Implications of progressive lung damage and post-TB sequelae for the health benefits of prompt TB diagnosis in high HIV prevalence settings: a mathematical modeling analysis.

Background: Untreated pulmonary tuberculosis (TB) causes ongoing lung damage, which may persist after treatment. Conventional approaches for assessing TB health effects may not fully capture these mechanisms. We evaluated how TB-associated lung damage and post-TB sequalae affect the lifetime health consequences of TB in high HIV prevalence settings. Methods: We developed a microsimulation model representing dynamic changes in lung function for individuals evaluated for TB in routine clinical settings. We parameterized the model with data for Uganda, Kenya, and South Africa, and estimated lifetime health outcomes under prompt, delayed, and no TB treatment scenarios. We compared results to earlier modelling approaches that omit progressive lung damage and post-TB sequelae. Findings: We estimated 4.6 (95% uncertainty interval 3.4-5.8), 7.2 (5.1-9.6), and 18.0 (15.1-20.0) year reductions in life expectancy due to TB under prompt, delayed, and no treatment scenarios, respectively. Disability-adjusted life years (DALYs) from TB were estimated as 8.3 (6.2-10.6), 12.6 (9.0-17.0), and 27.8 (24.1-30.6) under prompt, delayed, and no treatment scenarios, respectively. Post-TB DALYs represented 9-53% of total DALYs. Modelling approaches that omit progressive lung damage and post-TB sequelae underestimated lifetime health losses of TB by 48-57%, and underestimated the benefits of prompt treatment by 45-64%. Interpretation: Delayed initiation of TB treatment causes greater lung damage and higher mortality risks during and after the disease episode. In settings with co-prevalent TB and HIV, accounting for these factors substantially increased estimates of the lifetime disease burden and life expectancy loss caused by TB. Funding: NIH.