DIAGNOSIS IS NOT ENOUGH: EXTENSIVELY DRUG-RESISTANT TUBERCULOSIS. EPIDEMIOLOGICAL TRENDS, REGIONAL DISPARITIES, AND PROJECTIONS ACROSS SIX HIGH-BURDEN COUNTRIES

Abstract

Extensively drug-resistant tuberculosis (XDR-TB) — resistance to isoniazid and rifampicin plus fluoroquinolones and at least one additional Group A drug (bedaquiline or linezolid)2,3 — represents the most severe and least treatable form of tuberculosis in routine clinical use, and it continues to test the limits of the WHO End TB Strategy launched in 2014.1 This review synthesizes Global Burden of Disease (GBD) 2021 estimates5,10 and WHO Global Tuberculosis Report data (2024–2025)4,6 for six countries that together carry a disproportionate share of global TB and drug-resistant TB burden: India, the Russian Federation, Indonesia, China, the Philippines, and Pakistan.In 2021, global XDR-TB incidence stood at 24,036 cases, with an age-standardized incidence rate (ASIR) of 0.29 per 100,000 — a rate that has crept upward since 1990 (AAPC 0.01%) even as absolute case counts have grown faster.5 Among the six focus countries, the Russian Federation recorded the highest single-country incident case count (5,942 cases), while India carried the highest prevalent-case count (7,512), the highest death toll (2,815), and the highest DALY burden (99,599) of any country worldwide.5 At the regional level, Eastern Europe — driven overwhelmingly by Russia — recorded the highest XDR-TB rates of the four regions represented (ASIR 3.52 per 100,000; ASDR 18.96 per 100,000), roughly ten times the East Asian rate.5Weak but statistically significant inverse correlations were observed between sociodemographic index (SDI) and XDR-TB burden (ASDR r = −0.19, P < 0.01),5,11 though the relationship is far less pronounced than for MDR-TB overall,8 and health-system and historical-epidemic factors clearly modify it — Russia's high SDI has not translated into a correspondingly low XDR-TB burden.5 Treatment outcomes remain a persistent weak point: globally only 68% of people treated for MDR/RR-TB achieve treatment success, and just 44% of those estimated to develop MDR/RR-TB in 2023 were diagnosed and started on treatment at all.4,12 Bayesian age-period-cohort projections suggest continued upward pressure on global XDR-TB rates through 2035, though the uncertainty around these projections is wide.5Reversing current trajectories will require faster diagnostic scale-up, wider adoption of all-oral treatment regimens,15,16,17 and sustained investment in health systems in the highest-burden settings — with particular attention to the divergent drivers of burden in South Asia, Eastern Europe, Southeast Asia, and East Asia.