Reactivation of latent tuberculosis by an inhibitor of inducible nitric oxide synthase in an aerosol murine model
Article first published online: 8 NOV 2002
Volume 107, Issue 3, pages 350–357, November 2002
How to Cite
Botha, T. and Ryffel, B. (2002), Reactivation of latent tuberculosis by an inhibitor of inducible nitric oxide synthase in an aerosol murine model. Immunology, 107: 350–357. doi: 10.1046/j.1365-2567.2002.01511.x
- Issue published online: 8 NOV 2002
- Article first published online: 8 NOV 2002
- Received 2 February 2002; revised 29 April 2002; accepted 25 July 2002.
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.