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PUBLICATIONS FROM THE UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE

Studies on Epidemic Influenza
COMPRISING
Clinical and Laboratory Investigations

BY

Members of the Faculty

of the

School of Medicine

UNIVERSITY OF PITTSBURGH

1919

TABLE OF CONTENTS

PREFACE

This report is based upon a series of investigations carried on during the epidemic of influenza at Pittsburgh. This epidemic reached Pittsburgh about the last week of September, 1918, rapidly spreading through the community during the first days of October. Pittsburgh had been warned of its coming through the experience of Boston, where the epidemic made its appearance during the late days of August. To a certain extent the warning from the East permitted the making of preparations to control its ravages. But even with the attempt for the protection of public health the epidemic advanced with all its virulence, rapidly picking out the susceptible individuals and leading to a high death rate.

At the time of the coming of the epidemic there were stationed at Pittsburgh two military camps, comprising about 7,000 men. It was with the presence of the disease among these men that our investigations were chiefly concerned. The men at their respective camps (on the campus of the University of Pittsburgh and at the Carnegie School of Technology) were housed in barracks which had been erected only a short time previously. These barracks contained large dormitories, in which the individuals freely mingled with each other. In them there was no opportunity of complete isolation, and by this means of housing good opportunity was available for the propagation of any communicable infectious disease. The ordinary sanitary arrangements for these groups were well provided. The first cases of recognized influenza made their appearance on October 2. On this day two men were found with the disease and were isolated. On the following day there were four, and on the third day eight. It was soon recognized that the increasing number of the infected cases was growing so rapidly that definite arrangements for their segregation and care had to be undertaken. This was provided for on October 4, when the Elizabeth Steel Magee Hospital was in part taken over by the military authorities and wards were rapidly adapted for the coming epidemic. For the foresight in making the adequate arrangements for its control and management we shall always remain indebted to Major E. W. Day. His indefatigable work in the early days of the epidemic will always be remembered, and the fact that the epidemic was kept within reasonable bounds of control was the result of his stringent quarantine regulations along with the organization of his medical forces. Working under his direction, Capt. H. H. Hendershott undertook the management of the hospital and rendered most efficient service. The capacity of the hospital was soon overburdened, so that from a normal 150–bed institution it was on the sixth day of its conversion into an emergency hospital carrying more than 300 cases of influenza. This hospital in itself was unable to accommodate all of the cases falling ill, and provision for these had to be made in some of the municipal institutions. On October 5, 1918, the Medical School of the University of Pittsburgh undertook to provide the laboratory facilities for the emergency Military Hospital. It was at first intended to equip only those laboratory departments which were deemed essential for the clinical care of the patients in the wards. Inasmuch, however, as the epidemic of influenza was spreading with alarming rapidity throughout the city, it was deemed advisable to close the Medical School and to place at the disposal of the Military Hospital all the laboratory facilities which could in any way be of use in the care and study of the influenza patients. This permitted the establishment of departments in pathology, bacteriology, physiology, physiological-chemistry and clinical microscopy. The following workers partook in the investigations which were here carried out: Dr. Oskar Klotz, director of laboratories; physiology, Dr. C. C. Guthrie (chief), Dr. A. Rhode, Dr. M. Menten, Mrs. C. C. Macklin, Miss S. Waddell and Miss M. Lee; bacteriology, Dr. W. L. Holman (chief), Miss A. Thorton, Miss C. Prudent and Miss R. Jackson; pathology, Dr. Oskar Klotz (chief), Mr. A. D. Frost, Mr. J. L. Scott and Miss A. Totten; clinical microscopy, Miss R. Thompson, Mr. M. Marshall and Mr. H. Mock; records, Miss H. Turpin. Intensive work was undertaken by each over a period of about five weeks, when the epidemic was again on the road to disappearance and few new cases were being admitted. These laboratories discontinued their work at the Military Hospital on November 9.

The clinical observations which are contained in this report were made at the Mercy Hospital. This institution set aside upward of 100 beds for the care of the overflow which could not be accommodated at the Military Hospital. It is unfortunate that the clinical observations and the laboratory findings contained in this report were not made upon the same cases. With the number of cases suddenly thrust upon the medical staff of the army, it was not possible for them to devote detailed attention to clinical investigation. Furthermore, during the progress of the epidemic these medical officers were transferred to new posts, so that it was impossible to obtain a summary of the clinical findings at the Military Hospital by any of the officers who had but recently been detailed to the work. We were fortunate, however, that the clinical investigations were carried out on a similar group of cases to those studied by the laboratory, and it might be said that their clinical findings on the patients housed at the Mercy Hospital are parallel with those observed in other institutions. Necessarily the researches carried out during such an epidemic were intensive, and all the workers in the various branches feel that if they had to live through another such plague they would be much better prepared to approach their problem. During the heat of such investigations valuable time is often lost in perfecting methods of technique, and one sorrowfully finds oneself without available material when the technical work has been accomplished but the epidemic has passed by. In the studies in bacteriology we were fortunate in having some of the technical difficulties for the isolation of the B. influenzæ previously solved. It may be that this in part explains the broad success which Dr. Holman has had in isolating the B. influenzæ from so many cases. In other fields the road was less broken, and it was not until late in the course of the epidemic that results were obtained in the investigation which seemed to point to valuable leads.

Dr. S. R. Haythorn, director of the Singer Memorial Laboratory, early in the epidemic became interested in the protection of individuals against the infection. In certain quarters much was claimed for the immunity which could be conferred by vaccination, either by the inoculation of pure B. influenzæ vaccines or by mixed vaccines. Hoping for some results by the use of such vaccines, Dr. Haythorn undertook the preparation of these materials. The value of this procedure could only be estimated after the lapse of some time and at a period when the epidemic was again waning.

The clinical work at Mercy Hospital was carried on under the direction of Dr. J. A. Lichty, and assisted by Dr. W. W. G. Maclachlan, Dr. P. I. Zeedick, Dr. F. Klein and Dr. W. J. Fetter. By the close co-operation of the members of this group it was possible to put the clinical findings of one or other member to severe test, so that the recorded observations and deductions are of the greater value and less flavored by the personal element. This is of the more value, since, with the great amount of work which had to be done at the time of the height of the epidemic, it was often not possible for the same individual to bestow the amount of time upon each and all cases as he desired.

We are much indebted to Dr. Ogden M. Edwards, dean of the School of Medicine, for making available the facilities for carrying out the work, and for encouraging the publication of the reports.

Oskar Klotz.

Pittsburgh, June, 1919.

HISTORY AND EPIDEMIOLOGY OF INFLUENZA

By James I. Johnston, M. D.

The history of epidemic influenza extends back with definite authenticity to the Middle Ages, with a fair amount of assurance to the beginning of the Christian Era and with presumptive reliability even before that period. Beyond this statement, nothing definite can be said until the first epidemic reported by Short and found in the English Annals in the year 1510. This, the first reliable record, presented some features not unlike those occurring in the present epidemic. Two or three striking things stand out in this record—namely, the presence of nose bleed, pneumonia and the very great danger to gravid women. Here, for the first time, the meteorological conditions were elaborately studied and persistently dwelt upon. One other impressive thing, also reported by Short, was that in 1580 the disease showed a tendency to return after a period of quiescence. Attention is called to this because the epidemic, while it was exceedingly prevalent in the months of August and September, became pandemic in October and November. Another feature was that during the years intervening between 1580 and 1658 sporadic cases of this disease were frequently reported. During the latter year another epidemic appeared in the month of April. In 1657 and 1658 at London the summer was very warm, the winter came on early, there was much snow and the spring was very moist.

The prevailing opinion at this time, and the first stated by Willis, was that the widespread disease was due to the weather influences on the circulation, poisoning the blood of the patients, and “not blasts of malignant air.” The disease prevailed in the large cities, recurring again in the autumn in an extensive form through the villages and country. Sydenham, in his communication on the epidemic in 1675, wrote emphatically on the influence of the infection on pregnant women, and here used the term “tussis epidemicus” as a name for the disease. The summer of 1675 was wet with an inconstant autumn. La Grippe prevailed in France and Germany, according to Atmuller. In England in 1676, the autumn was pleasant, but suddenly became cold and moist. La Grippe then started in Germany during September after a summer and a beginning autumn which was very rainy. Molyneux in his description of the epidemic of 1693 in Dublin called attention to a feature, very striking to the recent pandemic, that the aged to a great extent escaped the infection. This would seem a somewhat unique feature until that epidemic is compared with the present one. In 1729 Morgagni and others stated that over all Europe the winter of 1728 was very rigorous, the spring was cold and the summer and autumn very variable, while January and February of that year were very moist. Huxham in his record of 1729, the fifth extensive one on record in the English Annals, which extended into 1733, stated from his study at Plymouth that the epidemic was exceedingly mild in the year 1733, and, with the exception of infants and consumptive old people, the mortality was very low. Like many of his predecessors, he emphasized greatly the conditions of the weather at the time and presented an elaborate study of it. The epidemic of 1732 was one of the longest and most persistent, extending up to 1737. All authors do not hesitate to attribute as a cause the very frequent variations of temperature which characterized this period. Of this epidemic Arbuthnot also emphasized the importance of the air, assigning the prevalence and widespread features of the disease to the thick and frequent fogs. From November, 1732, until March, 1733, this disease spread from Germany to Italy and thence to England. He called attention to a very striking feature—namely, that people in prisons and in hospitals escaped the disease. This, as we know, where such institutions are placed under preventive quarantine, is not such a unique feature during this present scourge. He, more than former writers, devoted pages to the elaborate and accurate description of instruments for meteorological observation and their findings, which meteorological records were published in detail, covering the whole period of a year—June, 1732, to June, 1733—with almost daily regularity. Huxham in 1737 in his record first used the term “epidemic catarrhal fever”—a name often used subsequently to describe this disease. Here attention was first called to the prostration which characterized the convalescents, and his belief that consumption frequently followed the disease. The next epidemic, which occurred in 1742 and 1743, was also reported by Huxham, who stated that the weather was very rigorous. This disease, according to his description, extended over all Europe, and the term “influenza” seems to have been first used by him during this time. The cases were mild in England, but more severe in Southern Europe. Whytt in his record of the epidemic of 1758 was the first who did not consider that the air condition or the seasons had the significance attributed to them by former writers, since the weather conditions during the prevalence of the disease were generally mild and dry. In Edinburgh at this time not even one out of seven escaped. Nevertheless, he did not hesitate to express his opinion that the disease did not spread by contagion from one person to another. One other observation of his is worthy of note, which is: that frequent relapses occurred when patients were re-exposed too soon after the first infection and such relapses were much more severe than the original disease.

The epidemic of 1762 called forth the opinion of Baker, emphasizing an opinion already expressed by Whytt, that the origin of epidemic disease is not due to changeable winds nor to their nature or character as recorded by the barometer. This epidemic also prevailed over all Europe and appears to have begun following sharp alterations of cold and moisture. In 1766 in Spain, France and other parts of Europe the epidemic appears to have begun after a warm summer, followed by an autumn moist and cold. In 1767 Heberden placed on record his observations during this period, but nothing new was reported. In 1775 the disease began in Germany in the summer after a dry and warm spring and spread over all Europe. During the prevalence of the disease in 1775 a questionnaire was sent to the leading English physicians, and letters from Fothergill, Sir John Pringle, Heberden, Reynolds and others seemed to express a consensus of opinion that weather conditions had nothing to do with the prevalence or spread of the disease, and that the cause and reason for its spread were unknown. Following sharp alterations in temperature in 1780, the disease appeared in France and then throughout the world. The epidemic of 1782 began in Russia, starting January 2 at St. Petersburg. The thermometer underwent a variation of 40 degrees and the same day 4,000 were afflicted with La Grippe. It reached Koenigsburg in March, Copenhagen in April, London in May, France in June and July, Italy in July and August, Spain and Portugal in August and September, and then reached America. Edward Gray, writing of the epidemic of 1782 for the first time, expressed emphatically his opinion on the contagiousness of the disease and stated what we now know—that close contact is necessary. To him also is attributed the opinion first mentioned by him, that there is a possibility of carriers in this disease. During this time Dr. Hamilton, in a published letter, protested against venesection in influenza, a practice long prevalent, and Hogarth called attention to the fact that the disease began in cities and villages first and that it was brought to these places by visitors from without.

The first American writer on this subject was Noah Webster in 1647 and 1655. Following him was Warren, writing of the epidemic of 1789 and 1790, just 100 years before the last and greatest epidemic which preceded the present one. Rush and Drake also reported this epidemic. During that epidemic which prevailed in America from September to December, 1789, and appeared again in the spring of 1790, President Washington suffered a very severe attack. The year before, in 1788, when the epidemic prevailed abroad, the summer temperature in Paris was very variable, variations of 8, 10 and 12 degrees occurring on various days. La Grippe predominated all the time. The same variations were true in Vienna. At the end of the year 1799 the epidemic struck Russia, following very cloudy, misty weather, was prevalent in Lithuania in January of the year 1800 and in Poland during February.

The next great epidemic occurred in 1802 and 1803, was very general, beginning in France and coinciding with a cold and moist autumn following a very dry summer. It was of six months’ duration in England. Many schools, jails, asylums and workhouses, although located in the area swept by this plague, at first escaped. As mentioned before, this striking feature has not been so unique in subsequent epidemics. One feature noticed here and commented upon freely was that elsewhere throughout the country there seemed to arise endemic foci. During this time there was also the prevailing belief that the disease was followed by phthisis. One other observation made here, which was accurate, lasting and is accepted today, was that no family was affected en masse, but always one individual case occurred first, to be followed by general infection of the others. At this time early bleeding was still adhered to. The French spoke of seven varieties of the disease, but one can only see in the classification emphasis laid on certain individual symptoms in this disease of complex symptomatology. During this epidemic pneumonia is said to have been very infrequent. The disease was particularly fatal to pregnant women, and the patients suffering from pulmonary tuberculosis were hurried off by the influenza.

Burns, writing of the epidemic of 1831, mentioned that in 1810 the disease was very widespread in China and Manila, and also emphasized the fact mentioned in many works that certain epidemics prevailed among animals at the same time, stating that in 1831 these diseases were of choleric nature. This epidemic began in 1830 in the East, reached Paris in the summer of 1831, reappeared in Europe in 1833, following the same route that cholera had taken in 1832. In the epidemic of 1833, Hingeston also laid great stress on the fact that horses were often affected. These features, as mentioned by Burns and Hingeston, are frequently quoted by authors, and such observations seem to have been widely accepted.

One of the greatest epidemics of influenza began in 1836 and extended until 1837, and was called at this time epidemic catarrh. It began in England in January, spread to France, and during all the time that it was in Paris there were continual penetrating rains with cold and humidity. At Montpelier on February 20, 1837, the thermometer passed from 12 to 15 degrees above to 2 and 3 degrees below zero, and it was then that La Grippe appeared suddenly. In reply to the circular letter sent out by the Council of the Provincial Medical Association of England, comprising 18 questions, the following opinions prevailed. The disease was greatest from September to February; the great prevalence of the epidemic in all parts of the kingdom was recognized—attacks were irrespective of age, sex or temperament; it was milder in children, and the aged suffered most from it. Further, the disease was extensive in all neighborhoods; the mortality was 1 in 50, old age predisposed to fatal termination, and the duration of the disease occupied two periods, one terminating in 4 or 5 days and one in 5 to 14 days. Also relapses were frequent; those exposed to employment in the open air were not more liable to the disease than others; there was no proof of the disease being communicated from one person to another, and influenza aggravated an existent pneumonia or pulmonary phthisis. And finally previous attacks of influenza offered no protection; the symptoms were uniform; the most common of unusual symptoms were those of meningitis, inflammation of the lungs and syncope, and aside from ordinary care and treatment, general venesection was not endorsed. Evidence of fine weather and good telluric conditions were at this time also appended. The same symptoms and complications, particularly those of the lungs, occurred irrespective of seasons, civilization or place. It was believed and stated that the plague described in Homer was probably influenza. For the first time there is noticed here a point well worth consideration—the association of other epidemics with influenza, either anticipating, following or superseding. That some such association may follow the present pandemic is not to be entirely ignored. For example, cholera is already reported as prevailing abroad, following an earlier influenza outbreak. During the period, as if anticipating bacteriology, one writer explained the epidemic in an article called “The Dust of Regular Winds,” and Groves (1850) wrote on “Epidemics Examined, or Living Germs as a Source of Disease.”

In 1846 and 1847 a slight epidemic occurred in London, Paris, Nancy and Geneva. In France during the last week of 1857, and extending into January and February, 1858, there was a mild epidemic. During this period there alternated frequent frosts with soft weather, misty and humid. Among the numerous small epidemics between 1837 and 1889, one occurred on the continent of Europe in 1860, but little of value or interest was noted. In Paris in March, after great and sharp variations in temperature, a series of epidemics extended from 1870 to 1875. These were unimportant. Atmospheric modifications occupied first rank in the minds of some as a cause for the outbreaks. Rapid changes from hot to cold or from cold to hot were given weight. Other undetermined modifications of conditions were probably important.

In a recent article published by Loy McAfee (J. A. M. A., 1917, 72, 445) he discussed the confusion which existed between the diagnosis of cerebro-spinal meningitis and epidemic influenza in 1863. These were believed the same by some—that is, the same disease of varying degree. There was a great diversity of opinion among clinicians at this time, and the American Medical Association appointed a committee to make an investigation. McAfee quotes from the Medical and Surgical History of the War of the Rebellion that in 1861 and 1862 an epidemic existed among the troops called epidemic catarrh, which was afterward changed to read acute bronchitis. In September, 1861, there existed an epidemic of influenza in one of the regiments which lasted more than two weeks, and in another camp there was a similar epidemic at the same time. It is stated that there were in all 168,715 cases among the white troops, with a mortality of 650, and 22,648 among the negro troops, with a mortality of 255, making about 4 per thousand, and over 11 per thousand, respectively.

The next great epidemic, and the last until the present, occurred in the years 1889 and 1892, and was pandemic in its nature. The death rate during this time was lower in the cities than in the country. This was probably due to the fact that the greatest mortality was among children and old people, and as old people were generally left in the country, this explains the observation. The highest number of deaths was among males, believed to be due to the exposure and fatigue of work. Forty per cent. of the world’s population was said to have been attacked during this period. The yearly or seasonal repetition, as shown in this pandemic, had occurred in other epidemics. In the great pandemic of 1889 and 1890, five decades after the last important epidemic, it was stated that the medical profession found itself confronted by a new disease of which it had knowledge through medical history, so also in our time few physicians recognized at first the reappearance of influenza. This 1889 epidemic is extensively reported in the literature, and has been elaborately worked out by many observers. One important feature has been emphasized by Leichtenstern, which, although recognized by the profession after the last epidemic had been fully reported and recorded, is not appreciated by the profession during the present epidemic—namely, that while shortly after the last epidemic there were smaller relightings of the infection throughout various parts of the country, those diseases which we erroneously call grippe or influenza, occurring commonly in the spring and fall, are in no way connected with the disease with which we are dealing, and which occurs at rather long intervals. Any speculation in regard to these periods, which history has shown to be fairly wide apart, has very little basis. This pandemic, like many of former days, is believed to have originated in Asia, and from there to have spread over Europe and hence over the world. The disease spread rapidly over countries, affected probably about 40 per cent. of the world’s population, disappeared rapidly after several weeks, was thought to have had nothing to do with weather conditions, had a great morbidity but small mortality, and affected all ages and occupations. There is no doubt, as stated by some, that the development of traffic and travel was a large factor in the rapid and extensive spread of influenza during this pandemic. The course which the disease followed, springing from its supposed beginning in Asia, has been fully and amply described by writers after that period, but the great rapidity of its dissemination over all countries is the most remarkable feature in the epidemiology of any disease. This, during 1889, made many prominent physicians disregard the opinion that influenza spread by contagion and accept again the opinion expressed by observers of epidemics in former ages, that miasma as a pathogenic agent was responsible for its distribution; but anyone who reads closely the history of this epidemic, and in the light of modern medical science, must feel that the rapidity of distribution was nowhere greater than the most speedy means of transportation. This very necessary close connection was demonstrated also in regard to the mode of spread of the disease; the large cities and the commercial centers were affected earlier, smaller and country districts followed later, railroad towns were more frequently attacked than isolated villages, and even from jails, prisons and workhouses, where quarantine was immediately attempted, as well as from remote villages where the disease had been brought, there could be traced a zone of infection spreading into the country. One interesting point was raised at this time—namely, that in some places it seemed to spread by leaps and bounds, and at other places radiating as stated above.

The old controversy of whether influenza is distributed in a radiating manner or in so-called leaps and bounds is believed to be settled by consensus of opinion that it occurs in both ways. An opinion expressed by the study at this time as to whether influenza spreads more rapidly than any other infectious disease is found in the statement that the contagion is markedly virulent, the micro-organisms are easily conveyed from their original seat in the mucous membrane by coughing, sneezing and expectoration, the great number of persons who, though slightly affected, carried on their ordinary way of life without hindrance, the probable longevity of the organisms in convalescents, the brief period of incubation of two or three days, the susceptibility of all people of every age and vocation, and the possibility of carrying the contagion by merchandise and even through short distances in the air, are all suggestive reasons for this. No one at present accepts the so-called miasmatic nature of the contagion. Proofs are ample to show that one case must be present in a locality or even family, although it may be frequently overlooked, from which the epidemic spreads. During this period of 1889 and 1890 the duration of the actual epidemic period in different localities in Europe was from four to six weeks. This was subsequently shown to be consistent with the recorded reports from the various cities in the United States. Following this pandemic in the first part of the year in 1891 there were numerous epidemic outbreaks in various parts of America, including New Orleans, Chicago, Boston, and simultaneously in England. Strange to say, at this time neither Germany nor France had such epidemics, although both were exposed by travelers, particularly from England and America. The question was raised at that time whether the Germans, French or other continental nations were more immune than Americans and English. In the fall of 1891 and the entire winter of 1892 the disease was extensively prevalent both in Europe and Northern America. In these later epidemics there was no definite direction of spread. They probably would come more clearly under the so-called radiation from numerous rural districts. In almost every case at the point of its origin in these countries the epidemic developed and spread slowly, lasting months and with very varying morbidity and mortality. They had none of the explosive characteristics of the pandemic. The general diminished morbidity of the later epidemic, the diminished geographic distribution of the disease and the scarcely recognizable character of its contagion, its slow development and extension over several months, the continuous diminution in frequency and in intensity since its onset in 1889, have been explained by presumptive successive lessening of susceptibility of the population, possibly due to acquired immunization. Observers at that time, as well as ourselves, could question this last statement.

There was observed one noteworthy thing about seasons. While the great pandemic of 1889 and 1890 had no definite connection with seasons, the epidemic types which followed in 1891 and 1892 seemed to show a lighting up in either spring or fall, remaining dormant in the summer months. It has also been shown by the history of former epidemics that almost all the pandemics started from Russia in the fall, winter and spring months. Such was the case in 10 of the great pandemics of 1729 to 1889. This, no doubt, was the reason so many of the former historical writers were impressed by seasons and meteorological conditions. The statement made by observers during the epidemic that influenza presented two phases, one pandemic and the other endemic, and that each follows different epidemiological rules, seems possible. The question raised during the last epidemic of the spread of the disease in families, the disease occurring at high altitudes and even at sea, we know does not interfere with the recognition of its spread by direct contagion. Definite examples of families or villages being infected by a returned member of such family or citizen from abroad are reported frequently, and even the appearance of the disease in isolated places has often been traced and verified from a definite source, to say nothing of the question of carriers and those supposed to be suffering from other diseases.

Striking examples are shown also in this epidemic that many institutions, frequently those isolated from the world, were markedly exempt until, through servants or outside visitors, the disease gained access to them. This gave a most favorable field for the study of invasion, spread and decline of the disease. Observations made at this time in regard to hospitals seemed to suggest that certain institutions were more or less exempt, although not closed institutions, while others suffered from the first. These two types of hospital invasion are hard to reconcile.

Great stress was laid in this epidemic upon the very great morbidity and the low mortality. Simple, uncomplicated influenza at this time was looked upon as a disease that was rarely dangerous to life. Studies have shown that after this period there seemed to have been lessened morbidity. As previously stated, nearly all the numerous pandemics at various times have had their origin in Russia and arose in the late autumn or winter months. This pandemic of 1889 and the succeeding severe epidemics in Europe and North America in the years of 1891 and 1892 occurred almost exclusively in the cold weather, the summer remaining free. It is generally believed now, and was at the end of that pandemic, that atmospheric or telluric conditions had nothing to do with the spread. The origin of epidemics following the pandemics seemed to be influenced in their recurrence by the season of the year. It was conceded by observers in that pandemic also that contagion might be carried by merchandise and even flies and healthy individuals.

1918 Epidemic in Large Cities

In the city of Boston during the week ending August 28, at the Naval Station at the Commonwealth Pier, 50 cases of influenza occurred and within the next two weeks more than 2,000 were reported in the naval forces of the First Naval District. Of these 5 per cent. developed broncho-pneumonia with a mortality of more than 60 per cent. From here it probably spread to Camp Devens and thence ran rapidly over the country. There can hardly be a question that it spread along the lines of traffic. Up to November 9 there were reported 3,339 cases among the civilian population of Boston. There were 3,430 deaths from influenza, the presumption being that these were due to bronchial pneumonia, although not reported as such. The deaths from all forms of pneumonia were reported as 942, making in all 4,372 deaths from September 7 to November 9. This discrepancy—that is more deaths than reported cases of influenza—is due to the fact that influenza was not made a reportable disease until the date of October 4, fully a month from the time the epidemic appeared. The weather conditions were generally fair and no noted abnormality is recorded as compared with other years. The statement of the Health Department of this city was that, after a practical disappearance of influenza in October, there was a slight recurrence in November and a more pronounced recurrence about the first of December, since which time the cases have slowly but steadily decreased, until at present—December 21—the fatalities attributable to influenza are about 20 daily.

In the city of New York the epidemic first appeared September 18. Up to and including December 27 there were reported to the Department of Health 136,061 cases of influenza and 21,388 cases of pneumonia. The number of deaths since September 18 was 11,725 attributed to influenza in the death certificates filed in the Health Department and 11,601 attributed to pneumonia. The epidemic reached its peak during the week of October 19, slowly subsided and was practically at an end on November 9. While the epidemic is reported as ending on this date, the mortality rate from influenza and pneumonia is still very much above normal. No particular features concerning the meteorological conditions were noted, except that in this city the weather was clear and delightful during the months of September and October when the epidemic was rampant.

In the city of Philadelphia on July 22 the Health Department issued its first health bulletin on so-called Spanish influenza, announcing the possible spread of this disease into the United States. On September 18 a warning was issued against an epidemic, the department starting a public campaign against coughing, sneezing and spitting. On September 21 the Bureau of Health made influenza a reportable disease. At this time the authorities stated an epidemic of influenza was recognized as existing among the civil population of similar type to that found in the naval stations and cantonments; that a large percentage of cases was accompanied by pneumonia; that patients should be isolated and attendants wear masks; that isolation be practiced for a period of ten days after recovery to prevent carriers; that patients be guarded against relapse and that the public be cautioned against large assemblages and crowded places, as well as to avoid coughing, sneezing and spitting. On October 3 the churches, saloons and theatres were closed, funerals were made private and food handlers were required to protect their wares. The number of cases reported from September 23 to November 8 was 48,131, but the Bureau states, from a rough estimate, the number of cases was probably 150,000. The total number of deaths reported was 7,915 from influenza and 4,772 from pneumonia in all its forms, the presumption being that the deaths during this period were due to influenzal pneumonia. The weather condition during this time is recorded as mild and fair.

The influenza cases began to be reported in Cleveland on October 5, and up to December 20, 22,703 cases had been recorded. Certificates recording deaths due to influenza alone numbered 2,497, while pneumonia amounted to 833. The epidemic was at its height in the latter half of October and the weather was spoken of as pleasant fall weather. During the week of October 26 the epidemic reached its greatest height, abated in the week ending November 23, increased later, but showed a drop for the week ending December 21.

The epidemic first reached Chicago on September 21, and from that date on it rapidly increased throughout the city for a period of 26 days until October 17, when it reached its maximum both in the number of deaths from influenza and from pneumonia. On that day the total number of deaths from influenza and from pneumonia reported was 2,395. From September 21 until November 16 there were reported 37,921 cases of influenza and 13,109 cases of pneumonia. On September 8 at the Great Lakes Naval Training Station, which is 32 miles north of the city, an extensive outbreak of influenza occurred. This was 13 days before the outbreak in the city of Chicago itself. Camp Grant, located at Rockford, 92 miles northwest of the city, suffered an outbreak on September 21. A suggestion of the likelihood that influenza was prevalent in this country in a mild and unrecognized form in the spring of this year is shown by the fact that numerous local outbreaks of acute respiratory diseases were brought to the attention of the Health Department of Chicago. These occurred especially in large office buildings and in industrial departments. The total number of deaths from influenza and pneumonia during 14 weeks was 51,915. This would indicate that a very great number of cases were not reported to the Bureau of Health until they died or else there must have been a large number of deaths due to lobar pneumonia. One naturally obtains from these figures the impression that the disease was not recognized for a long time, that the pneumonia must have been called lobar pneumonia, and that the actual figures gathered by this city, as well as others, must have been greatly confused at the onset of the epidemic. It is not unlikely that records from many of the army cantonments and naval stations may be considered from the same viewpoint. Weather conditions were considered normal at the height of the epidemic, the weather being dry. There has been a flare-up of influenza recently, but not in sufficient numbers to justify calling it epidemic.

In the city of Louisville, Ky., the epidemic started September 26, and the total number of cases up to December 21 is reported as being 9,445. Out of this number 772 deaths occurred from pneumonia. No distinction is made here between broncho-pneumonia and lobar pneumonia, but the presumption from the records of other cities at this time is that these were cases of broncho-pneumonia following influenza. The weather was described as being delightful fall weather. The statement is made by the authorities that while the epidemic is still prevalent, it is confined largely to children and is rapidly abating.

The first case in the city of St. Louis was reported about October 7, and up to December 23 there had been 31,531 cases reported to the Bureau of Health. They recorded 1,920 deaths with influenza given as a contributing cause. Preceding the time when the epidemic was at its height the weather was fair and warm, and the statement is made that, “without going into the matter exactly, we have been of the opinion that damp, rainy weather has been a help in controlling the disease.” The opinion was expressed by the Commissioner of Health that the disease had now abated.

No information could be obtained as to when the epidemic first reached the city of New Orleans, but during the months of October and November 43,954 cases of influenza were recorded. Of this number 2,188 died from a combination of influenza and pneumonia. They stated in their health report that during the period from January 1 to December 31 there were 239 deaths attributable to broncho-pneumonia. The weather was mild and on December 24 the epidemic was stated to have abated.

The city of Minneapolis recorded its first case on October 7, but the authorities expressed their belief that a few cases had appeared before that date. Up to December 21, 15,000 cases had been reported to the Bureau of Health and of these there had been 735 deaths from broncho-pneumonia. They had in their city a late, rainy fall and up to that period they had had no cold weather.

The record obtained from the city of San Francisco stated that the epidemic first appeared September 23 and that it was very widespread in that city early in October. There were two invasions and 53,260 cases reported. At the height of the epidemic more than 2,000 cases were reported in one week; 188 deaths occurred from influenzal pneumonia. The following week, after the institution of mask wearing, in which between 80 and 90 per cent. of the population concurred, it was stated that the number of cases decreased to about 200. It was stated that the weather was generally very fair during the epidemic.

From the city of Portland, Oregon, the following information was obtained: The epidemic first appeared October 11, with a second one toward the end of the year. There were 8,079 cases reported, with 658 deaths from influenza and 250 from pneumonia. Weather conditions were stated to be varied, but the health officer believed that during the worst wave the weather was clear and dry, with easterly wind. He believed that a decrease in influenza was noticed immediately after a Chinook wind and warm rain. Similar observations were made by Coutant in Manila.

A weather comparison of 12 large cities, well distributed over the United States, studied during this pandemic of influenza and checked with normal weather during that of many years, shows: Boston, fair with no abnormality; New York, clear and delightful, no abnormality; Philadelphia, mild and fair; Pittsburgh, mild and cloudy; Cleveland, pleasant fall weather; Chicago, normal and dry; Louisville, delightful fall weather; St. Louis, fair and warm-damp, rainy weather later seemed to control the epidemic; New Orleans, mild; Minneapolis, a rainy fall and no cold weather, which is unusual there; San Francisco, generally fair, and Portland, Oregon, clear and dry.

The Epidemic in Universities and Colleges

At Bryn Mawr College, in Pennsylvania, an institution devoted to the higher education of women, located within 10 miles of the city of Philadelphia, the epidemic occurred at the beginning of the college year—October 1. This college at the time had an enrollment of 465 students. There were 85 cases of influenza, with an additional 25 who suffered from influenza in their homes. There were no deaths from pneumonia. The weather conditions were clear and warm, and since November 29 there have been no new cases occurring in the college and only three or four of the students have been ill at their homes since that time.

Dates of the Appearance of Influenza Endemic in various Cities of the UNITED STATES
1918.

The enrollment at Smith College, Northampton, Mass., was 2,103, and the first case of influenza appeared with the arrival of the students on September 18 and reached its height on September 30. All group gatherings indoors were stopped from October 3 to October 18, and the epidemic was over by October 20. A recurrence began November 15 and continued until December 17. There were 182 cases in the first epidemic and 100 cases in the second. There were only two deaths from influenza pneumonia. During the rise of the epidemic the weather was rainy, followed by good, clear weather. The change in weather conditions seemed to make no difference. The second epidemic was still prevalent when the students left for their holidays.

In Wellesley College, where there were enrolled 1,593 students, the epidemic first appeared on September 18. Up to the middle of December they had had 280 cases. During six weeks of the epidemic 265 cases were reported and only one death occurred from broncho-pneumonia. For the most part, bright and sunny days were present, with only a few cloudy and rainy days. This college has not been without cases since September, but the epidemic lasted only about six weeks.

In a communication from Columbia University it is stated that the epidemic appeared during the week beginning September 22. No records were available for the student body at the time of inquiry, but in the Student Army Training Corps of 2,200 men between 8 and 9 per cent. had the disease during the period from October 1 to December 14. In this army group during this period two deaths from influenza and pneumonia occurred. The weather conditions in the city during this time were considered normal for fall weather—that is, mostly clear, with high winds. The opinion expressed was that the epidemic was still prevalent and increasing, and that a return wave seemed to be more virulent and affected the children of the city more than had the first one in the early fall.

There were enrolled at Harvard on October 1, 3,193 students. The first case of influenza occurred on September 20. There were 227 cases of influenza reported; of these there were 46 cases of broncho-pneumonia, with five deaths. There were two waves to the epidemic; the first wave height was in October and the second the last of November. The weather conditions were not severe nor particularly unfavorable at either time. The epidemic abated at the university largely because of the demobilization of the Student Army Training Corps. At that time it was still prevalent in Cambridge and Greater Boston.

At Yale University the disease first appeared in the New Haven Hospital on September 21. There were registered in all departments of the university 2,265 students. Up to the date of December 24, 1,013 cases have been treated. The number of deaths from broncho-pneumonia has been 249. At the height of the epidemic, which occurred in the third week of October, typical fall weather prevailed. An unusually clear, dry October with very little rain, much sunshine and rather low humidity was the weather report.

During the period of the epidemic at Princeton that university had 1,050 students, and the first cases appeared shortly after the opening of the college term on September 24. As a precautionary measure, every case, when even only suspicious, was sent to the infirmary. In all, there were about 70 cases in the university and about 45 cases from the United States School of Military Aeronautics. Only one member in the latter school died of pneumonia. There were no deaths among the students at the university. In this part of the country the weather was most delightful all autumn, being warm and dry, very little rain having occurred since the end of July. At the date of the inquiry the epidemic had disappeared—that is, about December 21—there being only two very mild cases under suspicion. In the town of Princeton, outside of the university, the conditions were much more serious than in the university itself. Influenza appeared in the homes of many of the poor people of the immigrant class, so that it was not uncommon for four or five members of one family to be infected at once. In one family of seven, five serious cases of pneumonia developed. An emergency hospital was opened by the authorities and 40 cases of pneumonia were treated. Of these approximately one-half died. At the time this report was furnished the epidemic seemed to have disappeared.

The number of students enrolled at the University of Virginia was 957. The first cases occurred as early as September 24. There were 290 of these in number, and three died of broncho-pneumonia. The epidemic was reported as having abated on December 15, but a few cases appeared after that date.

1918 Epidemic at Pittsburgh

At the Army General Hospital No. 24, located at Hoboken, a few miles outside of the city of Pittsburgh, on September 28 two soldiers were taken ill and, with the disease unrecognized, they were removed to the cantonment hospital at Point Breeze, within the city proper. The men were found a few days later to be suffering from influenza, and from this presumable source an epidemic spread rapidly among the troops and student soldiers located here.

From September 28 until November 20, 1,392 cases of influenza occurred among the enlisted men. How the infection reached the first two cases at Hoboken is not known. The command here consisted of the Student Army Training Corps of the University of Pittsburgh, and Carnegie Institute of Technology, Motor Mechanics of the University of Pittsburgh and the Ordnance and Quartermasters’ Department on detached service. The strength of this command was approximately 7,000. The first case appeared on September 30 and the diagnosis was made on the following day. Beginning October 13, all soldiers of this group were inoculated with two 1 cc. doses of vaccine, obtained from the New York State Board of Health. At the height of the epidemic there were about 840 soldier patients in the several hospitals of the city at one time. Cubicles were used in the hospitals, and in the barracks a floor space of 50 square feet was allowed to each man. The men slept alternately head to foot, with paper screens intervening, which were changed daily. In company formation they were instructed to gargle their throats and clean their teeth morning and night under the supervision of their officers. Strict military quarantine was maintained throughout the entire camp, no congregating was allowed, classes were suspended and only open-air drills were permitted. For the entire command there were 220 cases of pneumonia, with 99 deaths, an average mortality of 44 per cent. The dishes were boiled in the hospitals, and sanitary dishwashers were used in all mess halls. The kitchen help and personnel were inoculated with influenza vaccine, with apparently good results. The Magee Hospital, with 375 beds, was under strict military control. When this was full, all others were treated in the civilian hospitals.

In the city of Pittsburgh the disease was not made reportable until October 5. However, one case was reported on October 1, and it was known that there were a few isolated cases in Pittsburgh previous to that date. During the months of October, November and up to December 21 there were 23,268 cases of influenza reported, and the deaths were 1,374 from lobar pneumonia and 678 from broncho-pneumonia. We cannot but feel that most of the deaths reported during the period of the epidemic as lobar pneumonia were broncho-pneumonia associated with influenza. It was well known among civilians that true lobar pneumonia was exceedingly rare and has remained so up to the present time. This is especially noticeable, as this is the time of the year when lobar pneumonia is usually widespread in Western Pennsylvania. This district was particularly favored with a mild fall and winter. On October 1 the first case was reported, on October 15 the epidemic reached its peak—on that day 957 persons being reported ill with the disease. From October 16 until October 28 it maintained an average of 600 cases daily; from October 29 until October 31 there was a sharp decline from 600 cases daily down to 200 cases daily. From November 1 until December 21 the decline has been uniform, and on this latter date 58 cases of influenza and 7 of pneumonia were reported. The height of the epidemic was reached between October 15 and October 29. During the period of the epidemic in Pittsburgh, from October 1 until December 15, 62 days were recorded as cloudy, or partially cloudy, and only 14 days as clear, although the cloudy days seemed distributed and not in decided groups. The mean temperature for October was 58 degrees, with normal 54.9; for November, 44 degrees, normal 42.9; for December, 41 degrees, normal 34.7. The precipitation in October was 3.08, as against a normal of 2.36; in November, 1.79, with normal 2.55; and in December, 3.50, normal 2.73. From a study of these weather reports we see that the epidemic occurred during a period of abnormally warm, cloudy and slightly more moist autumnal season than usual, but these variations were relatively slight and far from decided. The confusion of diagnosis between lobar pneumonia and broncho-pneumonia, associated with or following influenza, occurred in the Pittsburgh health reports as well as in other cities. The presumption that almost all, if not all, of the cases reported as pneumonia of different types were really cases of influenzal pneumonia, seems justified.

Epidemic Incidents in Institutions and Towns of Western Pennsylvania

During the time the epidemic was at its height in Pittsburgh the Western Pennsylvania Institution for the Blind was in session. This school is located in the heart of the educational center and was surrounded by the barracks of the Student Army Training Corps of the University of Pittsburgh and the Carnegie Institute of Technology. When the influenza was recognized as epidemic in this neighborhood, the attending physician at this institution advised a quarantine against the public. The children were refused visitors in the buildings, and the usual week-end trips home were forbidden. This school was continuously in session from September 24 until November 30. During this time there was not a single case of influenza in the school and the children were free from any infectious disease. On December 1 the pupils returned to school after the Thanksgiving holiday, and one week later, on December 8, the first case of influenza appeared. In a period of five days following 15 cases developed. It was considered wise to close the school, and all well children were sent to their homes. The institution was kept closed until January 1, since which time no cases have developed. Very few of these children had influenza at home, and only one death occurred.

A reliable report, subsequently confirmed by the health officer, stated that in Masontown, Pa., the start and course of the epidemic were very striking. A dance was held in the town and the musicians were brought from nearby cities. One of the musicians employed was not very well upon his arrival, and became so ill that after the dance he was put to bed in the hotel. He was found to be suffering from influenza when examined the following day, and from him as the primary case the town was swept by the epidemic.

In Mercer, Pa., the physician to the Board of Health reported that during September they had a general epidemic of coryza and sneezing, with slight fever, which lasted for three or four days. This was looked upon by the people as hay fever. In the midst of this, or about September 16, a man, 74 years of age, who had been away from home, developed true influenza, followed by pneumonia, from which he recovered about October 10. Another man, employed in Greenville, a nearby town, where influenza was already prevalent, returned to his family here suffering from the disease. The whole family and all who were exposed to this family were infected. From this family as a focus the disease spread rapidly in every direction. There were about 350 cases in the town of 2,000 inhabitants, and there were 9 deaths. Sporadic cases have occurred since, ranging in number from one to a dozen at a time. These numbers do not include scores of cases called colds by the people, but it seems that all these cases had an influenza element.

In the town of New Castle it was not possible to trace the onset of the influenza epidemic to a definite case. As the health officer stated, several cases were reported at once.

The first case of influenza in Indiana, Pa., of which there was any definite knowledge occurred on September 15. A clothing merchant who had just arrived from New York, where he had been buying stock for his store, was the first case identified. The next case occurred several weeks later, the disease being contracted at the mining town of Coal Run, in Indiana County.

A man resident in Sharpsburg who had suffered from influenza visited friends in Fraser Township, Allegheny County, to convalesce. Previous to his coming that section had been free from the disease. He was still coughing at the time, and, moreover, he is said to have been a great talker and visited largely among the neighbors of his host. Threshings in that part of the township were going on and these he also attended. The date of his coming was October 13. By October 15 his hostess was taken ill. By October 16 some of the threshers were affected, and by October 17 enough were sick to break up the work of threshing. Eventually all the men engaged became ill, and 11 families were infected from this source.

Summary

Reviewing the history of former epidemics and pandemics, I have gained the impression, as have many others, that we are not dealing with any new disease. Further, our knowledge of this pandemic with its high incidence of broncho-pneumonia shows that it is in no way markedly different from that of former manifestations of influenza. One is impressed by the fact that in different outbreaks of this disease of complex symptomatology certain symptoms or complications have been prominent, overshadowing others, and making such complications the striking feature at the time. The failure to recognize that these varying features are merely different manifestations of one disease has resulted in much confusion. The observation made in the last epidemic—and one which can be endorsed during the present plague—is that influenza has been and is the most widespread, rapid and extensive of all diseases. One thing also that attracts attention at the present time is the long period existing between the several pandemics. Whether, as one observer during the present pandemic has stated, it requires a long period for the infection to become active and easily carried, or whether any possible reason can be suggested for these phenomena, admits of no satisfactory explanation. The outstanding feature during this epidemic is the complication of broncho-pneumonia, and yet, from very early times, this complication has been repeatedly spoken of as a striking characteristic. Reviewing the health reports from the large cities of deaths from pneumonia, the presumptive opinion seems justified that almost all, if not all, pneumonias reported as associated with influenza were of the broncho-pneumonia type. The infrequent presence, indeed the rare finding, of lobar pneumonia during this period in Pittsburgh seems to verify the aforesaid opinion. The great frequency and the high mortality of broncho-pneumonia were particularly noted during the present epidemic. During the present epidemic the great mortality among pregnant women was another striking feature, and yet this is by no means new, having been recorded by some of the earliest writers. Such also may be said of the recurrence of the disease in the same patient. One important observation brought out in the study of the pandemic of 1889 to 1892 was that the ordinary infections occurring in the spring and fall known as grippe or La Grippe are in no way connected with the pandemics which have occurred. There seems to be a consensus of opinions among the records of the more recent epidemics, as well as during the present pandemic, that weather conditions in no way influence the spread of the disease. Furthermore, a study of weather conditions throughout the United States, and particularly those of our own city, seem to bear out the truth of this observation. While clinicians during other epidemics expressed their belief in the incident of a primary case producing infection, it has only been during the present one that such an opinion has not been assailed. The large number of military training camps and cantonments have undoubtedly offered splendid opportunity for the spread of influenza. The futility of attempting to control it even under normal conditions is still questionable. Consistent with former reported invasions of the disease, the present epidemic lasted a definite period. This period was about six weeks in most of our large cities, colleges and institutions, extending approximately from October 1 to November 15.

It is imperative to note the accurate clinical observations recorded from the numerous epidemics of the past by men with far less data to go upon than is available at the present day. The high morbidity among the personnel of many of our hospitals and institutions where the infection occurred and the relatively low mortality deserve attention. This may be partly explained by the methods of treatment of those infected, but not entirely. The great likelihood of carriers of influenza, who either are not ill or who are suffering from very mild infection, is an observation also noted by former writers which cannot be ignored. The value of the masks has not been established, although they have been extensively used in many parts of the country. Frequent throat lavage was generally accepted as a rational preventive measure. Relightings of the disease have been noted in most of our cities after the subsidence of the epidemic. Vaccination against influenza is fully discussed in Dr. Haythorn’s paper in this series.

The presence of influenza in San Quentin prison, California, in April, 1918 (Public Health Reports, May 9, 1919); an epidemic of respiratory disease in Chicago in the spring of 1918; the report of Soper of influenza in our army camps in March and April, 1918; the occurrence of influenza in Porto Rico in June; influenza on a United States Army transport from San Francisco, as reported by Coutant, seem to point to the possibility that influenza had a footing in America long before the disease became pandemic. The view held by some that the beginning of influenza was in America, subsequently being transferred to Europe and then reimported here, is worthy of consideration. Coutant believed the disease originated in Manila, others that it traveled from “a permanent endemic focus in Turkestan,” and there are many other theories which attempt to discover the original source of the disease. The question is today an unsettled one. The pandemic of influenza in its severest form swept so suddenly over the world that before the profession realized it or had become stabilized it had changed its character and the great plague was gone. The consequence has been that we have really learned little that is new and have done scarcely more than establish on a firm basis many of the opinions formed after the great outbreak of some 30 years ago. Because transportation is today more rapid than it was at that time, so the spread of the disease has been correspondingly swift. Our modern life, the congregating crowds in theatres, moving-picture houses and in lecture halls, as well as of the men in our training camps, the development of street cars and the more frequent traveling by train—these and many more changes in our mode of living have served to aggravate the conditions favoring the widespread distribution of the infecting agent. A higher proportion of the population was, therefore, attacked than in any previous pandemic, and the period during which the disease was widely prevalent has for the same reason been relatively much shorter.

The characters differed somewhat in different regions, but the evidence shows clearly that we are not dealing with any new disease. It will be years before we are able to fully analyze the data that have been collected from such wide sources and by so large a body of trained men, so that important epidemiological facts may still be forthcoming from the material already at hand. We are too close to the events to get the most helpful perspective, and the object of this report has been to add, in however small a degree, to the general knowledge of this great pandemic as it has appeared to us in Pittsburgh and its surroundings.

A CLINICAL DESCRIPTION OF INFLUENZA AS IT APPEARED IN THE EPIDEMIC OF 1918–1919

By J. A. Lichty, M. D.

The epidemics of influenza which have been recorded from time to time during the past few centuries have always contributed an interesting chapter to the history of medicine. The protean character of the disease with its many complications is always an excuse for another attempt at the description of the clinical manifestations of a recent epidemic. This is not, however, the only incentive at the present time for describing the clinical aspect of the disease as it appeared in the epidemic through which we have just passed. The study of the disease from other aspects, such as the pathological, the bacteriological and the physiological, by well-organized groups of workers has made it necessary to co-ordinate, if possible, the clinical findings in every detail with these apparently basic principles. It would be interesting to review here the peculiarly fortunate circumstances which have led to the investigations. On account of the great war many temporary laboratory organizations which otherwise would not have existed were in operation, and these organizations, moreover, were keen to undertake any laboratory problem which might arise. The present epidemic presented the opportunity, and that the work was taken up with great enthusiasm is evidenced by the reports coming from the various army hospitals, base hospitals and civilian hospitals throughout the world. The permanent laboratories connected with medical schools and with institutions for medical research took up the problems with equal endeavor. This brief reference is made only to call attention to the fact that from such organizations a great mass of information has come which must be critically reviewed and coordinated before it can add to the permanent fund of our knowledge of the disease under consideration.

The material upon which the following clinical observations have been made is peculiarly adapted to review because it consists of two distinct groups of patients which were admitted to the Mercy Hospital. One group of 153 men was composed of soldiers between the ages of 18 and 23, which had been recently inducted into the Student Army Training Corps, and were living in barracks in the immediate vicinity of the hospital. Another group consisted of civilians (394), ranging from youth to old age, which came from various parts of the city and surrounding towns and country. The first group came to the hospital early, or as soon as the disease was recognized; the second group came usually after several days of illness had elapsed, or when a complication had already arisen. Many of this group had been ambulatory cases for the first part of the disease. The entire number of patients admitted to the Mercy Hospital from the first admission, September 21 to December 1, the end of the quarantine, was 547. After December 1 very few simple influenza cases were admitted. These 547 cases form the basis of the observations which will be referred to in this paper.

From the last great epidemic or pandemic of influenza, that of 1889 and 1890, have come clinical descriptions which should be reviewed before speaking of the clinical manifestations which have characterized the present epidemic as shown in the two groups studied.

One of the best descriptions of that epidemic was given by Dr. O. Leichtenstern in Nothnagel’s Encyclopedia of Practical Medicine. This contribution, among many others, describing the epidemic of 1889 and 1890 is one of the first to refer to the Pfeiffer bacillus as being etiologically associated with the disease. It differs, therefore, greatly from descriptions of previous epidemics. Leichtenstern says: “The typical influenza consists of a sudden pyrexia of from one to several days duration, commencing with a rigor, and accompanied by severe headache, generally frontal, with the pains in the back and limbs, by prostration quite out of proportion to other symptoms and marked loss of appetite.” He continues by saying that to these characteristic symptoms may be added the catarrhal phenomena arising from the affection of the respiratory tract, particularly the upper (coryza) and “occasionally” the lower, the trachea and bronchi. This description is so in accord with the symptoms of uncomplicated influenza as found in the present epidemic that very little need be added. Any difference which may occur in the description of the disease is likely to be accounted for by the peculiarity of onset, whether in the upper or lower respiratory tract, and by the different ways of interpreting complications which may have arisen. It is evident from this description that the upper respiratory tract was affected more generally than the lower in the epidemic of 1889 and 1890. In the present epidemic it can safely be said that the reverse was the usual state of affairs. It was a rather unusual occurrence when the affection was limited only to the nose, pharynx, larynx, trachea and larger bronchi. A very large number, no doubt, had a peculiar œdema, a so-called “wet lung,” which we shall discuss later; others went on to a capillary bronchitis or a bronchiolitis, and a large number had broncho-pneumonia. This sequence we shall attempt to show in the statistics at hand. In some cases the lesion in the lower respiratory tract seemed to be primary, there having been no initial coryza. At least none was observed and no history was obtained.

Prodromal Stage and Communicability

The length of the prodromal stage—the stage from the time of contact to the earliest onset of symptoms—has always led to interesting observations and discussion. In this epidemic we have rather definite information bearing upon this subject.

A young married farmer living in a rural community where no influenza had occurred up to the time of the present experience went to a city about 40 miles distant. On the train he sat in the same seat with a man who was apparently ill, and who was sneezing and coughing. He was in the city only a few hours, and was not in any place of congregation except the railway train. Forty-eight hours after his return to his home he noticed the first symptoms and began a mild course of influenza. About 50 hours later his wife was taken with the same symptoms, and in two days more their only child was afflicted. Other members of the household were also afflicted, and one of them died of pneumonia.

It might be interesting to quote a similar observation made by Macdonald and Lyth, of York, England, published in a recent issue of the British Medical Journal (November 2, 1918, p. 488), which corroborates this experience. They say: “We traveled from London together on Thursday, October 3, by train, leaving King’s Cross at 5.30 P. M., arriving in York at 9.30, and as we were leaving the carriage a young flying officer, who had come the whole way with us and was coughing and sneezing at intervals, informed us that he was ill and had had influenza for several days. On Saturday, October 5, we both became ill and had developed typical attacks of influenza. With both of us the illness developed suddenly with laryngitis; in both the first signs were a severe attack of coughing; and in both the time was noted fairly accurately as being between 2 and 2.30 P. M. One case was quite mild, the temperature never over 101. The other was more severe; the temperature arose to 104½ and the catarrh extended to the bronchi. His wife and two children also developed influenza, and in their case the symptoms showed suddenly, about 2 P. M., on Monday, October 7. Now we are convinced that we became infected from our traveling companion during the train journey—more likely toward the end of the journey; and if we take the time of infection as 9.30, this fixes the incubation period for both of us at a minimum of 41 hours, with a maximum margin of error of 4 hours. The three cases developing in the family of one of us point to a similar incubation period, as their illness started almost exactly 48 hours after his, and as it is likely that the infection would not take place until a few hours after the first symptom, the incubation period in these three cases must have been nearly the same as our own two.

“It can be readily understood that we were in no position to conduct extensive bacteriological examinations, but a culture taken from the posterior nares of one of us on October 10 with a guarded swab showed colonies of Pfeiffer’s bacillus and of micrococcus catarrhalis.”

This observation is so convincing, I have quoted it at length and in full.

The communicability of influenza has been observed by all, and the ease with which it passes from one individual to another noted. One observation made by us was of considerable interest. In a house where a patient lay sick with a severe attack of influenza for nearly three weeks several members of the household passed the door of the sick room a number of times daily, and yet they did not contract the disease. This is in marked contrast with the immediate contact between the two physicians and the young flying officer, who sat in the same railway carriage compartment for four hours. The same observation was made in the hospital among nurses in direct contact with patients. A large number of these contracted the disease, while those not immediately associated with influenza patients almost invariably escaped. This speaks strongly against the idea that the epidemic was a so-called “plague,” or that it passed without intermediate means through the air and pervaded all places.

From information thus far at hand it seems, therefore, that the prodromal stage, or stage of incubation, is one which covers about 48 hours, and that it is usually without symptoms unless it be a peculiar prostration which had been described by some patients. It would also appear from the experiences just narrated that it was necessary to be in rather close contact with a patient, so that there could be an exchange of respired air before infection could take place.

Duration of the Disease

In all descriptions of the disease the duration is spoken of as “several days, more or less,” “a three-day fever,” or “a seven-day fever.” Because of the careful supervision under which the soldiers were kept while in the barracks an excellent opportunity was afforded to note the duration of uncomplicated cases. The shortest time observed was 1 day, and the longest 10 days. The average duration of temperature among 87 soldiers without inflammation of the lungs or other certain complications was 6⅓ days. Among the civilians the shortest time of pyrexia was a few hours only, while the longest in 73 male patients was 14 days, and in 84 female patients was 16 days. The average length of pyrexia in the males was 4⅝ days, and in the females was 5¼ days.

While the very definite clinical description of the former epidemics of a so-called uncomplicated influenza seems to have served satisfactorily to the present time, the laboratory studies and the possibly more thorough clinical observations which have been carried out recently in this epidemic make it necessary to present anew the whole disease picture of influenza, with the hope of suggesting a classification more in accord with our present knowledge of the disease.

Forms and Varieties of Influenza

A few words as to “forms” or varieties of influenza might be helpful before suggesting a classification of symptoms. In former epidemics of influenza considerable importance was attached to the early manifestations or first symptoms as characterizing the “form” of influenza which was in evidence in the individual patient. These were reported as a “respiratory form,” a “nervous form,” a “gastro-intestinal form,” and other forms—circulatory, renal, psychic, etc. In the epidemic of 1889 and 1890 particularly these types were noted, and they have been described in the subsequent small epidemics, practically characterizing them as being of one or the other, and frequently as being without any respiratory symptoms. In the study of our group of cases in the present epidemic every effort was made to recognize the non-respiratory cases, but we were unable to find a single case which did not have definite respiratory symptoms, either early or late, in addition to any other symptoms present. Only occasionally were nausea, vomiting and diarrhea or tachycardia, or certain neuroses or psychoses, the leading symptoms. The respiratory symptoms in some cases seemed to be at the onset primarily of the lower respiratory system—that is, without the preliminary coryza. These usually ran a rapidly fatal course, characterized by marked cyanosis and confusingly irregular chest signs. We would say, therefore, in so far as our experience goes in this epidemic, we are not justified in speaking of any particular forms except the respiratory form, and whenever pronounced manifestations occurred justifying a characterization of any other form they could more easily be interpreted as a complication, or the manifestation of a coincident disease, or of a severe toxæmia.

The classification of the symptoms, therefore, takes into consideration largely those symptoms arising from the respiratory system. We are of the impression that the pathology demonstrated by Dr. Klotz and described by others justifies the following classification. Clinically we would recognize two distinct groups of epidemic cases.

The first includes those without lung involvement having symptoms arising from the upper respiratory tract, including the trachea and the larger bronchi. These were practically without any chest signs except for the rather indefinite signs of an acute bronchitis, and the only symptoms referable to the respiratory tract were a coryza, soreness of the throat, hoarseness and a cough of varying degree and character. If to these symptoms are added those of Leichtenstern just mentioned, one will have a good description of a so-called simple, uncomplicated influenza.

The second includes those with lung involvement and associated with physical chest signs, in some indefinite and confusing, while in others definitely conforming with the existing pathology. These symptoms and chest signs were those associated at one time with what appeared to be an acute œdema of the lungs. At another time the physical signs were those of a bronchiolitis (capillary bronchitis), or most frequently of a broncho-pneumonia, of an isolated type or of a massive type. Finally there were some forms of lobar pneumonia which at times we were unable to differentiate from a true lobar (croupous) pneumococcic pneumonia.

Influenza Without Lung Involvement

Of the group without lung involvement nothing further would seem necessary to be said in addition to what one finds in standard text-books describing the disease picture of former epidemics. The incidence of influenza of this type among our group was as follows: Of 153 soldiers 93, or about 60 per cent., had a so-called simple, uncomplicated influenza, and of the 394 civilians 185, or about 52 per cent., had no lung involvement. There are a few points in which the symptoms of the present epidemic seem to be so peculiar that they merit special consideration.

The Temperature

This can be described as showing a sudden rise to 102–104, at which point it is maintained for a few days, and subsides by lysis in a few days more. A typical chart is as follows:

CHART I

Or the temperature might fall one or two degrees for a day or so after the first rise, and then go up again for one or two more days, and subside by lysis as is shown in Chart II.

CHART II

This would occur without our being able to find any lung lesion unless we accept the acute œdema or wet lung as a complication, and this we were rarely able to recognize by any definite physical signs in the chest. Cyanosis frequently accompanied this second rise of temperature, and was later interpreted as being associated with the so-called wet lung. When the temperature remained up longer than five days it could safely be concluded that lung involvement must be present.

The Pulse and Respirations

The pulse was invariably slow, or rather out of proportion to the temperature. Even when the patient seemed very ill the pulse remained from 84 to 96, and of surprisingly good quality. This was noted also when some of the more severe pulmonary involvements or some complications arose. The pulse frequently did not become rapid until shortly before death. The respirations in an uncomplicated case also remained about normal. The rate was not accelerated until lung complications arose, and then a gradually increasing rate was often the first herald of oncoming danger and a sign of grave prognostic import. The relation of the pulse phenomena toward the end of a fatal case was most remarkable. The respiratory rate was accelerated, as has been noted above, but the pulse rate frequently remained unchanged, being characteristically slow. In a patient seen in consultation with Dr. Lester H. Botkin, of Duquesne, Pa., death took place while we were in the sick room. It was a case of apparently uncomplicated influenza of seven days’ duration. The respirations were rapid and the pulse was only 96. In the last five minutes of life the heart beats as observed with the stethoscope never varied, until they suddenly ceased; during the same time the respiratory efforts were only three agonal ones, the last being a minute or so before the last heart beat. There were no physical signs of consolidation at any time recognized in this case, but we feel that the lung, had we seen it at autopsy, would in all likelihood have shown the peculiar hemorrhagic and œdematous character so often observed in the fatal cases.

There were, of course, marked exceptions to the description of slow pulse and later rapid respirations observed. In some the pulse rate and respirations increased, together with or without definite signs of a grave complication.

Cyanosis

This was recognized early in the epidemic. It was sometimes preceded by a peculiar flushing of the face, such as accompanies belladonna poisoning. It might be noticed in the very first days of the attack. The cyanosis was looked upon as being a very early symptom of lung involvement. With our later knowledge from autopsies, and especially as shown by Dr. Klotz, we feel it was surely an accompaniment of, or may even have preceded, the changes in the lung which have been designated as œdematous, “wet” or cyanotic. At the earliest appearance of the cyanosis we were frequently unable to find any change in the physical signs of the chest. Of course, the indefinite signs of an acute bronchitis were present, and in some cases an additional “impaired resonance” was noted over one or both lower lobes, but when this was definitely present other more definite signs soon followed, and our case was shifted suddenly from Group I, i. e., without apparent lung involvement, to Group II, i. e., with definite lung involvement. This cyanosis was noticed first in the face, and frequently was marked on the dorsal surface of the hands. It was not unlike the cyanosis which may sometimes be seen when large doses of certain coal tar derivatives are taken. In fact, the question arose whether in the epidemic of 1889 and 1890, when the coal tar derivatives were prescribed with such freedom and with accompanying cyanosis and apparently such deleterious effects, the cyanosis may not after all have been due more largely to the infection than to the medication. After that epidemic it was said: “Influenza has slain its thousands, but the coal tar products have slain their tens of thousands.” There was no gross hæmaturia or hæmoglobinuria present in these cases, although a few red blood cells were seen microscopically. There was, however, epistaxis, sometimes early in the disease or later associated with the cyanosis. In a few cases there was hæmoptysis, which we regard as always arising in cases where the wet or hemorrhagic lung was present. Cyanosis in disease of the lungs, and especially in the terminal stage of lobar pneumonia, is a familiar and common occurrence, but the cyanosis observed in this epidemic seemed quite different from the ordinary. The points of difference were these: (a) it came early in the disease; (b) it seemed to be more generally present when very little lung involvement could be demonstrated physically, and was just as likely to disappear when more definite chest signs were demonstrable; (c) it was not associated with embarrassment of respiration; (d) it had no relation with a demonstrable circulatory disturbance. The pulse did not become rapid; the quality of the pulse did not change; the right heart was not dilated, as is so frequently the case in the terminal stage of a lobar pneumonia when cyanosis appears; (e) and finally there was no associated œdema of the lungs, or at least that œdema of the lungs which occurs in the later stage of lobar pneumonia, when the pulse becomes rapid, when there is rapid and labored respiration, when the right heart dilates, when there is cold perspiration, and when the signs of impending death are plainly evident. The cyanosis of influenzal pneumonia seemed to be due to an entirely different cause or combination of conditions from those present in lobar or pneumococcic pneumonia. The cyanosis of influenzal pneumonia was, therefore, most confusing, and became all the more so when it was recognized that it did not yield to the respiratory and circulatory stimulants usually employed when cyanosis is present. The inhalation of oxygen was resorted to rather routinely early in the epidemic. It seemed to temporarily influence the cyanosis, but the results were not permanent, and the outcome of the cases did not seem to be different from those in which oxygen inhalations were not used.

The blood pressure in those cases in which cyanosis was observed was invariably low. This seemed to be due to the infection, for in several private patients not belonging to this group of patients with previously known high blood pressures the blood pressure was observed as much lower throughout the course of the infection.

Leucopenia

The peculiar behavior of the white blood corpuscles will be discussed more fully in another paper of this series. Our remarks will deal more particularly with the clinical observations and interpretations. The leucocytes fell below the normal from the very onset of the disease; they varied very little regardless of great changes in temperature; they did not always increase, or if they did increase at all it was comparatively little, even in an extensive invasion of the lungs or in severe complications. Concerning the leucopenia we have no explanation to suggest, save that it is a clinical characteristic of the disease. Our first thought was that the infection came on so suddenly and profoundly there was no time for a leucocyte reaction. But when we recall other diseases associated with a leucopenia, notably typhoid fever, which does not come on with such suddenness, our explanation for the leucopenia of influenza does not seem to hold. The leucopenia must be simply a peculiar toxic blood reaction characteristic of the Pfeiffer bacillus invasion. Such an explanation has long been accepted in the Eberth bacillus infection.

Asthenia

A condition which was frequently noted by the patient was an indescribable weakness and prostration which appeared early, sometimes before any other symptoms were noted or before any elevation of temperature. The young soldier was in apparent perfect condition when he arose in the early morning. During the “setting up” exercises he did not feel so fit, and a few hours later appeared extremely weak. When his condition was called to the attention of the medical officers he was found to have a slight elevation of temperature and was sent to his bed.

In former epidemics, as also in this one, marked prostration was recognized as coming at the height of the disease and remaining persistently during convalescence. But it does not seem to be recorded as among the first symptoms.

Influenza with Lung Involvement

Of the group with lung involvement much may be written from a clinical standpoint, and much confusion may be brought about. Especially is this so if one has no definite idea of the pathology present, or if one enters into a discussion of the character of the infection—a point upon which there is as yet no unanimity of opinion. From the many reports which have been put forth from the base hospitals of the various cantonments, and also from the reports coming from civilian practice, it is evident that scarcely any two groups of laboratory men or any two individuals of those separate groups have the same idea as to the bacteriology and the pathology peculiar to this epidemic.

As long as there is this confusion and element of doubt in the minds of those to whom we are accustomed to look, the clinician must necessarily speak with considerable hesitancy, especially when he attempts to interpret the physical signs observed. In our own group the observations of Klotz, Guthrie, Holman and others have given us an interpretation of our clinical findings which, at present at least, is more or less satisfactory. We shall definitely keep in mind their observations and conclusions as we go on with the description of the physical signs of the chest in cases having lung involvement.

In the description of this group it will readily be seen that the lower respiratory tract stood the brunt of the infection. Of the 153 soldiers under our care, 60, or about 40 per cent., were recognized as having pneumonia. Of these, 34 had undoubted demonstrable signs, while 26 were questionable, and yet from the temperature and other symptoms we concluded there was a pneumonia. Of the 394 civilians, 189, or about 50 per cent., had pneumonia. Of this group there were again some 28 or 30 in which the diagnosis was doubtful, according to the ordinary way of making a diagnosis, but we felt sure from the temperature course that more than a simple influenza was present. In the description of the physical findings of the chest in these influenzas with lung involvement it will be readily seen why the diagnosis must sometimes be in doubt.

Before referring to the physical signs it might be well to describe the condition and general appearance of the patient when the lungs became involved. The patient who had been progressing with an apparently simple influenza, with no chest signs except those of bronchitis or tracheitis, occasionally slightly cyanotic, became more cyanotic, the elevation of temperature continued longer than three to seven days, or if it came to the normal began to rise again, his respirations gradually increased and the pain in the chest became well localized. One could safely assume that the patient had developed a lesion in the chest. This could not always be localized during the first few hours or on the first day. The evidence of increased bronchial disturbance was frequently recognized, and later impairment of resonance and diminished breath sounds associated with “a few crackles” were noted. This, so far as we can tell, may have been the only evidence of the stage of œdema or “wet lung.” After this, as the disease advanced, definitely increased vocal fremitus and rather definite tubular breathing with greater impairment of resonance were noticed. These signs were usually observed first at the apex of the left lower lobe, and from here they extended forward along the inter-lobar sulcus, or downward along the spinal column. If the lesion was noticed first on the left side, in a day or two it was found more or less definitely in the right lower lobe also. It seemed to occur more frequently first in the body of the right lobe, instead of in the apex of the lobe as on the left side. In both lobes it might spread to contiguous areas and form a massive consolidation, or it might be found in small separate areas, some of which would clear up in a day, while others would persist.

The expectoration was frothy, containing either blood or masses of yellowish, greenish purulent material floating in a watery sanguiolent or clear fluid, or enmeshed in frothy mucus. The amount of expectoration in some cases was enormous, but as a rule it was scanty. It was thick and ropy at times and distinctly annoying to the patient.

At this stage the physical signs were very much in accord with those of broncho-pneumonia. In a few hours sometimes, or in a day, the small areas of consolidation became confluent and massive consolidation was formed. It appeared as though the whole lobe would in time become solid, as in a true lobar pneumonia. Or the original areas may apparently have cleared and other areas involved, became the centers of massive consolidations. In many cases both lower lobes were thus similarly affected, and one had the physical signs of a double lobar pneumonia. However, nearly always a small angle of the lobe remained clear, thus differing from the entire lobe involvement characteristic of a true croupous pneumonia. Other signs, such as the absence of vesicular breathing and presence of the crepitant râle, moist râles of all sizes to very coarse râles, could be noted. As in certain stages of a complete consolidation, the lung might be dry; no râles present, but definite tubular breathing present. This in a day or two, or after a longer time, might give the signs of resolution. The stage of resolution, however, was almost invariably prolonged, sometimes extending over weeks. With these variable lung signs were often mingled the signs of a fibrinous or serofibrinous pleurisy, which occasionally but remarkably infrequently went on to effusion or empyæma.

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As stated above, the demonstrable pathology was in the lower lobe, and more frequently in the left than in the right, only occasionally in the middle lobe, and never, we might say, in the upper lobes. The very earliest definite signs were found at the apex of the left lower lobe.

This observation seems to be entirely contradictory to that of the pathologist, who found in 65 per cent. of all cases coming to autopsy a lesion in all the lobes of the lungs (Klotz). The only explanation we can give which seems at all satisfactory to us is that the pathology in the upper and middle lobes must not have been sufficient, or must have been of such a nature that it did not yield the physical signs, i. e., definite impaired percussion resonance, increased vocal fremitus and tubular breathing, with varying shades of moist râles—signs upon which we insisted before we were willing to state definitely that there is a demonstrable pneumonia present.

In this description it has been attempted to follow the order of invasion in a lung which seemed to go through the entire course of the disease. There were, necessarily, all degrees of the process, some cases showing few signs and yet being remarkably ill, and others all of the signs with very little other evidence of serious illness.

We were continually impressed with the notion that the pathology in the lung, at least the pathology demonstrable physically, did not tell the whole story of the case, and that the outcome depended as much or possibly more upon a general infection or toxæmia of which the recognized condition in the respiratory system was only a small part. We were particularly impressed with this in the success or failure following the application of any therapeutic measures. It was quite a common remark, therefore, in the wards of the hospital among those associated in the work that “the patient died too quickly to permit of the succession of the various stages of pneumonia”; or, in the autopsy room, that if the patient had lived long enough he would have had demonstrable, well-recognized pathology of the lung, instead of the cyanotic, wet, spongy lung which was found.

The temperature course in the pulmonary cases was characterized by its irregularities, and by its being entirely out of harmony with the extent and severity of the lung invasion in so far as it could be interpreted by the physical signs. The temperature as described in a simple influenza might not come to the normal in the time of three to seven days, and might even go higher, with no demonstrable chest signs, but with every other evidence of lung involvement. Later the temperature might come down by lysis, which was the usual way, and the chest signs gradually or suddenly become evident. The temperature might remain normal throughout the rest of the course, and a lobe or even both lower lobes of the lungs be as solid as in a true lobar pneumonia. Occasionally the temperature fell by crisis, but there was no associated change in the physical signs of the chest. In short, the temperature seemed to run a course entirely independent of the physical signs in the chest. In two remarkable cases seen in consultation on two consecutive days the physicians in charge declared that no signs of consolidation could be found, though all other evidences of pneumonia were present. In the 12 hours which had elapsed from the time the last examination was made the temperature fell by crisis. At the consultation, to the surprise of the family physicians, we found both lower lobes consolidated, it having occurred apparently with the crisis. Both patients were healthy-looking, robust, young men, and both recovered with delayed resolution. In the convalescence of such cases, if the patient got up too soon or if any other indiscretion took place, a relighting of the lung occurred. From the above description it can be readily seen that a diagnosis of the conditions in the chest in influenzal pneumonia was frequently impossible, because one had to abandon all his previous ideas of pneumonia, in so far as onset, crisis, blood picture, sputum, temperature, respiratory and circulatory phenomena, physical signs and prognosis were concerned.

Assistance from the laboratory was meager, especially in the early days of the epidemic. This was due largely to the inability to get laboratory workers in sufficient numbers to follow the work through, but more largely to the fact that we were unable to interpret the unusual laboratory results which were available. When we were once fully aware of the difficulties in diagnosis which confronted us, we utilized every practical means at our disposal. Among these was an examination of the chest with the X-ray. On account of lack of facilities and of help, it was impossible to make routine X-ray examinations of the chest in all cases. Besides, it was difficult to interpret the X-ray findings, on account of the unusual character of the lesions. Also, many of the patients were so desperately ill one hesitated to disturb them. We hear that other clinics had similar experiences, and that very little substantial help came from the X-ray, except in cases with complications. Several attempts were made to determine the kind of shadow, if any, the “cyanotic, œdematous, wet” lung would make, but no satisfactory observations have been forthcoming. From our own observations and from the discussions of other observers, it would seem to us that the stereoscopic examination of these chests is the only possible way of getting satisfactory plate readings in these cases where the pathology seems so lawless in its extent and peculiar in its distribution. This method of examination, however, demands facilities convenient at the bedside and perfect co-operation of the patient—difficult conditions to meet under the circumstances. In the acute cases, when the desire to make a diagnosis not only of the presence but of the extent of the disease was keen, X-ray examination was largely impractical. In cases of delayed resolution, or in cases with complications with prolonged convalescence, X-ray examinations were extremely helpful.

Diagnosis of Influenzal Pneumonia

In the consideration of any disease the well-trodden path of a painstaking history, a thorough physical examination, and reliable laboratory investigation, together with an intelligent interpretation, will usually lead to a definite diagnosis. In certain diseases, as is well known, the stress must be placed about equally on all of these factors, while in others one or other factor predominates. In influenzal pneumonia, until more is known of the etiology (bacteriology) and of the pathological changes and of the physiological disturbances, the controlling factor in the diagnosis (we feel embarrassed to admit) must be the history. This is true not only of the diagnosis of influenza with or without pulmonary involvement, but is also true of the diagnosis of the various complications, and will be found to be particularly true in the recognition of the bizarre sequelæ, which no doubt in the succeeding months or years will be attributed to or will follow in the train of influenza.

With the knowledge that there is a prevailing epidemic of influenza and that the manifestations are largely in the respiratory tract, any pulmonary disturbance will necessarily make one suspicious of the presence or the oncoming of an influenzal pneumonia in the patient under consideration. The history of the onset, as of simple influenza, is the greatest factor. This with a continued temperature, cough, cyanosis, slow pulse, continued asthenia, or even an unusual leucopenia, may have a greater weight in determining the diagnosis of lung involvement than will the apparently definite or, as it may happen, the confusing chest signs. To differentiate from ordinary bronchitis, broncho-pneumonia and catarrhal pneumonia, one need only refer additionally to the severity and persistency of the disease when it is of the influenzal type, as compared with the mildness of the ordinary type. To differentiate it from croupous pneumonia, one need only compare the confusing symptom picture of the influenzal pneumonia with the definite, clear picture of ordinary pneumonia; or the confusing kaleidoscopic chest signs of the one with the definite, clear-cut signs of the other. The laboratory thus far has been the smallest factor in making the diagnosis, in that sputum examinations, blood examinations, blood cultures and urine examinations are mostly negative in their results, or at least the findings are not specific. We do not, however, mean to indicate that these tests are not of the greatest value. The leucopenia is the one outstanding feature which seems to have separated this infection from other acute lung infections, excepting miliary tuberculosis. The differentiation of influenzal pneumonia from an acute tuberculous process in the lung may be difficult, especially if there is no reliable history available. However, the fact that pulmonary tuberculosis usually begins at the apices of the lungs and influenzal pneumonia at the bases or at the apices of the lower lobes is quite helpful. Of course, the examination of the sputum for tubercle bacilli will be a deciding factor.

The differentiation between influenzal pneumonia and diseases of the pleura is one which practically rarely needs to be made, for there seem to be very few cases of influenzal infection of the lungs in which the pleura is not also involved to a greater or lesser extent.

Complications

In considering the complications of influenza one again comes up squarely against the question: What is influenza and what is the specific micro-organism responsible for it? If the Pfeiffer bacillus is the specific cause, what pathology can be attributed to it? It has been an almost universal observation that the lesions in the lungs and pleura which characterized the group of cases with lung involvement rarely yielded a pure culture of the Pfeiffer bacillus, and that secondly in a large percentage of cases the Pfeiffer bacillus apparently was absent, and that other micro-organisms, such as the pneumococcus, streptococcus, micro-organisms commonly found in the pneumonic processes, were present and predominated. The question arises, therefore, may not all the influenzas with lung involvement be complications of influenza? It is our feeling that Pfeiffer bacillus is present throughout the respiratory tract in all cases, and while it may of itself produce a lesion like a broncho-pneumonia or a lobar pneumonia, it chiefly prepares the soil for other germs which may happen to be present, and which are more commonly found in the pneumonias. We, therefore, look upon the lesion commonly found in the lung as being a part of rather than a complication of influenza, and look upon lesions elsewhere, due to the influenzal or other micro-organisms, as a definite complication.

There is no doubt that the most frequent complication of influenza, especially in the present epidemic, is in connection with the pleural membranes. When one recalls that pneumonia rarely occurs without there being also a pleuritis, and also when one recognizes that in an influenzal infection of the lungs the specific micro-organism, together with any other micro-organism which may happen to be present, seems to run riot, apparently abandoning its usual mode of invasion, it can be readily understood why this complication is so frequent and so varied. The pleurisy was usually of the fibrinous type, and rarely was accompanied with demonstrable fluid. Of the 153 soldiers in only 3 was fluid detected in the chest, and of the 394 civilians only 10 showed fluid. In many more cases fluid was suspected, but X-ray examinations and free needling of the chest showed that we had misinterpreted the physical signs.

After our experience in the epidemic of pneumonia in the spring of 1918, when the disease was also so prevalent in the cantonments, we of course expected to see many cases of empyæma and lung abscess in the present epidemic. In this we were agreeably disappointed. Only one case of empyæma and only one case with abscess of the lung were found up to the time of collecting our data and the compiling of our statistics. Both of these were among the civilians. From our experience since the compiling of our statistics, we are inclined to believe that this low incidence of empyæma may not altogether represent the real state of affairs, as we have since received in the hospital several cases of empyæma, as well as of abscess of the lung, which seemed to have followed an influenzal infection which had occurred three or four months previously. One of these cases was a particularly remarkable one, in that the patient had already been admitted to the hospital twice since his initial attack of influenza in October for suspected pleurisy with effusion. We were unable to find any fluid with the needle, though we felt certain of having demonstrated it a number of times physically and with the X-ray. About eight weeks after the second admission, however, pus was found after several needlings in the left chest, axillary space, apparently along the inter-lobar sulcus. This case was a good example of many we have seen in which a pneumonia, or possibly, as we see it now, a pleurisy, or even a localized empyæma, seemed to confine itself about the sulcus or fissure between the upper and lower lobes of the lung. Frequently the process began posteriorly, apparently at the apex of the lower lobe, and traveled forward and downward across the axillary space until it appeared in the anterior part of the chest. In most cases we interpreted our signs as those of a consolidated lung, and scarcely knew whether the consolidation was in the upper part of the lower lobe or in the lower part of the upper, or in both. In some cases we suspected a localized empyæma or an abscess in the sulcus, but in none did we find pus after exploring with the needle until this recent case occurred. The passage of the needle in this case, which was done several times before pus was found, always gave the impression that it was going through dense fibrous tissue for some distance before the abscess was finally found. From this experience, and from the extensive and irregular invasion of the pleura which we have seen demonstrated at autopsies, there can be no doubt that the clinical history of the complications of influenza in this epidemic is not a closed chapter.

In six patients there was a purulent inflammation of the pharynx, larynx and trachea. It was extensive and produced profound general symptoms, dyspnœa and profuse purulent expectoration. The lungs were clear, but the patient seemed for a time in danger of death. The condition was considered a grave complication. There was only one case of acute sinusitis, one case of antrum disease, and only four cases of middle ear infection were recognized. This is in marked contrast to other epidemics which have occurred to our knowledge in the past fifteen years or more, and which have been spoken of as influenza or “grippe.” Disease of the tonsils, middle ear disease, mastoid disease and sinus disease occurred with great frequency in those sporadic epidemics. This again seems to show that the deep respiratory tract was more generally and more severely affected in this epidemic than the upper respiratory tract.

With the exception of the pleura, the serous membranes were remarkably free from infection. Only one case of acute endocarditis, three cases of meningitis (all pneumococcic), none of pericarditis, peritonitis or arthritis were recognized among the 547 cases of influenza.

The kidneys did not seem to be involved in the infection. Albumen was present in the urine, as might be expected in febrile conditions, but no evidence of acute clinical nephritis, such as suppression of urine, general œdema or uræmia, was recognized. The condition of the urine in this epidemic will be described more in detail in another paper of this series.

A peculiar pathological process in the muscles was brought to our attention by Dr. Klotz, who demonstrated a myositis or hyaline degeneration of the lower end of the recti abdominalis. This lesion is carefully described in the pathological section. After our attention had been called to this lesion we recognized several cases clinically having the same condition. One was in the right sterno-cleido-mastoid muscle and another was in the left ilio-psoas muscle. This last patient while he was convalescing developed a severe pain in the left hip, extending upward into the lumbar region and downward into the thigh. His decubitus was like that of one suffering with psoas abscess. Every test available was made to confirm this diagnosis, but all the findings were negative. The patient rested in the hospital, in bed, for some time, gradually improved, and eventually made a complete recovery.

In several cases we also detected an osteitis, especially of the bodies of the vertebræ. One was of the cervical vertebræ and the other of the dorsal. The first died after intense suffering. An autopsy was not obtained. The other had a plaster cast applied as in Pott’s disease, and improved sufficiently to leave the hospital in comfort. One hesitates under the circumstances to attribute these bone lesions definitely to the same infecting micro-organism which was responsible for the epidemic of influenza, as it might easily have happened that a coincident quiescent tuberculous lesion was present and relighted during the epidemic. However, in one case from the service of Dr. J. O. Wallace the possibility of the bone lesions being due to the Pfeiffer bacillus was demonstrated. This was a child of 16 months with an epiphysitis of the upper end of the tibia. The inflamed area was incised and pus was found. A smear at the time showed the B. influenzæ, which was grown in pure culture.

A most interesting complication noted in a few of our cases was a transient glycosuria. The first case brought to our attention was a middle-aged female, who complained of failure of vision. Upon making an ophthalmoscopic examination a papillitis of a mild type was noticed. This led to a careful study of the urine, and sugar was found in a small amount for a short period of three days, although the glycosuria readily disappeared by cutting down the carbohydrate intake, the vision came back to normal more slowly. In fact, it was almost one month before the symptoms and signs of the retinal change had entirely disappeared. It is interesting in this connection to recall similar cases referred to in Allbutt’s System of Medicine, vol. vi, on influenza, following the epidemic of 1890 in England. Other transient glycosurias showed no visual changes. We do not consider these to be true cases of diabetes mellitus. In all a transient hyperglycæmia was also noted.

Pregnancy

A condition which can scarcely be considered as a complication of influenza, but which, however, was a large factor in increasing the mortality among women, was pregnancy. Among the cases included in this study were five pregnant women, who came to the hospital and were referred to the medical service. As soon as a complication relative to the existing pregnancy arose they were referred to the Obstetrical Department. On account of the great amount of work in caring for the influenzal patients, and on account of the scarcity of physicians and nurses, we were unable to follow these cases closely enough to give any such definite data as we wish. Three miscarried or went into premature labor. Happily only one of them died. The two which did not miscarry recovered and left the hospital well.

We very soon recognized in consultation with the obstetricians that the pregnant woman was in a really dangerous condition if she contracted influenza. She was likely to have a termination of her pregnancy in the height of the infection, no matter how recent or how remote pregnancy had taken place. If pregnancy did not terminate, the chances of recovery were less than those of the non-pregnant woman; if it did terminate, the chances for recovery were still less. To the pregnant woman with pneumonia very little hope of recovery could be offered. I am indebted to Dr. Paul Titus, of the Obstetrical Department of the School of Medicine, University of Pittsburgh, for a report which includes the cases seen by himself and his assistant, Dr. J. M. Jamison, during this epidemic. Dr. Titus was kind enough to include in his report certain conclusions which merit consideration. The report is as follows: “A series of 50 cases, at all stages of gestation. Interruption of pregnancy occurred in 21, or 42 per cent., of the cases; 29, or 58 per cent., in which pregnancy was uninterrupted. Mortality of pregnant women developing epidemic influenza is higher than that of ordinary individuals, even though their pregnancy is undisturbed, since 14 of the 29 in whom pregnancy was not interrupted died, an incidence of 482
10 per cent. If a pregnant woman miscarries or falls into labor, the mortality increases to 809
10 per cent. (17 of the 21 in whom pregnancy was interrupted died). The period of gestation has less influence on the outcome than the interruption itself. Of 10 at term, 3 lived and 7 died after delivery.

“Two main features of this condition as a complication of pregnancy are: First, pregnant women developing epidemic influenza are liable to an interruption of their pregnancy (42 per cent. aborted, miscarried or fell into labor); second, the prognosis, which is already grave on account of the existence of pregnancy, becomes more grave if interruption of pregnancy occurs.

“The cause of the frequency of interruption of pregnancy is probably a combination of factors: (1) The theory of Brown-Sequard that a lowering of the carbon-dioxid content of the blood causes strong uterine contractions sufficient to induce labor. (2) The toxæmia causes the death of the fœtus, particularly if not mature, when it acts as a foreign body and is extruded (10 premature fœtuses were born dead, while 1 was born alive, although 9 out of 10 at full term were born alive and survived).

“The cause of the frequency of death following interruption of pregnancy is also due in all probability to a combination of factors: (1) Shock incident to labor. (2) Increase from muscular labor of carbon-dioxid in blood already overloaded by the deficiency of the diseased respiratory organs. (3) Sudden lowering of intra-abdominal pressure by the delivery. (4) Lowering of blood pressure by the hemorrhage of the delivery. (5) Strain of labor on an already impaired myocardium.”

If one had been told a year ago that an epidemic could occur which would result in the death of 60 per cent. of all pregnant women affected, it would have been thought too unlikely to warrant any consideration. Though the effect upon pregnancy of the acute infectious diseases forms an important chapter in the pathology of pregnancy, it seems that the profession, and in this the obstetrician is no exception, has never realized how pernicious and tragic the results of an influenzal epidemic can be in a community. From the experience in previous epidemics we cannot but feel that the infection in the present epidemic was unusually fatal. Whitridge Williams (“Text-book of Obstetrics”) speaks of the interruption of pregnancy as having occurred in 6 out of 7 cases with one observer, and in 16 out of 21 in another, while a third has found it only twice in 41 cases. However, none of these writers speaks of having had a death.

Sequelæ

In referring to some of the associated conditions of influenza one scarcely knows whether to consider them as complications or sequelæ. The pathological process certainly had its origin from the influenzal attack, but at times apparently assumed an inactive stage. The patient is usually free from any specific influenzal symptoms, but retains for a long time other symptoms referable to various organs, or he may have been normal for a shorter or a longer period and then suddenly develop symptoms apparently independent of the previous infection. It may be well to consider all such conditions which followed the febrile attack, whether immediately or more remotely, as sequelæ, and I shall therefore speak of them as such.

The first and probably the most interesting and confusing are the conditions found in the lungs following influenza. A chronic bronchitis, an old bronchiectasis, or a previous tuberculous lesion in whatsoever stage, may present acute symptoms and signs which are difficult to interpret. The question always arises in the individual case—is this a process due to the recent influenzal attack, or was it there before the attack? Is it of streptococcic, pneumococcic, or tuberculous origin? The history of previous diseases of the lungs may help to arrive at a diagnosis. The history of the severity of the influenzal attack is of very little help, because the apparently mildest attack may be followed by the most profound changes in the lungs, and the gravest attack with a history of definite lung infection may leave the lungs without a trace of the previous pathology. The physical examination is helpful, of course, in determining whether the lesion is at the apices or at the bases, and from this a reasonably safe inference may be drawn as to whether it is from a previous tuberculous lesion or a recent influenzal infection. The Roentgenologist depends almost entirely upon this localization. If the linear striæ are only at the apex, it is probably tuberculous; but if they are only at the base, or also at the base, it is likely to be an influenzal lung. In fact, the Roentgenologist with his present information is ready to admit that it is most difficult to speak definitely of the lungs in these cases. The possibility of confusing the post-influenzal lung with a tuberculous lesion is not peculiar to this epidemic. After the epidemic of 1889 and 1890 the same condition was observed by clinicians. Dr. Roland G. Curtin, of Philadelphia, in 1892 and 1893 conducted a series of clinics at the Philadelphia Hospital, in which he spoke of the “non-bacillary form of phthisis,” and showed case after case which he said might be diagnosed as pulmonary tuberculosis, but because of the recent epidemic and the absence of the tubercle bacillus he diagnosed them as post-influenzal lung.

In the present stage of our knowledge, many of these post-influenzal lungs will not be diagnosed properly until sufficient time is given for either the lung to clear up or the tubercle bacillus to appear in the sputum. We would emphasize the importance at the present time of finding the tubercle bacillus in all suspicious lung lesions before giving a positive opinion as to the tuberculous nature, even though the physical signs are very definite.

Another group of sequelæ is that due to thyroid disturbance, or disturbance of the endocrin system in general. Since the epidemic a number of patients have been seen who noticed an enlargement of a previously normal thyroid gland or greater enlargement of a previously hypertrophied gland. In the same way the symptoms of hyperthyroidism appeared, new in some or a recrudescence in others.

In some of these there was a disturbance of carbohydrate metabolism, as shown by an occasional glycosuria and an increase in the blood sugar, or by a possible disturbance of the suprarenals, as brought out by the administration of adrenalin hypodermatically (Goetsch test). In the application of this test in post-influenzal patients it appeared that the whole endocrin system was in a state of imbalance.

It appears to us not at all improbable that the so-called psychoneuroses of which fatigue, nervousness, irritability and tachycardia play such an important part might also be explained in the same way. These constitute a group of sequelæ which were frequently recognized after previous epidemics, and which are again coming to the foreground.

We are of the opinion, on account of the apparent absence of any specific pathology of the gastro-intestinal tract and its appendages during the attack of influenza, that the sequelæ referred to the digestive system are largely due to exacerbations of previous physiological disturbances or pathological processes. The patient with a previous peptic ulcer has a recurrence of his ulcer. The patient with an infection of the biliary tract has an acute exacerbation, or may have an attack of biliary colic. In fact, there seem to have been many more cases of this kind since the epidemic than before, and most of the patients date the time of the onset from a period soon after recovering from influenza.

Very few, if any, patients in our experience have exhibited sequelæ due to disease of the cardio-vascular or genito-urinary systems. It may be that these will appear later when the more remote effects of an acute infection are recorded.

A very commonplace sequel, but of more or less interest, is the tendency to furunculosis. Our attention was particularly called to the associated hyperglycæmia. The blood sugar readings varied from 0.2 to 0.41. There was no glycosuria, acetone or diacetic acid. We have no explanation to offer for this, although one might dilate readily on many attractive theories. The hyperglycæmia, one may add, was readily reduced by a lowered carbohydrate intake, which also had a curative action on the furunculosis.

Finally we would mention the peculiar epidemic which has been observed apparently over the world, encephalitis lethargica. We do not for a moment put ourselves on record as regarding this disease as a post-influenzal affair, but no one will deny that it has a peculiar time relation to the epidemic; and further, that its distribution is apparently identical. Its bacteriology seems to be unknown. Its local pathology in the mid-brain is not peculiar or at variance with encephalitis produced by known organisms. We have seen five cases; three of whom had had undoubted influenza, while the other two were entirely free from even the slightest suggestion of any type of illness previous to the attack. All of these cases recovered. It has been stated that following the 1890 epidemic a clinical condition was observed in Europe which bears a close resemblance to what has been termed at the present time encephalitis lethargica.

Prognosis and Mortality of Influenza

In giving a prognosis of influenza one has to take into consideration the peculiar manifestations of the disease, especially the possible and sudden changes which are liable to take place in the lungs. The points which lead one to feel that the outlook is grave occur in about the following order, which is also about the order of the severity of the symptoms. First, cyanosis. This usually appeared quite early and was considered a forerunner of definite lung infection. It may have been a symptom only of the “wet lung,” to which reference has been made, but it was usually followed with definitely recognized pathology in the chest, and it immediately made the outlook unfavorable. Second, continuation of elevated temperature. If the temperature fell to normal in three or four days, the outlook was, of course, good; but if it went up again, or if the temperature did not fall in that time, the chances were that there was a lung involvement, even though the chest signs were negative or only those of an acute bronchitis. Strange to say, however, when definite chest signs were once recognized, the height of the temperature or the continuation of fever was not so important a prognostic factor. Third, increase in pulse rate. The pulse, as was noted before, was unusually slow, even though the patient seemed desperately ill; when, however, it began to increase in rate the condition was usually very grave. Fourth, the extent of lung involvement. This was of very little prognostic value. Both lower lobes might be solid, and yet if there was no cyanosis and the pulse and respirations were satisfactory, the outlook was rather good. On the other hand, there might be the slightest involvement of the lung, and if the pulse were rapid and cyanosis present the outlook was grave. Fifth, depression and stupor, or loss of so-called “morale.” If the patient remained clear in his mind, bright and hopeful, no difference how extensive the involvement or how grave the symptoms, the prospect of recovery was better. This is, of course, not peculiar to influenza, but it seemed particularly striking during the epidemic. Sixth, a gradually rising rate in respiration, which often was not more than two per minute per day, if progressive, even in the absence of other untoward signs, conveyed a serious prognosis.

Our mortality among the civilians in comparison with the soldiers was exceedingly high. The first cases seen by us were among the soldier patients sent to the hospital. These were as fine a lot of healthy young men as one can well imagine. They came to the hospital comparatively early in the infection. After the first week it appeared as though our experience would be entirely different from those in other localities, for we had very few deaths. In another week our mortality began to rise, but never as high as among the civilians, as will be seen by the following figures.

Of the 153 soldiers 87 were without lung involvement, and of these none died; 66 had lung involvement, and of these 16 died. Mortality among the 153 was 10 per cent. Of the 394 civilians 157 were without lung involvement, and of these 1 died; 237 had lung involvement, or some other complication, and of these 93 died. Mortality among the 394 was 23.6 per cent.

It will be seen that the mortality in the civilians was more than twice as high as in the soldiers. It has already been mentioned that the soldiers were ordered to the hospital promptly. The civilian patients, on the other hand, were later in coming to the hospital, some of them appearing when they had already developed serious complications. Another factor in determining the mortality were the ages of the patients. The soldiers ranged from 18 to 34 years, with an average of 20 years. The civilians ranged from 6 months to 73 years, with an average of 30 years. Generally speaking, the greater the age the higher was the mortality.

A third factor which should be considered in determining the actual mortality is the result of later complications and sequelæ. The figures as given are those of 547 patients, 110 of whom had died in the Mercy Hospital and 437 of whom had been discharged therefrom between September 22 and November 30, 1918, the length of the quarantine. Those who were discharged had been up and about for a week or 10 days before leaving the hospital. From our experience with post-influenzal patients admitted to the Mercy Hospital since November 30, we are of the opinion that some of the patients discharged before November 30 as recovered may have later developed sequelæ which might have proved fatal. No follow-up system has been pursued as yet which enables us to speak definitely and statistically of the present condition of those discharged.

This compilation does not readily lend itself to drawing any more specific conclusions, but we cannot desist from expressing our opinion that in the clinical study of this recent epidemic we find very little that may not have been observed by clinicians in previous epidemics.

THE URINE AND BLOOD IN EPIDEMIC INFLUENZA

By Peter I. Zeedick, M. D.

Epidemic influenza, unlike other acute infectious processes as diphtheria and scarlet fever, seemingly attacks the kidney in a rather mild manner. This statement refers only to the uncomplicated cases, as other bacterial or toxic agents do play a part in the nephritides occurring so often with the pneumonias or other complications following influenza. It is, however, true that in many simple epidemic cases there is evidence of a transient mild nephritis, or possibly, more correctly stated, a nephrosis. Some writers observed albuminuria in 80 per cent. of the cases, while the incidence in other reports varies from 4 to 66 per cent. It is not always stated with reference to these figures that the patients clinically were free from the common complication—pneumonia. The findings of various observers differ greatly, but they all agree that acute nephritis as a serious sequel is somewhat rare.

In the literature of the past epidemics general acknowledgment has been accorded to the presence of albumin in the urine during the acute stage of the disease. Many times this has received no further notice or comment than “febrile albuminuria.” The association of occasional hyaline and granular casts has also been mentioned. One is impressed with the fact that the older observers laid but little emphasis on the urinary findings. It also seems to be true that nephritis as a clinical entity is not prone to follow the epidemics. In general, our conclusions from the last epidemic are about the same.

The data for this paper was obtained from examination of 994 specimens of urine from 750 patients; of this number 517 specimens were examined at the Magee Hospital, where members of the S. A. T. C., all young men, were treated, and 447 specimens from the Mercy Hospital, where, in addition to the S. A. T. C., we had men, women and children. On account of the large amount of material and work on hand, as a rule only one specimen of urine was examined from each patient, but where complications were suspected repeated daily examinations were made. We have grouped our results in tables, so that the various points may be more readily followed.

Table I shows the urinary findings of uncomplicated influenza cases admitted to the wards of the Mercy Hospital. None of these cases developed pneumonia and, after running the usual course, recovered. We would call attention to the fact that 25 per cent. showed albuminuria. The amount of albumin was never excessive, and very often was little more than a faint trace. On the other hand, we have had a few patients where a previous kidney lesion was known to be present, and naturally in these cases a heavy cloud of albumin was met with. The albuminuria was almost always a transient affair, lasting only during the acute part of the illness, and would rightly come under the class of febrile albuminuria. We regard it as being more the evidence of nephrosis than a nephritis. As a rule, the time for the appearance of albumin was after the fever had been present for at least two or three days. One rarely met with it in the short attacks of influenza where the temperature came to normal in less than 72 hours. A certain time factor appeared to be necessary in order for the nephrosis to develop. Another point of interest is the presence of red and white blood cells seen relatively frequently during the early days of the illness. One wonders if this finding is analogous to the bleeding from the nose and lung so often met with at the onset of the disease. The red blood cells were seen microscopically, and only very rarely did we encounter a smoky urine.

TABLE I

URINE ANALYSIS IN CASES OF UNCOMPLICATED INFLUENZA AT THE MERCY HOSPITAL

TABLE II

URINE ANALYSIS IN CASES OF UNCOMPLICATED INFLUENZA AT THE MAGEE HOSPITAL

The results shown in Table II illustrate the urinary findings at the Magee Hospital, and, as in the previous table, include cases of influenza which did not develop pneumonia. The specimens examined were obtained from young, healthy men, between the ages of 20 and 32, and showed albumin in 13 per cent. of the cases. This age factor probably accounts for the lower incidence of albuminuria for this group.

TABLE III

URINE ANALYSIS IN CASES OF PNEUMONIA (INFLUENZAL) AT THE MERCY HOSPITAL

Table III includes the urinary findings of patients diagnosed as influenzal pneumonia. In this table the term “Day of Disease” indicates the day on which the physical signs of pneumonia could be demonstrated, and not the day on which the patient was taken ill with influenza. The incidence of albuminuria—79 per cent.—is very high, while the presence of casts and red blood cells is low. These results are really what one would expect. As we have noticed in the late stages of uncomplicated influenza a greater tendency for urinary changes to become apparent, one would, therefore, most likely find considerable urinary disturbance in the pneumonia immediately following the epidemic disease. Pneumococcic pneumonia is prone to be accompanied by an albuminuria. So when we have both influenzal and pneumococcic etiological factors involved, it is but natural to have most of the patients showing signs of kidney disturbance. The amount of albumin present, although generally greater than in uncomplicated influenza, was not excessive. At times there was little more than a trace. We noted the relative scarcity of casts—a condition which differs greatly from our past experience in the ordinary lobar pneumococcic pneumonia. On the transient nature of this kidney involvement we have considerable positive evidence, but there is no question that the time required for the urine to return to normal is longer after pneumonia than uncomplicated influenza. We have observed but one or two cases which afterward returned to us presenting clinical signs of acute nephritis. In fact, in going over our hospital records of the winter and spring we noted that an unusually small number of acute nephritics have been admitted. This would seem to be evidence that, as has been noted in the past, the kidney is not a vulnerable organ in this epidemic disease.

TABLE IV

URINE ANALYSIS IN CASES OF PNEUMONIA (INFLUENZAL) AT THE MAGEE HOSPITAL

Table IV includes specimens obtained at the Magee Hospital from patients diagnosed as pneumonia. The results among these young students were very similar to those of the previous chart, where all ages were included. However, casts and red blood cells were more regularly noted.

From the four tables, we are able to note one or two common facts. In acute uncomplicated influenza albuminuria occurred 57 times in 447 specimens, or 13 per cent., at the Magee Hospital. Here we dealt entirely with the young adult. At the Mercy Hospital 88 positive results of albumin in 344 specimens, or 26 per cent., from patients of all types were recorded. The common total would be 781 specimens examined, and 141, or 17 per cent., showing albumin.

With the advent of pneumonia the incidence of albuminuria was increased. At the Magee Hospital it was seen 49 times in 70 examinations, or 70 per cent.; while at the Mercy Hospital 106 positive results were found in 133 specimens examined, a percentage of 79. The combined figures, therefore, would show 155 out of 203, or 76 per cent.

The incidence of albuminuria for the epidemic in all its phases would be, from our figures, 400 in 994 specimens, or 40 per cent.

Red blood cells were present in 5 per cent. of the influenza cases, and in 11 per cent. of the pneumonias. This was always a microscopic observation, save in the case of a slightly smoky urine. Even microscopically the red cells were not numerous. We noted them at times quite early in the disease in some of the severe cases which presented epistaxis and hematemesis. Possibly one might consider the early presence of red blood cells in the urine as a condition analogous to those just mentioned, although we never saw anything suggesting free hemorrhage from the kidney. It is probably better to regard the red cells as a manifestation of an acute nephrosis of toxic origin.

Casts were found in 35 per cent. of the cases showing albuminuria. We are inclined to feel that this observation is somewhat low, but at the same time we have noted that in uncomplicated influenza one frequently sees albumin without casts. We were also impressed with the fact that casts were not as prominent a feature in the influenzal pneumonias as they are in frank lobar pneumonia of essentially pneumococcic origin.

During the course of routine examinations several transient glycosurias were seen. Their transient character was the outstanding feature. The quantity of sugar was very moderate—our figures were never above 1 per cent.—and the daily amount of urine was always within normal limits. Acetone and diacetic acid were absent. A few observations on the blood sugar showed a rise (.2 to .25), which readily came to normal with treatment. Clinically these cases were not classed as diabetes mellitus, but rather as a nervous complication of influenza, involving in some way the carbohydrate metabolism, probably through the central nervous system. One case of special interest, which is mentioned elsewhere, was the association of glycosuria with almost total blindness from a very intense optic œdema. Sugar (1 per cent.) was present on the day of admission, while only a trace was noted on the two following days, and from then on the urine was free from sugar. How many days the sugar had been present before admission to the hospital we cannot say, but we could trace the failure of vision back to almost the day of its onset, which was three weeks previous to our first examination. The eye symptoms were the only complaints. The patient had had a moderately sharp attack of influenza a little over two weeks before the first sign of failure of vision had appeared. We may add that the vision returned slowly to normal several weeks after admission. The urine and blood sugar were normal, on a general diet, over a period of one month while in the hospital. Unfortunately, we have had no further record of this patient regarding the urine, but her vision still remains normal. Cases of this type were observed in England after the 1890 epidemic, and are referred to in Allbutt’s “System of Medicine,” vol. i, on influenza. Our other glycosuria cases did not present changes in the fundus of the eye. The glycosuria and glycæmia were transient, and we feel that they do not represent diabetes mellitus. Most of the patients of this class had long since recovered from an attack of influenza, and came to the hospital usually for treatment of various nervous conditions, which at times simulated neuritis, or otherwise one saw manifestations of general nervousness, not unlike hyperthyroidism. In all probability, we were dealing with a hyperglycæmia associated with a hyperactive thyroid gland. So, after all, the glycosuria, even though rare, is not bewildering. Symptoms and signs of toxic goitre in direct relation to the epidemic we claim to have seen, and one is justified, temporarily at least, in having the thyroid gland father our transient glycosuria.

In relation to the positive sugar findings, we have had numerous negative examples of almost equal interest. Furunculosis is a very common sequel of the epidemic. It is well known that in furunculosis there is a hyperglycæmia, but no glycosuria and no acetone or diacetic acid in the urine. All our blood sugar readings were above the normal, and at times unusually high. They varied from .2 to .41. This last unusually high amount was in a young physician with recurrent furunculosis following influenza. There was no glycosuria at any time. Elimination of carbohydrates not only brought the blood sugar to normal limits in the course of a week, but also assisted in the cure of the furunculosis, but in a longer time. In all of this group we saw no incidence of polyuria or glycosuria.

Hematology

There is very little evidence, as shown in the literature, that special study on the blood during past influenzal epidemics has been made. A few references to alterations in the count of cells have been reported for the last epidemic (1890), but they are, as a rule, very brief statements. Cabot notes a normal leucocyte count in two-thirds of the cases, and a moderate increase in the rest. Several observers call attention to the leucopenia during the height of the disease, with a subsequent rise after the temperature has fallen to normal. According to Rieder and Herman (American Journal of Medical Science, 1893, cv. 696), the leucocytes were not increased in simple influenza, and only very slightly in the pneumonia following this disease. Herman also noticed a decline in the leucocytes in pneumonia as a fatal ending ensued. This finding was one of the few recorded for the 1890 epidemic. Emerson (Emerson Clinic Diagnosis, 1911, 558) found in influenza almost one-half of the cases showing more than 10,000 leucocytes, some even reaching 25,000. He further notes that early in the disease the count may be low, 3,000 to 5,000, but it usually rose sharply, to fall again when the temperature comes to normal. He lays stress on obtaining a leucocyte curve for each case in order to get a true picture of what changes occur. The past epidemic has brought out many observations on this subject. They vary somewhat, as is to be expected, but a common factor seems to be more or less basic—namely, a leucopenia or a normal count is the most significant single blood picture we have of uncomplicated influenza. Further, a leucocytosis is fairly generally, and we believe correctly, interpreted as evidence of a secondary bacterial invasion in this particular epidemic, and usually of the respiratory system. The leucopenia is as much a part of the clinical picture of influenza as it is of typhoid fever. Leucocytosis always means secondary invasion by other organisms.

During the recent epidemic the clinical laboratory department of the School of Medicine, University of Pittsburgh, has made 747 blood counts on influenza cases. In most of the cases blood counts were made as a routine, while repeated counts were done only on selected patients.

The following table indicates the leucocyte count for our series, comprising the epidemic in all of its phases. There are a few general points which appear striking that we may refer to at this time, and leave until later the discussion of the minor details. One-third of the counts, including, as they do, many cases of pneumonia, showed a leucopenia, while 70 per cent. of the total number fell under 10,000. This last group contains more pneumonias and other complications than simple influenza. But 5 per cent. of the cases counted showed more than 20,000. All of these undoubtedly had pneumonia or some other complication. Comparing this finding with our experience in the past before the epidemic with the pneumococcic lobar pneumonia, one sees at once that, as far as this type of clinical observation is concerned, the two pneumonias are totally different. The writer remembers but one case of lobar pneumonia which showed a persistent white count falling below 10,000. Certainly in this community lobar pneumonia and low leucocyte counts were unusual combinations until the present epidemic. Further, the evident depression of leucocytosis even where there was an actual increase is indicated by 95 per cent. of our counts being below 20,000. This leads us to state that the pneumococcus, although present in practically all of our pneumonias, produced in only a small percentage of the bloods we examined its characteristic increase. The toxic factor of this influenzal epidemic certainly causes a marked change in the white cells of the blood.

TABLE V

The blood picture in uncomplicated influenza is a normal one for the red cells and the hæmoglobin, but the white cells are characteristically altered. We have made many observations on the red blood cells, and from all aspects the picture appears to be normal. Similarly, there is nothing significant about the hæmoglobin estimations. Where we have slight alteration in the red count and in the hæmoglobin it is probably safer not to attribute the change to the epidemic. We have no records showing a secondary anæmia due to the initial epistaxis.

A leucopenia or a normal count is what one should see in most of the uncomplicated influenzal cases. We are almost ready to say that any estimation above normal limits means secondary bacterial invasion. The count may remain low throughout the illness, rising to the normal rapidly as the temperature falls. We do not regard a leucocytosis at the end of an epidemic case as part of the blood picture. Our experience is that with convalescence the normal count returns and remains within normal bounds. Very often hidden sinus infection is responsible for some of the post-influenzal leucocytoses. The leucopenia may vary from a slightly subnormal count to a point well below 2,000. Most of the simple epidemic cases showed some degree of leucopenia. As far as we have been able to estimate, we are led to believe that one should not lay any special stress on the grade of leucopenia as being of prognostic significance in uncomplicated influenza. Many of the mildest clinical types showed very low counts, and vice versa. There is, however, a prognostic relation to be noted with reference to a falling white count in the pneumonia, but this we shall mention again later. The onset of the leucopenia corresponds to the onset of the disease. It was present with the earliest cases we examined, and remained fairly stationary, although we have records of its fluctuating slightly one way or the other. But one must remember in this regard the personal error in blood counting, and also particularly the error of the apparatus. For careful work only those counting chambers and pipettes should be used that have a Bureau of Standards certificate. The duration of the leucopenia was fairly close to the duration of the disease.

How many cases of influenza of several days’ illness having about 12,000 leucocytes, a few sticky râles in the chest, but no signs of definite consolidation, have been observed by the clinicians? These cases recover without further change, and the diagnosis is handed in as influenza without a complication being mentioned. In collecting the blood reports from this group the 12,000 cells accordingly must be considered as having occurred in a simple influenza. We hold that this is not a case of uncomplicated epidemic disease. There is undoubted evidence, as is acknowledged by the clinician, of a bronchiolitis; and how many lungs showing a bronchiolitis at autopsy fail to have a broncho-pneumonia? True it may not be demonstrable by our physical examination. This is often the origin of many high counts in what apparently is considered uncomplicated influenza.

The blood picture of the pneumonia following the epidemic was more or less constant, although at the same time the features of the count may be quite different. One could roughly divide the results into three groups: (1) leucocytosis, (2) leucopenia, (3) intermediate or normal. Some pneumonias could be followed during their course through all of these classes. Before discussing the white count we can briefly dismiss the other phases of the blood examination by stating that the red blood cells and hæmoglobin presented nothing by the usual examinations which was of special significance, or in any way characteristic.

As an example of the group showing a leucocytosis let us follow a patient through an acute influenzal attack, followed by a pneumonia with a subsequent recovery. An initial leucopenia, gradually or suddenly changing into a very moderate leucocytosis (10,000–15,000), was noted at the onset of the pneumonia. During the course of the complication the number of cells in the majority of cases increased, but rarely advanced beyond 20,000. With lysis or crisis the count dropped toward normal, and by the time the lung signs had disappeared the white cells were at the usual number, or very slightly increased. The point which seemed to us to be of importance was that, even although we had a leucocytosis, it was nothing like the count that one would expect for a lobar pneumonia. Of course, there were a few high counts, but looking at the group as a whole they were relatively low. There are a number of variations to this form of blood picture which we might briefly consider. We have observed secondary rises in the leucocyte count concurrent with a new lung involvement. This type was the one so prone to develop into a condition of non-resolution, fibrosis and ultimate death, with a continuous moderately high leucocytosis to the end. Another variation which we learned to fear was the fall of leucocytes to normal or subnormal after a primary rise, when the clinical course of the case in no way indicated a crisis or lysis pending. Seemingly, the longer the primary leucocytosis had been present the more serious was the subsequent leucopenia. We regard this form of secondary leucopenia, if one may use such a term, as a prognostic sign of some value. As in lobar pneumonia, a high leucocyte count has been, as a rule, a favorable feature.

The second group, or those showing a leucopenia throughout their course, was by no means an unusual thing. This is a cardinal point—in fact, one of the most striking clinical features of the epidemic. The leucopenia here does not have the prognostic value that it seems to have in the group just referred to previously. We have observed cases go through a pneumonia with 4,000–5,000 white cells in a relatively easy manner. When, however, the leucocytes fall to 3,000 or under, one may be reasonably sure that the outcome is doubtful, even with the general condition of the patient at the time favorable. In the pneumonias of this group which died the leucocytes have always fallen to about 2,000 cells. We have a number of observations taken from one-half to four hours before death showing counts in the immediate neighborhood of 2,000, but never below this number. Where recovery has taken place the cells go forward to the normal, more or less keeping pace with the general clinical picture.

Of group three there is not much to say, except that on one hand it tends toward a leucocytosis, and on the other to a leucopenia. This group comprises a considerable number of the pneumonias. We are not in a position to say anything regarding the relative mortality of this group. The development of a leucopenia from these cases after a period of some stability in the leucocytic curve is of bad prognostic import. Not infrequently we have noticed rather wild abrupt rises to 20,000 in the leucocytes toward the late half of the disease. This curve was nearly always sustained until the end, which, as a rule, was recovery.

We do not need to consider at any length the effect on the leucocyte count of complications not of lung origin. Acute sinuses in head, otitis media and meningitis always produced a variable moderate leucocytosis. The change was not so marked in meningitis, as our cases were all preceded by a pneumonia which had independently invoked a slight leucocytic response. As a complication of the pneumonia we have noted an abrupt rise following an acute pleuritis with effusion, and similarly after the onset of an empyema. These complications seemed to be able to induce a leucocytosis with more certainty and ease than the more serious pneumonic condition. Possibly, as they occurred toward the end of the infection, the toxic factor of the epidemic influenza was more or less spent, and the secondary invader had a freer hand to act in its normal way.

Differential counts were made in 194 cases, including influenza, influenzal pneumonia and influenzal complications. We have taken the average percentage of each type of cell for the groups, which are purely numerical divisions based on the leucocytic count. No differentiation is made for the various clinical divisions of the epidemic in the following table:

The differential count in general indicates an increase in the polymorphonuclear leucocytes as the total leucocytic number increases. This is really what one would expect. There also seems to be an increase of the large mononuclear cells, with a slight diminution in the small mononuclear elements, particularly in the count below 10,000. Abnormal cells were encountered very seldom. One can hardly say that the epidemic has a characteristic differential blood picture, except, perhaps, that an increase of the large mononuclears is present in the low counts. This, however, may hold true for any leucopenia.

Conclusions

1. Epidemic influenza is often accompanied by a transient slight albuminuria with a few red blood cells and casts. Acute nephritis as a clinical entity does not appear to be other than a rare sequel.

2. Epidemic influenza tends to produce a leucopenia.

3. A leucocytosis in influenza, as a rule, indicates a secondary infection.

4. The pneumonia following influenza shows, as a rule, but a very moderate leucocytosis, while, on the other hand, the presence of a leucopenia is by no means infrequent.

We are greatly indebted to Miss R. Thompson, Messrs. Mock, Frost, Marshall and Scott for their assistance in this work at the Magee Hospital.

THE TREATMENT OF INFLUENZA

By W. W. G. Maclachlan, M. D.

One may frankly say there is no specific treatment for influenza. Possibly we are in error in introducing the discussion, particularly on treatment with such a definite and unsatisfactory conclusion. The same statement has been made after all the previous pandemics, and one wonders whether a like remark is going to apply to the next similar scourge. The past two or three months should bring to the medical profession a certain humility which should stimulate a keener sense of research, especially as we now have at our disposal highly organized laboratories where unsolved problems can be viewed from almost any angle. Yet we are really, save here and there, putting our forces together in the study of the disease. It is obvious that a fleeting epidemic makes a most difficult subject for study, especially during a time when there is a paucity of physicians. May we not hope, however, that some researches on the disease may be forthcoming, so that we may safely feel that at least preventive or protective measures will be possible?

There is no one who is able to say that this or that drug has not been thoroughly tried. The alkalies, salicylates, antipyretics, quinine and the sedatives have all been freely used in the last as well as the present epidemic. Each group of drugs has its following, although it appears to be a general rule in this epidemic to use the antipyretics (coal tar products) as little as possible. From the distant past we have numerous records of treatment. Willis (1658) emphasized the value of sweating and the use of diaphoretics, but at the same time he states that in mild cases the cure is left to nature; Sydenham (1675) claimed considerable value in fresh air. He also paid more attention to restricting the diet, and was not favorable to the use of anodynes. One certainly obtains the impression from the records of past epidemics that many of the general principles in treatment were similar to what are now in vogue. Medicinal remedies, of course, varied greatly, but to enumerate them would be merely giving a résumé of the progress of therapeutics. Sufficient is it to say that influenza has certainly, since the earliest days, given therapeutists an ample opportunity to test their wares.

The outstanding respiratory complication, pneumonia, has added a very undesirable phase to the disease. In fact, the greater part of the mortality was due to this serious sequela. Some interesting points have been brought out in serum and blood therapy for this type of pneumonia. The use of whole blood or serum from convalescent patients in cases of pneumonia opens up a new and not unlikely fruitful means of treatment. The method of treatment possibly may be applicable as an emergency measure in other diseases, as has been shown in the case of scarlet fever and poliomyelitis. We also have the anti-pneumococcic sera available for therapeutic use. The drugs and the general treatment of the pneumonia are virtually the same for the last two epidemics.

The protean manifestations of the 1890 epidemic, with its unusual nervous sequelæ, have not been seen to any extent, as far as we yet know. In fact, the present epidemic appears to be relatively free from complications other than those occurring in the lung during the acute course of the disease. Hence, in all likelihood, there will be less of the nervous after effects to be treated. It is, however, too early to hope that the nervous system is going to escape.

In another part of this volume the vaccine therapy is discussed in detail, so that we shall not repeat what has been brought out in that article. We would, however, emphasize the value of honest and accurate clinical reports of the use of vaccines, in order to establish their present status in epidemic influenza. Overestimation and commercialism are very likely to ruin a method of treatment, even when it may be of value in a certain phase of the disease. If we do not carefully weigh the pros and cons of the vaccine treatment in this epidemic from a purely scientific and coldly neutral attitude, we are simply doing the public and ourselves an injustice.

The treatment of influenza as the disease presented itself to us in this community will be considered under three divisions—acute influenza, pneumonia, and other complications.

Acute Influenza

There is one important thing to be done in the treatment of influenza, whether the infection be mild or severe. Have the patient go to bed as soon as possible. In most of the acute attacks the individual went to bed of his own accord; but there were, unfortunately, too many instances where the patient refused to surrender, trying, as we say, to fight the attack. Some appeared to be able to accomplish this feat. But how many of our cases of fatal pneumonia can be clearly linked up with this group of the mild or subacute preliminary course? No matter how light the attack may appear to be, the patient should be told of the necessity of remaining in bed until the pulse, respiration and temperature have returned to the normal and remained normal for at least five days. At the onset a hot bath, with care to avoid chilling, followed by a drink of hot lemonade and a Dover’s powder, gave considerable relief to the patient.

The value of good nursing cannot be overestimated. The nurse must see that the patient is always well covered and kept warm, not even permitting him to rise in bed to reach for a drink; also the regulation of the temperature of the room should be carefully watched. The main point is to have plenty of fresh air. We have noticed that the patient appeared more comfortable if the air was slightly warmed. Water should be given at regular intervals. Under no consideration should an acute influenza case be allowed to get up to go to the toilet.

At the onset, and while the febrile attack is still present, there is little desire for food—but one does not need to worry about the question of nourishment in such an acute illness. Milk, cream, cocoa, gruels and fruit juices may be given at first, and as the fever subsides the diet increased. We have found that the appetite returned to normal very readily. In view of the urinary findings indicating a slight transient nephritis, meat broths are to be avoided until the convalescent stage is reached. We have been very guarded in recommending cold sponging in acute influenza. As a rule, it was not necessary. The icebag to the head is often of great value in the intense headache, which is so frequent. It is our opinion that in the treatment of uncomplicated influenza what has just been mentioned constitutes the important part. Most physicians would agree with this. However, when we advance to drug therapy, we come into the personal realm of likes and dislikes of drugs and methods of usage.

We do not intend in any way to give our views in a dogmatic manner, nor to touch upon all of the remedies that have been advanced. At the onset of the disease a moderate calomel purge, followed by a saline, was given in all cases. We were practically free from the so-called intestinal type of influenza which was seen in some other communities, consequently we did not hesitate to use calomel. Castor oil or magnesium sulphate was given afterward, as was found necessary. Abdominal distention was rarely seen, and when it occurred a plain soapsuds enema with turpentine was administered.

Quinine sulphate (gr. iii-v, three times a day) combined with phenyl-salicylate (gr. v) was a routine measure. We often noticed deafness after a very few doses of quinine. It was then discontinued. Acetyl-salicylic acid (gr. v, three to six times a day) seemed to have a palliative effect on the severe headaches, although during the height of the disease the general muscular aching did not appear to be relieved by its use. It was not used routinely. These drugs possibly made the patients more comfortable, but we were very skeptical as to their influence on the general infection. The raising of the leucocyte count by quinine in influenza appears very unlikely. The use of alkaline salts has been a general procedure, particularly as we are now on the alkaline wave of therapeutics. Sodium bicarbonate was added to the drinking water of all patients (two drams to the quart). We gave this salt for its diuretic effect. In a few cases more active diuresis by the alkalines was readily and easily produced by the use of “imperial drink” three or four times a day. We felt that good kidney elimination was of considerable importance.

The use of tartrates and citrates, as in “imperial drink” in a condition where we know some kidney impairment is present, is possibly flying in the face of danger—especially in view of the fact that these salts are so available in the production of experimental nephritis. But we have only to see their application in the human in mercury bichloride poisoning, where an intense nephrosis usually develops, to fully realize that these salts may be given without danger to the kidney. We do not suggest that the kidney lesions of influenza and mercury bichloride poisoning are the same. We are merely bringing out this point of analogy in support of their use in certain desirable cases.

The respiratory symptoms gave us more concern than any other phase of the uncomplicated case. The irritating, distressing, non-productive cough suggested both a sedative and expectorant. Ammonium chloride (gr. iii-v, t. i. d.) was the usual expectorant. It seemed to increase in value with the more chronic type of case. It is our impression with those acute hacking coughs that the sedatives produced more gratifying results. Elixir terpin hydrate with heroin, codeine and occasionally morphine were preferred. When good results were noted sedatives were given liberally. Steam inhalations combined with tr. benzoin co., followed by spraying the throat with medicated liquid petroleum, gave some relief. The tendency to œdema, however, as we saw it in the cases complicated by pneumonia made us hesitate to use inhalations. Possibly the fear was groundless. Morphine (grs. ⅙) was given for sleeplessness, and it was repeated if necessary.

Cardiac stimulants were rarely needed. The tincture of digitalis was the choice, but in the uncomplicated cases was very seldom used.

At the beginning of the epidemic we prescribed whisky in almost every case. Our idea was that it would have a sedative action. At the present time we are very doubtful of its value. Toward the end of the epidemic we used it very moderately. The results obtained possibly depended for the most part upon the type of patient. Some of the soldiers asked to have it discontinued, not from any moral point of view, while others wished more frequent doses. The elderly patients seemed to appreciate this remedial agent to a fuller extent.

Pneumonia

The pneumonia following the original infection was, from the standpoint of physical diagnosis, often difficult of diagnosis in its early stages. The infection commencing as an influenza would at times pass imperceptibly into pneumonia, and obviously the points brought out in the previous paragraphs on treatment were applied until the diagnosis of pneumonia had been established. Some new factors were peculiar to the pneumonia and demanded further changes in the handling of the cases.

We would again emphasize the value of careful nursing to conserve the patients’ strength. They should be kept warm, well covered, with plenty of fresh air. Water should be given regularly and abundantly. The diet should be light, one depending a good deal upon the severity of the case. We believe it is safer to limit the diet to fluids while the infection is still pronounced, but as soon as the crisis has passed one may increase the diet freely and fairly rapidly.

Regular elimination from the bowel should be helped by the use of castor oil every other day, the dosage made to comply with the patient. We noticed much less abdominal distention in this form of pneumonia than one is accustomed to see in the ordinary lobar pneumonia. If distention were present, plain soap enemas with turpentine gave very satisfactory results. Turpentine stupes also are of considerable value. Rest at night is needed. When a hypnotic was necessary we gave morphine (gr. ⅙), and repeated if the desired results were not obtained.

The day is coming when we are going to isolate our pneumonia cases. This was almost an impossibility during the stress of the past epidemic, but we know that temporary and fairly satisfactory methods can be applied. Many hospitals provided for a type of isolation. In a pneumonia ward sheets stretched between the beds keep the fine spray which a heavy cough always produces from spreading over the next two or three beds. This method is simple and can be easily carried out. We feel almost certain of having seen convalescent influenza cases develop pneumonia from the adjacent pneumonia patients. As much as is physically possible, the uncomplicated influenza and the pneumonia cases should be separated. Further, it is to be kept in mind that reinfection by another group of pneumococcus is quite possible, even in a ward containing only pneumonia patients.

We did not observe any special effect of quinine, salol, salicylates after the pneumonia had developed and, therefore, these drugs were discontinued. Digitalis in the form of the tincture was at first made a routine measure, but toward the middle of the epidemic we stopped this routine usage and gave it only as it appeared to be indicated. Our impression was that the heart was not involved as it is in ordinary pneumonia. A slow, full pulse, as was so often the rule, did not seem to require digitalis. For more rapid action of the drug one of the hypodermic digitalis preparations or strophanthin was given.

Caffein sodium benzoate or salicylate seemed to be of considerable value given hypodermically every two or three hours, the last dose at 4 P. M. Its action as a respiratory stimulant and also as a diuretic was what we desired to obtain. The drug was used fairly early in the pneumonia, and although it was never prescribed routinely we gave it frequently.

Atropine was indicated whenever signs of œdema were evident. Its action was not always successful, but in certain severe cases we believe that large repeated doses of atropine saved a few lives. One-fiftieth (1
50 gr.) grain hypodermically, repeated every hour for several doses, was usually well borne. We noticed twice in each of two cases after using small doses (1
100 every four hours) a peculiar rapid cyanosis not associated with dyspnœa develop. This reaction remained, however, for only a short time, about 15 to 20 minutes, but it was rather alarming while it lasted.

The drug therapy is not very satisfactory in lobar pneumonia, and it is less so in the form of pneumonia which follows influenza. There is practically nothing essentially new in the drug and general treatment of this serious complication over what was shown in 1890, or even in the earlier epidemics, save that our nursing and hygienic measures are undoubtedly better.

The addition of an immune serum (anti-pneumococcus serum No. 1) to the treatment of pneumonia is a milestone in the history of the handling of this disease, but we must keep in mind that the pneumonia of the past epidemic was not the usual pneumococcic lobar pneumonia. That the pneumococcus was present in a great many cases is shown in another article of this series, but we also know that the B. influenzæ was present in many, and that it played an active part in the disease is evidenced by the constant low blood count or actual leucopenia. A leucopenia in true lobar pneumonia is most unusual in the United States. The rarity of Type I pneumococcus was noteworthy. We were practically unable to get any anti-pneumococcic serum which was known to be of value at the time of the epidemic, so naturally could not apply this method of treatment as was desired. About half a dozen 50 cc. bottles were in possession of the army medical officers here, but they unfortunately could get no further supply after this was used. We would have liked very much to have combined the anti-pneumococcic serum in Type I cases with the citrated convalescent blood, as was used by us during the epidemic. The anti-pneumococcic chicken serum of Kyes should also be considered. This serum has had but a very localized trial, but from competent observers who have given it to a considerable extent in some of the army camps we are led to believe that it has a very definite value. Major Lawrence Litchfield informed the writer that he had observed excellent results with Kyes chicken serum during the past epidemic in the treatment of pneumonia. This serum was not available for our use. It is to be hoped that further experience with Kyes serum will be favorable, because from the practical standpoint in the treatment of pneumonia it has many commendable features. Again, we desire to point out that the use of anti-pneumococcus sera in influenzal pneumonia may not be a fair test of their true value.

Very early in the epidemic we realized that the pneumonia was of unusual severity and most difficult to treat satisfactorily. We were at once impressed by our helplessness, particularly in those patients showing cyanosis. Nothing we did seemed to vary the course of the pneumonia after this sign was evident.

Our work in the epidemic began about October 10 on receiving a large batch of soldiers, about 100, from the Student Army Training Corps of the University of Pittsburgh. At the end of the first week several points were impressed on our mind. Firstly, in the severe cases of pneumonia; and in the early part of the epidemic most of the pneumonia was severe, the mortality was excessive, much higher than we have been accustomed to experience in Pittsburgh, where, as a rule, our hospital ward pneumonia is a very severe infection. Secondly, the wide variation in the severity of the epidemic as presented in the student soldiers coming from identical surroundings and conditions, the mildness on the one hand and the malignant character of the influenza on the other, was a very striking feature. This led to our adopting a form of treatment which was quite successful.

We worked purely on the hypothesis that those individuals recovering from a mild or moderate influenza infection developed a higher grade of immunity than those in whom the disease was more severe or fatal, and this immunity could be transferred to another. This, of course, was merely inference. If the mild cases did present a higher immunity, one would naturally think that immune bodies would be present in the blood, and that in transfusion from cases which had recovered one might have a measure of therapeutic value for this epidemic. Recently Spooner, Scott and Heath and others have demonstrated specific agglutins in the serum of patients convalescing from the epidemic. On October 17 we gave whole citrated blood from a convalescent case of uncomplicated influenza to an influenzal pneumonia patient. The result in this case was strikingly good, and for the following five or six weeks this method was frequently used. We decided to give the whole blood instead of the serum, as we were able to treat the cases more readily and rapidly in this way. Our method of transfusion was, fortunately, very simple.

We had treated but a few cases when the report of McGuire and Redden appeared. These observers working in the Naval Hospital at Chelsea, Mass., presented very excellent results in the use of immune serum from convalescent influenza cases in the treatment of pneumonia. They reported 30 recoveries out of 37 cases, with 1 death, and 6 cases still under treatment at the time of their report. This form of treatment began at Chelsea on September 28, 1919. In Texas, on October 15, Brown and Sweet gave two cases of influenzal pneumonia citrated blood from convalescent influenza patients. Their two cases recovered. Our published results, although not showing such excellent figures as from the Chelsea observers, agree very well with their work.

Since that time a number of confirmatory reports have been brought forward. Ross and Hund have shown that this method has been of value in their hands, and recently a further statement from McGuire and Redden tends to confirm their first views as to the value of immune serum from convalescent patients. Their last report giving a mortality of 6 in 151 cases of pneumonia cannot be other than positive proof of the value of this method of treatment.

As the technical side of the work has been given in several articles, we hardly think it necessary to again review it in detail. A few phases should, however, be recalled. It would seem that either serum or the whole citrated blood may be used. Solis-Cohen and his group of workers believe that whole blood has stronger bactericidal properties than defibrinated blood or the plasma. But yet one cannot complain, even on a theoretical basis, against the results obtained with serum by McGuire and Redden. The use of whole blood increases the detail of the procedure, in that the agglutination reactions must be estimated. Unfavorable results in this regard also naturally cut down the supply of available donors. In a military hospital a dearth of donors does not arise, but in civilian practice the problem is very different. In our work we never gave more than 100 cc. of whole blood; usually the amount varied between 50 cc. and 75 cc. On account of the small amount we felt that isoagglutination would not be a serious factor, and in more than 200 injections we failed to see any evidence of ill results from this source. Giving up to 500 cc., as was done by Ross and Hund, is probably a different affair, and accurate agglutination tests are essential. We feel that if the case is treated sufficiently early in the disease as much good can be shown to occur after 50 cc. as after 100 cc. of blood. We do believe, however, that the pooling of sera, where one is able to carry out this method, as it means a liberal supply of donors, is really the method of choice. Syphilis must be ruled out, both clinically and serologically.

As we emphasized previously, the problem presented in the army hospital and in civilian practice is a little different. We have had some experience with both sides. Fortunately, the greater part of our work was with the Student Army Training Corps, where army conditions were more or less carried out. There was never any difficulty in getting donors. In fact, the idea of giving blood appealed to these young fellows. In civilian life it is, in our experience, a more difficult problem. The usual personnel of the public ward has always its fair percentage of positive Wassermann reactors, and the type of individual is quite different from the young soldier. For a relative or friend we could easily get a donor, but this group would cover only a small percentage of the cases one wished to treat. The technique of giving blood can be reduced to a very simple procedure, and by no means should be regarded as a difficult surgical undertaking. Combining the receiving apparatus of Ross and Hund (J. A. M. A., 72, 1919, p. 642) with the syringe method for giving the blood which we suggested in our previous article makes an ideal arrangement.

The results depend upon the time of treatment. The earlier the pneumonia is recognized the better are the chances of recovery. It is our belief that the majority of influenza cases which kept a fairly high temperature for more than four days had a lung lesion, even if we could not make out definite consolidation. As the convalescent influenza serum may have value only for the influenza infection, it would, therefore, appear but logical that a late pneumonia which almost always has other organisms present would not react as favorably. We have seen very few of the deeply cyanotic type recover even with serum. The essential rule is to treat them before this stage develops.

We have observed little or no change in the leucocyte count, even after successful treatment, and taking our group as a whole we are rather surprised at this result. Other observers have noticed a marked increase in the leucocytes as the case reacted favorably to the injections. We agree with McGuire and Redden that the patients with counts below 10,000, as a rule, show the best results. This possibly indicates that the influenza infection is predominating, and that the usual secondary invaders (pneumococcus and streptococcus) are at this time playing but a little part. Hence the value of early treatment is apparent.

From the published results of different workers and our own experience, we feel that influenza immune serum or whole citrated blood given early in the pneumonia is of undoubted value—in fact, almost specific. If the epidemic reappears next year, unless some other better method is forthcoming, we would advise its more general use, and would suggest the collection of pooled serum as early as possible in the epidemic.

At the end of this article there is appended a series of our ward record charts of patients who developed pneumonia following the influenza. These charts are shown to indicate the results of giving immune convalescent citrated blood in pneumonia. The ones presented are from some of the group which recovered. We have, of course, the charts from the fatal cases, but as they do not bring out any special point, save that there was little or no change after treatment, we are omitting them. It is not our idea, however, to give the impression that we have had nothing but success with this method of treatment. It might be well to emphasize some of the salient points which are brought out.

(1) The regularity of the drop in temperature after the injection is almost generally demonstrated.

(2) The occasional chill following the injection seemed to have no untoward results.

(3) The leucocytes show, as a rule, little or no variation after transfusion. Our work agrees with McGuire and Redden’s statement that the cases with a leucocyte count under 10,000 give the best results with immune serum.

(4) The time of injection in many of the cases was by no means ideal, in that the disease was advanced; and again in many the injection should have been repeated sooner. This, however, is no fault of ours.

(5) One injection of 50 cc. of citrated blood from a good donor, if given early enough, may be all that is necessary. Several charts bear out this statement.

(6) The day of disease is dated from the onset of the influenza. The demonstrable signs of pneumonia correspond roughly to the initial rise in temperature following the influenza. The day of disease of the pneumonia is not indicated on the chart, as this information we have obtained from the daily notes.

Complications

The epidemic was well spent before we observed many complications, save those referable to the lung. Later various forms of sequelæ have been appearing. One must guard, however, against the danger of attributing all of our ills to the past epidemic. We are not going to give in detail the treatment of these various conditions, nor even mention all of the many complications. The main points, however, we desire to emphasize.

We have previously considered pneumonia, which is the principal complication with simple influenza, and the two are closely allied. As an end result of the pneumonia, non-resolution and fibrosis of the lung are of first importance. We cannot say very much on the treatment of this condition. The duration varied from a few to several weeks, and recovery was infrequent. Our treatment aimed at supplying as much nourishment as was possible to give, with, in addition, good nursing. The treatment otherwise was purely of a general hygienic type. Tepid sponging appeared to give considerable relief from the profuse sweating these patients so often had. Drugs were of value only for some local effect. We wonder if carefully handled vaccine therapy at the onset of such a complication might not prove of some value. The autogenous would be the one of choice.

Empyema was not found to be as prevalent as one would imagine. With so much non-resolution of lung following the pneumonia we were surprised to see so little empyema. All delayed resolutions we explored with the needle, so we feel that the condition, if present, would have been recognized. The treatment of empyema need not be given any special emphasis. It is, as of old, a surgical affair. One or two new points in the technique have been brought out in the way of drainage, but possibly they have not been sufficiently tried to lay any stress upon them at present. Dakin’s solution in certain chronic cases appeared of value. Our empyema cases did well.

Pleurisy with effusion was observed a number of times, although it has been our experience to find a very few large effusions. Pleural puncture often gave negative results, even when the signs did appear to indicate the condition. We aspirated the fluid when present. The end results were always good. In only one case did we have to repeat the aspiration for reaccumulation of fluid.

Chronic bronchitis, accompanied at times with considerable dyspnœa, has been seen on several occasions. There is very likely associated with this condition some fibrosis of lung, and probably some organization of small bronchioles themselves. Expectoration has been variable, profuse or scanty, mucoid or purulent. We consider rest in bed, with as full a diet as possible to build up the general condition of the patient, the best form of treatment. These cases had little or no temperature, and consequently at first absolute rest was not considered necessary, but we now regard it as the essential part of the treatment. Atropine and heroin are of value at certain times. We confess to have seen very little benefit from the expectorants. We are rather surprised that this sequela is not of more frequent occurrence.

Phlebitis, in our series usually of the formal vein, occurred about as often as it does in typhoid fever. The end result, however, is much better than in typhoid. We have seen only one case where “the milk leg” has resulted. Rest and elevation of the limb were all that we required. In the acute stage, if pain was present, a light, carefully applied icebag was added. It is important to rest the limb for at least two or three weeks, and to caution the patient against remaining on the feet too long for some weeks after recovery.

We saw a great deal of acute sinus infection, often occurring even while the attack of influenza was present, but, as a rule, this complication followed the attack. At times several weeks intervened. The ethmoidal sinuses are most susceptible, but a considerable number of acute frontal sinus infections were noted, the latter often immediately following or occurring during the acute period of the influenza attack. The majority of these infections appeared transient, and disappeared with a little local treatment. In fact, in frontal sinusitis cold applications seemed to be all that was necessary. With some of the more chronic infections nose and throat surgery has been followed by relief of symptoms. Acute suppurative otitis media, considering the number of influenza patients, was not common. Ear drum puncture was done if necessary. We saw one case of acute mastoiditis develop. The mastoid process was opened and drained.

Acute suppurative meningitis, following or associated with pneumonia, appeared on three occasions. The pneumococcus was cultured from the spinal fluid in all cases. Anti-pneumococcus sera intraspinally (Type I or the Kyes serum) should be given. The Type I serum is of value in a similar group infection. We have had no experience with this method, but some recoveries from pneumococcus meningitis have been reported after the early use of serum given into the spinal canal.

Following the 1890 epidemic cases complaining of blindness or partial loss of vision, with optic œdema or neuritis and a glycosuria, were occasionally observed. We have seen one of this type, and several transient glycosurias without eye signs or symptoms. The glycosuria may be of nervous origin. Our method of treatment was one of elimination and rest. The gastro-intestinal tract was emptied with calomel, and afterward a morning saline was given for a few days. Hot packs were administered, one a day for about two weeks. The patient was instructed to drink as much water as possible, and we eliminated sugar, bread and the 20 per cent. vegetables from the diet. The glycosuria lasted for three days, while the vision, although beginning to improve at once after treatment, took five weeks to return to normal. The patient was kept in bed for three weeks. How long the glycosuria had been present before admission to the hospital we do not know. The transient glycosuria group without the eye manifestations required very little treatment. They also showed a transient hyperglycemia. A carbohydrate free diet very rapidly cleared up these cases. After a time we decided to watch the course of this group on a non-restricted diet, even with sugar, and we found that they all returned to normal (blood and urine), in a few days clearly indicating their transient nature. We do not regard this process as a diabetes mellitus. We do not give the hot packs, although free elimination by bowel was attained in all. These cases were recognized only through routine urine examination.

Furunculosis with a high blood sugar, in one case 0.41, without glycosuria was a very interesting complication. We saw a great deal of furunculosis, always with the increased blood sugar from 0.2 to 0.3, but never with glycosuria. Reducing the carbohydrates, or even a fast day with good intestinal elimination, had excellent results.

Neuritis and general debility have often been associated with nasal or tonsilar infection, which when surgically corrected led to the disappearance of symptoms and improvement of health.

Finally, we wish to refer to an isolated case of acute osteomyelitis which was incised, and from the purulent fluid present in the bone B. influenzæ was grown in pure culture. This is a very unusual complication, and is of particular interest on account of the positive bacteriological finding. The patient made an uneventful recovery.

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THE PREVENTION OF EPIDEMIC INFLUENZA WITH SPECIAL REFERENCE TO VACCINE PROPHYLAXIS

By Samuel R. Haythorn, M. D.

INTRODUCTION

In developing practical measures for the prevention or control of influenza epidemics, preventive medicine faces one of the most difficult problems of modern times. By means of quarantine, protective vaccination and instructions in personal hygiene many of the diseases which formerly ravaged the world have been brought under control. At first glance it would seem to be a simple matter to apply the principles which we have found successful against these diseases to influenza and let it go at that, but in the recent epidemic many of the formerly successful measures were tried and found to be either inefficient, inapplicable, or at least of doubtful value.

During the pandemic there was little time to think collectedly, and no time to analyze procedures, and even now it is far from easy to determine what things were done wisely and what things were of no practical value. There exists the greatest difference of opinion as to what measures should again be used when the need arises, and what ones should be discarded. For instance, there are confirmed exponents of prophylactic vaccines, and equally able men who are convinced of their uselessness; enthusiastic advocates of the face mask, and almost as many objectors; those who would close schools, churches, theatres, etc., and those who claim that such measures serve only to prolong the epidemic. One naval officer is said to have stated that he had accumulated figures either to prove or to disprove the usefulness of any preventive measure yet recommended. There is, in short, a chaos of opinions with followers who vary from the one extreme of believing there is “virtue in all things” to those of the other extreme who state that every susceptible person develops the disease in the degree of his susceptibility, regardless of any and all preventive measures used. While there remain so many points on which definite, concrete knowledge is lacking, and so much controversy over the relative value of various measures, this paper can do little more than state the facts and discuss their bearing on prevention as impartially as possible.

Great progress has been made in controlling contagious diseases in recent years—a fact which can be easily verified by anyone who will compare the sick reports of the Great World War with those of any war previous to the beginning of the present century. The diseases which have been most easily controlled have been those against which prophylactic vaccines or prophylactic sera have been developed. Smallpox, dysentery and typhoid fever have lent themselves readily to control by protective vaccination, while reliable temporary immunity can be afforded by the administration of sera for protection against diphtheria and tetanus. These are by no means all, but are probably the most striking illustrations; and with such examples before us, the greatest hope for the prevention of influenza apparently lies in the development of a prophylactic vaccine against it.

History of Prophylactic Vaccination in General

The name vaccine came from “vacca,” or cow, and was originally applied by Jenner (1796) to the virus taken from cowpox pustules for prophylactic inoculation against smallpox. It has come to be loosely applied to all forms of preventive inoculations except sera. We have, therefore, a variety of vaccines which differ in their nature and method of preparation. Some are produced by growing the virus in insusceptible animals, some are composed of attenuated viruses, and most common of all are the bacterial vaccines, sometimes called “bacterins,” which are prepared from killed cultures of bacteria. Sera are used in prophylaxis, as well as treatment, and are made by bleeding and separating off the serum from animals which have been immunized against the cause of the disease in question. Sera and vaccines are wholly different products, and the distinction should be made in discussing them, although there is a common tendency, particularly among lay writers, to use the words interchangeably. Smallpox is the classical example of a disease which can be completely controlled by universal vaccination. The parasite causing smallpox has never been certainly demonstrated, but over a century ago Jenner showed that cowpox, a localized, non-fatal disease, protected against smallpox. Modern methods have proven that a cow inoculated with smallpox virus develops cowpox, and that thereafter the virus loses its power to produce smallpox when it is returned to man. Instead, it causes a local pustule, and confers immunity to smallpox over a considerable length of time. Rabies is another example in which the exact cause of the disease is still in doubt, and in which a protective vaccine has proven of great value. Rabies vaccine was developed by Pasteur, and is prepared by drying the spinal cords of rabbits that have been killed by a highly virulent rabies virus. Typhoid, dysentery, pneumonia and several other diseases of known etiology have been more or less controlled by the use of vaccines made from their respective bacterial causes. These vaccines are of the “killed bacteria” type of vaccines, and credit for their application to human disease belongs to Sir Almroth Wright (1896). The preparation of bacterial vaccines is very simple. Bacteria which are known to cause a certain disease are isolated in pure culture, grown on artificial media, killed either by chemicals or heat, standardized either by counting, or drying and weighing, and suspended in salt solution for subcutaneous injection. Salt suspension vaccines are usually given in three or four increasing doses, about one week apart. Le Moignic and Pinoy (58) first elaborated a lipovaccine for triple typhoid vaccination, which was used extensively in France during the war. Whitmore, Fennel and Peterson have recently also advised the drying of killed bacteria and the suspension of them in oil. This method makes it possible to give a single massive dose of bacteria which is sufficiently large to completely immunize the individual against the disease, and which prolongs the immunizing period by allowing slow absorption over a period of several weeks. These vaccines are called lipovaccines, have been adopted in the United States Army as the standard typhoid vaccine, and promise in time to supersede the salt suspensions entirely from a commercial standpoint. Many other modifications in the preparation of bacterial vaccines have been advised, notably the class known as sensitized vaccines. These are prepared by incubating bacterial vaccines for a time with the serum taken from animals already immunized against them. The serum apparently absorbs many of the toxic substances, and permits the injection of more efficient doses. Besredka advised the use of living cultures which had been incubated with immune sera, on the basis that vaccines so prepared were very active and non-toxic. The sensitizing treatment, however, does not stop the growing powers of the bacteria, and vaccines of the Besredka type are generally considered dangerous and so are little used. Sensitized killed bacterial vaccines, on the other hand, are quite popular.

When a sufficiently large dose of vaccine is given to an individual there is usually a transient rise in temperature for from 12 to 48 hours; the local focus of injection becomes sore and inflamed, and a white count often shows an actual increase in the number of polymorphonuclear leucocytes in the general circulation. A series of doses are usually given. If after a few days blood is withdrawn from the patient and immuniological tests made, it will generally be found that the patient’s leucocytes take up bacteria, and particularly the type of bacteria of which the vaccine was composed, more readily and in greater numbers than the leucocytes of the ordinary individual. Wright and Douglas (52) and Neufeld and Rimpau (53) have shown that this effect of increased phagocytosis is brought about by the vaccine through the production of substances which act specifically on the bacteria and render them more susceptible to inclusion within the white cells. These substances belong to the group of antibodies, and are known as “opsonins” or “bacteriotropins,” and are specific for any given bacteria. Moreover, the serum of the patient will, as a rule, be found to have developed the faculty of agglutinating and bacteriolysing suspensions of the specific organism injected and of fixing complement in the presence of an antigen prepared from that organism. In animal work it has been possible to go still farther, for it can be shown that the resistance of the animal can be raised until it is no longer possible to kill it with the same dose which is found to be fatal for the unimmunized animals. Not only has animal work made it possible to determine the protective powers of vaccines, but it has also served to show the specific nature of the protective power and the relative extent to which “group” or “crossed” protection can be conferred by vaccinating with closely allied organisms—as, for instance, paratyphoid bacilli in typhoid fever. The non-toxic nature of vaccines is also determined by animal experiment before such preparations are injected into humans.

The most successful prophylactic bacterial vaccine which has been developed so far is that for typhoid fever. A comparison of the occurrence of typhoid fever in the United States Army before and since the use of anti-typhoid vaccine is all that need be cited to convince one of its value. At the time of the Spanish War there was no vaccination against typhoid fever, and there were 20,738 cases, with 1,580 deaths, among 107,973 men who remained in the camps in the United States during the war (54).

During the summer of 1911, the maneuver division of the United States Army, having 12,801 men, all of whom had been vaccinated against typhoid fever, were stationed at San Antonio, Texas. Two cases of typhoid fever developed among them, and neither case died. Among the civilian population of the city, living under usual conditions during the same time, there were 49 cases of typhoid fever, with 19 deaths. Since 1912, typhoid vaccination has been compulsory in the United States Army, and the largest epidemic of typhoid fever which I have found reported so far during the late war was that at Camp Greene (55), Charlotte, N. C., where 18 cases developed. Only 12 of these men had received the complete series of immunizing doses. For a complete discussion of the value of typhoid vaccine the interested reader is referred to Gay’s Monograph (56) on typhoid fever.