Typhoid, as seen in humans, is an allergic condition with an incubation period obligatory longer than 6 days. However, in experimental animals the same microbe induces a condition with a short incubation period, a fact which indicates a primary toxic pathogenesis. This difference can explain the striking difference in results with immune sera. The literature emphasizes great efficacy in experimental animals for various immune sera prepared against this microbe and its endotoxin (Chantemesse, Besredka, Kitasato, Wassermann, etc.), but no efficacy in the human disease.

In our experiments, when a sufficient amount of microbes, alive or dead, was injected at once, a primary toxic condition was induced in guinea pigs. The incubation period was brief. With the same microbe, alive or dead, we were able to obtain the allergic form in guinea pigs with repeated, daily injections of small amounts. The allergic form similar to that seen in humans was induced. After about 12 days, temperature started to rise and usually remained high for more than two weeks, even with the dead microbe if the injections were continued. If living microbes were used, the condition continued even without new injections. We even obtained positive hemoculture at this time. Under similar conditions, the same allergic form of typhoid also was induced in rabbits although much less consistently than in guinea pigs. An antityphoid serum obtained from rabbits showed activity against the toxic form of infection induced in guinea pigs. It was entirely ineffective against the allergic form when that was already present, although the total amount of microbes injected over a period of many days was smaller than was used to induce the toxic form. Injected before the 8th day, the same serum prevented the appearance of the allergic form of the experimental disease.


In the light of our concept, we studied tetanus pathogenesis in an effort to explain the classically emphasized separation between the so called small and big animal disease. (39) In mice, tetanus has a short incubation period and is manifested by localized contractions, while the disease of so called "big animals" starts with trismus after an incubation period of more than 6 days. Based upon incubation times, we considered tetanus to be the toxic form in small animals, the allergic form in large animals.

We could, in fact, induce a condition in mice manifested by trismus and epistotonus, and having an incubation period longer than 8 days, by daily repeated intravenous injections of small amounts of toxin. The special affinity of this toxin for the nervous system, and the strong bond between nervous tissue and toxin, limited the response to the antitetanic serum even of the primary form. If injected in time, however, the antitetanic serum controlled this primary form. The same serum appears to be highly effective in the prevention of the condition in animals which have been prepared for the allergic form, provided it is administered before the allergic manifestations have appeared. The same serum is totally inactive once the allergic condition is present.