Evaluating stratified T-SPOT.TB results for diagnostic accuracy in tuberculosis disease: a retrospective cohort study with sensitivities, specificities, and predictive values.

Objectives: To investigate the association between quantitative T-SPOT.TB values and the risk of incident and prevalent tuberculosis disease (TBD), identify risk factors, and evaluate test accuracy.

Methods: This retrospective cohort study followed patients tested consecutively with T-SPOT.TB at Aarhus University Hospital from 2010 to 2017 through 2022. Data on demographics, comorbidities, medications, and TB status were collected from patient records and national registries. Cox proportional hazards models with restricted cubic splines assessed the risk of incident TBD (occurring ≥3 months post-test) by quantitative spot counts. Cox and log-binomial regressions identified risk factors for incident and prevalent TBD (occurring between three months before and after the test). Sensitivity, specificity, and predictive values assessed test accuracy. T-SPOT.TB was the index test, and microbiologically and/or clinically confirmed TBD was the reference standard.

Results: Among 8,542 individuals with complete follow-up, 59 developed incident TBD over 67,456 person-years. Among 9,014 individuals tested once, 162 had prevalent TBD at the time of testing. The risk of incident TBD increased with higher spot counts, plateauing for tests with more than ten spots. The strongest risk factors for both incident and prevalent TBD were categorical T-SPOT.TB results: compared to negative tests (≤4 spots), adjusted hazard ratios for incident TBD were 5.0 (95%CI: 1.9, 13.1) for borderline (5-7 spots) and 8.0 (95%CI: 4.0, 15.7) for positive tests (≥8 spots). Adjusted risk ratios for prevalent TBD were 14.9 (95%CI: 7.7, 28.9) for borderline and 35.6 (95%CI: 21.4, 59.2) for positive tests. Sensitivities for incident and prevalent TBD were 54.0% (95% CI: 39.3, 68.2) and 78.4% (95% CI: 71.3, 84.5), respectively. Specificities were 84.8 (84.0, 85.4) and 83.7 (82.9, 84.4), respectively.

Conclusions: Incident TBD risk increases with T-SPOT.TB values but plateaus beyond 10 spots. Borderline and positive T-SPOT.TB results are strongly linked to TBD risk.