| Title: |
Genetic diversity and drug resistance profiles of Mycobacterium tuberculosis among Ethiopian children as determined by whole-genome sequencing |
| Authors: |
Abebaw, Yeshiwork; Ayele, Abaysew; Alemayehu, Dawit Hailu; Gebremicael, Gebremedhin; Diriba, Getu; Weldemariam, Atsbeha Gebreegziabxier; Zerihun, Betselot; Moga, Shewki; Adnew, Bethlehem; Melaku, Kalkidan; Getahun, Muluwork; Argaw, Rahel; Sheth, Anandi; Abebe, Markos; Abegaz, Woldaregay Erku |
| Contributors: |
Doucet-Populaire, Florence Claude; Fogarty International Center |
| Source: |
Microbiology Spectrum ; ISSN 2165-0497 |
| Publisher Information: |
American Society for Microbiology |
| Publication Year: |
2026 |
| Description: |
Ethiopia ranks 30th among the tuberculosis (TB) burden countries, with children representing a significant yet understudied population group. This study aims to investigate the genetic diversity and drug-resistant profile among Ethiopian children. We included children under 15 years of age diagnosed with culture-confirmed pulmonary TB/drug-resistant TB between January 2017 and June 2023. Phenotypic drug susceptibility testing and whole-genome sequencing were conducted for 85 Mycobacterium tuberculosis (MTB) isolates. Demographic data were combined with genomic information. Lineage 4 was the most dominant (77.6%), while lineage 2 was less common (1%). Within lineage 4, several sub-lineages were identified, with lineage 4.2.2.2 being notably the most predominant (48%). Most of these cases were from Oromia (58%), including the hotspot areas for lineage 4 that were identified at a 99% confidence level. Among 17 MDR/pre-XDR-TB isolates, lineages 3 and 4.2.2.2 were the dominantly observed lineages/sub-lineages, with proportions of 29% and 65%, respectively. Of the 85 cases, 30.5% were drug-resistant TB to at least one of the five first-line anti-TB drugs tested by phenotypic drug susceptibility testing. Of these 26 drug-resistant TB cases, 23 were concordant with whole-genome sequencing characterization. The most frequent resistance mutations to rifampicin were found in the rpoB gene, specifically p.Ser450Leu (88%), followed by isoniazid in the katG gene, p.Ser315Thr (86%). Multidrug-resistant TB was strongly associated with MTB lineages ( P = 0.007). This study identified high genetic diversity of M. tuberculosis and related drug-resistance mutations, with a strong concordance between whole-genome sequencing-based predictions and phenotypic drug susceptibility testing. IMPORTANCE Our findings revealed a high genetic diversity of Mycobacterium tuberculosis among Ethiopian children, with the most common lineage being lineage 4, specifically lineage 4.2.2.2, in which a higher frequency of multidrug-resistant ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1128/spectrum.02736-25 |
| Availability: |
https://doi.org/10.1128/spectrum.02736-25; https://journals.asm.org/doi/pdf/10.1128/spectrum.02736-25 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ ; https://journals.asm.org/non-commercial-tdm-license |
| Accession Number: |
edsbas.16F19DE7 |
| Database: |
BASE |