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Population structure and transmission analysis of drug-resistant Mycobacterium tuberculosis' complex strains from Namibia based on whole genome sequencing

O A Shavuka(1) L Mhuulu(1) V Dreyer(2,6) H Ekandjo(1) A Diergaardt(1) C Iipinge(3) N Ruswa(4) T Niemann(1,2,6) E Nepolo(1) M Claassens(1) G Günther(1,5) S Niemann(1,2,6)

1:University of Namibia School of Medicine.; 2:Research Center Borstel .; 3:Namibia Institute of Pathology.; 4:National Tuberculosis and Leprosy Program, Namibia.; 5:Bern University Hospital.; 6:German Center for Infection Research.

Namibia, characterized as a high tuberculosis (TB) burden country by the World Health Organization (WHO), faces significant challenges in combating TB, including the emergence of drug-resistant Mycobacterium tuberculosis complex (Mtbc) strains. Here we investigate the population structure, and transmission dynamics of drug resistant TB (DR-TB) in Namibia. Whole genome sequencing (WGS) was performed on 525 Mtbc strains collected between 2016 to 2023 across the country. Phylogenetic strain classifications, genomic resistance predictions, and core-genome multi-locus sequence typing analysis using SeqSphere (Ridom GmbH, Münster, Germany). Cluster analysis was done using a threshold of 12 alleles. Overall, most Mtbc strains were classified as belonging to the lineage 4 (L4; n=508), 15 belonged to the lineage 2 (L2, Beijing) and the two-remaining belonged to L1 and L3.  Following the new WHO definitions, 353 out of 416 multi-drug resistant (84.9%) Mtbc strains were grouped into 56 clusters ranging from 2 to 78 isolates. Twenty five out of 28 pre-extensively drug resistant strains (pre-XDR) (89.3%) were distributed among 9 clusters and 9 XDR (100%) strains were grouped into 4 clusters. All strains of the two largest clusters belonged to the LAM lineage (L4 sublineage). The analysis indicates that transmission of drug resistant Mtbc strains is an important component of the DR-TB epidemiology in Namibia, and that further investigations should be conducted to gain a better understanding of the factors contributing to transmission. Understanding all factors involved will enable the development of targeted TB control strategies, optimizing resource allocation and reducing the spread of DR-TB in Namibia.

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