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

Abstract

Purpose

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

Data Sharing Statement

Relevant data pertaining to this study will be provided upon a reasonable request to the corresponding author.

Acknowledgments

The authors would like to thank the Medical Microbiology Department at the University of Pretoria for their assistance with the laboratory work and appreciate the comprehensive assistance provided by the Department of Microbial, Cellular and Molecular Biology of Addis Ababa University. The authors would also like to thank the regional TB reference laboratories in Adama and Harar.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

The laboratory work was supported by University of Pretoria, Medical Microbiology Department.