AN EPIDEMIC OF TUBERCULOSIS WITH A HIGH-RATE OF TUBERCULIN ANERGY AMONG A POPULATION PREVIOUSLY UNEXPOSED TO TUBERCULOSIS, THE YANOMAMI INDIANS OF THE BRAZILIAN AMAZON

A survey of an emerging tuberculosis epidemic among the Yanomami India ns of the Amazonian rain forest provided a unique opportunity to study the impact of tuberculosis on a population isolated from contact with the tubercle bacillus for millennia until the mid-1960s. Within the Y anomami population, an extraordinary high prevalence of active tubercu losis (6.4% of 625 individuals clinically examined) was observed, indi cating a high susceptibility to disease, even among bacille Calmette-G uerin-vaccinated individuals. Observational studies on cell-mediated a nd humoral immune responses of the Yanomami Indians compared with cont emporary residents of the region suggest profound differences in immun ological responsiveness to Mycobacterium tuberculosis infection. Among the Yanomami, a very high prevalence of tuberculin skin test anergy w as found. Of patients with active tuberculosis, 46% had purified prote in derivative of tuberculosis reactions <10 mm; similarly 58% of recen t bacillus Calmette-Guerin vaccines exhibited skin test reactions <5 m m. The Yanomami also had higher titers of antibodies against M. tuberc ulosis glycolipid antigens (>70%) than the control subjects comprised of Brazilians of European descent (14%). The antibodies were mostly of the IgM isotype. Among the tuberculosis patients who also produced Ig G antibodies, the titers of IgG4 were significantly higher among the Y anomami than in the control population. Although it was not possible t o analyze T-cell responses or patterns of lymphokine production in vit ro because of the remoteness of the villages from laboratory facilitie s, the results suggest that the first encounter of the Yanomami Indian population with tuberculosis engenders a diminished cell-mediated imm une response and an increased production antibody responses, relative to other populations with extensive previous contact with the pathogen . These findings suggest that tuberculosis may represent a powerful se lective pressure on human evolution that over centuries has shaped the nature of human immune responses to infection.