Part 1

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

Page

History and Epidemiology of Epidemic Influenza 9–33

James I. Johnston, M.D., F.A.C.P., Assistant Professor of Medicine.

A Clinical Description of Influenza as It Appeared in the Epidemic of 1918–19 35–63

J. A. Lichty, Ph.M., M.D., Associate Professor of Medicine.

The Urine and Blood in Epidemic Influenza 65–79

P. I. Zeedick, M.D., Demonstrator in Medicine.

The Treatment of Influenza 81–95

W. W. G. Maclachlan, M.D., C.M., Assistant Professor of Medicine.

The Prevention of Epidemic Influenza with Special Reference to Vaccine Prophylaxis 97–153

S. R. Haythorn, M.D., Director of the Singer Memorial Research Laboratories.

Physiological and Physiological Chemical Observations in Epidemic Influenza 155–160

C. C. Guthrie, Ph.D., M.D., Professor of Physiology.

The Bacteriology of Epidemic Influenza with a Discussion of B. Influenzæ as the Cause of This and Other Infective Processes 161–205

W. L. Holman, B.A., M.D., Professor of Bacteriology.

The Pathology of Epidemic Influenza 207–293

Oskar Klotz, M.D., C.M., Professor of Pathology.

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.