Systematic review of the economic impact of novel Mycobacterium tuberculosis specific antigen-based skin tests for detection of TB infection compared with tuberculin skin test and interferon-gamma release assays.

The Purified Protein Derivative tuberculin skin tests (TST) and blood-based Mycobacterium tuberculosis (M.tb) specific interferon-gamma release assays (IGRA) are the currently used tests for identifying individuals with TB infection for preventive treatment. However, challenges around access and implementation have limited their use. Novel M.tb specific skin tests (TBST) such as Diaskintest, ESAT6-CFP10 (C-TST), C-Tb (also known as Cy-Tb), and DPPD may provide accurate and scalable options but evidence synthesis on their economic impact is lacking. We conducted two separate systematic reviews to compare the costs and cost-effectiveness of (1) the novel skin tests TBST (primary), and (2) TST and IGRA tests (secondary), to support WHO guideline development. We searched for articles presenting economic evaluations of the diagnostic tests using a health provider perspective and related to TB infection in humans. We considered papers written in English, Chinese or Russian. In the primary review, eight studies for novel TBST were found. One study in Brazil assessed cost-effectiveness of C-TST and Diaskintest and seven in Russia assessed the Diaskintest, while none evaluated C-Tb or DPPD. The review showed on average, Diaskintest kit costs (in 2021 USD) $1.60 (1.50 - 1.70), while full unit costs were estimated at $5.07. C-TST unit cost was $9.96. The second review found 32 articles on IGRA and/or the TST. These presented an average TST full unit cost of $37.88, and $87.81 for IGRA. Studies' quality for TBST was limited while high-quality studies were found for TST and IGRA tests. In conclusion, there is limited evidence regarding the costs and cost-effectiveness of novel TBST. Conversely, there is substantial evidence for TST and IGRA tests, but most studies were performed in high-income and low-TB burden settings and their cost-effectiveness varied between and within risk groups without clear economic consensus.