Molecular Epidemiology and Drug-resistance Pattern of Mycobacterium Tuberculosis Isolates from Amhara, Gambella and Benishangul-Gumuz Regions of Ethiopia
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Date
2022-03
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Addis Ababa University
Abstract
Background: Globally, tuberculosis (TB) has affected human beings for thousands of years and the emergence of drug-resistant tuberculosis has been a major obstacle to control the disease, especially in developing countries including Ethiopia.
Objective: The study investigated the molecular epidemiology and drug resistance pattern of M. tuberculosis circulating in the Amhara, Gambella and Benshangul-Gumuz regions of Ethiopia.
Methods: A cross-sectional study was conducted using 128 MTBC isolates that were obtained from presumptive TB/MDR-TB patients. A total of 127 recovered isolates were used to investigate drug resistance patterns with the indirect proportion method using the MGIT 960 system and the genotypic method at the Ethiopian Public Health Institute. Further, identification of mycobacterial strain types and mycobacterial lineages was done using spoligotyping. Data were managed using the Epi-info, SPSS version 25, SITVIT2, MIRU-VNTRplus and TBInsight databases.
Results: Of the 127 recovered mycobacterial isolates, 100 (78.7%) were sensitive to the four firstlineanti-TB drugs, but 27 (21.3%) were resistant to at least one anti-TB drug,20 (15.7%) were poly-resistant, 17 (13.4%) were multi-drug resistant and 2 (10.5%) were Pre-XDR. The highest gene mutations associated with INH and RIF resistance were observed in the katG MUT1 gene (S315T1) [20 (76.9%)] and rpoB gene (S531L) [10 (52.6%)], respectively. Further, the two preXDR cases showed mutations in the gyrA gene. Among the 127 spoligotyped isolates, 119 generated 43 different spoligotyping patterns; 87 (73.1%) generated 26 distinct spoligotype patterns; and 31 (26.0%) generated 17 different spoligotype patterns. The predominantly identified strains, family, lineages and sublineages were the SIT149 (19, 15.9%), T family (54, 45.4%), EuroAmerican (72,60.5%) and CAS1-Delhi (24, 20.2%), respectively. Additionally, Mycobacterium Africanum
(12,10.1%) was identified. Furthermore, drug resistance was significantly associated with previous TB history(X2=46.59; p<0,001) and previous TB treatment outcome (X2=47.677;p<0.001).
Conclusion: The study identified a significant proportion of drug resistant TB (monoresistance, MDR, Pre-XDR) which could imply the drug resistant TB is a major public health problem in the country. Although a diversified mycobaterium lineages were observed in this study, the Euro American lineage and East-African-Indian lineages were the predominant lineages with the respective CAS1-Delhi and T3-ETH sublineages that are strongly associated with the druresistant TB. Consequently, the country should focuse on the strategies that help for early detection and treatment of drug-resistant TB to halt the transmission of the disease. We recommend further molecular characterization of the unknown mycobacterial isolates, particularly using sequencing platforms and phenotypic drug susceptibility testing to first- and second-line drugs. Besides, the country’s tuberculosis control program should monitor patient adherence to ensure the patients complete the full course of treatment.
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Keywords
Drug resistance pattern, Ethiopia, genetic diversity, Molecular epidemiology, Mycobacterium tuberculosis, Spoligotyping