MOLECULAR CHARACTERIZATION OF GENE MUTATIONS ASSOCIATED WITH ISONIAZID AND RIFAMPICIN RESISTANCE IN MYCOBACTERIUM TUBERCULOSIS ISOLATES USING THE GENOTYPE MTBDRPLUS ASSAY IN KANO, NIGERIA
The rise of multidrug-resistant tuberculosis (MDR-TB), particularly strains resistant to rifampicin (RIF) and isoniazid (INH), poses a major challenge to TB control efforts in Nigeria. Rapid identification of resistance-conferring mutations is critical for timely and effective treatment. To determine the pattern of gene mutations associated with resistance to first-line anti-TB drugs using the Genotype MTBDRplus assay in Mycobacterium tuberculosis isolates from Kano State Nigeria, alongside socio-demographic and culture-based insights. This study was carried out at the North-West Zonal Tuberculosis Reference Laboratory, Aminu Kano Teaching Hospital (AKTH), Kano. Socio-demographic information of the study participants was obtained using structured data collection tools. A total of 401 sputum specimens were cultured, and the resulting Mycobacterium tuberculosis isolates were analyzed using the Genotype MTBDRplus assay to identify resistance-associated mutations in the rpoB, katG, and inhA genes. The distribution of mutation frequencies was subsequently compared across multidrug-resistant (MDR-TB), rifampicin monoresistant, and isoniazid monoresistant strains. Culture and drug susceptibility testing revealed MDR-TB in 41 (10.2%) patients, RIF monoresistance in 18 (4.5%), and INH monoresistance in 6 (1.5%). Males constituted 71.6% of participants, and the predominant age group was 25–34 years (35.4%). The most common mutations in MDR strains were rpoB S531L (41.5%), katG S315T1 (73.2%), and inhA C15T (17.1%). The rpoB WT8 probe was affected in 85.4% of MDR and 61.5% of RIF monoresistant strains. Among INH monoresistant isolates, mutations were equally distributed between katG S315T1 and inhA C15T (33.3% each). Less frequent inhA mutations such as A16G, T8C, and T8A were also observed. The Genotype MTBDRplus assay effectively detects resistance-associated mutations in MTB. The integration of molecular and demographic data offers a comprehensive understanding of MDR-TB epidemiology. The high prevalence of rpoB and katG mutations supports the assay’s role in guiding rapid MDR-TB diagnosis and region-specific treatment strategies in Nigeria.
Keywords: Mycobacterium tuberculosis, MDR-TB, Genotype MTBDRplus, drug resistance, rpoB, katG, inhA, rifampicin, isoniazid, socio-demographics, culture
*Correspondence: adoumar2014@gmail.com, 08032862715
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