Paucibacillary Tuberculosis in Mice after Prior Aerosol Immunization with Mycobacterium bovis BCG

To develop a murine model of paucibacillary tuberculosis for experimental chemotherapy of latent tuberculosis infection, mice were immunized with viable Mycobacterium bovis BCG by the aerosol or intravenous route and then challenged six weeks later with virulent Mycobacterium tuberculosis. The day after immunization, the counts were 3.71 ± 0.10 log₁₀ CFU in the lungs of aerosol-immunized mice and 3.65 ± 0.11 and 4.93 ± 0.07 log₁₀ CFU in the lungs and spleens of intravenously immunized mice, respectively. Six weeks later, the lungs of all BCG-immunized mice had many gross lung lesions and splenomegaly; the counts were 5.97 ± 0.14 and 3. 54 ± 0.07 log₁₀ CFU in the lungs and spleens of aerosol-immunized mice, respectively, and 4.36 ± 0.28 and 5.12 ± 0.23 log₁₀ CFU in the lungs and spleens of intravenously immunized mice, respectively. Mice were then aerosol challenged with M. tuberculosis by implanting 2.37 ± 0.13 log₁₀ CFU in the lungs. Six weeks after challenge, M. tuberculosis had multiplied so that the counts were 6.41 ± 0.27 and 4.44 ± 0.14 log₁₀ CFU in the lungs and spleens of control mice, respectively. Multiplication of M. tuberculosis was greatly limited in BCG-immunized mice. Six weeks after challenge, the counts were 4.76 ± 0.24 and 3.73 ± 0.34 log₁₀ CFU in the lungs of intravenously immunized and aerosol-immunized mice, respectively. In contrast to intravenously immunized mice, there was no detectable dissemination to the spleen in aerosol-immunized mice. Therefore, immunization of mice with BCG by the aerosol route prior to challenge with a low dose of M. tuberculosis resulted in improved containment of infection and a stable paucibacillary infection. This model may prove to be useful for evaluation of new treatments for latent tuberculosis infection in humans.