Patterns and implications of naturally acquired immune responses to environmental and tuberculous mycobacterial antigens in northern Malawi

Interferon (IFN)–g responsiveness to 12 purified protein derivative (PPD) and new tuberculin antigens from 9 species of mycobacteria was assessed, using a whole blood assay, in 616 young adults living in northern Malawi, where Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccination provides no protection against pulmonary tuberculosis. The prevalence of IFN-g responsiveness was highest for PPDs of M. avium, M. intracellulare, and M. scrofulaceum (the MAIS complex). Correlations between responsiveness paralleled genetic relatedness of the my-cobacterial species. A randomized, controlled trial was carried out, to assess the increase in IFN-g responsiveness to M. tuberculosis PPD that can be attributed to M. bovis BCG vaccination. The BCG-attributable increase in IFN-g response to M. tuberculosis PPD was greater for in-dividuals with low initial responsiveness to MAIS antigens than for those with high initial responsiveness. Although not statistically significant, the trend is consistent with the hypothesis that prior exposure to environmental mycobacteria interferes with immune responses to BCG vaccination. Geographical variation in the efficacy of Mycobacterium bovis bacille Calmette Guérin (BCG) vaccination against tuberculosi