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ORIGINAL RESEARCH article

Front. Public Health
Sec. Infectious Diseases: Epidemiology and Prevention
Volume 12 - 2024 | doi: 10.3389/fpubh.2024.1399731
This article is part of the Research Topic Innovative Tuberculosis Case Finding Interventions: Lessons From the Field View all 9 articles

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

Provisionally accepted
Basha Chekesa Basha Chekesa 1*Harinder Singh Harinder Singh 2Norberto Gonzalez-Juarbe Norberto Gonzalez-Juarbe 2Sanjay Vashee Sanjay Vashee 2Rosana Wiscovitch-Russo Rosana Wiscovitch-Russo 2Christopher L. Dupont Christopher L. Dupont 3Musse Girma Musse Girma 1Oudessa Kerro Oudessa Kerro 4Balako Gumi Balako Gumi 1Gobena Ameni Gobena Ameni 5*
  • 1 Addis Ababa University, Addis Ababa, Addis Ababa, Ethiopia
  • 2 J. Craig Venter Institute (Rockville), Rockville, California, United States
  • 3 J. Craig Venter Institute (La Jolla), La Jolla, California, United States
  • 4 The University of Tennessee, Knoxville, Knoxville, Tennessee, United States
  • 5 United Arab Emirates University, Al-Ain, Abu Dhabi, United Arab Emirates

The final, formatted version of the article will be published soon.

    Extrapulmonary 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. A cross-sectional study was undertaken on individuals with EPTB Patients from August 5, 2018, to December 30, 2019, 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. Our 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. The 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.

    Keywords: Extrapulmonary tuberculosis, drug resistance-conferring mutations, genetic diversity, Mycobacterium tuberculosis, Transmission dynamics, Whole-genome sequencing

    Received: 12 Mar 2024; Accepted: 30 Jul 2024.

    Copyright: © 2024 Chekesa, Singh, Gonzalez-Juarbe, Vashee, Wiscovitch-Russo, Dupont, Girma, Kerro, Gumi and Ameni. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Basha Chekesa, Addis Ababa University, Addis Ababa, Addis Ababa, Ethiopia
    Gobena Ameni, United Arab Emirates University, Al-Ain, Abu Dhabi, United Arab Emirates

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