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.
[Illustration: Respiratory Disease at Army Camps]
CHART XXIX.
[Illustration: Respiratory Disease at Army Camps]
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.