Vaccine Prophylaxis against Tularemia in Man

Abstract

IT is characteristic of tularemia that most patients develop a high degree of natural resistance after infection occurs. The mortality is low. Recovery confers lifelong immunity which protects against subsequent massive exposures with an effectiveness seldom encountered in bacterial diseases. Second attacks of disease are unknown. Local reinfections occur occasionally among immunes subjected to repeated exposures to virulent strains but, as Francis first indicated, they are either asymptomatic or associated with brief and mild constitutional symptoms.' One of us has recorded apparent immunity, due to vaccination, which successfully withstood accidental massive exposures to strains of high virulence.2 Although tularemia is of minor importance as a cause of death it has considerable social and economic importance in areas of high endemicity as a cause of prolonged morbidity and disability. Its capacity to disrupt normal activities of military encampments is recognized.3 The extreme ease with which infection is acquired, and the high infection rates among butchers and market men, scientific investigators, rabbit hunters and their wives and cooks who prepare game for the table, indicate the desirability of better methods of protection than those now in use. Preliminary experiments with heat killed and formalinized Bacterium tularense * suspensions demonstrated clearly that vaccines made by these methods, from either virulent or avirulent strains, provoked severe and extensive constitutional and local reactions upon initial injection into normal individuals. Reasonably well tolerated doses were so small that several months of daily injections were required to produce agglutinin titers to 1:320, a scheme tolerable for a few laboratory workers but impracticable for large scale use. The successful efforts of Ramon and his associates to diminish primary toxicity of toxins and of various bacteria without significant impairment of their antigenicity., by various chemicals, led us to try similar methods. We established the following specifications for an acceptable vaccine: