SECTION II.. Influenza Epidemics Since 1893.

INFLUENZA EPIDEMICS SINCE 1893.

In this section of our report we will describe with as great accuracy as our sources of information will permit, and in as great detail as space will allow the events which have led up to the epidemics of 1918–20 and the various phases of the epidemics themselves. Points of similarity with previous epidemics will be made obvious; the differences, when of significance, will be described and studied in detail.

OCCURRENCE SINCE 1893.

Attempts even today to determine when and where influenza has prevailed in the world since the great pandemic of the last century are met with great difficulties. There are several reasons for this, chief among which is the absence of definite characteristics by which the disease may be recognized. The isolated solitary case baffles positive diagnosis. Nearly every year there are reports in the literature of small outbreaks in institutions or communities in which the clinical picture is that of epidemic influenza. As a rule the conclusion has been in these cases that because the bacteriologic findings did not show a predominance of Pfeiffer’s bacillus the epidemic was not true influenza. This is particularly true in the outbreaks in which the streptococcus predominated. Today our views concerning the bacteriology have changed distinctly, and I believe it is safe to say that the predominance of a streptococcus in a local epidemic in no way rules out influenza, and that the only criteria by which we may judge are the clinical picture and the evidence of high infectivity, together with the epidemiologic characteristics of the local outbreak.

Period 1893–1918.—A review of the medical literature between 1889 and 1918 gives one a certain impression which may be summarized as follows: Between 1890 and 1900 the disease was in general more highly prevalent in most localities than at any time during the preceding thirty years. At no time during this decade did the annual death rate from influenza in England and Wales fall to anywhere near the figures that had prevailed consistently between 1860 and 1889. Between 1900 and 1915 there was a gradual diminution, but still not to the extent that had prevailed previous to 1889. Since 1915 there appears to have been a gradual increase. During the entire period there has been difficulty in distinguishing between the disease in question and other respiratory tract infections, particularly coryza, sore throat, tonsillitis, and bronchitis. Many of the local epidemics which appear probably to have been true influenza have had associated with them a high incidence of sore throats. We describe this as sore throat, rather than tonsillitis, because the clinician remarks that although the throat is sore there is little if any demonstrable inflammation of the tonsils.

Chart VIII published by Sir Arthur Newsholme, showing the death rate per million of population from influenza in England and Wales gives some idea of the prevalence of the disease in the first part of the interpandemic period in those countries. It should be remarked that the record is for deaths from influenza only.

For records in this country it is convenient to refer to the death rate in the State of Massachusetts; first, because the records in that State have been carefully kept for a long period; and second, because influenza has been carefully studied in this State during both epidemics by two most competent epidemiologists. For the period preceding 1889 we quote herewith from Abbott:

“For the past 45 years or more, or during the period of registration which began with the year 1842, no epidemic of influenza has prevailed within the State to such an extent as to have manifested itself in any serious manner in the annual lists of deaths. An examination of the registration reports for each year since 1842 shows that in no year were recorded more than 100 deaths from this cause; the highest number from influenza in a single year (92) occurred in 1857, and the least number (8) in 1884. The average annual number of deaths from this cause reported in the State for the period 1842 to 1888 was 38. The average number during the first half of this period was greater than that of the last half, especially when considered with reference to the increase of population. From these statistics of nonepidemic influenza between the years 1842 and 1888 it appears that its greatest prevalence, or rather the years in which the mortality from this cause was greatest, were also years of unusual mortality from pneumonia, and in some instances from bronchitis.”

Frost has charted the death rate per 100,000 from influenza and from all forms of pneumonia in Massachusetts by month, from 1887 to 1916. From it he concludes that the epidemic of 1889–1892 developed in three distinct phases, the first culminating in January, 1890, the second in April and May, 1891, and the third in January, 1892. The mortality was higher in 1891 than in 1890, and still higher in 1892, while in 1893, although there was no distinct epidemic, the pneumonia mortality for the year was even higher than that of 1892. Frost remarks that this corresponds to the experience in England, and that it apparently represents the general experience in other countries (see charts IX and X).

CHART VIII.

Death rates per million from influenza in England and Wales from 1845 to 1917. (Newsholme.) ]

CHART IX.

Monthly death rates per 100,000 from influenza and from pneumonia in Massachusetts from 1887 to 1916. (Frost.) ]

CHART X.

Monthly death rates per 100,000 from influenza and pneumonia in three cities of the United States from 1910 to 1918, inclusive. (Frost.) ]

In the absence of comparable statistics for Massachusetts in 1917 and 1918, Frost has studied for those years certain other localities, particularly Cleveland, San Francisco and New York City. The mortality in all of these places, as well as in Massachusetts, was fairly regular from 1910 to 1915, but in December of the latter year and January of 1916 there occurred in New York and Cleveland a sudden sharp rise in mortality. This was not shown distinctly in the San Francisco curve, but it was a rise which was almost universal and synchronous over the entire registration area. It is of interest as indicating the operation of some definite and widespread factor, and suggesting in this group of diseases an epidemic tendency which is perhaps, as Frost remarks, not sufficiently appreciated. In January of 1916 he found that influenza was reported to be epidemic in twenty-two states, including all sections of the country. The epidemic was very mild. In the early spring of 1918 there was another sharp rise, which we shall discuss in greater detail later.

Increase in 1900–1901.—Reference to Frost’s chart for Massachusetts shows that there was also a rise in the curve around 1900. At this time influenza was quite widely disseminated. Early in 1901 the Marine Hospital Service made a canvass of all the states and several foreign countries to determine the epidemic prevalence of influenza. The results of the canvass were published in the Public Health Reports. The records lack the detail, particularly in the description of clinical symptoms, that is desirable in arriving at an identification, but the universal agreement from all individuals reporting, in the comparatively high morbidity and remarkably low mortality, together with the widespread distribution, and the duration of the local epidemic leaves little doubt as to the identity.

Influenza was reported present in October of 1900 in Los Angeles, Milwaukee and New Orleans. In November it became prevalent in Toledo and Cincinnati and in New York City. In December the disease was present in Chicago, Albany, Philadelphia, San Francisco, Denver, Baltimore, Grand Rapids, Columbus, O., Portland, Me., Detroit, Albuquerque and Omaha. In January it was reported in New Haven, Boston, Washington, D. C., Indianapolis, Louisville, Ky., Wilmington, Del., Portland, Ore., and Juneau, Alaska.

Although the disease was mild, in some localities a high proportion of the population was attacked. Thus in New Haven it was estimated that 10 per cent. developed the disease, and in Los Angeles 20 per cent., while in Wilmington, 40,000 were estimated to have become ill. In certain small towns in Texas the incidence was especially high. In Pittsburgh, Texas, ten per cent.; Laredo, 15 to 20 per cent.; Hearne, 50 per cent.; and El Paso, 50 per cent. were attacked. The duration of the epidemic in most localities was from four to six weeks.

Thus we see that in October, November and December of 1900 and January of 1901 there was a widespread epidemic affecting all parts of the United States. Many additional records in the Public Health Reports coming from small towns have not been included in this summary.

At the same time an attempt was made to determine the prevalence in foreign countries and letters were sent to the various United States Consulates. It was discovered that the disease was mildly epidemic in Denmark in October, in Berlin in November, in Cuba, British Columbia, Ontario, Egypt, Paris, Mexico and the West Indies in December; in Flanders, Porto Rico, Honolulu, in January of 1901; in Malta in February, 1901; and in London and Ireland in March of that year. The following countries reported that they had no influenza at the time: Windward Islands, Jamaica, Bahamas, Brazil, India, Colombia, Costa Rica, Ecuador, Honduras, Persia, Philippine Islands, Spain, Switzerland. The disease was reported as being not of epidemic prevalence in the following localities: Marseilles, Paris, Bremen, Hamburg, Mainz, Stuttgart, Bristol, London, Liverpool, England as a whole, Scotland, Amsterdam, Naples, Constantinople.

Reports from Switzerland and from Brazil stated that there had been no influenza since the pandemic period 1889–1893. The death rate per 100,000 in Glasgow from influenza for 1896 was recorded as six; for 1897, twelve; for 1898, fifteen; 1899, twenty-two and for 1900, twenty-seven.

The disease was present in Lima, Peru in March, 1900, and at Malta in the same month. In Prague it was stated that ten per cent. of the population had been attacked in the winter of 1901. In Sivas, Turkey, fifty per cent. of a population of 50,000 were estimated to have been taken ill within the winter months. It was reported from Valencia, Spain, that there had been four or five visitations of influenza since the preceding pandemic, each recurring invasion presenting a milder and less expansive form than its predecessor. Very few deaths had been recorded as directly due to influenza, but an increased mortality followed the epidemics. In normal times the average mortality was ninety deaths per week. After a visitation of influenza the number had increased to as much as 160 per week. The population numbered 204,000.

Period from 1901 to 1915.—Between 1900, with its wide distribution of a very mild influenza, and 1915, there is very little mention of epidemic prevalence of the disease. References which appeared in the Public Health Reports during the interval are characterized chiefly by their brevity, and by the absence of descriptive detail. They should nevertheless be included.

In October of 1901 there was some increase of the disease in the Hawaiian Islands, 110 cases being reported on the island of Kauai.

At the same time, C. Williams Bailey reported a mild form of influenza existing in Georgetown, S. C., which was first considered to be hay fever in consideration of the presence of the rice harvest season, but which was finally decided, after careful investigation, to be true influenza.

On July 21, 1902, the U. S. Consul at Canton, China, telegraphed that influenza “was almost epidemic, plague sporadic in Canton.”

In 1903 the disease was reported as apparently prevalent at New Laredo, Texas.

Surgeon Gassaway, of the Marine Hospital Service, reported from Missouri, December 14, 1903, as follows: “There is a very decided increase in the number of cases of influenza in this vicinity. Two have been admitted within the last few days to this hospital, and several cases have appeared among the patients under treatment. In these cases the onset is sudden and the disease appears principally, at least at first, to be confined to the nose and throat.”

Measles and influenza were reported prevalent in Barbados, West Indies, during the month of December, 1904.

Sturrock describes a quite typical local epidemic in a British institution in 1905.

Influenza was epidemic in Guayaquil and various other places in Ecuador during the months of June and July, 1906.

Selter speaks of a true local epidemic of a disease clinically resembling influenza which occurred in 1908 and extended over the territory from France to the Rhine.

Hudeshagen mentions having examined bacteriologically cases of influenza in the year 1914.

Ustvedt relates his experience at the Ullevaal Hospital up to September, 1918. Since 1890 there had been cases reported every year from the high marks of 10,461 cases in Christiania in 1890 and 5,728 in 1901 to the lowest figure, 138 in 1906. “The cases listed as influenza in the last few years may have been merely a catarrhal fever. This is the more probable as the cases were restricted to the winter months, while influenza usually occurs at other seasons.”

Jundell believes that influenza is endemic at Stockholm, Sweden, hundreds of cases being reported there each year. During the years 1912–1919 Pfeiffer’s bacillus has been found in ten per cent. of those cases in which the diagnosis seemed certain.

A current comment in the Journal of the American Medical Association in 1912 remarks that epidemics of coryza, sore throat, and bronchitis usually have been called influenza or grip because of the characteristic contagiousness and the infectivity, the persistence of the symptoms, and the tendency to prostration and mental depression. But this diagnosis has not been satisfactorily confirmed by bacteriologists. An epidemic according to the Journal, which occurred in Boston and which was called sore throat, was studied by Richardson and others. They traced the contagion to a streptococcus which apparently was spread by means of milk. Müller and Seligman had recently carried out a study of an influenza epidemic among children in Berlin and concluded that the causative organism was a streptococcus, differing so much from the ordinary germ that they used the term “grip streptococcus.” Davis and Rosenau, according to the comment, had made a bacteriologic study of a recent epidemic of sore throat in Chicago, and had demonstrated as the exciting agent a streptococcus of peculiar characteristics, which in many respects resembled the organism described by Müller and Seligman. The Journal noted that these three epidemics occurring during the years 1911 and 1912 in widely separated communities were all caused by the streptococcus, and cautioned against the proneness to call all such epidemics grip. Today the predominance of the streptococcus would not necessarily rule out influenza in our minds.

In the winter of 1913, C. L. Sherman had occasion to study carefully fourteen cases of so-called influenza in the vicinity of Luverne, Minnesota. Bacteriologic smears and cultures were made from the throat and sputum in all cases. Bacillus influenzae was found in two of the fourteen; pneumococcus in four and streptococcus in all. Tubercle bacilli were found in one case. The onset of the disease was invariably abrupt. The fever in all cases ranged between 101° and 104°; symptoms indicative of infection of the upper respiratory tract were always present. There was more or less sore throat in all. There was either cough at the onset or else it appeared within 48 hours. Headache was complained of by twelve of the fourteen; pains in the back and in the limbs by thirteen, and nervous symptoms by six. Prostration out of all proportion to the fever and other symptoms prevailed. Two developed an otitis media and the streptococcus was isolated from the purulent discharge in both cases. One patient had a complicating empyema, and one an acute arthritis. Sherman also concluded that we are prone to call too diverse diseases influenza.

Walb stated in 1913 that at Bonn during the preceding years there had been numbers of cases of a febrile affection which seemed to be typical influenza, but for which the pneumococcus appeared to be responsible. They were never able to isolate the influenza bacillus, and according to their statement the Hygienic Institute at Bonn, as well as that at Berlin, had not “encountered an influenza bacillus within the preceding ten years.”

C. T. Mayer described in 1913 a case of influenza in Buenos Ayres which is of particular interest in view of one of the symptoms, cyanosis, which was so prominent a feature in 1918. This appears to have been an isolated case. The diagnosis wavered between miliary tuberculosis and pneumonic plague, because of the high fever and intense cyanosis, with nothing to explain the cyanosis on the part of the heart. There were signs of severe congestion of both lungs, and notable enlargement of the spleen. Bacteriologic examination was negative except for the presence of Bacillus influenzae and Micrococcus catarrhalis. The patient subsequently improved rapidly, and the lungs were entirely normal after thirty days, thus ruling out the other two diseases.

A London letter to the Journal of the American Medical Association dated February 5, 1915, runs as follows:

“Since the outbreak of the war the public health has been remarkably good, but the record is now being threatened in the case of London, at any rate, by an epidemic of influenza.

“The gastric symptoms which distinguished last year’s epidemic are absent. The disease is most infectious. Whenever it has seized the individual it has usually run through the entire household.

“Whole offices have succumbed, and as the mildness of the attack lures the sufferer to continue his normal occupation, the disease has a full opportunity of extending. A large number have resulted in pleuro-pneumonia; otherwise the chief symptoms are headache, fever, tonsillitis.”

Telling and Hann describe another clinical diagnosis of influenza, the diagnosis being concurred in by Sir James Goodhart and Sir Clifford Allbutt. The onset was absolutely sudden at a supper party on November 10, 1912. The patient had a slight rigor, and was compelled to go to bed. In the night he had a longer and more severe rigor, with a temperature of 103°. On the following morning he dressed, but another chill sent him back to bed with a temperature still 103°, pulse 110, regular, and remarkably dicrotic. There was no cough and no sore throat. Another chill occurred in the evening. On November 12th the patient had two chills, the temperature remaining steadily at 103° to 104°. The patient complained much of nausea but did not vomit. On November 13th the temperature remained up, there was no chill on this day; the spleen was large and easily felt for the first time. On the 14th note was made that there was no headache. On the 15th, 16th and 17th the temperature began to fluctuate. On the 18th there were two severe rigors, and by the 19th the temperature suddenly fell to normal, with drenching sweat. Throughout there was nothing to suggest pneumonia, and typhoid fever appears to have been successfully ruled out.

An epidemic of influenza which prevailed in the city of Pittsburgh, Pennsylvania, from December to February of 1907 and 1908, has been described by J. A. Lichty. He says that the epidemic was as widespread, though probably not quite as severe, as the pandemic of 1889. Whole families, including servants and all associated with the household, were afflicted in rapid succession. The onset was sudden and severe, the usual symptoms of pain, all over, being most pronounced. The temperature did not go unusually high, nor did it seem to be in accord with the severity of the symptoms when the patient took to his bed. In typical cases the attack lasted from two to three or four days. Peculiar to this epidemic seemed to be the general complaint of sore throat. Upon examination the throat rarely showed any other evidence of an abnormal condition than a rather dark cyanotic blush, which was most intense over the tonsils and faded out over the roof of the mouth. This was rarely associated with any swelling or fever. Sinusitis and otitis media seem to have been the two most frequent complications. The disease appeared to be particularly fatal for chronic invalids. It was highly contagious. Many of those physicians who were frequently exposed to the disease fell victims.

At the same time C. H. Jones described an epidemic of the same disease in Baltimore. The symptoms were described as headache, backache, limb-ache, with a slight elevation of temperature, seldom more than 102°. Catarrhal symptoms developed secondarily and were not so prominent a feature as in former epidemics. There were some gastric symptoms, usually consisting of vomiting and nausea. Jones quotes no statistics, but feels sure that the infection was more extensive than at any period since 1895.

Coakley and Dench describe throat and ear complications as they saw them in New York. From this we may assume that the disease was present at the same time in New York City.

The following chart, derived from the U. S. Vital Statistics Report shows the increase in the death rates from influenza in 1900 and 1901; that of 1907 and 1908, and finally an increase to 26.4 per 100,000 in 1916, which reflects the epidemic beginning in the latter part of 1915:

Influenza and Pneumonia Mortality in the United States Registration Area for Each Year Since 1900. ═════════════════╤═════════════════════════════════════════════════════ Year. │ Annual death rates per 100,000. ─────────────────┼─────────────────┬─────────────────┬───────────────── „ │ Pneumonia. │ Influenza. │ Combined │ │ │ diseases. ─────────────────┼─────────────────┼─────────────────┼───────────────── 1900│ 158.6│ 22.8│ 181.4 1901│ 133.5│ 32.2│ 167.7 1902│ 124.7│ 10.1│ 134.8 1903│ 122.6│ 18.5│ 141.1 1904│ 136.3│ 20.2│ 156.5 1905│ 115.7│ 18.8│ 134.5 1906│ 110.8│ 10.3│ 121.1 1907│ 120.8│ 23.3│ 144.1 1908│ 98.8│ 21.3│ 120.1 1909│ 96.3│ 13.0│ 109.3 1910│ 147.7│ 14.4│ 162.1 1911│ 133.7│ 15.7│ 149.4 1912│ 132.3│ 10.3│ 142.6 1913│ 132.4│ 12.2│ 144.6 1914│ 127.0│ 9.1│ 136.1 1915│ 132.7│ 16.0│ 148.7 1916│ 137.3│ 26.4│ 163.7 ─────────────────┴─────────────────┴─────────────────┴─────────────────

At best our information for these years is unsatisfactory. It is greatly to be desired that individuals who have access not only to the current medical literature, but also to the vital statistics and other records for all countries possessing reliable records, and who are versed in the newer mathematical methods of demography, establish definitely the influenza prevalence and distribution during these interpandemic years. The difficulty in this work is that mortality statistics are unreliable and morbidity statistics are lacking.

Influenza in 1915–1916.—Until the end of 1915 there was no widespread distribution in the United States similar to that of 1900 and 1901, but at that time there developed a widespread epidemic in this country of similar or possibly slightly greater severity than that of fifteen years previously. Reference to the last table will show that during 1916 the annual death rate from influenza as reported in the United States Vital Statistics reached the rate of 26.4 per 100,000. According to V. C. Vaughan the literature of that time shows that this epidemic originated in the West, first attracting attention at Denver, and gradually spread over the country.

Dr. Dublin of the Metropolitan Life Insurance Company gives the following table in which the deaths from influenza and pneumonia during the months of December, 1914, and January, 1915, are compared with deaths from the same cause during the months of December, 1915, and January, 1916:

═══════════════╤═══════════════════════════╤═══════════════════════════ Name of city │ Deaths reported as due to │ Deaths reported as due to │ influenza. │ pneumonia. ───────────────┼─────────────┬─────────────┼─────────────┬───────────── „ │ In 1915–16. │ In 1914–15. │ In 1915–16. │ In 1914–15. ───────────────┼─────────────┼─────────────┼─────────────┼───────────── Baltimore │ 57│ 12│ 219│ 101 Cincinnati │ 81│ 2│ 105│ 84 New Orleans │ 97│ 44│ 35│ 29 New York │ 494│ 62│ 2,067│ 1,207 Philadelphia │ 324│ 62│ 564│ 272 Providence │ 38│ 3│ 31│ 31 ───────────────┼─────────────┼─────────────┼─────────────┼───────────── Total │ 1,091│ 185│ 3,021│ 1,724 ───────────────┴─────────────┴─────────────┴─────────────┴─────────────

Dublin states that the Industrial Department of the Metropolitan Life Insurance Company, covering the entire country and embracing ten millions of people, had deaths in the periods above mentioned, as follows:

In December, 1914, and January, 1915, the number of deaths attributed to influenza was 165

While in the corresponding months of 1915–1916 the deaths attributed to influenza were 957

The deaths attributed to pneumonia in December, 1914, and January, 1915, were 1,468

While the number of deaths attributed to the same cause in December, 1915, and January, 1916, were 2,563

Coffey and others have reported an epidemic of influenza at Worcester, Mass. during the first three weeks of January, 1916. During the first three weeks of January, 1915, there were reported in that city twenty-two deaths from respiratory diseases, making a total of 14.9 per cent. of the total deaths. In the same period of 1916 there were reported ninety-three deaths from acute respiratory diseases in the same population.

Two of the more complete descriptions of the epidemic of the year 1915–16 are those by Mathers, and by Capps and Moody. Mathers reports that: “During the winter of 1915–1916 the United States was visited by a severe epidemic of acute respiratory infections which resembled in every detail the great epidemic of 1890. This outbreak was apparently first noticed in the Middle Western States, and it spread rapidly over the entire country, taking a heavy toll of human life. December and January were the months in which these infections were most prevalent, and the epidemic had almost completely lost its impetus by March, 1916. During the height of this epidemic in Chicago, sixty-one cases of the disease were studied bacteriologically, and the results form the basis of this paper.”

Mathers found hemolytic streptococci in forty-six instances, in all of which they predominated. Green producing streptococci were found thirty times, with one pure culture, and pneumococci thirty times with four pure cultures. Staphylococci were isolated in fifty cases; Micrococcus catarrhalis in six, and Friedländer’s bacillus in one case. The influenza bacillus was found in only one instance, and then in small numbers. The majority of the patients were studied early in the course of the disease, and in the earliest, hemolytic streptococci were almost constantly found, especially in the throat. In the atypical pneumonia which followed many of the attacks of grip, hemolytic streptococci predominated. In none of these was the Bacillus influenza found.

Mathers reported that coincident with the epidemic among humans there was an epizootic of so-called influenza among horses. The symptoms are very similar to that of the disease among humans. He isolated a streptococcus as the predominating organism in the horses. The streptococci from human and equine sources, although similar in many characteristics, differed widely in pathogenicity, and seemed to be highly parasitic for the specific hosts.

Capps and Moody found that in man most cases began rather abruptly, with coryza, pharyngitis, laryngitis, or bronchitis.

“The chief complications were inflammation of the accessory sinuses of the head, and bronchopneumonia, the latter being responsible for most of the fatalities. None of these symptoms taken alone would justify the distinctive name of grip. But the widespread and almost simultaneous onset of this fairly uniform symptom group and the rapid cessation of the epidemic after a few weeks reminded physicians generally of the great grip pandemic of 1889–1890. This resemblance was further strengthened by the unusual prostration lasting days or weeks after even mild attacks. The older practitioners can recall no similar epidemic during the twenty-five years intervening between 1890 and this year. The numerous epidemics of septic sore throat have all been entirely different in their symptomatology, and all were restricted to certain localities. The term “grip,” therefore, seems justified from a clinical standpoint.

“The public health reports offer evidence of an unusual prevalence of pneumonia in the larger cities. Nicolas calls attention to the fact that the incidence of grip was greatest in those cities in which the mortality from pneumonia was most strikingly increased.”

Capps and Moody found that as a rule the white blood counts in the individuals sick with influenza were 10,000 or less. A number showed true leucopenia. Less frequently there was a leucocytosis up to 15,000 or higher.

Influenza between 1916 and 1918.—Zinsser cites Dr. George Draper, who believes that he observed at Fort Riley in the winter of 1917 epidemic cases of influenza. He believes that for Europe too there is evidence that influenza was endemic during the years preceding the great outbreak, and that a number of minor epidemic explosions had occurred in the years just preceding 1918:

“MacNeal who has investigated military reports particularly, states that small epidemics occurred in the British Army in 1916 and 1917. A chart constructed by him from the American Expeditionary Force reports shows that a considerable rise in reported influenza cases took place in November and December, 1917, and in January, 1918, gradually declining toward spring. MacNeal, compiling the data available in the office of the Chief Surgeon, A. E. F., states that the influenza morbidity reported per 100,000 for succeeding months in 1917, were as follows:

July 321 August 438 September 404 October 1,050 November 1,980 December 2,480

“Robertson, who studied many of the secondary pneumonias which came to autopsy at this time found an unusual type of lobular pneumonia in which Pfeiffer bacilli were frequently found. In many of these cases the organisms could be obtained from the nasal sinuses and antra. Similar findings were reported by British bacteriologists (Hammond, Rolland and Shore, and Abrahams, Hallows, Eyre and French), who studied the cases that occurred in the reports by Austrian physicians in reference to outbreaks of typical influenza on the Austro-Russian front early in 1917.

“There seems little doubt, therefore, that for some years before the pandemic of 1918 influenza was endemic in many parts both of Europe and of America. As early as 1915–1916 Frost finds evidences of limited epidemic outbreaks in the United States. During the winter immediately preceding the true beginning of the pandemic small outbreaks occurred among the allied troops in France, the British troops in England and probably among American troops gathered in home concentration camps as well. MacNeal in a summary of the conditions prevailing among American troops in France concludes that epidemic influenza in that country originated from the endemic foci there existing, and that the disease was probably carried from Europe to the United States by shipping. The former assumption; namely, that the epidemic occurrence of the disease may have been due to the fact that an enormous and concentrated newly introduced material of susceptibles may have been lighted into flame at the numerous endemic smoulders, may well be correct. The latter, however, concerning the transportation of the disease from Europe to America may justly be questioned. For, in the first place, Frost’s studies have shown that prepandemic outbreaks were quite as frequent in the United States as in Europe during 1915 and 1916, and, though we have no proof of this, there is reason to believe that influenza was prevalent in concentration camps during 1917.”

Carnwath, after remarking that the epidemic began in the British Army in France in April, 1918, says that according to the reports of the Influenza Committee of the Advisory Board this was not the first time that Pfeiffer’s bacillus had appeared in the armies. On the contrary, it had frequently been found in cases of bronchopneumonia, especially during the winter of 1916–1917. It is doubtful, however, whether much importance, from the epidemiologic point of view, attaches to these sporadic findings of the Pfeiffer bacillus.

Influenza was reported in the year 1917, but this year, as well as the epidemic of 1916, becomes involved in a determination of the date of onset of the great pandemic of 1918.

THE PANDEMIC OF 1918.

The date and site of onset of the great pandemic are subjects concerning which there is no conclusive information. There have been small outbreaks of clinical influenza with epidemic tendencies at one place or another during nearly all of the intervening years since 1889. In all of them the question is open as to whether they were true influenza, and also assuming that some were true influenza, how many of them should be so included. There are some who believe that the increase of morbidity following the measles epidemic in the United States Army camps in the winter of 1917–18 is genetically associated with the great pandemic. In short, there is no one point in the last few years at which we may say that influenza which had previously been non-existent started at a focus and spread throughout the world.

It follows from the experience of 1889 that we should at least attempt to find an endemic focus and to follow the progression of the disease. It is safe to say that once having become pandemic the disease spread as it did thirty years previously. Experience in this country, where the autumn spread began in the New England States and continued West and South; knowledge of the late spread to remote localities; the fact that the disease first appeared in England, etc. in sea coast towns; the introduction of the influenza into new countries at seaport towns, after the arrival of infected ships, all coincide well with the past history.

But which of the several local epidemics of the preceding years was the direct progenitor of the great pandemic? In order to follow more clearly the development of the facts we will record here the various hypotheses that will come up for consideration as to the site of origin of the disease.

1. Influenza is endemic in some one locality, such as Turkestan in Asia, from which place the disease spreads throughout the earth at intervals, after having acquired in some way greatly increased virulence. The local outbreaks of interepidemic times are not due to the virus which causes the great pandemics and should be called pseudo-influenza in contrast to influenza vera. Following the pandemic it is true, however, that for a succession of years local outbreaks occur, due to the pandemic virus which has been left deposited in small endemic foci. These disappear in the course of a few years.

2. The second hypothesis is similar to the first, except that in it is considered the possibility of there being more than one endemic focus, at least two, one in the old world and one in the new. Although Leichtenstern believed in the first hypothesis he did not deny the possibility of the second.

“There have been in the past several well described influenza epidemics limited to North America. Furthermore true pandemics have occurred at the same time in North America and in Europe. We can suggest the hypothesis that there is a permanent endemic focus, just as in central Asia and Russia, existing in the southern part of North America. The following facts concerning the last pandemic period favor this idea.

“As early as May, 1889, influenza began in Athabasca (British North America) and in the summer of 1889, in Greenland. It is especially interesting to hear of an extensive influenza epidemic which in the middle or toward the end of December, 1889, broke out in the Northwest Territory of British North America, in Manitoba, in the Island of Vancouver, similar to that in the east of Canada and Quebec. A spread of the epidemic, which attacked Boston and New York on December 17th, to the above territories, far away and connected by very poor transportation facilities, is certainly improbable, especially in consideration of the time at which the two epidemics occurred.

“We are told that the invasion and the outbreak of influenza in these vast territories occurred at practically the same time at such widely separated places as Fort MacLeod, Saskatchewan, Prince Albert and other military posts, and furthermore in isolated Indian camps and tribes between which there was little or no communication.

“These facts also indicate that we are considering primary endemic pandemics analogous to the one which broke out in July, 1889, in Central Asia.”

3. The virus of influenza is more or less uniformly distributed throughout the world. We may say that it is endemic in many localities, as is the case with the meningococcus. Quite frequently in one locality or another the virus acquires increased virulence and causes a small local epidemic which may even spread to adjoining territories. It is possible that the virus in two or more separated localities may become more invasive simultaneously, thus causing widely separated and unrelated outbreaks. As a rule the virulence does not become so great as to cause a true pandemic, but at rare intervals, usually of decades, or thereabouts, the epidemic virus becomes so greatly enhanced, perhaps from passage to new territory and through non-immune individuals, that it eventually commences on its wild career around the earth. Perhaps the pandemic variety usually comes from one particular locality among the many endemic spots. Perhaps always from the same locality or perhaps at times even simultaneously from many different ones. It is possible even that an increased virulence develops simultaneously in all localities. This third hypothesis develops into a discussion as to whether the small interpandemic epidemics are true influenza or some other disease.

Again, Leichtenstern, although he does not favor it, recognizes the possibility of this theory:

“Whether the small local epidemics reported by Kormann in Coburg in 1878 and by O. Seifert in Würzburg in 1883 are the same as the true epidemic influenza is at present uncertain. Some of the complications, such as swelling of the neck glands, and especially frequently parotitis, purpura, scurvy, indicate that the epidemic in Russia, in 1856–1858, reported by Kasin, was not the true influenza.

“When W. Zülzer writes in 1886 of an epidemic in Berlin in which many thousands of individuals were attacked, the question might arise, is this the same influenza which three years later passed through the entire world and which in Berlin was believed by the same physicians to be a new disease?

“The evidence is better in the case of the epidemic reported by von den Velden in 1874–75. First, because of the complication with pneumonia and especially because at the same time the disease sprang up in several places in France, South Germany and the Rhine Provinces. It is very doubtful whether epidemics described in 1855 and 1862 in Iceland, in 1870 in Philadelphia, in 1875 in Scotland, in 1876 in the Fiji Islands, in 1887 in several places of England, in October, 1889 in Natal, in November, 1889 in Jamaica and Prince Edward Island, was the true influenza, even though the complications of pneumonia in the last named epidemics favor this assumption. As regards the influenza epidemic which attacked specially the school children of Pleshey and Great-Waltham and from which fifty per cent. became ill in November and December, 1889, whereas the pandemic was known to have begun there in January, 1890—the high percentage of school children that were attacked renders the conclusion that this was influenza very doubtful.

“It is an entirely different matter concerning the last epidemic in which the epidemiologic compilations, based on retrospective diagnoses suggest that in many places of Germany the ‘first case’ of even small epidemic outbreaks was observed as early as the summer and autumn of 1889; in other words, several months before the outbreak of the true pandemic in December.”

Leichtenstern believed that the so-called catarrhal fever and epidemics of “cold” which some have been accustomed to call grip or influenza are not the true disease, although he admits that there is no pathognomonic sign by which the diseases may be differentiated. He expected that search for the influenza bacillus which had recently been discovered would enable investigators to determine by its presence or absence whether or not these local epidemics are true influenza.

This, of course, would depend on the proof that the influenza bacillus is the cause of the disease. If the many local influenza outbreaks which Hirsch has collected in his exhaustive historical tables are the same disease as true influenza, then the picture of influenza must be considered as rather protean. Leichtenstern adds that this is a possibility which from present information we cannot deny. He writes: “If such is the case we must give the following epidemiological definition of influenza: Influenza is a specific, infectious disease usually occurring epidemically which, however, is endemic over the entire earth, as indicated by outbreaks of cases, and which, after years and decades have passed, breaks out in epidemic proportions. It is recognized nearly every year in one or another place on the earth where it becomes epidemic. From time to time from some point or center, or from several points, as for instance simultaneously in the old and new world, and for reasons unknown to us, an enormous increase in virulence of the specific virus occurs and with it a great increase in the contagiousness of the disease. Those are the times when influenza spreads in mighty epidemics over wide stretches of land and portions of the earth, or over the whole earth. Our common epidemic influenza or grip, occurring practically isolated or in very small outbreaks, belongs to the same type of disease as the pandemic variety, but is due to a mitigated form of the causative organism, one of decreased virulence and of shorter viability.

“Provisionally, however, we will hold until the proof has been obtained by bacteriological methods that influenza nostras and influenza pandemica are two entirely different diseases, just as are cholera nostras and asiatica. Accordingly, we will divide the diseases designated as influenza in the following way:

“1. Influenza vera, caused by the Pfeiffer bacillus.

“2. The endemic-epidemic influenza vera which arises from the germ remaining after the spread of the influenza pandemic and which is caused by the same germ, the bacillus of Pfeiffer. The duration of this endemic state of influenza vera may last years in single localities.

“3. The endemic influenza nostras, or pseudo-influenza or catarrhal fever, commonly called grip, a disease sui generis. The germs causing this disease are at present as little known as are those of cholera nostras.”

Parkes, in 1876, recognized these possibilities: “The exact spot has not been made out. Two opinions prevail. First, one focus; second, many foci. Each nation, in turn, attributes the disease to its neighbor and from the names so given one can follow the direction of the epidemic.” Noah Webster believed that in 1698, 1757, 1761 and 1781 it originated first in America. Hirsch believed that some of the epidemics had probably originated in North America.

We find then that after the pandemic of the last century the same epidemiologic questions had arisen that have come into such prominence during the present period. As a rule those who have quoted the epidemiologists of 1890 to 1900 have mentioned the first hypothesis and have failed to allude to the fact that the other two were considered. So we see that the subject was by no means settled even at that time, and that if we should discover that the 1918 pandemic cannot be traced to a single endemic focus our results will not be absolutely contradictory to those of the last century.

Returning to a consideration of the period 1916–1918, we observe from reference to Frost’s diagram that in the spring of 1918 there was a sharp and general rise in mortality from influenza and pneumonia. Frost reports that in the larger cities on the Atlantic seaboard this increase occurred generally during January, February and March, when pneumonia mortality normally reaches its maximum. The increase was not so evident in all these cities as it was in New York City. In the rest of the country, especially in the Central and Western States, the increase occurred in April, a month during which pneumonia mortality is generally on the decline, and was sufficient to constitute an unmistakable departure from the normal. The increased mortality rate extended quite generally into May and in some areas still longer. This is the first increase after 1916 that is pictured in the mortality statistics for the country at large.

There are some who believe that they saw influenza in mild form in the United States army in the year 1917. V. C. Vaughan has investigated this possibility and from a study of the sick and wounded charts decided that there was no relation between influenza and the pneumonia which was prevalent in 1917, and which usually was secondary to measles, being caused by the streptococcus in the majority of localities. The lack of association between influenza and pneumonia in 1917 and the direct association in 1918 is well brought out by a comparison of the figures in the two following charts, prepared by V. C. Vaughan:

Pneumonia as a Sequel to Respiratory Diseases. (All troops in United States in 1917.) ─────────────────┬─────────────────┬─────────────────┬───────────────── │ │ No. of cases │ Per cent. of Primary diseases.│ No. of cases. │ followed by │cases followed by │ │ pneumonia. │ pneumonia. ─────────────────┼─────────────────┼─────────────────┼───────────────── Measles │ 47,573│ 2,075│ 4.37 Scarlet Fever │ 1,966│ 54│ 2.75 German Measles │ 8,982│ 39│ 0.43 Bronchitis │ 41,233│ 20│ 0.049 Influenza │ 32,248│ 19│ 0.059 Meningitis │ 1,027│ 13│ 1.27 Tonsillitis │ 43,021│ 7│ 0.016 Pulmonary │ 6,799│ 6│ 0.088 tuberculosis │ │ │ Laryngitis │ 4,633│ 2│ 0.043 Diphtheria │ 1,163│ 1│ 0.086 Mumps │ 21,725│ 0│ 0.000 Pharyngitis │ 8,096│ 0│ 0.000 ─────────────────┴─────────────────┴─────────────────┴─────────────────

Influenza and Pneumonia in Last Four Months of 1918. Number of cases of influenza 338,343 Number of cases of influenza followed by pneumonia 50,700 Number of deaths from influenza-pneumonia 17,700

Stallybrass, who has studied the influenza and pneumonia deaths in Liverpool, England, since the 1889 pandemic, states that in every year there had been reflected in the curves evidence of periodic increase in deaths from influenza and pneumonia, and he states that from 1914 onward there has been a progressive increase in the annual number of influenzal deaths with the single exception of 1917.

It becomes evident that we cannot with the information at hand find any one locality in which the disease was prevalent sufficiently ahead of the pandemic and to the exclusion of other localities, so that we might determine accurately the site of origin. The next step will be, then, to discover as accurately as possible the date at which various communities were first definitely attacked by the great pandemic, and to search out the locality first affected.

DATE OF FIRST INCREASED PREVALENCE IN VARIOUS LOCALITIES.

From table II which gives the earliest recorded dates of increased prevalence in different localities, we can gain a fairly accurate idea as to the direction and manner of spread of the disease during the pandemic. Influenza was first noticed in the United States early in March, 1918. By the end of the month it had become more disseminated in very mild form over many of the States east of the Mississippi and a few West of that line. The following month the disease appeared in France. In the American Expeditionary Forces in France it first appeared at the base ports which were receiving troops from the United States. During this month the disease had reached the allied Western front, the German front had become infected and probably the disease had started on its travel inward into enemy country. In May the disease was reported present in Scotland, Spain, Greece and Egypt. In June England became infected, as also Switzerland, Germany, Austria and Norway. In this month the disease had reached as far as South America and India. In China, on the 15th of June, there was reported an epidemic of a disease resembling dengue which affected fifty per cent. of the population in Chefoo and Shanghai. This disease may well have been influenza. During July the disease had spread through Germany, appearing according to German reports in the cities toward the West earlier than in Berlin and other more Eastern cities, including Vienna. In July the disease was present in other countries of Europe and was again reported in China and India.

TABLE II. The spread of influenza in 1918. ═══════════╤════════════╤═════════════╤═══════════════╤════════════════ Month. │ Date. │ Country. │ City. │ Authority │ │ │ │ quoted. ───────────┼────────────┼─────────────┼───────────────┼──────────────── March │ │China │ │McNalty, │ │ │ │ Carnwath. │ │Japanese Navy│ │McNalty, │ │ │ │ Carnwath. │ │Japan │ │Jour. Am. Med. │ │ │ │ Assn. │ │ │Civilian │ │ │France │ Population at│MacNeal. │ │ │ Chaumont │ │ 5│United │ │ │ │ States │ │ │ │Kansas │Camp Funston │Opie. │ │Missouri │Kansas City │V. C. Vaughan. │ │Illinois │Chicago │Frost. │ │Ohio │Columbus │V. C. Vaughan. │ │Michigan │Detroit │V. C. Vaughan. │ 18│Georgia │Camp Greenleaf │V. C. Vaughan. │ │ │Atlanta │V. C. Vaughan. │ 28│S. Carolina │Camp Sevier │W. T. Vaughan. │ 30│Kansas │Haskell │Public Health │ │ │ │ Reports. ───────────┼────────────┼─────────────┼───────────────┼──────────────── │ │United │Various points │Public Health April │ │ States │ from Norfolk │ Reports. │ │ │ to Louisiana │ │ │Mississippi │Camp Shelby │V. C. Vaughan. │ │Georgia │Camp Hancock │Forbes and │ │ │ │ Snyder. │ 30│California │San Quentin │Stanley. │ │ │ Prison │ │ │France │ │Netter. │ │ │ │Chauffard. │ │ │ │Messary. │ │ │ │Longcope. │ │ │Brest (American│ │ 1│ │ Expeditionary│V. C. Vaughan. │ │ │ Forces) │ │ │ │British │ │ │ │ Expeditionary│Carnwath. │ │ │ Forces │ │ │ │Allied Western │Public Health │ │ │ Front │ Reports. │ 1│ │German Western │Gins. │ │ │ Front │ ───────────┼────────────┼─────────────┼───────────────┼──────────────── May │ │France │Chaumont │Zinsser. │ │Scotland │Glasgow Dunlop,│Carnwath. │ │ │ │Office │ │Spain │Madrid │ International │ │ │ │ d’Hygiène │ │ │ │ Publique. │ │Greece │Athens │Filtzos. │ │ │ │Teissoniere, │ │Macedonia │French Army │ Beguet and │ │ │ │ Jolly. │ │ │Egyptian │ │ │Egypt │ Expeditionary│Benjafield. │ │ │ Forces │ │ │Italian │ │MacNeal. │ │ Navy │ │ ───────────┼────────────┼─────────────┼───────────────┼──────────────── June │ │England │Portsmouth │Carnwath. │ 15│ │Birmingham │Public Health │ │ │ │ Reports. │ 1│Switzerland│Zürich │Office │ │ │ │ International │ │ │ │d’Hygiène │ │ │ │ Publique. │ 1│Germany │Frankfurt, A. │Deutsche. med. │ │ │ M. │ Wehnschr. │ 3│ │Strasbourg │Rose. │ │ │ (Alsace) │ │ 25│ │Bonn │Koepchen. │ At the end │ │{Berlin │Deutsche. med. │of the month│ │ {North & │ Wehnschr. │ │ │ South Germany│ │ Late│Austria │Vienna │Bohm. │ 15│Norway │Christiania │Public Health │ │ │ │ Reports. │ 15│China(?) │Chefoo │Public Health │ │ │ │ Reports. │ 16│Brazil │Santos │Public Health │ │ │ │ Reports. │ 22│India │Bombay │Public Health │ │ │ │ Reports. │ │Porto Rico │ │Atiles. │ │Philippine │ │Hernando │ │ Islands │ │ │ │ │ │ ───────────┼────────────┼─────────────┼───────────────┼──────────────── July │ 1│Germany │Dresden │Schmorl. │ │ │ │Office │ │Italy │ │ International │ │ │ │ d’Hygiène │ │ │ │ Publique. │ 13│Sweden │Malmo │ │ │ │Gothenburg │Frost and │ │ │ │ Sydenstricker. │ Late 27│Netherlands│Flushing │Public Health │ │ │ │ Reports. │ │China │Chungking │Public Health │ │ │ │ Reports. │ │India │Calcutta │Malone. ───────────┼────────────┼─────────────┼───────────────┼──────────────── August │ │India │Punjab │Jour. Am. Med. │ │ │ │ Assn. │ 3│West Indies│Guadeloupe │Public Health │ │ │ │ Reports. │ │United │Boston │Second Spread. │ │ States │ │ ───────────┼────────────┼─────────────┼───────────────┼──────────────── September │ │Denmark │ │Frost and │ │ │ │ Sydenstricker. │ 11│Republic of │ │Public Health │ │ Salvador │ │ Reports. │ 16│Honduras │ │Frost and │ │ │ │ Sydenstricker. │ 25│Bermuda │ │Frost and │ │ │ │ Sydenstricker. │ 30│Jamaica │ │Frost and │ │ │ │ Sydenstricker. │ │Mexico │Santa Cruz │Frost and │ │ │ │ Sydenstricker. │ 21│Canada │Victoriaville │Frost and │ │ │ │ Sydenstricker. │ │ │Quebec │ │ │ │Hamilton │ │ 30│Portugal │Lisbon │Public Health │ │ │ │ Reports. │ 28│Morocco │Tangier │Frost and │ │ │ │ Sydenstricker. │ 14│South Africa│ │Frost and │ │ Union │ │ Sydenstricker. │ 16│Senegal │Dakar │Public Health │ │ │ │ Reports. │ 16│Sierra │Freetown │Public Health │ │ Leone │ │ Reports. │ │Korea │ │Schofield. │ │United │West and South │ │ │ States │ from Boston │ ───────────┼────────────┼─────────────┼───────────────┼──────────────── October │ Early│Alaska │ │Governor’s │ │ │ │ Annual Report. │ 1│Russia │Archangel │Frost and │ │ │ │ Sydenstricker. │ │Peru │Lima │Soldan. │ │Uruguay │Montevideo │Frost and │ │ │ │ Sydenstricker. │ 25│Venezuela │ │Frost and │ │ │ │ Sydenstricker. │ 11│Guatemala │ │Frost and │ │ │ │ Sydenstricker. │ 12│Costa Rica │Limon │Frost and │ │ │ │ Sydenstricker. │ 26│Colombia │Begota, │Frost and │ │ │ Barranguilla.│ Sydenstricker. │ │ │Cartagena, │Frost and │ │ │ Peru. │ Sydenstricker. │ 9│Cuba │Camagney, │Frost and │ │ │ Nuevitas │ Sydenstricker. │ 22│Azores │ │Public Health │ │ │ │ Reports. │ 18│Canary │ │ │ │ Islands │ │ │ 19│Madagascar │ │Frost and │ │ │ │ Sydenstricker. │ 17│Australia │ │Frost and │ │ │ │ Sydenstricker. │ 19│New Zealand│ │Frost and │ │ │ │ Sydenstricker. │ │Hawaii │Honolulu │Frost and │ │ │ │ Sydenstricker. ───────────┼────────────┼─────────────┼───────────────┼──────────────── November │ │British │ │Rose. │ │ Guiana │ │ │ │Dutch │Paramaribo │Frost and │ │ Guiana │ │ Sydenstricker. │ 22│Samoa │Apia │Frost and │ │ │ │ Sydenstricker. │ │Arabia │Aden │Frost and │ │ │ │ Sydenstricker. │ │Iceland │ │Erlendsson. ───────────┼────────────┼─────────────┼───────────────┼──────────────── December │ │Paraguay │Paraguay, │Frost and │ │ │ Asuncion │ Sydenstricker. │ │Dominican │La Plata, │Frost and │ 19│ Republic │ Puerto Plata,│ Sydenstricker. │ │ │ Santo Domingo│ │ │Lapland │ │Macklin. │ 8│Society │ │Frost and │ │ Islands │ │ Sydenstricker. │ 3│Tonga │ │Frost and │ │ Islands │ │ Sydenstricker. │ │Fiji │ │Frost and │ │ Islands │ │ Sydenstricker. ───────────┴────────────┴─────────────┴───────────────┴────────────────

During its course through Europe influenza had developed a greatly heightened virulence and toward the end of August it again appeared in the United States apparently traveling in a reverse direction from that of its first spread and, entering the country at Boston, it spread to the West and South until the entire country was covered. The West Indies were invaded early in August and in the same month the disease had spread through India as far as the Punjab. In September the epidemic continued through the West Indies, attacked Mexico and Canada, and had attained such remote localities as the South Africa Union, Senegal and Korea. In October the spread was particularly distributed through South America, and in this month again remote localities such as Alaska, New Zealand, the Hawaiian Islands, Australia, and Madagascar were reached. Islands, which although not very remote, were isolated except for the arrival of occasional ships, such as Cuba, the Azores and the Canary Islands, were first reported attacked in October. In November the spread continued throughout the world, and among the more remote localities should be mentioned Samoa, Arabia, Iceland. In December, Lapland, the Society Islands and the Fiji Islands were invaded (see Chart XI).

CHART XI.

Cinematogram showing the spread of influenza in 1918 from a presumptive primary focus in the United States. ]

It is particularly of interest to follow the spread of the disease in Europe. Perhaps the chief characteristic is the distribution equally to the north and south of France, a country which appears to have been invaded early. In May it spread to Scotland and to Spain, Greece and Egypt. In June the spread was in three directions, to England and Norway on the North, to Switzerland, Germany and Austria on the East, and again into Spain and Italy on the South.

The correctness of the foregoing description of the spread of influenza depends first, upon the accuracy of the authorities quoted, and particularly upon our having discovered the earliest report for each country. The author believes that the information as obtained for the United States represents nearly the true state of affairs, and that the error present is negligible. The information obtained for France is based upon the statements of excellent investigators, Netter, Chauffard and Massary, for the French population, and MacNeal, Zinsser and Longcope, for the American Expeditionary Forces. Here the statements agree both for the military and for the civil population that there was no widespread influenza in France much before April 1st. Also, the author feels that the information for England and Scotland is authoritative and will not later be changed. It is based particularly upon the excellent reports by Carnwath, who has investigated the subject in great detail. The excerpts from the German literature, although not abundant, are practically unanimous in agreeing as to the date of invasion in Germany. The reports from the remaining countries of Europe have been less abundant, and frequently the author has been forced to rely upon a report by only one individual; but while the date may be in error, yet the month of occurrence is probably correct.

For other continents, Asia, Africa and South America, the reports as far as they go appear reliable, but it is impossible to prove that at an earlier date there was not a very mild epidemic in some one of these localities, similar to the earlier epidemic in the United States, which escaped detection. It is particularly important, in view of the 1889 experience, that we obtain if possible fuller information on the earliest time of the appearance of the disease in China and other parts of Asia, and that we determine whether there was a spread from that continent to America previous to March, 1918.

Several factors have added considerably to the difficulty in tracing the site of origin of the 1918 epidemic and its direction of spread. The principal of these have been the speed of modern travel, the character of modern commerce, and the existence of a state of war. The channels of the commerce of today radiate nearly from all points to all other points of the civilized world. No longer are there a few preeminent lanes of travel, such as there were in 1580 when the epidemic spread clearly from Constantinople to Venice and on to Hungary and Germany, finally finding its way to Norway, Sweden, Denmark and Russia. The war has made it difficult to know accurately the date and direction of spread in enemy countries. We have practically no information, except that in the public press, from Russia and the Balkan States. By October of 1918 the severe form of the disease had become prevalent in every continent, and by December it had reached the farthest islands of the Southern Pacific ocean.

The apparent difference in the direction of spread between 1889 and 1918 makes comparison of rapidity difficult. But if we take as our starting point the time at which each epidemic became prevalent in commercial centers of Europe and the time at which it finally reached localities well off the usual paths of commerce we will see that there is some difference, the disease spreading more rapidly in the recent epidemic, but that the difference is no greater than could be accounted for by the more modern means of communication. From April, 1918, when the disease appeared in France, to October, when it was reported in Madagascar, is six months. From October, 1889, with the disease prevailing in Petrograd, to July, 1890, when it appeared in Madagascar, is nine months. It required seven months after the disease became epidemic in France this time for it to appear in Iceland, and nine months in 1889–90.

The earliest recorded epidemic of influenza in the United States in the spring of 1918 (but which was not recognized to be such until later) appears to have been that at Camp Funston, described by Opie and his associates as having appeared in that Camp March 5th. The epidemic swept quickly throughout the Camp and spent itself as rapidly. A second wave appeared in April and in May a third, both of which were almost entirely limited to newly drafted men brought into camp subsequent to the preceding outbreaks. Correlated with each of these three outbreaks was a period of increased incidence of pneumonia and bronchitis, frequently occurring in influenza cases. These complicating diseases were prevalent in the organizations attacked by the influenza and maintained the same relation to the length of service of the men affected.

The next report of influenza in the United States was from the Oglethorpe camps, beginning about March, 18, 1918. Within two weeks every organization in Camp Forrest and the Reserve Officers Training Camp was affected. After about three weeks the epidemic subsided rapidly. Fourteen hundred and sixty-eight cases were sent to the hospital out of a total strength of 28,586. It is estimated that 2,900 cases had occurred. The clinical symptomatology and the epidemic characteristics were described in detail.

On March 28th the author had occasion to observe a similar epidemic at Camp Sevier, South Carolina, which appears to have attacked a smaller proportion of the troops in camp, but which showed the same epidemiologic picture. A note in the Public Health Reports states that on March 30, 1918, the occurrence of eighteen cases of influenza, of severe type, from which three deaths resulted, was reported at Haskell, Kansas. This is the earliest report we have been able to find concerning the disease in civil communities. That for Chicago was practically contemporary. The Commissioner of Health of Chicago states in his special report on the autumn epidemic, that in March, 1918, distinct epidemics resembling influenza were observed in certain portions of that city.

According to Public Health Reports, fevers of an undetermined nature were reported during April and May at various points from Norfolk to Louisiana. “An examination of the records and reports of the physicians who had treated these cases leads to the belief that these fevers were mainly influenza of mild type.” It is possible, however, that all cases reported were not of the same disease, and in one locality in Louisiana dengue may have occurred.

Fleisher states that during the latter part of March and early part of April, 1918, there occurred at Camp Wadsworth an epidemic of measles and practically concomitant with it an epidemic form of bronchopneumonia associated with empyema. During this time there were some 200 cases of measles and twenty-one cases of bronchopneumonia or empyema in which a hemolytic streptococcus was the causative agent. He makes no mention of any epidemic of influenza either in mild or severe form, occurring at this period.

Forbes and Snyder reported that during the month of April, 1918, a highly contagious, but comparatively mild infection of the respiratory tract was epidemic in Camp Hancock. Several thousand men in the command were infected, but relatively few were ill enough to be sent to the hospital. The only fatal case occurred early in the epidemic, and it was the observations made in this case which prompted the study made by Forbes and Snyder.

The fatal case had the subjective symptoms familiar to influenza. The physical findings were similar to those occurring in influenza in the later epidemics. The leucocyte count was 4,300. A blood culture showed in twenty-four hours a heavy growth of small non-motile, gram-negative bacilli which the authors concluded to be Bacillus influenzae. The leucocyte counts made at five hour intervals on a later date were respectively, 3,400, 2,200 and 2,300. A second blood culture taken on April 10th, a day later, also showed a pure culture of the same organism. The leucocyte count had risen to 5,600. At necropsy a confluent bronchopneumonia was found. There was no pleural effusion and the other viscera showed nothing remarkable. Bacillus influenzae was recovered from cultures taken from the lung and spleen.

Throughout this epidemic the clinical picture of the disease was characteristic. Nearly every patient gave as the initial symptoms backache, headache, slight cough or sore throat. Conjunctivitis and a marked injection of the soft palate were noted in ninety per cent. of the cases. In addition, a slight or moderate general adenopathy was often observed. The face was flushed and in a few cases the skin of the thorax presented a mild erythema. In three cases a provisional diagnosis of scarlet fever was made until the blood count showed a leucopenia. Leucopenia was characteristic of all cases.

During the early April epidemic at this camp, nasopharyngeal cultures showed an organism resembling Bacillus influenzae in seventeen out of thirty-three cases, but the identity of the organism was not established by subcultures. In ten cases in which sputum examinations were made, Bacillus influenzae was found in only four; streptococci were present in six. Blood cultures on twenty consecutive non-fatal cases, only one of which was complicated by bronchopneumonia, were all negative.

V. C. Vaughan reports that at Camp Shelby, Hattiesburg, Miss., there was in April a division of troops numbering about 26,000. An epidemic of mild influenza struck this camp in April, 1918, and within ten days there were about 2,000 cases. This included not only those who were sent to the hospitals, but also those who were cared for in barracks. This was the only division that remained in this country without change of station from April until the fall of 1918. During the summer this camp received 20,000 recruits. In October, 1918, the virulent form of influenza reached this camp. It confined itself almost exclusively to the recruits of the summer, and scarcely touched the men who had lived through the epidemic of April. Not only the 2,000 who had the disease in April, but the 24,000 who apparently were not affected, escaped the fall epidemic.

Vaughan also remarks that in March and April of 1918 there was an unusually high death rate from pneumonia in Atlanta, Ga., Kansas City, Mo., Detroit, Mich., and Columbus, Ohio, while in the autumn epidemic these cities suffered rather less than the average. In view of the experience at Camp Shelby he reasons that there was probably mild influenza in these cities in March and April of 1918. It may be stated that in the mortality statistics for 1918, the abnormally high death rates for respiratory diseases during March and April were present throughout the registration area of the United States.

The first reports that we have been able to discover concerning influenza on the Pacific Coast are for the month of April. Stanley reports three successive waves of epidemic influenza at San Quentin Prison, Cal. The first began on April 30, 1918, with the entrance into the institution of a prisoner who was sick on admission.

Following the disease in its possible spread to the next continent we are inclined to conclude that it was carried to France with the great body of men traveling to that country from the United States. MacNeal and Longcope both report that in the first outbreak in the American Expeditionary Forces the earliest recorded epidemic appeared about April 1, 1918, in a rest camp near Bordeaux. It reached its height April 22d and ceased May 5th. According to V. C. Vaughan a mild epidemic of influenza and pneumonia prevailed at Brest and in that vicinity from April 1st to July 31st, 1918. During this time fifty cases of influenza, twenty-six of which developed pneumonia, with two deaths were admitted to the United States Naval Base Hospital at Brest. The disease was prevalent at the same time among the French civil, military and naval groups in the same locality. We see then that in the American Expeditionary Forces at any rate the disease first occurred in two base ports receiving troops from the United States. In May, 1918, a second outbreak was reported from Tours, which lasted from May 1st to May 24th and affected 117 persons. Zinsser reports an epidemic at Chaumont during May and from this time until July more or less extensive epidemics occurred throughout the entire American Expeditionary Forces.

Longcope remarks that the disease was likewise prevalent at this time among the French population and in parts of the British Army. The Influenza Committee of the British Advisory Board determined that in the first British Army the disease became prevalent around May 18th. Carnwath states that in the British Army in France the epidemic began by a few local outbreaks in the first and second Armies in April and May, 1918. Later it spread to the first, third and fourth Armies and affected a very large proportion of the troops.

Small describes two epidemics of influenza in one of the largest General Hospitals of the British Expeditionary Force in France. He says that the first wave began in April, 1918.

The fact that MacNeal, as we have previously recorded, believed that there was influenza in France in 1917, must not be overlooked. Those earlier cases were scattered and did not so far as we know occur in the form of small epidemics. Even if these were true influenza it is reasonable to assume that they were sporadic cases and were not genetically associated with the epidemic spreading from America and daily increasing in virulence, which we are now following. MacNeal concludes that epidemic influenza in France originated from the endemic foci existing there, and that the disease was probably carried from Europe to the United States by shipping. The author’s opinion regarding the first direction of spread is that the reverse condition was the actual process. Zinsser likewise holds the latter view.

A most important observation made by MacNeal is that French physicians practicing among the civilian population were perfectly familiar with the disease when it appeared at Chaumont in April, 1918, that they designated it as La Grippe, and stated that it had been extensively prevalent in the civilian population of Chaumont from March 15th to May 15th, 1918. These observations of influenza occurring in France at almost the same date as the first outbreaks in the United States is a matter of great interest. It has also been stated by McNalty and by Carnwath, who quotes Kabeshima and Lee, that the disease was prevalent in epidemic form in China and Japan in March, 1918. We have here three foci from which the disease may have primarily originated. There are two possibilities; first, that it originated in all three foci (and perhaps others), and spread to all parts of the world from each; second, that the virus, distributed throughout the world, acquired high virulence in all three localities, causing small epidemic outbreaks, but that the virus from only one of these places finally became so exalted as to cause the pandemic. Did the pandemic disease originate simultaneously in France, in China and in the United States? One fact seems certain, that the influenza which attacked our troops in Europe was influenza imported from the United States. We have seen that it first appeared in the American Expeditionary forces at the base ports. Alberto Lutraria, Health Commissioner of Italy, has reported that the disease was brought to that country from America. A point of significance is the fact that during March and April there was an unusually large troop movement from the United States to the American Expeditionary Forces.

MacNeal says: “The suggestion that the epidemic was introduced from America is supported by the fact that it appeared at a time when large numbers of Americans were arriving in Europe, which is indeed an outstanding feature correlated in time with the onset of the epidemic.”

According to the report of the Influenza Committee, the disease was first seen in epidemic form in April and May in the British Armies in France, but that was not the first time that Pfeiffer’s bacillus had appeared within the armies. It had frequently been found in cases of bronchopneumonia, especially during the winter of 1916–17. Carnwath remarks that it is doubtful whether much importance from an epidemiologic point of view attaches to these sporadic findings of the influenza bacillus. In an outbreak of measles and rubella—complicated by purulent bronchitis—which attacked men belonging to the draft of troops from New Zealand between January 1st and March 8th, 1918, the bacillus influenzae was present in twenty-four of the forty sputa examined, and was grown in culture in twenty-one cases. Sellards made somewhat similar observations on measles patients at Camp Devens.

Concerning the French population, Chauffard, Messary and Netter, all remark that the first cases in France developed in April with possibly some cases before that time, and that there were undoubtedly cases in the German Army in April.

We see then that by April the disease has been transferred to France and is prevalent in the various armies. It is natural to assume that the battle front would present no great obstacle to the spread of the disease into the German Army. Gins remarks that the disease was present on the German West front among the troops as early as April, 1918, and that it spread from there more rapidly to the South than to the North.

During the month of May we observe the spread of the disease to Great Britain, where Carnwath, who has made an exhaustive study of the spread in Great Britain, believes that it was imported by the troops from France. Its first recorded appearance in Glasgow was in May. Dunlop, in reporting the successive epidemics in Scotland, observed that in addition to the three well marked epidemics there was a mild one recognizable in Glasgow in May, and that in that city the death rate rose from 14.1 to 20.1, and the weekly number of deaths from pneumonia and bronchitis from 36 to 107.

In England the disease first attracted attention in June, appearing first in the coast towns, chiefly at the beginning among the military and naval forces. The civilian population was severely affected only later. The ports which were earlier attacked were Portsmouth, Southampton and Liverpool. Inland towns suffered more severely later.

In the same month that the disease broke out in Scotland it appeared in Spain. The Inspector General of Health in that country reported that an epidemic of the disease began at Madrid in the last half of May, 1918, at a period when there was an unusually large gathering of people in the city. Within a short time it had spread rapidly through all the provinces. The increase in death rate became marked on the 27th of May and reached its peak on the 31st, at which time the rate was twice that of the average annual death rate for that period of the year. During the following week there was some oscillation around the peak and then the curve fell away. The epidemic was particularly severe at Madrid, Badajoz, and Seville. It was mild at Barcelona.

MacNeal remarks: “In Spain the disease appeared in epidemic form about the middle of May and this outbreak received great publicity, sufficient to lead to the popular appellation of Spanish influenza. The very rapid and extensive spread of the disease in Spain would indicate that it had been introduced from without rather than transformed from the endemic state in that country. This also appears to accord with the view of those who have studied the epidemic in Spain.”

Filtzos reports that influenza first appeared in Greece toward the end of May, 1918. The symptoms were slight and the people who were attacked suffered for three or four days with fever, accompanied by nervous symptoms. It was called at the time “Spanish Fever”. Beginning with September the epidemic became worse and caused a considerable rise in mortality. Complications with bronchopneumonia appeared. The decrease in incidence began toward the middle of December, 1918.

According to Benjafield, the pandemic first commenced in the Egyptian Expeditionary Force in May, 1918, but the maximum incidence was not reached until September and October. The cases during the earlier period of the epidemic were on the whole mild in type and of short duration, only a very small proportion being complicated by bronchopneumonia. The epidemic continued from November, through February, 1919, but the number of cases showed a marked decrease during the last two months.

The month of June saw the spread into England which we have already described, and the continuation from the German West front back into the enemy territory.

Rose reports that on the 3d of June, 1918, in Strasbourg the first cases of influenza were reported in his hospital and that by the 15th of the month the disease was practically epidemic. Wachter in reporting cases from Frankfurt a. M. says that the cases of influenza in that city appeared from the beginning of June, 1918. Schmorl remarks that influenza became epidemic in Dresden in the beginning of July, 1918. According to Koepchen, the disease was epidemic in Bonn the 25th of June.

An editorial comment in the Deutsche medizinische Wochenschrift, July 4, 1918, remarks that the influenza pandemic “which probably has spread from Spain in the last few days” has appeared in several places in Germany in the South and the North, and in Berlin. According to the information received up to that time the disease was of short duration and without severe complications. The issue of July 11th reports that the influenza epidemic appears to have already passed its peak in Berlin and that in Süddeutschland the spread of the epidemic has become very wide.

The Office International d’Hygiène Publique records that the pandemic spread throughout Switzerland towards the end of June, 1918, after having invaded a certain number of European states, coming from various army fronts. It was at first of mild severity.

Böhm states that the deaths from pneumonia and influenza in Vienna began to show an increase in the week ending July 30th. In August they returned to the normal rate. The second wave occurred in Vienna in the middle of September.

From the information at our disposal we are unable to determine from what direction the pandemic entered either Switzerland or Austria. The point of entry into Switzerland is of relatively little importance in tracing the spread on the continent of Europe. Presumably it entered from the north or northwest. The disease appeared in Berne in June, reaching its height in that canton in the middle of July and dying out in August (Sobernheim and Novkaovie).

Information of the place of entrance into Spain is also rather indefinite. We are told that Barcelona was one of the cities attacked early. Barcelona is situated on the Mediterranean near the French border and is quite directly connected by commerce with Marseilles and other French ports on the Mediterranean.

In June the disease had also spread to Norway and outside of Europe to the West Indies, South America, India and China. A short notice in the Public Health Reports tells us that epidemic influenza with an estimated number of 1,500 cases began in Christiania, Norway, about June 15th.

Atiles relates that influenza appeared in Porto Rico in June, soon after the arrival of a ship from Spain. It spread rapidly, and it is estimated that at one time fully eight per cent. of the entire population had the disease simultaneously, and that forty per cent. of the population were affected during the epidemic.

The Health Officer at Bombay made report in July, 1918, on an influenza-like disease then spreading throughout India. It was stated that the disease was introduced into Bombay from overseas by a transport which arrived May 31, 1918; that by June 22d the disease had become epidemic at Bombay, and that it was present in July, 1918, at Calcutta and Madras.

The rapid spread from Europe to distant India may be accounted for with the same mechanism as that by which the disease was spread from America to France and from France to England, viz. by army transports. The occurrence of the disease in Porto Rico appears to have been definitely connected with the arrival of a ship from Spain. A very short notice in the Public Health Reports tells us that influenza was reported present at Santos, Brazil, June 16, 1918. We are not informed as to how it reached that place.

We have discovered no mention of influenza in China in June. It was reported present in Chungking, China, July 27th. and at that time one-half of the population was stated to be affected. Dengue was reported prevalent at Chefoo, China, during the two weeks ended June 15, 1918, and a report from Shanghai of the same date describes the prevalence of a disease resembling dengue and affecting about 50 per cent. of the population. The disease in these two latter places may have been influenza.

The epidemic made its appearance in Korea in September, 1918. Schofield and Cynn, who report the epidemic, believe that the infection came from Europe via Siberia. The disease spread from North to South along the line of the Southern Manchurian Railway.

In August the disease was re-introduced into the United States and by the end of that month it had acquired a foothold in Boston and vicinity and rapidly spread to other parts of the country. The pandemic had crossed the Atlantic in both directions in six months’ time.

In 1918 as in 1889 there are excellent descriptions of the conveyance of the disease by vessels. The transfer from Spain to Porto Rico has been mentioned. Escomel says that the outbreak in Rio de Janeiro was ascribed to infection from a steamship from Spain, the same boat which later visited Buenos Ayres and started the epidemic in the latter city.

According to a report to the Journal of the American Medical Association from Mexico the epidemic invaded that country from the North at Laredo and followed the course from North to South. From a similar source the same Journal reports that the influenza spread from Buenos Ayres as a primary focus to Paraguay and there acquired greater virulence.

Hernando reports from the Philippine Islands that influenza was estimated to have attacked forty per cent. of the total population of 7,000,000 the mortality being about 2.5 per cent. of those attacked. The epidemic really began in June, although it did not assume great severity until October. The group of ages that suffered most were those between ten and twenty-nine years. The disease did not seem to be imported, since cases were returned before any ships arrived from infected countries, although after the importation of cases it assumed a more severe form. The June epidemic seemed to confer a certain degree of immunity during the second outbreak of the disease in October.

Erlendsson reports that the influenza when it appeared in Iceland in November, 1918, corresponded in character with that in other portions of the world. Macklin gives an interesting description of the epidemic as it occurred in Lapland. The onset in that territory was probably in November. He found that many individuals recovered in two or three days and were about their work again feeling perfectly well. If, however, they contracted pneumonia, about fifty per cent. died.

“The Laplanders had a very thorough if unsympathetic way of dealing with their cases. The settlements were composed of wooden huts, small but generally well made and warm. A common type consisted of but one room, used by the family for all purposes. Better class Laps had better huts, with two or three rooms. In each settlement one of the single-room huts had been set apart, and into this each case of sickness as it arose was unceremoniously pushed; and none were permitted to return to their own huts until completely recovered. Whilst there they received practically no attention, and no healthy person ever entered to attend to their wants. Occasionally a bowl of water or reindeer milk was hastily passed in at the door, or a huge chunk of reindeer meat thrown in, uncooked and uncarved.

“We visited every settlement within our reach and entered these huts. The stench on opening the door met one like a poison blast and the rooms were nearly always ill lighted and dark. The patients lay littered about the floor in a crowded mass, fully dressed in clothes and boots (most of them had no socks), and with no other cover but an occasional greasy rug. Although the outside air was cold and the ground snow-covered, the temperature inside, maintained by the combined mass of bodies, was generally sufficiently high. The patients in these huts included both sexes and all ages; some, when we entered, sat up and with flushed faces and dull, uncomprehending eyes watched us listlessly. Others lay restlessly twisting about, quite incapable of taking any interest or of answering any questions.”

The epidemic struck Alaska in October, invading first the towns of the sea coast, being very evidently brought thither by steamer. Travel to the interior was stopped and so the latter escaped, to a great extent, the outbreak. At Kodiak and on Cook Inlet, the mortality was extremely high. Whole villages of esquimaux lost their entire adult population. Many infants were frozen in their dead mothers’ arms.

Influenza in China.—We have been able to follow the pandemic quite consecutively as it has spread around the world, from a first outbreak in the United States in March, 1918. We repeat that the disease was presumably present in Europe and elsewhere previous to that time, as it was in America, but the particular virus which ultimately acquired sufficient virulence to produce the pandemic may well be that which came from North America. Did this virus arise from an endemic focus in this continent, or was it transported to us at a somewhat earlier date from Asia?

McNalty states that influenza was present in China and in the Japanese Navy in March of 1918. He gives no reference. Carnwath makes the same statement and gives as reference the report of Kabeshima and Lee. The author has not been able to obtain this report.

The Health Officer of Shanghai made the following report for May, 1918: “Towards the end of the month, reports were received of outbreaks of ‘fever’ which rapidly affected a large proportion of the employees of various offices, shops, police stations, etc. As a result of clinical and laboratory observations of cases admitted to the Chinese Isolation Hospital the disease was recognized as epidemic influenza. The same disease was reported to have appeared in Peking before reaching Shanghai, but subsequent reports showed that most of the river ports were almost simultaneously infected; that is to say the rate of spread conformed to the rate of conveyance by railways and boats of infected persons;”

In November of 1918 an editorial note in the China Medical Journal reads as follows:

“From nearly all parts of China reports are being sent to the newspapers of the occurrence of a severe epidemic of disease which seems to manifest itself in various forms. In Wusuch, where the disease is called ‘the five days’ plague’ the symptoms are said to be not unlike those of cholera, death in some cases ensuing in less than a day. In other cases it is complicated by severe and often fatal pneumonia. At Anking many cases have all the symptoms of typhoid fever, but the mortality is great and sudden. In one house four people died within a few hours of each other, and in another house eight persons out of eleven died. At Wuhu and other of the lower Yangtze ports it is said to resemble dengue fever and the mortality is so great that undertakers are finding it difficult to meet the demand for coffins. In Shansi, where the victims literally number thousands, the disease is regarded as influenza. In Peking fully fifty per cent. of the Chinese have been affected and the mortality has been heavy. Accurate reports from medical men in these cities would be very instructive.”

The author has the following personal communication from Doctor Arthur Stanley of the Health Department of the Shanghai Municipal Council. “Influenza fever appeared during the recent epidemic in Shanghai towards the end of May 1918. It swept over the whole country like a tidal wave. You may take it that it spread like most rapid extant means of transit. A primary source of origin was not made known.”

It is to be hoped that more definite and concurrent information will be forthcoming in the case of China. A thorough search of the literature as reviewed for China and Japan in the China Medical Journal reveals no description of the disease previous to April or May of 1918. Nevertheless we must assume that, until contradictory reports are made, the disease was present in those countries in March as stated by Carnwath.

AUTUMN SPREAD IN THE UNITED STATES.

By the first of July, 1918, convalescent cases of influenza began to appear among members of the crews of transports and other vessels arriving in Boston from European ports. The number of such cases on each ship was usually not more than four or five, but Woodward records that in one or two instances between twenty and twenty-five individuals were sick on incoming vessels. None of these were seriously ill, none were sent to the hospital, and none died. The disease in this class of persons did not become severe until late August. Woodward has found on inquiry among practising physicians that typical cases of influenza were seen with notable frequency in private practice in the vicinity of Boston during the month of August, and that they had developed no serious complications, the only after effect being the marked prostration.

These mild preliminary cases failed to attract attention; first, because of their relative scarcity, and second because of their benign character. Public attention was first directed to the influenza in Boston by the apparently sudden appearance during the week ending August 28th of about fifty cases at the Naval Station at Commonwealth Pier. Within the next two weeks over 2,000 cases had occurred in the Naval forces of the First Naval District. One week later there was a similar sudden outbreak in the Aviation School and among the Naval Radio men at the Massachusetts Institute of Technology. The first death in Boston was reported on September 8th.

The peak of daily incidence in Boston occurred around the first of October. In the week ending October 5th a total of 1,214 deaths from influenza and pneumonia was reported, while by the third week of October this total had fallen to less than 600, and for the week ending November 9th was down to 47. Around November 15th the number of cases rather suddenly increased and this recurrent wave lasted for about ten days. By the 25th the rate was back to what it had been around the first of the same month. On or about December 1st the incidence again rose and continued increasing daily, to reach its peak in a severe recrudescence around December 31st.

There are conflicting reports concerning the date of first appearance of the epidemic at Camp Devens, Massachusetts. Woodward says that a sudden and very significant increase was reported during the third week in August in the number of cases of pneumonia occurring in the army cantonment at Camp Devens, seeming to justify the statement that an influenza epidemic may have started among the soldiers there even before it appeared in the naval forces. Soper, on the other hand, as well as Howard and Love in their official report, place the date of the first case at Devens as September 7th. Soper remarks: “The Devens epidemic is supposed to have commenced on September 7, 1918, in D Company, 42d Infantry. On that date a case of supposed meningitis was sent to the hospital from this company; on the following day twelve cases were sent for observation. These proved to be influenza. By the 16th thirty-seven cases had gone from the same company.” Howard and Love state, “The first authentic cases of virulent influenza of the great autumn pandemic among troops in the United States appeared on September 7, 1918, at Camp Devens, Mass.” These statements by Howard and Love do not eliminate the possibility of earlier and less virulent unrecognized cases. Wooley, who was camp epidemiologist, reports that influenza began at Camp Devens on the 8th of September, 1918. It reached its acme on the 16th, 17th and 18th of the month and then rapidly declined, almost completely vanishing about the middle of November. He makes no observation as to whether a mild form of the disease was or was not present in the camp in March and April preceding.

Influenza entered Massachusetts at Boston. Reeks reports that it entered Connecticut at New London, the cases coming primarily from the experimental station and from Fort Trumbull, where vessels from foreign ports had discharged patients. He believes that the disease was first introduced by ships arriving in New London from abroad and by men from the Boston Navy Yard, but numerous foci developed in a short period of time in various parts of the state. Many of these had appeared by the middle of September, and the source, according to Winslow and Rogers, was traced to military establishments, chiefly Camp Devens. In Wallingford, Willimantic, Hartland, Rockville and Danbury, all of which towns were attacked early in the epidemic, investigation showed that the disease developed in each case two or three days after visits of soldiers from Camp Devens. In Connecticut the epidemic spread, beginning at New London, chiefly from east to west, reaching its peak in the Eastern section around October 4th, in the central section October 15th, and in the Western part of the state around October 24th. Towns which had been infected early by visitors from military establishments reached the climax sooner than other towns nearby. In spreading from New London north and west the large cities of Connecticut were successively invaded, New Haven and Hartford reaching their crest about ten days later than New London, while Fairfield County did not reach its acme until later than New Haven.

In the cities along the New England coast we see then that the disease reached epidemic proportions early in September. By September 21st it had become epidemic in a wide area along the Atlantic coast extending from the Southern part of Maine to Virginia, as well as in a number of localities scattered over the entire country. By September 28th, areas adjacent to the centers in which the epidemic had already appeared were affected, suggesting radial movement from these centers. By that time the greater part of the New England States, the North Atlantic and Central States, and some of the Gulf and Pacific Coast States had become involved. By October 5th the pandemic had apparently reached all parts of the country with the exception of the more isolated rural districts and some areas in the Central States and Mountain States. Within an additional ten days even these areas, with the exception of the very remote rural districts, had been reached by the epidemic. Within four weeks the disease had become distributed to all sections of the country, and within six weeks from its first epidemic prevalence in Boston practically the entire country had been invaded.

Sydenstricker in a preliminary report remarks on the fact that the disease reached an epidemic stage in a number of localities in the central, northern, southern and western sections at about the same time as it did in the area along the northeastern coast. “The possibility is suggested, therefore, that sources of infection existed in at least some of the larger population centers, well distributed through the country, some time before the disease appeared as a nation-wide epidemic. The apparent radial spread of the epidemic from certain centers would seem to strengthen this hypothesis. It may also be noted that there is evidence, the collection of which has not yet been completed, pointing to the existence of cases of the disease in various centers, probably widely distributed, weeks before they were definitely recognized as influenza. The possibility that these foci themselves had a common focus is by no means excluded, of course, but there is as yet no conclusive evidence that would warrant the statement that the starting point of the epidemic was Boston or any specific locality.”

Dublin, from a study of the statistics of the Metropolitan Life Insurance Company, finds that the virulence of the influenza, as indicated by the mortality rate, was greatest along the Atlantic Coast and became progressively less as it progressed westward. There was one exception. The mortality was high in San Francisco, higher than in other western communities. Dublin believes that quite possibly there was a double infection in San Francisco in the fall of 1918, one coming from the East and of small caliber, while the other came either by way of the Panama Canal or perhaps from Asia. The evidence in favor of two ways is that Dublin finds that the peak of incidence in San Francisco and in some other places on the Pacific Coast occurred sometime in advance of the similar peak at points inland from the coast. This is not brought out in Pearl’s chart, and the latter finds when considering the peak of deaths that the peak for San Francisco was late. The peak in that city, in Oakland, California, and in Los Angeles, was reached on the week ending November 2d. Few cities had as late death peaks. Cleveland and Pittsburgh reached their peak in the same week, St. Paul, Minnesota in the week ending November 16th, and St. Louis, Milwaukee and Grand Rapids not until the week ending December 14th. In the case of Milwaukee and St. Louis these were the high peak dates but they were second peaks. In the former the first peak occurred October 26th and in the latter November 2d. In Grand Rapids the increase in mortality was clearcut by the middle of October, although the peak was not reached until the week ending December 14th. These statistics would indicate that San Francisco was attacked, as evidenced by increase in death reports, relatively late, and at about the time that would be necessary for the disease to be carried across the continent.

In an article by Ely, Lloyd, Hitchcock and Nickson it is said that influenza first appeared in the Puget Sound Navy Yard, near Seattle, on September 17, 1918, and that it was introduced by a draft of 987 sailors received from Philadelphia, a number of whom arrived ill, or came down within a few hours after reaching their destination. As a result, Seattle and the State of Washington were infected somewhat ahead of the other West Coast States. According to the record, influenza did not assume epidemic proportions in the State of Oregon for nearly a month after this Navy Yard epidemic.

With army camps and cantonments situated in nearly every section of the country it is difficult to follow the general direction of spread from camp to camp. During the period of the epidemic, troop movements were in general from West to East toward points of embarkation rather than in the reverse direction. This was in the opposite direction to that taken by the pandemic. Away from the coast there were, however, many movements of troops from camp to camp, in the redistribution of forces. That these troop movements were not discontinued during the epidemic is indicated by the report of Howard and Love: “The virulent type of influenza had spread rapidly from camp to camp, from the Atlantic seaboard to the South and West, due to the continual interchange of personnel from infected to non-infected camps. Such movements of troops at this time were recognized as dangerous and inadvisable, and prompt recommendations were made by the Medical Department that such movements be discontinued or greatly restricted, if compatible with military interests, which, of course, were at the time paramount. The War Department was unable to approve any marked restriction of movement of men from camp to camp at this time. One result of the free inter-communication of military personnel was that practically all military stations in the United States were in the throes of the epidemic at the same time.”

In addition to this means of inter-communication we had the possibility of spread to the various camps by the ordinary course of civilian and commercial travel as in spread to different communities, and also the possibility of importing large amounts of virus at one time on the incoming trains with new draft troops.

Soper gives the following order for camps attacked:

═════════════════╤═════════════════╤═════════════════╤═════════════════ Order. │ Camp. │ Location. │ Date. ─────────────────┼─────────────────┼─────────────────┼───────────────── 1│Devens │Massachusetts │Sept. 12 2│Upton │New York │Sept. 13 3│Lee │Virginia │Sept. 17 4│Dix │New Jersey │Sept. 18 4│Jackson │South Carolina │Sept. 18 │ │ │ 5│Hoboken │New Jersey │Sept. 19 5│Syracuse │New York │Sept. 19 5│Gordon │Georgia │Sept. 19 5│Humphreys │Virginia │Sept. 19 6│Logan │Texas │Sept. 20 │ │ │ 6│Funston │Kansas │Sept. 20 6│Meade │Maryland │Sept. 20 7│Grant │Illinois │Sept. 22 7│Taylor │Kentucky │Sept. 22 8│Sevier │South Carolina │Sept. 23 │ │ │ 8│Lewis │Washington │Sept. 23 8│Newport News │Virginia │Sept. 23 9│Pike │Arkansas │Sept. 24 10│Beauregard │Louisiana │Sept. 25 10│Eustis │Virginia │Sept. 25 │ │ │ 11│Greene │North Carolina │Sept. 26 11│McClellan │Alabama │Sept. 26 12│Kearney │California │Sept. 27 12│Bowie │Texas │Sept. 27 13│Johnston │Florida │Sept. 28 │ │ │ 13│Sheridan │Alabama │Sept. 28 14│Sherman │Ohio │Sept. 29 14│Dodge │Iowa │Sept. 29 14│Shelby │Mississippi │Sept. 29 15│Custer │Michigan │Sept. 30 │ │ │ 16│Travis │Texas │Oct. 1 17│Cody │New Mexico │Oct. 3 18│Forrest │Georgia │Oct. 6 19│MacArthur │Texas │Oct. 7 20│Wadsworth │South Carolina │Oct. 11 │ │ │ 20│Wheeler │Georgia │Oct. 11 20│Greenleaf │Georgia │Oct. 11 ─────────────────┴─────────────────┴─────────────────┴─────────────────

Howard and Love have established definitely that the extension of the virulent influenza from Camp Devens to other camps south and west in September, 1918, can be traced in many instances directly to the interchange of military personnel from infected to non-infected camps. The height of the September outbreak in the United States Army extended over a period of about nine weeks, from Sept. 13th to November 15th, and during this period over 20,000 deaths occurred among troops in the United States alone in excess of the number that would have occurred, if the disease death rate for the corresponding period of the preceding year had prevailed.

It is interesting to note with respect to Camp Humphreys, Virginia, that there were possibly some sporadic cases previous to the autumn outbreak. Brewer in reporting on the epidemic in September and October records the first case as having occurred shortly after July 1st. He makes no mention of there having been any outbreak whatever prior to that date. Between July 1st and September 12th there were only sporadic cases diagnosed as influenza. The autumn outbreak began at Camp Humphreys September 13th and ended October 18th.

RECRUDESCENCES.

We have already seen from the work of Pearl that recrudescences following the original spread in any one locality were the rule rather than the exception in this country. He found that in sixty-five per cent. of the forty cities studied there were two distinct peaks in the mortality curve and in twenty per cent. there were three, while only fifteen per cent. had but one peak. The first peak was as a rule the highest. Although there was no absolute regularity in the time of occurrence of the recrudescences, Pearl established that the high peak cities had the second peaks on an average 7.1 weeks after the first, and the third peak on an average 13.1 weeks after the second. The two-peak cities are divided into two classes, the first comprising about a third of the total number, had the second mortality peak around eight weeks after the first, while the remaining two-thirds had the second peak about thirteen weeks after the first. The cycle in the epidemic wave appears to be nearly a multiple of seven weeks. He suggests that the smaller group of two-peak cities with early second peak may have been cities which at the time were presumably destined to show a third distinct wave and peak of mortality, but in which for some reason not now apparent the third wave did not eventuate. In contradistinction the larger group of two-peak cities with the second peak occurring around thirteen weeks after the first are presumably cities in which the complex of factors determining the form of the mortality curve was such as to lead definitely to a two and only two-peak curve. In three-peak cities the first interval was around seven weeks, the second around thirteen weeks. The two-peak cities with an interval around thirteen were probably not destined, according to Pearl, to have another repetition, but those with an interval of seven were presumably destined to have a second interval, the thirteen-week interval, which for some reason did not occur.

This raises the question of periodicity, a subject which we will discuss at a more appropriate place.

This experience of recrudescences was similar in the American Expeditionary Forces. The first outbreak lasted through April and May and into June. The second came in September and October. The spring epidemic had been characterized by mildness and was known as three-day fever, but in the autumn, complications of the respiratory tract predominated in the symptom complex. By August 18th a severe epidemic had occurred in an artillery camp at La Valdahon in the Jura Mountains, near Bezançon. Early in September a larger epidemic occurred in an artillery camp near Bordeaux. The epidemic in our troops in France, as well as in the French civil and military population, reached its height during October. The Service of Supply was more heavily affected than were the troops situated on the battle front. The morbidity rate appeared to have been almost the same as that in the United States. That it was not quite as high has been shown by Howard and Love. Longcope states that it prevailed particularly among the troops at the base ports where during a part of the epidemic transports laden with infected troops were being landed; in those organizations which contained the largest number of replacement troops; and in organizations being moved on troop trains, where the men were necessarily closely crowded.

The second outbreak subsided during the early part of November. A third occurred in January and February, very much as it had done in the United States. In the interval between the second and third recurrences there was no time at which the entire Expeditionary Forces were free from the disease. The author had occasion to study an outbreak occurring early in December in the 26th Division stationed in rest area at Montigny-le-Roi. In this outbreak the respiratory complications predominated, as in October, and the mortality was comparatively high. We had had occasion to study the same disease at Camp Sevier, South Carolina in September and early October, 1918, and in two different localities in France in December, 1918, and February, 1919, and found that the clinical characteristics were identical on both continents.

The more severe recurrence in England, in October, has been carefully studied. In fact this recurrence was almost universal in all countries. The autumn epidemic has been reported as being at its height in October, 1918, in such widely separated localities as the United States, England, France, Greece, Brazil, India, Japan and Korea.

In Europe at any rate the third wave occurring in the winter of 1919 was quite generally distributed. At about the same time the disease broke out in England, making a third wave in less than a year. Once again the third attack began less suddenly and less violently and resulted in a lower number of fatalities. During February there was reported to have been a great increase in the number of cases in Paris. It had terminated by March 27, 1919. In March the disease broke out anew, this time assuming grave proportions, not only in that city but in several of the Departments.

The second recrudescence has also been reported as being present in Spain.

On May 5, 1919, report was received from Buenos Ayres that in one of the concentration zones for naval troops located in the harbor there had been an epidemic of short duration, but with high morbidity, with two hundred cases being frequently reported each day.

Just as Pearl has observed a certain periodic recrudescence in the United States, there has been described a similar periodicity in England. The interval, however, is described as twelve weeks. The first wave began in July and died down about the end of August, running a two months course. Twelve weeks after the commencement of the first wave, at the beginning of October, the second appeared. It had disappeared around the middle of December. Again, twelve weeks from the beginning of the second wave, that is, in January, the third appeared.

RECURRENCES IN WINTER OF 1919–1920.

We distinguish between the flareups following the autumn spread of 1918, and which lasted until the spring of 1919, and yet another widely distributed recurrence in the winter of 1920. We have called the former recrudescences to distinguish them in point of time from the latter, but do not imply thereby any difference in the character or origin of the secondary waves. Between them all there occurred almost continuously isolated or solitary cases of influenza which served to keep the fires smouldering. In our own work in the city of Boston we found record of scattered infrequent cases of clinical influenza of apparently low infectivity in every month from March, 1919, until the recurrence in January, 1920.

Moreover, in some localities there were during this interval small epidemic outbreaks. Thus a report from Lisbon, Portugal, on June 1, 1919, states that the deaths from influenza in that city during the preceding two weeks had been more than the total deaths from all causes during the preceding four months. A report from London, October 30, 1919, states that during the preceding few weeks there had been in the ninety-six great towns of England and Wales a slight but gradual increase in the number of deaths attributed to the disease, and a coincident rise in the number of notifications of acute primary and acute influenzal pneumonia. The feeling at that time was that the increase was associated with prevailing meteorological conditions, and did not apparently signify more than the usual variation in respiratory diseases which was to be expected at that season of the year. On November 3, 1919, the disease was reported prevailing at Chile and it was spreading throughout Bolivia. At the same time influenza had spread over the entire country surrounding Buenos Ayres and had even reached the neighboring city of Montevideo. In the latter part of November more than 2,000 cases had been reported at Lemaies, about fifteen miles northeast of Granada, Spain.

The winter of 1920.—In the United States the death rates from influenza and pneumonia in the large cities over the entire country were below the usual average from May, 1919, until January 1, 1920. In the week ending January 17th there was a sharp increase in the influenza-pneumonia rate, which occurred simultaneously in Kansas City and Chicago. In the latter city an excess over the average was not reached until some days later, but the maximum mortality occurred in the week ending January 31st, while in Kansas City the mortality did not reach its height until one week later. New York, Washington, San Francisco, Milwaukee and St. Paul soon followed with an increase in the week ending January 24th, and in the subsequent two weeks many other cities were added to the list. By February 14th thirty-two out of the thirty-six large cities reporting had an increase in the death rate from influenza and pneumonia as compared with the same period in 1917. The maximum was reached at this time, and according to the Bureau of the Census reports there were 7,059 deaths from influenza and pneumonia during the week ending February 14th. In the next week the number of deaths from these causes in the cities reporting had dropped to 5,088. The February weekly average for 1917 was 1,489. In the week ending February 14th, 267,643 cases of influenza were reported from forty-one states; the excess annual death rate as compared with the average for the period from 1910 to 1916 was 1,319.

In general the 1920 recurrence was decidedly milder than the autumn outbreak of 1918. Certain cities, however, suffered severely, particularly Detroit, Milwaukee, Kansas City, Minneapolis and St. Louis. In these the death rate, while the epidemic lasted, was higher than that of 1918. The duration of the epidemic was generally, however, shorter in these cities. Columbus, Ohio, and Indianapolis suffered severely, but to a less extent than the cities just mentioned. In Chicago the death rate was not as high as in the fall of 1918, but it did rise far above the point reached during the 1889–90 outbreak, and the influenza in the last two weeks of January brought the total mortality for that month up to 5,149, the highest mortality in the history of the city with the exception of October, 1918.

We have already discussed the recurrent epidemic as it was studied in Detroit. The salient characteristics were a rapid and fairly symmetrical evolution, a shorter duration than in 1918, a lower morbidity with a higher mortality rate, and finally, a smaller total number of deaths than in 1918.

The 1920 recurrence was widespread. It was not confined entirely to the large cities. Semi-official reports from small towns and villages show very much the same conditions as were observed in the larger cities. On the whole, however, most communities, both large and small, suffered less severely than in the first spread. The few exceptions to this were distributed over the continent without uniformity.

The first among the large cities to show an increase in death rate from the epidemic was Kansas City, in which the mortality first climbed in the week ending January 17th. The following week there was an increased rate in Chicago, New York and Milwaukee, and one week later, Boston, Detroit, San Francisco and Philadelphia were affected. New Orleans was one of the last large cities affected, not showing a definite increase until the week ending February 14th. In contrast to the 1918 pandemic, the influenza of 1920 showed no clearcut direction of spread, and was as in the years following 1889 due, without doubt, to firing up of the pandemic virus as it had been left scattered in many endemic foci throughout the earth. There probably were instances of spread from the larger centers to outlying districts, but there was no continuous spread over large areas. The accompanying table shows clearly that the disease this year commenced in the center of the continent, a fact which would seem to disconnect it entirely from the late epidemics of 1919, occurring in Europe:

Annual death rates from all causes by week in certain large cities of the United States from week ending January 3d to week ending February 21st. ═══════════════╤═══════════════════════════════════════════════════════ City. │ Week Ending ───────────────┼───────────────────────────┬─────────────────────────── „ │ January. │ February. ───────────────┼──────┬──────┬──────┬──────┼──────┬──────┬──────┬────── „ │ 3│ 10│ 17│ 24│ 31│ 7│ 14│ 21 ───────────────┼──────┼──────┼──────┼──────┼──────┼──────┼──────┼────── Kansas City │ 16.3│ 15.8│ 19.3│ 32.7│ 39.5│ 61.5│ 44.0│ 29.1 Chicago │ 14.4│ 13.8│ 15.1│ 23.5│ 41.3│ 39.1│ 24.6│ 17.7 New York │ 14.0│ 15.3│ 14.6│ 19.5│ 28.0│ 35.0│ 35.1│ 24.8 Milwaukee │ 11.6│ 12.5│ 9.0│ 15.6│ 29.4│ 34.5│ 27.1│ 16.9 Detroit │ 13.7│ 13.0│ 14.2│ 15.5│ 33.9│ 60.9│ 42.9│ 21.6 Boston │ 16.8│ 16.9│ 14.1│ 16.8│ 20.3│ 27.1│ 33.7│ 32.1 San Francisco │ 16.5│ 15.4│ 19.6│ 19.2│ 22.9│ 25.2│ 31.8│ 28.8 Philadelphia │ 15.6│ 16.7│ 16.2│ 16.8│ 18.3│ 22.1│ 34.3│ 37.2 New Orleans │ 18.8│ 19.6│ 22.6│ 18.8│ 20.9│ 20.1│ 25.0│ 32.3 ───────────────┴──────┴──────┴──────┴──────┴──────┴──────┴──────┴──────

The relative severity of the two epidemics in certain of the large cities has been compared by H. F. Vaughan, and he has found as is seen by the table that Kansas City and Detroit, two of the early cities affected, had the highest mortality in 1920. Philadelphia in 1918 lost nearly three times as many people as Detroit did in 1920. Detroit was higher than Chicago in 1920, but lower in 1918.

Per cent. of population killed by influenza. ═════════════════╤═════════════════╤═══════════════════════════════════ │ 1920. │ 1918–1919. ─────────────────┼─────────────────┼─────────────────┬───────────────── │ First seven │ First seven │Twenty-one weeks. │ weeks. │ weeks. │ ─────────────────┼─────────────────┼─────────────────┼───────────────── Detroit │ 0.20│ 0.17│ 0.28 Chicago │ 0.12│ 0.34│ 0.41 Kansas City │ 0.24│ 0.30│ 0.63 Philadelphia │ 0.10│ 0.76│ 0.82 New Orleans │ 0.05│ 0.55│ 0.77 ─────────────────┴─────────────────┴─────────────────┴─────────────────

The following table taken from the “Final Influenza Bulletin,” by E. R. Kelley, Commissioner of Health in Massachusetts, shows distinctly the difference that must be always borne in mind between curves of influenza incidence and death curves. In his table the mortality climbed first on the week ending January 13th, as in the table above, but the increase in influenza cases began at least one week earlier. It is characteristic of influenza epidemics that the rise of mortality curves follows that of morbidity by about a week:

Influenza and pneumonia cases in Massachusetts in the first three months of 1920. ═══════════════════════════╤═════════════════════╤═════════════════════ │ Influenza. │ Lobar pneumonia. ───────────────────────────┼──────────┬──────────┼──────────┬────────── │ Cases. │ Deaths. │ Cases. │ Deaths. ───────────────────────────┼──────────┼──────────┼──────────┼────────── Week ending January 3d │ 41│ 0│ 109│ 9 Week ending January 10th │ 46│ 2│ 142│ 50 Week ending January 17th │ 58│ 0│ 145│ 52 Week ending January 24th │ 489│ 4│ 201│ 56 Week ending January 31st │ 4,495│ 48│ 313│ 96 Week ending February 7th │ 9,627│ 272│ 382│ 212 Week ending February 14th │ 10,747│ 133│ 583│ 140 Week ending February 21st │ 5,601│ 181│ 510│ 147 Week ending February 28th │ 2,375│ 147│ 313│ 114 Week ending March 6th │ 1,144│ 54│ 206│ 34 Week ending March 13th │ 490│ 31│ 130│ 54 Week ending March 20th │ 254│ 20│ 105│ 44 Week ending March 27th │ 147│ 14│ 102│ 94 Week ending April 3d │ 218│ 6│ 97│ 12 ───────────────────────────┴──────────┴──────────┴──────────┴──────────

In Massachusetts in the first three months of 1920 there were reported 35,633 cases of influenza and 3,158 of lobar pneumonia, with 906 deaths from the former disease and 1102 from the latter. The case rate per 100,000 from influenza was 883.4; from lobar pneumonia, 78.3; the death rate from influenza, 22.4; from lobar pneumonia, 27.4; and the fatality per cent. from the former disease was 2.5, and from the latter, 34.9.

The epidemics in Detroit and Boston both showed a symmetrical evolution and a single wave. This appears to have been the more frequent type of recurrence in this country. There are examples of the secondary curve. At the Great Lakes Naval Training Station the epidemic began during the week ending January 17th. On January 12th there were fifty-one cases. The peak was reached on the third day with the admission of 182 new cases during twenty-four hours. Although the peak came early the decline was less rapid and there were four secondary peaks, but the outbreak terminated on the twenty-fourth day. On the whole the epidemic was less severe than in 1918. Pneumonia was a complication in about ten per cent. of the reported cases of influenza at the training station.

On the European continent there were similar recurrences in the first three months of 1920. In the large towns of England the recorded deaths from influenza made an increase in a steady curve from sixty-six in the last week of January until the week ending March 27th. After that date there was a gradual falling off. That the situation was in no way as serious as it was at the same time in the American cities and in certain other parts of Europe is indicated by an annotation in the Lancet of March 6th. According to this annotation, the weekly totals of deaths attributed to influenza in London and the 96 great towns had on the whole tended to increase in the early part of 1920, but the absolute increment was so small and the necessary uncertainty of classification so great that no unfavorable inferences could be drawn from these fluctuations alone. On the other hand, the notifications of cases of pneumonia increased appreciably, too much to be set down as a mere chance fluctuation. But notification for this disease had not been in force long enough to enable accurate comparison. There were no indications of epidemic influenza in any of the large factories situated throughout the country. But on the other hand there was proof of the existence of epidemic influenza of an infectious, but relatively non-fatal type in certain large schools situated in the South and Southwest of England.

The annotation concludes that influenza was epidemic in a few localized English and Welsh communities, and that the type was similar to, but less severe than that of 1918–19.

In the city of Paris between the 11th and 31st of January there was a very definite increase in the death rate from inflammation of the respiratory tract above the average for other years.

Renon and Mignot studied 141 cases of influenza (71 men and 70 women) during January and February, 1920, at L’Hopital Necker. Fifteen of the 141 died. According to these observers the grip of 1920 attacked all ages in contradistinction to the 1918 epidemic which affected especially the young and vigorous. One-third of their group were over forty years of age, while some were seventy and eighty years old. In spite of this the disease remained relatively mild. Sixty-four were cases of simple grip. Forty-three had associated bronchitis and pulmonary congestion and edema. Twenty-seven had pneumonia. One had acute pulmonary edema. There were cases of influenza in tuberculosis individuals. One developed an acute serofibrinous pleurisy. One had purulent pleurisy, and one meningitis.

In Copenhagen there occurred between the 18th and 24th of January, 1920, 1,204 cases of influenza with four deaths; in the following week, from the 25th to the 31st of January, 7,445 cases with forty-two deaths; from the 1st to the 7th of February, 11,038 cases with 207 deaths; from the 8th to the 14th of February, 8,308 cases and 327 deaths. This is to be contrasted with the month of December, 1919, in which there were 1,845 cases of influenza in Denmark, of which only 272 were at Copenhagen. In Christiania, Norway, during the week of January 25th to 31st, there occurred eleven deaths from influenza, whereas during the preceding two weeks there had not been a single death from this disease.

In December, 1919, there were reported in Switzerland only 511 cases of influenza. During the month of January, 1920, this increased to 13,162, and in February to 83,008, the estimated population being 4,000,000. From February the disease decreased in prevalence. In Zurich, with a population of 210,000, the epidemic resulted in 14,534 cases. The first increase began around January 4th. The total number of cases for January was 1,071. In February the records of the four weeks showed 2,721, 4,140, 3,341 and 1,899 cases, respectively; in March the decrease was rapid, 886, 442 and 45 cases being reported in the first three weeks. The total number of deaths, mostly due to pneumonia, was 229, a mortality of 1.5 per cent.

During 1920 epidemics were also observed in Valencia, Santander and other towns in Spain, and in Mexico City. In the latter city the number of deaths was reported as 1,649, as contrasted with 3,000 in 1918.

INCUBATION PERIOD.

An accurate determination of the period of incubation in influenza presents great difficulties. The large number of cases with the consequent multiple opportunities for infection in the case of every individual add to the difficulty. Under any circumstances the period is very short. Parkes, many years before the 1889 epidemic, believed that an incubative period sometimes exists; that it was sometimes very short and sometimes of many days duration.

“In the Transactions of the College of Physicians it is stated that in the epidemic of 1782, seventeen persons came to London to an hotel, and on the following day three were attacked with influenza. Haygarth says that a gentleman came to Chester from London, on the 24th of May, 1782, ill of influenza; a lady, into whose family he came, was seized on the 26th, and was the first case in the town. Haygarth states, evidently with the view to point out the possibility of a direct contagion, that the gentleman was engaged to be, and was afterwards, married to this lady. In this case the longest possible incubative period was two days. In 1782 a family landed at Harwich, from Portugal, and came to London directly; the day after their arrival the lady, two servants and two children were all seized. Two men-of-war arrived at Gravesend from the West Indies; three Custom-house officers went on board; a few hours afterwards the crews of both vessels were attacked. Some other cases are on record where the incubative period, if it existed, could not have been more than a single day. On the other hand, some cases are on record in which the incubative period must have been two or three weeks.”

Leichtenstern believed that the usual incubation period is from one to three days although some cases have been reported in which it is without doubt no longer than twelve hours. Parsons in reporting for England also gives the incubation period as from one to three days as a rule.

It is reported in France in 1918 that in one institution thirty-one cases out of thirty-three individuals occurred within three days, all of them infected by one nurse.

MacDonald and Lyth report in the British Medical Journal for November, 1918, an interesting observation concerning the incubation period in influenza. These two individuals were traveling from London to York in the same compartment with an individual who was just convalescing from influenza. Exactly forty-one hours after being on the train with this individual, they both came down with the disease. One suffered lightly while the other was severely ill. The wife and two children of the latter contracted the disease in turn, and with them also the first symptoms appeared suddenly after a delay of about forty-eight hours.

Stanley, in studying the epidemics of influenza in San Quentin Prison, found that as a rule there was an increase in incidence following the Sunday picture shows. This usually occurred on Tuesdays and Wednesdays, giving an apparent incubation period of from thirty-six to sixty hours. He tabulated the records of twenty-nine individuals who had presumably become exposed at the show and found that the incubation period averaged about forty-eight hours.

The majority of observers give the incubation period as from twenty-four hours to four or five days, most often two or three days.

PREDISPOSING CAUSES.

Not every individual acquires influenza. There are those who assume that the disease is so wide spread that every individual in each community attacked has been actually exposed to the disease. In that case there must be a certain amount of natural immunity which protects around sixty to eighty per cent. of most populations from the disease. The other extreme would be that every exposed individual falls victim to the disease and that only twenty to thirty or forty per cent. are actually exposed. The true state probably lies between these two extremes.

Nevertheless it is a fact that some individuals naturally insusceptible to the disease fall victim as a result of the action of some extraneous force, something which lowers their resistance. Raw recruits in the army camps in the fall of 1918 contracted the disease in much greater proportion than did the hardened soldiers. Fatigue, intercurrent illness, environmental changes and exposure to inclement weather may all predispose to infection in the individual. Greenwood found that the compulsory rationing of food in England during the war was probably not a predisposing cause of infection. The incidence of the disease in the South Africa Union where food was abundant was even higher than that for the British Isles. Hamer calls attention to the fact that the ages of highest incidence during the pandemic were those ages in which the diet was perhaps more restricted than in other ages. This, however, is but one factor and cannot be accepted as conclusive.

It had been suggested that in the army camps in the United States typhoid vaccination during the epidemic predisposed to the disease. The similarity of the symptoms in vaccine reaction and in influenza may have suggested this. V. C. Vaughan has investigated this possibility and finds that those organizations in which anti-typhoid vaccine was discontinued for a time after the appearance of the influenza suffered quite as severely as those which submitted to vaccination.

Other predisposing causes, such as the incidence of crowding in a household and the sanitary surroundings of the individual will be discussed later.

PERIODICITY.

The phenomenon of occurrence of epidemic influenza in many countries, even on different continents almost simultaneously and often without any clearcut progressive spread from one of these countries to another raises the question of periodicity in influenza. Is this simultaneous occurrence due to some mechanism in the life cycle of the influenza virus whereby it regularly acquires increased invasiveness, no matter what its geographical distribution, or is it merely a feature of the meteorologic conditions that makes the epidemic appear to be simultaneous in widely scattered communities?

Influenza characteristically returns. An influenza period usually comprises from three to five years, with one or two very mild epidemics at the beginning which may frequently be overlooked, then of wide pandemic spread, to be followed by endemic recurrences for as long as two or three years. During these influenza periods the intervals between waves are frequently so nearly equal or multiples of each other as to force the question of a periodic law. Not only thus, but even on a larger scale does the disease appear with a certain uniform regularity. The great epidemics are separated frequently by intervals approximating decades. Stallybrass calls attention to the epidemic years in England, which are 1789–90, 1802–03, 1830–32, 1840–41, 1848–49 and 1851, 1854, 1869–70, 1879, 1890–91, 1898, and 1918–19. With the exception of 1854 all of these dates are around the end of a decennium.

Yet, again, in the successive waves of an individual epidemic, as has been pointed out by Pearl, there is very roughly some periodicity.

Are these admittedly obvious phenomena fundamental features of the life cycle of the influenza virus, or are they incidental, due to extrinsic causes, changes in the pabulum, in the host as an individual, or in the host as a community, or changes in climatic conditions? Is it a basic feature upon which we must build our conception of the epidemiology of epidemic influenza, or is it more a feature of chance? The evidence to date is conflicting and incomplete. The answer lies in the future.

Periodicity in the acute infections is not a new subject. It has been discussed in various other diseases, particularly in measles. For many years epidemiologists in many parts of the world have reported the observation of a periodicity in epidemics of measles. It is generally regarded as an established fact that each locality suffers from epidemic waves of this disease and that the period is somewhere about two years. In certain relatively small localities in England where registration statistics have been kept for many years the Health Officers count on an epidemic every two years. In some places the epidemic is expected to fall during the even years, while in others it occurs in the odd years.

Brownlee has been one of the foremost investigators in the periodicity of influenza, but since his communication on that subject was very brief, we take occasion to quote first from his article on the periodicity of measles, thereby gaining a more comprehensive knowledge of his theory, and at the same time becoming able to compare the periodicity in the two diseases.

“The common explanation of the periodicity of epidemics of children’s diseases is that the susceptible children take the disease in sufficient numbers to limit the further spread. The epidemic thus dies out to recur when a further sufficient number of susceptible children have accumulated. This is quite a feasible theory and certainly explains the periodicity of epidemics. The forms of epidemic curve which arise on this hypothesis are not unlike those actually found, the differences being no more than might be expected between a mathematical form based on a hypothesis and the natural conditions to which the hypothesis is only an approximation. This explanation, however, must fail if epidemics of different periods can be shown to exist in the same town at the same time, and I think this has been shown. In London, which on account of its size might be assumed deserving of special treatment, the existence of periods of different length have been demonstrated. In Edinburgh, Glasgow, and Birmingham also it has been shown that epidemics with periods in the neighborhood of ninety-eight weeks and one hundred and ten weeks intermix. The same epidemicity even applies to districts in London. In the West end of London we have almost a replica of what occurs in Glasgow, Birmingham and Edinburgh. The main period there is 97 weeks, the secondary period 109.5 weeks. In the South of London one period is that of 97 weeks, but almost equally prominent is that of 87 weeks. The whole evidence, therefore, seems to point to some condition in the organism which produces the disease as the potent cause of the difference rather than to the number of susceptible children. Compare the Paramoecium which under natural conditions divides asexually for several hundred times and then dies out unless conjugation takes place. The resting stage following conjugation persists for some time.

“There is, however, one point of great importance which must be considered. If an epidemic begin in a definite locality and spread from that locality, and if there is no loss of infectivity on the part of the organism, it is demonstrable that a similar proportion of the population should be attacked in each zone as the epidemic spreads outward. On the other hand, if the organism lose the power of infecting with the lapse of time, in each additional zone invaded the proportion of susceptible persons infected should become smaller and smaller. Of course this might not be true for any one epidemic, as in many parts of the area invaded the population might be more or less susceptible because of recent attack of the disease, but when an average of twenty outbreaks has been taken this effect should be eliminated, the number of times the invading organism comes into contact with an insusceptible population being balanced by the number of times which it meets one more susceptible than the average. The method of spread of epidemics on the average should thus give some indication regarding the laws which determine the course of the phenomenon. Now with regard to London, the clearest facts refer to the 87-weeks, the 97-weeks and the 109.5-weeks period. The 97-weeks period starts at the same time all over the city and there is no evidence of any special center. The infection seems generalized. With regard to the 87-weeks epidemic, however, the case is different. This seems to start in St. Saviour’s Parish and to spread thence to Camberwell, Lambeth, etc. In this epidemic the rate of spread can be definitely measured. The maximum occurs later and later as the distance from the center is increased and the percentage of children infected is also easily observed to fall as the time increases. With regard to the 109.5 weeks’ period epidemic the facts are similar though not quite so definite. This seems to show that for at least two strains of organisms the epidemic ceases because the organism has lost its power of infecting. It may be inferred that an epidemic ceases because the organism varies in its potency to cause infection. A cycle of epidemics now coinciding and now differing in their maxima can thus be explained. Some kind of life cycle exists in the infecting organism. In this life cycle high powers of infecting are attained probably after a resting state: a period of activity follows and gives place to a period of rest; the average length of the cycle is determined by the strain of the organism.”

There are certain drawbacks to Brownlee’s work and conclusions. We quote from V. C. Vaughan, who has discussed Brownlee’s work, not only because of his good summary of the difficulties and disadvantages of the method, but particularly because the same disadvantages and possibility of inaccurate conclusions hold in the case of influenza.

“There is no reason for supposing that the virus of measles is controlled in any way by our calendar. In order to get anywhere in determining any law of periodicity in epidemics we must know the morbidity and mortality of the disease by days, or at least by weeks. In different parts of a large city there may be, and undoubtedly are, epidemic waves of measles on the flow or on the ebb at the same time. The best work that has been done along this line is that of Brownlee, who has figured out epidemic waves of measles, based on the weekly numbers of deaths in London between 1840 and 1912.

“The figures presented by Brownlee are of great value, and his theory is fascinating and has much in its favor, not only in a study of epidemics of measles, but of the other infectious diseases of infancy and childhood, especially scarlet fever, whooping cough, and chicken-pox. In order to solve the problem of periodicity in measles we must have more exact information than we now possess. Brownlee’s figures pertain to deaths only. There are, so far as we know, nowhere in the world satisfactory statistics concerning morbidity in this disease. Deaths from measles are so largely determined by the care bestowed upon the sick and upon the extent to which secondary infection is prevented that we are inclined to hesitate about the acceptance of a death rate or number of deaths from this disease as an index to the virulence of the organism causing the disease; in other words, we are not convinced that the death rate in a given outbreak of this disease is a measure of the virulence of the organism causing it. This involves the question whether measles per se is a disease of wide variation in malignancy or are the widely different death rates observed in different epidemics due to secondary infections. The streptococcus, a common invader of the body during the progress of a measles infection, is known to possess a most variable degree of malignancy. We are inclined to the opinion that if all cases of measles could be recognized before secondary infection occurs and could be cared for ideally the death rate from this disease in different epidemics would be much more uniform than is now shown and would be low. The greatest danger to life in an attack of measles lies in the fact that the virus lowers the resistance of the body cells and opens gateways to more deadly organisms, such as the streptococcus. We believe that there are demonstrated facts which support these ideas. Quite uniformly in measles there is a well marked leukopenia. As we now interpret it, this means a decrease in the number of the forces that naturally protect the body against the invasion of foreign cells. Again as we interpret it, the failure of the body cells to respond to the tuberculin test during a course of measles or soon thereafter is evidence that the resistance of the body is lowered. If our interpretation on these points be correct we fail to see how deaths from measles can be properly employed as a standard in the measurement of the virulence of the organism of the disease.”

Recognizing then the obvious disadvantages of the method, we will turn to the work done on periodicity in influenza. We should call attention at this point to the fact that the establishment of periodicity would carry with it the assumption that the third of our three hypotheses concerning the origin of influenza is the correct one. For example, the July and autumn epidemic in England, as well as all occurring subsequent to them, would be due to a virus or several viruses which have been endemic in England since 1889, in fact since man has been in England, and the epidemics and their recurrences would be due to increase in the virulence of this local virus. The virus is distributed over the earth and may become virulent periodically in many countries at the same time, or if the periodicity is different on two continents the epidemics would occur at different times.

Periodicity is not a new hypothesis. Hirsch denied any periodicity distinct enough to be revealed by the comparatively crude statistical methods of his time. Periodicity if present can only be revealed by detailed and complicated mathematical procedures. Brownlee has investigated the weekly number of deaths from influenza in London between 1889 and 1896, and also up to the present time. He has compared these with the weekly number of deaths from bronchitis and pneumonia in London, the records of which have been available since 1870. By the method of the periodogram he showed that there was a regular periodicity of 33 weeks in deaths from influenza between the years 1889 and 1896, but that in later years there was some considerable aberration. He concluded that for some reason influenza periods tend to recur at 33-week intervals after the primary epidemic, and that the favorable season for its recurrence is from January to the end of May. Should the 33d week fall in other than these winter months the epidemic may be mild or even missed, appearing after another 33-week interval. Epidemic influenza does not assume a form which causes any large number of deaths until a bronchitic or pneumonic constitution has been established. The fatal form is usually a disease of the winter or spring. He also found that in the absence of influenza, bronchitis and pneumonia did not show a 33-week periodicity, but when associated with influenza these conditions also became periodic (33 weeks), and he assumes that this change is definitely associated with the appearance of influenza.

Between 1876 and 1890 there was no tendency to the 33-week periodicity with regard to bronchitis and pneumonia, but it was very marked between 1889 and 1896. During this epidemic period the deaths from pneumonia precede those from influenza by one week and those of bronchitis precede those of influenza by two weeks. The number of deaths from bronchitis and pneumonia ascertained by this method of grouping is fully twice the number obtained from influenza alone.

He believes that in these years, influenza appeared, on its epidemic onset, first with bronchitic symptoms, later with pneumonic symptoms, and lastly with those symptoms more definitely associated with influenza proper. When the several sets of deaths are added together in 33-week periods a very typical epidemic makes its appearance.

Brownlee finds that in the monthly statistics of Glasgow, Aberdeen, Massachusetts, etc., there has been nothing differing essentially from this phenomenon found in London.

Between 1876 and 1889 the annual curve for bronchitis and pneumonia shows two maxima, one at the end of January and the second in the middle of March. From March the decline in deaths from bronchitis is very rapid. The disease re-appears around the beginning of October. During the period 1889–96 the maximum number of deaths from bronchitis occurred in the second week of January and the last week of February. Both of these maxima are a fortnight before the maxima of the epidemics of influenza. This suggests that the advent of influenza has brought a change in the seasonal prevalence of bronchitis and supports the view that the earlier portion of the influenza epidemic is associated with bronchitic symptoms. The same phenomenon holds for pneumonia.

Brownlee was able to predict correctly the date of the recent 1920 epidemic. He did not attempt, however, to explain the short interval between the summer and autumn, 1918, epidemics in England. He speaks of the second as “aberrant.” In other words, it does not fall within his classification. October is not a high respiratory disease month. The epidemic should have been mild.

Stallybrass has confirmed Brownlee’s 33-week periodicity and suggests an explanation for the “aberrant” October epidemic. Using periodograms with a 33-week basis, and plotting deaths from influenza and respiratory diseases from January, 1890, through January, 1920, he finds that the most definite 33-week periodicity is shown during the years 1890–99. During this period there is one maximum, when all 33-week periods are superimposed, which occurs at the seventh week of the cycle. Beginning about 1899 a new maximum appears in the nineteenth week of the cycle, which continues to recur until the culminating point is reached in the week ending October 26, 1918. An additional 66 weeks carries the date forward to the first week in February, 1920. The maximum at the seventh week of the periodogram during the years 1899–1913 is greatly diminished from that in 1890–98. The periodogram for 1914–1919 shows clearly both maxima, that in the seventh and that in the nineteenth weeks.

We quote Stallybrass in some detail (see Chart XII):

“Dr. John Brownlee pointed out that from July 13th to March 1st (the maxima of the summer wave of 1918 and of the spring wave of 1919) is 33 weeks, but that the wave having its crest in this country on November 2, 1918, does not fall into the sequence, leaving one to infer that there were two strains of the influenzal virus in operation.

“I supplement his investigation by the weekly deaths occurring in Liverpool during the period 1890–1919 that were ascribed to influenza and to all respiratory diseases. Prior to 1890 there were no deaths attributed to influenza for a number of years.

“Closely corresponding with Brownlee’s observations on London by far the most definite periodicity is shown during the years 1890–1899, during which period there is one well marked maximumly at the seventh week of the cycle. During the period 1899–1913 a new maximum in the nineteenth week of the cycle comes into play and continues to recur until the culminating point is reached in the week ending October 26, 1918, a week earlier than in most English towns (Wave III); a further 66 weeks carries one forward to the first week in February of this year, as Brownlee pointed out, and the outbreaks that are being reported in Japan, Paris, Chicago, New York, etc., would show that this strain has punctually reappeared.

“There is also evidence in the table of a small maximum at the twenty-seventh week of the cycle in the earlier sub-period, and at the twenty-ninth week in the later sub-period; slight movements of the maxima forwards or backwards in the cycle over a number of years may, perhaps, indicate a periodicity slightly greater or less than 33 weeks. The twenty-ninth week of the cycle fell on the weeks ending May 18, 1918, and January 10, 1919. An examination of the figures in Dr. Hope’s annual report for Liverpool for 1918 shows that there was a definite wave of influenza reaching its crest on May 18th (Wave I), and there is also a definite rise in the deaths from influenza, respiratory diseases, and from all causes, making a small peak in the week ending January 3, 1919, but it is hidden by the enormous waves of October and March, so that it only appears as an irregularity in the curve; but it was noted at the time that influenza had not declined in Liverpool in January in the way that it had in practically all other English towns. These two waves do not appear to have played a large part in this country, but the outbreaks in the Grand Fleet in May, 1918, and also in Spain, Glasgow, etc., may, perhaps, be attributed to it. In the United States in January, 1919, it would appear to have played a much larger part. In a large number of American cities two waves are experienced, the first being the October wave; the crest of the second wave sometimes fell in March, as did one of the crests in this country, but in a number of instances, e.g., Cambridge, Washington, San Francisco, New Orleans, etc., it fell in January, or to be exact, in the thirty-first and thirty-second weeks of the cycle. The close relationship of Liverpool and Glasgow with the United States through the incoming stream of American troops may perhaps account for the presence of this May wave in these two towns, and not the rest of England.

CHART XII.

Periodogram based on the weekly influenza deaths in Liverpool between 1890 and 1919. The curves are based on a thirty-three week periodicity. (Stallybrass.) ]

“The third maximum in the fourth week of the cycle is represented during the late outbreak by the waves culminating in Liverpool, and also the greater number of English towns on the weeks ending July 13 (Wave II) and March 1 (Wave IV). This is a 33-week interval. This wave recurred at an interval of 32–34 weeks in a large number of English towns.

“Of 65 towns which experienced all three waves 47 (72 per cent.) had their maxima in the summer and spring epidemics within an interval of 32–34 weeks; but comparing the week in which any given town had its epidemic peak in the summer and autumn, and autumn and spring epidemics only 27 (41 per cent.) and 31 (47 per cent.) respectively fell within the limit of a week on either side. The time relationships of the maxima in summer and spring were much closer to each other than they were to the autumn maxima.

“If it should prove correct that there were three strains of the influenzal virus, each with a periodicity of about 33 weeks, and that simultaneously all three strains became enhanced in both virulence and infectivity, then we are faced with a phenomenon without an exact parallel, although the behavior of the meningococcal viruses during the war presents some points of similarity. So far the weight of evidence leans to such an exaltation of a widespread endemic strain or strains rather than to dissemination from any particular focus in the world. In any case doubtless a good deal of spread of infection took place.”

Spear takes exception to the work of Brownlee and Stallybrass, and points out that the periodogram is not applicable to the study of recurrent epidemics unless the recurring waves are of approximately uniform “amplitude.” In that case nothing could be less appropriate for this study than the influenza waves which vary from very small to extremely high, as in 1918.

Spear describes two simple tests which he applied to demonstrate the existence or non-existence of periodicity.

First he divided each of the last thirty years into 13 four-weekly periods, and tabulated the frequency with which the observed week of maximum mortality falls into one or other of the 13 groups. He discovered that the climax of an influenza prevalence falls more frequently in the second and third four-weekly period than in others—i.e., the months of February and March. Had there been a 33-week periodicity there would have been an equal number of these climaxes in each of the 13 divisions of the year.

Brownlee, according to Spear, was correct in his prediction that influenza would occur in February, 1920, for the reason that January or February is the most likely time for an influenza prevalence in any year.

Spear’s second test of periodicity consisted in plotting the interepidemic periods according to the number of weeks intervening. Were there a 33-week periodicity, he says, that nearly all interepidemic periods should fall in this group. As a matter of fact, more than twice as many periods fall in the 42–58 weeks interval than in any other interval. Fifteen fall within this period, six in the period 59–75 weeks, five in the period 8–24 weeks, and only four in the period 25–41 weeks. There was one in the period 76–92 and one 110 plus. Finally in the thirty years 1890–1919 there were thirty-two climaxes or peaks in the “influenza” mortality.

Spear concludes that if there is any periodicity it is around fifty weeks, or a year.

The fallacy in the work of Stallybrass and of Brownlee, according to him, is that the mortality in the third week of 1892, the twentieth week of 1891, and the tenth week of 1895, and in the big epidemic of 1918 so overshadowed all the other peaks that the smaller ones became lost in these larger waves.

Brownlee does not claim a 33-week periodicity during interepidemic periods. This part of Spear’s criticism is not valid.

Vaughan’s objections to the conclusions on measles hold equally well with regard to influenza. Finally, we must remember that in parts, at least, of the work of Brownlee and Stallybrass, they are not studying chiefly influenza deaths, but deaths reported as due to bronchitis and pneumonia.

After a study of the pros and cons of the question of periodicity the author submits by way of summary his conclusions:

1. Influenza does tend to recur at intervals. It has not been proven that these intervals are always of equal length.

2. At the present the opinions concerning the periods are divergent. We have the 33-week periodicity of Brownlee and Stallybrass, the one-year period of Spear, the seven-week intervals suggested by Pearl, and the apparent twelve-week recurrences in England in 1918 and 1919.

3. It is to be noted that particularly in the work of Stallybrass, in order to prove his periodicity, he finds it necessary at times to quote epidemics occurring, not in England, but in fairly remote parts of the world, as in the United States and Japan. We have shown that in the interval between 1918 and 1920 an epidemic could be discovered somewhere on the earth in many months, perhaps even in every month during this interval. It is to be regretted that following the criticism by Spear there has been no further report, so far as we know, by either Brownlee or Stallybrass.

4. It is quite possible, even probable, that influenza is endemic in mild form throughout the interpandemic years in England, as well as in many, or all other countries, but it is equally possible or probable that the particular virus which gave rise to the pandemic was not one which simultaneously increased in virulence in all countries, but was one which had its origin in one comparatively well localized focus.

5. Our own theory does not explain the autumn recurrence in 1918 in England, following that of May, June and July. We have traced the original spread to England and have left it at that point. We have again taken it up in the autumn when it became severe, and was returned to the United States. The interval of quiescence in England and elsewhere may need further explanation. Two alternative hypotheses suggest themselves: First, that the autumn recrudescence is entirely comparable to later ones, and is but a manifestation of the characteristic feature of recurrence in influenza. Had the autumn epidemic been mild and had it not so overshadowed all others, we would have classified it with those of early 1919 as being merely recrudescences of the summer spread. Evidence, particularly in favor of this, is the report of Greenwood previously mentioned which shows that in England the autumn spread partook of the nature of a secondary type of epidemic, as compared with the primary type in the summer.

The second hypothesis is that the occurrence in the summer in England of an epidemic due to a virus imported from America or France or China, with its consequent increase in morbidity, so enhanced the virulence of a local endemic British virus that the latter produced the autumn epidemic. We see no necessity for complicating the question by the assumption of this second hypothesis.

6. Whether or not there is a regular periodicity of a definite number of weeks in the case of influenza, the fact remains beyond cavil that one of the dominant characteristics of epidemic influenza is its recurrence at intervals. The evidence is ample that the disease is distributed throughout many countries in interepidemic times and that intermittent outbreaks of large or small extent occur.

The most striking phenomenon is the fact that in March of 1918 influenza is reported as having been present in China, in the United States and in France. It is scarcely possible that the disease in its epidemic form could have been carried from any one of these three points to the other two in the remarkably short time between the onset of the three outbreaks. We are faced with the phenomenon of a simultaneous exaltation of the influenza virus in three remotely separated countries of the world. This one fact more than any other indicates that the fluctuation in virulence is dependent upon some factor intrinsic in the virus itself and not upon environmental factors.

It is impossible at the present time to decide whether the world epidemic spread simultaneously from these three foci or whether in only one of these three the virus became so exalted as to produce pandemic prevalence. All we can say is that we are able to trace consecutively the spread of the influenza from the focus in the United States throughout the world. The information upon which we base our findings is not statistical, and as we have previously said this latter type of demographic study should be brought into use to either corroborate or disprove our findings.

VIRULENCE ENHANCEMENT.

Before attempting to study the mechanism of origin of the 1918 pandemic it is highly essential that we devote some attention to a consideration of the processes by which the germs of infection, particularly the virus of influenza, may develop an increase in virulence. Followers of the theory of periodicity would base virulence enhancement primarily on some intrinsic property of the virus itself. We know from past experience and particularly from animal experiments that this is not the only manner by which virulence may be increased.

As far as we know there is no new infectious disease. Individuals who delve into the history of the past inform us of more and more diseases which were well known to the ancients. We are frequently amazed at the variety of diseases now known to be infectious that were very correctly described by the Hippocratic writers. The infectious diseases are with us always and live nearly always in man, the host. There are few exceptions. Very few of the contagious viruses can live for any long period of time outside of the human body. A few, such as the plague bacillus, may live on other hosts, but these are the exception. The remarkable feature is that for long periods of time the virus exists in the host in a quiescent state and only at intervals does it become highly invasive and thereby produces epidemics of greater or less extent. Under what conditions does the metamorphosis of the microorganisms occur?

Topley, in the Goulstonian lectures, discusses this subject. He says: “The first difficulty with which we were faced in forming any theory of the spread of bacterial infection, which should conform to the known facts of epidemiology, was to find some explanation of the perpetuation of the virus during interepidemic periods. The bacteriologic data which have accumulated, especially during the last twenty years, have shown that the causative agents of specific diseases are to be found in apparently normal persons who give no history of having been in contact with the disease in question, as well as in contact with actual cases of the disease. Moreover, the organisms in question have been shown, in certain cases, to persist for long periods of time in or upon the tissues of their hosts, and we must always remember that the difficulty of bacteriologic technic is likely to lead to a serious under-estimate. Clinical and epidemiologic investigations have yielded confirmatory evidence, and we are thus left with a conception of the virus of a given disease being distributed fairly widely throughout the world as an apparently harmless parasite on the human host, but taking on during epidemic periods a new and sinister role, only to relapse again into comparative quiescence as the epidemic subsides.”

He explains the rise of the epidemic wave as follows: “There are at least three possible explanations—an increase in the power of the parasite to produce disease, a decrease in the resistance of the host, and some attraction in the surrounding circumstances which favor the transference of parasites from case to case without any alteration of the pathogenicity of the one or in the resistance of the other. The third of these hypotheses may, I think, be disregarded. That alterations in environment may be the determining cause in initiating an outbreak of bacterial disease is probable enough; but they will almost certainly act through the variations which they bring about in the other two factors. The whole of bacteriologic knowledge is clearly against the occurrence of a considerable epidemic in which the pathogenicity of the parasite and the resistance of the host remain constant. Again, while we may well believe a lowered resistance of a certain number of the host-species to be an important factor in the initiation of the process, yet we cannot believe that it is the whole story. The widespread ravages of many epidemics would seem altogether to preclude such an explanation. We seem forced therefore to the conclusion that an increase in the pathogenicity of the specific parasite is an essential factor in the rise of epidemics, excluding from this category small sporadic outbreaks which may be due to the introduction of a fully virulent parasite by a healthy carrier in some other way.”

If a disease like measles is quiescent in a given community it must be that in that locality the hosts and parasites are existing in a state of biological equilibrium. They are living in a state somewhat akin to symbiosis. Such a condition could be attained either by a diminution of the invasive powers of the parasite, or by an increase in resistance of the host. Probably both elements are active; as the relative immunity of the host rises the infectivity or virulence of the parasite must rise to an equal extent to maintain the equilibrium. If this were true we would find that in those localities in which the disease is endemic and where the population is relatively resistant there is a normally more virulent virus in existence. A stranger coming into such a community would, in view of his lower resistance to the virus, be more susceptible of becoming actively infected. There would, however, be little danger of an epidemic spread because the number of susceptibles would, roughly, be limited to the number of strangers in the community. If, however, an individual from the community carrying the more virulent virus were to travel to another community where the greater proportion of the population was relatively less immune the field would be fertile for the beginning of an epidemic. Furthermore, there is the possibility of an outbreak in the first community if there should occur gross changes in its constitution; another infectious disease, a redistribution of the population with greater crowding, anything to change the balance between host and parasite.

Theobald Smith has described this possibility very clearly:

“During the elimination of the more virulent races of microorganisms, there goes on as well a gradual weeding out of the most susceptible hosts. In a state of nature in which medical science plays no part, there must occur a slight rise in the resistance of individuals, due to selection and perhaps acquired immunity, which meets the decline of virulence on the part of microbes until a certain norm or equilibrium between the two has been established. The equilibrium is different for every different species of microorganism, and is disturbed by any changes affecting the condition of the host or the means of transmission of the parasite. One result of the operation of this law is the low mortality of endemic as compared with epidemic diseases. Certain animal diseases while confined to the enzootic territory, cause only occasional, sporadic disease, but as soon as they are carried beyond this territory epizootics of high mortality may result. Climate in some cases enters as an important factor, but the most important, perhaps, is the slight elevation in virulence brought about by a more highly resistant host. The most susceptible animals are weeded out and the rest strengthened by non-fatal attacks. The virulence of the microbe rises slightly to maintain the equilibrium. In passing into a hitherto unmolested territory, the disease rises to the level of an epizootic until an equilibrium has been established.

“The same is true of human diseases, among which smallpox is a conspicuous example. The great pandemics of influenza, which seem to travel from east to west every one or two decades, soon give away to sporadic cases, and the careful work of many bacteriologists would indicate that the influenza bacilli found at present have fallen to the level of secondary invaders, and are parasites of the respiratory tract in many affections.”

Smith describes his hypothesis that the tendency of microbes in perfecting the parasitic habit is to act solely on the defensive. The aim of microorganisms, if we may speak of such, is to become able to live unharmed on the host. If they kill the host they have lost their home. The biologic tendency would be in this case for diseases which were once acute to become more and more chronic and indolent.

The extremely virulent parasite, which kills its host, will die with the host unless it has effected a means of exit before its death and escapes into a new host. For this reason Pasteur failed to exterminate the rabbits of Australia. He believed that with races of the bacillus of rabbit septicemia, which were very virulent, and which destroyed life very quickly, all that would be necessary was to start the disease among the rabbits of Australia and that it would tend to spread and would kill off all of the rabbits. But the parasite killed the animals before it had perfected for itself a means of escape from the body and thereupon died.

“From the biologic standpoint which I have endeavored to present, we may conceive of all highly pathogenic bacteria as incompletely adapted parasites, or parasites which have escaped from their customary environment into another in which they are struggling to adapt themselves, and to establish some equilibrium between themselves and their host. The less complete the adaptation, the more virulent the disease produced. The final outcome is a harmless parasitism or some well-established disease of little or no fatality, unless other parasites complicate the invasion. The logical inference to be drawn from the theory of a slowly progressive parasitism would be that in the long run mortality from infectious diseases would be greatly reduced through the operation of natural causes. But morbidity would not be diminished, possibly greatly increased by the wider and wider diffusion of these parasites, or potential disease producers. The few still highly mortal plagues would eventually settle down to sporadic infections or else disappear wholly because of adverse conditions to which they cannot adapt themselves.

“In this mutual adaptation of microorganism to host, there is, however, nothing to hinder a rise in virulence in place of the gradual decline if proper conditions exist. In fact, it is not very difficult to furnish adequate explanations for the recrudescence and activities of many diseases today, though the natural tendencies are toward a decline in virulence. In the more or less rapid changes in our environment due to industrial and social movements the natural equilibrium between host and parasite established for a given climate, locality, and race or nationality is often seriously disturbed and epidemics of hitherto sporadic diseases result.

“These illustrations indicate that so-called natural law does not stand in the way of our having highly virulent types of disease, if we are ignorant enough to cultivate them. The microorganism is sufficiently plastic to shape itself for an upward as well as a downward movement. Among the most formidable of the obstacles toward a steady decline of mortality is the continual movement of individuals and masses from one part of the world to another, whereby the partly adapted parasites become planted as it were into new soil and the original equilibrium destroyed. These various races of disease germs become widely disseminated by so-called germ carriers, and epidemics here and there light up their unseen paths.”

An example of increasing virulence from changing environmental conditions, is the experience in the United States Army camps in 1917 and 1918 with the streptococcus. This microorganism, which at first was but a secondary invader, particularly to measles, became so exalted in virulence that it soon became the cause of primary disease. This is likewise true of the various secondary invaders of the influenza epidemics. They become so highly virulent that they dominate the picture in the later stages. The organisms included in this group are particularly the streptococcus, the various pneumococci, and the meningococcus. Probably the tubercle bacillus should be added to this list.

It requires a certain amount of time for such organisms to attain increased virulence. The earliest cases in any epidemic are comparatively very mild. Thus Major Billings, epidemiologist at Camp Custer, says that for the first five days of the autumn influenza epidemic in that camp the cases admitted to the hospital were very mild in character and were recorded as simple bronchitis and pharyngitis, of no great severity, the majority soon recovering. Five days after the first case was admitted, however, the entire symptom complex seemed to change, and the cases admitted to the hospital from then on were a very different and much more severe type. Major Billings, after going over the records, feels that both types of cases were the same disease, the second being a more severe form. Woolley reports essentially the same condition from Camp Devens.

The same phenomena were found in 1889. During the 1889 epidemic Prudden examined by current bacteriologic methods seven cases of influenza and six cases of influenza-pneumonia. In them he found staphylococcus pyogenes aureus, streptococcus pyogenes, diplococcus pneumoniae, and in other cases he found a streptococcus. He concludes that the use of culture methods and media commonly employed has brought to light no living germ which there is reason to believe has anything to do with causing the disease. He emphasizes the probable importance of streptococcus pyogenes in particular in inducing the various complications.

At this point we should include for the sake of completeness reference to a recent theory propounded by Sahli explaining influenza epidemics, a theory to which we do not subscribe. He believes that the pneumococcus, the streptococcus, the influenza bacillus, and possibly other organisms, form a complex group, an obligate complex, a symbiosis, a higher unit, which infects the organism as a unit. It is all of these organisms acting together which produce the influenza. After infection has occurred one or the other member of the group may develop preferentially. In favor of this he says that in one of his cases the sputum was swarming with influenza bacilli on one day, and that the next day the sputum was a thick pure culture of the pneumococcus. He says that if an ultramicroscopic germ should yet be discovered this would not invalidate the theory, but would merely add another member to the group forming the obligate complex virus unit.

Meteorologic conditions.—Formerly attempts were made to demonstrate etiologic relationships between the occurrence of influenza and unusual conditions of the atmosphere. In most cases no relationship has been discovered. Nevertheless it is conceivable that the changes in the atmosphere, particularly seasonal variations, might influence the virulence of the organism. It has been found that nearly all of the many epidemics apparently originating in Russia took their origin there either in the late autumn or in the winter months. The spread of influenza appears to be uninfluenced by atmospheric conditions, but the severity of the disease is definitely increased in the winter months, and Leichtenstern believes that the development of a primary spread from its point of origin is also influenced by the season. Hirsch found that out of 175 correlated pandemics or epidemics, 50 occurred in the winter between December and February, 85 in the spring from March to May, 16 in the summer from June to August and 24 in the autumn.

The soil plays no part in the spread of the disease. It prevails on every soil or geologic formation; on the mountain top, in the low malarial swamps, in the tropics and within the arctic circle. Volcanic eruptions, fogs, electrical conditions, ozone, direction of the wind, have all been considered in previous epidemics and successively eliminated as etiologic factors.

It must be stated, however, that Teissier, who investigated the influenza in Russia in 1890 and has compared his conclusions at that time with the results of investigation of the recent visitation, believes that some particular cosmic conditions suddenly enhanced the virulence of an endemic etiologic microorganism—probably some ordinary germ—and that this opened the portals to secondary infections.

Secondary invaders.—We have considered a possible manner in which the virulence of the organism causing influenza may become enhanced. Whatever this organism may be, another and equally important virulence enhancement occurs in the opportunist group of the germs, so-called secondary invaders of influenza. As we have previously remarked, it is a characteristic of influenza outbreaks in all communities that the earliest cases are very mild. Secondary infection has not as yet obtained a foothold. After about a week the character of the illness changes, becoming distinctly more severe. Billings reported that at Camp Custer in the autumn of 1918 cases admitted to the hospital during the first five days were very mild in character and were reported as simply bronchitis or pharyngitis of no great severity, the majority soon recovering. After this time the entire symptom complex seemed to change and the cases admitted to the hospital were of a very different and more severe type.

Benjafield reports that in the Egyptian Expeditionary Force the epidemic commenced in May, 1918, and that the cases occurring during the earlier portion of the epidemic were mild in type and of short duration, only a very small proportion being complicated by bronchopneumonia. Wooley found at Camp Devens that the first cases were of a mild form and were usually diagnosed “naso-pharyngitis, acute catarrhal.” After a few days the disease became more severe and pneumonia cases developed.

Bezançon found that among the repatriated French soldiers from Switzerland those cases occurring in May and June had a much lower severity than in the later epidemic. Zinsser’s description of the mild, earlier epidemic in Chaumont has already been quoted.

The secondary invaders of pathogenic importance are the various forms of the streptococcus and pneumococcus, the meningococcus, the staphylococcus, and probably the tubercle bacillus and the influenza bacillus. In the last epidemic as in that of thirty years previously, the chief complications were bronchitis and pneumonia. Capps and Moody found these to be the chief complications in December, 1915. Also they found a high incidence of sinusitis. This has been a feature of the last epidemic. Wooley cites a good example of the damage done by these opportunist organisms when they are present. Among the troops stationed at Camp Devens in the fall of 1918 pneumonia following influenza was particularly prevalent in a battalion of negroes from the South. This battalion had, a short time previously, passed through an epidemic of pneumonia and Wooley believes that many of the blacks were harboring the pneumococci which were only awaiting a favorable opportunity to invade their hosts. The influenza furnished the required opportunity.

That the meningococcus should be classed in this group is certain. The author observed at Camp Sevier cases of epidemic meningitis occurring in various influenza wards scattered throughout the hospital, with no demonstrable relationship. Usually there was but one case in a ward and almost invariably meningitis occurred when convalescence was beginning. No epidemic occurred in any ward. Others have reported actual epidemics of meningitis following influenza. Moss found that a large proportion of his influenza cases had the meningococcus in the circulating blood, as demonstrated by culture. Fletcher cultivated meningococci from the lungs in all of eleven autopsies, and in all eleven cases the influenza bacillus was also present.

In considering the effect of influenza on the death rate in general, and in considering the relationship of influenza to other diseases in general, it is important to distinguish those diseases which are apparently unrelated and those diseases which occur as direct complications or sequelae. Bronchopneumonia, bronchitis, empyema, otitis media, frequently tonsillitis and sometimes erysipelas, occur as sequelae. Meningitis should frequently be included in this group.

Not only is there an increase in certain other diseases following influenza outbreaks, genetically related, as we have seen, but also some observers, particularly Crookshank, believe that previous to epidemic influenza prevalences there occurs an increase in the incidence of other entirely unrelated infectious diseases, such as poliomyelitis. This theory of simultaneous increase in invasiveness of many apparently unrelated germs is comparatively new and will probably receive deep consideration in the future. For the present the information on the subject is so limited that attempted conclusions would have no value.

ORIGIN OF THE 1918 PANDEMIC.

In discussing the spread of the 1918 pandemic over the earth, the author has traced it from an apparent origin in the United States. Localized early epidemics are reported simultaneously in the United States, France, and China. From the literature at his disposal he has been unable to find convincing proof of an earlier origin in Asia, but he did emphasize at the time the necessity of a much more thorough study of influenza in all countries to be made by more competent statisticians. Nevertheless it is highly interesting to formulate an hypothesis which appears to meet all demands, on the assumption that the disease originated in America. In order to hold a theory with this basis we must assume that the third of our previously mentioned hypotheses of the origin of the disease is the more nearly correct.

Let us assume that in the interpandemic periods the influenza virus is widely distributed over the earth, existing in an avirulent form. The basis for this assumption is the previously described occurrence of localized epidemics in interpandemic periods. The occurrence of solitary cases, although of interest, could scarcely be considered as evidence of the widespread distribution of the virus, but in the case of the small outbreaks as in 1900, 1907 and 1915, and as in the numerous small outbreaks described by Hirsch, the character of the epidemic curve is characteristic. Let us, then, assume that the disease has been endemic in the United States, together with other localities. It requires no keen observation to discover in the years 1917 and 1918, Theobald Smith’s “movement of individuals and masses from one part of the world to another, whereby the partly adapted parasites become planted, as it were, into new soil, and the original equilibrium is disturbed.” Not only was there a tremendous redistribution and concentration of individuals in our camps in this country, but also there was a further disturbance of the equilibrium in the outbreak of other infectious diseases, particularly measles. The effect of the measles epidemic on the virulence of the streptococcus and allied organisms has been discussed; presumably the same occurred with respect to the influenza virus. Howard and Love report that approximately 40,512 cases of influenza were reported in the United States Army during 1917. They write:

“In 1917, the death rate for the acute respiratory diseases (influenza, pneumonias and the common types) increased to 1.71. During the fall of 1917, after the camps were filled with drafted men, acute epidemic diseases swept through a number of them. Measles was one of the most prevalent and one of the most fatal of the infectious diseases that occurred. It was noted during the fall and early winter that there were a number of cases of pneumonia which were unlike the pneumonia that ordinarily occurred. This was apparent both to the physicians in civil life and in the army camps. It was reported by all classes of practitioners that numerous cases of pneumonia were occurring which resembled the pneumonia following measles, but occurring among men who had not had measles recently. In a number of the camps, both in the north and in the south, rather extensive epidemics of pneumonia occurred and a number of deaths resulted. The same variety of pneumonia occurred in the late winter and spring of 1918. In many of the camps pneumonia was practically epidemic during March and April. In many camps a number of cases occurred later in the spring and summer. It was again reported by a number of medical men that these cases of pneumonia that were occurring were different from the types of pneumonia ordinarily encountered and very similar to pneumonia following measles, but, again, that the cases occurred among men who had not had measles recently.”

MacNeal has observed similar conditions in the American Expeditionary Forces in France in 1917:

“The American troops in France in 1917 began to show, as early as October, 1917, a very considerable rise in the influenza morbidity. The data available in the office of the Chief Surgeon, A. E. F., show an influenza morbidity per 100,000 of 321 in July, 438 in August, and 404 in September, rising to 1,050 in October, 1,980 in November, and 2,480 in December, 1917, in which month the total number of new cases of influenza reported was 3,520. That a considerable proportion of these cases were actual infections with the bacillus of Pfeiffer is proven by the necropsy findings in fatal cases of bronchitis and bronchopneumonia, especially those performed by Major H. E. Robertson at Army Laboratory No. 1, Neufchateau, in November and December, 1917, and January, 1918. In these cases the bacillus of Pfeiffer was found in the scattered patches of lung involved in the bronchopneumonia and also with great frequency in the cranial sinuses. These necropsy findings were, at the time, recognized as essentially new for young adult Americans, and, in a discussion at Army Laboratory No. 1, during December, 1917, they were considered as being of possible important significance for the future morbidity of American soldiers in France. In the British Army in France there is definite evidence of epidemics showing the same pathologic condition, during the winter of 1916–17, and at Aldershot in September, 1917. There can be little, if any doubt that this disease was essentially the same which attacked the American soldiers late in 1917.”

Schittenhelm and Schlecht have reported that a disease was studied among the German troops on the Eastern front which resembled greatly the influenza. It occurred from the beginning of August to the middle of October, 1917. It attacked simultaneously and in epidemic form units and divisions very widely separated over a large territory. It was characterized clinically by a very sudden onset, in the greater number of cases with chill, headache, pain in the extremities, sometimes thoracic pain and cough. The fever lasted seven to nine days. The spleen was enlarged in 11 per cent. of the individuals. There was diarrhea in 12 per cent., frequently conjunctivitis, and quite often a scarlatiniform rash. Bacteriologic examination of the blood was negative. There was usually leucopenia. No treatment seemed especially efficacious. Aspirin gave the best results. The authors call attention to the close similarity to influenza and also suggest that it might have been due to transmission by insects as in pappataci fever or in dengue.

Carnwath concluded that the finding of influenza bacilli in necropsies in British soldiers in 1917 was without epidemiologic significance in considering the origin of the 1918 pandemic. He had studied the disease among the British in detail and appeared to be of the opinion that the first influenza morbidity of significance among the British troops did not appear previous to April, 1918.

MacNeal further says: “The influenza rates per 100,000 of 1,050 in November and 2,480 in December, 1917, really indicate a greater relative prevalence of influenza at that time in the A. E. F. than occurred in the fall of 1918, when the respective morbidity rates were 826 in September, 2,176 in October, and 1,356 in November. The total number of American troops in France was relatively small during that winter—141,995 effective mean strength in December—so that the prevalence of influenza did not lead to the recognition of an actual epidemic. Furthermore, the overcrowding in quarters, which seems to have had a definite relation to many of the later explosive outbreaks, had not become such a distinct feature at that time. In addition, the cold, wet weather, exposure and unusual living conditions furnished explanations for the morbidity which were no longer adequate during the hot weather of May and June, 1918. Until May, 1918, therefore, the prevalence was that of an endemic disease, with perhaps an occasional outbreak suggesting epidemic character.”

We admit that MacNeal’s report furnishes excellent evidence of an independent origin in France. Two points should be borne in mind. First, that MacNeal’s figures are not for the French, but for the Americans who were transported to that country, and that we may consequently consider influenza among the American Expeditionary Forces as being possibly from the same source as influenza among the troops in our own country,—that the American Expeditionary Forces may be considered a subdivision of the American Army in the United States, equally well as a subdivision of the French population; second, that we have been unable to find detailed evidence of similar conditions occurring among the French troops or French population, where the conditions have been ripe in a way since 1914. MacNeal records that in March and April, 1918, there was a great increase in the number of troops brought over from the United States to France. Previous to that time there had been 287,000 in that country and during the two months 150,000 were added, with a consequent increase of more than fifty per cent.

We should insert a word of caution regarding the diagnosis of influenza among troops in the absence of any sign of an epidemic. Internists who served in base hospitals during the war will agree that a diagnosis of influenza is very frequently made on the admission card when the disease turns out to be some other malady. This was not equally true in all camps, but regimental surgeons could often be found who would transfer a patient to the hospital with the diagnosis of influenza used almost interchangeably with the diagnosis “Fever of unknown origin.” It would be interesting to see statistics from one or two of those base hospitals which were manned with especially competent internists, as to the frequency with which the admission diagnosis of influenza remained unchallenged in the hospital, during the year 1917.

There would be such cases in greater or smaller numbers. The magnitude of this number would not influence our hypothesis.

Aside from this discussion of the disease among our troops in France it is most important that we establish, if possible, the identity of the disease reported among British troops in Northern France during the winter of 1916–1917 and designated by the name “Purulent Bronchitis.” The disease first appeared in December, 1916. It reached its height during February and early March of 1917, and appears to have disappeared early in the spring. Hammond, Rolland and Shore report that during February and early March 45 per cent. of the necropsies under observation showed the presence of purulent bronchitis, and they remarked that the disease assumed such proportions as to constitute almost a small epidemic. They described the clinical aspects as follows:

“The cases which came under our notice can be divided broadly into two types: The first and more acute presents a clinical picture which closely simulates ordinary lobar pneumonia with a sustained temperature of about 103°, and expectoration at first blood-streaked—rather than rusty—which, however, rapidly becomes quite purulent. The pulse-rate in these cases is out of all proportion to the temperature in its rapidity. Dyspnoea and cyanosis are prominent features. The patient usually dies from ‘lung block,’ resulting in embarrassment of the right side of the heart on the fifth or sixth day. For the last day or two there is often incontinence of the feces, due, no doubt, to the condition of partial asphyxia. The mental state is one of torpor; delirium is the exception.

“The second and less acute type is marked by a more swinging temperature with a range of two or three degrees. The expectoration at first may be frothy and mucopurulent, but it very soon assumes the typically purulent character. This form may run a long course of from three to six weeks, during which time the patient wastes a great deal and has frequent and profuse sweats; indeed, at a certain stage the illness is most suggestive of acute tubercular infection, and it is only by repeated examination of the expectoration that the clinician can satisfy himself he is not really over-looking a case of acute pulmonary tuberculosis. The majority of our cases conforming to this type have ultimately recovered, but the convalescence is slow and tedious.

“Onset.—Whilst a history of a previous catarrhal condition lasting for a few days is often obtained, the disease quickly assumes an acute character; we have been able to observe this in patients admitted into this hospital with purulent bronchitis; we find the temperature is between 102° and 103°, the pulse 120 or over, and the respiration about 35. The patient frequently complains of shivering and looks pathetically miserable, but we have not seen an actual rigor. Despite his obvious shortness of breath, the sisters have noticed that, at any rate at first, he prefers a lateral position low down in the bed, and resents any attempt to prop him up.

“Cough.—This for the first day or two may be irritable and distressing, with a little frothy expectoration, but as the latter becomes more purulent the cough is less troublesome, and soon the patient is expectorating easily and frequently, until the later stages are reached; when owing to increasing asphyxia the patient becomes more and more torpid, the cough subsides, and hardly any secretion is brought up. This failure becomes an added factor in bringing about a rapidly fatal termination.

“Expectoration.—The sputum, with its yellowish-green purulent masses, is very characteristic, and may be one of the first indications of the serious nature of the illness the patient is suffering from.

“Temperature.—The fever of this complaint does not follow any very constant type. In nearly all our cases the pyrexia was of sudden onset, and for the first few days was more or less sustained at about 103°. Later it conformed more to the swinging type with a range of several degrees. In a few cases a curious gradual ante mortem drop has been observed.

“Pulse.—Tachycardia is a very constant feature throughout the illness. The rate is frequently well over 120, though the volume may remain surprisingly good until immediately before death.

“Some degree of dyspnoea is always present, and is usually progressive, though towards the end in the fatal cases when the mental acuteness is dulled by the increasing asphyxia the patient is not distressed by its presence. In some cases there have been paroxysmal exacerbations of the breathlessness, accompanied by a state of panic, in which the patient struggles wildly and tries to get out of bed in order to gain relief. Cyanosis is another prominent feature throughout the illness. At first it may not be more than duskiness, but in the later stages it becomes very evident. It is only slightly relieved by oxygen; this, no doubt, is partly explained by the difficulty in giving the oxygen efficiently, owing to the patient’s objection to any mouthpiece that fits at all tightly, and partly by the blocked condition of the bronchioles interfering with the absorption of the oxygen.

“The condition usually begins with the presence of a moderate number of sharp crepitant râles, often first heard in the region of the root of the lung; these quickly become generalized. In the majority of the cases signs of bronchopneumonia patches can be made out; these are generally situated near the root of the lungs. In a certain number of cases these patches spread and become confluent, giving practically all of the physical signs of a lobar pneumonia. As the disease progresses the air entry is diminished; on listening one is often struck by the small volume of sound heard. The resonance of the lungs may also be lessened. A slight pleuritic rub was heard in a few of our cases, but this was soon masked by the bronchitis signs.”

Detailed sputum examination in twenty cases showed the presence of the influenza bacillus in eighteen, and in ten out of these eighteen the organism was isolated by culture. The next most frequent organism found was the pneumococcus, which was present in thirteen cases. The streptococcus was found in five.

Abrahams, Hallows, Eyre and French report the same epidemic:

“A typical case is as follows. The onset is usually acute; the early symptoms are those of a ‘cold in the head.’ The temperature may be 101 or 102°, but there are no features to distinguish the condition from acute ‘coryza’ or febricula, so that in the majority of cases the patient does not report sick for two or three days, by which time he is sent to the hospital. At this state two features attract particular attention. First, the character of the expectoration: this consists of thick pale yellow, almost pure pus, not the frothy expectoration familiar in ordinary bronchitis; it has no particular odor and it becomes increasingly abundant until in a day or two it may amount to several ounces in the twenty-four hours. Secondly, the rapidity of the patient’s breathing: this may be so evident that pneumonia suggests itself, yet on examining the chest the only physical signs consist of few or many rhonchi scattered widely, but most marked at the bases of the lungs behind, associated with a wheezy vesicular murmur; resonance everywhere is unimpaired and bronchial breathing is absent. A little later a third point attracts notice; a peculiar dusky heliotrope type of cyanosis of the face, lips, and ears, so characteristic as to hall-mark the nature of the patient’s malady even on superficial inspection. By this time dyspnoea is very pronounced; respiration consists of short, shallow movements, which in bad cases amount almost to gasps, reminiscent of the effects of gas poisoning. Recovery at this stage may occur, but by the time the cyanosis has become at all pronounced the prognosis is extremely bad, though the number of days the patient may still live, in spite of the severity of his distress, is often surprising. The character of the sputum remains the same throughout, though sometimes it is blood-tinged or actual blood may be expectorated instead of, or in addition to, the more typical pale yellow pus. In the later stages of the illness areas of impaired note or of actual dullness may be found, particularly over the posterior aspects of the lungs, associated with bronchial breathing and crepitant râles. These may be due to the progression of the purulent bronchitis into hypostatic pneumonia, or into actual bronchopneumonia at the bases; or, on the other hand, they may be due to massive collapse of the lungs secondary to the bronchitis and obstruction of the bronchioles by pus. In a few cases, not necessarily the most serious, a frank lobar pneumonia has developed later, and has been followed by an empyema from which 15–30 ounces of thin pneumococcal pus has been aspirated—in one case alone was resection of a rib unavoidable. The condition, however, is not primarily a lobar or a bronchopneumonia, but a bronchitis, and although a small amount of basal bronchopneumonia has been present in one or two of our post-mortem examinations, in other fatal cases there has been no bronchopneumonia at all, not even the smallest portions of either lung being found to sink in water.

“We have no doubt that the condition is primarily an affection of the bronchi and bronchioles, and not of the alveoli, though the alveoli may be affected later if the patient survives long enough. In a typical post-mortem examination it would be difficult, or almost impossible, to define the actual cause of death unless one knew the clinical history.”

Abrahams and his collaborators describe in detail eight consecutive cases. A study of the type of onset may be of help in determining the character of the disease. The first patient had been subject to bronchitis for years. He had been ill with cough and some pyrexia for five days previous to his admission. There is no further description of his admission symptoms. Case two was admitted on March 17th, having taken ill the previous day with shivering, cold and pain in the chest. The temperature was 104°, the pulse-rate 118, and the respirations were 44. The patient was very restless and had much dyspnoea but was not cyanosed. The third patient had taken ill three days previous to admission with symptoms of cold in the head and a sore throat. He complained of headache and dry cough without expectoration, shortness of breath, and a pain behind the sternum.

Case four was admitted with a history of having been out of sorts with a cold and bronchial cough for ten days previously. On admission his temperature was 103°, pulse-rate 112 and respiration-rate 36. He had abundant blood-stained purulent sputum.

Case five is the first case that shows a type of onset distinctly resembling that of influenza. The patient had been ill three days with headache, cough and generalized pain previous to his admission. The temperature on admission to the hospital was 103°, pulse-rate 112, respiration-rate 20. There were no abnormal physical signs in the chest on admission. They did appear two days later. Case six related that he had been sleeping under canvas for three nights before coming to the hospital, and that during the first of these nights he was taken ill with a cold which became associated with a cough and increasing shortness of breath. On admission there was slight cyanosis, and dyspnoea was very pronounced. Shortly afterwards he became orthopnoeic, with heliotrope cyanosis. On the slightest exertion, such as turning over in bed, the cyanosis increased markedly, and although the respiration-rate remained under forty when he was at rest, on the least exertion it increased to nearly sixty. The sputum was purulent and abundant, pale yellow, not frothy and not blood-stained, and the day after admission contained Bacillus influenzae, pneumococcus and Micrococcus catarrhalis.

Case seven had been ill seven days before admission with cough and fever. On admission his temperature was 105°, pulse 116, respiration 24. Case eight gave a history of having had a cough for eight days previous to admission. This cough had not incapacitated him much at first, but he became progressively worse during the four days before admission, with increasing shortness of breath and abundant yellow sputum which he found it difficult to raise. On admission dyspnoea with cyanosis was very evident.

Even from these detailed clinical descriptions it is impossible to say definitely whether the disease was or was not influenza. There is no doubt, however, but that clinically the disease resembled more the so-called streptococcus pneumonias that were observed in the United States camps in the winter of 1917–18. The descriptions of the mode of onset are particularly at variance with the onset as we know it in influenza.

Those who believe that the influenza bacillus is the cause of influenza maintain that the finding of this organism in a large per cent. of cases by both groups of observers is valuable evidence. For reasons previously stated we cannot agree.

Description of the epidemic features is not detailed enough to be of assistance. The first group of authors remark that the disease constituted “almost a small epidemic.” The second group say that six out of eight cases in their series of candidly reported patients came from one command. The former report on twenty cases, the latter on eight. The latter remark that although they have dealt with only eight cases in detail, they had a much larger number altogether. Presumably there were a decidedly larger number of patients in both hospitals, but the actual number is not stated. In short, we do not know whether the disease appeared to be more or less epidemic than the apparently similar disease among our troops in the winter of 1917–18.

Both groups of observers have described in some detail the pathology of the cases which were necropsied. The author in attempting to obtain further comparative information has submitted the pathologic descriptions given by the British authors to Dr. E. W. Goodpasture, who has very kindly pointed out the points of similarity and difference between the gross and microscopic findings in these cases of purulent bronchitis, and the same findings in typical influenza. He says that the lung picture, as described, is not the same as that which was typical of the acute influenza observed in the autumn of 1918 and again in the winter of 1920. The characteristic picture in the latter is primarily an extensive involvement of the alveolar structure, while as Abrahams and his associates remarked, the condition in their case is primarily “an affection of the bronchi and bronchioles, and not of the alveoli, though the alveoli may be affected later, if the patient survives long enough.” Goodpasture states that the pathology as described by the British authors is very similar to the lung picture in interstitial bronchopneumonia described by MacCallum for the post-measles and primary bronchopneumonia among our troops in the winter of 1917–18. The streptococcus and the influenza bacillus were dominant organisms in MacCallum’s series. It also resembles the pathologic picture described by Pfeiffer in his original article on one of the late recurrences of the 1889–93 epidemics of influenza.

In summing up, we must admit that it is impossible to reach a definite conclusion, but that both clinically and pathologically the disease described among the British troops in 1916 and 1917 was not typical of influenza as we have known it more recently. The similar conclusion reached by Carnwath, presumably chiefly from epidemiologic considerations, has already been described. We do not deny that this “purulent bronchitis” may have been influenza. On the contrary, it is a part of our hypothesis that influenza under the proper conditions may become epidemic in practically any land. But we do believe that the evidence has not shown that the disease among the British troops in 1916 and 1917 was an etiologic precursor of the great pandemic.

To return to a discussion of influenza in China, we quote from an article by Cadbury in the China Medical Journal: “Unfortunately no health reports are available for the greater part of the Chinese Republic. We have consulted, however, the Health Reports of the Shanghai Municipal Council from 1898 to 1917, and among the total foreign deaths we find that only the following were attributed to influenza: 1899, one death; 1900, one death; 1907, four deaths; 1910, one death. After this no deaths are recorded from this cause up to and including the year 1917.

“In the Hongkong Medical and Sanitary Reports, which give the total deaths registered in the Colony, we have examined the records from 1909 to 1917. During these nine years only two deaths were attributed to influenza, and both occurred in 1909.

“From a personal letter from Dr. Arthur Stanley, Health Officer in Shanghai, dated February 11, 1919, I quote the following:

“‘As to influenza we had an attack beginning at the end of May and lasting through June and again in the latter part of October and lasting through November. The latter was somewhat more severe. The noteworthy features were general absence of catarrhal symptoms, congestive pharynx frequent, as also was a slight erythematous blush on the neck and chest, which made one think at first of scarlet fever. Fatal pneumonia common among the Chinese and Japanese, but among Europeans very little pneumonia.’

“In his report for May, 1918, Dr. Stanley says that the disease was reported to have reached Peking before it came to Shanghai, but subsequent reports showed that most of the river ports were almost simultaneously infected, the rate of spread conforming to the rate of conveyance by railways and boats of infected persons. The mortality was very low.

“Newspaper reports indicate that a third appearance of the disease in Shanghai occurred from the middle of February, 1919, which was still prevalent in April. The symptoms were much more severe.

“For Hongkong I quote from a personal letter from Dr. Hickling, the Principal Medical Officer of Health, dated January 29, 1919:

“‘The epidemic of influenza in the spring was a very mild one, so far as we can judge. The disease did not last more than a few days in most cases. The recent epidemic (October, November, December and January) has been much more severe, often lasting two or three weeks.’

“Only one death, which occurred on May 14th, was reported from Hongkong in the spring. In the later epidemic the deaths reported were as follows: October, 70; November, 95; December, 67. The first of these deaths occurred on October 5th. The figures for January had not been compiled, but the disease was diminishing.

“Dr. C. W. McKenny of Hongkong has kindly furnished me with the following facts: ‘During the first five months of 1918 there were twenty-two admissions for influenza to the Civil and Tung Wa hospitals (3 in May). In June there were 269 cases with three deaths. In July, August and September, 43 cases; and during October-November, 130 cases with four deaths....

“‘The June epidemic in Canton appeared first at the Pui Ying School, then among the employees of the Post Office, the staff of the Canton Hospital, the Canton Christian College, and the Kung Yee Hospital. The other schools entirely escaped. Eleven days were taken by the disease to spread from one part of the city to the various other parts.’”

Plague appeared in the north of China in 1917, originating apparently in inner Mongolia. The spread extended over quite an area, and it is reported that this epidemic of pneumonic plague has been more extensive than any since that of 1910–11. The disease was first reported prevalent in Patsebolong December 6, 1917. The diagnosis was confirmed bacteriologically, and there can be little doubt but that the cases of plague reported in various parts of China even up to March 18th were true plague, and not unrecognized influenza.