Prognostic value of interferon gamma release assays and tuberculin skin test in predicting the development of active tuberculosis: The UK PREDICT TB Cohort Study

Background Tackling tuberculosis (TB) requires testing and treatment latent tuberculosis in high-risk groups. The aim of this study was to estimate the predictive values of the tuberculin skin test (TST) and interferon gamma release assays (IGRAs) for development of active TB . Method A cohort of migrants and contacts of active TB patients were prospectively recruited in clinics, the community and primary care. Each participant received three tests (Quantiferon Gold In-Tube [QFT-GIT], TSPOT.TB and TST). A positive TST was reported using three thresholds: 5mm (TST5), 10mm (TST10), and 5mm in BCG-naïve or 15mm in vaccinated (TST15). Participants were followed for a median of 2.9 years. Incident TB cases were identified by national TB databases, telephone interview, and medical note review. Outcomes were ratio of incidence rate ratios and predictive values for TB development. Findings Ninety-seven (1.0%) of 9,610 participants developed active TB (77 of 6,380 with results for all 3 tests). In all tests, TB incidence was very low in test-negatives (1.2-1.6 per 1000 per year). Incidence rates in test-positives were highest for T-SPOT.TB (13.2, 95%CI: (9.9,17.4)), TST15 (11.1 (8.3,14.6)) and QFT-GIT (10.1 (7.4,13.4)). Positive results for these tests were significantly more predictive of progression than TST10 and TST5. However, TST5 identified a higher proportion of progressors than TST10, TST15, T-SPOT.TB and QFT-GIT. Interpretation IGRA-based or TST15 strategies appear most suited for screening. Although TST5 and TST10 detect more TB cases, they also classify more individuals who are unlikely to develop TB as testpositive. Funding source: National Institute for Health Research Health Technology Assessment Programme 08-68-01.