Exposure to Mycobacterium tuberculosis results in clinical
tuberculosis only in a small percentage of healthy individuals. In most instances the bacilli are controlled by the immune system and survive in a latent state within
granuloma. Immunosuppression, however, may result in reactivation of
infection, resulting in clinical disease. Using a low-dose
aerosol infection (30 colony-forming units) in mice, we describe a short-duration model for studying spontaneous and
drug-induced reactivation of anti-tuberculous
drug-treated,
latent tuberculosis infection. Although a 4-week treatment with
rifampicin and
isoniazid reduced the number of bacilli to undetectable levels, the
infection spontaneously reactivated following
therapy. By contrast, an 8-week treatment period induced a state of
latent infection, requiring immunosuppression to reactivate
infection. Finally, a 12-week treatment period eliminated the bacilli completely and
aminoguanidine did not induce reactivation of
infection. In view of the fact that
therapy in the selected protocol reduces the mycobacterial load to undetectable levels, the data suggest that an 8-week treatment period is necessary and sufficient to mount protective immunity in mice.