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

Florian Gehre,Samrat Kumar,Mebrat Ejo,Boatema Ofori-Anyinam,Dirk Berkvens,Martin Antonio,Bouke C De Jong,Lindsay Kendall,Oumie Secka,Emmanuel Abatih,Melissa Burke

doi:10.1371/journal.pntd.0004408

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.

Highlights

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]
By using stringent analytical tools we demonstrate for the first time a significant phylogeographic separation between western and eastern West Africa of the two M. africanum (West Africa 1 and 2) and of several major M. tuberculosis sensu stricto families, such as LAM10 and Haarlem 3
Tuberculosis is caused by bacteria belonging to the Mycobacterium tuberculosis complex (MTBc), which consists of seven major, phylogenetically distinct lineages and their families

Summary

Introduction

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]. It faces great challenges in controlling infectious diseases, such as tuberculosis (TB). MAF1 seems to be disappearing in some countries, the longitudinal development of MAF2 is not known Each of these phylogenetically distinct lineages can be further differentiated into mycobacterial families, such as, amongst others, the Latin-AmericanMediterranean (LAM) or Haarlem families within the Euro-American lineage [3]. 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

Methods

Results

Discussion

Conclusion