title: Patterns and implications of naturally acquired immune responses to environmental and tuberculous mycobacterial antigens in northern Malawi.
abstract: Interferon (IFN)-gamma 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-gamma responsiveness was highest for PPDs of M. avium, M. intracellulare, and M. scrofulaceum (the MAIS complex). Correlations between responsiveness paralleled genetic relatedness of the mycobacterial species. A randomized, controlled trial was carried out, to assess the increase in IFN-gamma responsiveness to M. tuberculosis PPD that can be attributed to M. bovis BCG vaccination. The BCG-attributable increase in IFN-gamma response to M. tuberculosis PPD was greater for individuals 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.
authors.affiliation: Karonga Prevention Study, Chilumba, Malawi.
authors.forename: G F
authors.initials: GF
authors.lastname: Black
authors.forename: H M
authors.initials: HM
authors.lastname: Dockrell
authors.forename: A C
authors.initials: AC
authors.lastname: Crampin
authors.forename: S
authors.initials: S
authors.lastname: Floyd
authors.forename: R E
authors.initials: RE
authors.lastname: Weir
authors.forename: L
authors.initials: L
authors.lastname: Bliss
authors.forename: L
authors.initials: L
authors.lastname: Sichali
authors.forename: L
authors.initials: L
authors.lastname: Mwaungulu
authors.forename: H
authors.initials: H
authors.lastname: Kanyongoloka
authors.forename: B
authors.initials: B
authors.lastname: Ngwira
authors.forename: D K
authors.initials: DK
authors.lastname: Warndorff
authors.forename: P E
authors.initials: PE
authors.lastname: Fine
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology*; D003429:Cross Reactions; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000097:blood; D008295:Malawi; D009161:Mycobacterium / Q000145:classification / Q000276:immunology*; D009164:Mycobacterium Infections / Q000276:immunology*; D009162:Mycobacterium avium / Q000145:classification / Q000276:immunology; D015269:Mycobacterium avium Complex / Q000145:classification / Q000276:immunology; D009163:Mycobacterium bovis / Q000145:classification / Q000276:immunology; D009170:Nontuberculous Mycobacteria / Q000145:classification / Q000276:immunology; D012882:Skin Tests; D018709:Statistics, Nonparametric; D014374:Tuberculin Test; D014376:Tuberculosis / Q000453:epidemiology; D014397:Tuberculosis, Pulmonary / Q000453:epidemiology / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D007371:Interferon-gamma