[Towards new strategies to combat mycobacterial diseases]

Infectious diseases account for more than 30% of deaths throughout the world, and we are increasingly faced with new and reemerging disease challenges. Infections caused by mycobacteria are the leading cause of death from infectious diseases around the world. Leprosy/Hansen's disease, caused by Mycobacterium leprae, primarily involves the peripheral nervous system and skin. Tuberculosis remains an important global health problem with approximately 1.9 billion people presently infected with M. tuberculosis. Infections with nontuberculous mycobacteria such as M. avium complex (MAC) constitute an important health problem, because most strains of MAC are resistant to antituberculous drugs. Mycobacteria are intracellular microbial pathogens. The infect macrophages cause chronic inflammation, such as granulomatous inflammation, and progressive scarring. Host defense against mycobacterial infection is controlled predominantly by the macrophage-cytokine-type 1 helper T (Th1) cell axis resulting in the expression of cell-mediated immunity. Development of cell-mediated, Th1(1) protective immunity to mycobacteria is considered a two-edged response, contributing to both clearance of infecting agents and tissue damage. In the second half of the 20th century, the conceptual approach to the management of established infectious diseases is antimicrobial chemotherapy. However, the successful implementation of antimicrobial chemotherapy is becoming increasingly difficult because of (1) an epidemic of immunocompromised patients, for whom antimicrobial therapy is less effective; (2) the emergence of new pathogens and the reemergence of old pathogens; and (3) widespread drug resistance. Antiinfective immunotherapy will be a new control strategy for mycobacterial diseases. It is also conceivable that therapeutic interventions to enhance the host immunity will be as effective as and possibly synergistic with antimicrobial drugs. We believe that the immune-based strategies will contribute to elimination of mycobacterial diseases.