Pattern and prevalence of rifampicin and isoniazid-resistant tuberculosis using genotype MTBDRplus assay in Ethiopia

Resistance-conferring mutations in Mycobacterium tuberculosis (Mtb) are primary drivers of therapeutic challenges. However, comprehensive resistance mutation profiles are lacking in low- and middle-income countries. This study assesses the patterns and prevalence of isoniazid (INH) or multidrug/rifampicin-resistant (MDR/RR) tuberculosis (TB) mutations. We used stored Mtb isolates obtained from smear-positive TB patients recruited from 32 health facilities as part of the drug resistance survey (DRS). Line probe assay (LPA) testing was conducted on phenotypically confirmed INH-resistant and MDR/RR Mtb isolates. A total of 65 MDR/RR and 62 mono-INH-resistant Mtb isolates were analyzed. LPA detects 93.8% of rifampicin-conferred mutations in phenotypically confirmed MDR/RR Mtb isolates. The most frequent mutations were found at rpoB codons 530-533 (63.9%), and the S531L mutation comprised 59% of the MDR/RR TB isolates. The katG315 mutations were observed in the majority of MDR/RR (98%) and mono-INH-resistant (91.6%) Mtb isolates. The proportion of katG315 mutations was higher in newly diagnosed INH-resistant TB patients (72.7%) than those who had had prior treatment (27.3%). In 29.5% of MDR/RR and 2.5% of mono-INH resistant Mtb isolates, resistance was inferred. This study reports the proportion of mutations conferring resistance to rifampicin and INH using isolates collected from the national DRS.

Drug resistance mutations vary by location, effectiveness of the national control programs, and the diagnostic methods employed. Rapid molecular diagnostic tests are the primary methods used to detect drug-resistant tuberculosis. Comprehensive resistance mutation profiles are often lacking in low- and middle-income countries. The goal of this study was to assess the patterns and frequencies of mutations conferring first-line drug resistance in Ethiopia using isolates collected from the drug resistance survey. The isolates were obtained before the implementation of rapid molecular tests. The findings will enhance our understanding of the patterns and frequencies of mutations that confer resistance, which is crucial for developing a comprehensive catalog of mutations.