What animal models can teach us about the pathogenesis of tuberculosis in humans

Technology that permits the reproducible infection of laboratory animals with virulent tubercle bacilli under conditions that simulate those under which humans are infected is now available. This technology has been used to investigate a series of fundamental questions about the pathogenesis of tuberculosis. An integrated view of the pathogenesis of tuberculosis has been constructed that combines studies from animal models and our understanding of the key events in the development of cavitary pulmonary tuberculosis in humans. This view, developed as a guide for further hypothesis testing, indicates that whether cavitary pulmonary tuberculosis develops by endogenous reactivation or by exogenous reinfection is determined solely by the route by which the tubercle bacillus reaches the apical-subapical region of the lung. It is in this region that the bacillus survives the cell-mediated immune response. This view of the pathogenesis of tuberculosis permits identification of the factors in a given geographic region that govern the probability of the development of cavitary pulmonary tuberculosis by one or the other pathway. Knowledge of these factors permits the identification of the appropriate strategies for tuberculosis control.