Immunogenic Mycobacterium africanum Strains Associated with Ongoing Transmission in The Gambia

Florian Gehre

, Martin Antonio, Jacob K. Otu, Neneh Sallah, Oumie Secka, Tutty Faal, Patrick Owiafe, Jayne S. Sutherland, Ifedayo M. Adetifa, Martin O. Ota, Beate Kampmann, Tumani Corrah, and Bouke C. de Jong

Author affiliations: Medical Research Council Unit, Fajara, The Gambia (F. Gehre, M. Antonio, J.K. Otu, N. Sallah, O. Secka, T. Faal, P. Owiafe, J.S. Sutherland, I.M. Adetifa, M.O. Ota, B. Kampmann, T. Corrah, B.C. de Jong); Institute for Tropical Medicine, Antwerp, Belgium (F. Gehre, B.C. de Jong); Imperial College London, London, UK (B. Kampmann); New York University, New York, New York, USA (B.C. de Jong)

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.

Tuberculosis (TB), caused by bacterial pathogens of the Mycobacterium tuberculosis complex (MTBC), is a major global health problem. Sub-Saharan Africa has the highest rate of TB per capita and the lowest case detection rate; although TB incidence is decreasing globally, incidence rates are increasing in most countries in the West Africa region (1). Moreover, almost half of all TB cases in West Africa are caused by infection with an unusual member of the MTBC, M. africanum, a lineage found exclusively in this region. Although M. africanum was initially described in Senegal in 1968 (2), and despite its importance and high prevalence in this region, relatively little is known about the bacterium (3). In general, M. africanum can be divided into 2 lineages: Afri_1, by SpolDB4 definition (4), corresponding to the green lineage 6 (5), which has the highest prevalence in Senegal, Mali, The Gambia, Guinea-Bissau, and Sierra Leone (3); and Afri_2 (4), corresponding to the brown lineage 5 (5), which is mainly found in the eastern part of West Africa, in countries such as Côte d’Ivoire, Ghana, Benin, Nigeria, and Cameroon (3).
Although transmission of M. africanum from host to host is a crucial element of the spread of the disease, the underlying biological mechanisms triggering transmission are elusive. We assessed transmission dynamics and interaction between the 2 mycobacterial populations in The Gambia, a country in western West Africa, and compared the local situation with previously published data from Guinea-Bissau, another country within the region (6). In particular, considering a recent publication suggesting that conserved mycobacterial T-cell epitopes may play a role in the transmission of the mycobacteria within the host population (7), we investigated whether differences in immunogenicity between M. tuberculosis and M. africanum strains (especially of the predominant Euro-American [EA] and Afri_1 lineages) could predict the success of certain sublineages to transmit and establish themselves within the human host population.