Chapter V: Section I: General Epidemiologic Considerations (1)

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).