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.

Factors associated with tuberculosis treatment initiation among bacteriologically negative individuals evaluated for tuberculosis: an individual patient data meta-analysis.

Background: Globally, over one-third of pulmonary tuberculosis (TB) disease diagnoses are made based on clinical criteria after a negative diagnostic test result. Understanding factors associated with clinicians' decisions to initiate treatment for individuals with negative test results is critical for predicting the potential impact of new diagnostics. Methods: We performed a systematic review and individual patient data meta-analysis using studies conducted between January/2010 and December/2022 (PROSPERO: CRD42022287613). We included trials or cohort studies that enrolled individuals evaluated for TB in routine settings. In these studies participants were evaluated based on clinical examination and routinely-used diagnostics, and were followed for ≥1 week after the initial test result. We used hierarchical Bayesian logistic regression to identify factors associated with treatment initiation following a negative result on an initial bacteriological test (e.g., sputum smear microscopy, Xpert MTB/RIF). Findings: Multiple factors were positively associated with treatment initiation: male sex [adjusted Odds Ratio (aOR) 1.61 (1.31-1.95)], history of prior TB [aOR 1.36 (1.06-1.73)], reported cough [aOR 4.62 (3.42-6.27)], reported night sweats [aOR 1.50 (1.21-1.90)], and having HIV infection but not on ART [aOR 1.68 (1.23-2.32)]. Treatment initiation was substantially less likely for individuals testing negative with Xpert [aOR 0.77 (0.62-0.96)] compared to smear microscopy and declined in more recent years. Interpretation: Multiple factors influenced decisions to initiate TB treatment despite negative test results. Clinicians were substantially less likely to treat in the absence of a positive test result when using more sensitive, PCR-based diagnostics.