Immunogenic Mycobacterium africanum strains associated with ongoing transmission in The Gambia

Abstract

In West Africa, Mycobacterium tuberculosis strains co-circulate with M. africanum, and both pathogens cause pulmonary tuberculosis in humans. Given recent findings that M. tuberculosis T-cell epitopes are hyperconserved, we hypothesized that more immunogenic strains have increased capacity to spread within the human host population. We investigated the relationship between the composition of the mycobacterial population in The Gambia, as measured by spoligotype analysis, and the immunogenicity of these strains as measured by purified protein derivative-induced interferon-γ release in ELISPOT assays of peripheral blood mononuclear cells. We found a positive correlation between strains with superior spreading capacity and their relative immunogenicity. Although our observation is true for M. tuberculosis and M. africanum strains, the association was especially pronounced in 1 M. africanum sublineage, characterized by spoligotype shared international type 181, which is responsible for 20% of all tuberculosis cases in the region and therefore poses a major public health threat in The Gambia.

Keywords: ELISPOT; Mycobacterium africanum; Mycobacterium tuberculosis; PPD; SIT; The Gambia; human hosts; immunogenicity; population structure; shared international type; spoligotyping; transmission; tuberculosis and other mycobacteria.

Figure 1

Spoligotyping results showing population structure of Mycobacterium tuberculosis and M. africanum, The Gambia, 2002–2009. A) All M. tuberculosis sensu stricto lineages (including Euro-American); B) Euro-American lineage; C) M. africanum lineages (Afri_1 and Afri_2). SIT, shared international type.

Figure 2

Linear regression analysis showing correlation between average quantitative purified protein derivative (PPD) response and recent transmission index (RTI_n−1) for Mycobacterium tuberculosis complex isolates, The Gambia, 2002–2007. Open diamonds and dashed line, M. tuberculosis sensu stricto, including Euro-American (EA) lineage (R² = 0.606); open squares and dotted line, M. tuberculosis EA lineage (R² = 0.7272); black circles and solid line, M. africanum Afri_1 lineage (R² = 0.7732). sfu, spot-forming units.