Molecular Epidemiology and Drug Resistance Analysis of Mycobacterium Tuberculosis Isolates from Central, Eastern and Southeastern Ethiopia
No Thumbnail Available
Date
2024-05
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Addis Ababa University
Abstract
Understanding the prevalent lineages, drug resistance mutations, and transmission dynamics of Mycobacterium tuberculosis complex (MTBC) across diverse regions is crucial for designing effective tuberculosis (TB) control strategies. In Ethiopia, comprehensive studies on the molecular epidemiology and drug resistance of TB are scarce, with existing research focused on specific regions like Addis Ababa and the north/southwestern parts. This study aimed to assess genetic diversity, transmission patterns, and drug resistance mutations among Mycobacterium tuberculosis complex (MTBC) isolates in central, eastern, and southeastern Ethiopia. Conducted between August 2018 and January 2019, it involved 232 culture-positive MTBC isolates from pulmonary TB patients referred to Adama and Harar TB reference laboratories. Spoligotyping identified prevalent lineages and sub-lineages, revealing a diverse population structure with six major lineages. The Euro-American (Lineage 4) and East-African-Indian (Lineage 3) lineages were dominant, comprising nearly 95% of isolates. High genetic diversity was observed, with 77 distinct spoligotype patterns. Dominant spoligotypes included SIT149/T3_ETH, SIT53/T1, SIT21/CAS1_Kili, and SIT41/Turkey, with a rare Beijing spoligotype (SIT541) detected in eastern Ethiopia. Strain clustering was significantly associated with individuals aged 25-34 years. Genotypic drug susceptibility testing identified mutations conferring resistance to rifampicin (RIF) and isoniazid (INH) in nearly 40% of isolates. Mutations for resistance to fluoroquinolones (FLQs) and second-line injectable drugs (SLIDs) were less frequent, observed in around 9% and 4% of isolates, respectively. Dominant mutations included S531L in rpoB for RIF, S315T in katG for INH, A90V in gyrA for FLQs, and WT1 in rrs for SLIDs. WGS of multidrug-resistant (MDR) MTBC isolates supported these findings, revealing detailed information on specific drug resistance mutations for an expanded list of drugs. The Euro-American (Lineage 4) and East-African-Indian (Lineage 3) remained the most prevalent genotypes among MDR MTBC isolates in East Ethiopia. Core genome Multi-locus Sequence Typing (cgMLST) analysis revealed recent MDR-TB transmission events in 46.7% of clustered isolates, with a high proportion from Diredawa city, suggesting localized transmission. One cluster was the Beijing sub-lineage of East Asian (Lineage 2), known for high transmission and drug resistance. In conclusion, this study highlights the diverse genetic structure and significant drug resistance mutations of MTBC isolates in central, eastern, and southeastern Ethiopia. The findings emphasize the dominance of specific lineages and sub-lineages, the presence of diverse mutations, and localized transmission hotspots. This underscores the need for tailored control strategies and comprehensive molecular surveillance to effectively address TB and MDR-TB in Ethiopia.
Description
Keywords
Drug Resistance Mutations, Ethiopia, Genetic Diversity, Line Probe Assays, Multidrug-Resistant Tuberculosis, Mycobacterium Tuberculosis Complex, Spoligotyping, Whole Genome Sequencing