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 ILLNESS | BLOOD | LUNGS | BRONCHUS |
| 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. aur. | S. 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).
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.
Fig. 27.—Unresolved pneumonia with peribronchial formation of fibrous tissue; bronchiectasis. Autopsy 487.
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 PER CENT POSITIVE | HEMOLYTIC STREPTOCOCCUS PER CENT POSITIVE | STAPHYLOCOCCUS PER CENT POSITIVE | B. INFLUENZÆ PER CENT 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 | |||||
| DAYS IN HOSPITAL | APPROXIMATE DAY OF DISEASE | NO. OF PATIENTS CULTURED | NO. WITH HEMOLYTIC STREPTOCOCCI | PER CENT WITH 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. | |||
| NUMBER EXAMINED | HEMOLYTIC STREPTOCOCCI PRESENT | PER CENT WITH HEMOLYTIC 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. | ||||
| DAYS IN HOSPITAL | NO. OF PATIENTS CULTURED | NO. WITH HEMOLYTIC STREPTOCOCCI | PER CENT WITH HEMOLYTIC 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.
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 MEASLES DURING INTERVALS OF 15 DAYS | TOTAL CASES PNEUMONIA FROM SAME | OF PER CENT INCIDENCE OF PNEUMONIAS | |||
| 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. | |||||||||||
| GROUPS | TOTAL NUMBER CULTURED IN GROUP | GROUP NO. NEGATIVE FOR B. INFLUENZÆ ON ADMISSION | RESULTS OF CULTURES TO DATE | GROUP NO. POSITIVE FOR B. INF. TO DATE | GROUP OF POSITIVES DEVELOPING TO DATE IN CASES NEGATIVE FOR B. INF. ON ADMISSION | PER CENT OF GROUP POSITIVE FOR B. INF. TO DATE | GROUP PER CENT OF POSITIVES TO DATE AMONG CASES NEGATIVE FOR B. INF. ON ADMISSION | ||||
| 1ST CULTURE | 2ND CULTURE | 3RD CULTURE | 4TH CULTURE | NO. IN EACH CLASS | |||||||
| I | |||||||||||
| 1st culture on admission | 426 | − | 274 | 152 | 35.6 | ||||||
| + | 152 | ||||||||||
| II | |||||||||||
| 1st and 2nd culture, after one week in hospital | 201 | 143 | − | − | 75 | 126 | 68 | 62.7 | 47.5 | ||
| − | + | 68 | |||||||||
| + | + | 29 | |||||||||
| + | − | 29 | |||||||||
| III | |||||||||||
| 1st, 2nd and 3rd cultures after two weeks in hospital | 94 | 69 | − | − | − | 22 | 72 | 47 | 77.7 | 68.1 | |
| − | − | + | 18 | ||||||||
| − | + | − | 13 | ||||||||
| − | + | + | 16 | ||||||||
| + | + | + | 8 | ||||||||
| + | − | + | 6 | ||||||||
| + | + | − | 4 | ||||||||
| + | − | − | 7 | ||||||||
| IV | |||||||||||
| 1st, 2nd, 3rd and 4th cultures after three weeks in hospital | 25 | 19 | − | − | − | − | 4 | 21 | 15 | 84 | 79. |
| − | − | − | + | 3 | |||||||
| − | − | + | + | 3 | |||||||
| − | − | + | − | 2 | |||||||
| − | + | + | + | 2 | |||||||
| − | + | − | + | 2 | |||||||
| − | + | + | − | 2 | |||||||
| − | + | − | − | 1 | |||||||
| + | + | + | + | 2 | |||||||
| + | − | − | + | 1 | |||||||
| + | − | + | + | 1 | |||||||
| + | + | + | − | 1 | |||||||
| + | − | − | − | 1 | |||||||
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.