Multiplication and survival of tubercle bacilli in the organs of mice.

Cultures of tubercle bacilli (typical bovine and human strains) known to differ in the severity of the lesions they induce in experimental animals, were injected in various doses into the cerebrum, peritoneal cavity, or blood stream of mice. Quantitative determinations of the numbers of living bacilli present in the tissues at different intervals of time after infection led to the following classification of the cultures tested:- (a) Certain well known variant forms of tubercle bacilli were found to be unable to multiply in vivo, although they could survive for many weeks in the tissues of mice. These organisms proved to be truly avirulent. (b) Other variant forms underwent multiplication in vivo, even when extremely small infective doses were used, but could not give rise to progressive disease. It is proposed to designate these strains, which produce only abortive infections, as "attenuated." Different levels of attenuation could be detected. The maximum numbers of living bacilli that were recovered from the tissues corresponded directly to the severity and duration of the abortive lesions that could be produced by the strain in guinea pigs or in mice and were characteristic for each strain tested. The two BCG substrains tested were found to differ markedly in their level of attenuation. (c) The cultures virulent for guinea pigs were also capable of establishing a progressive infection in mice even when small infective doses were used. In the case of the attenuated and virulent strains, the population of living bacilli present in the lungs was at first much lower than that in the spleen, but it continued to increase in the former organs throughout the period of observation. This was notably true in the case of the virulent cultures. In contrast, the numbers of living bacilli in the spleen rapidly reached a maximum in the case of all cultures and then decreased progressively. For a given infective dose, and a given interval of time after inoculation, the maximum levels of living bacterial population attained in the spleen and in the lungs proved to be a direct expression of the virulence of the strain.