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.

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.

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.

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.

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.

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.

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.

On admission 35.6 per cent of the patients were found positive for B. influenzæ. Repeated throat cultures were not confined to those appearing negative on this initial culture, but were made on all patients without regard to their being previously positive or negative. By a summation of the results of the weekly cultures of all patients, the percentage of patients carrying B. influenzæ rises from 35.6 per cent on admission, to 62.7 per cent after one week; to 77.7 per cent after two weeks; to 84 per cent after three weeks in the hospital.

To gain some idea of the rate of spread of B. influenzæ in wards receiving only patients whose throat cultures were negative for B. influenzæ on admission, a similar summation of the results of repeated throat cultures on patients in negative wards shows weekly increases from 47.5 per cent after one week, to 68.1 per cent after two weeks; to 79 per cent at the end of three weeks.

These results demonstrate quite clearly that the measles wards were saturated with B. influenzæ during the period of the influenza epidemic. Conditions within the measles wards with regard to B. influenzæ were not at all different from those in the camp community during this period. While no clinical methods could be relied upon to diagnose influenza in the presence of an acute attack of measles, there is every reason to believe that the occurrence of clinical influenza with measles was no less frequent than was its incidence in the camp at large, that is, about 20 to 25 per cent. That influenza played a large part in determining predisposition to the complications of measles in this series seems evident.

Hemolytic Streptococci with Measles at Camp Pike

Between September 15 and December 15, 1918, 867 cases of measles, admitted to the wards of the base hospital, were studied and handled according to the system outlined above. About one half of these cases appeared during the first month of the study. During this month hemolytic streptococci played a very insignificant rôle. This microorganism did not appear with alarming prevalence until after the wards had been thoroughly overcrowded. After the emergency, when better ward conditions were provided, S. hemolyticus carriers continued to develop in the wards and were removed when identified. The first S. hemolyticus carriers to develop in the wards were identified on October 8. The first case of streptococcus pneumonia developed on October 17, while streptococcus otitis as a complication of measles did not begin until a little later. During the latter two months of the study, S. hemolyticus became rampant in the wards. The streptococcus complications date their onset at some time during these two months.

Table LXI shows the number of admissions to the measles wards by weeks and the patients among them found to be carrying hemolytic streptococci. It also shows the number of S. hemolyticus carriers developing each week among patients under treatment in the “clean” wards, as identified by throat cultures repeated at weekly intervals. For purposes of orientation, the number of cases developing streptococcus pneumonia and otitis media with its subsequent mastoiditis are given for each week during the period of observation.

An admission to the measles ward can generally be regarded as an acute case of measles. There are a few exceptions to this statement and these are cases of measles treated in barracks and afterwards transferred to the base hospital. A relatively small number of such cases furnished 16 of the cases positive for hemolytic streptococci on admission to the measles ward.

An admission to the measles ward does not indicate admission to the hospital, because a considerable number of cases of measles developed from time to time among patients under treatment in the hospital for other conditions. Since these patients remained in other wards not subject to the same ward management and with no distinction between those positive and those negative for hemolytic streptococci, they cannot be included in figures to show the incidence of hemolytic streptococci in patients with measles at the time of admission to hospital from the camp. Two classifications of the 37 cases, positive when first observed, are necessary.

1. Division of cases according to days in the hospital before first culture was taken:

2. Classification according to stage of the disease:

The first classification shows only 13 cases positive when cultured on admission to the hospital and also during the acute stage of the disease; the incidence of S. hemolyticus in patients on admission is very low (1.76 per cent).

The second classification shows a slightly higher incidence for cases during the acute stage of the disease, regardless of whether they were admitted to the measles service from camp or from another service of the hospital (2.4 per cent). These findings conform with those at Fort Riley in a smaller series of cases and support the opinion that the hemolytic streptococci temporarily disappear from the throat during the acute onset of measles. Unfortunately controls among normal men in Camp Pike were not taken at intervals throughout the period of three months represented by this study of measles, but all controls taken show a higher incidence than that found among measles patients on admissions over a period of time comparable to that of the control series.

The gradual increase in the percentage of patients developing hemolytic streptococci in their throats in wards receiving only streptococcus free cases demonstrates that the admission culture and the subsequent weekly cultures, with the separation of all patients identified as carriers, did not suffice to control the spread of streptococcus in this group of cases. It is interesting to note that the greatest incidence of streptococcus carriers among these patients occurred three weeks after the height of the measles epidemic, when it became about four times that observed at the height of the measles epidemic.

When we consider the time relations of the streptococcus complications, it is noteworthy that they begin to appear somewhat after the appearance of streptococcus carriers and then increase parallel with the increase in the numbers of carriers. The relative number of complications developing among the first carriers which were identified is less than that among the carriers appearing later. This suggests an increase in virulence of hemolytic streptococci attending their wider dissemination.

Tables LXII and LXIII are introduced for the purpose of showing to what extent duration of stay in the hospital increases the individual’s chances of acquiring hemolytic streptococci. Table LXII includes all cases admitted to and treated in the measles wards. On repeated cultures, previous positives and negatives were cultured alike and the total positives reported for each week.

Table LXIII includes only those cases treated in the “clean” wards and known to be negative on previous culture.

A comparison of Tables LXII and LXIII gives some indication of what might have been expected if the carriers had not been removed from the treatment wards at weekly intervals. With the carriers removed from the “clean” cases and segregated in a separate ward so as to be removed effectively as sources of spread of the S. hemolyticus infection to clean cases, the percentage incidence with all cases considered rose to a point nearly twice as high as that ever reached in the wards where clean cases alone were allowed to remain. Had these carriers not been separated, and remained in contact with cases free from hemolytic streptococci, they would have served as just so many more sources of infection, and an incidence of at least twice that recorded for all cases combined, or four times that of the treatment wards, might have been expected. These results indicate that the weekly separation of carriers from clean cases did, to a considerable extent, lower the individual’s danger of acquiring S. hemolyticus infection while in the hospital.

Complications of Measles

In Table LXIV the complications developing in the measles patients under observation at Camp Pike are tabulated. In the division of the complications developing in “carriers” and “noncarriers” of the hemolytic streptococci, reference is made only to the records of the throat cultures. The division is therefore not dependent upon the bacteriology of the complications. For example, only 9 of the 12 cases of pneumonia developing in “carriers” were streptococcus pneumonias. On the other hand, the cases of mastoiditis following otitis media were almost invariably due to hemolytic streptococci. Of the 10 otitis cases occurring in “noncarriers,” 4 developed mastoiditis and 3 of these showed hemolytic streptococci on culture from the mastoid cells at operation. Missed cases of identification of S. hemolyticus by throat culture in cases which develop S. hemolyticus complications may arise from a number of causes. It is desired here only to direct attention to these discrepancies.

Pneumonia Following Measles.—Fifty-six cases of pneumonia following measles occurred during the period of observation in this group of 867 cases of measles. Of these, 9 were streptococcus pneumonias. This gives an incidence for streptococcus pneumonias of 1.04 per cent, while that for all the pneumonia is 6.4 per cent. There were 8 cases of lobar and 48 cases of bronchopneumonia. Seventeen fatal cases occurred giving a mortality rate of 30.4 per cent for the group. Five of these fatal cases occurred among the 9 streptococcus pneumonias. The mortality rate for the streptococcus pneumonia thus was 55.5 per cent; that for the nonstreptococcus group was 25.5 per cent. All 9 cases of streptococcus pneumonia developed empyema. In 7 cases it was diagnosed clinically; in 2 at autopsy only. No cases of empyema developed in the group of nonstreptococcus pneumonias.