Whole-genome sequencing-based genetic diversity, transmission dynamics, and drug-resistant mutations in Mycobacterium tuberculosis isolated from extrapulmonary tuberculosis patients in western Ethiopia

Autor: Basha Chekesa, Harinder Singh, Norberto Gonzalez-Juarbe, Sanjay Vashee, Rosana Wiscovitch-Russo, Christopher L. Dupont, Musse Girma, Oudessa Kerro, Balako Gumi, Gobena Ameni
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Frontiers in Public Health, Vol 12 (2024)
Druh dokumentu: article
ISSN: 2296-2565
DOI: 10.3389/fpubh.2024.1399731
Popis: BackgroundExtrapulmonary tuberculosis (EPTB) refers to a form of Tuberculosis (TB) where the infection occurs outside the lungs. Despite EPTB being a devastating disease of public health concern, it is frequently overlooked as a public health problem. This study aimed to investigate genetic diversity, identify drug-resistance mutations, and trace ongoing transmission chains.MethodsA cross-sectional study was undertaken on individuals with EPTB in western Ethiopia. In this study, whole-genome sequencing (WGS) was employed to analyze Mycobacterium tuberculosis (MTB) samples obtained from EPTB patients. Out of the 96 genomes initially sequenced, 89 met the required quality standards for genetic diversity, and drug-resistant mutations analysis. The data were processed using robust bioinformatics tools.ResultsOur analysis reveals that the majority (87.64%) of the isolates can be attributed to Lineage-4 (L4), with L4.6.3 and L4.2.2.2 emerging as the predominant sub-lineages, constituting 34.62% and 26.92%, respectively. The overall clustering rate and recent transmission index (RTI) were 30 and 17.24%, respectively. Notably, 7.87% of the isolates demonstrated resistance to at least one anti-TB drug, although multi-drug resistance (MDR) was observed in only 1.12% of the isolates.ConclusionsThe genetic diversity of MTBC strains in western Ethiopia was found to have low inter-lineage diversity, with L4 predominating and exhibiting high intra-lineage diversity. The notably high clustering rate in the region implies a pressing need for enhanced TB infection control measures to effectively disrupt the transmission chain. It’s noteworthy that 68.75% of resistance-conferring mutations went undetected by both GeneXpert MTB/RIF and the line probe assay (LPA) in western Ethiopia. The identification of resistance mutations undetected by both GeneXpert and LPA, along with the detection of mixed infections through WGS, emphasizes the value of adopting WGS as a high-resolution approach for TB diagnosis and molecular epidemiological surveillance.
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