TERIOLOGY; FILTER-PASSING VIRUSES; PARASITOLOGY) which cause disease, and with careful observation in the field as to the manner in which disease spreads from person to person, new view points have emerged. Most diseases have their special forms of spreading which account for practically all the cases. Thus measles (see INFECTIOUS FEVERS) and smallpox (q.v.) are exceed ingly infectious from person to person. Typhoid fever (q.v.) is nearly always carried by contaminated water or contaminated food. Cholera (q.v.) is spread by water and flies. Other diseases have been found to be practically non-infectious from person to person unless by means of an intermediate parasite. Thus typhus (see INFECTIOUS FEVERS) and trench fever are carried by lice, while yellow fever (q.v.) and malaria (q.v.) require the interven tion of the mosquito. The mode of spread of some diseases is still obscure. Among these scarlet fever must be placed. While direct infection undoubtedly takes place, a satisfactory elucidation of the problems of its dissemination has not yet been arrived at.
Disease-producing organisms possess two qualities: one, the power of causing the disease ; and the second the power of producing a severe attack of disease. The first may be termed infectivity and the second virulence. These qualities must not be confused. In
of fact, they are not constantly associated. In certain diseases the height of the epi demic seems to be associated with severe disease, in others with that of milder type. The former at least holds for a certain num ber of large epidemics of measles of which the statistics have been investigated. The latter is the case both in Glasgow and London in regard to the autumnal prevalence of scarlet fever.
That an epidemic might possess a definite form capable of calculation seems to have been advanced first by Farr. In 184o he graduated the decline of the great smallpox epidemic in England to the normal curve of error, and obtained a very close representation of the facts. He promised further discussion, but seems to have given none till 1867. In this year he returned to the subject in connection with the cattle plague, writing a letter to The Daily News, in which it was stated that though in the popu lar conception plague was advancing with such rapidity that all the cattle of the country might be destroyed, in reality the force of the epidemic was spent, and that if the form of the epidemic curve up to that point were taken as a basis of calculation the future course could be foretold. The prediction proved to be very near the truth.
The theory of the course of the epidemic, however, as a guide to the solution of the problem has unfortunately not proved so fertile as might have been hoped. Some facts are quite definite. The curve of the epidemic is often found to be symmetrical, the fall correspond ing closely to the rise, though in some diseases the ascent is more rapid than the descent, and in some the reverse. The equation of the curve which describes the majority of epidemics, as found by trial apart from theory, is where y is the number of cases at time t, t being measured from the centre of the epidemic.
Curves closely resembling that given by the above equation arise on a number of hypotheses, of which two are discussed. First, the organism may be assumed to possess at the beginning of the disease a high degree of infectivity, which decreases as the epi demic goes on. If the loss of infectivity is according to geometric law, the normal curve of error already used by Farr is the result. It is sufficient to state that on various probable hypotheses regard ing exposure to infection, etc., the normal curve may be so modified as to take the form found by observation. Secondly, a similar type of curve arises if we consider an epidemic dies out from lack of susceptible persons. It is not possible to distinguish statistically these hypotheses from the consideration of the epidemic form alone. In one case, however, the second hypothesis can be tested. If the form of the epidemic be calculated by assuming different degrees of infectivity on the part of the organism, an infectivity which remains constant during the epidemic, it is found that this curve becomes flatter the smaller the degree of infectivity.
Now with regard to plague in India, among brown and black rats living more or less in the same circumstances, it is observed that many more brown rats are infected than black. In such cir cumstances the form of the epizootic should be different in the two species if the decline is due to lack of susceptible individuals. As a matter of fact it is nearly identical : a fact which tells strongly in favour of the hypothesis that the epidemic ends because of loss of infectivity on the part of the organisms. This example would be crucial but for the fact that the flea on which the spread of the epizootic depends has a law of seasonal prevalence of its own.
In many cases, however, the only feasible explanation of the course of an epidemic is that the organism loses the power of in fecting as the epidemic proceeds. It is difficult to believe, for in stance, with regard to the great epidemic of smallpox in London in 1901-02, that there were only 8,000 people susceptible out of a population of 6,000,000. As the course of this epidemic was typi cal, rising and falling in the manner found to be characteristic, it cannot be argued that the decline was due to the action of the health authorities ; all they can have done was to limit the extent of the epidemic, leaving its course unchanged.
The next point requiring consideration is the periodicity in the epidemics of infectious diseases. Taking measles as an example, the common explanation is that each epidemic ends from the exhaustion of the number of susceptible persons, and that it is only when a new population of susceptible children has accu mulated that a further outbreak occurs. This explanation fails to account for many of the facts. Even after the very large epidemic of measles in Glasgow in 1906, it was found that nearly half of the children admitted to the fever hospitals immediately there after suffering from other diseases had not suffered from measles, so that there must have been, with the high infectivity of the epi demic, plenty of susceptible material. The disease subject to the most extensive enquiry hitherto has been measles. Using the method of the periodogram, the statistics of London and all the chief towns of the British Isles have been analysed. It is found that in almost no case is there only one period to be discovered. In London there are several, the chief of which is 97 weeks.
Periodicity in other diseases is well known. Thus in the city of Liverpool the epidemics of scarlet fever occurred at regular inter vals of four years from 1850-78. On one occasion alone was there an exception, when the interval between two epidemics was three years in place of f our. A similar periodicity of five years has been observed in Glasgow. There is one specially interesting example, namely, the occurrence of plague in Bombay. In many places, such as Hong Kong, the period between each epidemic is rigidly a year. In such a case the influence of the season of the year seems a sufficient explanation. But the case of Bombay is different. The first epidemic, in 1897, had its maximum about the 40th day of the year. From this point until the last year for which statistics are available (1918) the date of the maximum of the epidemic has steadily advanced into the year, advancing about 8o days in 20 years, or an average of four days a year. The conclusion must be arrived at that while some periodicities of disease are strictly sea sonal others are not so, and require some further explanation.
A further important application of mathematics to epidemiology has been made by Sir Ronald Ross in his studies on malaria (q.v.). Here the factors influencing the spread of the disease are numer ous. Rainfall and temperature, the number of persons carrying the organism in their blood, the number of mosquitoes and the proximity of the breeding-places of the mosquito to the abodes of men, are all capable of quantitative measurement, and of fur nishing guidance for suitable administrative measures.
The relationship of epidemics to cli mate has received much attention in recent years, though in many cases the cause of seasonal prevalence is elusive. Thus, why scarlet fever should be so regularly an autumnal disease is not at all clear. On many cases, however, much light has been thrown. The dis covery, for instance, that malaria was carried by the mosquito elucidates the seasonal distribution of that disease. A temperature of a certain height associated with pools of water is necessary for the rapid development of the mosquito, and also a certain degree of temperature for the development of the parasite in the mos quito. In the same way the zone to which sleeping sickness is limited is a narrow region in which the climate and environment are suitable to the life history of one particular tsetse fly. Much light has been thrown on the epidemiology of plague by the dis covery that it was carried to man from the rat by means of the flea. Humidity is necessary for the growth of the flea, and con sequently epidemics of plague can hardly occur at seasons of the year when it is warm and dry. Thus the epidemics of plague in Bombay, which have advanced progressively later and later into the year, now occur when the flea is no longer at its greatest prevalence. With this change the number of cases and deaths has greatly diminished.
As to the relation of epidemics to the organism which causes them, why an organism should be capable at one time of causing a great epidemic and at another only a few sporadic cases of a disease has not yet been found out. That organ isms do vary in the power of infecting in this manner is a truism to anyone who has administered in the health departments of a large city. At one time the merest contact with a case of smallpox, for instance, will give rise to a large number of cases. At another time a patient suffering from smallpox may even attend a theatre without giving rise to a case of infection.
A considerable amount of evidence has been accumulated that an organism, having found a suitable host, or succession of hosts, may have its virulence unusually exalted, and if the virulence can be exalted in this manner, it is probable that some similar condi tions may give rise to a great increase in the power of infection.
While an epidemic may in many cases be chiefly or even wholly due to the active condition of the causal organism, it is to be remembered that the vitality and environment of the persons affected must also play a part. Thus, for instance, typhus fever introduced into a crowded slum in which lice are plentiful will almost certainly cause considerable havoc, but even here the havoc will be determined to a certain extent by the season of the year. If the weather be cold the people are crowded together on account of the demand for warmth, and the chance of infection is increased. In addition, in the winter, food is often scarce, and consequently vitality is low. If, on the other hand, the invasion of the organism takes place during the summer, a large epidemic will be unlikely. But though these factors act, yet if an organism has an exalted state of activity an epidemic of the disease may occur at any season of the year, even the most unlikely. Plague, for in stance, especially in temperate climates, is essentially a disease of the warmer part of the year, yet it has been known occasionally to occur in large epidemics in the middle of winter, while epidemics of typhus of considerable size have been recorded in the summer time. The great epidemic of influenza (q.v.) in the autumn of 1918 is a striking example, such a season being a very unusual one for an outbreak of this disease. What role special susceptibility on the part of the population had in this case is not known.
Some other influences also act. There is some evidence that fatigue predisposes to enteric fever, an army on the march drink ing polluted water tending to have a larger number stricken than a similarly conditioned civil population. Further, it cannot be doubted that the accumulated effect of seasons may tend to de press health and increase susceptibility to certain diseases. The cumulative effect of winter cold may be, perhaps, traced in children in relation to death from whooping-cough, the average minimum temperature in the winter preceding the maximum number of deaths from whooping-cough by about six weeks, while the form of the two curves is very much the same. The deaths from whoop , ing-cough are due very largely to bronchopneumonia, yet the sea sonal distribution of whooping-cough is not identical with that of the latter disease. Thus scarlet fever, being an autumnal disease and following the hot summer, might in the same way be ascribed to depression produced by continued hot weather, making certain persons more susceptible to the disease. But as scarlet fever is a disease almost absent in warm climates this explanation can hardly be complete, and some other factor must be necessary. None of these questions have at present been sufficiently investigated.
Another point of importance requires special refer ence, and that is the problem of "carriers," as individuals infected with a disease and cured as regards themselves, but who yet con tinue to harbour and distribute the parasite, are called. Cholera follows the pilgrims' way, enteric fever the carrier cook, diphtheria the carrier school-teacher (see CARRIERS).
Recently, investigators in sev eral countries—Topley and his collaborators in England; Webster and others at the Rockefeller Institute, New York; Neufeld, Lange and others of the Robert Koch Institute in Berlin—have applied the experimental method to the study of epidemiological prob lems. The plan has been to study the course of an epidemic dis ease introduced into a herd of mice, its evolution under conditions better defined and more simple than obtain in nature. Greenwood and Topley, for instance, have watched the progress of a fatal in fectious disease of mice due to an organism of the Pasteurella group in a population of mice replenished wholly by the addition of normal animals over a period of more than three and a quarter years—that is, through a period much longer than the length of an average generation of mice. They have shown that in these cir cumstances the prevalence of the disease exhibits wave-like move ments, and that the intervals between successive exacerbations can be diminished merely by increasing the rate of immigration of normal animals. In infections of this type the regular immigra tion of healthy animals is sufficient to maintain the disease in definitely.
In field epidemiology much work has been done in developing a method of prophylaxis against diphtheria, rendered possible by the discovery that certain persons exhibit a peculiar skin reaction (the so-called Schick reaction) after the injection within the skin of a small quantity of the toxin produced by the bacillus of diphtheria (see INFECTIOUS FEVERS). It is thought that such persons are especially liable to develop the disease when exposed to infection, and that an outbreak may be controlled or prevented by the immunization of those who respond to this test. This immunization is obtained by the injection of small doses of a mixture of toxin and anti-toxin. The method has been employed on a large scale, particularly in America. It is, however, too early to express a decided opinion, since the statistical evidence which has been tendered has not always been free from ambiguity.
excellent general account of the progress of Bibliography.-An excellent general account of the progress of knowledge is contained in Haeser's Lehrbuch der Geschichte der Medizin and der epidemischen Krankheiten, 3rd ed. (1882) ; English epidemiological history is fully related in Dr. Charles Creighton's History of Epidemics in Britain, (1894) . A paper by M. Greenwood on the "Epidemiology of Plague in India," Journal of Hygiene, voL x., p. 349 (1910), gives examples of modern epidemiological methods; while his report "On the Rise, Spread, etc., of Epidemic Diseases," Internat. Congress of Medicine, Sec. 18, p. 49 (1913) , gives a full study with literature. Two papers by John Brownlee discussing "Theory of Epidemiology in Relation to Plague," Proc. Roy. Soc. Med., vol. xi., p. 86 (1918) , and the "Periodicities of Epidemics of Measles," Proc. Roy. Soc. Med., vol. xii., p. 77 (1919), give an account of the statistical and mathematical methods which may be used. Sir R. Ross's Prevention of Malaria (1910) and Sir R. W. Boyce's Yellow Fever and Its Prevention (191 I) discuss theory and practice in all their forms. For a summary of recent work on experimental epidemi ology, see M. Greenwood and W. W. C. Topley's paper, Journal oj Hygiene, vol. xxiv., p. 45 (1925) . A complete account of recent work on diphtheria is given in Diphtheria, Its Bacteriology, Pathology and Immunology, issued by the Medical Research Council (1923). See also J. D. Comrie, "The Effects of Volcanic Action in the Production of Epidemic Diseases," Edinburgh Med. Jn. (1927) ; K. Kisskalt, "Origi nating and Passing of Epidemic Diseases," Internat. Clin. (1926) ; K. Sudhof, "Epidemiologic Rules of the Past," Jn. Am. Med. Assn. (1925) ; F. G. Crookshank, "First Principles and Epidemiology," Proc. Roy. Soc. Med. (1919-2o) ; S. Flexner, "Epidemiology and Recent Epidem ics," Tr. Cong. Amer. Phys. and Surg. (1919) and Jn. Am. Med. Assn. (1919) ; A. L. Fourcade, "Chronique d'epidemiologie," Arch. de Med. et Pharm. Mil. (1922) ; F. H. Garrison, "The New Epidemiology," Mil.
Surg. (1923) ; H. B. Hemenway, "Epidemiology," Internat. Clin.
(1918) ; R. J. Reece, "Progress and Problems in Epidemiology." Lancet
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