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 AUTOPSY | RACE | LENGTH OF MILITARY SERVICE | DURATION OF ILLNESS | DURATION OF PNEUMONIA | CLINICAL DIAGNOSIS | PURULENT BRONCHITIS | LOBAR PNEUMONIA | PERIBRONCHIOLAR CONSOLIDATION | HEMORRHAGIC PERIBRONCHIOLAR CONSOLIDATION | LOBULAR CONSOLIDATION | PERIBRONCHIAL CONSOLIDATION | ABSCESS | INTERSTITIAL SUPPURATIVE PNEUMONIA | MULTIPLE ABSCESSES IN CLUSTERS | EMPYEMA | BRONCHIECTASIS | UNRESOLVED BRONCHOPNEUMONIA | ORGANIZING BRONCHITIS | BACTERIA IN SPUTUM | BACTERIA IN BRONCHUS | BACTERIA IN LUNG | BACTERIA IN BLOOD OF HEART |
| 229 | W | 1m | 12+ | 12+ | L | P | + | Pn. I. B. inf. | 0 | |||||||||||||
| 231 | W | 2m | 13 | 4 | B | P | + | |||||||||||||||
| 232 | W | 14d | 9 | 6? | B | + | Pn. IIa. B. inf. | Pn. IIa. | Pn. IIa. | |||||||||||||
| 233 | C | 11m | 5 | 2 | L | + | Pn. IIa. | Pn. | ||||||||||||||
| 236 | W | 3w | 8 | 7+ | L | + | Pn. IV. B. inf. | B. inf. Staph. | 0 | |||||||||||||
| 237 | W | 10d | 8 | 2 | L | + | + | N | E | St. h. | St. h. | |||||||||||
| 238 | W | 2d | 8 | 5 | L | + | Pn. IV. B. inf. | Pn. IV | ||||||||||||||
| 239 | W | 11d | 9 | 5 | L | + | Pn. II. | Pn. II. B. inf. | Pn. II. | |||||||||||||
| 240 | W | 13d | 8 | 4 | L | + | M | + | Pn. IV. | B. inf. | Pn. IV. | |||||||||||
| 241 | W | 14d | 5 | 5 | L | + | Pn. IV. B. inf. | Pn. IV. | ||||||||||||||
| 242 | C | 14d | 7 | 4 | L | P | + | + | Pn. IIa. B. inf. | Pn. IIa. | ||||||||||||
| 243 | W | 15d | 5 | 5 | L | + | M | Pn. IV. | ||||||||||||||
| 244 | C | 1m | 6 | 3 | B | P | M | + | + | + | Pn. IV. B. inf. | Pn. IV. B. inf. | 0 | |||||||||
| 246 | C | 2m | 6 | 3 | L | P | + | M | Pn. IIa. B. inf. | 0 | ||||||||||||
| 247 | W | 10d | 10 | 5 | L | P | M | + | + | Pn. IV. B. inf. | Pn. IV. | |||||||||||
| 248 | W | 1m | 4 | 2+ | I | + | E | St. h. | St. h. | St. h. | ||||||||||||
| 249 | W | 15d | 12 | 6+ | L | M | + | Pn. III. | ||||||||||||||
| 250 | W | 14d | 11 | 7 | L | M | + | E | Pn. IIa. B. inf. | Pn. IIa. | ||||||||||||
| 251 | W | 25d | 7 | 1 | B | P | + | + | + | + | St. h. | St. h. | ||||||||||
| 252 | W | 21d | 14 | 12 | B | P | M | + | Pn. II. B. inf. St. v. | Pn. II. B. inf. | 0 | |||||||||||
| 253 | W | 12d | 19 | 12+ | B | M | + | + | E | Pn. Ia. | Pn. II. B. inf. Staph. | Pn. II. B. inf. | Pn. II. | |||||||||
| 254 | W | 21d | 7 | 6+ | B | P | + | M | + | Pn. I. B. inf. | Pn. I. Staph | 0 | ||||||||||
| 255 | W | 12d | 5 | 4? | B | P | M | + | + | + | E | St. h. Pn. IIa. Staph. | St. h. | St. h. | ||||||||
| 256 | W | 17d | 8 | 4 | B | P | + | M | Pn. Staph. | Pn. IIa. | Pn. IIa. | |||||||||||
| 257 | C | 21d | 10 | 7+ | L | P | + | B. inf. Staph | Pn. I. | |||||||||||||
| 258 | W | 1m | 6 | 2+ | B | M | + | + | E | St. h. Pn. IV. B. inf. | St. h. | |||||||||||
| 259 | W | 3m | 4 | 1 | B | + | + | + | St. h. Pn. III. Staph. | St. h. | ||||||||||||
| 260 | W | 1m | 2 | 1 | L | + | 0 | |||||||||||||||
| 261 | W | 2m | 7 | 5+ | B | P | + | B. inf. Pn. IV. | 0 | |||||||||||||
| 262 | W | 12d | 5 | 4? | B | + | + | E | St. h. B. inf. | St. h. | St. h. | |||||||||||
| 263 | W | 21d | 7 | 5 | L | P | + | + | E | St. h. B. inf. Staph. | St. h. Staph. | |||||||||||
| 264 | W | 21d | 10 | 7 | L | + | Pn. IV. Staph. | St. h. Staph. | St. h. | St. h. | ||||||||||||
| 265 | W | 14d | 7 | 6+ | L | + | St. h. Staph. inf. | Pn. IV. B. inf. | St. h. | |||||||||||||
| 266 | W | 1m | 7 | 2 | L | + | + | St. h. | St. h. B. inf. | St. h. | St. h. | |||||||||||
| 267 | W | 2m | 22 | 10 | B | + | Pn. IV. | Pn. II. B. inf. | Pn. II. | Pn. II. | ||||||||||||
| 268 | W | 2m | 6 | 4? | L | + | Pn. III. B. | Pn. III. B. inf. St. h. | Pn. III. B. inf. St. h. | 0 | ||||||||||||
| 269 | W | 25d | 8 | 2 | L | + | Pn. IV. B. | Pn. IV. Staph. | Pn. IV. | 0 | ||||||||||||
| 270 | W | 17d | 18 | 3 | L | + | h | St. h. B. inf. Staph. | St. h. Staph. | St. h. | ||||||||||||
| 271 | W | 2d | 12 | 5 | L | P | + | St. h. Pn. IV. B. inf. | St. h. | St. h. | ||||||||||||
| 272 | W | 3m | 7 | 2 | L | + | St. h. | |||||||||||||||
| 273 | W | 1m | 8 | 4+ | L | + | + | N | E | St. h. B. inf. Staph. | St. h. Pn. IV. Staph. | St. h. | ||||||||||
| 274 | W | 2w | 9 | 5 | B | + | N | Pn. IV. | St. h. Staph. | St. h. | St. h. | |||||||||||
| 275 | W | 4m | 9 | 4 | L | M | + | + | N | St. h. B. inf. Staph. | St. h. B. inf. Staph. | St. h. Pn. IV. | ||||||||||
| 276 | W | 1m | 6 | 4+ | L | + | St. h. Staph B. inf. | St. h. Pn. IV. B. inf. | St. h. | |||||||||||||
| 277 | W | 21d | 10 | 3 | L | + | St. h. Staph | St. h. Staph | St. h. | |||||||||||||
| 278 | W | 2m | 16 | 6+ | L | + | E | St. h. B. inf. | St. h. | St. h. | ||||||||||||
| 279 | W | L | + | Pn. IV | Pn. IV. | |||||||||||||||||
| 280 | W | 21d | 8 | 8 | L | + | + | + | St. h. B. inf. Staph. | St. h. | St. h. | |||||||||||
| 281 | W | 21d | 9 | 5 | L | + | + | h | St. h. B. inf. | St. h. | ||||||||||||
| 282 | W | 1m | 10 | ? | B | + | + | E | Pn. IV. B. inf. | St. h. B. inf. Pn. II Staph. | St. h. Pn. II. | St. h. Pn. II. | ||||||||||
| 283 | W | 7d | 19 | 8 | B | P | + | + | + | M | + | B. inf. Pn. IV. Staph. | Staph. B. inf. | Pn. IV. | ||||||||
| 284 | W | 21d | 11 | ? | B | P | + | + | E | St. h. B. inf. Staph. | St. h. | St. h. | ||||||||||
| 285 | W | 11 | 9? | B | P | M | + | E | Pn. IIa. B. inf. | St. h. B. inf. | St. h. | St. h. | ||||||||||
| 286 | W | 20d | 9 | 4+ | L | P | M | + | Pn. IV. B. inf. Staph. | 0 | Pn. IV. | |||||||||||
| 287 | W | 3m | 12 | 4 | L | P | + | + | + | Pn. IV. B. inf. Staph. | Pn. IV. B inf. Staph. | Pn. IV. | ||||||||||
| 288 | W | 1m | 10 | 5 | B | P | M | + | h | + | E | + | St. h. B. inf. | St. h. B. inf. | St. h. | St. h. | ||||||
| 289 | W | 19d | 12 | 7 | B | P | M | + | M | + | Pn. IV. B. inf. Staph. | Pn. IV. | Pn. IV. | |||||||||
| 290 | W | 1m | 3+ | 3+ | B | + | St. h. B. inf. | St. h. | St. h. | |||||||||||||
| 291 | W | 2w | 18 | 11 | B | P | + | + | M | + | Pn. IV. B. inf. | B. inf. Staph. | 0 | 0 | ||||||||
| 292 | W | 3m | 5 | 5 | L | + | E | St. h. B. inf. | St. h. | |||||||||||||
| 293 | W | 2m | 3+ | 3+ | L | P | + | Pn. III. B. inf. | Pn. III. B. inf. | Pn. III. | ||||||||||||
| 295 | W | 1m | 12 | 5 | L | P | + | + | E | + | Pn. IV. St. h. | St. h. B. inf. | St. h. | |||||||||
| 296 | W | 16d | 18 | 3 | L | P | + | + | E | + | St. h. B. inf. | St. h. B. inf. | St. h. | |||||||||
| 297 | W | 1m | 5 | ? | I | P | + | B. inf. Pn. IV. St. h. | Pn. IV. B. inf. | 0 | ||||||||||||
| 298 | C | 21d | 13 | 10 | B | P | + | Pn. IIa. B. inf. | Pn. IIa. | |||||||||||||
| 299 | W | 28d | 9 | 3 | L | P | + | B. inf. Pn. IV. Staph. St. h. | ||||||||||||||
| 300 | C | 22d | 16 | 12+ | L | P | + | M | h | Pn. IIa. B. inf. | Pn. IIa. B. inf. | Pn. IIa. | ||||||||||
| 301 | W | 1m | 7 | 5 | B | + | Pn. IV. B. inf. Staph. St. h. | Pn. IV. | ||||||||||||||
| 302 | C | 5d | 6 | 3+ | B | + | Pn. IV. B. inf. | Pn. IV. | ||||||||||||||
| 303 | W | 1m | 7 | 3+ | L | + | Staph. Pn. IV. B. inf. | Pn. IV. B. inf. | ||||||||||||||
| 304 | W | 4m | 10 | 2? | L | + | St. h. B. inf. | St. h. B. inf. | ||||||||||||||
| 305 | W | 5m | 3+ | 3+ | L | + | B. inf. St. h. Pn. IV. Staph. | B. inf. St. h Pn. IV. Staph. | ||||||||||||||
| 306 | W | 1y | 6+ | 3 | B | + | B. inf. Pn. IV. Staph. | 0 | 0 | |||||||||||||
| 308 | W | 1m | 6 | 6 | L | + | + | Pn. IV. B. inf. St. h. Staph. | St. h. | Pn. IV. | ||||||||||||
| 309 | W | 1m | 4 | 2? | L | + | E | St. h. | St. h. | |||||||||||||
| 310 | W | 21d | ? | 3? | L | + | Pn. III. B. inf. Staph. | Pn. III. Pn. IV. B. inf. | ||||||||||||||
| 312 | W | 1m | 17 | 7 | L | P | M | + | h | N | + | Pn. IV. B. inf. St. h. | St. h. B. inf. Staph. | St. h. B. inf. | St. | |||||||
| 313 | W | 1y | 5 | 2 | B | + | St. h. B. inf. Staph. | St. h. | St. h. | |||||||||||||
| 314 | W | 1m | 3+ | 3+ | L | P | + | + | Pn. IV. B. inf. Staph. | Pn. IV. | Pn. IV. | |||||||||||
| 315 | W | 1m | 9 | 2 | B | + | Pn. IV. B. inf. Staph. | Pn. IV. | ||||||||||||||
| 316 | W | 1m | 11 | 4 | L | + | B. inf. | Pn. III. B. inf. | Pn. III. | |||||||||||||
| 317 | W | 13d | 9 | 2 | L | + | Pn. IV. B. inf. | Pn. IV. | ||||||||||||||
| 318 | W | 2m | 8 | 3 | L | + | Pn. IV. B. inf. | Pn. IV. B. inf. | ||||||||||||||
| 319 | W | 1m | 4+ | 4+ | B | P | + | St. h. Staph. | St. h. B. inf. Staph. | St. h. | ||||||||||||
| 320 | C | 5m | 1+ | 1+ | L | + | Pn. IIa. | Pn. IIa. | Pn. IIa. | |||||||||||||
| 321 | W | 28d | 4+ | 4+ | L | + | E | B. inf. | Pn. IV. B. inf. | Pn. IV. | ||||||||||||
| 322 | W | 10d | 8 | 6 | L | P | + | + | + | Pn. IV. | Pn. III. Staph. aur. | 0 | ||||||||||
| 323 | W | 2m | 12 | 4 | B | + | Pn. IV. B. inf. Staph. | 0 | ||||||||||||||
| 324 | W | 22d | 9 | 6 | B | + | Pn. I. B. inf. | 0 | Pn. I. | |||||||||||||
| 325 | W | 1m | 8 | 8 | B | P | M | N | + | + | St. h. B. inf. Staph. | St. h. | St. h. | |||||||||
| 326 | W | 1m | 5+ | 2 | B | P | + | h | St. h. B. inf. Staph. | St. h. B. inf. | St. h. | |||||||||||
| 327 | W | 1m | 4 | ? | B | + | ||||||||||||||||
| 328 | W | 5m | 13 | 3+ | L | P | + | Pn. III. Pn. IV. B. inf. Staph. | Pn. III. Pn. IV. B. inf. | Pn. III. | ||||||||||||
| 330 | W | 1m | 10 | 3 | L | M | N | + | E | Pn. IV. | Pn. IV. | |||||||||||
| 331 | W | 1m | 12 | 11+ | B | P | + | Pn. IV. | ||||||||||||||
| 332 | W | 1m | 17 | 3 | L | P | + | M | h | 0 | ||||||||||||
| 333 | W | 19d | 15 | 7 | L | P | M | + | + | + | Staph. aur. B. inf. St. h. | Staph. aur. Pn. IIa. St. h. | Pn. IIa. | |||||||||
| 334 | W | 14d | 16 | 5 | B | M | N | + | E | St. h. Staph | St. h. | |||||||||||
| 335 | W | 1m | 7 | ? | ? | + | St. v. B. inf. Staph. Pn. IV. | Pn. IV. | ||||||||||||||
| 336 | W | 2m | 12 | 6 | B | P | M | + | + | 0 | ||||||||||||
| 337 | W | 1m | 9 | 2? | L | + | Pn. IV. | |||||||||||||||
| 338 | W | 1m | 7 | 5+ | B | + | Pn. IV. | |||||||||||||||
| 339 | W | 2m | 9 | 6? | L | + | Pn. IV. | |||||||||||||||
| 340 | W | 35d | 8 | 3 | L | P | + | + | 0 | |||||||||||||
| 341 | W | 3m | 6 | 4+ | + | 0 | ||||||||||||||||
| 342 | W | 2m | 9 | 3? | L | P | + | + | ||||||||||||||
| 343 | W | 1m | 11 | 1? | L | + | E | Pn. IV. | Pn. IV. | |||||||||||||
| 344 | W | 4m | 13 | 6 | L | + | + | E | St. h. | |||||||||||||
| 345 | W | 1d | ? | 7 | L | P | + | + | + | E | Pn. III. St. h Staph. | |||||||||||
| 346 | W | 26d | 16 | 10 | B | P | + | M | + | N | B. inf. Pn. IV. | St. h. B. inf. | St. h. B. inf. | St. h. | ||||||||
| 347 | C | 3d | 10 | 3 | L | P | + | h | St. h. | |||||||||||||
| 348 | C | 4d | 8 | 8 | B | P | + | Pn. IIa. | ||||||||||||||
| 349 | W | 2d | 12 | 6 | L | P | + | Pn. III St. h | Pn. I. | |||||||||||||
| 350 | W | 2m | 6 | 2? | B | + | St. h. | |||||||||||||||
| 351 | C | 4m | 4 | 3+ | L | P | + | |||||||||||||||
| 352 | C | 2m | 8 | 4 | L | P | + | + | + | + | Pn. IIa. | |||||||||||
| 353 | C | 6m | 18 | 18 | L | P | + | E | Pn. I. B. inf. | B. inf. Pn. | Pn. IIa. | Pn. IIa. | ||||||||||
| 354 | W | 15d | 2+ | 2 | L | P | M | h | + | E | St. h. B. inf. Staph. | St. h. | St. h. | |||||||||
| 355 | W | 21d | 7 | 7 | B | P | + | + | E | St. h. B. inf. Pn. IV. Staph. | St. h. B. inf. Staph. | 0 | ||||||||||
| 356 | C | 5d | 8 | 4 | L | + | Pn. IV. | |||||||||||||||
| 357 | W | 1m | 10 | 6+ | L | + | + | + | Pn. IV. B. inf. | Pn. IV. | ||||||||||||
| 358 | W | 1m | 15 | 6? | L | + | E | Pn. IIa. | ||||||||||||||
| 359 | W | 1m | 7+ | ? | L | M | h | + | Pn. IV. | |||||||||||||
| 360 | W | 36d | 10 | 3 | L | P | + | + | + | 0 | ||||||||||||
| 361 | W | 3m | 8 | 2 | L | + | Pn. IV. | |||||||||||||||
| 362 | W | 4m | 15 | 13+ | L | + | St. h. | |||||||||||||||
| 363 | W | 3m | 8 | 1+ | L | P | + | Pn. IV. | ||||||||||||||
| 364 | W | 6d | 9 | 5+ | B | + | St. h. | |||||||||||||||
| 365 | W | 2m | 11 | 2 | B | + | + | + | Pn. IV. | Pn. IV. | ||||||||||||
| 366 | W | 6d | 8 | 1+ | B | + | M | Pn. IV. | ||||||||||||||
| 367 | W | 22d | 15 | 8+ | L | + | Pn. IV. | |||||||||||||||
| 368 | C | 4d | 15 | 11+ | L | P | + | M | Pn. I. | |||||||||||||
| 369 | W | 68d | 7+ | 4 | B | P | + | + | N | + | E | St. h. | St. h. | St. h. | ||||||||
| 370 | W | 17d | 17 | 14 | L | P | + | + | + | + | + | [No. St. h.] | Staph. aur. Pn. IV. B. inf. | Staph. aur | 0 | |||||||
| 372 | W | 1m | 17 | 5 | L | P | + | + | Mh | + | ||||||||||||
| 373 | W | 4d | 11 | 1? | B | + | St. h. | |||||||||||||||
| 374 | C | 4d | 10 | 5 | L | P | + | + | + | Pn. IV. | ||||||||||||
| 375 | C | 4d | 12 | 6 | L | P | + | + | + | 0 | ||||||||||||
| 376 | W | 1m | 10 | 7+ | B | P | + | + | M | + | E | + | [No. St h.] | St. h. B. inf. Staph. aur. | St. h. | St. h. | ||||||
| 377 | W | 1m | 7 | 4? | B | P | + | + | Pn. IV. | |||||||||||||
| 378 | W | 1m | 28 | 7 | B | P | + | + | E | + | St. h. B. inf. Pn. IIa. | St. h. B. inf. Pn. IIa. | Pn. IIa. | |||||||||
| 379 | W | 11m | 7 | 1 | B | + | + | E | B. inf. + | ? | Pn. IIa. | |||||||||||
| 380 | W | 3m | 11 | ? | B | P | + | + | + | Pn. III. | Pn. III. | |||||||||||
| 381 | W | 21d | 13 | 9? | L | P | + | + | E | + | St. h. Pn. II. Pn. IV. Staph. aur. | St. h. | ||||||||||
| 382 | W | 1m | 9 | 6+ | L | P | + | 0 | ||||||||||||||
| 383 | W | 2m | 9 | 2 | L | + | + | B. inf. Pn. III. St. h. | Pn. III. | |||||||||||||
| 384 | W | 1m | 13 | 5 | L | + | Pn. IV. | |||||||||||||||
| 385a | W | 3w | 12 | 6? | B | P | + | + | E | St. h. | St. h. | |||||||||||
| 385b | W | 2m | 11 | 4 | L | + | Pn. IV. | |||||||||||||||
| 385c | W | 24d | 17 | 10 | B | P | M | + | + | + | + | St. h. B. inf. | St. h. | |||||||||
| 386 | W | 1m | ? | 5 | L | P | + | + | Pn. III. B. inf. Staph. aur. | Pn. III. | ||||||||||||
| 387 | W | 3w | 19 | 9 | B | P | + | + | + | + | E | + | St. h. B. inf. Staph. aur. Pn. | Staph. alb Pn. II. B. inf. | St. h. | |||||||
| 388 | W | 3m | 11 | 7 | L | P | + | Pn. IV. | ||||||||||||||
| 389 | W | 1m | 15 | 15 | L | P | + | + | E | + | St. h. | St. h. | ||||||||||
| 391 | W | 25d | 13 | 13 | L | P | + | + | + | h | + | Pn. IV. | Pn. IV. | |||||||||
| 392 | W | 1m | 12 | 8+ | L | P | + | M | + | Pn. II. | ||||||||||||
| 393 | W | 1m | 20 | 4 | L | + | Pn. IV. | |||||||||||||||
| 394 | W | 21d | ? | ? | L | P | + | + | h | + | St. h. | |||||||||||
| 395a | W | 1m | 19 | 11? | L | P | M | + | + | E | + | St. h. B. inf. | St. h. | |||||||||
| 395b | W | 3m | 12 | 3? | B | P | + | h | E | Pn. IIa. | Pn. IIa. | |||||||||||
| 396 | W | 2m | 7 | 1+ | B | + | 0 | |||||||||||||||
| 397 | W | 21d | 22 | 14 | B | P | M | + | + | E | St. h. B. inf. | St. h. | ||||||||||
| 398 | W | 1m | 16 | 6? | B | P | + | M | + | + | 0 | |||||||||||
| 399 | W | 1m | 18 | 4 | L | + | Pn. IIa. | |||||||||||||||
| 400 | W | 1m | 15 | 11+ | L | + | Pn. IV. | |||||||||||||||
| 401 | W | 1m | 13+ | 9 | B | P | + | M | h | + | Pn. IV. | |||||||||||
| 402 | W | 1m | 14 | 8 | B | P | M | + | + | E | + | + | + | Pn. IV. St. h. | ||||||||
| 404 | B | P | + | + | ||||||||||||||||||
| 405 | W | 21d | 13 | 11+ | B | + | M | Pn. | ||||||||||||||
| 406 | C | 2d | 18 | 15? | L | P | + | + | E | Pn. IV. | ||||||||||||
| 408 | C | 1m | 13 | ? | L | P | + | + | 0 | |||||||||||||
| 409 | C | 6d | 12 | 9+ | L | P | + | + | M | 0 | ||||||||||||
| 410 | W | 35d | 13+ | 13+ | L | P | + | + | M | + | E | + | St. h. B. inf. Staph. aur. | |||||||||
| 411 | W | 3m | 16 | 2 | B | P | + | + | Pn. IIa. B. inf. | Pn. IIa. | ||||||||||||
| 412 | W | 1m | 15 | 13? | L | + | M | + | Pn. II. B. inf. | Pn. II. | ||||||||||||
| 413 | C | 2m | 13 | 8+ | L | P | + | + | Pn. III. B. inf. | Pn. III. | ||||||||||||
| 414 | C | 7d | 18 | 4 | L | P | + | Pn. IIa. B. inf. | Pn. IIa. | |||||||||||||
| 415 | C | 16d | 8 | 6+ | L | P | + | + | + | St. h. | 0 | |||||||||||
| 416 | C | 7d | 14 | 6? | L | P | + | Pn. IV. | Pn. IV. | Pn. IV. | ||||||||||||
| 418 | W | 2m | 19 | 4 | B | + | Pn. IIa. St. v. B. inf. | Pn. IIa. | ||||||||||||||
| 419 | W | 4m | 20 | ? | L | P | + | + | M | + | Pn. II. B. inf. | Pn. II. B. inf. | 0 | |||||||||
| 420 | W | 1m | 11 | 3 | B | P | + | M | + | E | + | + | St. h. B. inf. Staph. aur. | St. h. | ||||||||
| 421 | W | 21d | 19 | 15? | B | P | + | M | + | + | + | Pn. IV. St. h. | St. h. | |||||||||
| 422 | W | 3m | 11+ | 11+ | B | P | + | + | M | + | + | Pn. IIa. B. inf. | 0 | |||||||||
| 423 | W | 1m | 16 | 12? | B | P | + | M | E | + | + | St. h. B. inf. | St. h. | |||||||||
| 424 | W | 5y | 14 | 6 | L | P | + | + | Pn. IV. | |||||||||||||
| 425 | W | 1m | 29 | 14 | B | P | + | + | M | + | + | + | St. h. B. inf. Staph. alb. | St. h. | ||||||||
| 426 | W | 4m | 20 | 13 | ? | + | Pn. IIa. B. inf. | Pn. IIa. | ||||||||||||||
| 427 | W | 1m | 16 | ? | L | P | + | + | St. h. | St. h. | ||||||||||||
| 428 | W | 3w | 25 | 21 | L | P | M | + | + | E | + | St. h. B. inf. | St. h. B. inf. | St. h. | ||||||||
| 429 | C | 2m | 7+ | 5 | L | P | + | + | + | B. inf. Staph. alb | 0 | |||||||||||
| 430 | W | 2m | 16+ | 7 | L | P | + | + | N | St. h. B. inf. Staph. aur. | St. h. | |||||||||||
| 431 | W | 21d | 23 | 18 | L | P | + | + | + | + | 0 | 0 | ||||||||||
| 432 | W | 42d | 19 | 12+? | L | P | + | E | B. inf. Pn. IIa. | Pn. IIa. | ||||||||||||
| 433 | W | 1m | 19 | 17 | B | P | M | + | M | + | E | + | St. h. B. inf. Staph. aur. | 0 | ||||||||
| 434 | W | 4m | 14+ | 10 | L | + | + | E | St. h. B. inf. Staph. aur. | St. h. Staph. aur. | St. h. | |||||||||||
| 435 | W | 1m | 16+ | 2? | B | + | St. h. B. inf. | B. inf. + | St. h. | |||||||||||||
| 436 | C | 11m | 5 | 3+? | B | + | Pn. IIa. B. inf. Staph. aur. | Pn. IIa. | Pn. IIa. | |||||||||||||
| 437 | C | 5m | 11 | 7? | L | P | + | + | 0 | |||||||||||||
| 440 | W | 1m | 19 | 12? | L | P | + | + | + | M | + | + | B. inf. Staph. aur. | B. inf. Staph. aur. | 0 | |||||||
| 445 | W | 1m | 27 | 16? | P | M | h | + | + | Staph. aur. | Staph. aur. Pn. IV. | St. h. | ||||||||||
| 446 | W | 8d | 13 | ? | P | + | + | 0 | ||||||||||||||
| 447 | W | 8d | 10 | 2 | B | + | Staph. aur. | B. coli. Staph. aur. | 0 | |||||||||||||
| 448 | W | 70d | 17 | 14+ | L | P | + | + | Mh | + | 0 | 0 | 0 | |||||||||
| 449 | W | 2m | 27 | 13+ | B | P | + | + | + | E | + | + | St. h. B. coli. | St. h. B. coli. | St. h. | |||||||
| 452 | W | 4m | 14 | 9 | B | P | M | + | E | St. h. B. inf. | St. h. B. inf. | St. h. | ||||||||||
| 451 | C | 2m | 7 | 3+ | B | + | E | B. coli. Staph. St. v. | Pn. IIa. B. inf. | Pn. IIa. | ||||||||||||
| 455 | C | 26 | 22+ | B | + | + | E | St. h. B. inf. | St. h. | St. h. | ||||||||||||
| 456 | W | 1m | 23+ | 20+ | L | P | + | E | B. coli. | St. h. | ||||||||||||
| 457 | W | 17m | 17+ | 17+ | B | + | + | + | + | + | Pn. IV. B. inf. | |||||||||||
| 458 | W | 11m | 10 | 8+? | L | + | + | Pn. IV. B. inf. St. v. | 0 | |||||||||||||
| 459 | C | 10d | 6 | 3 | B | P | + | + | Staph. aur. Pn. IV. | 0 | ||||||||||||
| 460 | W | 1m | 17 | 17 | L | P | + | + | M | + | E | + | St. h. B. inf. Staph. | St. h. B. inf. | St. h. | |||||||
| 461 | C | 5d | 14 | 8+ | L | P | + | M | + | Staph. aur. Pn. I. St. h. | Pn. I. | |||||||||||
| 462 | C | 5d | 15+ | 12 | B | + | 0 | |||||||||||||||
| 463 | W | 3m | 20 | 12 | B | P | + | + | Mh | + | + | B. inf. Staph. | B. inf. Staph. | 0 | ||||||||
| 464 | C | 21d | 24 | 17? | L | P | + | B. inf. Pn. I. Staph. | B. inf. Pn. I. | 0 | ||||||||||||
| 465 | W | 1m | 24+ | 11 | LB | P | M | + | E | + | St. h. B. inf. Staph. St. v. | St. h. | St. h. | |||||||||
| 466 | W | 2d | 13 | 3 | B | + | + | Pn. IIa. | Pn. IIa. | Pn. IIa. | ||||||||||||
| 467 | W | 3m | 30 | 25? | B | P | + | + | + | E | + | St. h. B. inf. | 0 | St. h. | ||||||||
| 468 | W | 1m | 22+ | 6 | L | P | + | + | + | Staph. aur. B. inf. St. v. | B. inf. St. v. | 0 | ||||||||||
| 469 | W | 1m | 25 | 12 | B | P | + | + | + | |||||||||||||
| 471 | C | 6+? | 4 | L | P | + | Pn. IV. B. inf. Staph. aur. | Pn. I. Pn. IV. B. inf. | 0 | |||||||||||||
| 472 | W | 1m | 37 | 21 | B | P | + | + | + | + | E | + | + | B. coli. | St. h. B. coli. | St. h. | ||||||
| 473 | W | 2w | 28+ | 24 | B | P | + | + | E | + | + | + | B. inf. St. v. Staph. M. cat. | St. v. | Pn. III. | |||||||
| 474 | W | 1m | 36 | 31+ | L | + | + | E | St. v. B. inf. M. cat. | St. h. | St. h. B. inf. | |||||||||||
| 476 | W | 7d | 6 | 2 | B | P | M | + | 0 | |||||||||||||
| 477 | W | 5d | 9 | 5 | B | + | + | N | St. h. B. coli. | St. h. B. coli. | St. h. | |||||||||||
| 478 | W | 2m | 9 | 3 | L | + | St. h. | St. h. | ||||||||||||||
| 479 | C | 8d | 29 | 15 | L | P | + | M | N | B. inf. St. h. Staph. M. cat. | St. h. Staph. aur. | St. h. | ||||||||||
| 480 | W | 4m | 31+ | 29 | B | + | + | E | Staph. aur. St. v. | Staph. aur. B. inf. St. v. | B. coli. St. | |||||||||||
| 482 | W | 2m | 11 | 5+ | B | P | + | + | + | M | + | B. inf. Pn. IV. St. h. | B. inf. Pn. IV. | 0 | ||||||||
| 485 | W | 3d | 9+ | 3+ | B | P | M | + | E | St. h. B. inf. Staph. aur. B. coli. | St. h. | St. h. | ||||||||||
| 487 | W | 21d | 55 | 40 | B | P | + | + | E | + | + | B. inf. St. h. | B. inf. | St. h. | ||||||||
| 488 | W | 4d | 16 | 8 | L | P | M | + | E | + | St. h. Pn. IIa. | St. h. | St. h. | |||||||||
| 489 | C | 8d | 11 | 4 | B | P | + | + | M | + | B. inf. Pn. IV. | Pn. IV. B. inf. | 0 | |||||||||
| 494 | W | 2m | 11 | 3 | L | + | h | + | E | St. h. B. inf. | St. h. B. inf. | St. h. | ||||||||||
| 498 | W | 1y | 6 | 1? | L | + | N | St. v. | St. v. Staph. aur. Staph. alb. | St. v. | ||||||||||||
| 499 | W | 5m | 36 | 5 | B | P | M | E | + | St. h. B. inf. | 0 | St. h. | ||||||||||
| 504 | W | 3m | 6 | 3 | L | M | + | E | St. h. B. inf. Staph. | St. h. | St. h. | |||||||||||
| 506 | W | 8m | 7+ | 2? | B | + | Pn. IV. B. inf. Staph. aur. M. cat. | Pn. IV. Staph. aur. | Pn. IV. | |||||||||||||
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.
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.