Detection and characterization of mutations in genes related to second-line anti-tuberculosis drugs resistance in mdr tb

Introduction: Drug-resistant tuberculosis is a major global health issue. Multidrug-resistant TB (MDRTB) and extensively drug-resistant TB (XDR-TB) are particularly concerning. Conventional phenotypic methods being cumbersome and time consuming, molecular assays for the detection of mutations that are associated with resistance to anti-TB drugs have emerged as an important tool for rapid diagnosis. Aims and Objectives: To determine and characterize mutations associated with resistance to second line anti-TB drugs in MDR TB. Methods: First line LPA Conrmed MDR TB and/ or mono rifampicin or mono isoniazid resistant cases were subjected to second line LPA (MTBDRsl ver 2.0 kit)) and banding patterns of resistant cases were obtained. These were then subjected to extended phenotypic DST (Gold Standard) using MGIT 960 for Moxioxacin – 1.0µg/ml, Kanamycin -2.5µg/ml, Capreomycin -2.5µg/ml. Results: The study analysed 1580 samples subjected to SL LPA and found that 37.65% were sensitive to both FQ and SLID. FQ resistance accounted for 60.56% and SLID resistance for 17.02%. Resistance to both seen in 15.15% samples. The most common mutation associated with FQ resistance was gyr A gene at codon D94G, for SLID resistance it was in rrs gene (A1401G) and eis gene (C-12T,G-10A). Conclusion: It was observed that there is a high prevalence (62.34%) of second-line anti-TB drug resistance and mutations in gyrA, gyrB (for FQ), rrs ( for SLID) and eis promoter regions (for low level kanamycin) were signicantly associated with secondline anti-TB drug resistance.