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Background  Systematic screening for active tuberculosis (TB) is a strategy which requires the health system to seek out individuals, rather than waiting for individuals to self-present with symptoms (i.e., passive case finding). Our review aimed to summarize the current economic evidence and understand the costs and cost-effectiveness of systematic screening approaches among high-risk groups and settings.    Methods  We conducted a systematic review on economic evaluations of screening for TB disease targeting persons with clinical and/or structural risk factors, such as persons living with HIV (PLHIV) or persons experiencing homelessness. We searched three databases for studies published between January 1, 2010 and February 1, 2020. Studies were included if they reported cost and a key outcome measure. Owing to considerable heterogeneity in settings and type of screening strategy, we synthesized data descriptively.    Results  A total of 27 articles were included in our review; 19/27 (70%) took place in high TB burden countries. Seventeen studies took place among persons with clinical risk factors, including 14 among PLHIV, while 13 studies were among persons with structural risk factors. Nine studies reported incremental cost-effectiveness ratios (ICERs) ranging from US$51 to $1980 per disability-adjusted life year (DALY) averted. Screening was most cost-effective among PLHIV. Among persons with clinical and structural risk factors there was limited evidence, but screening was generally not shown to be cost-effective.    Conclusions  Studies showed that screening is most likely to be cost-effective in a high TB prevalence population. Our review highlights that to reach the “missing millions” TB programmes should focus on simple, cheaper initial screening tools (i.e., symptom screen and CXR) followed by molecular diagnostic tools (i.e., Xpert®) among the highest risk groups in the local setting (i.e., PLHIV, urban slums). Programmatic costs greatly impact cost-effectiveness thus future research should provide both fixed and variable costs of screening interventions to improve comparability.    Supplementary Information  The online version contains supplementary material available at 10.1186/s12879-021-06633-3.

Tuberculosis screening costs and cost-effectiveness in high-risk groups: a systematic review