Abstract
Background Latent tuberculosis infection (LTBI) screening in healthcare settings remains crucial for tuberculosis control. Current screening methods include the Mantoux tuberculin skin test (TST) and interferon-gamma release assay (IGRA), but their comparative effectiveness in healthcare worker screening remains unclear. Objective This study aims to compare the diagnostic performance of the TST and the IGRA QuantiFERON-TB Gold Plus (QFT-Plus) in the detection of LTBI among healthcare workers at King Fahad Armed Forces Hospital in Jeddah. As no definitive gold standard for LTBI exists, QFT-Plus was used as the reference comparator: the primary objective was to quantify agreement between the two tests, while identification of an ROC (receiver operating characteristic)-derived optimal TST induration threshold was a secondary, exploratory objective. Methods A retrospective cohort study was conducted between January and November 2020, analyzing data from immunocompetent employees with documented Bacillus Calmette-Guérin (BCG) vaccination status. TST was performed using the Mantoux technique, and QFT-Plus testing was conducted according to manufacturer protocols. Statistical analysis included determination of sensitivity, specificity, and predictive values and ROC curve analysis. Because no gold standard for LTBI exists, these measures describe agreement with QFT-Plus rather than true diagnostic accuracy. Follow-up data were obtained from electronic medical records to assess progression to active tuberculosis over a five-year period. Results Among 201 participants, QFT-Plus and TST identified 11.4% and 38.3% positive cases, respectively. TST demonstrated 87.0% sensitivity and 68.0% specificity compared to QFT-Plus, with positive and negative predictive values of 26.0% and 97.6%, respectively. Receiver operating characteristic (ROC) analysis identified an optimal TST threshold of 10.5 mm, with an AUC (area under the curve) of 0.871 (95% CI: 0.805-0.937). This threshold was derived and assessed in the same dataset without independent validation and is therefore exploratory. Demographic analysis revealed no significant differences in TB positivity rates across age groups, gender, or nationality (p > 0.05). Most participants (99.0%) had documented BCG vaccination, which may explain the higher rate of TST positivity relative to QFT-Plus, consistent with reduced TST specificity in this cohort. Additionally, during a five-year follow-up period, none of the individuals with discordant results (TST-positive/IGRA-negative) progressed to active tuberculosis. Conclusion Relative to QFT-Plus, TST showed higher comparator-based sensitivity but lower comparator-based specificity, suggesting potential for over-diagnosis in BCG-vaccinated healthcare workers. Because QFT-Plus is an imperfect comparator rather than a gold standard, and because the 10.5 mm threshold was not independently validated, these findings are preliminary and apply to the healthcare worker cohort studied; they should not be read as definitive diagnostic accuracy or as a generalizable screening recommendation. A five-year follow-up demonstrated no progression to active tuberculosis among individuals with discordant TST-positive/IGRA-negative results.