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

V Dreyer(1,5) B R Adegbite(2,3,4) J P A A Abdul(2) A A Adegnika(2,3) S Niemann(1,5) M P Grobusch(2,3,4)

1:Molecular and Experimental Mycobacteriology, Research Center Borstel - Leibniz Lung Center; 2:Centre de Recherches Médicales de Lambaréné (CERMEL), Lambaréné, Gabon; 3:Institut für Tropenmedizin, Universität Tübingen & German Center for Infection Research, Tübingen, Germany; 4:Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam Infection & Immunity, Amsterdam Public Health, University of Amsterdam, Amsterdam, The Netherlands; 5:German Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Borstel, Germany

Gabon ranks amongst the high tuberculosis (TB) burden countries with more than 700 new cases of rifampicin-resistant (RR)/multidrug-resistant (MDR) TB cases emerging every year. This study aimed to investigate drug resistance profiles of Mycobacterium tuberculosis complex (Mtbc) strains isolated from suspected TB patients in Gabon (2012-2022).

Whole Genome Sequencing (WGS) was used for phylogenetic classification, resistance prediction, and cluster analysis (5 SNPs threshold) of 430 Mtbc strains.

Strains of the four 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 are represented by M. africanum strains (L5 and L6). The proportion of resistance (any resistance to first-line tuberculosis drug) was 30%, with 12% (n = 52) being at least MDR, and six showing additional Fluorochinolone resistance. The overall cluster rate was 64%, which was the same in non-MDR and MDR Mtbc strains. However, the clustered MDR Mtbc strains fall into two large outbreaks, one belonging to the sublineage L4.1.2.1 (n=27) and one to the sublineage L2.2.1 (n=6). Strains belonging to the largest Haarlem MDR outbreak were sampled throughout the whole 10-year study period. 

In conclusion, our study provides the first insights into genetic structure of Mtbc strain populations in Gabon. Although the majority of cases are caused by L4 Mtbc strains, M. africanum strains contribute also to the TB epidemiology in Gabon. The MDR epidemic is mainly driven by one dominant L4 clone that has been spreading for about a century in the country.

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