BACKGROUND: Improvements in and expansion of tuberculosis (TB) diagnosis and treatment have yielded a growing population of TB survivors, with an estimated 155 million alive in 2020. While TB is preventable and curable, there is accumulating evidence of elevated chronic disease risk among survivors. Research objectives: (1) estimate the relative risk of non-TB mortality among TB survivors compared with controls, (2) systematically review the literature on cardiovascular disease (CVD) in TB and latent TB infection, (3) estimate the relative risk of airway disease among respiratory TB survivors compared with controls, and (4) estimate the relative risk of depression among TB survivors compared with controls, mediated by hospital length of stay (LOS).METHODS: A cohort of immigrants to British Columbia, Canada, 1985-2015, with linked health administrative and TB registry data was used for retrospective cohort studies of TB survivor health. Cox proportional hazards (PH) and time-varying models were used in statistical analyses. Causal mediation analysis of depression, mediated by hospital LOS, estimated depression risk. A prospectively registered systematic review and random-effects meta-analysis of TB and CVD was performed. RESULTS: In a time-varying Cox regression of non-TB mortality, an adjusted hazard ratio (aHR) of 1.69 (95% CI:1.50-1.91) was observed between TB exposed and non-TB exposed time. In the systematic review and meta-analysis, we found increased risk of major adverse cardiovascular events (MACE) among TB patients compared with non-TB controls (pooled RR = 1.51; 95% CI: 1.16-1.97). A higher risk of airway disease among respiratory TB survivors compared with non-TB controls was observed in our Cox PH regression (aHR=2.08; 95% CI: 1.91-2.28). In the causal mediation analysis of depression, TB survivors had aHR=1.24 (95% CI: 1.14-1.34) for depression by TB, decomposed into a natural direct effect of aHR=1.11 (95% CI: 1.02-1.21) and indirect effect of aHR=1.11 (95% CI: 1.10-1.12), indicating 50% (95% CI: 35-82%) mediation through hospital LOS.CONCLUSION: TB survivors face higher mortality from non-TB causes, and higher risk of airway disease, CVD, and depression, compared with non-TB controls. Chronic disease screening and models of care development are needed to support TB survivors’ health-related quality of life, during and after TB treatment.
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