Prevalence of gene mutations associated with isoniazid resistance in drug-resistant tuberculosis: a study from Limpopo, South Africa

Abstract

Background: The mechanisms involved in isoniazid (INH) resistance are complex, and determining the kind of INH resistance conferred is essential in shaping patient-tailored tuberculosis (TB) regimens and avoiding cross-resistance. This study aimed to determine the prevalence of INH resistance-causing mutations linked with multidrug-resistant tuberculosis (MDR-TB) in Limpopo Province.
Methods: We examined 424 line probe assay (LPA) (MTBDRplus, Hain Lifescience, Nehren, Germany) results from the Limpopo TB reference laboratory to evaluate the prevalence of mutations in catalase-peroxidase (katG) or enoyl-acyl carrier protein reductase (inhA). We stratified the findings by drug resistance category. Data were analysed using the Statistical Package for the Social Sciences (SPSS) version 29. The frequencies of katG and inhA mutations were calculated, and a chi-square test was used to determine significant associations between mutations and demographic and clinical variables. A p-value less than 0.05 was considered significant.
Results: In MDR-TB and extensively drug-resistant tuberculosis (XDR-TB) isolates, the frequency of inhA mutations without a concomitant katG mutation was 14% and 27%, respectively. The frequency of inhA mutations with or without a katG mutation was 30.3% and 82.8%, respectively. The INH mono-resistance, MDR-TB, and pre-XDR-TB showed katG dominance of 71%, 69%, and 60%, respectively. Age and gender were associated with one or more mutations (p < 0.021).
Conclusion: In Limpopo, katG mutations are the predominant mechanism of INH resistance, particularly in MDR-TB and INH monoresistant cases, while inhA mutations are more common in pre-XDR-TB and XDR-TB.