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 - PubMed (original) (raw)

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 O Sousa et al. Proc Natl Acad Sci U S A. 1997.

Abstract

A survey of an emerging tuberculosis epidemic among the Yanomami Indians 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 Yanomami population, an extraordinary high prevalence of active tuberculosis (6.4% of 625 individuals clinically examined) was observed, indicating a high susceptibility to disease, even among bacille Calmette-Guérin-vaccinated individuals. Observational studies on cell-mediated and humoral immune responses of the Yanomami Indians compared with contemporary residents of the region suggest profound differences in immunological responsiveness to Mycobacterium tuberculosis infection. Among the Yanomami, a very high prevalence of tuberculin skin test anergy was found. Of patients with active tuberculosis, 46% had purified protein derivative of tuberculosis reactions <10 mm; similarly 58% of recent bacillus Calmette-Guérin vaccines exhibited skin test reactions <5 mm. The Yanomami also had higher titers of antibodies against M. tuberculosis 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 IgG antibodies, the titers of IgG4 were significantly higher among the Yanomami than in the control population. Although it was not possible to analyze T-cell responses or patterns of lymphokine production in vitro because of the remoteness of the villages from laboratory facilities, the results suggest that the first encounter of the Yanomami Indian population with tuberculosis engenders a diminished cell-mediated immune 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 selective pressure on human evolution that over centuries has shaped the nature of human immune responses to infection.

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Figures

Figure 1

Figure 1

Distribution of tuberculin PPD skin reactions among the Yanomami population. BCG-vaccinated (n = 411) (empty bars); non-BCG-vaccinated (n = 144) (filled bars).

Figure 2

Figure 2

Distribution of PPD reactions among active pulmonary tuberculosis patients. Yanomami Indian population (n = 26) (empty bars); other Brazilian patients of European descent (n = 42) (filled bars).

Figure 3

Figure 3

M. tuberculosis glycolipid DAT antibodies in tuberculosis patients and total population among Yanomami Indians and a control population of other Brazilians. Total antibodies is measured by OD 540 nm of protein. The Yanomami have lower IgG DAT antibodies (P = .038) among the tuberculosis patients (Left), but higher DAT IgG in the general population (Right) (P < 0.001). In contrast, the IgM DAT antibodies in the Yanomami are elevated (P < 0.001) in both tuberculosis patients (Left) and in the total population (Right).

Figure 4

Figure 4

Levels of IgG4 antibodies to M. tuberculosis glycolipid DAT. The Yanomami Indians (Right) have significantly higher IgG4 antibodies than the control Brazilian population (Left) (P < 0.001).

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