Experimental Epidemiology, 1936 (; backlinks; similar):
The studies outlined in the report above have been in progress for some 15 years and they form an attempt to place the science of epidemiology on an experimental basis. They are laborious and costly and the authors justify both the labour and the expense involved in the introduction. Although it is well known that animal hosts and their microbial parasites vary in resistance and infectivity respectively, and that many other factors play their part in the form which an epidemic disease takes, when all the odd pieces of knowledge are added together the answer is only a working hypothesis and not a conclusion. In other words, the many questions regarding epidemics can only be answered by finding out actually what happens in an infected herd, not by deducing what might happen from knowledge of what occurs in individual hosts. The herd must be the universe of study.
The experiments on which the report is based have involved the use of between 100,000 and 200,000 mice, and a brief outline of the general methods of experiment are given. It has been possible to maintain herds for months or years infected with bacterial parasites such as Salmonella typhimurium and Pasteurella muriseptica without any cross-infection and to watch the effect of various methods of interference on the spread of infection. Experiments have also been made with herds infected with the virus disease ectromelia.
From statistical analyses of the results, it is concluded that in herds of mice living in close and continuous contact and subject to the continuous or intermittent immigration of susceptibles, the disease will never normally die out. It might happen that the disease would become extinct but such an event would be a mere accident of small numbers. The form of the mortality curve depends mainly upon the rate of immigration and the equilibrium between hosts and parasites is fundamentally unstable and, when disturbed, the system tends to pass through a period of violent fluctuations before equilibrium is again established. The average resistance of surviving mice increases with survival in the herd but never becomes absolute. The great majority eventually succumb to the reigning disease.
Selection, both by death of the more susceptible, and by natural immunization, plays a part in the increased resistance displayed by surviving mice, and the latter is probably the more important. An infected herd is a highly complex system, consisting of mice suffering from a fatal infection, others in a state of infection-equilibrium that ends in death or recovery at some later period, others undergoing natural immunization by an infection of slighter degree, and a small minority not yet infected. The differences in the form which epidemics display are due to the state of equilibrium established in this complex system, which may be shifting or temporarily stabilized.
The level of mortality in a herd, the proportion of immunizing to fatal infections, and the degree to which infection occurs, are largely determined by the characters of the bacterial strain with which the epidemic is initiated. It is considered that virulence and infectivity may vary, a highly potent “epidemic” strain possessing both these characters.
Apart from changes in the conditions of contact, the only important method of interfering with the normal course of events in the infected herds is artificial immunization. It has not, however, under the conditions of these experiments, approached the successes recorded from the field. As with natural immunization, so artificial immunization has appeared to be more effective against the virus disease (ectromelia) than against the bacterial disease (mouse typhoid). In no case, however, is the immunity attained complete, the immunized mice eventually dying from the prevailing disease. Infection of immunized animals is common and in ectromelia, and probably in the bacterial diseases, many of the immunized and infected mice are infective for normal animals. It is, therefore, unlikely that, even if it were possible to devise a method of immunization more effective in lowering mortality than those employed by the authors, infection could be eliminated from the herds and so render safe the admission of susceptible immigrants.
As stated in the preface: “the experimental epidemic affords a more natural, and more severe, method of testing the value of any prophylactic procedure than assays carried out by more artificial tests on individual animals. It can never, of course, replace field observations made under completely natural conditions; but it may well indicate possible solutions to many of the more important practical problems, and so direct the field epidemiologist along the most fruitful lines of inquiry.”
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