Clinical epidemiology, genetic diversity, and drug susceptibility patterns by whole genome sequencing of Mycobacterium tuberculosis complex isolates in Gabon from 2012 to 2022

Abstract

Objectives: This study aimed to investigate genotypic characteristics and drug resistance profiles of Mycobacterium tuberculosis complex (Mtbc) strains isolated from patients with suspected tuberculosis (TB) in Gabon. Methods: We performed whole genome sequencing of 430 Mtbc strains cultured between 2012 and 2022. Phylogenetic strain classification, genomic resistance prediction, and cluster analysis were also performed. Results: Strains from four major Mtbc lineages, L4 (n = 372; 65%), L5 (n = 46; 11%), L2 (n = 6; 1,4%), and L6 (n = 3; 0,7%), were observed. Interestingly, more than 10% of the strains were represented by Mycobacterium africanum strains (L5 and L6), with L4 strains being dominant. The subclassification of L4 strains showed that L4.6.2.2 (Cameroon, n = 116) was the most prevalent. The proportion of resistance (any resistance to first-line TB drugs) was 30%, with 12% (n = 52) being at least multidrug-resistant (MDR) and six showing additional fluoroquinolone resistance. The overall cluster rate was 64% in non-MDR and MDR Mtbc strains. Conclusion: Although most Mtbc infections are caused by L4 M. tuberculosis strains, M. africanum strains also contribute to TB epidemiology in Gabon. The MDR epidemic is mainly driven by one dominant L4 Haarlem outbreak clone that has been spreading for approximately a century in the country.