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482 Anti-choleraic inoculations.— During an epidemic of cholera in Spain, in 1885, Ferran instituted a system of prophylactic inoculation. He injected hypodermically ordinary laboratory cultures of the cholera vibrio obtained directly from cholera corpses. No attempt was made to regulate or standardize in any way the virulence of the cultures. The results were not encouraging. As accidents were frequent, the Government put a stop to the practice.

In 1893 Haffkine, after elaborate experiments on the lower animals, commenced a system of anticholera vaccinations, using a pure virus of a fixed and known strength. This virus he prepared by passing the cholera vibrio through a series of guineapigs by means of intraperitoneal injections. In this way the microbes were increased in toxicity to a definite point beyond which their virulence could not be exalted. Cultures so prepared gave rise, when injected hypodermically, not only to a general but also to a local reaction, the latter being so severe that it ordinarily ended in extensive sloughing and ulceration. To avoid this undesirable result, a milder vaccine was prepared by cultivating the strong vaccine in artificial media at a temperature of 39° C., and in an atmosphere kept constantly renewed. By first injecting under the skin of animals this milder vaccine it was found that such a measure of protection was conferred that subsequent injection of the strong virus was no longer followed by violent local reaction. Having satisfied himself that the subcutaneous injection of these two vaccines conferred immunity against the cholera vibrio in the lower animals, Haffkine, with the approval and aid of the Government, proceeded to use them in man on a large scale in India. Up to 1895,70,000 injections of living cholera bacilli had been made in 43,179 individuals. In no instance did any bad result ensue. While admitting that the value of his method has not been fully proved, Haffkine claims that the results are sufficiently encouraging to justify a continuation of these inoculations on a larger scale.

The symptoms which these injections produce are