Whole-genome sequencing illuminates the evolution and spread of multidrug-resistant tuberculosis in Southwest Nigeria.

Madikay Senghore,Tumani Corrah,Kayode Salako,Gemma L Kay,Mark J Pallen,Emmanuel Idigbe,Emma L Doughty,Florian Gehre,Phillip Butcher,Martin Antonio,Adam Witney,Aderemi Kehinde,Nneka Onyejepu,Bouke De Jong,Jacob Otu,Igor Mokrousov

doi:10.1371/journal.pone.0184510

Abstract

Nigeria has an emerging problem with multidrug-resistant tuberculosis (MDR-TB). Whole-genome sequencing was used to understand the epidemiology of tuberculosis and genetics of multi-drug resistance among patients from two tertiary referral centers in Southwest Nigeria. In line with previous molecular epidemiology studies, most isolates of Mycobacterium tuberculosis from this dataset belonged to the Cameroon clade within the Euro-American lineage. Phylogenetic analysis showed this clade was undergoing clonal expansion in this region, and suggests that it was involved in community transmission of sensitive and multidrug-resistant tuberculosis. Five patients enrolled for retreatment were infected with pre-extensively drug resistant (pre-XDR) due to fluoroquinolone resistance in isolates from the Cameroon clade. In all five cases resistance was conferred through a mutation in the gyrA gene. In some patients, genomic changes occurred in bacterial isolates during the course of treatment that potentially led to decreased drug susceptibility. We conclude that inter-patient transmission of resistant isolates, principally from the Cameroon clade, contributes to the spread of MDR-TB in this setting, underscoring the urgent need to curb the spread of multi-drug resistance in this region.

Highlights

In humans and other animals, tuberculosis (TB) is caused by a group of related mycobacterial species that form the Mycobacterium tuberculosis complex (MTBC) [1, 2]
The Cameroon clade from Lineage 4 is the most common genotype of M. tuberculosis isolated from patients with active pulmonary tuberculosis in parts of West Africa including Nigeria [9,10,11,12,13]
This study suggests that this genotype is on the rise and is an important source of multidrug-resistant tuberculosis (MDR-TB) in Southwest Nigeria

Summary

Introduction

In humans and other animals, tuberculosis (TB) is caused by a group of related mycobacterial species that form the Mycobacterium tuberculosis complex (MTBC) [1, 2]. The human-associated species M. tuberculosis and M. africanum form seven distinct phylogenetic lineages that. The Cameroon clade from Lineage 4 is the most common genotype of M. tuberculosis isolated from patients with active pulmonary tuberculosis in parts of West Africa including Nigeria [9,10,11,12,13]. A unique feature of MTBC in West Africa is the presence of two M. africanum lineages, human-associated ecotypes that cause up to 40% of tuberculosis in parts of West Africa [14]

Methods

Results

Discussion

Conclusion