Mutations in <i>Mycobacterium tuberculosis</i> that Confers Resistance to First Line and Second Line Anti Tuberculosis agents in Western Kenya

Abstract

Background: Tuberculosis drug resistance remains a global, regional as well as a national public health concern, and is driven by point mutations in the Mycobacterium tuberculosis genome. However, their frequencies vary geographically and that affects the general applicability of antimicrobial agents as opposed to regional tailored or individualized chemotherapy.

Materials and Methods:  In this prospective cross-sectional study, sputum samples were collected from 256 tuberculosis clinical suspects attending various health facilities in Kisumu County between November 2020 and October 2021. The study aimed to describe the Mutations in Mycobacterium tuberculosis that confers resistance to first and second-line anti-tuberculosis agents in Kisumu County, Western Kenya. Detection of mutations conferring resistance to anti-tuberculosis drugs was carried out using GenoType MTBDRplus and GenoType MTBDRsl.

Results: Out of a sample of 256 Tuberculosis suspect cases, 145 were Mycobacterium tuberculosis bacilli confirmed, out of which 32 (22%) were from new TB cases and 113(78%) retreatment. High isoniazid-resistant strains had mutations in the promoter region of the inhA gene at codon -15 with an amino acid change of S315T1, while low isoniazid-resistant strains had mutations in the katG gene at codon 315. Among rifampicin-resistant strains, four isolates displayed mutations at codon 526 to 529 in the rpoB gene with an amino acid change of H526Y and one isolate displayed mutation at codon 530 to 533 in the rpoB gene with an amino acid change of S531L. The MDR strains had mutations in the rpoB and katG genes. Additionally, greater variability of mutations was exhibited among retreatment and HIV-positive cases. No drug resistance-conferring mutations were detected against second-line anti-tuberculosis drugs.

Conclusion: A greater variability of mutations was observed from isoniazid and rifampicin resistance in retreatment cases compared to new cases and additional mutations were more associated with HIV positive cases compared to HIV negative cases.