Evaluation of TST/C-TST combination for latent tuberculosis infection screening: diagnostic performance and cost-effectiveness compared to TST/IGRAs

Background The interferon-gamma release assays (IGRAs) are characterized by their complexity and reliance on specific instrumentation. The recombinant Mycobacterium tuberculosis (MTB) fusion protein skin test (C-TST) utilizes the same MTB fusion protein as IGRAs. If the C-TST demonstrates consistent results and greater cost-effectiveness, it could potentially replace IGRAs and be used alongside the tuberculin skin test (TST) for the screening of latent tuberculosis infection (LTBI). This study aims to assess whether the TST/C-TST screening strategy offers superior diagnostic efficacy and cost-effectiveness compared to the conventional TST/IGRAs strategy, thereby evaluating the potential application of the combined C-TST and TST approach for LTBI screening. Methods The study population consisted of young males, aged 18 to 40 years, who attended the outpatient clinic of a hospital in 2023. These participants underwent TST and C-TST, followed by IGRAs between October and December 2023. The sensitivity, specificity, and reliability of the screening results were assessed. Furthermore, a hybrid decision tree and Markov model were utilized to evaluate the costs and health outcomes associated with five active screening strategies-TST, C-TST, IGRAs, TST combined with C-TST, and TST combined with IGRAs-from a societal perspective over a 20-year period. Results In this study, valid results were obtained from 1412 participants: 202 individuals completed three tests, while 1210 completed two tests. The sensitivity for the TST, the C-TST, and IGRA (QFT-GIT) was 92.7%, 52.9%, and 58.8%, respectively, with corresponding specificities of 56.0%, 83.6%, and 83.6%. Notably, the C-TST and IGRA (QFT-GIT) exhibited high concordance, as indicated by a Kappa value of 0.869. However, through a simulation-based analysis of this single-center cohort, which consisted exclusively of male participants and included a small subgroup subjected to all three tests, and under predefined model assumptions, the combination of TST and C-TST emerged as a more effective screening strategy. This combination achieved an AUC of 0.821, achieved the optimal balance between accuracy and cost-effectiveness. Conclusion Within the context of this study, the novel screening strategy that integrates TST and C-TST demonstrates promising efficacy and economic advantages when compared to the traditional TST/IGRAs approach for the detection of LTBI.