Under all circumstances, rabies needs an incubation time of more than 5 days. From our point of view, therefore, it has to be considered an allergic condition. When the rabies virus was passed repeatedly through the brains of rabbits, incubation time became continuously shorter and ultimately was fixed at 6 or even 5 days. Classically, this progressively shortened incubation time is interpreted as being due to progressively increased virulence of the virus after these passages. In the light of our concept of the pathogenesis of infectious disease, a reduction of incubation time is the result of increased virulence only in cases of primary direct toxic pathogenesis. In the allergic condition, which has an entirely different pathogenic mechanism with the incubation period related to the time necessary for the body to produce coagulant antibodies, a shorter incubation would correspond to a different change. It results from a greater facility of the organism for manufacturing antibodies against the infectious agent. In the case of rabies, a short incubation period of 5 days for a "fixed virus" would mean that the organism is able to manufacture allergic antibodies more easily, and consequently earlier. Apparently, antibody production is more difficult for the "street virus" which has a longer incubation time. The fixed virus consequenUy appears to be not only a brain adapted virus, but also a weaker antigen, against which the body and especially the nervous system is more easily able to manufacture allergic antibodies.

The possibility of using the fixed virus as a vaccine in an individual already infected with street virus can be explained by differences in the relationship between the organism and the two viruses. Usually the street virus has a much longer incubation time, indicating that the body needs much more time to manufacture the allergic antibodies. The same as the animal is able to make allergic antibodies in a short time against the fixed virus, the vaccinated individual will be able to manufacture more rapidly also the protective neutralizing antibodies against the same changed fixed virus. The neutralizing antibodies will thus appear earlier and act against the "street virus" before the organism in general and the nervous system in particular has made allergic antibodies against it.

It is possible, however, that an additional factor may intervene in this case. In vaccine, we use an allergic complex as it is present in the nervous system. This corresponds to a further step in the general process of immunity and its presence could shorten still more the time necessary for the appearance of protective neutralizing antibodies.

The concept of rabies, clinical and experimental, as an allergic condition has recendy received confirmation through the results obtained with a specific antirabies serum (Koprowski). With no curative capacity, this serum is able to prevent the disease if it is injected before the appearance of the clinical condition, even if only shortly before. It helps in cases where no more time is left for active immunity to be established by the body itself as a response to the vaccine. This passive immunity is consequently indicated for the case in which vaccination starts late. The serum, with no curative effect once the clinical condition has started, has a preventive effect, a fact which accords with the concept of rabies as a condition with allergic pathogenesis.

Syphilis And Tuberculosis

Syphilitic chancre has the characteristics of an allergic condition. The first lesion, often a small blister on a nonindurated base, shows a minimal reaction in spite of its richness in treponemas. It is only after an incubation of about 9 days that the intensive reaction appears, with the characteristic induration. Because of this, the chancre can be considered to be a specific allergic manifestation. The positive lutein reaction also corresponds to an allergic response. The appearance of secondary manifestations also can be indicative of allergic pathogenesis, but with another antigen than the treponema involved.

Several possible antigens have to be considered. One would consist of constituents of the microbe itself against which the body needs almost one month to manufacture specific coagulant antibodies. Another antigen would correspond to constituents of the body itself becoming heterogeneous under the influence of the treponema. A lipido proteinic antigen seems plausible. Complement fixation, flocculation, and other diagnostic tests for syphilis use antigens which are not directly obtained from the microbes but usually correspond to lipido proteic fractions of organs, such as heart. In the original reaction of Wassermann, the antigen was an extract from organs rich in treponema, such as the liver of stillborn infants with heredosyphilis. This would favor the hypothesis that a secondary antigen is involved and that it has its origin in the body constituents heterogenized through the influence of the spirochetae. A similar antigen would account for the pathogenesis of the secondary manifestations. By extending this concept, the tertiary lesions and parasyphilitic manifestations can also be seen to be of similar allergic pathogenesis, with other newly formed antigens involved. Secondary antigens would conceivably develop in tuberculosis as well. While the primary tuberculous chancre can be seen as an allergic manifestation having the lipido protein of the microbe as antigen, the cavern formation can be attributed to a secondary antigen.

It appears highly probable that it is these "secondary" antigens, together with the inability of the organism to manufacture efficient immune antibodies, that keep the defense in the allergic stage and impart to both tuberculosis and syphilis not only their chronic character but also their clinical gravity. The allergic pathogenesis explains also the inefficiency of all the tentatives to obtain sera against these conditions.