We have previously shown that young adults living in a rural area of northern Malawi showed greater
gamma interferon (IFN-gamma) responses to purified
protein derivatives (
PPD) prepared from environmental mycobacteria than to
PPD from Mycobacterium tuberculosis. In order to define the mycobacterial species to which individuals living in a rural African population have been exposed and sensitized, we tested T-cell recognition of recombinant and purified
antigens from M.
tuberculosis (38 kDa, MPT64, and ESAT-6), M. bovis (MPB70), M. bovis BCG (
Ag85), and M. leprae (65 kDa, 35 kDa, and 18 kDa) in >600 non-M. bovis BCG-vaccinated young adults in the Karonga District of northern Malawi. IFN-gamma was measured by
enzyme-linked
immunosorbent assay (ELISA) in day 6 supernatants of diluted whole-blood cultures. The recombinant M. leprae 35-kDa and 18-kDa and purified native M. bovis BCG
Ag85 antigens induced the highest percentages of responders, though both
leprosy and
bovine tuberculosis are now rare in this population. The M.
tuberculosis antigens ESAT-6 and MPT64 and the M. bovis
antigen MPB70 induced the lowest percentages of responders. One of the subjects subsequently developed
extrapulmonary tuberculosis; this individual had a 15-mm-diameter reaction to the Mantoux test and responded to M.
tuberculosis PPD,
Ag85, MPT64, and ESAT-6 but not to any of the
leprosy antigens. We conclude that in this rural African population, exposure to M.
tuberculosis or M. bovis is much less frequent than exposure to environmental mycobacteria such as M. avium, which have
antigens homologous to the M. leprae 35-kDa and 18-kDa
antigens. M.
tuberculosis ESAT-6 showed the strongest association with the size of the Mantoux skin test induration, suggesting that among the three M.
tuberculosis antigens tested it provided the best indication of exposure to, or
infection with, M.
tuberculosis.