Prevalence and Genetic Analysis of Isoniazid-Resistant Tuberculosis in Eastern Uttar Pradesh, India

Background Tuberculosis (TB) is an airborne bacterial infection caused by Mycobacterium tuberculosis. It continues to pose a major threat, India bore the highest TB burden accounting for 27% of global cases in 2022. The emergence of drug resistance, especially primary medications such as isoniazid (INH), hinders treatment and containment efforts. Genetic alterations in the katG and inhA genes are the main contributors to INH resistance, resulting in high and low levels of resistance, respectively. Objectives This study investigates the genetic mutational patterns of INH resistance in TB cases, focusing on their prevalence and association with demographical, geographical, and clinical features.  Methods A cross-sectional prospective study was conducted in our tertiary care center located in eastern Uttar Pradesh (UP), India, from June 2022 to May 2024. A total of 6,954 highly suspected TB cases, including pulmonary and extra-pulmonary samples, were evaluated. After fluorescence microscopy, line probe assay (LPA) was used to analyze 1,998 (28.73%) sputum-positive samples for katG and inhA mutations, which confer INH resistance. Results Among 1,998 sputum-positive samples tested with LPA, valid results were obtained for 1,993 cases. Of these, 131 (6.57%) showed INH resistance, with high-level INH resistance detected in 102 (77.86%) cases, predominantly linked to katG MUT1 (S315T1) mutations. Low-level resistance was identified in 29 (22.14%) cases, primarily associated with inhA MUT1 (C-15T) mutations. Among INH resistance cases, females were significantly younger than males (mean age 28.49±14.16 vs. 40.65±16.03; p-value<0.001), but male cases were higher than female (86[65.64%] vs. 45[34.35%]; p-value=0.039). However, age distribution was comparable between high and low-level INH resistance. Geographically, Gorakhpur emerged as a hotspot for high-level resistance 40/102 (39.21%), while Deoria had the highest prevalence of low-level resistance 9/29 (34.48%). Conclusion Our study identified the prevalence of katGmutations in high-level and inhA mutations in low-level INH resistance in eastern UP, India. This highlights the need for region-specific public health strategies, including better joint management of comorbidities and enhanced diagnostic capacity to address the burden of drug-resistant TB in this high-prevalence region.