Epidemiologic trajectories and burden of multidrug-resistant tuberculosis (MDR-TB) mortality across South Asia: An analysis of Global Burden of Disease data (1990–2023) with machine learning forecasting to 2050

Background: Multidrug-resistant tuberculosis (MDR-TB) remains a major public health challenge in South Asia, which bears a disproportionate global burden. Comprehensive, longitudinal analyses of MDR-TB mortality trends, stratified by country and sex, with forward-looking projections are limited. Methods: We conducted a retrospective analysis using data from the Global Burden of Disease Study 2023 to examine age-standardized mortality rates (ASMR) attributable to MDR-TB in South Asia and its countries (Bangladesh, Bhutan, India, Nepal, Pakistan) from 1990 to 2023. Trends were assessed by sex, and estimated annual percentage changes (EAPC) were calculated via log-linear regression. Seasonal Autoregressive Integrated Moving Average (SARIMA) models were employed to forecast ASMR through 2050, with 95% prediction intervals. Results: Regional ASMR rose from 0.25 per 100,000 (95% UI: 0.03-0.88) in 1990 to a peak of 6.34 (95% UI: 2.56-13.56) in 2010, declining to 3.63 (95% UI: 0.54-9.80) by 2023, driven predominantly by India and Pakistan. Nepal exhibited consistent declines (EAPC: -2.44%; 95% CI: -3.21 to -1.66), while Pakistan showed the highest increase (EAPC: 6.16%; 95% CI: 3.21-9.19). Males consistently had higher ASMR across all settings. Forecasts suggest continued declines toward near-elimination in Bangladesh, Bhutan, and Nepal, but potential substantial rebounds in India, Pakistan, and regionally, with upper prediction intervals exceeding 20-40 per 100,000 by 2050 in high-burden scenarios. Conclusion: Despite progress in some countries, MDR-TB mortality remains elevated in populous nations, with persistent male excess. Projections highlight risks of resurgence without intensified interventions. These findings underscore the urgent need for tailored, gender-sensitive strategies and enhanced regional collaboration to achieve End TB targets in South Asia.