Revisiting cost-effectiveness of TB infection screening using IGRAs: focus on a comprehensive approach

Introduction: Tuberculosis infection (TBI) is defined as a non-infectious and non-symptomatic condition when an immune response to Mycobacterium tuberculosis is detected. Approximately 10% of those with TBI are likely to progress to TB disease in their lifetime with a risk being significantly higher in those living with HIV, close contacts of active TB cases, healthcare workers (HCW) and other risk groups. True prevalence of TBI in Africa is unknown but estimated at 30 to >80% being the highest in HCWs, close contacts, and miners [Basera et al., 2017].World Health Organization (WHO) recommends TBI testing and preventive treatment in high risk groups regardless of settings. However, given a high prevalence of TBI in Africa and other TB endemic areas, consensus on TBI screening strategies, specifically with regards to selection of diagnostic tests, is still lacking. Value-based healthcare, shifting from diagnostic performance to ensuring that patients receive the best possible care with optimal outcomes, is especially relevant in Africa where cost-effectiveness of diagnostic tests will play a major role in healthcare policies. Methods: High costs have long been considered among major obstacles for implementation of WHO-endorsed Interferon-Gamma Releasing Assays (IGRA) in endemic settings [Faust et al., 2020]. Until recently, there has been lack of evidence on cost-effectiveness of IGRA assays in TB endemic areas and some studies suggested that skin tests (including tuberculin, TST and newer antigen tests, TBST) could offer some cost savings. However, these studies relied exclusively on unit costs not considering other direct and indirect costs associated with lower specificity of TST and operational challenges of skin tests including subjectivity, challenges related to the administration, and reporting test results as well as high dropout rates leading to higher labor costs [Kontsevaya I 2024]. Results: We developed an economic model based on a decision tree used to capture outcomes relating to LTBI screening followed by a Markov model that simulated the lifetime costs and benefits of the patients, thus representing a true patient's journey and accounting for any additional costs associated with the test performance. This model was evaluated in medium and high TB incidence settings including Malaysia and Côte d'Ivoire demonstrating that TBI screening in migrants and household contacts of active TB is cost effective compared to TST, thus offering a sustainable solution for resource-constrained settings [Barker et al., 2023; N'Guessan RK et al., 2024]. These findings were in line with TBI screening framework evaluated in Peru [Brumwell et al., 2023] and a similar study conducted in Colombia [Navarro et al., 2024]. Conclusions: These studies demonstrate that IGRA tests are likely to be cost-effective in high TB burden populations when economic analysis considers expenses beyond unit costs, accounting for long-term consequences and broader outcomes.