A systematic review of risk factors for death in adults during and after tuberculosis treatment [Review article]

BACKGROUND: Despite effective anti-tuberculosis chemotherapy, case-fatality rates of up to 25% are described in both industrialised and resource-poor settings. An understanding of the factors predisposing to poor outcome may allow the development of adjunctive treatment strategies or closer clinical monitoring in high-risk individuals. OBJECTIVES: To describe the definitions and timing of deaths due to tuberculosis (TB), and the reported range of risk factors for death. METHODS: All electronically available studies investigating risk factors for death in TB patients from 1966 to 2010 were analysed. Included were peer-reviewed reports of cohort, case control or cross-sectional studies with the primary objective of determination of quantitative effect estimates of the relationship between risk factors and death in adults treated for TB. Many studies were limited by their retrospective design, reliance on data from registries and charts, and risk of reporting bias. RESULTS: Most studies reported risk factors for all-cause mortality throughout anti-tuberculosis treatment. In the context of high TB incidence and human immunodeficiency virus (HIV) prevalence, risk factors for death are HIV positivity, advancing immunosuppression, smear-negative disease and malnutrition. In regions of low TB incidence and HIV prevalence, risk factors include non-infective comorbidities, sputum smear-positive disease and alcohol and substance misuse. CONCLUSIONS: There remains a need for prospective clinical studies, particularly with a focus on deaths occurring during the first months of anti-tuberculosis treatment. Qualitative research should be used to further explore the relationship between sex and health-seeking behaviour, and to optimise delivery of health care to socially marginalised groups.