A Pilot Study on the Utility of Whole Genome Sequencing for Detecting Drug Resistance in Mycobacterium tuberculosis in the Current Scenario.
PURPOSE: Whole Genome Sequencing (WGS) comprehensively detects all drug-resistant mutants, which can help in the early initiation of specific treatment for the patient. But there is a need to evaluate the performance of WGS in comparison with Line Probe Assays (LPA) and Phenotypic Drug Susceptibility Tests (pDST). METHODS: Consecutive sputum samples (58) found positive for Mycobacterium tuberculosis (MTB) by GeneXpert were tested for first-and second-line LPA, pDST and WGS for anti-tubercular drugs. RESULTS: Of 58, 34 (58.6%) culture isolates were resistant to one or more drugs. Resistance detected by WGS was as follows: Isoniazid 23(39.6%), Rifampicin 21(36.2%), FQs 21(36.2%), Ethambutol 18(31%), Linezolid 12(20.6%), Streptomycin 8(13.8%), Kanamycin 6(10.3%), Amikacin and Capreomycin 5(8.6%), Para-amino salicylic acid 1(1.7%) and Ethionamide 1(1.7%). No resistance was detected to Pyrazinamide, Bedaquiline, Clofazimine, Delamanid and Pretomanid. Lineage 3(EAI) was the most predominant 23(39.6%) followed by Lineage 2: 13(22.4%). Intermediate Resistance (IR) and potential novel mutations were observed in a few cases, CONCLUSION: Overall accuracy for first-line drugs between pDST vs WGS was >98% &pDST vs LPA >95%, while for second-line drugs accuracy was >96% and >90% respectively. IR and potential novel mutations should be followed up closely to understand their clinical significance.