RESUMEN
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. Research in context: Evidence before this study: Research on long-term sequalae among tuberculosis (TB) survivors has focused on describing the prevalence and nature of these post-TB sequalae, and quantifying their contribution to the overall burden of TB disease. There is limited evidence describing how improvements in TB diagnosis and prompt treatment initiation could affect the overall health losses associated with TB, inclusive of post-TB sequelae. We searched PubMed from database inception until July 19, 2024, with no language restrictions for studies reporting how TB diagnosis and treatment affect post-TB sequelae and lifetime health losses, using the search terms "(tuberculosis OR TB) AND (post-TB OR post-tuberculosis) AND (diagnos*) AND (treat*) AND (model*)". We retrieved 21 publications based on this search. Of these, one study reported a mathematical modeling approach for estimating lifetime health outcomes and costs by considering the delay in diagnosis, post-TB sequelae, and treatment discontinuation among TB patients in Brazil, but did not simulate changes in lung function during the TB episode.Added value of this study: To our knowledge, this is the first study to investigate the effects of timeliness of TB diagnosis on progressive lung damage and lifetime health outcomes for individuals with TB. To do so, we constructed a mathematical model simulating changes in lung function before, during, and after TB treatment, and simulated multiple counterfactual scenarios for a cohort of individuals presenting to primary health services with undiagnosed TB disease in Uganda, Kenya, and South Africa. We compared the results of this analysis to the estimates produced by earlier modelling approaches that do not represent TB-associated lung damage or post-TB sequelae.Implications of all the available evidence: The results of this analysis showed that post-TB sequelae represent a substantial share of the overall health losses associated with TB, and that better post-TB lung function (resulting from a shorter duration of untreated TB disease) is a major contributor to the overall health benefits of prompt TB diagnosis and treatment. These results are not accurately captured by earlier modelling approaches that did not consider TB-associated lung damage or post-TB sequelae. The findings of this analysis contribute to the evidence base describing how TB interventions can influence lung function dynamics during and after TB disease, and the resulting changes in disability and mortality due to TB.
RESUMEN
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.