Research Article: A Mycobacterial Perspective on Tuberculosis in West Africa: Significant Geographical Variation of M. africanum and Other M. tuberculosis Complex Lineages

Date Published: March 10, 2016

Publisher: Public Library of Science

Author(s): Florian Gehre, Samrat Kumar, Lindsay Kendall, Mebrat Ejo, Oumie Secka, Boatema Ofori-Anyinam, Emmanuel Abatih, Martin Antonio, Dirk Berkvens, Bouke C. de Jong, Melissa Burke.

Abstract: BackgroundPhylogenetically distinct Mycobacterium tuberculosis lineages differ in their phenotypes and pathogenicity. Consequently, understanding mycobacterial population structures phylogeographically is essential for design, interpretation and generalizability of clinical trials. Comprehensive efforts are lacking to date to establish the West African mycobacterial population structure on a sub-continental scale, which has diagnostic implications and can inform the design of clinical TB trials.Methodology/Principal FindingsWe collated novel and published genotyping (spoligotyping) data and classified spoligotypes into mycobacterial lineages/families using TBLineage and Spotclust, followed by phylogeographic analyses using statistics (logistic regression) and lineage axis plot analysis in GenGIS, in which a phylogenetic tree constructed in MIRU-VNTRplus was analysed. Combining spoligotyping data from 16 previously published studies with novel data from The Gambia, we obtained a total of 3580 isolates from 12 countries and identified 6 lineages comprising 32 families. By using stringent analytical tools we demonstrate for the first time a significant phylogeographic separation between western and eastern West Africa not only of the two M. africanum (West Africa 1 and 2) but also of several major M. tuberculosis sensu stricto families, such as LAM10 and Haarlem 3. Moreover, in a longitudinal logistic regression analysis for grouped data we showed that M. africanum West Africa 2 remains a persistent health concern.Conclusions/SignificanceBecause of the geographical divide of the mycobacterial populations in West Africa, individual research findings from one country cannot be generalized across the whole region. The unequal geographical family distribution should be considered in placement and design of future clinical trials in West Africa.

Partial Text: West Africa consists of 15 countries with 245 million inhabitants (S1A Fig), 13 of which belong to the world’s 42 countries with the lowest human development index [1]. Consequently, it faces great challenges in controlling infectious diseases, such as tuberculosis (TB). Clinical trials investigating the local health needs are much needed to understand and tackle the TB epidemic in West Africa.

We confirmed that modern Euro-American strains are the predominant lineage followed by the two M. africanum lineages. Although the polyphyletic T1 family [26] is rather equally distributed across the whole region, we find geographical variations of other families. While western West Africa shows a high genetic diversity from a multitude of mycobacterial families, the MTBc of Eastern West Africa is mainly composed of two dominant families (LAM10 and MAF1). Although other West and Central African countries observed a replacement of MAF1 and MAF2 with modern strains [10,11,14,27], our longitudinal analysis from The Gambia did not confirm these findings and MAF2 remains an important cause of TB in the country. The exact mechanism of how MAF2 can maintain a stable prevalence of 35% over the last decade within The Gambia (despite a slower progression to disease when compared to M. tuberculosis [28]) is not fully understood.



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