Influenza

by Warren T. Vaughan

Periodicity.

The phenomenon of occurrence of epidemic influenza in many countries, even on different continents almost simultaneously and often without any clearcut progressive spread from one of these countries to another raises the question of periodicity in influenza. Is this simultaneous occurrence due to some mechanism in the life cycle of the influenza virus whereby it regularly acquires increased invasiveness, no matter what its geographical distribution, or is it merely a feature of the meteorologic conditions that makes the epidemic appear to be simultaneous in widely scattered communities?

Influenza characteristically returns. An influenza period usually comprises from three to five years, with one or two very mild epidemics at the beginning which may frequently be overlooked, then of wide pandemic spread, to be followed by endemic recurrences for as long as two or three years. During these influenza periods the intervals between waves are frequently so nearly equal or multiples of each other as to force the question of a periodic law. Not only thus, but even on a larger scale does the disease appear with a certain uniform regularity. The great epidemics are separated frequently by intervals approximating decades. Stallybrass calls attention to the epidemic years in England, which are 1789–90, 1802–03, 1830–32, 1840–41, 1848–49 and 1851, 1854, 1869–70, 1879, 1890–91, 1898, and 1918–19. With the exception of 1854 all of these dates are around the end of a decennium.

Yet, again, in the successive waves of an individual epidemic, as has been pointed out by Pearl, there is very roughly some periodicity.

Are these admittedly obvious phenomena fundamental features of the life cycle of the influenza virus, or are they incidental, due to extrinsic causes, changes in the pabulum, in the host as an individual, or in the host as a community, or changes in climatic conditions? Is it a basic feature upon which we must build our conception of the epidemiology of epidemic influenza, or is it more a feature of chance? The evidence to date is conflicting and incomplete. The answer lies in the future.

Periodicity in the acute infections is not a new subject. It has been discussed in various other diseases, particularly in measles. For many years epidemiologists in many parts of the world have reported the observation of a periodicity in epidemics of measles. It is generally regarded as an established fact that each locality suffers from epidemic waves of this disease and that the period is somewhere about two years. In certain relatively small localities in England where registration statistics have been kept for many years the Health Officers count on an epidemic every two years. In some places the epidemic is expected to fall during the even years, while in others it occurs in the odd years.

Brownlee has been one of the foremost investigators in the periodicity of influenza, but since his communication on that subject was very brief, we take occasion to quote first from his article on the periodicity of measles, thereby gaining a more comprehensive knowledge of his theory, and at the same time becoming able to compare the periodicity in the two diseases.

“The common explanation of the periodicity of epidemics of children’s diseases is that the susceptible children take the disease in sufficient numbers to limit the further spread. The epidemic thus dies out to recur when a further sufficient number of susceptible children have accumulated. This is quite a feasible theory and certainly explains the periodicity of epidemics. The forms of epidemic curve which arise on this hypothesis are not unlike those actually found, the differences being no more than might be expected between a mathematical form based on a hypothesis and the natural conditions to which the hypothesis is only an approximation. This explanation, however, must fail if epidemics of different periods can be shown to exist in the same town at the same time, and I think this has been shown. In London, which on account of its size might be assumed deserving of special treatment, the existence of periods of different length have been demonstrated. In Edinburgh, Glasgow, and Birmingham also it has been shown that epidemics with periods in the neighborhood of ninety-eight weeks and one hundred and ten weeks intermix. The same epidemicity even applies to districts in London. In the West end of London we have almost a replica of what occurs in Glasgow, Birmingham and Edinburgh. The main period there is 97 weeks, the secondary period 109.5 weeks. In the South of London one period is that of 97 weeks, but almost equally prominent is that of 87 weeks. The whole evidence, therefore, seems to point to some condition in the organism which produces the disease as the potent cause of the difference rather than to the number of susceptible children. Compare the Paramoecium which under natural conditions divides asexually for several hundred times and then dies out unless conjugation takes place. The resting stage following conjugation persists for some time.

“There is, however, one point of great importance which must be considered. If an epidemic begin in a definite locality and spread from that locality, and if there is no loss of infectivity on the part of the organism, it is demonstrable that a similar proportion of the population should be attacked in each zone as the epidemic spreads outward. On the other hand, if the organism lose the power of infecting with the lapse of time, in each additional zone invaded the proportion of susceptible persons infected should become smaller and smaller. Of course this might not be true for any one epidemic, as in many parts of the area invaded the population might be more or less susceptible because of recent attack of the disease, but when an average of twenty outbreaks has been taken this effect should be eliminated, the number of times the invading organism comes into contact with an insusceptible population being balanced by the number of times which it meets one more susceptible than the average. The method of spread of epidemics on the average should thus give some indication regarding the laws which determine the course of the phenomenon. Now with regard to London, the clearest facts refer to the 87-weeks, the 97-weeks and the 109.5-weeks period. The 97-weeks period starts at the same time all over the city and there is no evidence of any special center. The infection seems generalized. With regard to the 87-weeks epidemic, however, the case is different. This seems to start in St. Saviour’s Parish and to spread thence to Camberwell, Lambeth, etc. In this epidemic the rate of spread can be definitely measured. The maximum occurs later and later as the distance from the center is increased and the percentage of children infected is also easily observed to fall as the time increases. With regard to the 109.5 weeks’ period epidemic the facts are similar though not quite so definite. This seems to show that for at least two strains of organisms the epidemic ceases because the organism has lost its power of infecting. It may be inferred that an epidemic ceases because the organism varies in its potency to cause infection. A cycle of epidemics now coinciding and now differing in their maxima can thus be explained. Some kind of life cycle exists in the infecting organism. In this life cycle high powers of infecting are attained probably after a resting state: a period of activity follows and gives place to a period of rest; the average length of the cycle is determined by the strain of the organism.”

There are certain drawbacks to Brownlee’s work and conclusions. We quote from V. C. Vaughan, who has discussed Brownlee’s work, not only because of his good summary of the difficulties and disadvantages of the method, but particularly because the same disadvantages and possibility of inaccurate conclusions hold in the case of influenza.