Genetic mutations associated with rifampicin and isoniazid resistance in MDR-TB patients in North-West India

Abstract

Effective tuberculosis (TB) control has been hindered by the emergence of multidrug-resistant TB (MDR-TB). To analyse the frequency of drug resistance among presumed cases of drug-resistant TB in the state of Punjab, India, and to determine the frequency of various genetic mutations detected using the line-probe assay (LPA). Eight hundred patients with presumptive drug-resistant TB were enrolled under the programmatic management of drug-resistant TB under India's Revised National Tuberculosis Control Programme. Sputum samples from these patients were subjected to smear microscopy and LPA. Clinicodemographic details along with drug resistance patterns and genetic mutations were studied. After excluding non-eligible samples, 545 samples were analysed, of which 290 (53.2%) showed resistance. Isoniazid and rifampicin (RMP) monoresistance were detected in respectively 9.3% (51/545) and 18% (98/545) of samples, while MDR was present in 25.8% (141/545) of samples. Of the MDR-TB cases, 2.1% (3/141) were treatment-naïve, while 90.8% (128/141) were on retreatment. The most common mutation conferring RMP resistance was S531L. All patients undergoing retreatment for TB should be tested for drug susceptibility at the initial evaluation. Factors responsible for high MDR-TB and heteroresistance in Punjab need further studies.