeks in │ │ │ │ - hospital │ │ │ │ - „ │ „ │ „ │ „ │ „ - „ │ „ │ „ │ „ │ „ - „ │ „ │ „ │ „ │ „ - „ │ „ │ „ │ „ │ „ - „ │ „ │ „ │ „ │ „ - „ │ „ │ „ │ „ │ „ - „ │ „ │ „ │ „ │ „ - ───────────┼────────┼──────────┼────────┼───────── - IV │ │ │ │ - 1st, 2nd, │ │ │ │ - 3rd and │ │ │ │ - 4th │ │ │ │ - cultures │ 21│ 15│ 84│ 79. - after │ │ │ │ - three │ │ │ │ - weeks in │ │ │ │ - hospital │ │ │ │ - „ │ „ │ „ │ „ │ „ - „ │ „ │ „ │ „ │ „ - „ │ „ │ „ │ „ │ „ - „ │ „ │ „ │ „ │ „ - „ │ „ │ „ │ „ │ „ - „ │ „ │ „ │ „ │ „ - „ │ „ │ „ │ „ │ „ - „ │ „ │ „ │ „ │ „ - „ │ „ │ „ │ „ │ „ - „ │ „ │ „ │ „ │ „ - „ │ „ │ „ │ „ │ „ - „ │ „ │ „ │ „ │ „ - ───────────┴────────┴──────────┴────────┴───────── - -On admission 35.6 per cent of the patients were found positive for B. -influenzæ. Repeated throat cultures were not confined to those appearing -negative on this initial culture, but were made on all patients without -regard to their being previously positive or negative. By a summation of -the results of the weekly cultures of all patients, the percentage of -patients carrying B. influenzæ rises from 35.6 per cent on admission, to -62.7 per cent after one week; to 77.7 per cent after two weeks; to 84 -per cent after three weeks in the hospital. - -To gain some idea of the rate of spread of B. influenzæ in wards -receiving only patients whose throat cultures were negative for B. -influenzæ on admission, a similar summation of the results of repeated -throat cultures on patients in negative wards shows weekly increases -from 47.5 per cent after one week, to 68.1 per cent after two weeks; to -79 per cent at the end of three weeks. - -These results demonstrate quite clearly that the measles wards were -saturated with B. influenzæ during the period of the influenza epidemic. -Conditions within the measles wards with regard to B. influenzæ were not -at all different from those in the camp community during this period. -While no clinical methods could be relied upon to diagnose influenza in -the presence of an acute attack of measles, there is every reason to -believe that the occurrence of clinical influenza with measles was no -less frequent than was its incidence in the camp at large, that is, -about 20 to 25 per cent. That influenza played a large part in -determining predisposition to the complications of measles in this -series seems evident. - - - Hemolytic Streptococci with Measles at Camp Pike - -Between September 15 and December 15, 1918, 867 cases of measles, -admitted to the wards of the base hospital, were studied and handled -according to the system outlined above. About one half of these cases -appeared during the first month of the study. During this month -hemolytic streptococci played a very insignificant rôle. This -microorganism did not appear with alarming prevalence until after the -wards had been thoroughly overcrowded. After the emergency, when better -ward conditions were provided, S. hemolyticus carriers continued to -develop in the wards and were removed when identified. The first S. -hemolyticus carriers to develop in the wards were identified on October -8. The first case of streptococcus pneumonia developed on October 17, -while streptococcus otitis as a complication of measles did not begin -until a little later. During the latter two months of the study, S. -hemolyticus became rampant in the wards. The streptococcus complications -date their onset at some time during these two months. - -Table LXI shows the number of admissions to the measles wards by weeks -and the patients among them found to be carrying hemolytic streptococci. -It also shows the number of S. hemolyticus carriers developing each week -among patients under treatment in the “clean” wards, as identified by -throat cultures repeated at weekly intervals. For purposes of -orientation, the number of cases developing streptococcus pneumonia and -otitis media with its subsequent mastoiditis are given for each week -during the period of observation. - -An admission to the measles ward can generally be regarded as an acute -case of measles. There are a few exceptions to this statement and these -are cases of measles treated in barracks and afterwards transferred to -the base hospital. A relatively small number of such cases furnished 16 -of the cases positive for hemolytic streptococci on admission to the -measles ward. - - TABLE LXI - - S. HEMOLYTICUS CARRIERS IDENTIFIED BY THROAT CULTURE AMONG ADMISSIONS; THOSE - DEVELOPING AMONG PATIENTS UNDER TREATMENT IN THE STREPTOCOCCUS “CLEAN” - MEASLES WARDS; S. HEMOLYTICUS COMPLICATIONS ACCORDING TO THEIR DATES OF ONSET - - ════════╤══════════════════════╤══════════════════════╤══════════════════════ - GROUPING│ │HEMOLYTIC STREPTOCOCCI│ PRINCIPAL - OF CASES│ ADMISSION CASES │ HOSPITAL CASES │ COMPLICATIONS DUE TO - BY WEEKS│ │ DEVELOPING │ HEM. STREP. - ────────┼────────┬──────┬──────┼────────┬──────┬──────┼──────┬──────┬──────── - „ │ │ NO. │ PER │ │ NO. │ PER │ │ │ - │ NO. │ POS. │ CENT │ NO. │ POS. │ CENT │ │ │MASTOID- - │ CASES │ HEM. │ POS. │ CASES │ HEM. │ POS. │PNEUM.│OTITIS│ ITIS - │CULTURED│STREP.│ HEM. │CULTURED│STREP.│ HEM. │ │ │ - │ │ │STREP.│ │ │STREP.│ │ │ - ────────┼────┬───┼───┬──┼──────┼────────┼──────┼──────┼──────┼──────┼──────── - Sept. 15│ │ │ │ │ │ │ │ │ │ │ - to │ 23│252│ 1│ 3│ 1.2│ 0│ 0│ 0│ 0│ 0│ 0 - Sept. │ │ │ │ │ │ │ │ │ │ │ - 21 │ │ │ │ │ │ │ │ │ │ │ - Sept. 22│ │ │ │ │ │ │ │ │ │ │ - to │ 25│ „ │ 1│„ │ „ │ 23│ 0│ 0│ 0│ 0│ 0 - Sept. │ │ │ │ │ │ │ │ │ │ │ - 29 │ │ │ │ │ │ │ │ │ │ │ - Sept. 30│ │ │ │ │ │ │ │ │ │ │ - to │ 95│ „ │ 0│„ │ „ │ 24│ 0│ 0│ [91]1│ 0│ 0 - Oct. 6│ │ │ │ │ │ │ │ │ │ │ - Oct. 7 │ │ │ │ │ │ │ │ │ │ │ - to │ 109│ „ │ 1│„ │ „ │ 121│ 4│ 3.3│ 0│ 0│ 0 - Oct. │ │ │ │ │ │ │ │ │ │ │ - 13 │ │ │ │ │ │ │ │ │ │ │ - ────────┼────┼───┼───┼──┼──────┼────────┼──────┼──────┼──────┼──────┼──────── - Oct. 14 │ │ │ │ │ │ │ │ │ │ │ - to │ 223│494│ 7│19│ 3.8│ 175│ 8│ 4.6│ 1│ 0│ 0 - Oct. │ │ │ │ │ │ │ │ │ │ │ - 20 │ │ │ │ │ │ │ │ │ │ │ - Oct. 21 │ │ │ │ │ │ │ │ │ │ │ - to │ 156│ „ │ 5│„ │ „ │ 451│ 35│ 7.7│ 2│ 3│ 0 - Oct. │ │ │ │ │ │ │ │ │ │ │ - 27 │ │ │ │ │ │ │ │ │ │ │ - Oct. 28 │ │ │ │ │ │ │ │ │ │ │ - to │ 71│ „ │ 6│„ │ „ │ 333│ 29│ 8.7│ 1│ 12│ 1 - Nov. 3│ │ │ │ │ │ │ │ │ │ │ - Nov. 4 │ │ │ │ │ │ │ │ │ │ │ - to │ 44│ „ │ 1│„ │ „ │ 263│ 45│ 17.1│ 3│ 8│ 11 - Nov. │ │ │ │ │ │ │ │ │ │ │ - 10 │ │ │ │ │ │ │ │ │ │ │ - ────────┼────┼───┼───┼──┼──────┼────────┼──────┼──────┼──────┼──────┼──────── - Nov. 11 │ │ │ │ │ │ │ │ │ │ │ - to │ 31│117│ 4│13│ 11.1│ 149│ 46│ 30.8│ 0│ 5│ 5 - Nov. │ │ │ │ │ │ │ │ │ │ │ - 17 │ │ │ │ │ │ │ │ │ │ │ - Nov. 18 │ │ │ │ │ │ │ │ │ │ │ - to │ 41│ „ │ 4│„ │ „ │ 93│ 7│ 7.5│ 0│ 2│ 2 - Nov. │ │ │ │ │ │ │ │ │ │ │ - 24 │ │ │ │ │ │ │ │ │ │ │ - Nov. 25 │ │ │ │ │ │ │ │ │ │ │ - to │ 19│ „ │ 0│„ │ „ │ 48│ 7│ 14.6│ 0│ 3│ 2 - Dec. 1│ │ │ │ │ │ │ │ │ │ │ - Dec. 2 │ │ │ │ │ │ │ │ │ │ │ - to │ 26│ „ │ 5│„ │ „ │ 52│ 12│ 23.1│ 0│ 3│ 0 - Dec. 8│ │ │ │ │ │ │ │ │ │ │ - ────────┼────┼───┼───┼──┼──────┼────────┼──────┼──────┼──────┼──────┼──────── - Dec. 9 │ │ │ │ │ │ │ │ │ │ │ - to │ 4│ │ 2│ │ │ 47│ 12│ 25.5│ 1│ 0│ 0 - Dec. │ │ │ │ │ │ │ │ │ │ │ - 15 │ │ │ │ │ │ │ │ │ │ │ - ────────┴────┴───┴───┴──┴──────┴────────┴──────┴──────┴──────┴──────┴──────── - -An admission to the measles ward does not indicate admission to the -hospital, because a considerable number of cases of measles developed -from time to time among patients under treatment in the hospital for -other conditions. Since these patients remained in other wards not -subject to the same ward management and with no distinction between -those positive and those negative for hemolytic streptococci, they -cannot be included in figures to show the incidence of hemolytic -streptococci in patients with measles at the time of admission to -hospital from the camp. Two classifications of the 37 cases, positive -when first observed, are necessary. - -1. Division of cases according to days in the hospital before first -culture was taken: - - Days in Hospital No. of cases - 0–1 (admission) 15 (2 not acute) - 2–7 10 - More than 7 12 - -2. Classification according to stage of the disease: - - During acute stage 21 cases - After acute stage 16 cases - -The first classification shows only 13 cases positive when cultured on -admission to the hospital and also during the acute stage of the -disease; the incidence of S. hemolyticus in patients on admission is -very low (1.76 per cent). - -The second classification shows a slightly higher incidence for cases -during the acute stage of the disease, regardless of whether they were -admitted to the measles service from camp or from another service of the -hospital (2.4 per cent). These findings conform with those at Fort Riley -in a smaller series of cases and support the opinion that the hemolytic -streptococci temporarily disappear from the throat during the acute -onset of measles. Unfortunately controls among normal men in Camp Pike -were not taken at intervals throughout the period of three months -represented by this study of measles, but all controls taken show a -higher incidence than that found among measles patients on admissions -over a period of time comparable to that of the control series. - -The gradual increase in the percentage of patients developing hemolytic -streptococci in their throats in wards receiving only streptococcus free -cases demonstrates that the admission culture and the subsequent weekly -cultures, with the separation of all patients identified as carriers, -did not suffice to control the spread of streptococcus in this group of -cases. It is interesting to note that the greatest incidence of -streptococcus carriers among these patients occurred three weeks after -the height of the measles epidemic, when it became about four times that -observed at the height of the measles epidemic. - -When we consider the time relations of the streptococcus complications, -it is noteworthy that they begin to appear somewhat after the appearance -of streptococcus carriers and then increase parallel with the increase -in the numbers of carriers. The relative number of complications -developing among the first carriers which were identified is less than -that among the carriers appearing later. This suggests an increase in -virulence of hemolytic streptococci attending their wider dissemination. - -Tables LXII and LXIII are introduced for the purpose of showing to what -extent duration of stay in the hospital increases the individual’s -chances of acquiring hemolytic streptococci. Table LXII includes all -cases admitted to and treated in the measles wards. On repeated -cultures, previous positives and negatives were cultured alike and the -total positives reported for each week. - -Table LXIII includes only those cases treated in the “clean” wards and -known to be negative on previous culture. - - TABLE LXII - - INCIDENCE OF HEMOLYTIC STREPTOCOCCI IN THROATS OF MEASLES CASES WITH - REFERENCE TO PERIOD IN HOSPITAL - - (All cases treated in the wards) - - ═════════════════╤═════════════════╤═════════════════╤═════════════════ - PERIOD IN MEASLES│ NO. CASES │NO. POSITIVE FOR │PER CENT POSITIVE - WARD │ CULTURED │ HEMOLYTIC │ FOR HEMOLYTIC - │ │ STREPTOCOCCI │ STREPTOCOCCI - ─────────────────┼─────────────────┼─────────────────┼───────────────── - (Admission) │ 867│ 37│ 4.2 - 1 week│ 768│ 84│ 10.9 - 2 weeks│ 479│ 109│ 22.8 - 3 weeks│ 240│ 63│ 26.2 - 4 weeks│ 133│ 44│ 33.1 - 5 weeks│ 82│ 26│ 31.7 - 6 weeks│ 53│ 14│ 26.4 - 7 weeks│ 25│ 8│ 32.0 - 8 weeks│ 13│ 1│ 7.7 - 9 weeks│ 9│ 1│ 11.1 - 10 weeks│ 6│ 0│ 0 - 11 weeks│ 5│ 0│ 0 - ─────────────────┴─────────────────┴─────────────────┴───────────────── - - TABLE LXIII - - WEEKLY DEVELOPMENT OF HEMOLYTIC STREPTOCOCCI IN THROATS OF PATIENTS - TREATED IN “CLEAN” WARDS - - ═════════════════╤═════════════════╤═════════════════╤═════════════════ - PERIOD IN MEASLES│ NO. CASES │NO. POSITIVE FOR │PER CENT POSITIVE - WARD │ CULTURED │ HEMOLYTIC │ FOR HEMOLYTIC - │ │ STREPTOCOCCI │ STREPTOCOCCI - ─────────────────┼─────────────────┼─────────────────┼───────────────── - 1 week│ 738│ 67│ 9.1 - 2 weeks│ 424│ 74│ 17.4 - 3 weeks│ 195│ 34│ 17.4 - 4 weeks│ 92│ 16│ 17.4 - 5 weeks│ 46│ 7│ 15.2 - 6 weeks│ 26│ 4│ 15.4 - 7 weeks│ 14│ 3│ 21.4 - 8 weeks│ 8│ 0│ - 9 weeks│ 5│ 0│ - 10 weeks│ 4│ 0│ - 11 weeks│ 3│ 0│ - ─────────────────┴─────────────────┴─────────────────┴───────────────── - -A comparison of Tables LXII and LXIII gives some indication of what -might have been expected if the carriers had not been removed from the -treatment wards at weekly intervals. With the carriers removed from the -“clean” cases and segregated in a separate ward so as to be removed -effectively as sources of spread of the S. hemolyticus infection to -clean cases, the percentage incidence with all cases considered rose to -a point nearly twice as high as that ever reached in the wards where -clean cases alone were allowed to remain. Had these carriers not been -separated, and remained in contact with cases free from hemolytic -streptococci, they would have served as just so many more sources of -infection, and an incidence of at least twice that recorded for all -cases combined, or four times that of the treatment wards, might have -been expected. These results indicate that the weekly separation of -carriers from clean cases did, to a considerable extent, lower the -individual’s danger of acquiring S. hemolyticus infection while in the -hospital. - - - Complications of Measles - -In Table LXIV the complications developing in the measles patients under -observation at Camp Pike are tabulated. In the division of the -complications developing in “carriers” and “noncarriers” of the -hemolytic streptococci, reference is made only to the records of the -throat cultures. The division is therefore not dependent upon the -bacteriology of the complications. For example, only 9 of the 12 cases -of pneumonia developing in “carriers” were streptococcus pneumonias. On -the other hand, the cases of mastoiditis following otitis media were -almost invariably due to hemolytic streptococci. Of the 10 otitis cases -occurring in “noncarriers,” 4 developed mastoiditis and 3 of these -showed hemolytic streptococci on culture from the mastoid cells at -operation. Missed cases of identification of S. hemolyticus by throat -culture in cases which develop S. hemolyticus complications may arise -from a number of causes. It is desired here only to direct attention to -these discrepancies. - -=Pneumonia Following Measles.=—Fifty-six cases of pneumonia following -measles occurred during the period of observation in this group of 867 -cases of measles. Of these, 9 were streptococcus pneumonias. This gives -an incidence for streptococcus pneumonias of 1.04 per cent, while that -for all the pneumonia is 6.4 per cent. There were 8 cases of lobar and -48 cases of bronchopneumonia. Seventeen fatal cases occurred giving a -mortality rate of 30.4 per cent for the group. Five of these fatal cases -occurred among the 9 streptococcus pneumonias. The mortality rate for -the streptococcus pneumonia thus was 55.5 per cent; that for the -nonstreptococcus group was 25.5 per cent. All 9 cases of streptococcus -pneumonia developed empyema. In 7 cases it was diagnosed clinically; in -2 at autopsy only. No cases of empyema developed in the group of -nonstreptococcus pneumonias. - - TABLE LXIV - - COMPLICATIONS DEVELOPING IN 867 CASES OF MEASLES AT CAMP PIKE. DISTRIBUTION - OF COMPLICATIONS BETWEEN 242 “CARRIERS” AND 625 “NONCARRIERS” OF HEMOLYTIC - STREPTOCOCCI FROM SEPTEMBER 15 TO DECEMBER 15, 1918 - - ═════════════╤═════════════════════════════╤══════╤══════════════════════════ - NAME OF │ │TOTAL │ - COMPLICATION │ NUMBER OCCURRING IN │NUMBER│ PER CENT IN - ─────────────┼──────────┬─────────┬────────┼──────┼─────┬──────────┬───────── - „ │ │ │ CASES │ │ │ │ - │ │ │WITH IN-│ │ │ │ - │ │ │COMPLETE│ │ │ │ - │ │ “NON- │ RECORD │ │ │ │ “NON- - │“CARRIERS”│CARRIERS”│ OF │ │ │ HEM. │CARRIERS” - │ OF HEM. │ OF HEM. │ THROAT │ │ ALL │ STREP. │ OF HEM. - │ STREP. │ STREP. │CULTURES│ „ │CASES│“CARRIERS”│ STREP. - ─────────────┼──────────┼─────────┼────────┼──────┼─────┼──────────┼───────── - Pneumonia │ 12│ 44│ 0│ 56│ 6.4│ 5.0│ 7.0 - Otitis media │ 31│ 11│ 6│ 48│ 5.5│ 12.8│ 1.8 - Mastoiditis │ │ │ │ │ │ │ - (following │ │ │ │ │ │ │ - otitis │ │ │ │ │ │ │ - media) │ 15│ 4│ 4│ 23│ 2.6│ 6.2│ 0.6 - Local │ │ │ │ │ │ │ - meningitis │ │ │ │ │ │ │ - (extension │ │ │ │ │ │ │ - from │ │ │ │ │ │ │ - mastoid) │ 2│ 0│ 0│ 2│ │ │ - Frontal │ │ │ │ │ │ │ - sinusitis │ 1│ 0│ 0│ 1│ │ │ - Ethmoidal │ │ │ │ │ │ │ - sinusitis │ 0│ 1│ 0│ 1│ │ │ - Suppurative │ │ │ │ │ │ │ - arthritis │ 1│ 0│ 0│ 1│ │ │ - Cervical │ │ │ │ │ │ │ - adenitis │ 1│ 0│ 0│ 1│ │ │ - Acute │ │ │ │ │ │ │ - bronchitis │ 4│ 2│ 0│ 6│ │ │ - Acute │ │ │ │ │ │ │ - tonsillitis│ 4│ 1│ 0│ 5│ │ │ - Acute │ │ │ │ │ │ │ - laryngitis │ │ │ │ │ │ │ - and aphonia│ 1│ 0│ 0│ 1│ │ │ - Acute │ │ │ │ │ │ │ - pleurisy │ 2│ 1│ 0│ 3│ │ │ - Erysipelas of│ │ │ │ │ │ │ - face │ 0│ 1│ 0│ 1│ │ │ - Epidemic │ │ │ │ │ │ │ - meningitis │ 0│ 1│ 0│ 1│ │ │ - ─────────────┴──────────┴─────────┴────────┴──────┴─────┴──────────┴───────── - - Note.—The percentages of incidence of pneumonia and otitis media in the - “carrier” and “noncarrier” groups are at direct variance. It would appear - from these findings that streptococci very readily invade the middle ear from - the throat and set up grave disorders. The invasion of the lung from the - throat occurs with less frequency. Hemolytic streptococci perhaps never - initiate the pneumonic processes and can be regarded as more or less - accidental secondary invaders. - -The relation of these pneumonias following measles, to the influenza -epidemic has been discussed. The time relations between the onsets of -measles and that of the subsequent pneumonia vary widely. There appears -to be nothing constant in the length of time between the onset of -measles and that of the pneumonia. In 30 of the cases this period is -less than ten days; in the remaining 26 cases, it ranges from ten to -thirty-two days (Chart 4). - -In the ward treatment of these cases of pneumonia, they were divided -into three groups according to their clinical characters and according -to the results of throat and sputum cultures. - - (_a_) Streptococcus pneumonias 9 cases - (_b_) Pneumonia with hemolytic streptococci in the throat - without symptoms referable to the streptococcus 13 cases - (_c_) Pneumococcus pneumonias not carrying hemolytic - streptococci 34 cases - -The streptococcus-free cases were treated in a separate ward. Cases were -admitted to this ward directly from the “clean” measles wards, but only -after a throat culture taken prior to their transfer had been negative -for the hemolytic streptococcus. - -The other two groups were treated together in another ward, but in -strictly separate compartments of it. This precaution was carried out on -the assumption that patients with an acute streptococcus pneumonia were -real sources of danger in the ward because of a heightened virulence of -the organism causing the grave symptoms. The pneumonias subsequently -developing hemolytic streptococci in their throats, without their -presence modifying the course of the pneumonia, came to be regarded as -being in the same class with uncomplicated cases of measles carrying -hemolytic streptococci, in so far as their being potential sources of -danger in a ward is concerned. - -[Illustration: - - Chart 4.—Shows the time interval between the onset of measles and the - onset of the subsequent pneumonia in the 56 cases of pneumonia - following measles at Camp Pike. Each case is represented by one of - the small blocks measured along the ordinate. The onset of measles - in all cases is represented by the line at the extreme left of the - chart. The onset of pneumonia in each case is indicated by the limit - of the block marked off in days to the right of this line. -] - -(_a_) =Streptococcus Pneumonias.=—Nine cases of streptococcus pneumonia -developed. Of the 867 cases of measles studied, 242 showed throat -cultures positive for the hemolytic streptococci at some period of their -stay in the hospital. It appears then that 3.7 per cent of the patients -carrying hemolytic streptococci in their throats developed streptococcus -pneumonia. Thirty-seven cases had positive throat cultures when first -observed on admission to the measles wards. It is significant to note -that not a single case of pneumonia of any kind developed among these -cases. - - MEASLES PNEUMONIA; STREPTOCOCCUS GROUP - - Case 98, O. McN. Onset of measles, Sep. 19; admitted to hospital - Sep. 21; onset of bronchopneumonia, Oct. 21; of empyema, Oct. 23. - Recovered from pneumonia; convalescent in empyema ward. - - _Bacteriology._—1. Throat culture for: (_a_) S. hem.: Sep. 21, −; - 28, −; Oct. 9, −; 20, −; 23, +; Nov. 2, −; 9, −; 15, −; (_b_) B. - influenzæ: Sep. 21, +; 28, −; Oct. 9, +. 2. Pleural fluid (culture) - S. hem. Oct. 23, +. - - Case 141, J. G. G. Autopsy No. 438. Onset of measles, Sep. 28; - admitted to hospital, Oct. 1; onset of bronchopneumonia, Oct. 6; of - otitis media (bilateral), Oct. 12; died, Oct. 18. - - _Bacteriology._—1. Throat culture for: (_a_) S. hem., Oct. 2, −; 6, - −; 8, −; (_b_) B. influenzæ, Oct. 2, −; 6, +; 8, +. 2. Autopsy - cultures: Heart blood, negative; left lung, Pneumococcus II - atypical, B. influenzæ and S. viridans; right lung, S. hem. and B. - influenzæ; right bronchus, S. hem. and B. influenzæ. - - Case 147, S. W. Autopsy No. 442. Onset of measles, Oct. 1; admitted - to hospital, Oct. 2; onset of bronchopneumonia, Oct. 17, with chill - and rapid development; died, Oct. 18. - - _Bacteriology._—1. Throat culture for: (_a_) S. hem., Oct 2, −; 9 −; - 15, −; 18, +; (_b_) B. influenzæ, Oct. 2, −; 9, −; 15, −; 18, −. 2. - Autopsy cultures: Heart blood, S. hem.; right main bronchus, S. hem. - and B. influenzæ. - - Case 281, T. M. Onset of measles, Oct. 6; admitted to hospital Oct. - 9; onset of bronchopneumonia, Oct. 21; of empyema, Oct. 23; - recovered from pneumonia; convalescent in empyema ward. - - _Bacteriology._—1. Throat culture for: (_a_) S. hem., Oct. 10, −; - 20, −; 24, +; Nov. 2, +; 9, +; 15, +; (_b_) B. influenzæ, Oct. 10, - −; 20, +. 2. Culture from pleural fluid, Oct. 23, S. hem. - - Case 285, J. H. Onset of measles, Oct. 4; admitted to hospital, Oct - 9; onset of lobar pneumonia, Oct. 29; of empyema, Nov. 9; - convalescent in empyema ward. - - _Bacteriology._—1. Throat cultures for: (_a_) S. hem., Oct. 11, −; - 20, −; 24, +; 29, −; Nov. 2, −; 9, −; (_b_) B. influenzæ, Oct. 11, - −. 2. Cultures from pleural fluid, Nov. 9 and 13, S. hem. - - Case 714, W. H. Onset of measles, Oct. 26; admitted to hospital, - Oct. 28; otitis media, Nov. 8; onset of bronchopneumonia, Nov. 9; of - empyema, Nov. 17; convalescent in pneumonia ward. - - _Bacteriology._—1. Throat cultures for: S. hem., Oct. 28, −; Nov. 4, - −; 12, +; 23, +; 30, +; Dec. 7, +; 12, −. 2. Sputum: Nov. 10, - Pneumococcus II atypical, S. hem. and B. influenzæ. - - Case 730, W. S. Autopsy No. 491. Onset of measles, Oct. 26; admitted - to hospital, Oct. 29; onset of bronchopneumonia, Nov. 10; of - empyema, Nov. 11; of cervical adenitis, Nov. 5; died, Nov. 15. - - _Bacteriology._—1. Throat culture for: S. hem., Oct. 30, −; Nov. 4, - +. 2. Sputum: Nov. 10, S. hem. 3. Pleural fluid: Nov. 11, S. hem. - Autopsy bacteriology: Heart blood, S. hem.; right main bronchus, B. - influenzæ, B. coli; right lung, S. hem. and B. influenzæ; right - pleura, S. hem.; peritoneum, S. hem. - - Case 751, P. B. Autopsy No. 492. Entered hospital, Oct. 19; onset of - measles, Oct. 30; of bronchopneumonia, Nov. 5; of right empyema, - Nov. 12; died, Nov. 16. - - _Bacteriology._—1. Throat cultures for: S. hem., Nov. 1, −; 4, +; - 15, +. 2. Sputum: Nov. 13, B. influenzæ and S. hem. 3. Autopsy - cultures: Heart blood, S. hem.; right lung, S. hem., Pneumococcus - IV, B. influenzæ, B. coli; pericardium, negative; right pleura, S. - hem.; peritoneum, S. hem. - - Case 880, B. McN. Autopsy No. 507. Onset of measles, Nov. 30; - entered hospital, Dec. 3; onset of bronchopneumonia, Dec. 11; of - empyema, Dec. 14; died, Dec. 14. - - _Bacteriology._—1. Throat cultures for: S. hem., Dec. 3, −; 5, −; - 12, +. 2. Cultures from pleural fluid, Dec. 14, S. hem. 3. Autopsy - cultures: Heart blood, S. hem.; right main bronchus, S. hem., B. - influenzæ, staphylococcus (a few); left lung, S. hem.; left pleura, - S. hem. - -The average period in the hospital before the development of the -streptococcus pneumonia is about two weeks. Cases 98 and 285 were in the -hospital thirty and twenty days respectively before the onset of -pneumonia. There is a record of from one to four negative throat -cultures on each case before streptococcus was found in the throat. This -enables us to fix the onset of the pneumonia with reference to the -appearance of the streptococcus in the throat. - -Case 141 stands alone as representing a class in which S. hemolyticus -was implanted upon a pneumococcus pneumonia during its course. In this -instance two throat cultures on alternate days after the onset of the -pneumonia were negative for hemolytic streptococci. Unfortunately the -last record of a throat culture is for one taken ten days before the -fatal termination of the case, and it can only be stated that the S. -hemolyticus infection was implanted within the last ten days of the -course of the pneumonia, perhaps on or about October 12 when bilateral -otitis media developed. - -In Cases 285 and 730 hemolytic streptococci were found in the throats -five and six days respectively before the onset of pneumonia. They -represent the 2 cases of pneumonia which developed in patients isolated -in the streptococcus “carrier” ward. Case 285 is of particular interest -for several reasons. It is the only case of lobar pneumonia in the group -and happens also to be the only case from which B. influenzæ was not -obtained. S. hemolyticus was found only once on throat culture, i.e., -five days before the onset of the pneumonia. Three throat cultures after -the onset of the pneumonia were negative. The case ran the course of a -lobar pneumonia. Eleven days after the onset (November 9) a small amount -of pleural fluid was diagnosed. Aspirated fluid on this date and again -four days later showed many streptococci in smears and pure cultures of -S. hemolyticus. - -The remaining 6 cases belong to a group in which hemolytic streptococci -were first identified in the throats after the cases had been reported -to the laboratory as pneumonia suspects to be examined by culture before -transfer from the measles ward. In all these cases the culture taken at -this time was positive while all cultures taken before were negative. In -some cases, _e. g._, Cases 98, 147, and 281, throat cultures taken only -one or two days before the onset of the pneumonia were negative. In -these cases the onset of the pneumonia and the appearance of the -streptococcus in the throats appear to be simultaneous. - -It should be noted that the period between the appearance of the -hemolytic streptococci in the throat and the development of the -pneumonia is very short in all cases. In this small group of cases S. -hemolyticus infection which has complicated pneumonia has been acquired -at or near the time of onset of the pneumonia. - -(_b_) =Pneumonia with Hemolytic Streptococci in the Throat without -Symptoms Referable to the Streptococcus.=—Thirteen cases of pneumonia -associated with measles developed into S. hemolyticus “carriers” without -having the course of the disease affected by the presence of the -organism in the throat. Cases 705, 872, and 188 are of interest in that -hemolytic streptococci were identified in the throats from one to six -days prior to the onset of the pneumonia. In spite of their presence, -the symptoms, course and outcome of the pneumonia were apparently -unaffected. One of these cases (Case 872) died. Autopsy showed lobar -pneumonia with no signs of invasion of the lung by hemolytic -streptococci. Cultures at autopsy showed that pneumonia was due to a -pneumococcus, Type II atypical. A few hemolytic streptococci were found -in culture from the right main bronchus. - -Of the remaining 10 cases 1 developed S. hemolyticus in a throat culture -at the end of the first week of the pneumonia; 3 during the second week; -1 during the third week, and 5 further along in the convalescent period. -In 8 cases hemolytic streptococci appeared in the throat, at a time when -invasion of the lower respiratory tract by the streptococcus might be -expected, and yet none of them developed evidence of streptococcus -pneumonia. The 9 cases with hemolytic streptococci appearing late in -convalescence are not of particular interest, since the dangers of lower -respiratory invasion are much reduced after the acute stage of the -pneumonia has passed. Three of these cases (Cases 678, 725 and 398) did -however develop ear complications directly referable to the -streptococcus invasion of the throat. Two of them terminated in -mastoiditis with operation. These cases emphasize the greater tendency -of S. hemolyticus to invade the middle ear rather than the lung. - -In 3 fatal cases of pneumococcus pneumonia in which during life no -hemolytic streptococci were found by throat culture, a few hemolytic -streptococci were found at autopsy in culture from the main bronchi, -along with predominating growths of pneumococci and B. influenzæ. In 2 -instances there was frank lobar pneumonia and in the third -bronchopneumonia; there was no evidence to show that hemolytic -streptococci had any relation to the pneumonia which was found. - - MEASLES PNEUMONIAS; GROUP CARRYING HEMOLYTIC STREPTOCOCCI - - Case 705. Onset of measles, Oct. 25; admitted to hospital, Oct. 27; - onset of bronchopneumonia, Nov. 10; acute pleurisy, Nov. 16; - convalescent in pneumonia ward. - - _Bacteriology._—1. Throat cultures for: S. hem., Oct. 27, −; Nov. 4, - −; 11, +; 15, +; 23, −; 30, −; Dec. 7, −; 12, −. 2. Sputum: Nov. 10, - Pneumococcus II atypical, S. hem. and B. influenzæ. - - Case 872. Autopsy No. 508. Onset of measles, Nov. 29; admitted to - hospital, Nov. 30; onset of lobar pneumonia, Dec. 10; died, Dec. 14. - - _Bacteriology._—1. Throat cultures for: S. hem., Nov. 30, −; Dec. 5, - +; 10, +; 12, +; 14, +. 2. Autopsy culture: Heart blood, - Pneumococcus II atypical; right main bronchus, Pneumococcus II - atypical, B. influenzæ, S. hem. (a few); left lung, Pneumococcus II - atypical; left pleura, Pneumococcus II atypical. - - Case 188. Onset of measles, Oct. 3; admitted to hospital, Oct. 4; - onset of bronchopneumonia, Oct. 14; recovered and discharged from - hospital, Nov. 24. - - _Bacteriology._—1. Throat cultures for: (a) S. hem., Oct. 5, −; 8, - +; 12, +; 19, +; 20, +; 27, −; Nov. 2, −; 9, +; 15, −; (b) B. - influenzæ, Oct. 5, −; 8, −; 12, +; 19, +. - - Case 678. Onset of measles, Oct. 23; admitted to hospital, Oct. 25; - onset of bronchopneumonia, Nov. 2; of otitis media, Nov. 9; of - mastoiditis, Nov. 13; mastoid operation, Nov. 20; still under - treatment. - - _Bacteriology._—1. Throat cultures for: S. hem., Oct. 25, −; Nov. 4, - −; 5, −; 12, +. 2. Sputum: Nov. 3, Pneumococcus Type IV, and B. - influenzæ. 3. Culture from mastoid bone at operation, Nov. 20, S. - hem. - - Case 389. Admitted to hospital, Oct. 2, with diagnosis of influenza; - onset of bronchopneumonia, Oct. 7; onset of measles, Oct. 13; - phlebitis (right leg), Oct. 22; otitis media, Oct. 31; recovered. - - _Bacteriology._—1. Throat cultures for: (a) S. hem., Oct. 16 −; 20, - −; 27, +; Nov. 2, +; 9, +; 15, −; 23, −; 30, −; Dec. 7, −; 12, −; - (b) B. influenzæ, Oct. 16, −. - - Case 725. Onset of measles, Oct. 18; one week in measles barracks; - admitted to hospital, Oct. 27; onset of lobar pneumonia, Oct. 23; - otitis media, Nov. 7; mastoid operation, Nov. 20; still under - treatment. - - _Bacteriology._—1. Throat cultures for: (_a_) S. hem., Oct. 29, −; - Nov. 1, −; 5, −; 12, +; (_b_) B. influenzæ, Oct. 29, +. 2. Sputum: - Nov. 2, Pneumococcus II atypical. B. influenzæ. 3. Culture from - mastoid at operation, Nov. 20, S. hem. - -(_c_) =Pneumococcus Pneumonias not Carrying Hemolytic -Streptococci.=—Thirty-four cases of pneumonia following measles went -through their entire course in the hospital with no throat culture -positive for hemolytic streptococci. In some of these cases there are -records of twelve negative throat cultures. Eleven fatal cases occurred -in this group. Autopsy findings and bacteriology showed in each instance -that S. hemolyticus was not the cause of the pneumonia. - -=Measles During the Course of Pneumonia.=—Eleven cases of pneumonia -which developed measles during the course of the pneumonia came under -observation. Hemolytic streptococci appeared in the throats of 3 of -these patients during convalescence, but there was no evidence that it -invaded the lung. In one fatal case autopsy showed that there was no -streptococcus pneumonia; pneumonia followed influenza and the onset of -measles occurred three days after the onset of bronchopneumonia. - -=Bacteriology of Pneumonia Following Measles.=—When observations made -during life are combined with the results of postmortem cultures, the -bacteriology of 35 of the 56 cases is available and is as follows: -Pneumococcus Type II atypical in 36 per cent, Type IV in 22.9 per cent, -Type I in 2.8 per cent, Type III in 2.8 per cent, hemolytic streptococci -in 22.4 per cent, and B. influenzæ in 88.6 per cent of these cases. - -=Otitis Media and Mastoiditis Complicating Measles.=—The occurrence of -otitis media and mastoiditis complicating measles in patients harboring -hemolytic streptococci in their throats has already been presented -(Table LXIV). The bacteriology of these complications was not studied by -this commission. The records of the base hospital laboratory at Camp -Pike contain reports of twenty-nine cultures made at operation from pus -in the middle ear and the mastoid bone. Hemolytic streptococci were -found in 22 of these cases. Throat cultures were in accord with these -positive findings in all except a few instances. The throat culture -serves as a fairly reliable index of the bacterial nature of these -complications. By combining our records of throat cultures with the -results of the cultures from the lesions, hemolytic streptococci were -obtained from 37 of the 48 cases of otitis media. In 23 cases of -mastoiditis following the otitis media, hemolytic streptococci were -demonstrated in all except 2. It is evident that the great majority of -these complications were due to hemolytic streptococci. - -The relation between the appearance of hemolytic streptococci in the -throat and the onset of the otitis is recorded in all except 4 of the 31 -instances of otitis media occurring in patients with throat cultures -positive for hemolytic streptococci. These four patients had positive -throat cultures when first observed and represent the only patients who -carried hemolytic streptococci when admitted to measles wards and -developed complications. - -The first of these patients had been under treatment in an otologic ward -during a month before measles developed. Measles caused a recurrence of -disease of the ear with double mastoiditis requiring bilateral -operation. Two other patients had been in the hospital ten and eleven -days respectively before they were admitted to the measles ward; on -admission to the ward otitis media was present in one patient and in the -other it developed six days later. The fourth patient was admitted to -the measles wards directly from the camp, and culture from the throat on -the day of admission showed the presence of S. hemolyticus. Two weeks -later at the time of onset of otitis media, culture from the throat -contained no hemolytic streptococci. Repeated cultures during the next -three weeks were negative. No complications of otitis media developed -and no direct cultures from the ear are recorded. - -[Illustration: - - Chart 5.—Shows the time relation between the identification of - hemolytic streptococci in the throats and the development of otitis - media in 27 cases shown to be due to hemolytic streptococci. The - onset of otitis media is represented by the ordinate marked ○. The - number of days before or after the onset of the otitis, within which - the throat culture which proved positive for hemolytic streptococci - was taken, is marked off along abscissæ to the left and right of - ordinate ○ respectively. On the curve plotted these symbols are - used: A circle represents a throat culture positive for hemolytic - streptococci in a case of otitis media without extension to mastoid. - The plus sign represents a throat culture positive for hemolytic - streptococci in a case of otitis media with mastoiditis and - osteitis. - -] - -In this series of cases (Chart 5) the appearance of S. hemolyticus in -the throat and the onset of otitis media are very closely associated in -those patients in whom further extensions of the streptococcus infection -occurred. In instances in which appearance of streptococci and of otitis -media are separated by an interval of more than seven days, no further -extension occurred. In 8 cases in which this interval is seven days or -less there has been no further extension of the infection. - - - The Dissemination of Hemolytic Streptococci in Wards - -Beginning October 24 cultures for the identification of carriers of -hemolytic streptococci were made from all patients in a ward and -repeated at intervals of one week. Prior to this time individual -patients had been examined at intervals of one week, so that an entire -ward was never studied on any particular day. This system did not -identify and remove all “carriers” in a ward at a given time and was -abandoned because it failed to show the conditions present. -Investigation of wards as units proved much more satisfactory. - -The studies made in four of the double wards used for the care of -patients with measles are presented in Table LXV. During the time of -this study hemolytic streptococci were more prevalent than at an earlier -period. - -Cultures from the throats of all patients entering these wards were -negative for S. hemolyticus on admission. The table showing the -incidence of “carriers” of hemolytic streptococci each week in these -wards demonstrates: - -1. The separation of “carriers” and “noncarriers” by throat culture made -on admission does not prevent the increase of streptococcus “carriers” -in wards. - -2. Removal of all “carriers” found by cultures on admission and at -weekly intervals is inadequate. - - TABLE LXV - - WARD CONDITIONS WITH REFERENCE TO HEMOLYTIC STREPTOCOCCUS INFECTION - - ═══════╤════════╤════════╤═════════╤═════════════╤═════════════════════ - DATE OF│ NO. │ NO. │PER CENT │COMPLICATIONS│ - CULTURE│PATIENTS│POSITIVE│POSITIVE │ ASSOCIATED │ - │CULTURED│ HEM. │ HEM. │ WITH HEM. │ REMARKS - │ │ STREP. │ STREP. │ STREP. WITH │ - │ │ │ │ DATES OF │ - │ │ │ │ ONSET │ - ───────┼────────┼────────┼─────────┼─────────────┼───────────────────── - Ward 57│ │ │ │ │ - 11–3 │35 │1 │2.8 │ │ - 11–10 │13 │2 │15.5 │None │ - 11–17 │16 │6 │37.5 │ │ - ───────┼────────┼────────┼─────────┼─────────────┼───────────────────── - Ward 58│ │ │ │ │Wards 57 and 58 - │ │ │ │ │ served by same ward - │ │ │ │ │ staff. - 11–3 │38 │7 │18.4 │Otitis media:│ „ - 11–10 │11 │4 │36.4 │11–8 1 case │Members of staff - │ │ │ │ │ cultured on 11–5, - │ │ │ │ │ 11–12 and 11–19. No - │ │ │ │ │ positives - 11–17 │6 │2 │33.0 │11–7 1 case │ „ - ───────┼────────┼────────┼─────────┼─────────────┼───────────────────── - Ward 49│ │ │ │ │ - │ │ │ │Otitis media:│ - 10–25 │37 │7 │18.9 │10–25 2 cases│ - 11–1 │31 │3 │9.7 │10–26 1 case │ - 11–8 │35 │9 │25.7 │10–28 1 case │ - 11–15 │32 │18 │56.3 │11–15 1 case │ - 11–22 │16 │7 │43.8 │11–18 1 case │ - │ │ │ │11–27 1 case │ - ───────┼────────┼────────┼─────────┼─────────────┼───────────────────── - Ward 50│ │ │ │ │Wards 49 and 50 - │ │ │ │ │ served by same ward - │ │ │ │ │ staff. - 10–25 │29 │2 │3.4 │Otitis media:│ „ - 11–1 │43 │2 │4.6 │11–8 1 case │Ward staff cultured: - │ │ │ │ │ 11–5 1 positive - │ │ │ │ │ 11–12 1 positive - │ │ │ │ │ 11–26 2 positives - 11–8 │32 │3 │9.4 │11–13 1 case │ „ - 11–15 │20 │11 │55.0 │11–22 1 case │ „ - 11–22 │11 │0 │0.0 │ │ „ - ───────┼────────┼────────┼─────────┼─────────────┼───────────────────── - Ward 41│ │ │ │ │Case of pneumonia - │ │ │ │ │ developing on 11–9 - │ │ │ │ │ was transferred to - │ │ │ │ │ the “clean” - │ │ │ │ │ pneumonia ward - │ │ │ │ │ without a throat - │ │ │ │ │ culture to warrant - │ │ │ │ │ its transfer; last - │ │ │ │ │ culture 11–4 - │ │ │ │ │ negative; culture - │ │ │ │ │ 11–12 in pneumonia - │ │ │ │ │ ward positive - 10–28 │45 │4 │8.9 │Streptococcus│ „ - │ │ │ │pneumonia: │ - 11–4 │34 │9 │26.5 │(11–9 1 case)│ „ - 11–11 │12 │8 │66.6 │11–10 1 case │ „ - Ward closed—No patients. │Otitis media:│ „ - 11–21 │13 │0 │0.0 │10–29 1 case │ „ - 11–28 │8 │4 │50.0 │11–4 1 case │ „ - 12–5 │12 │4 │33.3 │11–5 1 case │ „ - 12–12 │4 │3 │75.0 │11–11 1 case │ „ - │ │ │ │11–27 1 case │ „ - │ │ │ │12–3 1 case │ „ - ───────┼────────┼────────┼─────────┼─────────────┼───────────────────── - Ward 42│ │ │ │ │Wards 41 and 42 - │ │ │ │ │ served by same ward - │ │ │ │ │ staff. - │ │ │ │Streptococcus│ „ - │ │ │ │pneumonia: │ - 10–28 │32 │0 │0 │11–10 1 case │ „ - 11–4 │43 │7 │16.3 │12–11 1 case │ „ - Ward closed—No patients. │Otitis media:│Ward staff cultured: - │ │ 11–5 2 positive - │ │ 11–12 2 positive - │ │ 11–26 2 positive - │ │ 12–2 1 positive - 10–21 │16 │4 │25.0 │10–29 1 case │ „ - 11–28 │12 │1 │12.5 │12–3 1 case │ „ - 12–5 │20 │10 │50.0 │12–6 1 case │ „ - 12–12 │14 │7 │50.0 │ │ „ - ───────┼────────┼────────┼─────────┼─────────────┼───────────────────── - Ward 59│ │ │ │ │The 3 cases of - │ │ │ │ │ streptococcus - │ │ │ │ │ pneumonia acquired - │ │ │ │ │ S. hemolyticus - │ │ │ │ │ infection while - │ │ │ │ │ patients in the 16 - │ │ │ │ │ bed south section - │ │ │ │ │ of this ward - │ │ │ │Streptococcus│ „ - │ │ │ │pneumonia: │ - 10–24 │37 │6 │16.2 │10–17 1 case │ „ - 10–31 │27 │5 │18.5 │10–21 1 case │ „ - 11–7 │9 │3 │33.3 │10–29 1 case │Case developing 10–29 - │ │ │ │ │ was removed from - │ │ │ │ │ section a few days - │ │ │ │ │ before onset of - │ │ │ │ │ pneumonia - 11–12 │7 │1 │14.3 │Otitis media:│ „ - │ │ │ │11–1 1 case │ „ - ───────┼────────┼────────┼─────────┼─────────────┼───────────────────── - Ward 60│ │ │ │ │Wards 59 and 60 - │ │ │ │ │ served by same ward - │ │ │ │ │ staff. - │ │ │ │Streptococcus│ „ - │ │ │ │pneumonia: │ - 10–24 │22 │1 │4.5 │10–21 1 case │Ward staff cultured: - │ │ │ │ │ 11–5 0 positive - │ │ │ │ │ 11–12 1 positive - │ │ │ │ │ 11–19 0 positive - 10–31 │17 │2 │11.7 │Otitis media:│ „ - 11–7 │8 │1 │12.5 │10–31 1 case │ „ - 11–12 │6 │1 │16.6 │ │ „ - ───────┴────────┴────────┴─────────┴─────────────┴───────────────────── - -When the streptococcus complications are traced back to the wards in -which the streptococcus infection of the throat was acquired, it is -found that with the exception of Case 141 (already cited) all the -streptococcus pneumonias arose from two double wards. Wards 41 and 42 -furnished 4 cases at times when streptococcus was rampant in them and 3 -of these cases arose within a period of a few days. Wards 59 and 60 -furnished 4 cases, very closely associated. In 3 cases the streptococcus -infection was acquired in a section of Ward 59 containing 16 beds. These -patients were in beds, of which the positions are represented by numbers -2, 5, and 7, along one side of the ward. The fourth instance of -pneumonia appeared at the same time in Ward 60, which was attended by -the same ward personnel, but no other connection can be established -between this case and the other three. - -The otitis media appeared in patients scattered throughout those wards -for measles in which the weekly incidence of “carriers” was rising -rapidly. This relation is illustrated by Wards 58, 50, and 41. The same -observation applies to streptococcus pneumonia arising in Wards 41 and -42. In Ward 41 the weekly percentage of carriers are October 28, 8.9, -November 4, 26.5 and November 11, 66.6. On November 9 and 10 the first 2 -cases of streptococcus pneumonia arising from this ward developed. At -the same time, November 10, a third case appeared in another part of -this same ward unit (Ward 42) where the spread of hemolytic streptococci -had been very active. These observations suggest that hemolytic -streptococci may build up its virulence as the result of rapid -dissemination to such a degree that it is capable of causing grave -complications. - -The relation of complications to “carriers” in Wards 59 and 60 is -different from that in the wards just cited. Wards 59 and 60 were opened -on October 9 and before October 17; when the first case of fulminating -streptococcus pneumonia occurred, only three “carriers” had been found -in them. From October 17 to 24 when the record in Table LXV begins eight -“carriers” were removed. The appearance of a case of severe -streptococcus pneumonia in an unusually clean ward was followed by the -rapid development of “carriers,” and the appearance within twelve days -of 3 other cases of streptococcus pneumonia, 2 of which were in beds -close to the first case. This sequence suggests focal dissemination of a -streptococcus from a case in which it had suddenly assumed high -virulence. - -An outbreak of infection with S. hemolyticus was recognized on November -12 in a measles-pneumonia ward which had been opened for several weeks -and had continued free from streptococcus. In three patients hemolytic -streptococci were found by throat cultures. Inquiry revealed that a -nurse in this ward, recognized as a streptococcus “carrier” the week -before, had been retained on duty. Two patients well advanced in the -course of their pneumonias, had acquired S. hemolyticus demonstrated by -throat examination. Both patients developed otitis media with mastoid -extension requiring operations. Cultures from both at operation showed -hemolytic streptococci. - -The third patient, with acute pneumonia, had been sent into the ward on -November 11 from Ward 42, which at the time was a highly infected ward; -no culture of the throat was made before transfer. This patient -developed streptococcus pneumonia with empyema requiring subsequent -operation. - -=Discussion.=—At Camp Funston, where the prevalence of S. hemolyticus in -the measles wards did not rise above that among normal men in the camp -at large, 112 consecutive cases of measles were treated without a single -complication due to hemolytic streptococci. - -At Camp Pike, the investigation began at the onset of a small epidemic -of measles at a time when hemolytic streptococci were an almost -negligible factor. The epidemic of measles was followed throughout its -course; and, with the passing of the epidemic, there was an increase in -the prevalence of hemolytic streptococci which assumed alarming -importance in the production of complications. - -The epidemic of measles was in part superimposed upon the epidemic of -influenza, so that deductions concerning complications strictly due to -measles became impossible. It is evident that influenza played a -considerable part in producing the complications of measles at Camp -Pike. - -The dissemination of hemolytic streptococci through measles wards was -controlled only in part by the methods used. This partial control may -have served to limit the incidence of streptococcus pneumonia, nine -instances occurring among 867 cases of measles. - -In the ward treatment of measles effort should be directed to prevent -the exposure of patients free from hemolytic streptococci to S. -hemolyticus “carriers.” By this means the rate of development of S. -hemolyticus “carriers” may be reduced. - -Measures which should be adopted are as follows: - -1. Adequate wards should be prepared in advance for the treatment of -measles. The rather gradual onset of epidemics of measles makes this -provision possible. - -2. The separation of S. hemolyticus “carriers” from other patients -should be enforced. Observation wards, where strict technic to prevent -transfer of infection is practiced and where throat cultures are made on -admission, are essential. Those wards should be promptly evacuated to -wards for the care of S. hemolytic “carriers” on the one hand and for -“noncarriers” on the other. As far as possible patients should be -admitted to a ward until it is filled and then another ward should -receive consecutive cases in the same manner. It is desirable to have -all cases in each treatment ward in the same stage of the disease. With -this system of ward rotation convalescent wards are necessary, so that -cases requiring a period of hospitalization longer than the average may -be segregated, thus rendering treatment wards available for another levy -of acute cases. - -3. Strict ward technic elaborated to prevent transfer of bacterial -infection from one patient to another must be employed. - -4. Throat culture for identification of “carriers” is laborious but -essential. An accurate method for identifying and reporting “carriers” -as speedily as possible must be employed. A competent bacteriologist is -essential. A twenty-four hour interval between culture and its report is -desirable. The following scheme is recommended: - -(_a_) A culture from the throat made on admission to the observation -ward (first day in hospital). - -(_b_) A culture made on the first day in the treatment ward (third day -in hospital). - -(_c_) A culture made one week later (tenth day in hospital). - -If the ward incidence of hemolytic streptococci reaches 10 per cent, -especially in a filled ward, the cultures should be repeated on the -thirteenth day in the hospital. If the incidence of “carriers” of -hemolytic streptococci increase rapidly, cultures on alternate days -should be made so that “carriers” may be removed from the ward. Wherever -possible, culturing of the treatment wards as units should be practiced. - -5. Patients developing acute symptoms in any way suggestive of infection -with S. hemolyticus should be immediately isolated; culture from the -throat should be made at once and final disposal of the patient should -depend upon its result. - - - Carriers of Hemolytic Streptococci - -During the winter of 1917–18, with the establishment of the army camps, -it very soon became evident that in many of the serious and fatal -complications of measles and other respiratory diseases, hemolytic -streptococci were playing a very important rôle. The epidemic prevalence -of hemolytic streptococci among hospital cases, and later among men on -duty in the camps, was established by bacteriologic studies. Prior to -this time in civil life, hemolytic streptococci under epidemic -conditions had been studied in milk-borne epidemics of septic sore -throat, such as are reported from Chicago in 1911–13[92]; from Boston in -1911[93]; and from Baltimore in 1911–12[94]. Contact air-borne infection -has not been emphasized in considering the dissemination of hemolytic -streptococci. Smillie[95] reports a few cases of hemolytic streptococcus -throat infections which he attributes to contact infection. Conditions -within the army camps were such as to suggest the dissemination of -hemolytic streptococci by contact air-borne infection. Some knowledge of -the percentage of individuals showing positive throat cultures became -desirable at the very beginning of studies of contact dissemination of -hemolytic streptococci. - -Smillie found that only one of 100 normal throats harbored the Beta -hemolytic streptococci of Smith and Brown. Levy and Alexander[96] report -the presence of hemolytic streptococci in 83.2 per cent of healthy men -at Camp Taylor, and hemolytic organisms (not definitely identified as -streptococci) in 14.8 per cent of recruits arriving at Camp Taylor. -Irons and Marine[97] found hemolytic streptococci among 70 per cent of -healthy men at Camp Custer. - -Among measles patients on admission to the hospital at Fort Sam Houston, -Cole and MacCallum[98] report 11.4 per cent and Cummings, Spruit and -Lynch,[99] 35 per cent of throat cultures positive for hemolytic -streptococci. At Camp Taylor, Levy and Alexander report 77.1 per cent -positive among 388 cases of measles on admission to the hospital. - -The spread of hemolytic streptococci in measles wards was shown by Cole -and MacCallum when on admission 11.4 per cent of cases had positive -throat cultures, 38.6 per cent after from three to five days, and 56.8 -per cent after from eight to sixteen days in the ward. In our study of -hemolytic streptococci with measles at Camp Funston, 2.6 per cent of the -cases had positive throat cultures on admission, 12.8 per cent after -three to ten days, and 24.1 per cent after eight to twenty-three days in -the hospital. In a similar study at Camp Pike we found 1.7 per cent -positive on admission; 10.9 per cent after one week; 22.8 per cent after -two weeks; 26.2 per cent after three weeks; and, 33.1 per cent after -four weeks in the hospital. - -=Hemolytic Streptococci in the Throats of Normal Men.=—The percentage of -normal individuals harboring hemolytic streptococci in their throats was -investigated in three distinct classes of men, classified according to -the degree of exposure to contact infection. - -The first group includes men largely from country districts, cultured -within an hour after being assembled by their local draft board. The -laboratory car “Lister” was sent to Hot Springs, Ark. to meet the -November draft of men to be sent to Camp Pike. These men were returned -to their homes when the armistice was signed, so that there was no -opportunity to study them after they had lived under camp conditions. - -The second group includes men on duty in Camps Funston and Pike. These -men, while largely from country districts, had been living crowded -together in the camp for a period varying from a few weeks to several -months. - -The third group includes normal men resident in the base hospitals at -Ft. Riley and Camp Pike. This group includes at Camp Pike the medical -personnel of the measles and measles pneumonia wards and represents -individuals most exposed to contact infection with hemolytic -streptococci. On the other hand, the group includes doctors, nurses and -seasoned medical detachment men who are perhaps less susceptible to -respiratory infections than are raw recruits. - -The results of studies of these groups are presented in Tables LXVI and -LXVII. - - TABLE LXVI - - HEMOLYTIC STREPTOCOCCI IN THROATS OF NORMAL MEN NOT RESIDENT IN THE - BASE HOSPITAL - - ═════════════╤═══════╤════════╤════════╤═══════════════════════════════ - PLACE OF │NO. OF │ NO. │PER CENT│ REMARKS - STUDY │ CASES │POSITIVE│POSITIVE│ - DATE │ │FOR HEM.│FOR HEM.│ - │ │ STREP. │ STREP. │ - ─────────────┼───────┼────────┼────────┼─────────────────────────────── - Camp Funston,│ 274│ 60│ 21.9│Men on duty in camp including - Kan., │ │ │ │ 201 white and 73 colored; in - Aug., 1918.│ │ │ │ great part newly drafted men - ─────────────┼───────┼────────┼────────┼─────────────────────────────── - Camp Pike, │ 337│ 25│ 7.4│Largely white men on duty in - Ark., │ │ │ │ camp - Nov. 5 to │ │ │ │ - Dec. 10, │ │ │ │ - 1918 │ │ │ │ - ─────────────┼───────┼────────┼────────┼─────────────────────────────── - Hot Springs, │[100]64│ 0│ 0.0│Men from country districts, - Ark., │ │ │ │ assembled by the local draft - Nov. 12, │ │ │ │ board - 1918 │ │ │ │ - ─────────────┴───────┴────────┴────────┴─────────────────────────────── - - TABLE LXVII - - HEMOLYTIC STREPTOCOCCI IN THROATS OF NORMAL MEN RESIDENT IN THE BASE - HOSPITAL - - ═════════════╤═══════╤════════╤════════╤═══════════════════════════════ - PLACE OF │NO. OF │ NO. │PER CENT│ REMARKS - STUDY │ CASES │POSITIVE│POSITIVE│ - DATE │ │FOR HEM.│FOR HEM.│ - │ │ STREP. │ STREP. │ - ─────────────┼───────┼────────┼────────┼─────────────────────────────── - Ft. Riley, │ 24│ 7│ 29.2│14 convalescent patients in a - Kan., │ │ │ │ surgical ward; 10 laboratory - Aug., 1918 │ │ │ │ workers - ─────────────┼───────┼────────┼────────┼─────────────────────────────── - Camp Pike, │ 153│ 22│[101]7.5│Personnel of measles wards - Ark., │ │ │ │ - Sept. 10 to│ │ │ │ - Nov. 30, │ │ │ │ - 1918. │ │ │ │ - ─────────────┴───────┴────────┴────────┴─────────────────────────────── - -The group of men studied at Hot Springs represents individuals among -whom there was little chance for contact dissemination of hemolytic -streptococci. It is a control series of men from outlying districts -examined before their throat bacteriology has been complicated by the -interchange of mouth organisms which occurs when a group of men are -crowded into close quarters. The entire absence of hemolytic -streptococci by the throat culture method is noteworthy. By multiplying -the chances of identifying hemolytic streptococci by making parallel -cultures from the saliva, and from the peritoneal exudates of mice -inoculated with saliva, hemolytic streptococci were found, in small -numbers, in 3 instances. The findings in this group were only three -throats lightly infected with hemolytic streptococci. They are in direct -contrast with the findings among individuals living in camps under -crowded conditions and are in accord with the findings among recruits -arriving in camp as recorded by Levy and Alexander. - -In the second group, men living for a time in camp, the findings at Camp -Funston and at Camp Pike show rather striking differences. The lower -percentage incidence at Camp Pike is the more remarkable since the -studies were made soon after the influenza epidemic had swept the camp -and made necessary the hospitalization of about 20 to 25 per cent of the -camp population. - -In the third group, namely, individuals resident in the hospital, -percentage rates at Camp Funston are slightly higher than for men -resident in camp. This difference disappears for the entire group at -Camp Pike if we consider a single throat culture, as we must for the -sake of comparison. The majority of these individuals at Camp Pike -served in measles wards from which patients carrying hemolytic -streptococci were removed at weekly intervals. Seven and one-half per -cent of the ward personnel were positives when first cultured. An -additional 7.5 per cent acquired the streptococcus while under -observation. - -=Duration of the “Carrier” State.=—Unfortunately there are very few -observations with regard to the duration of the “carrier” state which -can be determined only by repeated cultures at short intervals. We have -made no observations of the duration of the “carrier” state in healthy -men. Two hundred and forty-two individuals carrying hemolytic -streptococci were identified in the ward treatment of measles. All -except 37 of these cases were “noncarriers” when first observed. The -remaining 205 include 166 contact “carriers” and 39 patients with acute -symptoms of infection by hemolytic streptococci. - -The complete record of throat cultures on these cases is presented in -Table LXVIII. - -=Group I= includes 37 cases positive for hemolytic streptococci on -admission. - -(_a_) Twenty-two of these remained positive throughout the period of -observation. Four patients became negative after one or two weeks and -later showed positive findings, leaving the hospital as positives. These -are classified as “irregular.” The results of culture were as follows: -Cultured once only, 7; positive after one week, 7; positive after two -weeks, 6; positive after three weeks, 2; irregular, 4. - - TABLE LXVIII - - RESULTS OF THROAT CULTURES IN 242 HOSPITAL PATIENTS IDENTIFIED AS “CARRIERS” OF - HEMOLYTIC STREPTOCOCCI; CULTURES TAKEN AT WEEKLY INTERVALS - - ═════╤════╤════╤════╤════╤════╤════╤════╤════╤════╤════╤════╤════╤═══════╤═════ - GROUP│1st │2nd │3rd │4th │5th │6th │7th │8th │9th │10th│11th│12th│No. of │ No. - │Cul-│Cul-│Cul-│Cul-│Cul-│Cul-│Cul-│Cul-│Cul-│Cul-│Cul-│Cul-│Contact│with - │ture│ture│ture│ture│ture│ture│ture│ture│ture│ture│ture│ture│ “Car- │Acute - │ │ │ │ │ │ │ │ │ │ │ │ │riers.”│Hem. - │ │ │ │ │ │ │ │ │ │ │ │ │ │Strep. - │ │ │ │ │ │ │ │ │ │ │ │ │ │Com- - │ │ │ │ │ │ │ │ │ │ │ │ │ │pli- - │ │ │ │ │ │ │ │ │ │ │ │ │ │ ca- - │ │ │ │ │ │ │ │ │ │ │ │ │ │tions - ─────┼────┼────┴────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - =I=│=37=│ =Cases= │ │ │ │ │ │ │ │ │ │ │ - ─────┼────┼────┬────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ +│ │ │ │ │ │ │ │ │ │ │ │ 7│ - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ +│ + │ │ │ │ │ │ │ │ │ │ │ 7│ - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ +│ + │ + │ │ │ │ │ │ │ │ │ │ 6│ - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ +│ + │ + │ + │ │ │ │ │ │ │ │ │ 2│ - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ +│ − │ │ │ │ │ │ │ │ │ │ │ 8│ - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ +│ − │ − │ │ │ │ │ │ │ │ │ │ 1│ - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ +│ − │ − │ − │ − │ │ │ │ │ │ │ │ 1│ - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ +│ + │ − │ │ │ │ │ │ │ │ │ │ 1│ - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ +│ − │ + │ │ │ │ │ │ │ │ │ │ 2│ - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ +│ − │ − │ − │ − │ + │ + │ + │ │ │ │ │ 1│ - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ +│ + │ − │ − │ + │ + │ + │ │ │ │ │ │ 1│ - ─────┼────┼────┴────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - =II=│=67=│ =Cases= │ │ │ │ │ │ │ │ │ │ │ - ─────┼────┼────┬────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ + │ │ │ │ │ │ │ │ │ │ │ 26│ 3 - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ + │ + │ │ │ │ │ │ │ │ │ │ 12│ 5 - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ + │ + │ + │ │ │ │ │ │ │ │ │ 2│ 2 - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ + │ − │ │ │ │ │ │ │ │ │ │ 9│ 1 - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ + │ − │ − │ │ │ │ │ │ │ │ │ 0│ 1 - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ + │ + │ − │ │ │ │ │ │ │ │ │ 2│ 1 - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ + │ + │ + │ + │ − │ − │ + │ − │ │ │ │ 1│ - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ + │ − │ + │ │ │ │ │ │ │ │ │ 2│ - ─────┼────┼────┴────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - =III=│=74=│ =Cases= │ │ │ │ │ │ │ │ │ │ │ - ─────┼────┼────┬────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ + │ │ │ │ │ │ │ │ │ │ 38│ 5 - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ + │ + │ │ │ │ │ │ │ │ │ 5│ 3 - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ + │ + │ + │ │ │ │ │ │ │ │ 4│ 1 - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ + │ + │ + │ + │ │ │ │ │ │ │ 0│ 2 - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ + │ − │ − │ − │ │ │ │ │ │ │ 0│ 1 - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ + │ − │ │ │ │ │ │ │ │ │ 4│ - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ + │ + │ − │ − │ − │ − │ │ │ │ │ 1│ - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ + │ + │ − │ │ │ │ │ │ │ │ 0│ 2 - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ + │ + │ − │ − │ − │ │ │ │ │ │ 1│ - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ + │ + │ + │ + │ − │ │ │ │ │ │ 0│ 1 - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ + │ − │ + │ │ │ │ │ │ │ │ 1│ - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ + │ − │ + │ + │ │ │ │ │ │ │ 2│ - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ + │ − │ + │ + │ + │ │ │ │ │ │ 1│ - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ + │ − │ − │ + │ + │ │ │ │ │ │ 1│ - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ + │ + │ + │ − │ − │ + │ │ │ │ │ 1│ - =IV=│=34=│ =Cases= │ │ │ │ │ │ │ │ │ │ │ - ─────┼────┼────┬────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ − │ + │ │ │ │ │ │ │ │ │ 12│ 4 - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ − │ + │ + │ │ │ │ │ │ │ │ 5│ - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ − │ + │ + │ + │ │ │ │ │ │ │ 4│ - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ − │ + │ − │ │ │ │ │ │ │ │ 3│ 1 - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ − │ + │ − │ − │ │ │ │ │ │ │ 1│ - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ − │ + │ + │ − │ │ │ │ │ │ │ 1│ - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ − │ + │ + │ + │ − │ │ │ │ │ │ 1│ - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ − │ + │ − │ − │ + │ + │ │ │ │ │ 1│ - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ − │ + │ + │ − │ − │ − │ − │ − │ │ │ 0│ 1 - ─────┼────┼────┴────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - =V=│=16=│ =Cases= │ │ │ │ │ │ │ │ │ │ │ - ─────┼────┼────┬────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ − │ − │ + │ │ │ │ │ │ │ │ 1│ 1 - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ − │ − │ + │ + │ │ │ │ │ │ │ 1│ 1 - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ − │ − │ + │ − │ │ │ │ │ │ │ 3│ 1 - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ − │ − │ + │ − │ − │ │ − │ │ │ │ 0│ 2 - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ − │ − │ + │ − │ − │ − │ − │ − │ │ │ 1│ - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ − │ − │ + │ + │ − │ │ │ │ │ │ 1│ - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ − │ − │ + │ − │ + │ │ │ │ │ │ 2│ - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ − │ − │ + │ + │ − │ │ + │ │ │ │ 1│ - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ − │ − │ + │ + │ − │ − │ − │ + │ │ │ 1│ - ─────┼────┼────┴────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - =VI=│ =7=│ =Cases= │ │ │ │ │ │ │ │ │ │ │ - ─────┼────┼────┬────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ − │ − │ − │ + │ │ │ │ │ │ │ 1│ - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ − │ − │ − │ + │ + │ │ │ │ │ │ 2│ - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ − │ − │ − │ + │ − │ │ │ │ │ │ 3│ - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ − │ − │ − │ + │ − │ − │ │ │ │ │ 1│ - ─────┼────┼────┴────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - =VII=│ =4=│ =Cases= │ │ │ │ │ │ │ │ │ │ │ - ─────┼────┼────┬────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ − │ − │ − │ − │ + │ │ │ │ │ │ 2│ - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ − │ − │ − │ − │ + │ + │ │ │ │ │ 1│ - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ − │ − │ − │ − │ + │ − │ − │ − │ − │ − │ 1│ - ─────┴────┼────┴────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - =VIII= =3=│ =Cases= │ │ │ │ │ │ │ │ │ │ │ - ─────┬────┼────┬────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ − │ − │ − │ − │ − │ + │ │ │ │ │ 2│ - ─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼───── - │ −│ − │ − │ − │ − │ − │ − │ + │ + │ + │ │ │ 1│ - ─────┴────┴────┴────┴────┴────┴────┴────┴────┴────┴────┴────┴────┴───────┴───── - -(_b_) Eleven of the patients entering as positives became negative, 10 -after one week and 1 after two weeks. - -This group of cases furnishes no data concerning the duration of the -“carrier” state, since all cases were positive when first observed. In -30 per cent of instances, hemolytic streptococci disappeared within the -first two weeks of observation. - -=Groups II to VIII= include 205 patients who became positive at some -time during their stay in the hospital. The arrangement in groups -depends upon the length of time the patients remained in the hospital -before acquiring S. hemolyticus. Ninety-five of these patients had no -further cultures after the initial positive culture. Fourteen appear as -“irregular,” as defined above. These two classes of cases are omitted in -the following summary of these groups. The initial positive culture is -arbitrarily considered the day of infection and subsequent cultures mark -off weekly intervals. - -(_a_) Thirty-nine patients had acute infections due to hemolytic -streptococci. Thirteen of these patients passed from observation after -their initial positive culture. The cases with repeated cultures after -initial positive may be summarized as in Table LXIX. - - TABLE LXIX - - ═════════════════════════════╤═════════════╤═════════════╤═════════════ - │NO. PATIENTS │NO. BECOMING │ PER CENT - │ CULTURED │ NEGATIVE │ BECOMING - │ │ │ NEGATIVE - ─────────────────────────────┼─────────────┼─────────────┼───────────── - Recultured after one week │ 26│ 7│ 26.9 - Recultured after two weeks │ 14│ 8│ 57.1 - Recultured after three weeks │ 7│ 4│ 57.1 - Recultured after four weeks │ 2│ 2│ 100.0 - ─────────────────────────────┴─────────────┴─────────────┴───────────── - -The records within this small group of cases indicate that hemolytic -streptococci tend to disappear with the passing of the acute infection. - -(_b_) One hundred and sixty-six contact “carriers” are included in -Groups II to VIII. Eighty-two of these passed from observation after -their initial positive culture and 14 appear as “irregular.” The cases -with repeated throat cultures after the initial positive are summarized -in Table LXX. - - TABLE LXX - - ═════════════════════════════╤═════════════╤═════════════╤═════════════ - │NO. PATIENTS │NO. BECOMING │ PER CENT - │ CULTURED │ NEGATIVE │ BECOMING - │ │ │ NEGATIVE - ─────────────────────────────┼─────────────┼─────────────┼───────────── - Recultured after one week │ 70│ 26│ 37.1 - Recultured after two weeks │ 22│ 9│ 40.9 - Recultured after three weeks │ 5│ 5│ 100.0 - Recultured after four weeks │ 4│ 4│ 100.0 - ─────────────────────────────┴─────────────┴─────────────┴───────────── - -These records indicate that contact carriers in great part harbor -hemolytic streptococci during short intervals. A longer period of -observation after the disappearance of hemolytic streptococci would have -been desirable in many instances. Some patients were followed with -consistently negative cultures during three, four and five weeks after -hemolytic streptococci had disappeared. - -It is difficult to explain those instances in which negative cultures -are interposed between positives. Where one negative interrupts positive -cultures, it is possible that the throat culture failed to demonstrate -hemolytic streptococci which were present. Such cases in this series -fall within the limits of the percentage error of throat culture -identification. Where two or three, or even four negative cultures -intervene, reinfection is not impossible. - -=Relation of S. Hemolyticus “Carriers” to the Complications of Acute -Respiratory Diseases.=—In the present study of measles it has been shown -that pneumonia following measles has been no more common in “carriers” -than in “noncarriers.” Nevertheless, pneumonia occurring in badly -infected wards has been modified by streptococcus complications. - -More cases of otitis media have appeared in “carriers” than in -“noncarriers.” The possibility that mild otitis media, which would -ordinarily pass unnoticed, might become evident as the result of -streptococcus invasion must be considered. Levy and Alexander have made -an important contribution to our knowledge of the rôle of hemolytic -streptococci in measles. They find that “carriers” of hemolytic -streptococci among measles patients are especially predisposed to -complications following measles. - -Their cases were drawn from a camp population highly saturated with S. -hemolyticus “carriers.” In the organization from which 89 per cent of -their patients with measles came, there were 83 per cent hemolyticus -“carriers” among men on duty. Among patients with measles, throat -cultures were positive for hemolytic streptococci on admission in 77 per -cent. It is evident that all patients with measles have been exposed to -hemolytic streptococci during the first day or two after admission. -Failure to carry streptococcus would appear to be dependent upon ability -to resist it rather than upon lack of opportunity for acquiring it. Of -388 cases observed by Levy and Alexander only 79 were “noncarriers” of -hemolytic streptococci on admission, and of these, 27 became positive -while under observation; only 52 remain as “noncarriers” of hemolytic -streptococci. This small group must be regarded as a highly selected -one, composed of individuals more than ordinarily resistant to hemolytic -streptococci and perhaps to all complications of measles. The chances -are that these 52 cases placed under any circumstances might very well -have been among the large number of measles cases in which no -complications develop. - -Furthermore, it is not unlikely that any complication of measles may be -modified by a streptococcus secondarily when about 85 per cent of the -cases show S. hemolyticus in the throat. The complications in the cases -of Alexander and Levy appear to have been caused in large part by -streptococcus, but a complete bacteriologic study of them is not -recorded. Complications among streptococcus “carriers” are not identical -with complications due to the streptococcus, and it is desirable to know -what percentage of complications actually due to hemolytic streptococci -occurred among the 85 per cent of patients with measles who carried -hemolytic streptococci. - -=Summary.=—No hemolytic streptococcus complications occurred in 112 -cases of measles observed at Ft. Riley, among which streptococcus -“carriers” rose from 2.6 per cent on admission to 24.1 per cent before -discharge from the hospital. The percentage of “carriers” of hemolytic -streptococci among normal men in the camp supplying these cases was -about 25.5 per cent. - -The influenza epidemic and a small epidemic of measles occurred in part -simultaneously at Camp Pike during September and October, 1918. The -complications following measles at Camp Pike were to a considerable -extent dependent upon the combined effects of influenza and measles. - -Thirty-five per cent of the measles patients showed throat cultures -positive for B. influenzæ on admission to the hospital. On repeated -cultures, this rose to 84 per cent before discharge. - -Ward separation of cases of measles carrying hemolytic streptococci in -their throats and cases not carrying these organisms were practiced in -handling this epidemic. Of 867 cases of measles treated in this manner, -37 were positive for hemolytic streptococci on admission, and 205 -developed positive throat cultures for these organisms during their -period of observation in the hospital. - -At Camp Pike, the percentage incidence of S. hemolyticus “carriers,” on -admission to the measles wards, was 4.2 per cent. In cases recultured -after one week, it was 10.9 per cent; after two weeks 22.8 per cent; -after three weeks 26.2 per cent; and after four weeks 33.1 per cent. The -weekly development of “carriers” in the “clean” treatment wards was -during the first week 9.1 per cent; during the second week 17.4 per -cent; during the third week 17.4 per cent; and during the fourth week -17.4 per cent. - -The principal complications of these 867 cases of measles at Camp Pike -were: pneumonia, 56 cases; otitis media, 48 cases, with subsequent -mastoiditis in 23 cases, 2 of which had extensions to the meninges and -brain. The greater part of the pneumonia occurred early in the period of -observation, while most of the otitis media occurred later. Incidence of -hemolytic streptococci was low during the pneumonia period and high -during the prevalence of otitis media. - -Hemolytic streptococci complicated 9 of these pneumonias; caused a large -percentage of otitis (bacteriology incomplete), and 21 of the 23 cases -of mastoiditis. - -The bacteriology of 35 of the 56 pneumonias showed: Pneumococcus Type II -atypical, in 36 per cent, Type IV in 22.9 per cent, Type I in 2.8 per -cent and Type III in 2.8 per cent; hemolytic streptococci in 22.4 per -cent; and B. influenzæ in 88.6 per cent. - -The culturing of wards as units revealed widespread contact -dissemination of hemolytic streptococci, at times 25 to 50 per cent of -the patients in a ward becoming “carriers” within the period of a week. -Streptococcus pneumonias, otitis media and its complications were -furnished in large part by wards in which active dissemination occurred. - -Streptococcus complications did not occur among 37 patients who were -“carriers” of hemolytic streptococci when admitted to the hospital. - -The epidemic dissemination of hemolytic streptococci occurs in measles -wards, and is a serious danger. Many, patients whose throats become -infected, develop no symptoms. In some instances streptococcus invades, -and renders much more serious lesions caused by other microorganisms. - -Methods to prevent transfer of infection within the ward and separation -of “carriers” from “noncarriers” in different wards are efficient in -keeping epidemic dissemination of hemolytic streptococci under control. -Frequent throat cultures and prompt report of the results of cultures -are essential. - -The dissemination of B. influenzæ in patients with measles was not -controlled by segregation of “carriers” and “noncarriers” of this -organism as identified by throat cultures in separate wards. - - - - - CHAPTER VI - THE PATHOLOGY AND BACTERIOLOGY OF PNEUMONIA FOLLOWING MEASLES - - EUGENE L. OPIE, M.D.; FRANCIS G. BLAKE, M.D.; JAMES C. SMALL, M.D.; AND - THOMAS M. RIVERS, M.D. - - -Among 18 autopsies upon men who have died with pneumonia following -measles there are pulmonary lesions representing almost every type of -pneumonia which has been found in association with influenza. In most -instances pneumonia made its appearance during the second week of -measles and death occurred during the third week. Of 16 instances in -which the record is definite, pneumonia had its onset during the first -week of measles in 4 instances, during the second week in 11 instances, -and in one instance (Autopsy 390) perhaps not referable to measles in -the fifth week. The duration of pneumonia varied from three to -thirty-two days; in 10 instances it did not exceed one week, in 5 -instances it was between one and two weeks and in one instance, -thirty-two days. When the duration of pneumonia exceeded ten days some -evidence of chronic pulmonary disease was found at autopsy. - -The same lack of correspondence between clinical diagnosis and pulmonary -lesions noted with influenza was found following measles. In accordance -with the prevailing opinion concerning the character of pneumonia -following measles, the diagnosis of bronchopneumonia was made in 13 -instances and in all of these cases bronchopneumonia was found at -autopsy. The diagnosis of lobar pneumonia was made 5 times and was -correct only once. Nevertheless, lobar pneumonia was present 4 times, -but was recognized only once (Autopsy 486.) Failure to recognize lobar -pneumonia, was doubtless due in part at least to its association with -purulent bronchitis and peribronchiolar pneumonia (Table LXXI). - - TABLE LXXI - - ═══════╤════╤════════╤════════╤═════════╤═════════╤══════════╤═════════ - NO. OF │RACE│ LENGTH │DURATION│DURATION │CLINICAL │ PURULENT │ LOBAR - AUTOPSY│ │ OF │ OF │ OF │DIAGNOSIS│BRONCHITIS│PNEUMONIA - │ │MILITARY│ILLNESS │PNEUMONIA│ │ │ - │ │SERVICE │ │ │ │ │ - ───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼───────── - 390 │ W │ 1m. │ 35 │ 6 │ L │ │ - │ │ │ │ │ │ │ - 438 │ W │ 2m. │ 22 │ 12? │ B │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - 439 │ W │ 10d. │ 14 │ 11? │ B │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - 441 │ W │ 1m. │ 16 │ 11 │ B │ P │ - │ │ │ │ │ │ │ - 442 │ W │ 1m. │ 17 │ 2+ │ L │ P │ - │ │ │ │ │ │ │ - 443 │ W │ 21d. │ 23 │ 14 │ B │ P │ - │ │ │ │ │ │ │ - 444 │ W │ 1m. │ 9 │ 3 │ B │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - 450 │ W │ 29d. │ 19 │ 5 │ B │ │ + - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - 453 │ W │ 36d. │ 13 │ 6 │ B │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - 481 │ W │ 54d. │ 4+ │ 3? │ B │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - 484 │ W │ 42d. │ 20 │ 7 │ B │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - 486 │ C │ 6d. │ 17 │ 8 │ L │ P │ + - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - 491 │ W │ 2m. │ 19 │ 5 │ B │ │ - │ │ │ │ │ │ │ - 492 │ W │ 49d. │ 20? │ 11? │ L │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - 496 │ W │ 1m. │ 43 │ 32 │ L │ P │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - 505 │ C │ 4m. │ 16 │ 6 │ B │ P │ + - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - 507 │ C │ 5m. │ 14 │ 3 │ B │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - 508 │ C │ 2m. │ 16 │ 5 │ B │ │ + - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - │ │ │ │ │ │ │ - ───────┴────┴────────┴────────┴─────────┴─────────┴──────────┴───────── - - ═══════╤═══════════════╤═══════════════╤═════════════╤═════════════ - NO. OF │PERIBRONCHIOLAR│ HEMORRHAGIC │ LOBULAR │PERIBRONCHIAL - AUTOPSY│ CONSOLIDATION │PERIBRONCHIOLAR│CONSOLIDATION│CONSOLIDATION - │ │ CONSOL. │ │ - │ │ │ │ - ───────┼───────────────┼───────────────┼─────────────┼───────────── - 390 │ M │ │ + │ - │ │ │ │ - 438 │ + │ │ + │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - 439 │ M │ + │ + │ - │ │ │ │ - │ │ │ │ - 441 │ + │ + │ + │ M - │ │ │ │ - 442 │ M │ │ + │ - │ │ │ │ - 443 │ + │ │ │ M - │ │ │ │ - 444 │ M │ + │ + │ - │ │ │ │ - │ │ │ │ - 450 │ M │ │ │ - │ │ │ │ - │ │ │ │ - 453 │ + │ │ + │ M - │ │ │ │ - │ │ │ │ - 481 │ + │ │ + │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - 484 │ + │ │ + │ M - │ │ │ │ - │ │ │ │ - 486 │ │ │ │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - 491 │ │ + │ │ - │ │ │ │ - 492 │ M │ + │ + │ M - │ │ │ │ - │ │ │ │ - │ │ │ │ - │ │ │ │ - 496 │ + │ │ + │ - │ │ │ │ - │ │ │ │ - 505 │ │ │ │ - │ │ │ │ - │ │ │ │ - 507 │ │ │ │ - │ │ │ │ - │ │ │ │ - 508 │ M │ │ │ M - │ │ │ │ - │ │ │ │ - │ │ │ │ - ───────┴───────────────┴───────────────┴─────────────┴───────────── - - ═══════╤═══════╤════════════╤═════════╤═══════╤══════════════ - NO. OF │ABSCESS│INTERSTITIAL│MULTIPLE │EMPYEMA│BRONCHIECTASIS - AUTOPSY│ │SUPPURATIVE │ABSCESSES│ │ - │ │ PNEUMONIA │ IN │ │ - │ │ │CLUSTERS │ │ - ───────┼───────┼────────────┼─────────┼───────┼────────────── - 390 │ │ │ │ │ - │ │ │ │ │ - 438 │ + │ │ │ E │ - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - 439 │ │ │ │ │ + - │ │ │ │ │ - │ │ │ │ │ - 441 │ │ │ │ │ + - │ │ │ │ │ - 442 │ N │ + │ │ E │ - │ │ │ │ │ - 443 │ │ │ │ │ + - │ │ │ │ │ - 444 │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - 450 │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - 453 │ │ │ │ │ + - │ │ │ │ │ - │ │ │ │ │ - 481 │ │ │ │ │ + - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - 484 │ │ │ │ │ + - │ │ │ │ │ - │ │ │ │ │ - 486 │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - 491 │ │ + │ │ E │ - │ │ │ │ │ - 492 │ + │ │ │ E │ + - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - 496 │ │ │ │ │ + - │ │ │ │ │ - │ │ │ │ │ - 505 │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - 507 │ N │ + │ │ E │ - │ │ │ │ │ - │ │ │ │ │ - 508 │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - │ │ │ │ │ - ───────┴───────┴────────────┴─────────┴───────┴────────────── - - ═══════╤════════════════╤══════════╤════════╤════════╤════════╤════════ - NO. OF │ UNRESOLVED │ORGANIZING│BACTERIA│BACTERIA│BACTERIA│BACTERIA - AUTOPSY│BRONCHOPNEUMONIA│BRONCHITIS│ IN │ IN │IN LUNG │IN BLOOD - │ │ │ SPUTUM │BRONCHUS│ │OF HEART - │ │ │ │ │ │ - ───────┼────────────────┼──────────┼────────┼────────┼────────┼──────── - 390 │ │ │No S. │ │ │Pneum. - │ │ │Hem. │ │ │II a - 438 │ + │ │B. inf. │S. hem.,│Pneum. │0 - │ │ │ │B. inf. │II, S. │ - │ │ │ │ │vir., │ - │ │ │ │ │B. inf.,│ - │ │ │ │ │S. hem. │ - 439 │ │ + │No S. │B. coli │Pneum. │0 - │ │ │hem. │ │IIa, S.│ - │ │ │ │ │aur. │ - 441 │ │ │ │B. inf.,│B. inf.,│0 - │ │ │ │S. aur. │S. aur. │ - 442 │ │ │No S. │B. inf.,│ │S. hem. - │ │ │hem. │S. hem. │ │ - 443 │ + │ │No S. │B. inf.,│B. coli.│0 - │ │ │hem. │B. coli.│ │ - 444 │ │ │B. inf. │Pneum. │Pneum. │Pneum. - │ │ │ │IIa, B.│IIa, │II a. - │ │ │ │inf. │B.inf. │ - 450 │ │ │B.inf., │B. inf.,│B. inf. │Pneum. - │ │ │No. S. │Staph. │ │IV. - │ │ │hem. │ │ │ - 453 │ │ │ │Pneum. │Pneum. │Pneum. - │ │ │ │I, B. │I. │I. - │ │ │ │Inf. │ │ - 481 │ + │ │No S. │B. inf.,│B. inf. │0 - │ │ │hem. │Pneum. │ │ - │ │ │ │IIa, │ │ - │ │ │ │S.hem. │ │ - 484 │ + │ │Pneum. │B. inf.,│ │0 - │ │ │IV, B. │Diploids│ │ - │ │ │inf. │ │ │ - 486 │ │ │No S. │B. inf.,│B. inf. │0 - │ │ │hem. │Pneum. │ │ - │ │ │ │IIa, S.│ │ - │ │ │ │hem., │ │ - │ │ │ │Staph. │ │ - 491 │ │ │S. hem. │B. inf.,│S. hem.,│S. hem. - │ │ │ │B. coli.│B. coli.│ - 492 │ + │ │S. hem.,│ │S.hem., │S. hem. - │ │ │B. inf. │ │Pneum. │ - │ │ │ │ │IV, B. │ - │ │ │ │ │coli., │ - │ │ │ │ │B. inf. │ - 496 │ + │ + │B. inf.,│B. inf. │0 │0 - │ │ │no S. │ │ │ - │ │ │hem. │ │ │ - 505 │ │ │No S. │Pneum. │Pneum. │Pneum. - │ │ │hem. │II a., │II a. │II a. - │ │ │ │S. hem. │ │ - 507 │ │ │S. hem. │S. hem.,│S. hem.,│S. hem. - │ │ │ │B. inf.,│S. aur. │ - │ │ │ │S. aur. │ │ - 508 │ │ │S. hem. │Pneum. │Pneum. │Pneum. - │ │ │ │IIa, B.│II a. │II a. - │ │ │ │inf., S.│ │ - │ │ │ │hem. │ │ - ───────┴────────────────┴──────────┴────────┴────────┴────────┴──────── - -=Changes in Bronchi.=—The changes in the bronchi do not differ in -character from those associated with pneumonia following influenza. -Purulent bronchitis recognized at autopsy by the presence of -mucopurulent material in the small bronchi was found in a much larger -proportion of instances in this group of autopsies occurring in 13 of 18 -instances (72.2 per cent), whereas it was present in only 55.6 per cent -of autopsies on individuals with pneumonia following influenza. There -was peribronchial hemorrhage recognizable on gross examination in 3 -autopsies and microscopically in 3 additional instances. - -Bronchiectasis was present in a considerable proportion of these -autopsies, dilatation of bronchi being noted in 7, but it was usually -moderately advanced and at times limited to the bases of the lungs. The -short duration of respiratory disease perhaps explains the infrequency -of advanced bronchiectasis. The incidence of the lesion is greater with -measles (43.7 per cent) than with influenza (22.4 per cent). - -Microscopic changes in the bronchi do not differ from those found after -influenza. Evidence of acute inflammation, often hemorrhagic in -character, is found within the lumen of the bronchus and in the tissues -immediately in contact with the lumen. Not infrequently the epithelium -is lost; there is superficial necrosis and deposition of fibrin upon the -surface and within the tissue. In the deeper tissues of the bronchial -wall there is infiltration with lymphoid and plasma cells, which in the -larger bronchi is particularly advanced about the mucous glands of which -the acini exhibit degenerative changes. With the onset of chronic -changes new formation of fibrous tissue occurs in the wall of the -bronchus and in the contiguous interalveolar walls. The lining -epithelium often loses its columnar cells and assumes a squamous type. - -Changes in the bronchi with bronchiectasis have been similar to those -following influenza. Weakening of the wall permitting dilatation is -brought about by necrosis extending outward from the lumen a varying -distance into the bronchial wall and permitting the formation tears -which diminish resistance to intrabronchial pressure. - -=Lobar Pneumonia.=—Lobar pneumonia following measles occurred in 4 -instances. Onset in these cases was on approximately the 9th, 10th, -11th, or 14th day of measles; the onset of bronchopneumonia bore a -similar time relation to the onset of measles, the average interval -being nine days. Hepatization with lobar pneumonia was in 1 instance -red, in 3 instances gray, and in all save 1 instance the consolidation -was firm and coarsely granular on section. In the exceptional instance -the greater part of the right upper lobe was laxly consolidated and -rather finely granular but the microscopic appearance was in all -instances that of lobar pneumonia. Lobar pneumonia in 2 of these cases -was associated with purulent bronchitis present in parts of the lung -that had not undergone consolidation, whereas in the other 2 instances -there were acute bronchitis and peribronchiolar pneumonia recognized by -microscopic examination. - -In one instance hepatization of the lung presented some noteworthy -features. - - =Autopsy 450.=—G. D., white, aged twenty-one, a farmer, resident of - Arkansas, had been in military service twenty-nine days. Onset of - illness began on October 2, nineteen days before death, and on - admission on the same day the diagnosis of measles was made. Signs - of pneumonia, regarded as bronchopneumonia, were recognized five - days before death. Three days later there was otitis media and - paracentesis was performed. On October 3 and 10 neither S. - hemolyticus nor B. influenzæ was found in the sputum; on October 17 - and 20 S. hemolyticus was not found but B. influenzæ was present. - - =Anatomic Diagnosis.=—Acute lobar pneumonia with gray and red - hepatization in right upper and lower lobes; edema and peribronchial - hemorrhage in left lung. - -[Illustration: - - Fig. 29.—Lobar pneumonia following measles, showing extension of - gray hepatization from lower to upper lobe through a defect in the - septum separating the two lobes. Autopsy 450. -] - - The entire lower lobe of the right lung (Fig. 29) with the exception - of a narrow air-containing zone in contact with basal surface is - firmly consolidated. The greater part of the consolidated tissue is - yellowish gray, firm and coarsely granular. The uppermost part of - the consolidated tissue is softer than elsewhere as if it has - undergone autolysis. The lowermost part of the consolidated tissue - in a zone from 2.5 to 3.5 cm. in breadth is firmly consolidated but - deep red. The bronchi contain stiff plugs of fibrin. In the upper - lobe continuous with the consolidated part of the lower is a - semicircular patch of yellowish gray consolidation. It overlies the - line of the interlobular cleft at the site of a break in its - continuity. Consolidation appears to have spread from the lower lobe - into the upper at the site where the alveolar tissue of the two - lobes is continuous but is absent from that part of the upper lobe - separated from the lower by the interlobular cleft. This - semicircular patch of yellowish gray consolidation is separated from - air containing tissue of the upper lobe by a zone of red - hepatization about 1 cm. in thickness. - - Bacteriologic examination showed the presence of Pneumococcus IV in - the blood of the heart; B. influenzæ alone was obtained from the - right lower lobe and B. influenzæ and staphylococcus from the left - main bronchus. - -The distribution of lobar pneumonia in the foregoing autopsy indicates -that it has spread like a wave from the upper part of the lower lobe -(Fig. 32) penetrating into the upper where the alveolar tissue of the -two lobes is in contact; gray hepatization is everywhere separated from -air containing tissue by an advancing zone of red hepatization. - -It may be assumed that lobar pneumonia was caused by Pneumococcus II -atypical in 3 instances although it was recovered from the lungs only -twice, for in the third instance (Autopsy 486) it was found in the -bronchus and in the inflamed pleural cavity; pneumococci were doubtless -previously present in the lung, but had disappeared at least from that -part from which the culture was made. Pneumococcus IV was evidently the -cause of pneumonia in 1 instance (Autopsy 450), for it was found in the -blood of the heart although it was absent in the culture from the lung. - -Little significance can be attributed to the observation that B. -influenzæ was present in pure culture in the lungs from Autopsies 450 -and 486, for the presence of Pneumococci IV in the blood of the heart in -Autopsy 450 and of Pneumococcus II atypical in the pleura in Autopsy 486 -furnishes evidence in view of the occurrence of lobar pneumonia that -pneumococci had disappeared from the lungs. B. influenzæ was found both -in the lungs and bronchus or in the bronchus alone in 3 of these 4 -cases. - -The relation of hemolytic streptococci to the lesion is of interest. In -3 of 4 instances of lobar pneumonia this microorganism had entered the -bronchi but was not found in the lungs or in the heart’s blood; and -gross and histologic examination showed none of the lesions which are -usually caused by it. In 1 instance (Autopsy 508) hemolytic -streptococci, absent from the throat when the patient was admitted to -the hospital with measles sixteen days before death, appeared in a -culture made five days later and was subsequently found three times; it -had penetrated into the bronchus but failed to reach the lung. -Observations made upon lobar pneumonia following influenza have shown -the relative insusceptibility of lobar pneumonia with gray hepatization -to secondary infection with hemolytic streptococci (p. 160). Autopsy 508 -demonstrates that occurrence of hemolytic streptococci in the sputum of -a patient with pneumonia does not furnish conclusive proof of the -existence of streptococcus pneumonia. - -=Bronchopneumonia.=—Bronchopneumonia has been found in every instance of -pneumonia following measles save 3, namely in Autopsy 486, Autopsy 505 -with lobar pneumonia and Autopsy 507 with interstitial suppurative -pneumonia. It is not improbable that further histologic study might have -demonstrated small patches of peribronchiolar pneumonia, for purulent -bronchitis was present in the two autopsies with lobar pneumonia. This -small group of cases has reproduced all of the important features of -bronchopneumonia following influenza. Hemorrhagic peribronchiolar -consolidation characterized by the presence of small gray spots -clustered about terminal bronchi upon a homogeneously red background has -been found in 5 of 18 instances of pneumonia with measles. Pfeiffer -regarded this lesion as characteristic of the pneumonia of influenza. -Peribronchiolar patches of consolidation with no surrounding hemorrhage -were found in 14 instances, being recognized first by microscopic -examination in half of this number. Lobular consolidation occurred in 11 -autopsies and peribronchial fibrinous pneumonia was present in a third -of the autopsies on patients with pneumonia of measles. - -Bronchial, peribronchial and intraalveolar hemorrhage is much more -commonly associated with the pneumonias of influenza than with the more -familiar types of acute bronchopneumonia. Exuded blood may undergo -absorption; and with bronchopneumonia which, persisting unresolved, has -assumed the characters of a chronic lesion, it is common to find -mononuclear cells often in great abundance filled with brown pigment -derived from the hemoglobin of red blood corpuscles. - -Autopsy 439 is an example of acute hemorrhagic bronchopneumonia; there -are red lobular and confluent lobular patches of consolidation which -upon the pleural surface have a blue or purplish color. In the dependent -part of the left lung occupying a large part of the lower lobe there is -lax, red consolidation marked by gray or yellowish gray spots of -peribronchiolar pneumonia and in this lobe bronchi are encircled by -zones of hemorrhage. Pneumococcus II atypical was obtained from the -lung. In Autopsy 444 the lesion has the same hemorrhagic character -although lobular patches are in a stage of grayish red hepatization. -Pneumococcus II atypical has been found in the heart’s blood, and with -B. influenzæ in lungs and bronchus. Autopsy 441 is an example of the -occurrence of conspicuous nodules of peribronchiolar consolidation in -some parts of the lungs with the same lesion in other parts on a -background of hemorrhage. B. influenzæ and S. aureus have been found in -both lungs and bronchi. - -Steinhaus[102] states that the pneumonia of measles is never lobular -inflammation but occurs in small patches several of which may be found -in a single lobule. - -Chronic fibroid pneumonia following measles characterized by cellular -infiltration and proliferation of the interstitial tissue of the lung -has been described by Bartels,[103] Steinhaus,[104] Hart,[105] -MacCallum[104] and others. - -[Illustration: - - Fig. 30.—Unresolved bronchopneumonia with measles showing new - formation of fibrous tissue about a bronchus and in immediately - adjacent alveolar walls; partially obliterated alveoli occur in the - peribronchial fibrous tissue. Autopsy 481. -] - -[Illustration: - - Fig. 31.—Unresolved bronchopneumonia with measles showing a nodule of - chronic fibrous pneumonia surrounding a respiratory bronchiole. - Autopsy 481. -] - -The incidence of unresolved bronchopneumonia among instances of -bronchopneumonia following measles is higher than that among -bronchopneumonias following influenza. There have been 6 instances of -chronic or unresolved bronchopneumonia among 18 pneumonias following -measles, namely 33.3 per cent. The incidence of unresolved -bronchopneumonia among 241 autopsies on pneumonia following influenza -has been 21, namely 8.7 per cent. The essential features of this chronic -lesion have been as follows: (_a_) chronic peribronchiolar pneumonia -indicated by the presence of firm nodules of peribronchiolar -consolidation which have considerable resemblance to miliary tubercles. -Induration of the nodule occurs because the walls of alveoli surrounding -and adjacent to a respiratory bronchiole (Fig. 31) become thickened and -infiltrated with cells and there is organization of exudate within the -alveoli. New formation of fibrous tissue (Fig. 32) occurs where the -acute inflammatory reaction of peribronchiolar consolidation is most -advanced (p. 169 and compare with Figs. 3 and 4), namely, about the -respiratory bronchiole, alveolar duct and the proximal parts of the -infundibula, disappearing as the distal half of the infundibulum is -approached. Distention of the alveoli explaining the distention of the -lung and its failure to collapse on section is a noteworthy feature of -the lesion. (_b_) Chronic peribronchial inflammation (Fig. 30) with new -formation of fibrous tissue about the smaller and medium-sized bronchi -extending into immediately adjacent alveolar walls and often associated -with organization of peribronchial fibrinous pneumonia. (_c_) Chronic -lobular inflammation with changes similar to those just cited, -distributed throughout entire lobules. (_d_) Moderate thickening of -interlobular septa. Bronchiectasis may be associated with the chronic -lesion (Autopsies 443, 481, 484, 492 and 496) but with one exception -(Autopsy 443) has been only moderately advanced. Suppurative pneumonia -with abscess formation has occurred twice (Autopsies 438 and 492). - -[Illustration: - - Fig. 32.—Unresolved bronchopneumonia with measles showing chronic - pneumonia about a respiratory bronchiole and alveolar duct; alveoli - about the proximal parts of three distended infundibula are filled - with polynuclear leucocytes, whereas inflammatory changes disappear - as the distal parts of the infundibula are approached. Autopsy 481. -] - -With acute bronchopneumonia following measles the average duration of -pneumonia, determined by the date upon which physical signs of pneumonia -were first recognized and in consequence subject to some error, was -seven days; in instances of chronic bronchopneumonia the average -duration of pneumonia has been fifteen days. - -The bacteriology of acute bronchopneumonia following measles is shown in -Table LXXII. - - TABLE LXXII - - ════════════╤═══════╤═══════════════╤════════════════╤═════════════════ - WITH NO │SPUTUM │ BACTERIA IN │ BACTERIA IN │ BACTERIA IN - SUPPURATION │IN LIFE│BLOOD OF HEART │ LUNGS │ BRONCHI - ────────────┼───────┼───────────────┼────────────────┼───────────────── - Autopsy 390│ │Pneum. II atyp.│ │ - 439│ │0 │Pneum. II atyp. │B. coli - │ │ │ S. aur. │ - 441│ │0 │B. inf., S. aur.│B. inf., S. aur. - 444│B. inf.│Pneum. II atyp.│Pneum. II atyp. │Pneum. II atyp. - │ │ │ B. inf. │ B. inf. - 453│ │Pneum. I │Pneum. I │Pneum. I, B. inf. - With │ │ │ │ - suppuration:│ │ │ │ - 442│S. hem.│S. hem. │ │B. inf., S. hem. - 491│S. hem.│S. hem. │S. hem., B. coli│B. inf., B. coli - 507│S. hem.│S. hem. │S. hem., S. aur.│S. hem., B. inf., - │ │ │ │ S. aur. - ────────────┴───────┴───────────────┴────────────────┴───────────────── - -It is noteworthy that pneumococci have been recovered from the heart’s -blood or lung in all but 1 (Autopsy 441) of 5 instances of acute -bronchopneumonia with no suppuration and is doubtless the cause of this -pneumonia. Pneumococcus II atypical has been found in 3 of 4 instances -of lobar pneumonia following measles and is present in 3 of these 5 -instances of bronchopneumonia. - -Where suppuration has been found, hemolytic streptococci have been -present in the sputum, in the heart’s blood and either in the lungs -(Autopsy 491) or in the bronchi (Autopsy 442) or in both (Autopsy 507). -In these instances pneumococci have not been found, though in view of -the readiness with which pneumococci disappear from the lungs it is -possible that they have been the primary cause of bronchopneumonia. - -The bacteriology of 6 instances of unresolved bronchopneumonia following -measles is given in Table LXXIII. - - TABLE LXXIII - - ════════════╤═══════╤═══════════════╤════════════════╤═════════════════ - WITH NO │SPUTUM │ BACTERIA IN │ BACTERIA IN │ BACTERIA IN - SUPPURATION │IN LIFE│BLOOD OF HEART │ LUNGS │ BRONCHUS - ────────────┼───────┼───────────────┼────────────────┼───────────────── - Autopsy 443│ │0 │B. coli │B. inf., B.coli - 481│ │0 │B. inf. │B. inf., Pneum. - │ │ │ │ II, atyp., S. - │ │ │ │ hem. - 484│Pneum. │0 │0 │B. inf., - │ IV., │ │ │ diphtheroids - │ B. │ │ │ - │ inf. │ │ │ - 496│Pneum. │0 │0 │B. inf. - │ IV., │ │ │ - │ B. │ │ │ - │ inf. │ │ │ - With │ │ │ │ - Suppuration:│ │ │ │ - Autopsy 438│B. inf.│0 │Pneum. II atyp.,│S. hem., B. inf. - │ │ │ S. vir. B. │ - │ │ │ inf. S. hem. │ - 492│St. │S. hem. │S. hem., Pneum. │ - │ hem.,│ │ IV, B. coli, │ - │ B. │ │ B. inf. │ - │ inf. │ │ │ - ────────────┴───────┴───────────────┴────────────────┴───────────────── - -Whereas with acute bronchopneumonia death has been accompanied and -perhaps caused by bacterial invasion of the blood by pneumococci or -streptococci in 5 of 7 instances, with unresolved or chronic -bronchopneumonia, bacteriemia has been present only once, namely, in -Autopsy 492 in which with suppurative pneumonia hemolytic streptococci -have entered the blood. It is probable that pneumococci have likewise -had an important part in the causation in these instances of -bronchopneumonia which have run a chronic course but in all save 2 cases -(Autopsies 438 and 492) have disappeared from the lungs. Pneumococcus II -atypical has been found twice. - -B. influenzæ has been found in association with acute bronchopneumonia -in the lungs in 1 of 6 examinations and in the bronchi in 5 of 6 -examinations. These figures indicate that it is present in small numbers -if at all in the consolidated lung tissue but is relatively abundant in -the bronchi. With chronic bronchopneumonia B. influenzæ has been found -in every instance, in half of the examinations of lungs and in all of -the examinations of bronchi. In 1 instance (Autopsy 481) B. influenzæ -has been found in pure culture in the lung; Pneumococcus II atypical has -been found in the bronchus and has perhaps disappeared from the -pneumonic lung, since this microorganism is often destroyed in the late -stages of pneumonia so that its demonstration at autopsy is no longer -possible. In 1 instance B. influenzæ found in the bronchus has been the -only microorganism isolated at autopsy, although the sputum during life -contained B. influenzæ and Pneumococcus IV. - -=Suppurative Pneumonia.=—Suppurative pneumonia with formation of -abscesses has occurred in 2 autopsies with pneumonia following measles -(Autopsies 438 and 492), both instances of chronic bronchopneumonia. In -Autopsy 438 the lower and posterior part of the left lower lobe has been -consolidated and has had on section a cloudy, grayish red color; within -this area of consolidation and immediately below the pleural surface -there have been opaque, yellow spots where the tissue has been softer -than elsewhere. Microscopic examination shows that the tissue has here -undergone widespread necrosis so that all nuclear stain has disappeared; -at the edges of the necrotic tissue polynuclear leucocytes are often -present in large numbers, but necrosis is much more conspicuous than -suppuration. In the necrotic tissue and at its edges streptococci are -present in vast numbers. Hemolytic streptococci have been grown both -from the lung and from the bronchus, but these have not been the only -microorganisms present, for Pneumococcus II atypical and S. viridans -have been obtained from the lungs and B. influenzæ from lungs and -bronchus. - -In Autopsy 492 with chronic bronchopneumonia the posterior half of the -right lower lobe is laxly consolidated, deep red in color and with the -cloudy appearance often associated with streptococcus pneumonia; upon -this background are peribronchiolar spots of yellow color, in places -well seen below the pleura; in the corresponding part of the left lower -lobe similar nodules have been converted into small abscesses by central -suppuration. There is empyema on the right side, fibrinopurulent -pericarditis, and purulent peritonitis. Hemolytic streptococci had been -found in the sputum three times, the first examination being thirteen -days before death. This microorganism is found in pure culture in the -blood of the heart and with Pneumococci IV, B. coli and B. influenzæ in -the lung. Hemolytic streptococci were found in the right pleural exudate -and peritoneum. - -The pneumonias following measles give opportunity to consider the -relationship of suppurative interstitial pneumonia to unresolved or -chronic bronchopneumonia, which is characterized by infiltration and -proliferation of the fibrous tissue of the lungs. A number of those who -have studied the pneumonia of measles have recognized that this chronic -interstitial lesion is a common sequela of measles. MacCallum has -designated the lesion “interstitial bronchopneumonia,” and has included -under this name its acute stage in which the interstitial character of -the lesion is not more evident than with other forms of acute -bronchopneumonia. He has regarded S. hemolyticus as the cause of -“interstitial bronchopneumonia” following measles. A review of the -autopsies which he has described shows that he has included under the -same designation typical instances of interstitial suppurative pneumonia -associated with suppurative lymphangitis. Instances of unresolved, -chronic or “interstitial” bronchopneumonia and of interstitial -suppurative pneumonia which we have observed after measles, demonstrate -that the two lesions are distinguishable both by their anatomic -characters and by their etiology. - -Three instances of suppurative interstitial pneumonia occurred among the -pneumonias following measles (Autopsies 442, 491 and 507). The lesion is -characterized by suppuration of the interlobular septa and particularly -noteworthy is the occurrence of suppurative lymphangitis, lymphatics -being immensely dilated and distended with purulent fluid so that their -irregularly dilated, beaded appearance is recognizable upon the section -of the lung. In the group of pneumonias following measles this lesion -has not been associated with unresolved or chronic bronchopneumonia; no -nodular tubercle-like foci of bronchopneumonia have been found at -autopsy, and there has been no thickening of the interstitial tissue. -The lesion has accompanied confluent lobular pneumonia in 2 instances -(Autopsies 442 and 491). In the third instance (Autopsy 507) there was -in the neighborhood of the suppurative lesions diffuse consolidation -which had the cloudy, gray red color of streptococcus pneumonia, but -this consolidation was not lobular in distribution. - -The etiology of interstitial suppurative pneumonia established by study -of instances following influenza is confirmed by Table LXXII (p. 345) -showing the bacteriology of instances of acute bronchopneumonia -following measles. Pneumococci are almost invariably found in -uncomplicated instances of bronchopneumonia and hemolytic streptococci -have been absent, whereas in 3 instances of suppurative interstitial -pneumonia hemolytic streptococci have been found in the sputum during -life, in pure culture in the blood of the heart and in the lungs and -bronchus (missed in the bronchus in one instance, Autopsy 507). In the 3 -instances of the disease B. influenzæ has been found in the bronchi. - -Table LXXIII shows that suppuration has accompanied unresolved -bronchopneumonia (“interstitial bronchopneumonia”) in 2 instances -(Autopsies 438 and 492), but in these instances the interlobular tissue -of the lung has not been the site of suppuration and there has been no -suppurative lymphangitis. Localized abscesses have been formed; -hemolytic streptococci, as with abscesses following influenza, have been -found. - -Empyema has occurred only 5 times in association with pneumonia -following measles and in these 5 instances has been associated with -suppurative pneumonia caused by hemolytic streptococci. In Autopsy 492 -there was fibrinopurulent pleurisy on both sides. Aspiration had been -performed 3 times and at autopsy the right pleural cavity contained 150 -c.c. of purulent fluid. In small pockets, corresponding to shallow oval -depressions upon the anterior surface of the lung, fluid was walled off -from the general cavity. The pericardial cavity contained 25 c.c. of -turbid yellow fluid containing yellow flakes of fibrin and the -peritoneal cavity contained thick purulent fluid. Hemolytic streptococci -present in the heart’s blood and lung were recovered from the right -pleural cavity and from the peritoneum. Among 3 instances of empyema -accompanying interstitial suppurative pneumonia, in 1 (Autopsy 491) -there were walled off pockets of fluid similar to those just described. -Aspiration of the right pleural cavity had been performed 3 times; at -autopsy 100 c.c. of fibrinopurulent fluid was found on the right side -and 450 c.c. on the left. There was general purulent peritonitis and the -peritoneal cavity contained 350 c.c. of thick yellow pus. Hemolytic -streptococci were obtained from the heart’s blood, right lung, right -pleural cavity and peritoneum. - -Among 4 instances of lobar pneumonia following measles there was -serofibrinous pleurisy 3 times; in 1 instance there is no record of -pleural change. In 1 instance of lobar pneumonia (Autopsy 505) the right -pleural cavity contained 800 c.c. of serofibrinous exudate and the -pericardial cavity contained 510 c.c. of opaque, yellow seropurulent -fluid; Pneumococcus II atypical in pure culture was obtained from the -blood, lung and pleural and pericardial exudates. Among 9 instances of -bronchopneumonia following measles there was fibrinous pleurisy 3 times, -serofibrinous 3 times, and no recorded lesion of the pleura 3 times. -Empyema, like suppurative pneumonia following measles, is in most -instances, but not constantly, caused by invasion of hemolytic -streptococci. - -The foregoing study has shown that pneumonia which has followed measles -has reproduced all of the lesions usually found after influenza. There -is no pulmonary lesion peculiar to measles. Lobar pneumonia follows the -disease in some instances, but bronchopneumonia with purulent bronchitis -is more common. The same tendency to hemorrhagic inflammation found with -the pneumonia of influenza is seen after measles. Unresolved pneumonia -with chronic inflammatory changes in the interstitial tissue of the lung -has all of the characters of the similar lesion following influenza but -has been found in a larger proportion of the pneumonias of measles. - -B. influenzæ has been found in the bronchi in 14 of 16 examinations, -namely in 87.5 per cent of fatal instances of pneumonia. In 1 instance -in which B. influenzæ has not been found at autopsy, it has been -isolated from the sputum during life. It is not improbable that B. -influenzæ has been constantly present in the inflamed bronchi both after -influenza and measles. It is noteworthy that the outbreak of pneumonia -following measles has been in part coincident with, in part slightly -subsequent to, an epidemic of influenza which has exposed every -individual in the camp to infection with this disease. - -B. influenzæ has been found in the lung with the pneumonia of measles in -7 of 17 examinations, namely, in 41.2 per cent of instances. The -microorganism with measles, as with influenza, is found in the inflamed -lung only half as frequently as in the bronchi. It appears to be -peculiarly adapted for multiplication within the bronchial tubes, and -its isolation from the inflamed lung in less than half of the cases of -pneumonia is perhaps referable to its presence in the small bronchi and -bronchioles. The presence of B. influenzæ in the lungs in pure culture -in 3 instances at first sight suggests that the microorganism produces -pneumonia, but a more intimate survey of these cases gives little -support to this view. In Autopsy 450 B. influenzæ has been found in pure -culture in the lung, but Pneumococcus IV has been isolated from the -blood of the heart and has been with little doubt the cause of typical -lobar pneumonia present in this instance. In Autopsy 486 the condition -is almost identical, for in the presence of lobar pneumonia B. influenzæ -has been found in the lung in pure culture, but Pneumococcus II atypical -has been isolated from the pleural cavity and from the bronchus; in both -autopsies the pneumococci which have caused lobar pneumonia have -disappeared from that part of the consolidated lung from which a culture -has been made; and here doubtless its invasion has been effectively -resisted although it is still present in other organs. In Autopsy 481 in -which B. influenzæ has been isolated from the lung in pure culture, the -part of pneumococci in the production of the fatal disease is less -evident; in this instance, Pneumococcus II atypical, S. hemolyticus and -B. influenzæ have been isolated from the bronchus. - -The presence of microorganisms which have a well-established etiologic -relation to pneumonia explains the occurrence of pneumonia and makes -unnecessary the assumption that B. influenzæ, which is present in the -lungs in less than half of the instances examined, is essential to the -production of the pneumonic consolidation. In view of the -well-recognized etiology of lobar pneumonia we may conclude that this -lesion is referable to the pneumococci (Pneumococcus II atypical in 3 -instances and Pneumococcus IV in 1 instance) isolated from the autopsies -in which this lesion occurred. Pneumococcus (Pneumococcus II atypical in -3 instances and Pneumococcus I in 1 instance) has been isolated from the -lungs or heart’s blood in 4 of 5 instances of acute bronchopneumonia -unaccompanied by suppuration. With unresolved bronchopneumonia with no -suppuration, pneumococci have been in no instance found in the lungs or -blood though their presence in the washed sputum during life or in the -bronchus at autopsy suggests the possibility that they may have -disappeared from the lungs. - -In all instances in which suppuration has occurred hemolytic -streptococci have been found in the lungs or blood, or in both. The -occurrence of pneumococci in the lungs in 2 of 5 instances of -suppurative pneumonia indicates that infection with S. hemolyticus is in -some instances at least superimposed upon acute bronchopneumonia caused -by pneumococci. Bronchopneumonia in 3 instances has the character of -that caused by pneumococci. It is probable that the sequence of -infection frequently observed after influenza, namely, bronchial -infection by B. influenzæ, followed by pneumonia caused by pneumococci, -followed in turn by infection by hemolytic streptococci with necrosis or -suppuration, is not uncommon after measles. - -=Pneumonia Associated with Acute Infectious Diseases Other than -Influenza and Measles.=—A small group of autopsies have been excluded -from the list of those which accompanied the epidemic of influenza, -because pneumonia has been associated with an acute infectious disease -to which it is perhaps secondary. These few instances of pneumonia, like -those following measles reproduce characters of the pneumonia following -influenza and may be in part referable to influenza which has attacked -an individual suffering with typhoid fever, mumps or scarlet fever. - -In 2 instances pneumonia followed typhoid fever and appeared on -September 23 and 26 shortly after the epidemic of influenza had become -evident. In the following autopsy there was acute lobar pneumonia which -appeared ten days after onset of typhoid fever. - - =Autopsy 245.=—O. H., white, aged twenty-one, a farmer, resident of - Oklahoma, had been in military service twenty-one days. Onset of - illness was on September 13 with chill, headache, cough and nausea. - The patient was admitted two days later with the diagnosis of acute - bronchitis. On September 20 the abdomen was tense, the spleen was - enlarged and rose spots were present. Signs of lobar pneumonia were - found September 23. Death occurred September 25, twelve days after - onset of typhoid fever and two days after recognition of pneumonia. - - =Anatomic Diagnosis.=—Typhoid fever with necrotic ulcers in lower - ileum and in colon; hyperplasia of ileocecal lymphatic nodes; acute - splenic tumor; parenchymatous degeneration of liver and kidneys; - acute lobar pneumonia with gray hepatization in left lower lobe and - red hepatization and edema in left upper lobe and in right lung; - serofibrinous pleurisy on left side. - - The left pleural cavity contains 75 c.c. of yellowish gray turbid - fluid. Over the left lower lobe there is a layer of fibrin. The - upper half of the lobe is firmly consolidated, pinkish gray and - coarsely granular; the bronchi contain plugs of fibrin. The lower - and posterior part of the lower lobe is consolidated deep red and - edematous. The left upper lobe is edematous and a layer in the - lowermost part in contact with the lower lobe is deep red and - consolidated. The left lung weighs 1,490 grms. The lower half of the - right upper lobe and the posterior border of the lower is - consolidated deep red and edematous; the lung weighs 970 grms. - - Bacteriologic examination shows that the blood of the heart contains - Pneumococcus II atypical. - -The foregoing autopsy is of interest because typical lobar pneumonia -appears to have spread from the left lower lobe, where consolidation is -firm and gray, to the adjacent part of the upper lobe where -consolidation is red and edematous. - -The second instance of pneumonia following typhoid fever is an instance -of suppurative pneumonia caused by S. aureus. - - =Autopsy 329.=—J. B., white, aged twenty-two, laborer, resident of - Oklahoma, had been in military service two days before onset of - symptoms of typhoid fever. He was admitted to the hospital on August - 27 and B. typhosus was found in cultures from the blood on September - 2 and 3. Acute bronchitis appeared on September 26 when the epidemic - of influenza had almost reached its height. A diagnosis of - bronchopneumonia was made on the day preceding death, which occurred - forty-one days after onset of typhoid fever and eleven days after - onset of bronchitis. - - =Anatomic Diagnosis.=—Typhoid ulcers of ileum; acute splenic tumor; - acute bronchopneumonia with red hemorrhagic peribronchiolar and - lobular consolidation in right lung; multiple abscesses forming a - circumscribed group in left upper lobe; purulent bronchitis. - - The pleural cavities contain no excess of fluid. The lungs are - voluminous and there is interstitial emphysema. Below the pleura are - bluish red spots of lobular consolidation; in the right upper lobe - is a large patch of red consolidation marked by yellowish gray spots - in clusters. In the external and upper part of the left upper lobe - is a patch of gray consolidation within which, beneath the pleura, - there are small abscesses grouped to form a cluster 1.5 cm, across. - - Bacteriologic examination demonstrates no microorganisms in the - blood of the heart; of two cultures from the left lung one contains - S. aureus in pure culture, the other S. aureus and a few colonies of - Pneumococcus IV. Cultures from the left main bronchus and from the - mucopurulent exudate in a small bronchus both contain B. influenzæ, - S. aureus and Pneumococcus IV. - -In the foregoing case bronchitis has appeared thirty days after onset of -typhoid fever on September 26, immediately preceding the height of the -epidemic of influenza. In association with hemorrhagic bronchopneumonia -there is suppurative pneumonia with small abscesses forming a -circumscribed group below the pleura; there is no empyema. The lesion -has the characters of the staphylococcus abscesses following influenza, -and S. aureus is found in association with the lesion; B. influenzæ is -identified in two cultures from the bronchi. - -In 2 instances pneumonia was associated with parotitis which was -diagnosed mumps. - - =Autopsy 403.=—C. T., colored, aged twenty-five, a laborer, resident - of Arkansas, had been in military service one month. Illness began - September 27 with swelling of face behind jaw and difficult - mastication; the patient was admitted to the hospital on the same - day with the diagnosis of mumps. Pneumonic consolidation was - recognized on October 8. Death occurred October 13, sixteen days - after onset of illness and six days after recognition of pneumonia. - - =Anatomic Diagnosis.=—Acute lobar pneumonia with red and beginning - gray hepatization of lower and parts of upper and middle right - lobes; acute bronchopneumonia with lobular consolidation in left - lung; purulent bronchitis; bronchiectasis in left lung. - - The lower lobe of the right lung with the exception of the anterior - and basal edge is firmly consolidated; the posterior part of the - middle lobe and a small corner at the posterior and lower part of - the upper lobe is similarly consolidated. The consolidated tissue is - gray and coarsely granular on section. The remainder of the lung is - dry and voluminous, and the bronchi contain purulent fluid. The left - lung contains red and gray patches of consolidation, from 0.2 to 3 - cm. across. Bronchi contain purulent fluid and in the lowermost - parts of both upper and lower lobes are moderately dilated. - - Bacteriologic examination shows that the blood of the heart contains - Pneumococcus III. - -It is noteworthy that there was in this case, as in many instances of -influenza, both lobar and bronchopneumonia. Purulent bronchitis was -present and there was bronchiectasis throughout one lung. - -In the following case the diagnosis of mumps may be questioned since the -lesion of the parotid has characters of terminal suppurative parotitis. - - =Autopsy 417.=—H.W.D., white, aged twenty-four, a farmer, resident - of Oklahoma, had been in military service one month. He said that he - had had pneumonia four times. He was admitted to the hospital - delirious and the diagnosis of lobar pneumonia was made. Parotitis - regarded as mumps appeared five days before death and suppuration - occurred on the right side of the face. Death of the patient - occurred thirteen days after admission to the hospital. - - =Anatomic Diagnosis.=—Acute bronchopneumonia with lobular - consolidation in both lungs; suppurative pneumonia with necrosis and - beginning abscess formation in left lung; purulent pleurisy in left - side; purulent bronchitis; bronchiectasis; acute parotitis. - - The left pleural cavity contains 100 c.c. of purulent fluid of - creamy consistence. The left lung is voluminous and bound to the - chest wall in places. There are numerous patches of lobular - consolidation. At the apex of the lung there is a large area of - consolidation, 7 cm. across, where the tissue is cloudy gray and - soft in consistence. In the upper lobe is a well-defined patch of - grayish yellow color, 6 by 2 cm., with opaque yellow edges; purulent - fluid escapes from the cut surface. Bronchi throughout the lung are - widely dilated and contain purulent fluid. The right lung is - voluminous and contains lobular patches of consolidation; bronchi of - this lung are widely dilated. - - Bacteriologic examination shows the presence of hemolytic - streptococci in the blood of the heart; hemolytic streptococci and - B. influenzæ in the lung, and hemolytic streptococci, B. influenzæ - and S. aureus in a main bronchus. - -In association with bronchopneumonia there have been necrosis and -beginning abscess formation with empyema, the suppurative lesions being -caused by hemolytic streptococci which had finally entered the blood -stream. There was purulent bronchitis, and the lungs had the voluminous -character often associated with this lesion; there was beginning -bronchiectasis. B. influenzæ was obtained both from the lung and from -the bronchus. - -In 2 instances (Autopsies 323 and 335) the diagnosis of scarlet fever -was made in patients suffering with pneumonia following influenza. These -lesions have been included in the list of influenzal pneumonias. In the -following instance the patient was admitted with scarlet fever, later -developed acute follicular tonsillitis, and finally suppurative -pneumonia caused by hemolytic streptococcus. - - =Autopsy 311.=—E. J., white, aged twenty-two, a tinsmith and - automobile repairer, resident of Arkansas, had been in military - service three months. Onset of illness was on September 18 with - headache and sore throat. The patient was admitted September 24 with - the diagnosis of scarlet fever; two days later there was acute - follicular tonsillitis. Pneumonic consolidation on the right side - was recognized October 2, three days before death. - - =Anatomic Diagnosis.=—Acute suppurative pneumonia with three small - abscesses below pleura of right lower lobe; acute fibrinopurulent - pleurisy on both sides; serous pericarditis. - - The right pleural cavity contains 1500 c.c. of turbid, dirty yellow - fluid containing masses of fibrin; the left cavity has 500 c.c. of - similar contents. The pericardium contains 30 c.c. of turbid fluid - containing a small quantity of fibrin; there are ecchymoses below - the epicardium. The right lung is collapsed and in the lower lobe - contains three small subpleural abscesses, the largest of which is - 1.5 cm. across. - - Bacteriologic examination shows the presence of hemolytic - streptococci in pure culture in the blood of the heart and in the - right lung. From the right main bronchus are obtained hemolytic - streptococci, B. influenzæ, Pneumococcus IV and a few staphylococci. - -In this instance there has been infection with streptococcus which is a -common sequela of scarlet fever. In the absence of evidence of -bronchopneumonia there has been abscess formation below the pleura with -empyema and pericarditis. B. influenzæ has been found in the bronchus. - -The pneumonias found in association with measles reproduce the -characters of the pneumonias described in association with influenza. -Particularly noteworthy is the occurrence of lobar pneumonia, -hemorrhagic peribronchiolar pneumonia, interstitial suppurative -pneumonia, severe bronchitis with bronchiectasis and unresolved -bronchopneumonia. In the presence of an epidemic of influenza attacking -more than one fourth of the population of a camp, those suffering with -diseases, such as measles, typhoid fever, mumps, etc., are unlikely to -escape entirely, and it is probable that the tendency to the occurrence -of pneumonia present in association with these diseases will be -increased. The close resemblance between the pneumonias which we have -found with the diseases mentioned, on the one hand, and the pneumonias -of influenza on the other, both being characterized by the occurrence of -hemorrhagic, suppurative and chronic pulmonary lesions, indicates that -influenza has had a part in the production of the pneumonia found with -measles and some other infectious diseases during the progress of the -epidemic of influenza. - - - - - CHAPTER VII - SUMMARY OF THE INVESTIGATION AND CONCLUSIONS REACHED - - EUGENE L. OPIE, M.D. - - -There is no reason for believing that the influenza which prevailed in -this country differed in any essential feature from that of previous -epidemics and particularly of the pandemic of 1889–90. Our studies have -shown that an organism with the morphologic and cultural characters of -B. influenzæ of Pfeiffer has been constantly found in association with -the disease, and so frequently demonstrated in association with its -pulmonary complications that there is little doubt of its constant -presence. The bronchial and pulmonary complications of influenza present -characters which, while varied, are not usually observed in the absence -of epidemic influenza, and in this pandemic agree with those of the -former pandemic so far as it is possible to determine from the -descriptions available. - -Especially noteworthy is the severity of the changes within the -bronchial passages. Clinical studies have shown that purulent bronchitis -has occurred in 36 per cent of instances of influenza. The sputum with -this condition has contained B. influenzæ in all instances, but although -there were no signs of pneumonia it has been constantly associated with -other microorganisms, namely, pneumococci (in 11 of 13 instances), S. -hemolyticus, S. viridans, M. catarrhalis, etc. - -Identification of the bacteria which have been present in the bronchi of -those dead with pneumonia following influenza have determined what -microorganisms have penetrated into the lower respiratory passages. B. -influenzæ has been found so frequently (80 per cent) that there is good -reason to believe that it has been constantly present and has not been -isolated in every instance because it has been overgrown by other -microorganisms on the plates or after long continued illness has -disappeared from the bronchi. Mixed infections of B. influenzæ and other -microorganisms are constantly found in the inflamed bronchi; -combinations of B. influenzæ and pneumococci, B. influenzæ and hemolytic -streptococci or these combinations with staphylococci or the four -organisms together are common. Other microorganisms such as B. coli, S. -viridans, M. catarrhalis and diphtheroid bacilli are not infrequently -associated with those which have been mentioned. - -Purulent bronchitis has been found in 137 of 241 autopsies; its -bacteriology differs in no respect from that which has just been -described and indeed no line can be drawn between this condition and the -bronchitis invariably present with the pneumonias of influenza. Other -evidence of profound injury to the bronchi is the frequent occurrence of -hemorrhage in a zone ensheathing the smaller bronchi, and the common -occurrence of bronchiectasis when the fatal disease has lasted more than -two or three weeks. - -Microscopic study demonstrates that the changes in the bronchial walls -are such as destroy the defences against invasion by microorganisms. The -bronchial epithelium undergoes destruction which is not infrequently -limited to the superficial ciliated cells, but often complete loss of -epithelium occurs. The mucous glands of the larger bronchi exhibit a -special susceptibility to injury, and in the early stages of the lesion -profound degenerative changes are found in the secreting cells, whereas -at a later stage chronic inflammatory changes are almost invariably -present. - -Pneumonia following influenza is in most instances bronchopneumonia, but -typical lobar pneumonia has been found in autopsies representing 40.7 -per cent of pneumonias of influenza. Lobar pneumonia is frequently -accompanied by purulent bronchitis, and in a considerable number of -autopsies (34 of 98 with lobar pneumonia) lobar and bronchopneumonia -have occurred in the same individual. - -Statistics based upon the clinical diagnosis of lobar and -bronchopneumonia following influenza are so inaccurate that they have -little if any value. Notwithstanding careful study of the symptomatology -of the disease, lobar and bronchopneumonia following influenza are not -accurately distinguishable by the means usually employed, and an -erroneous diagnosis has been recorded on the patient’s history in 36.6 -per cent of 227 fatal cases with autopsy. A diagnosis of suppurative -pneumonia is rarely if ever made. The difficulties of diagnosis are in -part explained by the frequent association of lobar pneumonia with -purulent bronchitis, with bronchopneumonia or with both, and by the -occurrence of bronchopneumonia with confluent lobular consolidation -involving a large part of a lobe or whole lobes. - -There are many defects in the present knowledge of the symptomatology of -the pneumonias under consideration. The symptoms of suppurative -pneumonia are not clearly defined. Many of these deficiencies might be -supplied by further application of the time-honored method of comparing -the clinical course of the disease with the changes found at autopsies, -supplemented by bacteriologic studies made during life and confirmed -after death. - -With peribronchial pneumonia bronchi of medium size, on the cut surface -of the lung, are surrounded by sharply defined zones of pneumonic -consolidation perhaps 0.5 cm. in radius, and this lesion furnishes -conclusive proof that the inflammatory process can extend directly -through the bronchial wall reaching all alveoli within a limited -distance for these alveoli bear no relation to the distribution of the -terminal bronchi of the affected bronchus. This peribronchial pneumonia -is usually characterized by fibrinous exudate, and pneumococcus has been -found either in the blood of the heart or in the lung in all of 6 -instances in which peribronchial consolidation has been recognized at -autopsy; in half of these autopsies Pneumococcus Type II has been -isolated and this relationship is especially noteworthy because Type II -has been uncommonly associated with the pneumonias of influenza. - -=Lobar Pneumonia.=—The distribution of lobar pneumonia has repeatedly -furnished evidence that the process spreads like the peribronchial -lesion directly through the tissue of the lung and is not necessarily -disseminated by way of the bronchial tree. Pneumococci doubtless enter -the lung by way of the bronchi; the occurrence of lobar pneumonia in -frequent association with influenza which exhibits a peculiar capacity -to destroy the defences of the lower respiratory passages is in harmony -with this view. The presence of pneumococci in the blood furnishes no -evidence that infection is hematogenous, for bacterial infections, -particularly at their onset, are frequently accompanied by bacteriemia. -The wave-like spread of lobar pneumonia may be indicated by a narrow -zone of red hepatization separating a large patch of firm, gray -consolidation from engorged but air containing lung tissue. A -semicircular patch of consolidation not infrequently extends from the -left lower lobe into the upper lobe at the site where the interlobular -cleft is absent. This patch may be firm and gray in continuity with -similar consolidation in the lower lobe but surrounded over its convex -surface by a zone of red hepatization. - -There is no reason to doubt that the lobar pneumonia which we have found -with influenza has been constantly caused by pneumococci. We have -encountered no instance of lobar pneumonia caused by the capsulated -bacillus of Friedländer. The incidence of different types of pneumococci -in the lung with lobar pneumonia has been as follows: Type IV, 32.4 per -cent; Type II, atypical, 26.5 per cent; Type III, 17.6 per cent; Type -II, 5.9 per cent; Type I, 2.9 per cent; no pneumococci found 14.7 per -cent. It is noteworthy that this distribution of types is in sharp -contrast with the lobar pneumonia of civil life with which Types I and -II constitute the cause of two-thirds of all instances, and is in -agreement with the etiology of the pneumonias found in an army camp -(Funston) in the absence of influenza in epidemic proportion. - -=Bronchopneumonia.=—Bronchopneumonia is associated with intense -bronchitis penetrating to the finest bronchioles and is characterized by -consolidation distributed in such definite relation to the bronchial -tree that dissemination of the inflammatory irritant by way of the -bronchi is evident. Consolidation occurs (_a_) in foci affecting alveoli -in immediate proximity to the respiratory bronchioles and in consequence -clustered about the terminal bronchi, the intervening alveolar tissue -containing air; (_b_) in foci of the same character surrounded by -intraalveolar hemorrhage which occupies all alveolar tissue between -adjacent foci; (_c_) throughout whole lobules or groups of lobules, -intervening lobules being unaffected; (_d_) surrounding bronchi of -medium size like a sheath. - -The lobar pneumonia of influenza is characterized by frequent -association with purulent bronchitis and bronchopneumonia. The -bronchopneumonia of influenza exhibits characters which serve to -distinguish it from other forms of bronchopneumonia; (_a_) The -associated lesions of the bronchi are unusually severe; purulent exudate -accumulates within the lumen and the lining membrane is destroyed. (_b_) -Pneumonia is frequently hemorrhagic with accumulation of blood within -the alveoli and within and surrounding the bronchi. (_c_) There is -unusual susceptibility of the injured bronchi and of the pulmonary -tissue to secondary invasion by streptococci and staphylococci with -consequent necrosis and suppuration. (_d_) Bronchiectasis frequently -accompanies bronchitis. (_e_) Bronchopneumonia frequently fails to -resolve and the lesion assumes the character of a chronic pneumonia. - -With bronchopneumonia pneumococci are found with B. influenzæ in the -bronchi and lungs in nearly half and in the blood in approximately -one-third of instances of the disease, but hemolytic streptococci, -staphylococci, S. viridans, B. coli, M. catarrhalis and other -microorganisms are very frequently found in various combinations: they -undoubtedly have a part in the production of the lesion. Mixed infection -of the lung and even of the blood with pneumococci and hemolytic -streptococci is often found, and study of the sputum during life has -repeatedly shown that pneumococci alone are present shortly after the -onset of the disease, whereas hemolytic streptococci appear later or are -first discovered at autopsy. In such instances pneumococci have not -infrequently disappeared from the lung and at autopsy hemolytic -streptococci alone are demonstrable. - -The part which B. influenzæ has in the production of bronchopneumonia is -of great interest. This microorganism is demonstrable by cultures in at -least three-fourths of all instances of bronchopneumonia but is obtained -from the inflamed lung tissue in less than half. In no instance of -pneumonia have we found B. influenzæ unassociated with other -microorganisms, whereas repeatedly pneumococci have been the only -microorganism demonstrable in the lung and very frequently the only -organism present in the blood. In view of the difficulty of -demonstrating the microorganism in plates overgrown by other bacteria, -it is probable that its incidence in the bronchi is much higher, if it -is not constantly present, whereas its isolation from the lung is in -part referable to its presence in the small bronchi where it can be -readily demonstrated by cultures or by microscopic preparations. We have -been almost uniformly unsuccessful in demonstrating the microorganism in -the alveoli of the lung. Goodpasture and Burnett,[106] who have devised -a special method for the demonstration of B. influenzæ in tissues, have -found few of these microorganisms in the alveoli of the lungs. - -Pneumonia characterized by the occurrence of small (peribronchiolar) -spots of leucocytic pneumonia upon an almost homogeneous background of -intraalveolar hemorrhage, was regarded by Pfeiffer as the characteristic -lesion produced by his microorganism. B. influenzæ in our autopsies has -borne the same relation to this lesion which it has exhibited to other -forms of bronchopneumonia; pneumococci have been present with -approximately the same frequency and hemolytic streptococci have often -been found. - -=Streptococcus Pneumonia.=—The occurrence of streptococcus pneumonia -with suppuration occurring in the trail of influenza was frequently -observed during the pandemic of 1889–90. It is now well recognized that -the streptococcus concerned is one capable of causing hemolysis. -Suppurative pneumonia referable to hemolytic streptococci is of two -types which are readily separable by their anatomic characters: (_a_) -One or several abscesses are situated below the pleura and accompanied -by empyema. Their relation to severe lesions of the bronchi is not -infrequently demonstrable, for a destructive lesion of the bronchial -wall has penetrated into the surrounding alveolar tissue so that -necrosis of tissue and subsequent abscess formation occur in continuity -with the bronchial lumen. The localization of the abscess below the -pleura is referable to the greater severity of the lesions of the small -bronchi which are most numerous at the periphery, to the greater -severity of these bronchial lesions at the bases of the lung, and to the -relation of lymphatics within the interior of the lung to those of the -pleura. It is not improbable that stasis of lymph caused by thrombosis -of the lymphatics has a part in the production of abscess. Preceding or -accompanying abscess formation, the lung tissue undergoes consolidation -and in a wide area about the abscess has a homogeneous gray cloudy -appearance occasionally mottled by opaque patches of necrosis. (_b_) -Interstitial suppurative pneumonia is a lesion not infrequently found in -association with influenza (21 times among 241 autopsies) and rarely, if -ever, seen in its absence. There are few references to this lesion in -the pathologic literature of the English language and those of German -origin in great part refer to the period of the pandemic of 1889–90. The -lesion is essentially suppurative lymphangitis, and both thrombosis and -suppuration of the lymphatics are widespread throughout the affected -lung. In proximity to the inflamed lymphatics and the surrounding -interstitial septa, lung tissue throughout parts of the lobes or even -throughout a whole (lower) lobe has undergone consolidation and has the -gray, cloudy appearance of streptococcus pneumonia. - -=Staphylococcus Pneumonia.=—Abscesses produced by staphylococci differ -in anatomic characters and sequelæ from those caused by hemolytic -streptococci. Small abscesses occur in one or several localized -clusters; these abscesses are grouped about a bronchus and have their -origin in its terminal branches. This relation may be readily -demonstrated in microscopic sections. The lesion tends to remain -localized and pneumonic consolidation is limited to the immediate -neighborhood of the group of abscesses. There is no lymphangitis and the -lesion is not accompanied by empyema. - -=Empyema.=—Empyema is almost invariably associated with suppurative -pneumonia caused by hemolytic streptococci. Among our autopsies purulent -fluid has been found in the pleural cavity 55 times; it occurred 15 -times among 178 instances of lobar or bronchopneumonia and 50 times -among 60 instances of suppurative pneumonia referable to S. hemolyticus. -In our experience hemolytic streptococci and pneumococci are the only -microorganisms which exhibit a noteworthy capacity to penetrate from the -lung to the pleural cavity. We have not found nonhemolytic streptococci -(_e. g._, S. viridans) in association with empyema. - -Staphylococcus has failed to invade the pleural cavity even when a -pulmonary abscess has been present below the pleura, and in the only -instances in which staphylococci have been isolated from the pleural -cavity thoracotomy had been performed for empyema caused by hemolytic -streptococci (2 instances) or an abscess communicating with both -bronchus and pleura. B. influenzæ has been found in the pleural cavity -with empyema only once and in this instance cannot be regarded as the -cause of the lesion, for it has accompanied hemolytic streptococci. - -=Bronchiectasis.=—Bronchiectasis has been frequently found as a sequela -of the severe bronchitis of influenza and there has been abundant -opportunity to study the lesion in process of development. These -observations have furnished a satisfactory explanation of its etiology -and pathogenesis. Infection of the bronchi by B. influenzæ, accompanied -by a variety of other microorganisms, notably hemolytic streptococci and -staphylococci, has caused profound changes in the bronchial wall -beginning with destruction of the epithelial surface, and followed by -necrosis penetrating partially or completely through the wall and -occasionally extending into the surrounding alveolar tissue. The -difference between the atmospheric pressure within the bronchi and the -lower inspiratory pressure within the surrounding alveoli, accentuated -by forced inspiration at intervals and by occlusion of the bronchioles -with mucopurulent exudate, ruptures the necrotic tissue and produces -longitudinal fissures which are recognizable both macroscopically and -microscopically. In consequence of the separation of the edges of these -fissures by intrabronchial pressure the circumference is increased. -These rents in the wall are limited and partially healed by fibrinous -pneumonia about them, by new formation of fibrous tissue from the -bronchial wall, and adjacent interalveolar septa, by organization of -fibrin within adjacent alveoli and finally by growth of epithelium over -the denuded surfaces. - -Bronchitis caused by B. influenzæ and pyogenic micrococci with necrosis -of the bronchi wall is the essential factor in the production of -bronchiectasis, but advanced bronchiectasis is found only in those -individuals who have survived the onset of illness during several weeks, -for dilatation under the influence of positive intrabronchial and -negative extra-bronchial pressure occurs slowly. - -=Unresolved Bronchopneumonia.=—Unresolved lobar pneumonia has not been -recognized among instances of pneumonia following influenza, but -unresolved bronchopneumonia is of frequent occurrence and has well -definable gross and microscopic characters. There are purulent -bronchitis, bronchiectasis and distention of the lung tissue, so that it -fails to collapse; particularly characteristic are the indurated foci of -peribronchiolar pneumonia, which being firm and sharply defined, have -the appearance of miliary tubercles. When the process is sufficiently -long continued there are recognizable patches of fibroid pneumonia. -Microscopic examination shows that the lesion is characterized by -organization of fibrinous exudate not only within the alveoli but within -bronchioles as well, and by thickening of the alveolar walls, thickening -of fibrous tissue about the bronchi and blood vessels, and thickening of -interstitial septa. These changes may occur as peribronchiolar patches -of consolidation, producing tubercle-like nodules, or may involve areas -of hemorrhagic peribronchiolar or of lobular consolidation, or may be -limited to the immediate neighborhood of bronchi (peribronchial). - -No peculiarity of the bacterial flora of the bronchi or of the lung -offers a satisfactory explanation of the failure of pneumonic exudate to -resolve. Mixed infections have been common and S. hemolyticus, -staphylococci, pneumococci, S. viridans, B. coli, etc., have been found -in association with B. influenzæ but the incidence of these -microorganisms has not been greater than with bronchitis. The lesion has -occurred in association with B. influenzæ and pneumococci unassociated -with other microorganisms. It seems probable that the severity of injury -to the bronchial and alveolar walls accompanied by recurring bacterial -invasion or by continued infection with B. influenzæ and one or several -cocci, is the factor concerned in the inhibition of resolution and the -production of chronic pneumonia. If the disease does not result in early -death, chronic pneumonia has an opportunity to manifest itself. - -In this investigation of the bacteriology and pathology of influenza and -its complications, certain microorganisms have been found so frequently -that it is desirable to discuss the pathogenicity of each and to define -the character of the lesions which it causes. - -=Bacillus Influenzæ.=—The microorganism has been constantly found in -association with influenza when cultures and animal inoculations have -been made from various parts of the respiratory tract within from one to -five days after the onset of the disease at a time when there have been -acute symptoms of the disease. - -It is often identified with difficulty in the presence of other -microorganisms and may be overlooked when a single culture is made. -Repeated cultures from the throat alone made from the fourth to the -eighth day after admission to the hospital, at a time when temperature -had fallen to normal, have demonstrated the presence of B. influenzæ in -30.5 per cent, whereas the incidence of the microorganism in similar -cultures on admission had been 63.4 per cent. The incidence of B. -influenzæ in the present epidemic of influenza is not less than that -found by Pfeiffer in the epidemic which he studied in 1892. - -Nevertheless we have found that B. influenzæ is frequently an inhabitant -of the mouth and throat of normal individuals. By inoculation of mice -with the saliva or sputum of 76 patients with influenza, the -microorganism has been found in 80.3 per cent; by inoculation of mice -with the saliva of 185 normal men at army cantonments, it was found in -41.6 per cent; by inoculation of mice with saliva from 50 recruits -immediately after they were assembled from isolated farming communities -where only a few cases of influenza had occurred, it was found in 22 per -cent. Figures for the same groups examined by a single throat culture -were as follows: 65.7 per cent, 25.9 per cent and 0 per cent. - -Experiments which we have performed on monkeys show that inoculation of -the nasopharynx with B. influenzæ obtained from patients with influenza -is followed by ill-defined symptoms associated with the presence of B. -influenzæ within the throat. After from two to eleven days the symptoms -and the microorganism disappear. Injection of B. influenzæ into the -trachea causes bronchitis and the microorganism may be recovered from -the inflamed bronchi two or three days after inoculation. - -The constant association of B. influenzæ with influenza suggests that it -is the cause of the disease. Its widespread occurrence in the throats of -normal individuals does not contradict this view, since pneumococci long -indistinguishable from those which usually cause lobar pneumonia are -commonly found in the throats of healthy men. It is possible that B. -influenzæ is a secondary invader, entering the respiratory tract when -susceptibility is increased by an unknown virus causing influenza; but -there is no convincing evidence in favor of this view. It is desirable -to determine if microorganisms having the characters of B. influenzæ -found with influenza differ in type from those found in the throats of -healthy men and if the invasion of the respiratory tract by B. influenzæ -is followed by the appearance of immunity reactions in the serum of the -patient. Experiments on monkeys demonstrate the pathogenicity of the -microorganism. - -The relation of B. influenzæ to the bronchitis of influenza indicates -that it has a part in the production of the pulmonary sequelæ of -influenza. The microorganism has been found by a single culture from the -bronchial passages in 80 per cent of instances of bronchitis with fatal -pneumonia following influenza and is probably constantly present, -usually in immense number, in the bronchial mucus. It is obtained from -the pneumonic lung in only about 40 per cent of instances, and -microscopic examination of prepared tissue shows that a bacillus with -the morphology of B. influenzæ is often demonstrable in the bronchial -passages but seldom in the alveoli of the lung. The microorganism is -well adapted to multiply under conditions present in the bronchi but -doubtless readily disappears from the alveoli which are the site of an -inflammatory reaction. The microorganism has an important part in the -production of the associated mucopurulent and hemorrhagic inflammation -of the bronchi, but it is rarely if ever found in pure culture, being -associated with a considerable variety of pyogenic cocci and -occasionally bacilli. Infection of the bronchi with B. influenzæ in -immense numbers offers an explanation of the severity of the -inflammatory process within the bronchi, and of the subsequent -dilatation and other chronic changes which occur in them. The presence -of the microorganism and the accompanying injury to the ciliated -epithelium and mucous glands are important factors in lowering the -resistance of the bronchial passages to secondary bacterial infection. - -We have obtained no evidence that B. influenzæ alone is capable of -causing pneumonia. Its occurrence in less than half of all pneumonic -lungs is explainable, in part at least, by its presence in the terminal -bronchi which are cut across whenever the lung is punctured for culture. -B. influenzæ alone has been found only once among 153 pneumonic lungs -from which cultures were made, and in this instance (Autopsy 487) S. -hemolyticus present in the blood of the heart, pleural cavity and -bronchus doubtless had a part in the production of the associated -pneumonia. Pfeiffer maintained that the lesion we have designated -hemorrhagic peribronchiolar consolidation was characteristic of -infection with his microorganisms. With this lesion B. influenzæ has -been found in the lungs in slightly more than half of our autopsies but -never alone, pneumococci being found in a third, hemolytic streptococci -in more than a half and staphylococci in a fourth of the lungs examined. - -B. influenzæ has relatively little capacity to penetrate from the -bronchi into the lung tissue and rarely penetrates into the pleural -cavity (once with Pneumococcus III, once with S. hemolyticus and once in -pure culture), and only once has it been found in the blood of the -heart, in this instance in company with S. hemolyticus. Capacity of the -microorganism to penetrate from the bronchi into other tissues, both in -man and as our experiments have shown in the monkey, is increased by -association with pyogenic cocci. - -=Pneumococcus.=—Lobar pneumonia following influenza, like lobar -pneumonia in civil life unassociated with influenza, has been caused by -pneumococci, but there is the notable difference that the pneumococci -usually found are those types which are commonly present in the mouths -of healthy men, namely, Types IV, III and atypical II and not the -so-called fixed types, namely, Types I and II, which represent the usual -cause of lobar pneumonia unassociated with influenza. It appears that -influenza increases susceptibility to lobar pneumonia, so that it is -frequently caused by microorganisms which under other conditions are -less capable of producing this lesion. The association of the -pneumococci usually found in the mouth with the lobar pneumonia of -influenza does not exclude the possibility that pneumococci transmitted -from one individual to another, when newly recruited troops are brought -together, have an important part in the production of pneumonia. - -Bronchopneumonia is frequently caused by pneumococci and the types which -are recovered from the lung and blood do not differ from those found -with lobar pneumonia, those usually present in the mouth being -predominant, but the incidence of pneumococci with bronchopneumonia has -been much less than with lobar pneumonia. Both lobar and -bronchopneumonia caused by pneumococci have undergone secondary -infection with hemolytic streptococci in a large proportion of instances -and both pneumococci and streptococci are often recovered at autopsy. -Nevertheless, the bacterial flora of the bronchi and lungs is much more -varied with broncho than with lobar pneumonia, and it is evident that -microorganisms other than pneumococci are capable of causing -bronchopneumonia. - -In instances of bronchopneumonia associated with pneumococci, fibrin has -been abundant in the alveolar exudate. - -The pneumococcus exhibits a notable tendency to produce an inflammatory -process which extends through the bronchial walls and from one alveolus -through the alveolar walls to those adjacent, for in 6 instances in -which the bronchi were surrounded by pneumonic consolidation -recognizable at autopsy, pneumococci were uniformly the causative agent, -Pneumococcus Type II, otherwise rarely found, being present in half of -these cases. - -Pneumonia caused by one type of pneumococcus does not necessarily confer -immunity from other types of pneumococci, and with somewhat limited -opportunity we have observed a number of instances in which, following -recovery from pneumonia caused by one type of pneumococcus, a second -attack of pneumonia, usually fatal, has been associated with pneumococci -of a different type. This recurring pneumonia in a considerable -proportion of the relatively small number of instances observed has been -produced by Pneumococcus Type II which otherwise has been seldom found -among the cases which we have studied. The virulence of this -microorganism doubtless explains its ability to cause recurrent -pneumonia. - -=Streptococcus Hemolyticus.=—Secondary infection with S. hemolyticus is -a common event during the course of lobar pneumonia following influenza. -It is noteworthy that this streptococcus infection of the lung has -almost invariably occurred in the stage of red hepatization, whereas -with gray hepatization, when the alveoli are filled with polynuclear -leucocytes, S. hemolyticus rarely invades the lung. It is possible that -infection with S. hemolyticus tends to prolong the stage of red -hepatization. - -The most significant change produced in the pneumonic lung by -streptococci is necrosis. When after death with lobar pneumonia -hemolytic streptococci, usually associated with pneumococci, are found -both in the lungs and blood of the heart, the lung contains patches of -necrosis recognized microscopically, in which the alveolar walls and -exuded cells have uniformly lost their nuclei. Microscopic examination -demonstrates the presence of chains of streptococci in immense number in -these necrotic foci; elsewhere chains of streptococci occur but are much -less abundant. In some instances streptococci exhibit a tendency to -enter lymphatics and to cause acute lymphangitis with lymphatic -thrombosis and edema of the adjacent interstitial tissue. - -Hemolytic streptococci have been more frequently found in association -with broncho- than with lobar pneumonia. In 24.5 per cent of instances -of lobar pneumonia, doubtless in all instances caused by pneumococci, -hemolytic streptococci have invaded the lungs and in 12.6 per cent of -instances have found their way into the blood. With bronchopneumonia -hemolytic streptococci have been obtained from the lungs in 29.8 per -cent of instances and from the blood of the heart in 34.3 per cent. - -With lobar pneumonia there is little doubt that pneumococcus has been -the primary cause of pneumonia, but with bronchopneumonia pneumococci -have been less frequently found. It is difficult to determine how often -hemolytic streptococci have invaded a bronchopneumonic lesion, caused by -pneumococci because pneumococci tend to disappear. In numerous instances -in which the sputum had been studied during life, it was evident that -pneumonia was primarily referable to pneumococci, and hemolytic -streptococci made their appearance in the sputum late in the disease or -were first recognized at autopsy. - -When hemolytic streptococci occur in association with bronchopneumonia, -foci of pulmonary necrosis similar to those found under the same -conditions with lobar pneumonia have been repeatedly found by -microscopic examination. In the patches of necrosis, cocci in chains are -much more abundant than in the tissue elsewhere. - -In some instances of pneumonia, caused by hemolytic streptococci, opaque -gray or yellowish gray patches of necrosis occur upon a background of -flaccid homogeneous consolidation which has a peculiar cloudy, gray -color. This mottled consolidation may implicate an entire lower lobe and -has the characteristic features neither of lobar nor of -bronchopneumonia. More frequently the lesion is less widespread and -necrosis occurs in one or several spots which undergo softening so that -finally a small abscess cavity may be formed; it is surrounded by -pneumonic consolidation which is soft and has the cloudy appearance -described above. These pulmonary abscesses are almost invariably -situated below the pleural surface; the adjacent pleural cavity is -infected by streptococci and there is purulent inflammation of the -pleura. - -Streptococcus infection, which has been described, doubtless has its -origin in the bronchi, for in favorable sections it is not infrequently -possible to demonstrate that necrosis extends through the bronchial -walls into the surrounding alveolar tissue and is followed by -suppuration with abscess formation. Localization of abscesses below the -pleura is in part at least referable to transmission of streptococci by -way of the lymphatics. - -Streptococci in the lung, as in other tissues, often invade lymphatics -and produce an acute inflammatory reaction within and about these -vessels. The peculiar lesion which may be designated suppurative -interstitial pneumonia is a suppurative lymphangitis associated with -inflammation and edema of the interstitial tissue. Lymphatics invaded by -streptococci are the site of acute lymphangitis; occlusion by fibrinous -thrombi occurs and finally the immensely distended lymphatics, filled -with purulent fluid, take a characteristic nodular or beaded form and -pus flows from them when they are cut. Streptococci are present in vast -numbers. Suppurative inflammation may extend to the surrounding -interstitial tissue which is distended by inflammatory edema. This -interstitial suppurative pneumonia extends up to the pleural surface and -empyema is almost invariably associated with it. The lesion is seldom -seen in the absence of influenza. - -One of the most significant characters of S. hemolyticus is its ability -not only to enter the bronchi and penetrate into the tissue of the lung, -but to find its way into more distant structures, namely, the pleural -cavity, pericardial sac and peritoneal cavity and to penetrate into the -blood. Among 121 examinations, hemolytic streptococci were found in the -bronchi in 47.9 per cent; among 153 examinations of the lung it was -present in approximately the same proportion, namely, 50.3 per cent; -among 218 examinations of the blood it was found in 39 per cent. In 4 of -5 fatal pneumonias in which the organism has penetrated into the bronchi -it has ultimately found its way into the blood. - -=Nonhemolytic Streptococci.=—In contrast with S. hemolyticus -nonhemolytic types have rarely been encountered in association with the -pneumonias of influenza. S. viridans has been found only 5 times among -153 autopsies in which cultures have been made from the lung and has -been invariably associated with other microorganisms. In no instances -have nonhemolytic streptococci been found with empyema. In one autopsy -with lobular bronchopneumonia S. viridans has been isolated from the -blood of the heart and in this instance it has been found in the -bronchus and lung as well. This type of streptococcus is evidently -little adapted to invade the bronchi and produce lesions of the lung and -adjacent tissues. - -=Staphylococci.=—Staphylococci have been very frequently isolated from -the bronchi in association with the pneumonias of influenza, being found -in approximately half of our autopsies. Their isolation in cultures from -the lung in a fourth of the autopsies examined is in part perhaps -referable to their presence in the small bronchi cut across when the -lung is punctured for cultures. S. aureus shows little ability to invade -the pleura, being found in association with empyema only 3 times; in -these autopsies there has been opportunity for entrance from the -exterior through thoracotomy wounds in 2 instances and from a bronchus -in free communication with an abscess which had ruptured into the -pleural cavity in 1 instance. - -Abscesses of the lung caused by staphylococci have been found in a small -number of autopsies and have exhibited characters which differ from -those ordinarily seen in association with S. hemolyticus. Small, sharply -defined abscesses are grouped about terminal bronchi, so that they occur -in one or several isolated clusters. Microscopic examination -demonstrates that these abscesses have arisen by destruction of the -bronchial walls and extension of suppuration into the surrounding -alveolar tissue; clumps of staphylococci are found in sections through -the abscess, and cultures made from the pus within the abscess cavity -demonstrate the presence of S. aureus or albus, but the microorganism -may be missed if the culture is made from the adjacent lung tissue. It -is noteworthy that there is little tendency for the staphylococcus to -infect the pleura for even though these clusters of abscesses have been -situated just below the pleura, there has been no associated empyema. - -Staphylococci have scant tendency to enter the blood and have been -obtained from the blood of the heart only once, in this instance with -hemolytic streptococci. - -=Pneumonia of Measles.=—Pneumonia following measles has been responsible -for a considerable part of the deaths occurring in the United States -Army during the period of the war. The importance of measles as a factor -in the production of pneumonia is illustrated by the history of -pneumonia at Camp Funston from the establishment of the camp in -September, 1917, until September, 1918. Pneumonia following measles -occurred throughout the year; but in association with the high incidence -of measles during the second half of November and the first half of -December, 1917, there was an outbreak of related pneumonia characterized -by frequent empyema and a mortality of 45.3 per cent. - -During the period of our investigation at Camp Funston there were 112 -cases of measles, but no pneumonia occurred among them. At Camp Pike, -during the period of observation, there was an outbreak of measles -almost coincident with the epidemic of influenza, and among 867 cases -pneumonia occurred in 56, otitis media in 48, and mastoiditis in 23. -Pneumonia following measles was almost coincident with that of -influenza, and it is not improbable that the epidemic of influenza had -an important part in the production of pneumonia in individuals -suffering with measles. - -In 9 of 56 instances of pneumonia following measles at Camp Pike, S. -hemolyticus had invaded the lung and caused pneumonia; among 48 -instances of otitis media following measles a very large proportion were -caused by hemolytic streptococci, and 21 of 23 instances of mastoiditis -were caused by the same microorganism. No complication caused by S. -hemolyticus occurred among 37 patients who carried this microorganism -when admitted to the hospital. - -A special study has been made to determine if those patients with -measles who carry S. hemolyticus in their throats are especially -susceptible to complications during the course of measles. The low -incidence of streptococcus “carriers” among those admitted to the -hospitals with measles was noteworthy both at Camp Funston (2.67 per -cent) and at Camp Pike (4.2 per cent). Indeed, it was found at both -places that the incidence of hemolytic streptococci in the throats of -normal men in the camp was higher (Camp Funston 21.9 per cent; Camp Pike -7.4 per cent) than that in the throats of those admitted with measles. -While in the hospital there was a gradual increase of the incidence of -S. hemolyticus, so that in three weeks it had risen to 19 per cent at -Camp Funston and to 26.2 per cent at Camp Pike. It seems not improbable -that hemolytic streptococci disappear from the throat in the early -stages of measles, so that they are not demonstrable by cultural -methods. During the course of the disease in the hospital ward the -number of those with S. hemolyticus has increased in some wards with -great rapidity, infection being apparently transmitted from one -individual to those adjacent. At Camp Funston the incidence of S. -hemolyticus in the throats of those convalescent with measles was almost -identical with that among normal men in organizations from which the -patients had come, but at Camp Funston the percentage of hemolytic -“carriers” among convalescents was much higher than that obtained among -normal men in the camp. - -The demonstration of S. hemolyticus in the throat of a patient suffering -with pneumonia is not conclusive proof that the lungs have been invaded -by this microorganism. Pneumonia in individuals carrying S. hemolyticus -in the throat may pursue a favorable course and exhibit no evidence that -the microorganism has found its way into the lung. In some instances -hemolytic streptococci have been found in the bronchi at autopsy yet -none have entered the lung or blood and the lung exhibits none of the -lesions which are referable to hemolytic streptococci. Nevertheless, the -occurrence of S. hemolyticus in cultures from the throat of a patient -with pneumonia suggests the probability that he is suffering with -streptococcus pneumonia. - -Pneumonia following measles studied in 18 autopsies upon patients who -died during or shortly after the epidemic of influenza, exhibited all -the characters exhibited by the pneumonias of influenza. In 4 instances -there was typical lobar pneumonia; bronchopneumonia was found in all but -3 instances, being associated with lobar pneumonia twice. All the -noteworthy features of the bronchopneumonia of influenza have been -reproduced among these instances of pneumonia with measles; there is -severe injury to the bronchi, and purulent bronchitis has been present -in 13 instances; pneumonia has frequently had a hemorrhagic character, -hemorrhagic peribronchiolar pneumonia occurring in 5 instances; -secondary infection of the pneumonic lungs with hemolytic streptococci -has been common; bronchiectasis has been associated with bronchitis (in -8 instances) when purulent bronchitis has persisted several weeks; and -unresolved bronchopneumonia has been more frequent (6 instances or -one-third of the autopsies) than with influenza. - -The bacteriology of pneumonia following measles has been the same as -that of influenzal pneumonia. B. influenzæ is found with few exceptions -in the bronchi and much less frequently in the pneumonic lungs. - -Pneumococci have been obtained from the blood or lungs in 5 of 13 -instances of lobar or bronchopneumonia unaccompanied by suppuration; -when suppuration has been absent no hemolytic streptococci have been -found. Pneumococci concerned in the production of pneumonia of measles, -as with influenzal pneumonia, have been types usually found in the -mouth; Pneumococcus II atypical has been found 6 times, Type IV once, -Type I once. - -Hemolytic streptococci have invaded the pneumonic lung in 5 instances. -They have produced subpleural abscesses accompanied by empyema in 2 -instances. Interstitial suppurative pneumonia, a lesion repeatedly found -in consequence of secondary infection with S. hemolyticus following -influenza and rarely found in this country, at least in the absence of -an epidemic of influenza, has occurred 3 times among 18 instances of -pneumonia following measles. - -The foregoing observations show that the pneumonia following measles, -which has occurred almost coincidentally with pneumonia accompanying -epidemic influenza has reproduced the lesions found with influenzal -pneumonia. They indicate that influenza attacking patients with measles -has had a part in the production of this pneumonia. - -=The Transmission of Streptococcus Pneumonia.=—The importance of -streptococcus as a cause of pneumonia following influenza was recognized -during the pandemic of 1889–90. Patients suffering with pneumonia -following influenza or measles are susceptible to infection by S. -hemolyticus and this streptococcus pneumonia may be transmitted from one -patient to another throughout a ward in which patients with pneumonia -are assembled. There is no evidence that primary pneumonia caused by S. -hemolyticus has prevailed as an epidemic in the army or elsewhere in the -absence of preceding infection with influenza or measles. - -Our autopsies demonstrate that at least half of all deaths which have -occurred at Camp Pike have been caused by hemolytic streptococci which -have invaded the lung and entered the blood. It is significant that this -mortality had its origin in the first half of the epidemic of influenza -at a time when the military and medical organization of the camp was -confronted with an unforeseen emergency which overwhelmed all agencies -for the care of disease. Curves prepared by referring cases of pneumonia -in which autopsy demonstrated the nature of the fatal infection back to -the date of the onset of influenza, demonstrate that fatal streptococcus -pneumonia was frequently acquired during the early period of the -epidemic, the maximum number of cases occurring September 23 and 24 and -became gradually less common as a sequela of the influenza which began -at a later period. Fatal pneumococcus pneumonia had its origin with -increasing frequency at a later period, the maximum incidence following -influenza which had its onset September 29 and 30. Overcrowding of -influenza patients in infirmaries, ambulances and hospital had an -important part in the dissemination of streptococcus pneumonia among -influenza patients whose disease might otherwise have pursued a benign -course. - -The most important factor in the high incidence of streptococcus -pneumonia has been the spread of the disease in the hospital wards. On -September 24 the base hospital contained 2,789 patients, although it had -been planned to care for only 2,009. With the progress of the epidemic -the number of admissions increased very rapidly, so that on September 30 -the hospital contained 3,587 patients and on October 5, 4,233. After -September 24 the milder cases of influenza were treated in barracks. The -pressing need of diminishing the overcrowding of the hospital was fully -recognized and adjacent barracks were transformed into hospital wards; -between October 3 and 6, 1,362 patients were transferred from the -hospital to these quarters. - -In the main hospital, during the period of overcrowding 20 wards for -patients with pneumonia were added to the two which already existed. -These hastily organized and overcrowded wards have been attacked by -outbreaks of streptococcus pneumonia, which during certain periods have -been fatal to more than two-thirds of those who have been admitted with -pneumonia, whereas in the two long established wards for pneumonia -isolated cases of streptococcus infection, which have appeared, have -failed to spread to other patients and pneumococcus pneumonia with few -exceptions has been found in those who have died. In one newly -established ward 67.5 per cent of those admitted within a period of -three days have died, and in all of the 23 autopsies which have been -performed, streptococcus pneumonia has been found. In another ward 50 -per cent of all who have been admitted during a period of one week have -died, and among the autopsies performed on these individuals -pneumococcus pneumonia has been found in 6 and streptococcus pneumonia -in 14. The sputum of 9 patients in this ward has been examined on -admission, and pneumococci, but no streptococci, have been found. All -these patients have died, and infection with S. hemolyticus has been -found at autopsy in 7. - -=Transmission of Pneumococcus Pneumonia.=—Our study of secondary ward -infection has not only shown that patients with pneumococcus pneumonia -following influenza are susceptible to infection by S. hemolyticus, but -that patients suffering with pneumonia caused by one type of -pneumococcus may be infected with another type during the course of the -disease or after convalescence has begun, the second infection being -acquired from patients in adjacent beds. Pneumonia caused by Type IV has -ended in crisis and has been followed by a period of normal temperature; -recurrent pneumonia has been fatal and Pneumococcus Type II has been -found in the organs at autopsy. Pneumonia caused by Type I has been -followed by recurrent pneumonia caused by Pneumococcus II atypical -acquired from a patient in the next bed. These secondary pneumococcus -infections acquired within the hospital are apparently not uncommon. - -=Prevention of the Transmission of Pneumonia.=—The essential factor in -the management of influenza and pneumonia is such isolation of each -patient that microorganisms cannot be transmitted from one to another or -from attendants or others to patients. This condition may be fulfilled -by the separation of patients in rooms or isolated compartments -especially constructed for the treatment of pneumonia and by the -employment of all possible means to prevent the transmission of -infection from one patient to another by physicians, nurses and -orderlies. It is desirable to examine attendants to determine if they -carry hemolytic streptococci in their mouths and to exclude those who -are found to be “carriers.” - -Influenza is a self-limited disease which, in the absence of -complications implicating the lower respiratory tract, is of relatively -mild character. When death occurs as the result of influenza it is with -very rare, if any, exceptions referable to pneumonia; we have invariably -found pneumonia in those who have died in consequence of influenza. The -individual attacked by influenza may carry within his upper respiratory -passages pneumococci or hemolytic streptococci capable of invading the -bronchi and causing pneumonia, but in most instances the microorganism -which produces serious pulmonary complications is derived from others -with whom the influenza patient has come into contact. The greatest -source of danger to one with influenza is contact with patients who have -acquired pneumonia, and this danger is immensely increased when -infection with S. hemolyticus makes its appearance among pneumonic -patients. Hospital epidemics of streptococcus pneumonia will be -prevented when the disease is dreaded as much as puerperal fever or the -hospital gangrene of former years, and widespread knowledge of the -suppurative pneumonias of influenza will bring a clear recognition of -the fatal character of streptococcus infection in patients suffering -with pneumococcus pneumonia. - -Overcrowding of barracks has been an important factor in the propagation -of acute respiratory disease and in the transformation of otherwise -trivial influenza into fatal pneumonia. Crowded troop trains have -doubtless had a part in disseminating infection among newly assembled -recruits. Should these dangers be recognized they may be avoided by -appropriate measures which will promote rather than retard those -military aims which must be placed foremost in time of war. It may be -possible by adequate expenditure to avoid the death of thousands of -recruits within one month of their entrance into military service. - -A second factor in the increase of death rate from pneumonia is the -overcrowding and confusion of hospital facilities in the presence of an -epidemic disease. When troops are maintained in camps precautions should -be taken to provide effective safeguards against the overcrowding of the -base hospital. - -Isolation of each patient with pneumonia is the most effective way of -protecting him from infection and of preventing him from becoming a -possible source of danger to others. The effectiveness of this isolation -will depend upon the separation of patients by some means more effective -than the cubicles composed of sheets heretofore employed, upon an -aseptic technic sufficiently rigid to prevent the transfer of pyogenic -infection to pneumonia patients, and upon the exclusion from the ward of -those who harbor S. hemolyticus. - -Even should each patient be completely isolated from his neighbors, no -effort should be neglected to determine, as far as possible, the nature -of the infection with which he suffers. In the presence of an -overwhelming epidemic such as that which attacked our army camps, the -bacteriologic work which is required may be far beyond the facilities -which are available and in many instances it may be wholly impossible. -Nevertheless effective control of streptococcus pneumonia will depend -upon its recognition as soon as it appears, and bacteriologic -examination of the sputum offers the readiest means for its -identification. The routine performance of autopsies will furnish an -index of the success of the measures in force, and the discovery of -suppurative pneumonia will suggest the presence of imminent danger. - -However perfect the organization of pneumonia wards and however accurate -the aseptic technic in force, it is desirable to separate as far as -possible those infected with streptococcus from those who are free from -this infection, so that the accuracy of the technic in force may not be -put to too severe a test. When streptococcus pneumonia has appeared in a -ward it should be closed to further admissions. - -Those who are concerned in the planning and construction of military and -other similar hospitals might well give special attention to the -possibility of epidemics such as those which we have experienced, and -special provision might be made to avoid overcrowding in the presence of -a demand far in excess of the routine need for hospital facilities. In -the construction of these hospitals appropriate provision should be made -for the care of patients with pneumonia. Medical officers should receive -detailed instruction in the organization and conduct of wards designed -for the treatment of pneumonia. - - - - - APPENDIX - EXPERIMENTAL INOCULATION OF MONKEYS WITH BACILLUS INFLUENZÆ AND - MICROORGANISMS ISOLATED FROM THE PNEUMONIAS OF INFLUENZA - - EUGENE L. OPIE, M.D.; ALLEN W. FREEMAN, M.D.; FRANCIS G. BLAKE, M.D.; - JAMES C. SMALL, M.D.; AND THOMAS M. RIVERS, M.D. - - -Experiments were undertaken at Camp Pike in December, 1918, to determine -whether bacteria freshly isolated from patients suffering with influenza -and pneumonia during the outbreak of influenza and its associated -pneumonias were capable of producing similar diseases when introduced -into the respiratory passages of monkeys. The number of animals -available for the study was limited. The attempt was made (_a_) to -determine if B. influenzæ produces in monkeys a disease comparable to -influenza of human beings, and (_b_) to determine so far as possible, -with the limited opportunity, the character of the lesions produced by -combinations of pneumococcus or S. hemolyticus with B. influenzæ and to -compare these lesions with lesions produced by pneumococcus or by -hemolytic streptococcus alone. - -Pfeiffer[107] found monkeys alone susceptible to invasion by B. -influenzæ and obtained no evidence of multiplication of the -microorganism within the body of any other animal. A suspension -containing mucus from the sputum of a patient with influenza was -injected into a monkey. There was elevation of temperature and the -animal died after seven days. Lobular patches of atelectasis occurred -along the sharp edges of the lungs and the adjacent bronchial branches -contained mucus. Cultures on agar from the bronchi remained sterile. -Microscopic examination showed the presence of bacilli resembling B. -influenzæ. Death was caused, the author states, by an abscess at the -site of inoculation and not by the process in the lungs. Three monkeys -received each 0.5 c.c. of bouillon containing a blood agar culture -injected into the lung through the chest wall. There was elevation of -temperature lasting from three to five days with return to normal every -morning. There was cough but little evidence of illness. B. influenzæ -was introduced by a platinum loop into the nose of a monkey. Febrile -reaction is recorded lasting four or five days. Pfeiffer found that -guinea pigs and mice were resistant to the microorganism. Large doses -injected intravenously caused in rabbits intoxication with dyspnea and -evidence of profound muscular weakness. - -Kamen[108] used a culture of B. influenzæ which was nonpathogenic for -mice, but when it was inoculated into the peritoneal cavity with -streptococcus both influenza bacilli and streptococci appeared in the -blood. Jacobson[109] found that B. influenzæ appeared in the blood and -viscera of mice killed by intraperitoneal inoculation of B. influenzæ -mixed with cultures of streptococcus either living or killed by heat. B. -influenzæ which had successively passed through mice, simultaneously -inoculated with killed streptococci, acquired such virulence that it was -capable of producing septicemia when inoculated alone. - -Richie[110] introduced by lumbar puncture a suspension of two blood agar -cultures of B. influenzæ obtained from the meninges of a patient with -influenzal meningitis into the subdural space of a rhesus monkey. Death -occurred in eighteen hours and there was beginning meningitis. B. -influenzæ was present in the exudate in abundance. - -In two species of monkeys Wollstein[111] produced fatal meningitis by -injecting suspensions of B. influenzæ into the subdural space by lumbar -puncture. - -During the course of our investigation of pneumonia and influenza, -sputum of approximately 400 normal individuals or patients with -influenza was injected into the peritoneal cavity of mice. B. influenzæ -was found in approximately 150 instances. In only 4 instances was B. -influenzæ found in pure culture in the blood; in all other mice in which -B. influenzæ appeared in the blood it accompanied pneumococcus or S. -hemolyticus. - -Before experiments were performed cultures were made from the throats of -all monkeys in order to exclude the presence of B. influenzæ. Blood agar -plates inoculated with a swab applied to the nasopharynx failed to show -in any instance B. influenzæ, pneumococci, or hemolytic streptococci. -Streptococci causing green discoloration of blood agar were usually -found. - -=Inoculation of the Nose and Pharynx with B. Influenzæ.=—B. influenzæ -was introduced into the nose and pharynx of two healthy monkeys. An -actively growing culture of the microorganism made on alkaline blood -agar and sixteen hours old was used. The culture was the first -subculture from a growth obtained from the nose and throat of a patient -with influenza. A cotton swab moistened with broth was applied to the -surface of the culture. It was introduced into the nostrils and smeared -over the pharynx of the animals. A swab moistened with sterile broth was -applied to the nose and pharynx of a third monkey as a control; cultures -from this animal kept in a cage removed from those inoculated failed to -show B. influenzæ. - - EXPERIMENT 1 - - November 21, 1918.—Small female monkey; throat culture: negative. - November 23.—10:20 A.M.—White blood corpuscles, 16,700; polynuclear - leucocytes, 68 per cent; small lymphocytes, 17.5 per cent; large - lymphocytes, 8 per cent; large mononuclears, 1 per cent; - eosinophiles, 2.5 per cent; basinophiles, 0.5 per cent. 10:30 - A.M.—Mucous membranes of nose and throat were inoculated with B. - influenzæ as described above. November 25.—The animal appears sick - and is huddled in back of its cage; the nose is running. White blood - corpuscles, 13,500; polynuclear leucocytes, 44 per cent; small - lymphocytes, 30 per cent; large lymphocytes, 22 per cent; large - mononuclears, 3 per cent; eosinophiles, 1 per cent. 3:40 P.M.—Free - epistaxis occurred after culturing of nose; the swab was discolored - with old brownish blood indicating previous epistaxis. Nose culture: - B. influenzæ present in abundance; Gram-positive cocci present. - Throat culture: negative for B. influenzæ. November 28.—Monkey is - more active and appears to be fairly well. Nose and throat cultures: - negative for B. influenzæ. December 4.—Monkey is apparently well. - - EXPERIMENT 2 - - November 21, 1918.—Small male monkey. Throat culture: negative. - November 23.—10:10 A.M.—White blood corpuscles, 10,900; polynuclear - leucocytes, 52 per cent; small lymphocytes, 18 per cent; large - lymphocytes, 25 per cent; large mononuclears, 3 per cent; - eosinophiles, 2 per cent. 10:15 A.M.—Mucous membranes of nose and - throat were inoculated by means of moist swab with 4 strains of B. - influenzæ recently isolated from acute cases of influenza. November - 24.—Monkey is quiet and takes no interest in surroundings. November - 25.—Animal appears sick and remains huddled at back of its cage. - Nose culture: B. influenzæ present. Throat culture: B. influenzæ - present. Swab applied to nose is stained brown with old blood - indicating previous epistaxis. November 26.—Animal is still sick; - nose is running. White blood corpuscles, 14,400; polynuclear - leucocytes, 61 per cent; small lymphocytes, 23 per cent; large - lymphocytes, 15 per cent; large mononuclears, 1 per cent. November - 27.—White blood corpuscles, 11,300. November 28.—Nose culture: - negative for B. influenzæ. Throat culture: B. influenzæ present. - November 29.—Animal is active, but still appears sick. White blood - corpuscles, 19,300. December 4.—Monkey appears well. Throat culture: - B. influenzæ present. - -These animals were sick two and six days following inoculation. There -was discharge from the nose. In both instances there was epistaxis. The -temperature of the animals was subject to such wide variation in -relation to external temperature that it could not be used as an index -of the progress of the disease. There was no leucocytosis, but in one -animal there was some increase in the numbers of leucocytes during -recovery. In one animal B. influenzæ present in the nose after two days -was absent after four days. In the other animal the organism was -repeatedly found in the nose and throat and was still present in the -throat eleven days after inoculation. The two animals suffered with a -self-limited disease resembling many cases of influenza. - -=Introduction of Bacillus Influenzæ into the Trachea.=—In the attempt to -reproduce the bronchitis which occurs in a considerable proportion of -all cases of influenza and is almost invariably associated with B. -influenzæ, this organism was introduced into the trachea of monkeys. In -Experiment 3 a suspension containing young cultures of freshly isolated -B. influenzæ was introduced into the trachea by a silver catheter passed -through the glottis and larynx into the trachea. - -Young cultures of B. influenzæ, subcultured only once after isolation -from early cases of influenza, were used. The microorganism was -recovered in abundance by throat swab two days later and again from the -bronchus at autopsy three days after inoculation. Tuberculosis of -mesenteric lymph nodes, of intestine and of liver and several small -tuberculous nodules in the lung were found at autopsy. A secondary -invasion of the lung by staphylococci had occurred. There was bronchitis -with an inflammatory infiltration of the subepithelial tissue of the -bronchi by lymphoid and plasma cells. Bronchopneumonia was present, and -the bronchi and many of the alveoli contained blood. These changes do -not differ essentially from the changes found in many instances of -pneumonia following influenza. - -In three instances cultures of B. influenzæ were injected into the -trachea by means of a hypodermic syringe. - -In one of these experiments (Experiment 4) intratracheal injection of 2 -c.c. salt solution suspension of B. influenzæ (isolated at autopsy from -bronchus of the monkey used in Experiment 3), representing growth on 1½ -blood agar plates, was made with a needle inserted into trachea just -above the suprasternal notch. On the following day a throat culture -contained B. influenzæ in abundance. Three days after inoculation the -monkey appeared to be very sick and there was profuse nasal discharge. -The animal coughed and sibilant râles were heard over the chest. There -was no leucocytosis. A throat culture contained B. influenzæ. Four days -after inoculation the monkey was still sick and weak, but appeared much -improved and was killed. The trachea and large bronchi contained thick -viscid mucus. In the middle lobe of the right lung was a patch of -grayish red, airless tissue, firmer than the lung substance elsewhere. -Cultures from the trachea, bronchus and lung contained a variety of -microorganisms, but B. influenzæ was not recovered. - -In two additional experiments (Experiments 6 and 7) cultures of B. -influenzæ forty-eight hours old were injected into the trachea of -monkeys. The microorganism was recovered in cultures made from the -pharynx two days later. These animals were only slightly sick. - -=Introduction of B. Influenzæ and S. Hemolyticus into the Trachea.=—In -view of the frequent association of B. influenzæ and S. hemolyticus in -the sputum of patients with streptococcus pneumonia following influenza -and in the bronchi and lungs of those who have died with this disease, -the two microorganisms were injected simultaneously into the trachea of -monkeys. - -B. influenzæ and S. hemolyticus in Experiment 7 produced bronchitis and -bronchopneumonia. There was acute inflammation of the interstitial -tissue of the lung, and acute lymphangitis with numerous polynuclear -leucocytes within the lumen of the lymphatics was present. B. influenzæ -and S. hemolyticus were present in the trachea at autopsy four days -after inoculation. It is probable that part of the injected culture -entered the tissue outside the trachea, for an abscess was formed in -this situation. It is noteworthy that acute pericarditis occurred and -both S. hemolyticus and B. influenzæ were found in the pericardial -exudate. B. influenzæ not infrequently exhibits this tendency to -penetrate in association with other bacteria localities which it does -not invade independently. - -In a second experiment (Experiment 8) in which B. influenzæ and S. -hemolyticus were injected into the trachea, both microorganisms were -recovered from the throat on the day following inoculation; on the fifth -day S. hemolyticus alone was recovered and on the sixth day a throat -culture was negative both for S. hemolyticus and B. influenzæ. - -=Introduction of B. influenzæ and of Pneumococcus or of Pneumococcus -Alone into the Trachea.=—In two experiments B. influenzæ and -Pneumococcus Type III were simultaneously injected into the trachea. - -In Experiment 9 a large male monkey was used and intratracheal injection -made with syringe and needle of 5 c.c. salt solution suspension of -Pneumococcus Type III and B. influenzæ (growth on 5 blood agar plates of -mixed cultures of Pneumococcus III and B. influenzæ). On the following -day the animal was very sick, lying on the floor of its cage, and was -dead two days after inoculation. - -The dosage of bacteria in this experiment was large. The lesions in -gross appearance and microscopically resembled those seen in many -instances of pneumonia following influenza. In the trachea there was -loss of ciliated epithelium, congestion of the subepithelial tissue, -hemorrhage and infiltration with plasma cells. The lungs were -consolidated and red and there were hemorrhage and edema. B. influenzæ, -as in human cases, was abundant in the bronchi, less abundant in the -consolidated lung, being present though scant in the left lung, and -absent in cultures from the right. B. influenzæ as in Experiment 8 with -streptococcus had entered the left pericardial cavity in company in this -experiment with Pneumococcus III. - -In Experiment 10 a very large monkey received by intratracheal -injection, made with syringe and needle, 5 c.c. salt solution suspension -of Pneumococcus III and 3 strains of B. influenzæ, (2 recently isolated -from cases of influenza and 1 from autopsy in a case of postinfluenzal -pneumonia). The animal died twenty-four hours later. - -This simultaneous introduction of B. influenzæ and Pneumococcus III in -large quantity has produced rapidly fatal pneumonia with lobar -distribution. Hepatization was homogeneous and red, and outside the -consolidated parts of the lung there was hemorrhage and edema. The -lesion resembled that found when death has occurred within a few days -after the onset of pneumonia following influenza, but had no distinctive -characters establishing its relation to pneumonia following influenzæ. - -In Experiment 11 Pneumococcus III alone in small amount was introduced -into the trachea of a small monkey. The animal was very sick, but its -condition improved and recovery seemed probable. The animal was killed -seven days after inoculation, and typical lobar pneumonia with gray -hepatization was found at autopsy. - - EXPERIMENT 11 - - November 20, 1918.—Small monkey; throat culture: negative for B. - influenzæ, pneumococcus and S. hemolyticus. November 28 and December - 6.—Nose and throat cultures again negative for B. influenzæ. - December 9—4:30 P.M.—Intratracheal injection with syringe and needle - of 0.33 c.c. of an eighteen hour broth culture of Pneumococcus Type - III. December 10.—The animal is sick, huddled up in his cage with - head down; there is rapid respiration with expiratory grunt and the - mucous membranes are moderately cyanotic. There is frequent cough. - Throat culture: Pneumococcus III present in abundance. December - 15.—The animal appears to be better. Respirations are still rapid - but less labored. December 16.—The animal is improving but very weak - and emaciated. - - =Autopsy.=—The pleural cavities contain no fluid. On the right side - are several strands of fibrin. The right lower lobe with the - exception of a small patch at the summit and the lower part of the - middle lobe are voluminous, have a dull gray surface covered by a - scant layer of fibrin and are firmly consolidated. On section the - consolidated tissue has a gray color and is conspicuously granular, - the granulation resembling, on a slightly smaller scale, that seen - in human lobar pneumonia. The bronchi contain a small amount of - viscid fluid. - - =Bacteriology.=—Direct smears from the trachea and the lower lobe of - the left lung contain Gram-positive diplococci. Cultures from the - trachea and from the blood of the heart contain Pneumococcus III. - Cultures from the left lower lobe, from the liver and from the - spleen remain sterile. - - =Microscopical Examination.=—There is abundant infiltration of the - subepithelial tissue of the trachea with plasma cells. Superficial - ciliated epithelium is in places lost. At one point is a small focus - of hemorrhage. Alveoli in the consolidated part of the lungs contain - polynuclear leucocytes and fibrin and exhibit the appearance seen in - lobar pneumonia in man. - -[Illustration: - - Fig. 33.—Experimental lobar pneumonia in the stage of gray - hepatization produced by injection of Pneumococcus III into the - trachea of a monkey (Experiment 11). The alveoli are uniformly - filled with plugs of fibrinous exudate. -] - -In Experiment 12 B. influenzæ was injected into the trachea and two days -later identified in a culture made from the pharynx; four days after -inoculation Pneumococcus IV was injected into the trachea. The animal -was killed seven days after the first inoculation, and three days after -inoculation with pneumococcus. The lower half of the upper lobe of the -right lung and the greater part of the lower and middle lobes were -consolidated. The pleural surface of the consolidated areas was dull red -and covered by a small amount of fibrin. The lower lobe, with the -exception of a small part at the summit, was very firmly consolidated, -on section pinkish gray in the anterior part and deep red in a small -zone at the posterior border. The cut section was conspicuously -granular. The trachea and bronchi contained mucus. Cultures from the -trachea, the right lung and the right pleural cavity contained -Pneumococcus IV in pure culture. Alveoli in the consolidated part of the -lung were filled with polynuclear leucocytes and fibrin. - -Lobar pneumonia has been produced by the introduction of Pneumococcus IV -into the trachea. It is doubtful if preceding inoculation of B. -influenzæ has influenced the course of the disease. - - -The foregoing experiments have shown that B. influenzæ introduced into -the nasopharynx or into the trachea of monkeys is capable of causing -lesions of the mucosa of these structures; the microorganism persists -within the nasopharynx or trachea and is recoverable during a variable -period of from two to eleven days after inoculation. Spontaneous -infection of monkeys with B. influenzæ has not been observed. The -animals infected with the microorganism are ill during several days, but -the experimental disease like most instances of human influenza is self -limited. Following inoculation of the nose and throat of monkeys with B. -influenzæ there is discharge from the nose, tendency to epistaxis and -absence of leucocytosis. - -Bronchitis was produced by the introduction of B. influenzæ into the -trachea of monkeys, and the microorganism was recovered from the -nasopharynx two and three days following inoculation. There was no -leucocytosis. In two experiments death occurred following inoculation, -and in both instances it was found that the animal suffered with -tuberculosis which had produced only trivial lesions of the lungs. In -both animals staphylococci were obtained from the internal organs. There -was bronchitis with changes in the bronchi which, although not -characteristic, resembled those found in association with B. influenzæ -in man. It is noteworthy that B. influenzæ is usually found mixed with -other bacteria in the bronchi of those who have died with bronchitis and -pneumonia following influenza. In the experimental animals there was in -places superficial loss of ciliated epithelium, exudation of polynuclear -leucocytes, infiltration of the subepithelial tissue with plasma cells -and hemorrhage into this tissue. - -In one instance simultaneous injection of B. influenzæ and S. -hemolyticus, freshly obtained from autopsy upon a man dying with -pneumonia following influenza, caused bronchitis and bronchopneumonia; -there were acute lymphangitis and infiltration of the interstitial -tissue of the lung with polynuclear leucocytes such as occurs in human -cases, but the lesion had not proceeded to suppuration. - -In man B. influenzæ is usually found in greatest abundance upon the -mucosa of the respiratory passages, less frequently it invades the -alveoli of the lungs and is almost invariably found in association with -other microorganisms. In company with other microorganisms B. influenzæ -penetrates into tissues outside the lungs. In Experiment 7 it has -entered the pericardium, with streptococcus, and in Experiment 9 with -pneumococcus. When B. influenzæ and streptococcus are injected into the -peritoneal cavity of a mouse both organisms appear in the blood, whereas -in the absence of streptococcus, B. influenzæ seldom leaves the -peritoneal cavity. - -Typical lobar pneumonia has been produced for the first time in monkeys -by injecting pneumococci (in quantity as small as 0.33 c.c. of -suspension) into the trachea. With the animals available it has not been -possible to adjust the dosage of the two microorganisms so that the -influence of one upon the other might be determined. Pneumococcus III, -in small quantity, introduced into the trachea has produced typical -acute lobar pneumonia in the stage of gray hepatization. A similar -lesion has been produced with Pneumococcus IV obtained from the lung of -a man dead with pneumonia. - - - - - INDEX - - - A - - Abscess of lung, bacteriology of, 203 - empyema with, 233 - healing of, 208 - measles with, 347 - parotitis with, 356 - pathogenesis of, 205, 375 - scarlet fever with, 357 - staphylococcus causing, 199, 225, 366, 377 - S. hemolyticus causing, 199, 365 - - Autopsies, table of, 118, 120, 335 - - Autopsy protocols, No. 280, 226; - No. 286, 226; - No. 312, 254; - No. 322, 228; - No. 330, 214; - No. 333, 229; - No. 370, 229; - No. 376, 206; - No. 379, 215; - No. 380, 204; - No. 387, 206; - No. 397, 223; - No. 406, 204; - No. 416, 204; - No. 420, 279; - No. 425, 229; - No. 428, 280; - No. 433, 280; - No. 445, 257; - No. 465, 238; - No. 467, 208; - No. 473, 236; - No. 474, 221; - No. 487, 273; - No. 499, 224; - No. 504, 238 - - - B - - Bacillus influenzæ, 369 - bronchi and, 178, 215, 346 - bronchitis and, 153, 371 - experimental inoculation with, 389 - history of, 25 - influenza and, 30, 42, 43, 46, 49, 76, 370 - isolation of, 30, 32, 38, 44 - measles with, 26, 40, 43, 295, 351 - meningitis and, 26 - normal men carrying, 34, 42, 45, 369 - pathogenicity of, 26, 48, 370, 387, 396 - pneumococcus pneumonia with, 62, 178 - pneumonia with, 72, 75, 76, 173, 364, 371 - - Bronchi, inflammation of mucous glands of, 146 - - Bronchiectasis, 239, 269, 355, 367 - abscess with, 254 - bacteriology of, 244 - bronchitis with, 245 - measles with, 336 - pathogenesis of, 245, 259 - - Bronchiolitis, organizing, 264 - - Bronchitis, 40, 142, 195, 359 - bacteriology of, 56, 150, 164, 359, 371 - bronchiectasis with, 245 - chronic, 262 - clinical course of, 58 - measles with, 336 - organizing, 264 - purulent, 47, 56, 60, 63, 74, 143, 149, 153, 360 - - Bronchopneumonia, 60, 63, 66, 162, 360, 363 - bacteriology of, 68, 163, 171, 176, 181, 184, 189, 194, 197, 345, 364 - fibrin with, 182 - lobar pneumonia with, 155, 157 - measles with, 340 - secondary infection by S. hemolyticus with, 172, 177, 181, 374 - - - C - - Carriers of B. Influenzæ, 46, 101, 369 - of S. hemolyticus, 99, 285, 287, 298, 303, 309, 310, 315, 319, 321, - 332, 379 - - Cartilage, atrophy with bronchiectasis of, 254 - - Contact infection in influenza, prevention of, 98 - in measles, 289 - in pneumonia, prevention of, 98 - - Cubicles to prevent contact infection, 98, 290 - - Cyanosis, 144 - - - E - - Empyema, 64, 67, 224, 226, 233, 304, 366 - abscess of lung and, 233 - encapsulated, 235 - interstitial suppurative pneumonia with, 216, 234 - measles with, 349 - pneumococcus, 236, 350 - streptococcus, 233, 350 - - Endophlebitis, 219 - - - H - - Hemorrhagic and edematous consolidation with bronchopneumonia, 188 - peribronchiolar consolidation with bronchopneumonia, 163, 173, 272, - 340 - - Hepatization with bronchopneumonia, 179, 181 - with lobar pneumonia, 160 - - - I - - Influenza, B. influenzæ with, 30, 73 - bronchitis with, 55, 56 - clinical course of, 28, 53, 73, 80 - coryza with, 54 - cyanosis with, 54 - epidemic in fall of 1918, 52, 108, 359 - epidemic in spring of 1918, 47 - fever with, 53 - gastrointestinal symptoms with, 55 - laryngitis with, 54 - lobar pneumonia and, 161 - measles and, 292, 319, 331, 351, 357, 380 - pandemic of 1889–90, 109, 115 - pandemic of 1918–19, 27, 359 - pharyngitis with, 54 - pneumococcus with, 33 - pneumonia with, 55, 59, 74, 81, 139 - pulmonary lesions of, 137 - pulse with, 54 - secondary infection with, 28, 45, 57, 95 - sputum with, 55 - S. hemolyticus with, 103 - - Interstitial bronchopneumonia, 261, 278, 348 - suppurative pneumonia, 199, 209, 366, 376 - bacteriology of, 214 - chronic inflammation with, 221 - empyema with, 216, 234 - healing of, 222, 224 - measles with, 348 - pericarditis with, 237 - - - L - - Lobar pneumonia, 60, 63, 154, 360, 362 - bacteriology of, 64, 156, 164, 339, 362 - bronchopneumonia with, 155, 157 - experimental production in monkeys of, 394, 397 - influenza and, 161 - measles with, 337 - purulent bronchitis with, 60, 63, 66 - secondary infection by hemolytic streptococci with, 64, 159, 340, 374 - spread in lung of, 339, 354 - typhoid fever with, 353 - - Lobular consolidation, confluent, 188, 341 - with bronchopneumonia, 163, 178, 272, 341 - - Lymphatics, suppurative inflammation of, 217, 218, 376 - thrombosis of, 217, 218 - - Lymphangitis, experimental production with S. hemolyticus of, 392 - - - M - - Masks to prevent contact infection, 98, 290 - - Mastoiditis, 303, 312, 332 - - Measles, 119, 288 - B. influenzæ with, 26, 40, 43, 295 - bronchiectasis with, 336 - bronchitis with, 336 - bronchopneumonia with, 340 - complications of, 303, 378 - empyema with, 349 - influenza and, 292, 319, 331, 351, 357, 380 - interstitial suppurative pneumonia with, 348 - lobar pneumonia with, 337 - pneumococcus pneumonia with, 312 - pneumonia and, 292, 303, 312, 332, 334, 378 - secondary infection with, 282 - S. hemolyticus with, 285, 287, 297, 319, 330, 331, 353, 378 - suppurative pneumonia with, 345, 347 - unresolved bronchopneumonia with, 342 - - Methods, 29, 51, 283, 291 - - Mortality of pneumococcus pneumonia, 140 - of pneumonia following influenza, 139 - of streptococcus pneumonia, 140 - - Mumps, 119, 355 - - - N - - Necrosis with bronchopneumonia caused by S. hemolyticus, 186, 375 - with lobar pneumonia caused by S. hemolyticus, 160, 374 - with S. hemolyticus, 199, 200 - - - O - - Oedema, interstitial, 209 - - Organization of pneumonic exudate, 197 - - Otitis media, 289, 303, 312, 317, 329, 332 - - - P - - Peribronchiolar consolidation with bronchopneumonia, 163, 166, 267, 340 - - Pericarditis, 64, 237 - - Peribronchial consolidation with bronchopneumonia, 163, 192, 361 - hemorrhage, 189 - - Peritonitis, 238 - - Phagocytosis of red blood corpuscles, 272 - - Pneumococcus, 372 - bronchitis and, 153 - bronchopneumonia with, 165, 184, 373 - empyema, 236 - experimental lobar pneumonia with, 393 - influenza with, 33 - lobar pneumonia with, 158, 372 - pneumonia, 60, 75, 104 - clinical course of, 62 - measles and, 312, 332 - mortality of, 140 - secondary pneumococcus infection with, 61 - secondary streptococcus infection with, 62 - transmission of, 91, 383 - secondary infection in pneumonia with, 91 - - Pneumonia, B. influenzæ causing, 72, 76, 371 - bacteriology of influenza and, 60, 74, 107 - bacteriology of measles and, 351 - chronic fibroid, 273 - clinical course of influenza with, 62 - diagnosis of, 136, 334, 361 - dissecans, 209 - immunity following, 373 - influenza with, 59, 76, 81, 109, 360 - measles and, 119, 292, 303, 312, 332, 334, 378 - mumps and, 119 - pneumococcus, see Pneumococcus pneumonia - prevention of, 98, 319, 383 - scarlet fever and, 119 - secondary infection with, 83, 106 - spread through lungs of, 194, 373 - staphylococcus, see Staphylococcus pneumonia - streptococcus, see Streptococcus pneumonia - S. hemolyticus in throat with, 310, 329, 379 - - Pseudoinfluenza bacilli, 26 - - - S - - Scarlet fever, 119, 356 - - Squamous transformation of bronchial epithelium, 149, 251, 275, 336 - - Staphylococcus, 153, 377 - pneumonia, 112, 225, 354, 366 - pneumonia, pathogenesis of, 230 - - Streptococcus empyema, 233 - hemolyticus, 374 - bronchitis with, 153 - dissemination in wards of, 315 - experimental production of acute - lymphangitis with, 392 - identification of, 283 - influenza with, 103 - lobar pneumonia with, 64, 159 - measles with, 285, 287, 297, 330, 331, 345, 353, 378 - normal men with, 285, 322 - secondary infection in pneumonia with, 84, 106, 178, 204, 374 - nonhemolytic, 376 - peritonitis, 238 - pneumonia, 60, 70, 75, 115, 307, 365 - bacteriology of, 71 - clinical features of, 71 - measles with, 303, 305, 307, 318 - mortality of, 140 - transmission of, 84, 381 - viridans, 377 - - Suppurative pneumonia, 199, 347 - with measles, 345, 347 - - - T - - Thrombosis of capillaries with bronchopneumonia, 184 - - Typhoid fever, lobar pneumonia with, 353 - staphylococcus pneumonia with, 354 - - - U - - Unresolved bronchopneumonia, 261, 266, 342, 368 - bacteriology of, 276 - interstitial suppurative pneumonia with, 278 - ------ - -Footnote 1: - - Report of the Surgeon General, U. S. Army to the Secretary of War, - 1918, p. 44. - -Footnote 2: - - Stillman, F. G.: A Study of Atypical Type II Pneumococci, Jour. Exper. - Med., 1919, xxix, 251. - -Footnote 3: - - Opie, E. L., Freeman, A. W., Blake, F. G., Small, J. C., Rivers, T. - M.: Pneumonia at Camp Funston, Jour. Am. Med. Assn., 1919, lxxii, 108. - -Footnote 4: - - Vaughan, V. C., and Palmer, G. T.: Communicable Diseases in the - National Guard and National Army of the United States, Jour. Lab. and - Clin. Med., 1918, iii, 635. - -Footnote 5: - - Miller, J. L., and Lusk, F. B.: Jour. Am. Med. Assn., 1918, lxxi, 702. - -Footnote 6: - - Report of the Surgeon General to the Secretary of War, 1919, i, 637. - -Footnote 7: - - MacNeal, W. J.: The Influenza Epidemic of 1918 in the American - Expeditionary Forces in France and England, Arch. Int. Med., 1919, - xxiii, 657. - -Footnote 8: - - Pfeiffer: Ztschr. f. Hyg., 1893, xiii, 357. - -Footnote 9: - - Wollstein: Jour. Exper. Med., 1916, viii, 681. - -Footnote 10: - - Kretz: Wien. klin. Wchnschr., 1897, x, 877. - -Footnote 11: - - Süsswein: Wien. klin. Wchnschr., 1901, xiv, 1149. - -Footnote 12: - - Liebscher: Prag. med. Wchnschr., 1903, xxviii, 85. - -Footnote 13: - - Jehle: Ztschr. f. Heilk., 1901, xx, n. s. 2, Int. Med. - -Footnote 14: - - Davis: Jour. Infect. Dis., 1906, iii, 1. - -Footnote 15: - - Lord: Boston Med. Sur. Jour., 1905, clii, 537, 574. - -Footnote 16: - - Boggs: Am. Jour. Med. Sc., 1905, cxxx, 902. - -Footnote 17: - - Wollstein: Am. Jour. Dis. Child., 1911, i, 42. - -Footnote 18: - - Rosenthal: Comp. rend. Soc. Biol., 1903, lv, 1500. - -Footnote 19: - - Wollstein: Jour. Exper. Med., 1915, xxii, 445. - -Footnote 20: - - Med. Sup. October 1, 1918 also Jour. Am. Med. Assn., 1918, lxxi, 1573. - -Footnote 21: - - Opie, Freeman, Blake, Small, and Rivers: Jour. Am. Med. Assn., 1919, - lxxii, 108. - -Footnote 22: - - Vaughn and Palmer: Jour. Lab. and Clin. Med., 1918, iii, 635. - -Footnote 23: - - Soper: Jour. Am. Med. Assn., 1918, lxxi, 1899. - -Footnote 24: - - Cole and MacCallum: Jour. Am. Med. Assn., 1918, lxx, 1146. - -Footnote 25: - - Hammond, Rolland, and Shore: Lancet, London, 1917, ii, 41. - -Footnote 26: - - Abrahams, Hallows, Eyre, and French: Lancet, London, 1917, ii, 377. - -Footnote 27: - - Public Health Reports, U.S.P.H. Service, 1919, xxxiv, 33. - -Footnote 28: - - Blake: Jour. Exper. Med., 1917, xxvi, 67. - -Footnote 29: - - Avery: Jour. Am. Med. Assn., 1918, lxx, 17. - -Footnote 30: - - Dunn: Jour. Am. Med. Assn., 1918, lxxi, 2128. - -Footnote 31: - - Fantus: Jour. Am. Med. Assn., 1918, lxxi, 1736. - -Footnote 32: - - Keegan: Jour. Am. Med. Assn., 1918, lxxi, 1051. - -Footnote 33: - - Christian: Jour. Am. Med. Assn., 1918, lxxi, 1565. - -Footnote 34: - - Blanton and Irons: Jour. Am. Med. Assn., 1918, lxxi. 1988. - -Footnote 35: - - Hall, Stone and Simpson: Jour. Am. Med. Assn., 1918, lxxi, 1986. - -Footnote 36: - - Synnott and Clark: Jour. Am. Med. Assn., 1918, lxxi, 1816. - -Footnote 37: - - Friedlander, McCord, Sladen and Wheeler: Jour. Am. Med. Assn., 1918, - lxxi, 1652. - -Footnote 38: - - Brem, Bolling and Casper: Jour. Am. Med. Assn., 1918, lxxi, 2138. - -Footnote 39: - - Ely, Lloyd, Hitchcock, and Nickson: Jour. Am. Med. Assn., 1919, lxxii, - 24. - -Footnote 40: - - Camp Lewis Pneumonia Unit: Jour. Am. Med. Assn., 1919, lxxii, 268. - -Footnote 41: - - Jour. Am. Med. Assn., 1918, lxxi, 2068. - -Footnote 42: - - Wolbach: Bull. Johns Hopkins Hosp., 1919, xxx, 104. - -Footnote 43: - - Spooner, Scott and Heath: Jour. Am. Med. Assn., 1919, lxxii, 155. - -Footnote 44: - - Kinsella: Jour. Am. Med. Assn., 1919, lxxii, 717. - -Footnote 45: - - MacCallum: Jour. Am. Med. Assn., 1919, lxxii, 720. - -Footnote 46: - - Pritchett and Stillman: Jour. Exper. Med., 1919, xxix, 259. - -Footnote 47: - - Hirsch and McKinney: Jour. Am. Med. Assn., 1918, lxxi, 1735. - -Footnote 48: - - Parker: Jour. Am. Med. Assn., 1919, lxxii, 476. - -Footnote 49: - - Opie, Freeman, Blake, Small and Rivers: Jour. Am. Med. Assn., 1919, - lxxii, 556. - -Footnote 50: - - See discussion on pages 115 to 118. - -Footnote 51: - - Isolated by blood culture on Sept. 23. Patient recovered. - -Footnote 52: - - Stillman: Jour. Exper. Med., 1916, xxiv, 651. - -Footnote 53: - - Stillman: Jour. Exper. Med., 1919, xxix, 251. - -Footnote 54: - - Haller and Colwell: Jour. Am. Med. Assn., 1918, lxxi, 1213. - -Footnote 55: - - Doust and Lyon: Jour. Am. Med. Assn., 1918, lxxi, 1216. - -Footnote 56: - - Held in receiving ward 40 hours because of admission of case of - meningococcus meningitis to ward by mistake. - -Footnote 57: - - Finkler, D.: Infectionen der Lunge durch Streptococcen und Influenza - Bacillen, Bonn, 1895. - -Footnote 58: - - Ribbert: Anatomische und bacteriologische Beobachtungen über - Influenza, Deutsch. med. Wehnschr., 1890, xvi, 61, 301. - -Footnote 59: - - Pfeiffer: Die Aetiologie der Influenza, Ztschr. f. Hyg. 1893, xiii, - 357. - -Footnote 60: - - Leichtenstern, O.: Influenza, Nothnagel’s Specielle Pathologie und - Therapie, Wien, 1896, vol. ii, pt. 2. - -Footnote 61: - - Krannhals: Quoted by Leichtenstern. - -Footnote 62: - - Cruickshank: Brit. Med. Jour., 1895, i, 360. - -Footnote 63: - - Birch-Hirschfeld: Schmidt’s Jahrbücher, 1890, ccxxvi, 110. - -Footnote 64: - - Kuskow, N.: Zur pathologischen Anatomie der Grippe, Virchow’s Archiv., - 1895, cxxxix, 406. - -Footnote 65: - - Keegan, J. J.: The Prevailing Epidemic of Influenza, Jour. Am. Med. - Assn., 1918, lxxi, 1051. - -Footnote 66: - - Symmers, D.: Pathologic Similarity between Pneumonia of Bubonic Plague - and of Pandemic Influenza, Jour. Am. Med. Assn., 1918, lxxi, 1482. - -Footnote 67: - - Opie, E. L., Freeman, A. W., Blake, F. G., Small, J. C., Rivers, T. - M.: Pneumonia Following Influenza, Jour. Am. Med. Assn., 1919, lxxii, - 556. - -Footnote 68: - - LeCount, E. R.: The Pathological Anatomy of Influenzal - Bronchopneumonia, Jour. Am. Med. Assn., 1919, lxxii, 650. - -Footnote 69: - - MacCallum, W. G.: Pathology of the Pneumonia Following Influenza, - Jour. Am. Med. Assn., 1919, lxxii, 720. - -Footnote 70: - - Lyon, M. W.: Gross Pathology of Epidemic Influenza at Walter Reed - Hospital, Jour. Am. Med. Assn., 1919, lxxii, 924. - -Footnote 71: - - Goodpasture, E. W. and Burnett, F. L.: The Pathology of Pneumonia - Accompanying Influenza, U. S. Naval Medical Bull., 1919, xiii, No. 2. - -Footnote 72: - - Wolbach: Comments on the Pathology and Bacteriology of Fatal Influenza - Cases as Observed at Camp Devens, Mass., Bull. Johns Hopkins Hosp. - 1919, xxx, 104. - -Footnote 73: - - Cummings, J. G., Spruit, C. B., and Lynch, C.: The Pneumonias: - Streptococcus and Pneumococcus Groups, Jour. Am. Med. Assn., 1918, - lxx, 1066. - -Footnote 74: - - Cole, R. and MacCallum, W. G.: Pneumonia at a Base Hospital, Jour. Am. - Med. Assn., 1918, lxx, 1146. - -Footnote 75: - - Miller, J. L., and Lusk, F. B.: Epidemic of Streptococcus Pneumonia - and Empyema at Camp Dodge, Iowa, Jour. Am. Med. Assn., 1918, lxxi, - 702. - -Footnote 76: - - MacCallum, W. G.: Pathology of the Epidemic of Streptococcus - Bronchopneumonia in the Army Camps, Jour. Am. Med. Assn., 1919, lxxii, - 720. - -Footnote 77: - - Stone, W. J., Phillips, B. G., and Bliss, W. P.: A Clinical Study of - Pneumonia Based on 871 Cases, Arch. Int. Med., 1918, xxii, 409. - -Footnote 78: - - Opie, E. L., Freeman, A. W., Blake, F. G., Small, J. C., and Rivers, - T. M.: Pneumonia at Camp Funston, Jour. Am. Med. Assn., 1919, lxxii, - 108. - -Footnote 79: - - Jour. Am. Med. Assn., 1919, lxxii, 556. - -Footnote 80: - - Miller, W. S.: Am. Rev. Tuberc., 1919, iii, 65. - -Footnote 81: - - Wadsworth, A. B.: A Study of Organizating Pneumonia. Jour. Med. - Research, 1918, xxxix, 147. - -Footnote 82: - - Kaufmann: Spezielle Pathologische Anatomie. 1909, ed. 5, p. 260. - -Footnote 83: - - Beitzke: Respirations Organe. Aschoff’s Path. Anat., 1913 ed. 3, Vol. - II, p. 308. - -Footnote 84: - - Chickering, H. T. and Park, J. H.: Staphylococcus Aureus Pneumonia, - Jour. Am. Med. Assn. 1919, lxxii, 617. - -Footnote 85: - - Stone, W. J., Phillips, B. G., and Bliss. W. P.: A Clinical Study of - Pneumonia Based on 871 Cases. Arch. Int. Med., 1918, xxii, 409. - -Footnote 86: - - Loc. cit., p. 110. - -Footnote 87: - - Lord, F. T.: Infections of the Respiratory Tract with Influenza - Bacilli, Boston Med. and Surg. Jour., 1905, clii, 537, 574. - -Footnote 88: - - Boggs, T. R.: Influenza Bacillus in Bronchiectasis, Am. Jour. Med. - Sc., 1905, cxxx, 902. - -Footnote 89: - - Thornton and Pratt: Bull. Johns Hopkins Hosp., 1908, xix, 230. - -Footnote 90: - - Two cases positive for hemolytic streptococci on this examination were - negative on next examination. - -Footnote 91: - - S. hemolyticus infection implanted upon a pneumococcus pneumonia. - Place in Table indicates onset of pneumonia and not appearance of - streptococcus complication. - -Footnote 92: - - Capps, J. A., and Davis, D. J.: Arch. Int. Med., 1914, xiv, 650; - Illinois Med. Jour., November, 1912. - -Footnote 93: - - Windsor, C. E. A.: Jour. Infect. Dis., 1912, x. 73. - -Footnote 94: - - Hamburger, L. P.: Jour. Am. Med. Assn., April 13, 1912, lviii, 1109. - -Footnote 95: - - Smillie, W. S.: Jour. Infect. Dis., 1917, xx, 45. - -Footnote 96: - - Levy and Alexander: Jour. Am. Med. Assn., 1918, lxx, 1827. - -Footnote 97: - - Irons and Marine: Jour. Am. Med. Assn., 1918, lxx, 687. - -Footnote 98: - - Cole and MacCallum: Jour. Am. Med. Assn., 1918, lxx, 1146. - -Footnote 99: - - Cummings, Spruit and Lynch: Jour. Am. Med. Assn., 1918, lxx, 1066. - -Footnote 100: - - Sputum or saliva cultures on 50 of these men yielded 1 positive for S. - hemolyticus. Sputum or saliva injected intraperitoneally into white - mice and cultures made from the peritoneal exudate of such mice, - yielded 2 additional positives in the same group of 50 men. These 3 - positive cases showed very few colonies of hemolytic streptococci. - -Footnote 101: - - Per cent positive, on one culture only. Repeated throat cultures, - average two per person as follows: - - Cultured No. Cases Positives Once 153 11 Twice 90 7 3 times 39 3 - 4 times 15 1 - -Footnote 102: - - Steinhaus: Ziegler’s Beitr. 1901, xxix, 524. - -Footnote 103: - - Bartels: Virchows Arch. f. path. Anat.; xxi. - -Footnote 104: - - Loc. cit., p. 116. - -Footnote 105: - - Hart: Deutsch. Arch. f. Klin. Med., 1904, lxxix, 108. - -Footnote 106: - - Goodpasture, E. W., and Burnett, F. L.: The Pathology of Pneumonia - Accompanying Influenza, U. S. Nav. Med. Bull., 1919, xiii, No. 2, P. - 21. - -Footnote 107: - - Pfeiffer: Ztschr. f. Hyg., 1893, xiii, 357. - -Footnote 108: - - Kamen, L.: Centralbl. f. Bakteriol., 1901, xxix, Erste Abt. 339. - -Footnote 109: - - Jacobson, G.: Arch. de méd. expér. et d’anat. path., 1901, xiii, 425. - -Footnote 110: - - Richie, J.: Journal Path. and Bacteriol., 1910, xiv, 615. - -Footnote 111: - - Wollstein, M.: Am. Jour. Dis. Child., 1911, i. 42. - ------------------------------------------------------------------------- - - - - - TRANSCRIBER’S NOTES - - - 1. Silently corrected typographical errors and variations in spelling. - 2. Archaic, non-standard, and uncertain spellings retained as printed. - 3. Footnotes have been re-indexed using numbers and collected together - at the end of the last chapter. - 4. Enclosed italics font in _underscores_. - 5. Enclosed bold font in =equals=. - - - - - -End of the Project Gutenberg EBook of Epidemic Respiratory Disease, by -Eugene Lindsay Opie and Francis G. 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