Part 3

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.