03553nas a2200637 4500000000100000008004100001260001300042653001500055653001000070653002400080653001600104653001000120653001100130653001100141653002100152653001200173653001100185653000900196653001800205653002400223653002500247653003100272653003200303653002100335653002400356653001800380653002000398653001700418653001600435100001200451700001100463700001700474700001700491700001500508700001600523700001400539700001200553700001200565700001300577700001400590700001500604700001400619700001500633700001300648700001400661700001200675700001600687700001200703700001500715245017500730856006900905300001100974490000700985520190900992022001402901 2003 d c2003 Jul10aAdolescent10aAdult10aAntigens, Bacterial10aBCG Vaccine10aChild10aFemale10aHumans10aInterferon-gamma10aleprosy10aMalawi10aMale10aMycobacterium10aMycobacterium bovis10aMycobacterium leprae10aMycobacterium tuberculosis10aRecombinant Fusion Proteins10aRural Population10aSpecies Specificity10aT-Lymphocytes10aTuberculin Test10aTuberculosis10aVaccination1 aBlack G1 aWeir R1 aChaguluka SD1 aWarndorff DK1 aCrampin AC1 aMwaungulu L1 aSichali L1 aFloyd S1 aBliss L1 aJarman E1 aDonovan L1 aAndersen P1 aBritton W1 aHewinson G1 aHuygen K1 aPaulsen J1 aSingh M1 aPrestidge R1 aFine PE1 aDockrell H00aGamma interferon responses induced by a panel of recombinant and purified mycobacterial antigens in healthy, non-mycobacterium bovis BCG-vaccinated Malawian young adults. uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC164276/pdf/0255.pdf a602-110 v103 a

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.

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