Influenza

by Warren T. Vaughan

“There is no reason for supposing that the virus of measles is controlled in any way by our calendar. In order to get anywhere in determining any law of periodicity in epidemics we must know the morbidity and mortality of the disease by days, or at least by weeks. In different parts of a large city there may be, and undoubtedly are, epidemic waves of measles on the flow or on the ebb at the same time. The best work that has been done along this line is that of Brownlee, who has figured out epidemic waves of measles, based on the weekly numbers of deaths in London between 1840 and 1912.

“The figures presented by Brownlee are of great value, and his theory is fascinating and has much in its favor, not only in a study of epidemics of measles, but of the other infectious diseases of infancy and childhood, especially scarlet fever, whooping cough, and chicken-pox. In order to solve the problem of periodicity in measles we must have more exact information than we now possess. Brownlee’s figures pertain to deaths only. There are, so far as we know, nowhere in the world satisfactory statistics concerning morbidity in this disease. Deaths from measles are so largely determined by the care bestowed upon the sick and upon the extent to which secondary infection is prevented that we are inclined to hesitate about the acceptance of a death rate or number of deaths from this disease as an index to the virulence of the organism causing the disease; in other words, we are not convinced that the death rate in a given outbreak of this disease is a measure of the virulence of the organism causing it. This involves the question whether measles per se is a disease of wide variation in malignancy or are the widely different death rates observed in different epidemics due to secondary infections. The streptococcus, a common invader of the body during the progress of a measles infection, is known to possess a most variable degree of malignancy. We are inclined to the opinion that if all cases of measles could be recognized before secondary infection occurs and could be cared for ideally the death rate from this disease in different epidemics would be much more uniform than is now shown and would be low. The greatest danger to life in an attack of measles lies in the fact that the virus lowers the resistance of the body cells and opens gateways to more deadly organisms, such as the streptococcus. We believe that there are demonstrated facts which support these ideas. Quite uniformly in measles there is a well marked leukopenia. As we now interpret it, this means a decrease in the number of the forces that naturally protect the body against the invasion of foreign cells. Again as we interpret it, the failure of the body cells to respond to the tuberculin test during a course of measles or soon thereafter is evidence that the resistance of the body is lowered. If our interpretation on these points be correct we fail to see how deaths from measles can be properly employed as a standard in the measurement of the virulence of the organism of the disease.”

Recognizing then the obvious disadvantages of the method, we will turn to the work done on periodicity in influenza. We should call attention at this point to the fact that the establishment of periodicity would carry with it the assumption that the third of our three hypotheses concerning the origin of influenza is the correct one. For example, the July and autumn epidemic in England, as well as all occurring subsequent to them, would be due to a virus or several viruses which have been endemic in England since 1889, in fact since man has been in England, and the epidemics and their recurrences would be due to increase in the virulence of this local virus. The virus is distributed over the earth and may become virulent periodically in many countries at the same time, or if the periodicity is different on two continents the epidemics would occur at different times.

Periodicity is not a new hypothesis. Hirsch denied any periodicity distinct enough to be revealed by the comparatively crude statistical methods of his time. Periodicity if present can only be revealed by detailed and complicated mathematical procedures. Brownlee has investigated the weekly number of deaths from influenza in London between 1889 and 1896, and also up to the present time. He has compared these with the weekly number of deaths from bronchitis and pneumonia in London, the records of which have been available since 1870. By the method of the periodogram he showed that there was a regular periodicity of 33 weeks in deaths from influenza between the years 1889 and 1896, but that in later years there was some considerable aberration. He concluded that for some reason influenza periods tend to recur at 33-week intervals after the primary epidemic, and that the favorable season for its recurrence is from January to the end of May. Should the 33d week fall in other than these winter months the epidemic may be mild or even missed, appearing after another 33-week interval. Epidemic influenza does not assume a form which causes any large number of deaths until a bronchitic or pneumonic constitution has been established. The fatal form is usually a disease of the winter or spring. He also found that in the absence of influenza, bronchitis and pneumonia did not show a 33-week periodicity, but when associated with influenza these conditions also became periodic (33 weeks), and he assumes that this change is definitely associated with the appearance of influenza.

Between 1876 and 1890 there was no tendency to the 33-week periodicity with regard to bronchitis and pneumonia, but it was very marked between 1889 and 1896. During this epidemic period the deaths from pneumonia precede those from influenza by one week and those of bronchitis precede those of influenza by two weeks. The number of deaths from bronchitis and pneumonia ascertained by this method of grouping is fully twice the number obtained from influenza alone.

He believes that in these years, influenza appeared, on its epidemic onset, first with bronchitic symptoms, later with pneumonic symptoms, and lastly with those symptoms more definitely associated with influenza proper. When the several sets of deaths are added together in 33-week periods a very typical epidemic makes its appearance.

Brownlee finds that in the monthly statistics of Glasgow, Aberdeen, Massachusetts, etc., there has been nothing differing essentially from this phenomenon found in London.

Between 1876 and 1889 the annual curve for bronchitis and pneumonia shows two maxima, one at the end of January and the second in the middle of March. From March the decline in deaths from bronchitis is very rapid. The disease re-appears around the beginning of October. During the period 1889–96 the maximum number of deaths from bronchitis occurred in the second week of January and the last week of February. Both of these maxima are a fortnight before the maxima of the epidemics of influenza. This suggests that the advent of influenza has brought a change in the seasonal prevalence of bronchitis and supports the view that the earlier portion of the influenza epidemic is associated with bronchitic symptoms. The same phenomenon holds for pneumonia.

Brownlee was able to predict correctly the date of the recent 1920 epidemic. He did not attempt, however, to explain the short interval between the summer and autumn, 1918, epidemics in England. He speaks of the second as “aberrant.” In other words, it does not fall within his classification. October is not a high respiratory disease month. The epidemic should have been mild.

Stallybrass has confirmed Brownlee’s 33-week periodicity and suggests an explanation for the “aberrant” October epidemic. Using periodograms with a 33-week basis, and plotting deaths from influenza and respiratory diseases from January, 1890, through January, 1920, he finds that the most definite 33-week periodicity is shown during the years 1890–99. During this period there is one maximum, when all 33-week periods are superimposed, which occurs at the seventh week of the cycle. Beginning about 1899 a new maximum appears in the nineteenth week of the cycle, which continues to recur until the culminating point is reached in the week ending October 26, 1918. An additional 66 weeks carries the date forward to the first week in February, 1920. The maximum at the seventh week of the periodogram during the years 1899–1913 is greatly diminished from that in 1890–98. The periodogram for 1914–1919 shows clearly both maxima, that in the seventh and that in the nineteenth weeks.