Host-parasite relationships in experimental airborne tuberculosis. VII. Fate of Mycobacterium tuberculosis in primary lung lesions and in primary lesion-free lung tissue infected as a result of bacillemia.

Evidence suggests that in humans tuberculous disease usually arises at apical or subapical sites in the lungs seeded as a consequence of an early bacillemic phase of the infection. This study examined the fate of bacilli transported via the bloodstream to metastatic sites in the lungs of guinea pigs after aerosol infection with approximately two viable virulent Mycobacterium tuberculosis. The results revealed that, even after logarithmic-phase multiplication of bacilli in primary lesions had been terminated, bacilli seeded via the bloodstream to metastatic sites in the lung were able to multiply. These observations, made in an animal model that mimics the conditions under which tuberculosis develops in human subjects, challenge the relevance of systemic macrophage activation in experimental airborne tuberculosis in guinea pigs.

Host-parasite relationships in experimental airborne tuberculosis. VI. Influence of vaccination with Bacille Calmette-Guérin on the onset and/or extent of hematogenous dissemination of virulent Mycobacterium tuberculosis to the lungs.

Guinea pigs vaccinated with bacille Calmette-Guérin (BCG) and unvaccinated guinea pigs were challenged by the respiratory route six weeks or six months after vaccination and sacrificed at various intervals after challenge. The six lobes of the lung were cultured separately, and the percentage of culture-positive lobes was calculated, as well as the log10 number of virulent bacilli recovered. The latter was subjected to an analysis of variance, which compared the fate of bacilli in the four largest lobes with the fate of those in the two smallest lobes. The results indicated no difference between the six-week and six-month intervals between vaccination and challenge. In the longer intervals between challenge and sacrifice, small numbers of secondary lesions could be seen on the lobes of the BCG-vaccinated animals. It was concluded that vaccination with BCG retarded the onset and/or reduced the extent of hematogenous dissemination of virulent mycobacteria to the lungs.

Approaches to the validation of animal test systems for assay of protective potency of BCG vaccines.

Three animal test systems, two in guinea-pigs and one in mice, have been examined to differentiate the ability of three BCG vaccines with respect to their ability to protect the animals against infection when challenged with virulent bacilli. One test system showed great promise and was examined in greater detail in order to explain the mechanism of protection. These studies are continuing in order to test a series of BCG vaccines that will be given to groups of children and their protective effect observed.

Host-parasite relationships in experimental airborne tuberculosis. V. Lack of hematogenous dissemination of Mycobacterium tuberculosis to the lungs in animals vaccinated with Bacille Calmette-Guérin.

The influence of bacille Calmette-Guérin (BCG) on the pathogenesis of experimental airborne tuberculosis was studied. In a model that approximates the conditions under which man is vaccinated and infected, BCG-vaccinated and unvaccinated guinea pigs were infected by the respiratory route with an inoculum that resulted in the inhalation and retention (by each animal) of approximately three virulent tubercle bacilli (Mycobacterium tuberculosis strain H37Rv). Hematogenous seeding of the lungs occurred in unvaccinated animals about three weeks after aerosol infection but did not occur in BCG-vaccinated animals. Furthermore, the lungs of BCG-vaccinated animals failed to kill H37Rv that was introduced intravenously; however, evidence of mycobacteriostatic activity was found throughout the lungs. In view of the importance of hematogenous dissemination to the apex of the lungs in the establishment of pulmonary tuberculosis in man, the foregoing observations suggest a means by which vaccination with BCG may confer acquired resistance to tuberculosis.