Profile and Frequency of Mutations Conferring Drug-Resistant Tuberculosis in the Central, Southeastern and Eastern Ethiopia

Mulualem Agonafir,1 Gurja Belay,1 Adey Feleke,1 Nontuthuko Maningi,2 Feven Girmachew,3 Melese Reta,2,4 P Bernard Fourie2 1Department of Microbial, Cellular and Molecular Biology, College of Natural and Computational Sciences, Addis Ababa University, Addis Ababa, Ethiopia; 2Department of Medical Microbiology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa; 3Ethiopian Public Health Institute, Addis Ababa, Ethiopia; 4Department of Medical Laboratory Sciences, College of Health Sciences, Woldia University, Woldia, EthiopiaCorrespondence: Mulualem Agonafir, Department of Microbial, Cellular and Molecular Biology, College of Natural and Computational Sciences, Addis Ababa University, P.O. Box 34738, Addis Ababa, Ethiopia, Tel +251911446959, Email macagonafir@gmail.comPurpose: Advances in molecular tools that assess genes harboring drug resistance mutations have greatly improved the detection and treatment of drug-resistant tuberculosis (DR-TB). This study was conducted to determine the frequency and type of mutations that are responsible for resistance to rifampicin (RIF), isoniazid (INH), fluoroquinolones (FLQs) and second-line injectable drugs (SLIDs) in Mycobacterium tuberculosis (MTB) isolates obtained from culture-positive pulmonary tuberculosis (TB) patients in the central, southeastern and eastern Ethiopia.Patients and Methods: In total, 224 stored culture-positive MTB isolates from pulmonary TB patients referred to Adama and Harar regional TB laboratories between August 2018 and January 2019 were assessed for mutations conferring RIF, INH, FLQs and SLIDs resistance using GenoType®MTBDRplus (MTBDRplus) and GenoType®MTBDRsl (MTBDRsl).Results: RIF, INH, FLQs and SLIDs resistance-conferring mutations were identified in 88/224 (39.3%), 85/224 (38.0%), 7/77 (9.1%), and 3/77% (3.9%) of MTB isolates, respectively. Mutation codons rpoB S531L (59.1%) for RIF, katG S315T (96.5%) for INH, gyrA A90V (42.1%) for FLQs and WT1 rrs (100%) for SLIDs were observed in the majority of the isolates tested. Over a 10th of rpoB mutations detected in the current study were unknown.Conclusion: In this study, the most common mutations conferring drug resistance to RIF, INH, FLQs were identified. However, a significant proportion of RIF-resistant isolates manifested unknown rpoB mutations. Similarly, although few in number, all SLID-resistant isolates had unknown rrs mutations. To further elucidate the entire spectrum of mutations, tool such as whole-genome sequencing is imperative. Furthermore, the expansion of molecular drug susceptibility testing services is critical for tailoring patient treatment and preventing disease transmission.Keywords: drug resistance, Ethiopia, line probe assay, mutation, tuberculosis