The Multifactorial Determinants of Tuberculosis Mortality: A Global Comprehensive Epidemiological Analysis and Framework for Disease Elimination

This study presents a comprehensive analysis of tuberculosis (TB) epidemiology, with particular emphasis on elucidating the determinants that differentiate TB infection from fatal outcomes. Through systematic examination of demographic, clinical, socioeconomic, and healthcare system factors, this research illuminates the complex, multifactorial nature of TB mortality. Our findings demonstrate pronounced disparities in mortality across age demographics, with individuals above 55 years experiencing disproportionately elevated fatality rates (case-fatality ratio nearly three times that of younger adults, p<0.001) despite peak incidence occurring in younger cohorts. Clinical comorbidities, particularly HIV co-infection (45% mortality rate; RR 3.0, 95% CI 2.8-3.2), malnutrition (62% mortality rate), and drug resistance (37% mortality rate), emerged as significant mortality risk modifiers. Analysis of healthcare system factors revealed that delayed diagnosis (OR 3.8, 95% CI 3.5-4.1), limited access to drug susceptibility testing, and treatment adherence challenges substantially influence mortality outcomes. Perhaps most notably, socioeconomic determinants—including healthcare access, food security, housing quality, and income level—demonstrated marked gradients between surviving and deceased tuberculosis patients. The geographical distribution of TB mortality exhibits striking regional concentration, with South-East Asia and Africa collectively accounting for approximately 69% of global TB deaths. Building upon these findings, we propose a comprehensive framework for TB elimination that transcends traditional biomedical paradigms to address the fundamental social and economic determinants of TB transmission, progression, and mortality.