Comparison of Influenza with Other Epidemic Diseases.
A certain amount of knowledge concerning the epidemiology of influenza may be gained by a comparison of the epidemic features of that disease with those of other epidemic diseases, particularly measles and the exanthemata, meningitis, the plague, and certain diseases of the lower animals. Influenza is described as a disease with distinctive epidemiologic characteristics, the chief of which are found only in epidemic spreads. Thus one of the fundamental characteristics of these epidemics is supposed to be the primary type of wave, the wave characterized by rapid rise, quasi-symmetrical evolution, and a concentration closely grouped around the maximum. “This is found in no other disease. In no other type of epidemic does the curve rise as rapidly to a peak or fall as swiftly, nor is the epidemic completed in as short a time.”
The secondary type of curve, that which is more frequently found in recurring influenza epidemics, characterized by a more gradual ascent, a still more gradual decline and a longer duration, is found frequently in the curves for other diseases; it is much less characteristic. We shall attempt by a comparison of epidemic influenza with these other diseases to explain the cause for this characteristic primary curve, so as to gain a further insight into the epidemic features of the disease.
There are certain characteristics held by epidemic influenza in common with other diseases. There are certain resemblances between it and epidemic meningitis; in certain ways it resembles measles and there are some points of similarity to the pneumonic form of plague. The fact that it cannot be compared with one of these diseases to the exclusion of the others renders deductions more complicated.
Epizootics.—Soper has written at some length on a comparison of influenza in man with the so-called influenza among horses. The close resemblance in many features is striking.
Epizootics of a disease apparently resembling influenza have been described among horses from before the Christian Era. A disease believed to have been influenza was recorded as having occurred B.C. among horses in Sicily. According to Parkes the epidemic which attacked the army of Charlemagne in 876 attacked at the same time dogs and birds. Finkler describes an epizootic among horses in 1404 A.D. There were other epizootics in 1301, 1711 and 1870 to 1873. In 1901 a severe outbreak occurred in America, and one has also been described by Mathers as occurring in Chicago in the winter of 1915–16. These epidemics of a disease clinically resembling influenza have frequently occurred among horses at the same time with true epidemics of influenza in man. Nevertheless there has been no clear cut evidence to prove that the disease is the same.
Leichtenstern discusses the incidence of respiratory disease among animals, particularly household pets during epidemics of influenza. He comes to the conclusion that human influenza is a disease limited entirely to the human race and having no connection with animal disease. This is particularly true with regard to diseases reported among cats, dogs, canaries and other captive birds. He also believes that the epizootics among horses which have been reported from time to time as occurring with influenza epidemics have nothing to do with the disease in man. The symptoms are frequently very similar, but epizootics have frequently occurred at times when there was no epidemic of disease among humans.
Abbott concluded that during the great horse epidemic of 1872 which bore a strong resemblance to influenza the disease was not unusually prevalent among men except in a few limited localities; while other infectious diseases, such as measles, small pox, scarlet fever and cholera infantum were unusually prevalent in that year.
Soper writes that, “Economically, influenza is the most important disease of horses in temperate climates. The mortality among remounts has been many times greater from influenza than from all other diseases put together. It is estimated that over 25,000 horses purchased by the British Government in America and Canada, during two years of the war, died in those countries while awaiting shipment to Europe. In a circular issued January 12, 1918, by the Surgeon General of the United States Army to the veterinarians of remount depots, it was stated that the losses from influenza among American army horses amounted to over $100,000 a week. The disease spoken of as influenza in the horse has many other names. It is commonly called pink-eye, shipping fever, stable pneumonia and bronchitis. By some influenza is not believed to be a single disease, but a group of diseases. By others it is considered to be a definite entity, varying in its symptom complex at different times and with various horses. Infectious laryngitis and infectious pharyngitis seem to be independent diseases. Two forms of influenza are generally distinguished: catarrhal and pectoral.”
Even after the last pandemic of influenza the question has again arisen as to the identity of the disease among animals. Orticoni and his co-workers observe that there was an extensive epizootic among horses at the time of the 1918 epidemic in the area which they had under observation. There have been other similar reports. The popular press, during the height of the 1918 spread, reported that there was a highly fatal influenza infesting the monkeys of South Africa and that the baboons were dying in scores, their dead bodies being found on the roadsides and in the vicinity of homesteads. Another report tells of the influenza decimating the big game in Canada, and yet another tells of the havoc wrought among the buffalos and other animals in the United States National Parks. These reports have not been corroborated by scientific observations.
Soper has analyzed the subject of so-called influenza among horses. He finds that the disease is quite generally distributed, that it has many points of close similarity to the influenza of man, but that it is a distinct and separate disease. The two diseases are not identical and neither can be transmuted into the other.
“Briefly, the symptoms, as stated in a recent publication of the United States Department of Agriculture, are sudden onset; fever in some cases preceded by chill; great physical prostration and depression of nervous force; sometimes injected mucous membranes, especially those of the eye, and loss of appetite. In uncomplicated cases the fever abates after about a week and there is a general restoration to health. Pneumonia is one of the frequent complications and is always serious. The death rate varies between two and seven per cent. The most usual form is the catarrhal type. The attack may last only two or three days; in other cases the course may extend to two weeks, in which event it takes the animal a long time to get well. Horses which have passed through this form of disease may be considered to have recovered two weeks after the disappearance of the fever.
“The diagnosis of influenza depends as much upon its epidemiological aspects as upon the symptoms. Law bases it on the suddenness of the attack, its epizootic character, the numbers attacked in rapid succession and over a large area as compared with ordinary contagious pneumonia, the sudden and extreme prostration, the mildness of the average case, the congestion of the upper air passages, the watering and discoloration of the eyes, and the history of the case. Points of interest in the history are the arrival of the infected horses within a few days from an infected place, or coming through such a place, or the attacking of new arrivals in a previously infected stable, or the known advance of the disease toward the place where the patients are located.”
Soper found that the progress of the epidemic of 1872–73 among the horses in this country was as generalized, but much slower than the progress of the recent pandemic among human beings, the rapidity of progress corresponding with the rapidity of the transport of the horses at that time. Just as we have found in the case of influenza so also at that time the spread only followed lines of communication and actual contact between horses.
It is highly interesting that attempts to transfer the disease from horse to horse experimentally met with the same degree of failure that was experienced in similar attempts to transfer influenza experimentally from man to man. In fact Lieut. Col. Watkins Pitchford of the British Army Veterinary Corps in a report in July, 1917, stated that it was impossible to produce infection experimentally. Nose bags were kept upon horses with profuse nasal discharges and high temperature, and these nose bags were then used to contain the food of other horses without infection taking place.
There are several other points of resemblance between horse influenza and human influenza. The mortality from influenza among horses is under ordinary circumstances between two and seven per cent., and is highest in horses worn out by fatigue after a long railroad journey, among fat horses out of condition, and among horses which have been driven after they were sick. The death rate in the simple catarrhal form of influenza rarely exceeds one-half of one per cent., while in the pectoral form it is never less than four or five per cent., and may reach 16 per cent. The only measure of prevention which has been found wholly satisfactory is strict isolation. Usually influenza occurs in horses who have newly arrived in a stable from elsewhere. Practically all the newly arrived horses and country horses are almost alone susceptible. Soper, who has studied the records, such as they are, in the army veterinary corps, and also the records from the Bureau of Animal Industry, concludes that they show nothing to indicate that any general epizootic of influenza occurred among horses during the year 1918 corresponding to, or connectable with the pandemic of influenza among human beings. There was influenza among the horses, but he does not think it was extensive enough to be allied with influenza among human beings. He concludes that there are two types of influenza among horses, first a mild form which nearly all horses get when transferred to a contaminated stable, after which there develops immunity, and the second type, a true epizootic which may sweep the entire country, attacking practically every horse. A most suggestive result of his study lies in the fact that predisposing influences play a most important part in the production of serious influenza among horses.
Aside from noting a certain similarity between the epizootic of so-called influenza in horses and influenza as we know it in man, we cannot acquire much additional information concerning influenza itself from a consideration of this subject. The important conclusion is that in several of the most important epidemiologic features the two diseases are similar and that the study of human influenza may be furthered by critical studies of influenza in horses. We shall attempt to demonstrate that influenza in a similar manner is not unlike other epidemic diseases.
Asiatic cholera.—There are those who claim that the disease should be compared with Asiatic cholera which remains constantly endemic on the banks of the Ganges and at intervals spreads from there throughout Indo-China, and formerly at times throughout the civilized world. Those who compare influenza with this disease believe that this is additional evidence in favor of a single focus of endemicity of influenza.
Epidemic meningitis.—On the contrary the disease may well be compared with epidemic meningitis. The germ of this disease, distributed throughout the world, is usually in an avirulent form and produces no epidemic of meningitis. Only an occasional case arises. There are certain localities in which the disease is particularly prevalent at all times. We may speak of these as endemic foci, but must remember that at the same time the virus is distributed elsewhere. Thus South Carolina, Missouri and Kansas have been shown to be localities in which meningitis has been more or less widely distributed for some years.
We can carry the analogy still farther. During the concentration of forces early in the war, camps were established at Columbia, S. C. and at Fort Riley, Kansas. In these camps, Jackson and Funston, there very rapidly developed quite extensive epidemics of cerebrospinal meningitis. Here and in Camp Beauregard, the incidence of the disease was out of all proportion to that in the other camps. Just as the exaltation of virulence of the influenza virus has been favored by gross changes in the environment, the occupation, the density of, and the disease incidence in the host as a community, so also do these appear to have been factors in the development of a meningitis prevalence in the army. It was more prevalent in those camps situated in the territories where the disease was particularly endemic, but was also present in all camps. Had the meningococcus been able to assume the high degree of virulence and invasiveness possessed by the influenza virus it is reasonable to assume that a pandemic spread would have begun in one of the two or three camps where the disease was especially prevalent. It would have spread thence and have attacked those camps in which a mildly virulent meningococcus had already been causing disease. Just as in influenza the pandemic spread would have been due not to the universally distributed virus, but to the one or few which finally acquired the greatest exaltation of virulence.
We see then that the followers of both theories—that of the single focus and that of an extensive distribution—can quote other infectious diseases in support of their theory, but the evidence in favor of similarity to Asiatic cholera is not complete. The disease is not similar. The mode of transmission is entirely different. The infection is chiefly of the gastro-intestinal tract, while that in influenza is chiefly respiratory. Since 1816 there have been five pandemics of Asiatic cholera, the last occurring in 1883 and all of them traceable to a primary focus in India. Frequently it was carried from India by the faithful, to Mecca and from there was readily distributed throughout Europe. In the last pandemic the disease spread throughout the old world and reached New York harbor, but was refused admission.
Plague.—The similarity in clinical symptomatology, in gross pathology and the apparent similarity in manner of spread and epidemic features between influenza and the pneumonic form of plague has suggested to some that the best comparison should be made with the latter disease. Here again is a disease which is endemic in Asia and spreads elsewhere only at intervals. If we go back into the history of the plague we will discover that formerly it was distributed more or less throughout the civilized world. The plague is supposed to have been known to the children of Israel at the time of the exodus from Egypt. The Egypt of the Pharaohs was a country of great salubrity. Hygienic measures were excellent. The inhabitants built aqueducts, disposed of their dead hygienically, reared temples, maintained law and order, developed the elements of literature and science and devised and employed simple machinery. But as early as the exodus, Egypt had lost its salubrity. This is indicated by many passages in the Bible. The plague was present in that country during this period. Sticker believes that the pest among the Philistines spoken of in the First Book of Samuel, when the captured army was returned with five golden emerods and five golden mice, was the bubonic plague.
Thucydides describes a plague in Athens occurring before Christ. This is generally believed to have been “the plague.” The time of the earliest appearance of the disease in Italy is not known but it was well established there in the first century of our era. The plague was endemic in Italy at that time and it developed in epidemic form with each increase in susceptible material. At about 68 A.D. the disease spread over the whole of Asia, Northern Africa and Europe. Exacerbations of the disease are described in the years 80, 88 and 92 A.D. In Rome they occurred in 102, 107 and 117 A.D. The disease was present in Wales in 114 A.D. In 167 an unusually severe outbreak of the plague occurred in Rome. There were other outbreaks in the Roman army in 173, 175 and 178. Had we the space to record here the history of the plague we would find that the disease was widely distributed throughout Europe for several hundreds of years, that it was particularly prevalent in certain areas and that at intervals it spread from one or a few foci, throughout the continent.
We can compare the epidemic features of influenza with these other contagious diseases, but we will always find some points of difference from one or another. Let us consider again for a moment epidemic meningitis. There is no combination of predisposing causes, environmental, meteorologic or bacteriologic which will produce epidemics of cerebrospinal meningitis in the absence of the meningococcus itself. The organism causing the disease must be present before the disease will occur. The specificity of the invading organism in the different diseases will always produce some variation among the epidemiologic features. Other things being equal, that locality in which this germ is most extensively distributed will be the locality in which epidemics, when they do break out, will be most extensive.
In the case of our army camps, those individuals carrying the disease virus from the endemic foci to the camps were not the ones who fell ill. Generally it was those, coming from other areas in which meningitis was not extensively distributed and who had, therefore, not acquired an increased resistance to the disease, who fell ill. But after the disease had acquired increased virulence at Camp Jackson, not only did it occur in the troops at that camp, but it also became quite extensive throughout the civilian population, presumably among those who had previously been exposed to it in its endemic form.
In our comparison of influenza with other infectious diseases we wish to show particularly that the disease is not in a class by itself, but that its epidemiologic features are not unlike those of other respiratory infections, that the manner of spread and the mode of infection are similar to those of the other diseases. Nothing unusual or unknown need be called into use in explaining any differences. Those differences that very palpably exist can be explained by facts which we already know. Leichtenstern, thirty years ago, believed that the disease was similar in its manner of spread to other infectious diseases. He observed this particularly in the earliest and the latest phases of epidemic spreads where cases were scattered. He saw that in households the disease attacked some and spared others even of those intimately connected with the sick, just as was the case in diphtheria or meningitis. He writes: “Comparing these later periods the disease evidences the same contagious characteristics as the other endemic contagious diseases, such as scarlet fever, measles, diphtheria, epidemic cerebrospinal meningitis, etc.”
Parkes made very similar observations even before the 1889 epidemic.
Measles.—A comparison of influenza and measles will offer some explanation of the differences between the epidemic constitution of the former and that of the other respiratory diseases.
We are accustomed to think of measles as a disease which, like meningitis, is disseminated throughout the civilized world, and which although constantly with us causes only sporadic cases. True epidemics of measles do occur, even when there is no gross change in the constitution of the population. We have discussed examples of this particularly in London. Flare-ups of measles prevalence are in fact so much the rule that in certain localities health officers anticipate a measles epidemic about once in two years. Furthermore measles has been known more than once to occur in extensive epidemic form, attacking large proportions of the population invaded. We know that there is an immunity to measles which is nearly absolute in those who have once acquired the disease. The epidemics have, therefore, occurred exclusively in those localities where the proportion of immune individuals was relatively small. According to Noah Webster in 1772 measles appeared in all parts of America and was accompanied by an unusually high mortality. In Charleston 800 or 900 children died of the disease. The following year measles “finished its course and was followed by a disorder of the throat.”
In 1781 measles disappeared from the Faroe Islands, and for the following sixty-five years there was not a case of this disease anywhere on any of the seventeen islands constituting the inhabited parts of this group. When the disease was finally re-introduced into these islands, it spread throughout the population, attacking practically every individual in a relatively short interval of time, showing a much higher attack rate than did influenza in 1918. There was this difference, that the only individuals who did not acquire measles on its re-introduction into the islands were those who had had it sixty-five years before. Panum did not find an authentic case of recurrence in the same individual. There was not a single instance of second attack of measles, although the shortest possible interval between the previous attack and the subsequent exposure was sixty-five years.
In 1875 measles first reached the inhabitants of the Fiji Islands. The disease was introduced by the King of the Fiji Islanders and his escort, upon their return from New South Wales. The entire population of the islands was estimated at 150,000 and it is officially stated that there were 40,000 deaths from measles in the ensuing period. In certain islands and villages where more exact information was secured, it was found that from twenty-seven to twenty-eight per cent. of the people died. Panic, insanitary conditions and ignorance of how to care for the sick resulted in this high mortality. V. C. Vaughan has remarked that when measles is introduced into a population with a susceptibility of 100 per cent. “it strikes down so many at practically the same time that adequate care for the sick is impossible.” The rapidity with which the population is invaded is practically as great as it is during influenza epidemics.
It is the opinion of the author that the phenomenon which contributes chiefly to the occurrence of influenza in epidemics and pandemics, and which causes the characteristic curves of a primary influenza wave, is the absence of any permanent immunity. We have shown in our discussion that no immunity is proven to exist after a year and a half or two years at the most. Measles occurring in a non-immune population spreads through that population with the same high rate as does the influenza. In Charts XXVIII and XXIX we find the curves of incidence of measles in certain of the United States Army camps in the fall and winter of 1917–18. The simplest curve is that for Camp Wheeler. Here the type is similar to that found in the primary wave of influenza. There is a quasi-symmetrical evolution and the concentration is closely grouped around the maximum. The total duration of the epidemic is short, not being much over eight weeks. The troops at this camp were predominantly rural. The disease starting in this group of relatively non-immunes spread rapidly until presumably all susceptible material was exhausted. Compare Camp Wheeler with those camps where the population was chiefly urban. Here the wave is of longer duration, is not as high, the increase is slower, the decrease is more gradual and the concentration is not grouped so closely about the maximum. In the case of the other camps with chiefly rural population, the curve is not as simple as is the case with Camp Wheeler, and there are at times secondary curves as in the case of Camp Bowie, but the essential similarity to the curve at Camp Wheeler and the difference from the curves at Devens, Dix, Custer and Grant is striking. It may be that the double waves are explained by acquisition of new bodies of troops, by the introduction of new susceptible material. On this question we have no exact information.
CHART XXVIII.
CHART XXIX.
This experience was equally true during the Civil war. Although there are no exact reports, it appears that measles prevailed in the Confederate army and was much more highly fatal than in the Union army.
A recurrent influenza epidemic usually takes the form of a secondary wave, particularly so if it follows the primary wave within a short period of time. The difference in the character of the wave is due to the fact that there is still a comparatively large concentration of immune individuals, immunized by having had the disease during the primary spread. The secondary type of the influenza wave corresponds with the measles curves for the urban camps. There are all gradations in influenza from the typical primary wave down to a very much flattened wave of relatively long duration, and even on to the stage of endemicity, with no discernible wave. In 1920 the recurrent epidemic partook more of the form of a primary wave, because in most individuals the period of immunity had been completed by January and February, 1920.
If we could, by some means, induce an immunity which would last for long periods of time, pandemic influenza would disappear from the earth and the disease would be relegated to the comparatively minor position now occupied by measles. The disease would be constantly endemic, frequently breaking out in small epidemics, but never becoming pandemic. This is one object that should be held in view by the immunologists and bacteriologists. But it is not so simple. Even were a successful vaccine discovered, it is doubtful whether any considerable group of the population could be persuaded to take it as often as would be necessary. Universal vaccination against small pox has never been carried out. The same would be true at the present time with regard to influenza.
There is another similarity between measles and influenza. Measles is as infectious as is influenza. It is as readily transmitted and the mode of transmission is probably the same or very similar. In both diseases we are made poignantly aware of the great contagiousness of the disease, and yet in neither disease has there ever been conclusive evidence of experimental transmission from man to man. Several have reported attempts to transfer measles, but in each case the evidence of infection has been incomplete. The work of Hektoen has been quoted in particular, but Sellards, after carefully reviewing his work, concludes that the evidence of infection is insufficient. Moreover Hektoen’s patients were not exposed subsequently to measles infection in the natural way.