IMMUNOTHERAPY FOR TUBERCULOSIS - INVESTIGATIVE AND PRACTICAL ASPECTS

Modern immunotherapy for tuberculosis is designed to enhance antibacterial immunity and switch off the immune mechanism of tissue damage by promoting maturation of type 1 CD4+ and cytotoxic CD8+ T lymphocytes, leading to destruction of intracellular bacilli. These intracellular organisms are the reason chemotherapy has to be so prolonged, and may be the persistent bacteria that are responsible for reactivation years after infection. Noncompliance with therapy is a major cause of failure of tuberculosis control and of increasing drug resistance, especially in the developing world. A combination of chemotherapy to kill rapidly metabolising extracellular bacilli and some intracellular organisms, with immunotherapy effective against slowly metabolising intracellular bacilli, should lead to fewer treatment failures and shorter treatment regimens. A suspension of heat-killed Mycobacterium vaccae NCTC 11659 has proved effective in pilot investigations. Randomised double-blind placebo-controlled studies have shown that a single injection of M. vaccae, given early in chemotherapy, halves treatment failure rates and reduces deaths during treatment. Even when M. vaccae had to be given with very inadequate chemotherapy, clinical condition and clearing of bacilli from the sputum were much improved. Promising results have been obtained in the treatment of multidrug-resistant tuberculosis, and in patients co-infected with HIV. Radical new approaches to the treatment of tuberculosis are badly needed, and although definitive trials have still to be completed, the evidence available suggests that immunotherapy with M. vaccae is a powerful and cheap addition to the treatment armamentarium.