1966 Volume 19 Issue 4 Pages 181-199
1. A resting condition of tubercle bacilli was obtained after residual growth of a streptomycin-dependent strain on the antibiotic-lacking Sauton synthetic liquid medium. Infection experiments were conducted using vaccines and challenge inocula prepared from the non-proliferating resting cells thus induced in vitro.
2. Mice and guinea pigs immunized with the resting vaccine were poorly protected against intravenous challenge infection with virulent tubercle bacilli. However, when the same vaccine was used concurrently with supply of streptomycin to the host to permit its temporary multiplication, a strong immunity was induced.
3. Further comparative studies on these two modes of vaccination, particularly concerning the relation between immunizing dose, extent of vaccine multiplication and degree of protection, indicated that the main factor of viable vaccine responsible for immunity production is not the total amount of viable cells, but their performance of multiplication in the host.
4. In a reverse type of experiment where the resting bacilli were used as a challenge inoculum for preimmunized mice, it was found that the resting bacilli were not destroyed in those animals.
5. From these observations, the author was led to an idea that resting tubercle bacilli do not stimulate the host in a manner to produce protection, and at the same time they are insensitive to preformed immunity, thus establishing an “indifferent” type of parasitism or a latent infection. In fact, the streptomycin-starved resting bacilli survived in the mouse spleen maintaining nearly constant viable counts for the period as long as 9 weeks.
6. An additional observation was that antituberculous agents such as isoniazid and kanamycin were not effective for eliminating the resting bacilli in vivo, suggesting the possible presence of a delicate “host-parasite-drug relationship”.
7. A paradoxal situation in tuberculous infection is that acquired immunity capable of preventing proliferation of the virulent forms of the bacilli cannot eradicate their resting forms. This point was discussed considering the present investigation as an enlightening model.