SECTION I.. _general Epidemiologic Considerations._

General Epidemiologic Considerations.

Those who seek to find in a study of the epidemiology of epidemic influenza the secret of the causation of the disease, and its ultimate eradication, are probably predestined to at least partial failure. We must call upon the bacteriologist for information as to the causative organism, and in time he may be able to furnish us with satisfactory prophylactic measures, particularly with a successful vaccine.

But while pure epidemiologic studies will not demonstrate the ultimate factor in the etiology, nevertheless these studies do subserve several most important functions. The bacteriologist, the immunologist, the serologist have accumulated a wealth of information since the 1918 pandemic, but as far as definite conclusions concerning the causative agent of the disease are concerned we are no nearer to the truth than we were at the time when Pfeiffer made his original observations. There is no incontrovertible evidence by which one may say that the influenza bacillus is or is not the cause of the disease. We must therefore await further studies and future discoveries. But we cannot await idly in the knowledge that new epidemics of the dread disease will surely come, probably mild ones in the next few years, and certainly severe ones again within a few decades. We must amass all of the available information concerning the mode of action of the disease, its manner of spread, its degree of infectivity, its distribution and the mode of its recurrences, and try to formulate from a study of the available facts some means of protecting ourselves against the epidemic, if not of preventing it entirely.

In short, in the present state of the bacteriologic knowledge of the disease, we may say that the epidemiologic features are the only facts upon which we have to build in planning our defense. Today, the practical work in the eradication of influenza must depend chiefly, if not solely, on the general methods of preventive medicine.

Many valuable monographs have been written on the subject, particularly following the pandemic of 1889–1893, but these have all emphasized features and phases of the disease which seemed at that time to be particularly important. Facts which seemed of extreme importance to the earlier writers are today in some instances considered relatively unimportant, while other phenomena which were but touched upon by the former investigators today have assumed deep significance. For this reason it is worth while to reproduce here the observations made in previous epidemics, and to correlate them with the facts developed in the abundant literature of the last few years, and to draw therefrom inferences as to the life and habits of the influenza virus, and conclusions as to the means of interrupting its progress.

HISTORICAL.

The history of influenza can justly be divided into two phases, the first ancient, and the second modern. The latter period begins with the 1889 pandemic. By that time the science of bacteriology had altered our concepts of the etiology of disease and epidemiologists had begun to avail themselves of statistical methods of analysis. For the purposes of this paper, therefore, consideration will be given chiefly to the epidemic of 1889, and a summary of earlier epidemics will be made merely to refresh our minds concerning the antiquity of the disease and the periods of its occurrence. References to the earlier epidemics will be made more particularly in the special discussions later, where points of similarity or difference will be brought out. Further than that it is unnecessary to go in the history of the disease, for the several excellent monographs of 1890 to 1900 tell the historical story in a manner that could scarcely be improved upon.

The great antiquity of epidemic influenza is a fact which I think may be admitted in spite of some who hesitate to accept it because of lack of convincing descriptive evidence. Some believe that the epidemic of the year 412 B.C., described by Hippocrates and by Livy, was an epidemic of influenza. Some have suggested that the epidemic described by Thucydides was the same disease. Parkes remarks that the epidemic pervading the Athenian Army in Sicily in 415 B.C., recorded by Diodorus Siculus, has been supposed to have been influenza. Finkler, in referring to a report by Diodorus of a pestilence occurring in 395 B.C., which broke out in the Greek Army at the siege of Syracuse, and which killed off the soldiers murderously, says that this could not have been influenza. He regards as sufficient argument the fact that the mortality was high. After the epidemic of 1918, one is more inclined to believe that the epidemic in Sicily may well have been true influenza. We must remember that previous to the last few pandemics the stories have been fragmentary in character and were told, not by physicians, but chiefly by the historians of the time, men who have desired to impress their readers with some idea of the horrible ravages of the disease, and who have doubtless in some instances transmitted the impression of monstrous mortality rates. The early historians were much given to figures of speech, many of which were very telling in conveying the impression desired. Finally, the writers of the middle ages and of earlier times had little or no statistical material on which to base their conclusions. I have no doubt that a historian who during the 1918 epidemic of influenza might have limited his observations entirely to the disease as it occurred at Camp Sherman, Ohio, and who saw 125 robust soldiers dying each day, would have truly written that the disease killed off the soldiers murderously. A further statistical argument in favor of considering the epidemic among the Greek soldiers as quite possibly influenza is the fact that as shown by present day findings these men were all of the age in which the mortality is highest, and were living under sanitary conditions which predispose to high incidence and high mortality.

According to Parkes, in 827 A.D., an attack of “cough” which spread like the plague was recorded. In 876, Italy and later the whole of Europe was attacked, and the army of Charlemagne, returning from Italy, suffered greatly. “Dogs and birds were attacked at this time.” In 976 the whole of France and Germany was attacked by a fever whose principal symptom was cough. There is also record of diseases which may have been influenza which were seen in Germany and France in 927 and in England in 996 and 997. All of these records are indefinite and from their nature unconvincing to a critical student. Several investigators have gone over these past records up to 1889 with the idea of determining definitely what plagues were, and which were not, true influenza. The criteria used by the various investigators have differed slightly in some instances. For instance, one chooses to use the record of low mortality in widespread epidemics as the chief characteristic of pandemic influenza, while another emphasizes principally the complications.

The experience of recent years has amply demonstrated that influenza may be characterized by a high mortality or a low mortality; that pneumonia may be prevalent or relatively rare during an epidemic. These features are not truly characteristic of influenza itself. They are phenomena which depend chiefly for their existence on secondary invasion with organisms other than the causative agent of influenza. It may be that the influenza virus itself is capable of producing pneumonia, but it is generally accepted that an overwhelming majority of the complicating pneumonias are due to secondary infections. One perusing the former literature today would hesitate to state that an ancient epidemic was not influenza merely because it was accompanied by high mortality, nor would he wish to say that it was not this disease because there was no mention of a high incidence of pneumonia. We have had both types within the last few years, as in March and April, 1918, when the disease appears to have been accompanied by a very low mortality and a low incidence of pneumonia, and in October of the same year when the pneumonia incidence and the death rate were both relatively much higher.

Attention should be called to a certain inaccuracy which has appeared in the literature and which has resulted in some instances in a misunderstanding of the entire history of influenza. Finkler says: “According to August Hirsch the first influenza epidemic occurred in 1173 and he places it in his work as the first out of eighty.” This has given the impression to some that influenza was unknown previous to that date. Leichtenstern has quoted Hirsch more accurately and thereby given an entirely different meaning to the statement. “August Hirsch says that the first epidemic that can be definitely said to be influenza occurred in 1173.” Jordan also conveys the latter impression. He remarks that the first extensive, well described epidemic of influenza occurred in 1510.

Hirsch places the first authoritative influenza epidemic in the year 1173; Zeviani in 1293; Gluge in 1323; Schweich, Biermer and Ripperger in 1387; while Saillant, Thompson, Zuelzer and Leichtenstern accept nothing prior to the first pandemic of 1510 as being unquestionably influenza. It should be remarked here that opinion is not unanimous in every case as to the identity of all epidemics following 1510.

Hirsch concluded that there have been about eighty epidemics since that of 1173. Parkes states that in the fourteenth century there were six epidemics, in the fifteenth seven, in the sixteenth eleven, in the seventeenth sixteen, in the eighteenth eighteen, while in the first half of the nineteenth ten epidemics are on record.

Table I shows in brief review the occurrence of the more important epidemics since the year 1173. Like all similar summaries given in tabular form it possesses the disadvantage of telling only parts of the entire story, and those in only a very general way, but it will suffice as a resumé and for the emphasis of certain phenomena to which attention will be later directed.

Concerning the epidemic of 1889, it is usually stated that it had its origin in Bokhara in May of that year. As will be seen from the table influenza was present also in Greenland and the Hudson Bay territory in the spring of 1889. The possibility of simultaneous origin in at least two localities in that year will be discussed later. The epidemic remained in Bokhara until August of the same year, after which time it slowly traveled to Siberia where at Tomsk traces of the disease were observed with certainty in October. At that time it was also observed in the Caucasus and in European Russia. It appeared in Petrograd in October, 1889, and remained epidemic until December of that year. The spread of this epidemic throughout the world is indicated in the following table adopted from Leichtenstern:

Spread of Influenza in 1889–90.

═══════════════════════════════════════════════════════════════════════ Month. 1889–90. ─────────────────────────────────────────────────────────────────────── First (October) St. Petersburg, Moscow, Courland, Livonia, Finland. Second Berlin, Paris, Vienna, Sweden, Denmark. Third London, Holland, Belgium, Balkan States, North America. Fourth Capetown, Egypt, Honolulu, Mexico, Japan, Hong Kong. Fifth San Francisco, Buenos Ayres, India, Sierra Leone, Scilly Islands. Sixth Chili, Kamerun, Zanzibar, Basutoland, Tasmania. Seventh British Bechuanaland, Barbados. Eighth Gold Cost, Natal. Ninth Trinidad. Tenth Iceland, Madagascar, China, Senegal. Eleventh Kashmir, Katunga. ───────────────────────────────────────────────────────────────────────

Between the years 1889 and 1893 according to Leichtenstern there was no period altogether free from influenza. Here and there individual cases or small epidemics sharply localized were observed. In 1893 another epidemic appeared in many places and became quite widespread. There was not, according to this author, the definite geographic progression that had been observed in 1889. This was but a recrudescence, a lighting up from endemic foci remaining after the first wide spread. In the first half of 1893 there was a light spring epidemic, and in November of the same year a larger epidemic swept over the whole of Europe. The height of the latter was reached chiefly in December.

The influenza incidence subsequent to 1893 will be discussed later.

TABLE I. Influenza epidemics previous to 1889. ═════╤══════════════╤═════════════╤══════════════╤═══════════════╤══════════════ Date.│ General │ Site of │ Direction of │ Localities │ Rapidity of │ features. │ origin. │ spread. │ affected. │ spread. ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1173│Rather meagre │Unknown. │ │Described in │Not known. │description. │ │ │Italy, Germany,│ │ │ │ │England. │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1239│Described by │Described in │ │Invaded all of │ 1311│Zeviani. │France. │ │France. │ │Records not │ │ │ │ │definite. Not │ │ │ │ │generally │ │ │ │ │accepted. │ │ │ │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1323│Mentioned by │ │ │ │ │Hirsch, Gluge │ │ │ │ │and Zeviani. │ │ │ │ │Most believes │ │ │ │ │it was a │ │ │ │ │typhoid │ │ │ │ │epidemic. │ │ │ │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1327│Mentioned by │ │ │Described in │ │Zeviani, │ │ │Italy. │ │Hirsch and │ │ │ │ │Gluge. Rather │ │ │ │ │doubtful. │ │ │ │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1358│Described by │ │ │Savoy, Germany,│ │Zeviani. Not │ │ │France, │ │generally │ │ │Catalonia. │ │accepted. │ │ │ │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1387│(Zeviani, │Italy. │ │Italy, France, │ │Schweich, │ │ │Strasbourg, │ │Gluge, Hirsch │ │ │Southern │ │and │ │ │Germany. │ │Ripperger.) │ │ │ │ │Characteristic│ │ │ │ │description. │ │ │ │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1403│A very short │France. │ │Described in │ │epidemic. │ │ │France. In 1404│ │(Gluge, │ │ │it invaded │ │Ripperger, │ │ │Flanders and │ │Pasquier.) │ │ │Germany │ │ │ │ │(Hirsch). │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1411│Described only│Described │ │Described by │ │in Paris. │only in │ │Pasquier as in │ │Extent │Paris. │ │Paris. │ │unknown. │ │ │ │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1414│Characteristic│ │ │In Italy and │ │description. │ │ │France in │ │ │ │ │February and │ │ │ │ │March. In the │ │ │ │ │Danube district│ │ │ │ │between January│ │ │ │ │and April. │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1427│Very │ │ │Described in │ │characteristic│ │ │France. │ │description. │ │ │ │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1438│Cited only by │ │ │Described in │ │Zeviani. │ │ │Italy. │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1482│Very limited │ │ │ │ │description by│ │ │ │ │Mezeray. │ │ │ │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1510│Widespread │Malta (?) │Generally, │Malta, Sicily, │ │over all of │(Webster and │from South to │Spain and │ │Europe. │Hancock │North. │Portugal, │ │ │report that │ │Italy, France, │ │ │it began in │ │Hungary, │ │ │Africa). │ │Germany, │ │ │ │ │Holland, │ │ │ │ │England, │ │ │ │ │Norway. │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1557│All of Europe.│Conflicting │General │Asia, │4 months from │ │information │direction from│Constantinople,│Italy to │ │(Asia?). │South to North│Sicily, Italy, │Netherlands. │ │ │in Europe. │Spain, │Sicily in │ │ │ │Dalmatia, │June. Nimes in │ │ │ │Switzerland, │July. Italy in │ │ │ │France, │August. Madrid │ │ │ │Netherlands, │in August. │ │ │ │England. │Dalmatia in │ │ │ │ │September. │ │ │ │ │Netherlands in │ │ │ │ │October. ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1562│Uncertain │ │Only small │ │ 1563│information. │ │epidemics at │ │ │ │ │most. │ │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1580│True pandemic │Orient │From Asia to │Orient, North │France in May. │covering the │(Hirsch) │Constantinople│Africa, │Germany and │Orient, Africa│Africa and │and in Europe │Constantinople,│Hungary in │and Europe. │Malta │from South to │Malta, Venice, │August. │ │(Pechlin). │North. │Sicily, Italy, │England and │ │ │ │Spain, Hungary │Rhine Valley │ │ │ │and Germany to │in September. │ │ │ │the Baltic, │Saxony in │ │ │ │Bohemia, │October. │ │ │ │France, │ │ │ │ │Belgium, │ │ │ │ │England, │ │ │ │ │Denmark, │ │ │ │ │Sweden. │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1587│Apparently │ │ │Described in │ │quite │ │ │Italy and │ │localized. │ │ │Germany. │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1591│High │ │ │ │ │mortality. │ │ │ │ │Indefinite │ │ │ │ │information. │ │ │ │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1593│Spread over a │Said to have │Uncertain. │ │ │wide area in │commenced in │ │ │ │Europe. │Belgium, │ │ │ │ │“following a │ │ │ │ │violent │ │ │ │ │earthquake,” │ │ │ │ │and gradually│ │ │ │ │extended over│ │ │ │ │all the │ │ │ │ │cities of │ │ │ │ │Europe. │ │ │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1626│Local. │ │ │Described in │ │ │ │ │Italy. │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1627│In America. │ │Spread from │ │ │ │ │North America │ │ │ │ │to West Indies│ │ │ │ │and Chili. │ │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1647│In America │ │ │ │ │(Webster). │ │ │ │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1658│Local. │England (?). │ │Described in │ │ │ │ │England and in │ │ │ │ │Treptow near │ │ │ │ │Stettin. │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1675│Over Western │Germany (?). │ │Germany, │Germany in │Europe. │ │ │Hungary, │September, │ │ │ │England, │England and │ │ │ │France. │France in │ │ │ │ │October and │ │ │ │ │November. ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1688│Apparently │England(?). │ │Described only │ │localized in │ │ │in England and │ │Great Britain │ │ │Ireland. │ │and Ireland. │ │ │ │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1693│England and │Dublin(?). │ │Dublin, Oxford,│One month from │the adjacent │ │ │London, │Dublin to │continent. │ │ │Holland, │London. │ │ │ │Flanders. │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1709│A period of │In 1712, │1712, spread │Italy, France, │Six months 1712│extensive │onset in │from Germany │Belgium, │from Germany │endemics. │Germany. │to Holland and│Germany, │to Italy. │ │ │Italy. │Denmark. │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1729│First epidemic│Usually │Russia through│Moscow, Sweden,│Moscow in │said to have │designated as│Sweden, │Poland, │April, 1729. │originated in │Russia │Poland, │Silesia, │Sweden in │Russia and │(Moscow). F. │Germany, etc. │Austria, │September, │first │Hoffman │to Italy and │Hungary, │England in │described as │claimed to │perhaps North │England, │November. │entering │have seen the│America. │Switzerland, │Paris in │Europe from │epidemic in │ │France, Italy, │December. Rome │the Northeast │Halle in │ │Iceland. │in February, │rather than │February, │ │ │1730. │the Southeast.│1729. │ │ │ │First spread. │ │ │ │ │Pandemic │ │ │ │ │period. │ │ │ │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1732│Second spread.│ │Over Europe │ │Germany in │Pandemic │ │and America. │ │November. │period. │ │According to │ │France in │ │ │Pelargus it │ │January, 1733. │ │ │again followed│ │Spain and │ │ │the route from│ │Italy in │ │ │Russia through│ │February. │ │ │the North of │ │ │ │ │Europe and │ │ │ │ │then South. │ │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1737│Not generally │ │ │England, North │ │recognized. │ │ │America, │ │ │ │ │Barbados, │ │ │ │ │France. │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1742│Slow spread │Began either │Occurred in │Germany, │Germany in 1743│from Germany. │on the shores│Germany in │Switzerland, │January, 1742. │Recurrences in│of the Baltic│Jan. and Feb.,│Italy, France, │England in │Germany up │Sea or in │1742, and then│Holland, │April, 1743. │until 1745. │single cities│disappeared to│Belgium, │ │ │in Germany. │reappear in │England. │ │ │ │Switzerland in│ │ │ │ │the spring. │ │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1757│A period of │Began either │France, │Barbados, │Villalba 1758│related │first in │Scotland, │Germany, │states that 1761│epidemics with│North America│America, │Austria, │the epidemic 1762│complicated │and spread │Finkler states│Hungary, │in 1767 had 1767│geographic │thence to │that in 1762 │Denmark, │traveled over │pictures and │Europe or │influenza │England, │the whole of │without clear │else began │first started │Ireland, │Europe in a │cut direction │spontaneously│in Germany and│Alsace. │period of two │of spread. │in both │spread thence │ │months. │ │hemispheres. │in a very │ │ │ │ │irregular way │ │ │ │ │over Western │ │ │ │ │Europe. Gluge │ │ │ │ │and Hirsch │ │ │ │ │state that in │ │ │ │ │1767 the │ │ │ │ │disease │ │ │ │ │appeared │ │ │ │ │simultaneously│ │ │ │ │in Europe and │ │ │ │ │North America.│ │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1775│Slow spread │First │First spread │Germany, Italy,│Invaded Vienna 1776│through │appearances │to Vienna, and│Austria, │in June. Made │Western │in Autumn of │after a │England, │appearance in │Europe. │1775 in │quiescence │Ireland, │Italy in │ │village of │broke out in │France. │September. In │ │Clausthal in │France and │ │England and │ │the Harz │England and │ │France in │ │mountains. │possibly │ │October, │ │ │spread to │ │November and │ │ │America and │ │December. │ │ │China. │ │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1780│Western Europe│January, 1780│Spread to │ │Three months 1781│and possibly │in France. │Alsace, │ │from France to │Brazil and │ │Germany and │ │Brazil. │China. │ │Italy, and in │ │ │ │ │March reported│ │ │ │ │in Rio de │ │ │ │ │Janiero. │ │ │ │ │Appeared in │ │ │ │ │Sept. 1780 on │ │ │ │ │Southern coast│ │ │ │ │of China. │ │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1781│One of the │China and │Through │China, India, │Moscow, 1782│most │perhaps India│Siberia and │America, │January, 1782. │widespread │in Autumn of │Russia to │Russia, Riga, │Riga, │pandemics. │1781 │Petrograd, │Germany, │February. │Abundant │(Hirsch). │Finland, Riga,│England, │Germany, │literature. │English │Germany, etc. │Scotland, │March. │ │writers │ │Netherlands, │England, │ │connect onset│ │Ireland, │April. │ │with │ │France, Italy, │Scotland, May. │ │occurrence of│ │Spain. │Ireland, │ │influenza in │ │ │France and │ │the British │ │ │Italy, June. │ │Army in │ │ │Spain, August. │ │India, Nov., │ │ │ │ │1781. Wittwer│ │ │ │ │and others │ │ │ │ │begin its │ │ │ │ │history in │ │ │ │ │Petrograd in │ │ │ │ │January, │ │ │ │ │1782. │ │ │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1788│Throughout all│Russia, in │West and │Russia, │Seven months 1789│of Europe. One│March, 1788. │South. Spread │Germany, │required to │year later in │“Apparently │in America in │Hungary, │cover this │America. │independent │1789 │Denmark, │territory. │ │origin in │throughout │England, │ │ │America in │United States │Scotland, │ │ │Sept., 1789.”│from New York │France, Italy, │ │ │ │North and │Switzerland. │ │ │ │South and │ │ │ │ │finally │ │ │ │ │touching the │ │ │ │ │West Indies, │ │ │ │ │South America │ │ │ │ │and Nova │ │ │ │ │Scotia. │ │ │ │ │Recurrences in│ │ │ │ │single cities │ │ │ │ │of U. S. in │ │ │ │ │1790. │ │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1799│Local epidemic│Origin in │Spread West │Russia, │ 1800│confined to │Russia. │and South. │Galicia, │ │Northeastern │ │ │Poland, │ │Europe. │ │ │Germany, │ │ │ │ │Denmark. │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1802│Local endemic │First │No clear cut │France, │ 1803│outbreaks │reported in │direction. │Germany, Italy,│ │covering │France. │Recurrences │England, │ │considerable │ │until 1805–08.│Switzerland, │ │territory │ │General │Central Europe.│ │which follow │ │dissemination │ │ │the last │ │throughout │ │ │period by a │ │North America │ │ │quiescence of │ │in 1807. │ │ │five months. │ │ │ │ │There appears │ │ │ │ │to have been │ │ │ │ │an │ │ │ │ │unassociated │ │ │ │ │epidemic early│ │ │ │ │in 1800 in │ │ │ │ │China and one │ │ │ │ │in Brazil. │ │ │ │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1811│Several │1807, onset │Usually from │North and South│1815, one 1815│epidemics in │in │New England │America. │month from 1816│North America │Massachusetts│West and │ │Boston to New 1824│and to some │in February. │South. │ │York, and five 1826│extent in │1815, onset │ │ │months to │South America.│in Boston in │ │ │South Carolina │ │September. │ │ │and Brazil. │ │1824, onset │ │ │1824, three │ │in Boston in │ │ │months from │ │October. │ │ │Boston to │ │ │ │ │Georgia. ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1827│Widespread │ │ │ │ │epidemics │ │ │ │ │throughout │ │ │ │ │Eastern Russia│ │ │ │ │and Siberia. │ │ │ │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1830│Extensive │China in │To Manila in │Entire earth. │Ten months 1833│influenza │January, │September, │ │from China to │period made up│1830. │1830. Later to│ │Russia. Four │of two or │ │South Sea │ │months from │three pandemic│ │Islands and │ │Russia to │periods. │ │India. │ │Germany. Two │ │ │Appearance in │ │additional │ │ │Russia in │ │months through │ │ │October, 1830,│ │France, │ │ │with │ │England, │ │ │subsequent │ │Scotland, │ │ │spread West │ │Sweden, │ │ │and South and │ │Belgium, │ │ │on to North │ │Switzerland. │ │ │America (Feb.,│ │Six months │ │ │1832). │ │from Germany │ │ │ │ │to Italy. ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1833│Second │Probably │After an │Europe. │Petrograd in │pandemic in │Asia. │interval of │(America │January. │above period. │ │one year │appears to have│Berlin and │ │ │Europe was │escaped this │Constantinople │ │ │again visited │second │in March. │ │ │with an │epidemic.) │Denmark and │ │ │extensive │ │Sweden, France │ │ │plague which │ │and Great │ │ │attacked the │ │Britain in │ │ │same countries│ │April, Italy │ │ │in about the │ │in May. │ │ │same order. │ │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1836│Third spread │Origin rather│West and South│Europe, Faroe │Almost 1837│in above │obscure, │as previously.│Islands, │simultaneous │period. │possibly in │ │Mexico,(?) │invasion at │ │Russia. │ │India, Java. │Petrograd, │ │ │ │ │Sweden, │ │ │ │ │Denmark, │ │ │ │ │Germany and │ │ │ │ │England; │ │ │ │ │Egypt, Syria, │ │ │ │ │France, │ │ │ │ │Ireland, │ │ │ │ │Holland, and │ │ │ │ │Switzerland │ │ │ │ │one month │ │ │ │ │later. Italy, │ │ │ │ │Spain and │ │ │ │ │Portugal yet │ │ │ │ │another month │ │ │ │ │later. ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1838│Every year in │ │ │1838, February;│ 1847│this period │ │ │Island of │ │with the │ │ │Bourbon and │ │exception of │ │ │Iceland. │ │1840 showed, │ │ │1838, November;│ │according to │ │ │Australia and │ │Hirsch, some │ │ │New Zealand. │ │local │ │ │1839, │ │epidemic. │ │ │Abyssinia. │ │ │ │ │1841, Germany, │ │ │ │ │Hungary, │ │ │ │ │Ireland. │ │ │ │ │1842, Belgium, │ │ │ │ │England, │ │ │ │ │France, Egypt, │ │ │ │ │Chili. │ │ │ │ │1843, Germany, │ │ │ │ │England, │ │ │ │ │Iceland, │ │ │ │ │France, │ │ │ │ │Siberia, the │ │ │ │ │United States. │ │ │ │ │1844, Germany, │ │ │ │ │England, │ │ │ │ │Switzerland, │ │ │ │ │Cayenne. │ │ │ │ │1845, Germany │ │ │ │ │and │ │ │ │ │Switzerland. │ │ │ │ │1846–1847, │ │ │ │ │France, Russia,│ │ │ │ │Constantinople,│ │ │ │ │Brazil, │ │ │ │ │England, │ │ │ │ │Denmark, │ │ │ │ │Belgium, │ │ │ │ │Switzerland. │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1847│Epidemic │Origin │Spread not │All of the │ 1848│period │uncertain. │definite, │countries of │ │throughout │ │North America │Western Europe,│ │Europe without│ │in 1848. │West Indies, │ │clear cut │ │ │New Zealand, │ │direction of │ │ │Newfoundland, │ │spread. │ │ │Sandwich │ │ │ │ │Islands, Egypt,│ │ │ │ │Algiers, West │ │ │ │ │Coast of │ │ │ │ │Africa. │ ─────┼──────────────┼─────────────┼──────────────┼───────────────┼────────────── 1850│Epidemics │ │1857, began in│1850–51, │1855, only one 1889│covering │ │August in │particularly │month between │larger or │ │Panama and │throughout the │Petrograd and │smaller │ │spread to West│whole Western │Italy. │territory │ │Indies and up │coast of South │ │every year, │ │and down the │America with │ │but none to │ │Pacific Coast.│later spread to│ │compare in │ │Prevailed in │California & │ │intensity with│ │Europe in │Europe. │ │those of 1831,│ │December. │1852, │ │1833, 1836 and│ │ │Australia, │ │1847. │ │ │Tasmania, South│ │ │ │ │America. │ │ │ │ │1853, Faroe │ │ │ │ │Islands. │ │ │ │ │1854, Bavaria. │ │ │ │ │1855, Europe, │ │ │ │ │spreading │ │ │ │ │rapidly West │ │ │ │ │and South from │ │ │ │ │Petrograd. │ │ │ │ │Later in same │ │ │ │ │year, Brazil. │ │ │ │ │1857–58, │ │ │ │ │widespread │ │ │ │ │epidemic in │ │ │ │ │both │ │ │ │ │hemispheres. │ │ │ │ │1860–70, very │ │ │ │ │irregular │ │ │ │ │appearances in │ │ │ │ │Australia, │ │ │ │ │Tasmania, │ │ │ │ │Philadelphia, │ │ │ │ │the Bermudas, │ │ │ │ │Holland, │ │ │ │ │California, │ │ │ │ │France, │ │ │ │ │Switzerland, │ │ │ │ │Africa, │ │ │ │ │Germany, │ │ │ │ │Belgium, │ │ │ │ │Russia, │ │ │ │ │Denmark, Sweden│ │ │ │ │and Turkey. │ │ │ │ │1874–75, │ │ │ │ │Extensive │ │ │ │ │spread in │ │ │ │ │America, │ │ │ │ │Germany and │ │ │ │ │France, with │ │ │ │ │recurrence one │ │ │ │ │year later in │ │ │ │ │eleven areas of│ │ │ │ │the United │ │ │ │ │States. │ │ │ │ │1879, America. │ │ │ │ │1885–88, │ │ │ │ │Re-appeared │ │ │ │ │each year in │ │ │ │ │Petrograd. │ │ │ │ │1889, (Spring) │ │ │ │ │Greenland and │ │ │ │ │Hudson Bay │ │ │ │ │territory. │ │ │ │ │(May) Bokhara │ │ │ │ │in Turkestan │ │ │ │ │from where the │ │ │ │ │great pandemic │ │ │ │ │of 1889–90 is │ │ │ │ │usually said to│ │ │ │ │have taken its │ │ │ │ │origin. │ ─────┴──────────────┴─────────────┴──────────────┴───────────────┴──────────────

Table I shows that prior to 1510 the information was so limited as to be not entirely conclusive. We must rely upon the fragmentary descriptions of writers located usually in or near the intellectual centers who described the disease as they saw it in their city or country. We have no way of ascertaining what other countries were invaded, and we possess no method by which we may enumerate the “silent areas,” countries which in the absence of a chronicler have not been able to transmit their story.

There have been fourteen very widespread epidemics since 1510, all of which might appropriately be designated as pandemics. They are those of 1510, 1557, 1580, 1593, 1729, 1732, 1762, 1782, 1788, 1830, 1833, 1836, 1847, 1889 and 1918. Some of these have spread farther than others according to the records, but in nearly all we have reports of influenza being present in practically every country provided with a historian. We may find from the table another group in which there have been more or less extensive epidemics, apparently related, but without any general direction of spread. Such are the epidemics of 1709–12, 1757–67, 1802–03, 1838–47 and the period 1850–59. Finally, there are at least ten periods during which relatively small areas have been affected with epidemic influenza. Such for instance is the year 1688 when the disease was apparently localized in Great Britain and Ireland; in the year 1693 when England and the adjacent continent were involved, with little spread elsewhere; and again in 1742, when there was a slow spread through Germany into adjacent countries with recurrences in the former up until 1745.

In England the following epidemics have been recorded, some of them in great detail: 1510 and 1557, described by Thomas Short; 1658 by Willis; 1675, by Sydenham; 1729–1743 by Huxham; 1732–33 by Arbuthnot; 1758 by Whytt; 1762 by Baker and Rutty; 1767 by Heberden; 1775 by Fothergill, who collected observations from many physicians; in 1782 by Gray, Haygath and Carmichael Smith; 1803 by Pearson and Falconer, and a great number of others; 1833 by Hingeston and others; 1837 by Streeten, Graves, and Bryson, etc.; 1847 by Peacock, Laycock and many others; also those of 1855 and 1889–93.

According to Stallybrass, epidemic crests have been reached in England in 1789–90, 1802–03, 1830–32, 1840–41, 1848–51, 1854, 1869–70, 1879, 1890–91, 1898 and 1918 to 1920. The periodicity in multiples of ten years in this latter group is remarkable.

The disease appears to have visited North America in the years 1627, 1647, 1729, 1732, 1737, 1762, 1782, 1789, 1811, 1832, 1850, 1857, 1860, 1874, 1879, 1889, 1900, 1915–1916 and 1918–20. Abbott speaks particularly of the years 1647, 1655 and 1697–98, 1732, 1762 and 1782 and 1889 as being years of especial epidemic prevalence in this country.

CLINICAL AND EPIDEMIOLOGIC IDENTIFICATION.

Up to the present time we have discovered no one characteristic by which we may say that a case or an epidemic is positively influenza. We have had to rely on the general symptomatology, which indeed is sufficiently characteristic, although so nearly like the symptoms of certain other diseases as to make us hesitate to make an absolute diagnosis, and on the epidemic characteristics. The necessity of an absolute criterion in the clinical diagnosis is particularly felt in the presence of an isolated interepidemic case, or a small endemic outbreak. It is at this point that the opinions of epidemiologists diverge, a divergence which results in two schools of thought in the explanation of the endemic source of epidemic influenza. Are the interepidemic cases and the small localized epidemics due to the virus which causes the great pandemics; are they influenza vera, or are they entirely different diseases with similar symptomatology, caused by some other microorganism and should they be designated by some other name? Thus Leichtenstern remarks: “When we go over the records of the years 1173 to 1875, and particularly those of the last century, when the information has been more extensive and more accurate, we find that scarcely a year has passed without news of the epidemic occurrence of influenza at some point or other of the earth. Some of these local and territorial epidemics are merely endemic recurrences of the great pandemics which have left the germ deposited in the various localities. Others of these small epidemics probably have nothing to do with influenza vera, but are local outbreaks of catarrhal fever.”

Contrary to the usual belief, influenza is a disease of quite definite and distinct characteristics, both clinical and epidemiological. The symptoms are clear cut, with sudden onset, severe prostration out of all proportion to the clinical symptoms and to the fever, headache and pain in the back, general body pains, and fever of greater or less degree. There is usually a lack of leucocytosis or a true leucopenia. In uncomplicated influenza there are as a rule no localizing symptoms. There may be a slight soreness of the throat, or a slight cough, but these are at best mild. The fever lasts from three to five days and disappears, while at the same time all of the symptoms clear up with the exception of the profound prostration, which as a rule continues for some time, rendering convalescence surprisingly slow. The pain in the back may remain for a week or so. This is the description of uncomplicated influenza.

The manner of spread of epidemic influenza is constant in a primary epidemic and the epidemic as a whole has certain features which render it characteristic. The sporadic case has as a rule the same quite clear cut clinical symptomatology, but it fails to manifest the one feature most characteristic of epidemic influenza—a high degree of contagiousness. Further, although the symptoms in themselves are characteristic, there is no one pathognomonic sign by which one may say, “this is a case of influenza,” and, finally other disease conditions such as tonsillitis, frequently resemble it so much as to cause error in diagnosis.

This becomes, then, one of the problems in the study of influenza epidemiology. It is a matter of first importance to determine once and for all whether true influenza is with us always, or whether it appears only at the time of the great pandemics. Upon the answer to this question more than upon any other one thing rests our choice of methods of eradication. Any procedures of preventive medicine that may be undertaken on the assumption that the source of pandemic influenza is to be found in one or a few endemic foci, such as the one supposed to exist in Turkestan, would fail utterly should the true condition be that of a universal distribution of a relatively avirulent virus which from time to time from some unknown cause assumes a highly increased virulence.

Before becoming involved in this very complicated question, let us familiarize ourselves completely with the characteristics of the pandemic and epidemic variety of the disease.

GENERAL CHARACTERISTICS OF EARLY EPIDEMIC OUTBREAKS.

We have described the symptomatology of uncomplicated influenza. It is rare that this clinical picture is seen alone during the height of an epidemic. Complications, chiefly of the respiratory tract, as a rule occur in such a large proportion of individuals that they very nearly dominate the picture. Although caused by various microorganisms, all of which appear to be secondary factors the results are so characteristic that in the past, descriptions of influenza epidemics have usually been descriptions of the complications of epidemic influenza. Most influenza epidemics are complicated. But we do know from the experience of recent years as well as from history that relatively uncomplicated epidemics of influenza have occurred, and that when they do so occur a predominant characteristic has been the extreme mildness.

It is a fundamental characteristic of pandemic influenza that early cases in widespread epidemics, as well as in “pre-epidemic increases” are very mild, with a minimum of respiratory complications and with exceedingly low mortality. It is because we are better acquainted with the more severe variety that, when these mild precursors appear we are always in doubt for a time as to their true identity.

In spite of our 20th century erudition, the influenza when it first appeared in mild form in the American Expeditionary Forces in 1918, for a lack of better knowledge as to its cause was called “three-day fever.” In Italy in the same year the designation of the disease progressed from pappataci fever through “Spanish grip” and “summer influenza,” until finally it was designated influenza, pure and simple. Sampietro in Italy particularly discussed the possibility of the disease being pappataci fever.

Belogu and Saccone, who wrote in May of 1918, decided that the epidemic was not influenza in spite of the manifest clinical similarity, chiefly because of the absence of signs of secondary invasion, such as nervous symptoms, gastro-intestinal symptoms, and pneumonia, and especially because of the rapid recovery after defervescence. They also considered the possibility of pappataci fever and dengue, and ruled out both. They discussed calling the condition “influenza nostras,” but reached no definite conclusion. Trench fever was also considered by some. United States Public Health Reports for 1918 record that dengue was reported prevalent at Chefoo, China, during the two weeks ended June 15th, 1918. One week later there was a paragraph stating, “Prevalence of a disease resembling dengue and affecting about fifty per cent. of the population was reported at Shanghai, China, June 15, 1918.” It is not impossible that this was influenza.

Zinsser reminds us that Hayfelder, when he saw the influenza as it spread in Petrograd in November of 1889, remarked its close clinical similarity to the description of an epidemic of dengue which had prevailed in Constantinople during the preceding September. Hayfelder, in studying the 1889 epidemic at its onset in Russia and the East, wrote of “Sibirisches Fieber” which was first looked upon as malaria owing to the apparently complete absence of the complicating lesions habitually associated in our minds with influenza.

The same difficulty in early identification was experienced in this country in 1918. At the end of March of that year the author who was stationed at Camp Sevier, South Carolina, was one of a Board of Officers appointed to investigate a disease which had broken out among troops stationed at that camp. At that time the line troops consisted of three infantry regiments and three machine gun battalions. On the day following a parade in the city of Greenville a considerable number of men in three out of the six organizations suddenly took ill. There were a few isolated cases in other organizations, but in the one infantry regiment and two machine gun battalions the regimental infirmaries were filled, and some cases were sent to the base hospital. Nearly all were very mildly ill and exhibited the symptoms of pure uncomplicated influenza as described above. The onset was sudden, there were the usual pains and aches, the bowels were regular, there was a feeling of discomfort in the pit of the stomach in many instances, and there were no sore throats and very little cough. Recovery was as a rule very rapid, although about a dozen of the entire number developed pneumonia and some of these died. Physical examination of those only mildly ill and who remained in the regimental infirmary showed as a rule nothing, but in some instances scattered fine moist rales near the hilus of the lungs. In some of the organizations the disease was definitely spread down rows of company tents. Careful bacteriologic examination was made at the time and the predominating organisms were found to be a gram-negative coccus resembling micrococcus catarrhalis, and a non-hemolytic streptococcus. This was in uncomplicated cases.

The Board decided that the disease should be called influenza, but our only basis for such decision were the clinical symptoms and the contagious character. At that time none of us dreamed of any possible connection with a severe epidemic to occur later, and laboratory search for influenza bacilli which was carefully made in view of the clinical diagnosis showed none of these organisms to be present.

At about the same time a similar epidemic was being experienced at Fort Oglethorpe, Ga. V. C. Vaughan, in describing this epidemic, remarks: “A disease strongly resembling influenza became prevalent in the Oglethorpe Camp about March 18, 1918. It soon assumed pandemic proportions. Within two weeks every organization in Camp Forrest and the Reserve Officers Training Camp was affected.

“The symptoms were as follows: Headache, pain in the bones and muscles, especially the muscles of the back, marked prostration, fever, sometimes as high as 104 degrees. Sometimes there was conjunctivitis, coryza, a rash and possibly nausea, recovery taking place in a few days.

“In all organizations the epidemic was first located in companies before it became general.

“The incubation period was short, not over one or two days.

“Some organizations suffered more than others for no apparent reason.

“It is probable that the epidemic disease was recently brought to these camps. If it is genuine influenza, and the epidemiological features no less than the leading symptoms seem to point to that disease, there is here offered the most reasonable explanation of the outbreak which is now possible. No other disease spreads so fast or is so prostrating, considering its symptoms.”

We will quote at some length from the report of Zinsser of the Chaumont epidemic in France in 1918, because of the excellence of the description, and particularly because Zinsser has followed three successive epidemics with successive increases in the complications and corresponding transformations in the clinical picture. It is worthy of special note that he has remarked that the influenza, as first seen at Chaumont, showed nothing in the symptoms that would suggest a predominant respiratory tract infection.

“It will be useful to discuss briefly the early cases as we saw them during the Chaumont epidemic, not because the observations made there add much that is new from a clinical point of view, but because they will remove any possible ambiguity concerning our conception of influenza in its pure uncomplicated form.

“As far as we can judge the little outbreak at headquarters was typical of the first advent of epidemic influenza in many places. The population of the town, at the time, consisted of a large office personnel attached to the military administration, scattered as to billets and places of work; of military units living in barracks and eating at common messes; and of the townspeople. The epidemic descended upon individual military units with the suddenness of a storm, striking a considerable percentage of the men, perhaps most of the susceptible material, within less than a week, and ending almost as abruptly, with only a few isolated cases trailing behind. Among the more scattered office workers and among the townspeople it was disseminated more gradually and trailed along for a longer period.

“These early cases were clinically so uniform that a diagnosis could be made from the history alone. The onset was almost uniformly abrupt. Typical cases would become ill suddenly during the night or at a given hour in the day. A patient who had been perfectly well on going to bed, would suddenly awake with a severe headache, chilliness, malaise and fever. Others would arise feeling perfectly well in the morning, and at some time during the day would become aware of headache and pains in the somatic muscles.

“The typical course of these cases may be exemplified by that of J. T. W., a draftsman attached to the 29th Engineers. He was perfectly well until May 20th, working regularly, his bowels and appetite normal, considering himself healthy. On May 21st, at 4:30 A.M. he awoke with a severe headache. He arose, forced himself to eat breakfast and tried to go to work. He began to feel feverish and chilly. At the same time his headache became worse, with pains in the back, and burning in the eye balls. At 2 P.M. he reported sick, and was taken to the hospital with a temperature of 102.8 degrees. At midnight his temperature dropped to 101.6 degrees, and came down to normal by noon of the 22d. As he recovered he developed a slight sore throat, great soreness of the legs and a very slight cough. He recovered completely within a few days.

“These cases with a few exceptions developed no rashes. One or two of them had blotchy red eruptions which we felt incompetent to characterize dermatologically. The leucocyte counts ranged from 5,000 to 9,000. A very few went above this. Sometimes there was a relative increase of lymphocytes, but this was by no means regular. The few spinal fluids that were examined were normal. As to enlargement of the spleen, we can say nothing definitely.

“Soon after this we observed the disease in a Division, the 42d, then holding a part of the line in front of Baccarat. Here it had already developed a somewhat different nature, due, we believe, to the fact that the men of this Division were not, as were those at Chaumont, living in a rest area, but were actively engaged in military operations, working, sleeping, and eating under conditions that involved greater fatigue, less protection against weather, and greater crowding in sleeping quarters. The Baccarat cases were much more frequently catarrhal; sore throats, coughs and more serious respiratory complications were more common. However, they were usually coupled unmistakably with an underlying typical influenzal attack, sudden onset, pains and short lived fever. Moreover, there were a great many of the entirely uncomplicated cases interspersed with the others.

“Still later, in September, October and November, respiratory complications were so frequent and severe, came on so early in the disease, and the pneumonia mortality became so high, that the fundamental identity of these later cases with the early three-day fever might easily have been lost sight of by observers who had not followed the gradual transformation.

“In consideration of these facts, it is apparent that etiological or other investigations can throw no light upon the problems of influenza unless they are carried out with clearer understanding of the differentiation between the complications and the basic disease.

“The serious respiratory infections of the bronchi and lungs we can set down with reasonable certainty as complications due, certainly in the overwhelming majority of cases, to secondary bacterial invaders. It is a matter of considerable difficulty, however, to know exactly where the basic disease stops and the complications begin; and whether we must regard the mild sore throat and conjunctival injection which so often accompany the simple cases as a part of this basic clinical picture, or as the simplest variety of complication. This is much more than an academic question, since, as we shall see, the bacteriological analyses of such lesions have played an important role in etiological investigations.”

SYMPTOMS IN FORMER EPIDEMICS.

The difficulty in making a decision in the presence of an epidemic is very similar to that of deciding whether the epidemics of former times were in each case influenza. Some few have been recorded in which the description has corresponded fairly well to that of primary uncomplicated influenza. Thus, concerning the epidemic of 1557 in Spain, Thomas Short wrote as follows: “At Mantua Carpentaria, three miles from Madrid, the epidemic began in August.... There it began with a roughness of the jaws, small cough, then a strong fever with a pain of the head, back, and legs. Some felt as though they were corded over the breast and had a weight at the stomach, all of which continued to the third day at furthest. Then the fever went off, with a sweat or bleeding at the nose. In some few, it turned to a pleurisy or fatal peripneumony.”

Most of the descriptions, however, have been of a general character and include descriptions of the complicated periods of the epidemic. One of the more complete of the early descriptions was that by Lobineau in 1414, who wrote: “C’était une espèce de rhume, qui causa un tel enrouement que les chastelets furent obligez d’interrompre leurs séances; on dormoit peu et l’on souffroit de grandes douleurs à la teste, aux reins et par tout le reste du corps; mais le mal ne fut mortel que pour les vieilles gens de toute condition.”

With this exception we possess no very good or complete description of influenza prior to the epidemic of 1510. After that time they have as a rule been detailed enough to enable identification. Hirsch bases his conclusions concerning the year 1173 chiefly on the following quotation: “Sub hisdem diebus universus orbus infectus ex aeris nebulosa corruptione, stomacho catarrhum causante generalem tussim, ad singulorum perniciem, ad mortem etiam plurimorum immissam vehementer expavite.” Nearly all that we have to go on in this description is the widespread incidence of the disease and the presence of respiratory symptoms, particularly cough. In 1323 the description emphasizes only the high morbidity. Thus, Pietro Buoninsegni writes: “In questo anno e d’Agosto fu un vento pestilenzia le per lo quale amalò di freddo e di febbre per alcuni dì quasi tutte le persone in Firenze e questo madesimo fu quais per tutta Italia.” The same author describes the epidemic of 1327, emphasizing again the high morbidity and in addition the low death rate: “In detto anno e mese fu quasi per tutto Italia corruzione di febbre per freddo; ma pochi ne morirono.” Again in 1387, he emphasizes the same two features.

Pasquier, in writing of the epidemic of 1403 in France, says: “En Registres de Parlement on trouve que le vingt-sixième jour d’avril 1403 y eut une maladie de teste et de toux, qui courut universellement si grande, que ce jour-là le Greffier ne pût rien enrégistrer et fut-on contraint d’abandonner le plaidoyé.” Here the high morbidity and the symptoms, particularly cough and pain, are emphasized. In 1414, Baliolanus describes again the high morbidity and symptoms, particularly cough and hoarseness: “Eoque frigore humanis corporibus concepto ... tussis maxima atque raucitas orta unde nullus pene ordo, aetas et sexus liber evasit.” In 1411, Pasquier writes the following: “En 1411 y eut une autre sorte de maladie dont une infinité de personnes furent touchez, par laquelle l’on perdoit le boire, le manger et le dormir ... toujours trembloit et avec le estoit si las et rompu que l’on ne l’osoit toucher en quelques parts. Sans qu’aucune personne en mourut.”

Subsequent to 1510 descriptions have been as a rule more definite. There are, however, exceptions to this statement and these fall in the epidemics concerning which there is some dispute.

MANNER OF SPREAD.

More characteristic and more important from an epidemiologic standpoint than the symptomatology in general, as we have discussed it, is the mode of development of the epidemic as a whole.

Human intercourse.—Before the days of bacteriology the contagiousness of the disease was little discussed. Its infectiveness was in fact not universally established until the epidemic of 1889–1890. One of the first writers who attempted to see in the influenza a contagious disease was Ch. Calenus who wrote in 1579: “Contagiosum dico morbum, quia etsi quidem ab occulta quadam coeli influentia, principaliter eum profisci haud dubium est ... eo in loco quo jam grassabatur inter homines citius eos invadabat, qui cum affectis frequenter conversabantur, quam eos, qui a consuetudine affectorum studiose abstinebant.” This keen observer saw that those who carelessly exposed themselves to close contact with cases of influenza were more likely to develop the disease than those who protected themselves in every way possible. The “contagious” school first developed in England, where Haygarth, Hamilton, Gray, Hull, Duggard, Bardsley, and others, in 1775–1803 described the disease as being not in the air, but in a specific contagion. Others who considered influenza a contagious disease were Simonin, Lombard, Petit de Corbeil (1837), Blanc (1860), and Bertholle (1876).

Watson (1847) quotes Cullen as saying that this species of catarrh proceeds from contagion. He, himself, is not convinced of this fact. He says the visitation is too sudden and too widely spread to be capable of explanation in that way. “There are facts in the history of influenza which furnish a strong presumption that the exciting cause of the disorder is material, not a mere quality of the atmosphere; and that it is at least portable. The instances are very numerous, too numerous to be attributed to mere chance, in which the complaint has first broken out in those particular houses of a town at which travelers have recently arrived from infected places.... What I wish to point out now is the fact that the influenza pervades large tracts of country in a manner much too sudden and simultaneous to be consistent with the notion that its prevalence depends exclusively upon any contagious properties that it may possess.”

Parkes, writing in Reynolds’ System of Medicine in 1876, views the subject more as we see it today: “The rapidity of the spread would seem at once to negative any connection between human intercourse and the propagation of the disease; yet there is some affirmative evidence. It does not appear to follow the great lines of commerce; but when it has entered towns and villages in which the investigation can be carried on, it is curious how frequently the first cases have been introduced, and how often the townspeople nearest the invalids have been first affected. In this country especially, Haygarth in 1775 and 1782, and Falconer in 1802, collected so many instances of this that they became convinced that its propagation was due entirely to human intercourse. So also, when it passes through a house, it occasionally attacks one person after another. But if it is introduced in this way it afterwards develops with marvelous rapidity, for we cannot discredit the accounts of many thousands of persons being attacked within a day or two, which is quite different from the comparatively slow spread of the contagious diseases. This sudden invasion of a community makes it, to many persons, appear highly improbable that any effluvia passing off from the sick should thus so rapidly contaminate the atmosphere of a whole town.

“Still, we must remember how singularly, of late years, the knowledge of the introduction of cholera by persons coming from infected districts has increased, and how very striking are the instances of this kind already recorded in several works on influenza.

“In some cases, again, isolation or seclusion of a community, as in prisons, has given immunity; or at least that community has not been attacked.”

The great rapidity of spread has caused even in 1918 some temporary doubt as to the contagiousness of the disease. Thus, Zinsser wrote:

“The opinion of direct and indirect transmission from man to man is also well supported by a detailed study of the epidemiology of individual outbreaks. In our own experience with epidemics such as those at Chaumont, Baccarat and other places, the suddenness with which the malady attacked large numbers of people at almost one and the same time, caused me at first to be exceedingly skeptical of accepting transmission by contact as the only means of conveyance. We considered food and insect transmission as possibilities, and tried our best to find grounds for involving such agencies. But in every case we were forced to return to the conclusion that direct and indirect contact between men came nearest to doing justice to all observed facts.”

There have been many examples reported from personal experience to show that influenza is transmitted from man to man. Two objections, however, have had to be met, before this view was generally accepted. First, it has been claimed by some that the disease spread more rapidly from an assumed focus than individuals could travel, and second, that instances were on record of cases occurring spontaneously in isolated communities. Yet a third argument formerly raised against the contagious character of the disease was the claim that it broke out in mass attacks, that large numbers became ill on the same day without the occurrence of isolated antecedent cases. The splendid work of epidemiologists following the 1889 epidemic appears to have answered all of these objections. Many, such as Leichtenstern, have gone into great detail on this subject. In fact, at that time this was the question of greatest importance. Today we assume the correctness of the hypothesis, and pass on to consideration of other subjects of more recent development. We will, therefore, review very hurriedly some of the evidence quoted to prove that influenza is transmitted only from man to man and only by human intercourse.

Isolated places.—Has it ever been shown that individuals completely isolated from communication with communities where influenza is present have, during an epidemic, developed the disease? Leichtenstern, after a comprehensive review, concludes as follows: “We have not a single example on record where influenza has attacked individuals in completely isolated localities, as on mountain tops and mountain passes. Study of this has been undertaken in Switzerland by F. Schmid. The same has been true of ships at sea, as has been shown chiefly from the English Marine Reports. There have been reports of influenza occurring in mid-ocean and particularly in the earlier epidemics, but the information has been insufficient.”

Parkes at even an earlier period observed: “I cannot but consider that we require better evidence of ships being attacked in mid-ocean. In some of the quoted instances the ships had been at a port either known to be infected or in which influenza was really present, although it had not become epidemic. As we are ignorant of the exact period of incubation some men may have been infected before sailing.”

Critical investigation into stories of spontaneous infection in isolated localities such as ships at sea and island lighthouses will quite invariably demonstrate that these popular reports have been distortions of the actual facts. One or two examples will suffice. Abbott records an example: “An impression having gained some credence that influenza had appeared on board the squadron of naval vessels which sailed from Boston in December, 1889, while on their course across the Atlantic and before their arrival in Europe, a letter was addressed by the writer to the Bureau of Medicine and Surgery of the United States Navy for information upon this point, to which a reply was received, as follows:

“The ‘Chicago,’ ‘Boston,’ ‘Atlanta’ and ‘Yorktown’ left Boston December 7, 1889, for Lisbon, Portugal. The first three arrived at Lisbon on December 21st without having touched at any port en route. The ‘Yorktown’ arrived at that port December 23d, having, stopped about twenty-four hours at Fayal, Azores.... Influenza first appeared on the ‘Chicago’ December 23d, on the ‘Boston’ December 28th, on the ‘Atlanta’ December 30th and on the ‘Yorktown’ December 28th.

“Influenza was prevailing in Lisbon at the date of arrival of the squadron.”

In March, 1920, the author was notified of a somewhat similar story which he undertook to trace. The results show well the inaccuracy of verbal transmission through several individuals. A letter was first sent to the Quarantine Officer at Portland, Maine: “It has been reported to us that in a lighthouse just outside of Portland, Maine, there has been a rather interesting prank played by influenza. We are told that three men and one woman live in the lighthouse; that during the 1918 influenza epidemic the woman contracted the disease while none of the men became sick, and that in the present epidemic all three of the men became sick with the disease and the woman remained well. It was claimed that they had had no communication with the mainland for some time before the men became ill,” etc.

The reply was as follows: “I have inquired of the Light House Inspector’s office in Portland and they know of no stations to which the terms of your inquiry would apply.

“At the Boon Island station, there are three keepers with families. At the Half Way Rock station, there are three keepers but no woman. The Inspector does not seem to know of any station where there are three men and one woman.”

A second letter, sent to the Inspector of Lighthouses at Portland brought corroborative information:

“The Boon Island Light Station was stricken by this epidemic in the following manner: The keeper, his wife and five children were all stricken, the keeper himself having had the hardest battle, having apparently been subject to same while ashore in Portsmouth, N. H. after provisions, supplies, etc. The 2d assistant’s wife and two children were also stricken, but the 2d assistant, himself, and the 1st assistant keeper did not contract the malady in spite of the fact that they were all confined on a small island working together at the station.

“During the year 1920 none of the keepers or their families, consisting of thirteen in number, were affected. The Halfway Rock Light Station where three keepers are employed did not contract this malady either in the years 1918 or 1920.

“For your information I might add that during the inspection trip in the months of January, February and March, 1920, all of the light stations in this district were visited, and it was found that they were all enjoying good health and had not been visited by the epidemic, with the possible exception of three stations which are located either on the mainland or close to where the keeper or his family were able to visit the nearby cities or towns.”

Although it has not been shown that completely isolated places have been visited by the disease, there is abundant evidence that such places have remained influenza free as long as the isolation has remained complete. Islands and lighthouses, which have not been in communication with the mainland, individuals living isolated on mountain tops, and ships at sea remained free from influenza even in the presence of a pandemic, as long as they did not come into communication with individuals sick with the disease. The following places remained free from influenza throughout the 1889 epidemic: the Isle of Man, several of the islands of the West Indies, particularly the Bahamas, Granada and St. Lucia, also the British Honduras, British Guiana, and the Seychelle Islands.

Even in 1918, when the paths of commerce reached nearly every portion of the world, we have examples of relative immunity of isolated places. Thus we know that the Esquimaux were attacked late in the course of the pandemic, and we have the statement of Barthélemy who traveled in 1919 to some of the oasis towns of the Sahara Desert, and there discovered that there had not only been no influenza up to that time, but also that they had not even heard of the pandemic.

Another type of isolated place is the closed institution. As early as 1709, Lancisi remarked that the prisons of the Inquisition in Rome remained free from influenza. Twenty-one prisons in Germany in 1889–90 remained entirely free from the disease. This was true of 39 prisons in England, some of which were in cities where the epidemic was most extensive. Linroth, who observed this same phenomenon in Sweden, makes the wise remark that, “the influenza conquers more easily the space of 500 to 1,000 kilometers than it does the small barrier made by a prison wall.” A convent in Charlottenburg housing one hundred women remained entirely free during the 1889–90 epidemic.

As a rule institutions of this sort have been unable to maintain a complete quarantine throughout the period of an epidemic, and the relative immunity has been demonstrated more in late invasions, at a time when the restrictions have become somewhat lax. Thus, in 1918, Winslow and Rogers, report that in an orphan asylum in New Haven, Connecticut, which had completely escaped during the month of October when the epidemic was at its height, one of the Sisters and the priest in charge came down with influenza about December 15th. By the 27th of December 127 cases had occurred in the institution within twenty-four hours, and by January 7th there had been 424 cases, with seven deaths out of a total population of 464. The probable source of the sudden outbreak of December 27th seems to have been the Sister first affected who, when convalescent, resumed her duties in the kitchen, which included the inspection and handling of the milk given out to the children.

Crowd gatherings.—Yet another phenomenon which would lead us to conclude that human intercourse is the most potent factor in the transmission of influenza is the fact that there is frequently a high increase in the influenza rate following crowd gatherings. Parkes observed long ago that persons in overcrowded habitations, particularly in some epidemics, suffered especially, and several instances are on record of a large school or a barracks being first attacked and the disease prevailing there for some days, before it became prevalent in the towns around.

In England, the weekly market played an important role in the spread of the disease in 1889. One frequently saw such reports as that: “The first case of influenza was a man who went to London daily.” Or, “All the earliest cases were men going to London daily, while their wives and families were later affected.”

In the epidemics at San Quentin Prison, it was noted that apices of incidence usually occurred on Tuesday and Wednesday. During the first epidemic it was these days of the second and third weeks. Stanley sees a direct connection between this fact and the fact that every Sunday morning large groups of the men were crowded together in a comparatively small auditorium where they saw moving pictures. On Sunday, October 20th, they sought to eliminate this source of spread by having a band concert in the open air, but the prisoners crowded around the band and were loud in their cheers, and on the following day there was a large increase in hospital admissions.

On November 24th after the second epidemic had apparently ceased the picture shows were again started after having been closed for over six weeks. The following Tuesday and Wednesday twenty-four well defined new cases were admitted to the hospital. On Thanksgiving Day there was a field meet between the various departments of the prison. About 200 prisoners took active part, while 1,600 prisoners were spectators. The meet was held in the open air, but the prisoners were closely packed and they cheered and yelled. For the three days following this celebration there were 9, 5 and 8 patients admitted respectively.

In discussing the recrudescence of influenza in Boston in November and December, Woodward remarks as follows:

“Whether or not it may be more than a succession of coincidences it is certainly of interest to note that the November outbreak of influenza showed itself three days after the Peace Day celebration on November 12th, when the streets, eating places and public conveyances were jammed with crowds; that the December epidemic began to manifest itself after the Thanksgiving holiday, with its family re-unions and visiting; and that reported cases mounted rapidly during the period of Christmas shopping, reaching a maximum a week after the holiday.” That this may have been a coincidence is indicated by the fact that, according to reports by Pearl and others this was not consistently true in other large cities.

Dr. Meredith Davies records the case of a hostel in Wales accommodating 200 students. Infection was introduced on October 19th on the occasion of a dance attended by some students from an infected institution in the neighborhood. Four cases occurred on the 20th and within the short space of five days seventy-nine students out of the 200 were attacked.

Parsons found numerous similar examples in the epidemic of 1889. In 1918 it was frequently observed that among American Soldiers in France, those troops quartered in barracks suffered a much more rapid spread of the disease than those billetted out among the houses of the towns.

Mass attack.—Another argument formerly raised against the contagious character was the claim that it broke out in mass attack, and large numbers became ill on the same day without the occurrence of isolated antecedent cases. The first cases of such epidemic diseases as the plague and small pox became a matter of record because of the accompanying high mortality, while in influenza, with its relatively low death rate the record usually begins only after a comparatively large mass of individuals have been attacked.

Watson in 1847 observed as follows: “Although the general descent of the malady is, as I have said, very sudden and diffused, scattered cases of it, like the first droppings of a thunder shower, have usually been remembered as having preceded it. The disorder is most violent at the commencement of the visitation; then its severity abates; and the epidemic is mostly over in about six weeks. Yet the morbific influence would seem to have a longer duration. In a given place nearly all the inhabitants who are susceptible of the distemper suffer it within that period, or become proof against its power. But strangers, who, after that period, arrive from uninfected places have not, apparently, the same immunity.”

Parkes in 1876 observed that, “When the disease enters a town it has occasionally attacked numbers of the inhabitants almost simultaneously. But more frequently its course is somewhat slower; it attacks a few families first and then in a few days rapidly spreads; the accounts of thousands of persons being at once attacked at the onset of the disease are chiefly taken from the older records, in which the suddenness of the outbreak is exaggerated. Frequently, perhaps always, in a great city the outbreak is made up by a number of localized attacks, certain streets or districts being more affected than others, or being for a time solely affected, and in this way it successively passes to different parts of the city. It has generally occurred in a great city before appearing in the smaller towns and villages round it and sometimes these towns, though in the neighborhood, have not been invaded for some weeks.

“In some cases and perhaps a large number, it breaks out after persons ill with influenza have arrived from infected places.

“The decline in any great town is less rapid than its rise, and usually occupies from four to six weeks, or sometimes longer.”

Detailed studies of the Munich epidemic of 1889 and numerous similar studies of the recent epidemic, which will be referred to later, have shown a period of two or three weeks of steadily increasing numbers of cases before the height of the epidemic was reached.

Droplet infection and spread through inanimate objects.—The actual mode of spread of the virus of influenza from one individual to another is unknown. The more generally accepted explanation is that the infecting agent leaves the body through the respiratory tract, usually in the spray of coughing or talking; contagion is by droplet infection, as is sometimes the case in other respiratory infections. Thorne and others have called attention to the capillary congestion of the conjunctivae very early in the disease. They suggest that possibly the mucous membrane of the eye is the site of infection.

There has recently been considerable discussion concerning the spread of influenza through inanimate objects.

Leichtenstern reviews the reports of 1889–93 in which influenza was supposed to have been transmitted through wares, merchandise and other inanimate objects. He concluded that the evidence in all of the cases cited was insufficient for conclusive proof. Such an example was the supposed importation of the disease in goods sent from Russia to the Grands Magazins du Louvre at Paris. In one day 100 people became ill and in a few more 500 were sick with influenza. The explanation was that the germs had been imported in goods sent from Russia to the store. Detailed investigation showed that this could not have been the case because no goods had been received from Russia for a period of three years. Another example is that of one of the two winter caretakers at the St. Gothard Hospice. One of the two men went down into the valley where he purchased supplies. Ten days after his return the man who had remained in the Hospice fell ill with influenza while his comrade remained well. It was stated that influenza was introduced into Basel by goods shipped to that place from the Magazins du Louvre in Paris. The first case occurred in a man who had been working at unpacking these goods.

Lynch and Cumming believe that droplet infection plays but a minor role in the spread of sputum-borne diseases, but that insanitary methods of washing dishes and eating utensils was the chief cause for the high rates of “sputum-borne” infections both in army and civilian life in 1918. They found that among 31,000 troops eating from tableware which was cleaned by kitchen police, the influenza rate was 51 per 1,000, while among 35,000 eating from mess kits which each individual washed himself the rate was 252 per 1,000. “Eighty-four per cent. of the cases occurred among those whose hands were contaminated by washing their own eating utensils.”

Among 17,236 employees of hotels, restaurants and department stores, who ate from machine washed dishes, there occurred 349 cases of influenza, while among 4,175 who ate from hand washed dishes there were 429 cases. The rate was but 20 per 1,000 in the former, while in the latter group it reached 103 per 1,000. Here again the chances of infection between the two groups were as one is to five.

These authors have records covering 252,186 individuals in scattered institutions in the United States. Among those eating from machine washed dishes the rate was 108 per 1,000 while those eating from hand washed dishes suffered at the rate of 324 per 1,000. The ratio was 1 to 3 between the two groups. Seventy-five per cent. of the cases occurred in that group which ate from dishes not disinfected with boiling water. They do not state the number of individuals in each of the two groups.

Lynch and Cumming claim that in the act of coughing only a few organisms are expelled from the mouth, rarely over 1,500, and conclude that transmission by direct contact through the air route but rarely, if ever, takes place. While about 1,500 organisms are expelled onto the floor by an act of coughing, a sterile glove wiped across the lips may pick up nearly 2,000,000 organisms. Such organisms may be readily transferred to inanimate objects which are handled by many people.

Hemolytic streptococci and pneumococci may be isolated with great regularity from the hands of carriers or patients, from table ware, inanimate objects touched by these patients, and from floor dust. Diphtheria and tubercle bacilli have been isolated from the hands and eating utensils of patients. The average count of a large number of restaurant dishwater specimens was 4,000,000 bacteria per c.c. The temperature of this water averaged 43° C. and the dishes were practically never scalded. The water was often so highly polluted, “that the dishes are more highly contaminated after they are washed than before washing begins. The spoon or fork is often freer from organisms just after being used by the restaurant patron than when taken from the restaurant’s polluted dish water.”

Major John S. Billings, epidemiologist at Camp Custer, reported that one of the larger organizations did not properly observe the regulation requiring that all mess kits and table equipment be properly sterilized. The disease appeared early and spread unusually rapidly in this particular organization.

In summarizing the subject of transmission through utensils, we may say that the evidence is suggestive but inconclusive. It is possible, even probable, that this is one mode of transmission. That it is the most important has not been proved. Lynch and Cumming do not take into consideration that the regiments with more sanitary methods of cleansing the dishes are apt to be those regiments with more sanitary habits throughout their daily routine. Those restaurants using mechanical dish washers are usually the cleaner restaurants.

Pontano in Italy is quoted by the Office International d’Hygiène Publique as having observed in his epidemiological study that there was a constant connection between the living conditions and the severity of the complications. Notable differences were observed in neighboring houses according to the hygienic conditions of the various households.

Healthy carriers and convalescents.—Leichtenstern, who apparently accepted the Pfeiffer bacillus as the cause of influenza, did not believe that the disease could be transmitted by healthy carriers. He based this assumption on the statement, made by Pfeiffer, that the influenza bacillus was only found in acute influenza cases. In the past few years it has been abundantly shown, however, that the influenza bacillus can and does exist on the mucous membranes of healthy individuals.

The outbreak in an orphan asylum in New Haven has been previously described. There the probable source of the sharp outbreak of December 27th seemed to be the sister who, on convalescence, resumed her duties in the kitchen. There she inspected and handled the milk served to the children. This suggests the possibility of infection being propagated by convalescents and by food.

At present we do not know whether or not a patient remains infectious after the acute symptoms have subsided; we are ignorant as to whether a convalescent patient can transmit the disease; and we are not certain whether the organism found in healthy carriers is virulent or not. The information at hand strongly indicates that apparently healthy individuals may transmit the infection, but the wide distribution of the disease, with multiple possible sources of infection for each individual, and the relative insusceptibility of experimentally exposed individuals has made it impossible so far to answer these questions satisfactorily.

GENERAL MANNER OF SPREAD IN INDIVIDUAL LOCALITIES.

Having discussed the mode of propagation of influenza among individuals we will follow the disease as it attacks one person after another in a community and study the epidemiologic picture, drawn no longer with the individual as a unit, but with the community as the unit.

We must here distinguish between a primary epidemic, the first wave of a progressing pandemic, and the secondary type in which may be grouped those large or small recurrences which light up for a period of one to three or more years after the primary wave.

Primary type of epidemic.—One of the first important statistical studies on this subject was that of P. Friedrich who charted the influenza morbidity in Munich between the months of December, 1889, and February, 1890. Similar observations have been made by Parsons, Raats, Linroth, and H. Schmid, following the 1889 epidemic.

Between the occurrence of the first known case of influenza and the time of the first very definite increase in influenza incidence in a community, which interval may be termed the invasion period, there is as a rule two weeks. During this period, of course, more and more cases are occurring, but remain usually sufficiently isolated to attract no public notice. From this point the epidemic develops very rapidly and reaches its peak, usually within two or at most three weeks. In another two or three weeks the incidence has fallen away nearly to normal. The epidemic period comprises from four to six weeks, or, including the invasion period, an entire duration of six to eight weeks. This is the picture produced in a community by a primary uncomplicated epidemic of influenza. Greenwood well describes the salient features of a primary epidemic as “first a rapid and quasi-symmetrical evolution, and second, a frequency closely concentrated around the maximum.” In other words the duration is short, the rise to a peak rapid, and the subsequent fall equally rapid. He showed that in the July and August, 1918 epidemic in Great Britain nearly 80 per cent. of the total incidence in the localities studied was grouped within three weeks time. His curve corresponds so well with that of the Munich epidemic that he is able to superimpose them (Chart I). The rapid rise to a peak, almost explosive in character, more characteristic of this disease than of any other, is to be explained by the high degree of invasiveness of the organism, by the short period of incubation, by the fact that many of the sick continue at their work, thus spreading the disease, and by the non-immunity of large masses of people, together with the fact that the transmission of a respiratory infection is accomplished much more easily than is any other type of infection.

The author holds that the infrequency of immunity is a most important factor in the production of this type of outbreak. The mode of transmission of influenza is the same as that of other respiratory diseases. The infectivity is probably no greater than that of measles, although that indeed is relatively great. The means of transmission are presumably the same in each. Were we able to develop an immunity for influenza of as high degree and permanence as we possess against measles, pandemics of influenza would disappear. We wish to emphasize that the primary type of curve is a phenomenon not peculiar to influenza, but that under certain circumstances it may be found in other infectious diseases, and that it would be found more frequently in the other diseases if the immunity developed against them was of as short duration as it appears to be against influenza. If, for example, measles were to break out in a large group of individuals, none of whom had had the disease, the type of curve would be the same. We will produce evidence supporting our theory under another subject. Of course, other factors such as short incubation period and unusual opportunities for spread through mildly ill individuals play a not unimportant role.

CHART I.

The curves of incidence of influenza in Munich, and of deaths in London during the 1889 and subsequent epidemics. (Greenwood.) ]

Secondary type of epidemic.—There is a decided difference between the curve of a primary wave as it appears in the onward rush of a new pandemic and that of a secondary wave occurring at a greater or less interval following the primary spread. A secondary epidemic affects, according to Greenwood, a relatively small proportion of the population, is slower in reaching its maximum, and thereafter declines slowly and irregularly, more slowly than it increases. The distribution of the curve is less symmetrical and there is less concentration around the maximum. A secondary epidemic may be characterized by a much higher fatality than a primary one.

We believe that the configuration of a secondary type of wave is due chiefly although not entirely to a certain degree of residual immunity in a large number of individuals remaining from the first spread. There is a striking similarity between Chart I and Chart XXVIII, the latter showing the measles incidence in epidemics among rural or chiefly non-immune troops in the United States army. Chart XXIX shows a similar epidemic among urban or chiefly immune individuals. Here the curves correspond more to those of a secondary type of influenza epidemic. Thus we see that, in the absence of immunity, other infectious diseases may produce the primary type of curve, and that this curve is not a feature of influenza alone.

A striking difference between the two types of waves of influenza is the uniformity and relative constancy of the primary type as contrasted to the great variation in the secondary type. The story of the first spread of influenza in one community is usually similar to that of its spread in any other community. Certain exceptions will be alluded to later. But in the case of recurrent epidemics we may find them more severe or much milder; we may find that they attack a large number of individuals or a very few; we may even find an entire absence of recurrent epidemics in certain communities. The primary curves are relatively uniform; the secondary curves are variable.

Between 1889 and 1894 in England there were four epidemics. The first was primary, symmetrical, and lasted between December and February, 1889–90. The second was asymmetrical and much more fatal in the localities studied by Greenwood. It occurred in the spring and summer of 1891. There was a third epidemic in the autumn and winter of 1891–92 and a fourth occurred from November, 1893 to January, 1894. The third epidemic, according to Greenwood, showed some tendency to revert to the primary type in respect to symmetry, while the fatality rate partook of the character of a secondary epidemic.

Creighton writes: “That which chiefly distinguishes the influenza of the end of the nineteenth century from all other invasions of the disease is the revival of the epidemic in three successive seasons, the first recurrence having been more fatal than the original outbreak, and the second recurrence more fatal (in London at least) than the first. The closest scrutiny of the old records, including the series of weekly bills of mortality issued by the parish clerks of London for nearly two hundred years, discovers no such recurrences of influenza on the great scale in successive seasons.”

Greenwood, who has studied this subject in great detail in England, discusses Creighton’s remarks as follows: “He would be a bold man who challenged the accuracy of Creighton upon a point of historical scholarship, and I have only to suggest that there are faint indications of increased mortality in years following primary epidemics of influenza prior to the nineteenth century. Thus 1675 was a year of primary epidemic influenza, fully described in Sydenham’s Observationes Medicae.

“The nature of the succeeding constitutions is not clear, but the deaths ‘within the bills’ for 1676 were considerably more numerous than in 1675, although smallpox, fever and ‘griping of the guts’ were noticeably less fatal.

“In the English Responsoria (1, 54) the epidemic constitution of 1679 is described as a recurrence of that of 1675—that is, as having the features of primary epidemic influenza. In the five following years intermittents prevailed, and in one (1684) the mortality much exceeded that of 1679, although the deaths from smallpox were fewer. Again, a hundred years later, in 1782, there was a famous summer epidemic of influenza in London which gave rise to much discussion. The London mortalities in 1782 and 1783 were, however, almost equal, when the smallpox deaths (which were nearly three times as numerous in 1783 as in 1782) are subtracted from the total mortality of each year.

“Whether these vague indications are sufficient to permit of our thinking that the epidemic constitution of 1889–94 was not entirely unprecedented is disputable. But the contrast of the latter period with the preceding single epidemic of 1847–48 is striking; that was a primary epidemic without important sequelae.

“We have now to consider whether our experience this year is concordant with that of the early nineties, a reversion to the earlier type, or a new phenomenon.”

After comparing the 1889 curves with those for the July, 1918, outbreak in England, Greenwood concludes: “I believe that the evidence just presented establishes a substantial identity between the summer outbreak of 1918 and the primary wave of 1889–90. We do not need to appeal to any new factor arising out of the war to account for it.

“I next consider the secondary epidemic which we are now experiencing (October, 1918). Evidently our knowledge of the events in 1891 would lead us to feel no surprise at the emergence of a secondary wave, although we could not be sure that the precedent of 1847 would not be followed.

“The summer epidemic of 1918 in the Royal Air Force included nearly 80 per cent. of the total incidence within the three weeks containing the maximum, and the Munich epidemic included just over 80 per cent. within the same limits. Now if the current epidemic has reached its maximum, not more than 65 per cent. of the incidence will probably be so concentrated, and the duration will therefore be longer than in the summer; if, as suggested by the ratio of the last two ordinates, the maximum is not yet attained, then the quota of the three first weeks is likely to be still smaller and the complete duration still longer.

“The diagram of factory sickness leads to the same inference, which is that, from the standpoint of prevalence, the present is a typical secondary epidemic, congruent with that of 1891.

“It appears, then, that the origin of the summer epidemic must be explained upon such epidemiological principles as will account for the primary wave of 1889–90, that the current outbreak is in pari materia with that of 1891, its excessive mortality being mainly due to the accident of season, aided by the special circumstances of overcrowding and fuel shortage which are due to the war. In a word, this is not essentially a war epidemic.”

Wutzdorff found that in some towns, particularly in North Germany, the 1891–1892 wave was almost as extensive as that of 1889–90 had been in other places, but that in general the morbidity in Germany was much lower. He bases these conclusions on a study of the extent of crowding in the hospitals in the two years, on statistics of government physicians, etc.

In Europe the recurrent epidemics of 1891 increased as a rule very gradually, developed slowly, reached their high point frequently after many weeks, and as gradually decreased. The epidemic duration in the winter of 1891–92 lasted four or five months. The morbidity in spite of the longer duration was decidedly less. This is very different from the explosive appearance of 1889 when the peak was reached in fourteen days and the whole epidemic had been completed in six to eight weeks. There were some exceptions to this rule, as in Yorkshire, England, where the epidemic broke out suddenly between the 11th and 13th of April, 1891, had reached its peak after ten days, and for another twenty days declined. Especially interesting was Sheffield, where the first spread began gradually and ran a slow course, while the second epidemic of 1891 began explosively, lasted a short time and declined rapidly, but showed a significantly greater mortality than that of 1889.

The experiences in various communities in the United States have been not unlike those described for European cities. Abbott in describing the successive epidemics in Massachusetts remarked that the 1889–90 spread manifested itself by a sudden rise in the mortality from influenza and pneumonia, beginning about December 20th and culminating in the middle week of January, thereafter falling off quite suddenly in February to about the usual rate for these diseases. The second epidemic two years later began with a more gradual rise in October and November and then increased sharply in December, continued for nearly three weeks at its maximum in January, and declined nearly as sharply as in the previous epidemic two years before.

Winslow and Rogers who have studied the 1918 epidemic as it affected the various towns of Connecticut observed that the outbreak in a given community generally occupied a period of from six to eight weeks, and was steep and abrupt in communities which were badly hit, flatter and more gently sloping in those which escaped lightly. Also the outbreak was more severe in communities receiving the infection early than in those later affected.

Mortality curves.—Pearl has studied the epidemic constitution of influenza in forty-two of the large cities of the United States. He has plotted the annual death rate per 1,000 population from all causes in each week, from the week ended July 6, 1918, up to January 1, 1919, and observed a very distinct difference in the type of curve for deaths from all causes during the epidemic period in the various cities. These differences have been chiefly in respect to the severity and suddenness with which they were attacked. Thus Albany, Boston, Baltimore, Dayton and Philadelphia show an initial explosive outbreak of great force, while Atlanta, Indianapolis, Grand Rapids, Milwaukee and Minneapolis exhibit a much slower and milder increase of the mortality rate. In Albany and Baltimore the curve of the first epidemic outbreak rises to a peak and declines at about the same rate. In Cleveland and St. Paul, on the other hand, the rate of ascent to the peak is very rapid, while the decline is slow and long drawn out.

Some of the cities, such as Albany, show but a single well defined peak in the mortality curve. Others, such as Boston, New Orleans and San Francisco show two peaks; while still others, like Louisville, show three well marked peaks.

Usually the first was the highest and the second and third were progressively lower. Milwaukee and St. Louis, on the other hand, showed second peaks higher than the first. The usual phenomenon, however, was a large first wave followed by smaller ones.

The highest, or maximum peak rate of mortality during the epidemic varied greatly, from 31.6 per 1,000 in the case of Grand Rapids, to 158.3 per 1,000 in the case of Philadelphia.

The death rates which were of the most frequent occurrence were, generally speaking, rates below 70 per 1,000 per week.

The date of the week in which the maximum peak rate occurred was earliest in Boston and Cambridge, where it occurred October 5th, and latest in Grand Rapids, Milwaukee and St. Louis (December 14th). Thirty-one of the 40 cities studied had attained the peak rate of mortality prior to November 2d. In the case of Milwaukee and St. Louis the maximum peak was the second peak, whereas in Grand Rapids it was the first peak that was so late. Sixty-five per cent. of the 40 cities showed two distinct peaks in the mortality curve, while 15 per cent. had one peak, and 8 or 20 per cent. had three peaks.

“It appears clearly that there was a definite tendency for the two-peak cities to fall into two groups in respect of the time elapsing between first and second peaks. About a third of them had the second mortality peak around eight weeks after the first peak. The remaining two-thirds had the second peak, on the average, about thirteen weeks after the first. The three-peak curves had the second peak on an average 7.1 ± 0.3 weeks after the first, and the third peak on an average 13.1 ± 0.3 weeks after the second. The cycle in the epidemic waves would therefore appear to be nearly a multiple of seven weeks rather than the ten weeks tentatively deduced from the dates of peaks. There the process of averaging obscured the true relations.”

Duration of explosive outbreak.—The range of the duration of the first outbreak of epidemic mortality is great, varying from five weeks in Richmond, Virginia, to twenty-three weeks in Atlanta, Georgia. Twenty of the cities, one-half the total number, showed a duration of ten weeks or less, while in the other half the duration was eleven weeks or more. The mean duration of epidemic mortality in the first outbreak was 11.90 ± 0.55 weeks. The ascending limb of mortality rate was rapid in nearly all cities. The descending limb was usually slower. In 34 of the 40 cities it required four weeks or less time for the mortality rate to pass from normal to its epidemic peak. But in only half as many (17) of the cities did the rate come down from its peak to normal again in a period of four weeks or less. The mean time from normal mortality rate to peak was 3.90 ± 0.21 weeks. The mean time from peak mortality rate to normal was 8.00 ± 0.50 weeks. Thus it took about twice as many weeks for the mortality curve to come back from its peak to normal, as were required for the increase from normal to peak at the beginning of the explosion. This is on the average. The ascending limb occupied about a month and the descending limb two months.

Pearl’s curves which have been copied in this report (Charts II to VII) enable us to follow his conclusions. Pearl offers a partial explanation for the variations in the different cities. There can be no doubt but what many factors play a role in the causation of these variations, and it is to be regretted that up to the present no statistics for smaller, more homogeneous communities have as yet been reported which could be compared with Pearl’s excellent work on the large cities of the country. Were his work supplemented by records from smaller towns in which the varying factors are less numerous, in which there is less occupational variation, additional conclusions could probably be reached. The unfortunate feature is that as a rule statistics from the smaller cities and towns are less reliable.

From a detailed mathematical study of influenza in 39 of our largest cities, done chiefly by the means of multiple correlation, with the hope of being able to explain the differences in the epidemic curves of weekly mortality in the various cities, Pearl concludes as follows:

“The general conclusion to which we come from an examination of the correlation data assembled to this point is that these four general demographic factors, density of population, geographical position, age distribution of population, and rate of recent growth in population, have practically nothing to do, either severally or collectively, with bringing about those differences between the several cities in respect to explosiveness of the outbreak of epidemic mortality in which we are interested. Significantly causal or differentiating factors must be sought elsewhere.”

CHART II.

Death rates from all causes by weeks in certain large cities of the United States during the winter of 1918–19. (Pearl.) ]

CHART III.

Death rates from all causes by weeks in certain large cities of the United States during the winter of 1918–19. (Pearl.) ]

CHART IV.

Death rates from all causes by weeks in certain large cities of the United States during the winter of 1918–19. (Pearl.) ]

CHART V.

Death rates from all causes by weeks in certain large cities of the United States during the winter of 1918–19. (Pearl.) ]

CHART VI.

Death rates from all causes by weeks in certain large cities of the United States during the winter of 1918–19. (Pearl.) ]

CHART VII.

Death rates from all causes by weeks in certain large cities of the United States during the winter of 1918–19. (Pearl.) ]

Concerning geographical position, he did find some slight relationship with linear distance from the city of Boston, where the epidemic was supposed first to have begun in this country:

“This result means that the greater the linear distance of a city from Boston the less explosive did the outbreak of epidemic mortality in that city tend to be. This is in accord with the general epidemiological rule that the force of an epidemic tends to diminish as it spreads from its primary or initial focus. It must be noted, however, that the correlation coefficient in this case is not large. It is barely past the value where it may safely be regarded as statistically significant. This fact may probably be taken to mean that influenza does not follow the epidemiological law referred to with anything like such precision as do some other epidemic diseases, notably poliomyelitis.”

These factors having been found to be of little value in his attempt to explain the varying curves in the 39 different cities, Pearl next correlated the explosiveness of the epidemic mortality with deaths from all causes, deaths from pulmonary tuberculosis, from organic heart disease, from acute nephritis and Bright’s disease, from influenza, from pneumonia (all forms), from typhoid fever, from cancer and from measles, in the various cities.

“The outstanding fact which strikes one at once from this table is the high order of the correlation which exists between the explosiveness of the outbreak of epidemic mortality in these communities and the normal death rate from certain causes of death in the same communities. In the first four lines of the table the correlation coefficients range from about 6 to more than 10 times the probable errors. There can be no question as to the statistical significance of coefficients of such magnitude.

“The highest correlation coefficient of all is that on the first line of the table, for the correlation of epidemicity index with death rate from all causes. The existence of this high correlation at once indicates that an essential factor in determining the degree of explosiveness of the outbreak of epidemic influenza in a particular city was the normal mortality conditions prevailing in that city. In the group of communities here dealt with, those cities which had a relatively high normal death rate had also a relatively severe and explosive mortality from the influenza epidemic. Similarly, cities which normally have a low death rate had a relatively low, and not sharply explosive, increase in mortality during the epidemic.

“It will also be noted that the correlation in the next three lines of the table, namely those of pulmonary tuberculosis, so-called, organic diseases of the heart, and chronic nephritis and Bright’s disease, are of the same order of magnitude as that between the death rate from all causes and the explosiveness of the epidemic outbreak of influenza.”

Pearl suggests that this correlation might arise because of differences in the constitution of populations in the different cities, or, that it was a factor of geographical position, such as the distance from the Atlantic seaboard; but that even after correction of the results for age distribution and geographical position, the net correlations were actually higher than were the gross uncorrected correlations.

“We may conclude that the most significant factor yet discovered in causing the observed wide variation amongst these 39 American cities in respect of the explosiveness of the outbreak of epidemic influenza mortality in the autumn of 1918 was the relative normal liability of the inhabitants of the several cities to die of one or another of the three great causes of death which primarily result from a functional breakdown of one of the three fundamental organ systems of the animal body, the lungs, the heart and the kidneys.”

Winslow and Rogers studied the relation of the pneumonia death rate from 1901 to 1916 to the influenza death rate of 1918 in 40 large cities of the United States and found a distinct correlation. The cities which have been characterized by a high pneumonia rate in the past are precisely the cities which suffered most severally in the 1918 outbreak. This is not due especially to virulent types of pneumonia organisms in certain sections of the country because they found this same high correlation between total death rates and influenza death rates, in the same cities.

They believe that these high correlations may be the result of weaknesses in the population due to high incidences of organic diseases and tuberculosis in earlier years, or more probably that the correlation is an indirect one, due to the relation between each of the factors studied and one or more underlying conditions affecting both, such as age distribution of the population, race distribution, or social and economic conditions in the various cities studied. Or, finally, it may be that the high rate from tuberculosis and organic disease in 1916 was due to these latter factors, while the high incidence of influenza was due chiefly to proximity to the original focus of infection. None of these explanations are considered entirely satisfactory.

It is important to call attention to the fact that the American observers quoted have been studying the death rate from influenza as it is revealed in the increase of death rate from all causes, whereas Leichtenstern and Wutzdorff, and Greenwood, in his studies in the Royal Air Force have concerned themselves with morbidity. The comparison of morbidity and mortality cannot be easily made as we will show when discussing these two subjects, so we cannot conclude that the work of Pearl and of Winslow and Rogers is at variance with the other work quoted. The mortality curves form another characteristic of the local spread of influenza in a community.

It is characteristic of influenza that the curve of deaths does not fall as rapidly as does the curve for influenza cases. Thus in morbidity curves we may expect to find a symmetrical curve for a primary epidemic, but the mortality is rarely if ever symmetrical, the curve rising rapidly and falling very much more slowly.

Morbidity curves in 1920 recurrences.—The curves of influenza incidence in the recurrence of 1920 have varied in different localities, but in certain communities where the record has been carefully reported the epidemic appears to be characterized by a symmetrical evolution and usually a lower death rate as compared with 1918. The curve of incidence in the State of Massachusetts in January, February and March, 1920, is symmetrical, if anything falling away more rapidly than it ascends, and the duration is at least ten weeks. The crest of the influenza wave in Massachusetts was reached on February 4th, 5th and 6th. The peak is recorded as being in the week of February 7th.

During the 1920 epidemic the author made a house-to-house canvass in six representative districts in the city of Boston covering a population of 10,000 individuals. The curve of incidence of influenza corresponds closely with the curves for the city and the state as a whole. The peak was reached in the same week, the week ending February 7th, the curve was symmetrical, and the duration of the entire epidemic was about the same. The morbidity rate for 1920, according to our influenza census, was but half of that for 1918 for the same population. The recurrent epidemic as we will show later was decidedly milder (see Chart XVIII).

In Detroit the 1920 epidemic reached its peak for morbidity on the 9th day, and that for mortality on the 16th. In 1918 the morbidity peak was not attained until the 15th day and the death peak on the 22d. The recurrent outbreak had nearly run its course within three weeks. The following comparison between the influenza incidence in 1918 and 1920 in Detroit is taken from a report by H. F. Vaughan, Commissioner of Health for that city. In it is shown a comparison of the total figures on the twenty-seventh day of each of the two epidemics:

A Comparison of the 1918 and 1920 Epidemics of Influenza in Detroit. Statistics Made to Include Through the Twenty-seventh Day of Each Epidemic. ═══════════════════╤════════════╤════════════╤════════════╤════════════ │ │ │ Normal │ Excess │ │Deaths from │ influenza │ influenza │ Influenza │ influenza │ and │ and │ cases │ and │ pneumonia │ pneumonia │ │ pneumonia │ deaths for │deaths above │ │ │this season │ normal ───────────────────┼────────────┼────────────┼────────────┼──────────── 1920 (Jan.–Feb.) │ 11,202│ 1,642│ 197│ 1,445 1918 (Oct.–Nov.) │ 16,423│ 1,286│ 124│ 1,162 ───────────────────┴────────────┴────────────┴────────────┴────────────

There had been fewer cases reported on the twenty-seventh day of the 1920 epidemic, but these had resulted in a greater number of deaths. On this day the recurrent epidemic had run its course, while the 1918 one was still in full swing. On the twenty-seventh day of 1918 there were 137 influenza cases reported and 49 deaths. On this day in 1920 there were but 24 cases and 34 deaths. Thus the second outbreak was of shorter duration, but was more deadly while it lasted.

Seven weeks of the 1920 epidemic in Detroit killed 0.20 per cent. of the population, two out of every one thousand people. A similar period at the beginning of the epidemic of 1918 witnessed the death of 0.17 per cent. of the population. This was a smaller number, but the epidemic at this time had not completed its course, and continued to be more or less prevalent for twenty-one weeks, resulting finally in the death of 0.28 per cent. of the population. The recurrent epidemic was more highly fatal, but, being of shorter duration, Detroit actually suffered less from it.

SPREAD IN COUNTRIES AND CONTINENTS.

The spread of influenza is usually not limited to a single community. Almost invariably it will travel on to another locality, carried thither by human intercourse, and will there build again a local epidemiologic picture more or less modified by changes in the environment and changes in the virulence of the virus itself.

Spread, in primary waves.—Reference to the table of epidemics in history will show that in many of the epidemics and in most of the widespread epidemics and pandemics there appears to have been a definite, clearcut, direction of spread from one locality to others. In the recent literature there has appeared considerable discussion concerning the site of origin, the endemic focus of pandemic influenza. Briefly the question raised is as to whether there are single or multiple foci. We will for the time ignore this perplexing question. In either case, after the influenza virus has once attained such communicability as to produce a pandemic it does follow a direct course over countries and continents. This may be followed in resumé in our table.

The disease does not at any time spread more rapidly than the available speed of human communication between the areas affected. If influenza does appear simultaneously in two widely separated communities without having been brought there from a common source it must be that it arose spontaneously from simultaneous increase in virulence of the virus in those localities.

Influenza was prevalent in Turkestan, Western Asia, in May of 1889. It spread first to Tomsk in Siberia and did not appear in Petrograd until the end of October. By the middle of November it had reached Berlin and Paris, and one month later it was epidemic in New York and Boston. Four months had been required for the disease to reach Petrograd from Bokhara in Turkestan, while within two months thereafter it had traveled from Russia to the United States. In both cases the rapidity of spread corresponded to the rapidity of the means of communication of the locality; the caravan in Turkestan and the transatlantic liner to America. North America was widely infected in January of 1890. So, also, Honolulu, Mexico, Hong Kong, Japan. Ceylon first experienced the epidemic early in February, India at the end of the month, Borneo and Australia on the first of March, Mandalay towards the first of May, China and Iceland in July, Central Africa in August and Abyssinia in November of 1890.

It should be noted that influenza was reported to have been prevalent in Greenland at about the same time that it was in Bokhara. There appears to have been no relationship between these two outbreaks.

The spread of the pandemic may be followed also by recording the period of greatest mortality in the various cities. This period at Stockholm followed that at Petrograd by three weeks, and that of Berlin by another week. The period for Paris was a week later than for Berlin, that for London another week later, and that for Dublin three weeks later than that for London. The week of highest mortality in Dublin was later than that for New York or Boston.

The earlier epidemics progressed more slowly. That of 1762 prevailed in Germany in February, in London in April, in France in July, and in America in October. In 1782 it attacked London in May, Exeter two weeks later and Edinburgh early in June. In 1830–1832 the spread from Moscow and Petrograd through Germany required no less than eight months to cover the latter country.

In 1872 the time required for spread from Leipzig to Amsterdam was eighteen days, the same time that was required for a merchant in the latter town to reach Leipzig.

There are many instances on record in which influenza has passed by small towns in its onward course to attack a larger city and only at some later date has the small town, not on the main line of communication, been affected. Not only is the speed of transportation between two communities of importance, but also the volume of the transportation undoubtedly plays a part in the rapidity of development in a second locality. When the disease is carried by a vessel the first places to be attacked are the seaports and the coast towns, be the land a continent or an island. From there it spreads inland either rapidly or slowly according to the transportation facilities. Formerly the question was raised whether influenza spread in continuous lines or radiated in circles. Naturally it follows the direct lines of communication, most of which are radially distributed around large centers.

Leichtenstern calls attention to the fact that in the 1898 epidemic, as in the previous one, the general direction of spread was from East to West across Europe. This was also true of the epidemics of 1729, 1732, 1742, 1781, 1788, 1799, 1833, and 1889.

There have been in Europe two general routes followed by pandemics, a Northern one through Russia and following the lines of travel into Germany and through the countries of Europe; and a Southern path coming from Asia, through Constantinople, and entering Europe from the South, particularly Italy. With the latter, after reaching Europe, the spread is northerly; with the former it is southerly, and usually Spain was the country last infected.

In the United States as well, pandemic influenza usually has spread from East to West, entering the country at or near New York or Boston, and spreading West and South. This was true in the autumn epidemic of 1918.

Spread in recurrences.—As a rule the manner of spread of a secondary epidemic following the primary pandemic wave is quite different. At a longer or shorter interval following the first spread the disease breaks out anew in one locality or another, sometimes simultaneously in widely separated districts. Sometimes we can distinguish a direction of spread in the relatively small community affected, it frequently being observed that the disease will start up in a large city which has experienced the illness during the first pandemic, and from there will spread to small nearby localities which may have remained free until that time. Again, any clearcut direction of spread may be entirely lacking. It is rare indeed that an epidemic following another by a short interval will follow a definite line over an entire country or continent. Such an example is, however, to be found in the epidemic of 1833, which traveled over Europe from Russia, spreading to the west and the south and following practically the identical path that it had taken in 1830. Even so it was not as widespread, for while the epidemic of 1830 had covered the entire earth, America appears to have escaped the second epidemic.

These disseminated and independent outbreaks are believed to arise from endemic foci in which the virus has been deposited during the progress of its first spread and in which the germ has survived until it has acquired once again exalted virulence.

Usually these endemic outbreaks show in their local configuration, a secondary type of wave. That this is not always the case we have already indicated. The epidemic of 1732–1733 was a recurrence of that of 1729–1730. The epidemic of 1782 had as its source the epidemic of the years 1780–1781. The epidemic of 1788 recurred until 1800, and was quite possibly associated with those of 1802, 1803 and 1805–1806. That of 1830 recurred in 1831–1832. Next we have in 1833 the true pandemic originating in Russia. Recurrences of the epidemic of 1836–1837 were found in 1838 and in 1841. Those spreads which occurred in 1847 and 1848 found successors in the year 1851. In 1890 the influenza outbreaks were as a rule single or isolated and occurred in only a few places of Europe, particularly in Lisbon, Nürnberg, Paris, Copenhagen, Edinburgh, Riga, London, etc. It is reported that there was an unusually severe local outbreak in Japan in August, 1890. In 1891 no general direction of spread was manifested, yet in heavily populated areas, or states rich in lines of communication, especially those of Europe and North America, one could frequently trace some definite direction followed by the disease within these relatively small territories.

A. Netter made the following observation at that time: “La Grippe a fait des explosions simultanées ou successives, et on n’a pu en aucune façon subordonner ces différents foyers comme cela avait été possible en 1889–90. Il parait y avoir eu des reveils de l’épidémie sur divers points.”

Leichtenstern describes the subsequent spread of the disease: “The transfer of the disease by ships which played such an important role in the first epidemic appeared to be insignificant in 1891, in spite of the fact that influenza was present in many of the English colonies. The third real epidemic spread of influenza was a true pandemic which began in the autumn (October) of 1891 and lasted through the whole winter until the spring of 1892. It involved all of Europe and North America and spread to all other lands, but here again the geographic distribution followed no rule. There was no spread of influenza from a central point, no continuous spread following lines of communication, and there was no longer an early predominance in the cities lying on the lines of communication or in the larger cities and commercial centers, as had been the case in the first epidemic. In England in 1891 the first outbreaks occurred frequently in country districts. The epidemic raged nearly four months in the northern part before it finally reached London in May. The same was true of Australia.

“One peculiarity of the recurrent epidemic lay in the much more contagious character of the disease and the remarkably greater mortality. In Sheffield the mortality in the recurrent epidemic was greater than in the pandemic, even though the epidemic picture was that of a primary wave.”

By way of summary of our knowledge of the primary and secondary spread in general up to the epidemic of 1918, we may enumerate the more important characteristics:

1. Occurrence of true pandemics at wide intervals, primarily intervals of several decades.

2. Indefinite knowledge and conflicting evidence regarding site and manner of origin.

3. Apparent transmission chiefly or entirely through human intercourse.

4. Rapid spread over all countries, the rapidity roughly paralleling the speed of human travel.

5. Rapid evolution of the disease in the communities where outbreaks occur, with nearly equally rapid subsidence after several weeks’ duration.

6. Apparent lack of dependance on differences of wind or weather, seasons or climate.

7. Generally low mortality in contrast to enormous morbidity. Variation in the incidence of disastrous secondary infections.

8. Tendency to successive recurrences at short intervals.