Part 27

It has been the experience of many that during influenza epidemics other acute specific infectious diseases appear to diminish, both in number of cases and in extent. At Camp Sevier, for example, two measles wards had been quite constantly full of patients up to the time of the fall influenza epidemic, while during the time of the epidemic one ward appeared sufficient to hold all cases of measles. In the stress of the epidemic this difference was probably more apparent than real, and certainly is not to be taken as of statistical value.

Vaughan and Palmer report for all troops in the United States that, “Without exaggeration it may be said that for the time being at least, influenza and pneumonia suppressed other infectious diseases. Typhoid fever increased to a barely noticeable degree. The death rate from this disease was somewhat higher, but the total number is so small as to barely warrant comment, and not to justify any definite conclusion. Scarlet fever and malaria were both lower than during the summer. In fact, there was but one scarlet fever outbreak of any importance and that occurred at Camp Hancock. Within two weeks over 300 cases were reported and this marks the largest scarlet fever epidemic that occurred in the camps in this country at any time. Meningitis increased although it did not reach the prevalence of the previous winter. The weekly incidence curve for all troops in this country suggests that meningitis was in some instances a sequel to influenza. The greatest meningitis incidence corresponds with the influenza peak. Diphtheria showed no material increase. Deaths from tuberculosis were higher in the autumn than in the two previous periods, the death rate rising from 18 per 100,000 during the summer to 46 in the autumn. The rate for the previous winter was 15.”

In 1889 Abbott was unable to find satisfactory evidence of a connection between influenza and other epidemic diseases, although as he mentions, such connection had often been affirmed. Instances in support of each position were to be found in the literature of the time.

P. Friedrich, after an exhaustive study of the literature, following the 1889 pandemic, concluded that there was no relationship whatever between the incidence of influenza and other acute infections. Wutzdorff reached the same view after studying the various diseases during the influenza recrudescences and recurrences. Finally, Ripperger concluded likewise.

It may be remarked that following 1918 there have been several articles written concerning the relationship between influenza and certain other diseases. These are difficult to correlate and in most instances so many additional factors play a part that the conclusions drawn are perhaps not entirely well grounded. Sylvestri found that in his experience malaria patients escaped the influenza during the pandemic. He believes that it was the malaria rather than the quinine which was responsible for the apparent immunity. On the contrary others have observed, if anything, an increase in malarial patients.

Fränkel and Dublin found that during the pandemic period deaths from whooping cough increased. The difficulty of differentiating between whooping cough and influenza as a cause of death is apparent.

It seems quite certain that deaths from organic diseases of the heart increase during and following influenza epidemics and are due probably to the inability of the weakened patients to resist the added burden. Fränkel and Dublin found an increase in deaths from this cause. This was also observed to be true in Spain and other localities.

Jordan has compared the curves of influenza with those of acute coryza among school children of Chicago and finds that the period of highest incidence of colds in October, 1918, occurred in the second week of school and that it preceded the corresponding period of influenza by seven weeks. There were three peaks in the curve for colds and only two in that for influenza. The period of highest incidence of colds follows the first peak of the influenza curve by one week, while during the week of greatest prevalence of influenza there is a sharp fall of the number of cases of colds. The third peak for colds occurred one week after the height of the influenza curve. As a rule the colds curve runs at a higher level than that for influenza. A striking fact is that the portion of the curve for influenza contained within the period November 23d to December 7th, is almost the exact opposite of the corresponding portion in the curve for colds. How much of this is due to the factor of diagnosis is difficult to say.

_Encephalitis lethargica._—It is not within the scope of our report to discuss in detail this disease. Its apparent relationship with influenza, in point of time, if not otherwise, calls for special mention. In 1712 a disease followed a pandemic of influenza, occurring particularly in Germany, where it was known under the name of “Tübingen Sleeping Sickness.” In the spring of 1890, according to Netter, a disease of similar character called “Nona” was distributed especially in Northern Italy and Hungary and scattered more or less diffusely over a large part of Europe. Preceding the last influenza pandemic the disease was first reported in Vienna in the winter of 1916–17. Cases were seen in Paris in February and March, 1918, and the first official report of the disease in England seems to have been on January 26, 1918. In the spring of 1918 there were 168 officially reported cases in England with 37 deaths. The disease seems to have disappeared there in June, 1918, and reappeared in the autumn of the same year. The first cases in the United States were reported by Pothier at Camp Lee, Va. Following the great influenza pandemic cases of lethargic encephalitis have appeared in all parts of the world. It has been present in England, France, Belgium, Switzerland, Austria, Greece, Italy, and other countries of Europe, South America, Mexico, the United States, Australia, Queensland, New South Wales, and Algiers. There was an increase of encephalitis lethargica concomitant with the increase of influenza in the early months of 1920. Thus, in Switzerland 440 cases were reported during February, 1920. The 1920 epidemic of influenza in that country had almost ceased by the middle of March, while that of lethargic encephalitis had greatly decreased. One hundred and forty-one cases of the latter disease appeared in the canton of Zürich alone.

Is epidemic encephalitis a disease sui generis or is it a form of influenza?

The consensus of opinion has been that it is a separate disease. There is, however, no way of telling how close is the relationship to the influenza itself. If lethargic encephalitis is a sequel to influenza, is it caused by the same germ? Flexner points out that in 1916, when the first cases of encephalitis appeared or at least were recognized in Austria, the epidemic of influenza had not yet appeared. In England, France and the United States the epidemics of the two diseases were more or less coincidental. He believes that little weight can be given the supposed coincidence of influenza and the “sleeping sickness” of 1712, and that it is highly improbable that the semi-mysterious affection, “nona,” which dates from 1890 was definitely a sequel of influenza. He concludes that the outbreak of encephalitis either antedated the pandemic of influenza of 1918, or that the two diseases more or less overlapped; that is, although probably quite by accident, they prevailed concurrently. He prefers for the time being at least to regard them as independent diseases.

Crookshank believes that encephalitis lethargica is a distinct disease, but that it occurs frequently as an antecedent of or coincident with influenza, together with increase in the existence of poliomyelitis and certain other diseases.

Nevertheless the association in point of time and place between influenza and lethargic encephalitis cannot be lightly overlooked. As we have seen, Flexner’s criticism that encephalitis antedated the influenza is not valid, because the latter was present in 1916. We must await fuller evidence on this subject.

SECTION VII.

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.