Do higher quantitative interferon gamma release assay or tuberculin skin test results help to predict incident tuberculosis? Data from the UK PREDICT study

<b>Background:</b> We examined whether higher test thresholds for QuantiFERON Gold-in-Tube (QFT-GIT), T-SPOT.TB and the tuberculin skin test (TST) could improve prediction of incident TB. <b>Methods:</b> We extended follow-up of a UK cohort of 9,610 adult TB contacts and recent migrants to a median of 4·7 years. We calculated incidence rates, sensitivities, specificities and predictive values for incident TB in ordinal strata for quantitative test results of QFT-GIT, T-SPOT.TB and TST (with adjustment for prior BCG). <b>Results:</b> TB incidence rates increased in higher ordinal strata for all tests (p&lt;0·0001). For QFT-GIT, incidence rates (per 1,000 person-years) increased from 1·10 (95% CI 0·79-1·54) in the &lt;0·35 IU/mL stratum, to 10·02 (6·83-14·72) for ≥4·00 IU/mL. For T-SPOT.TB, rates increased from 1·10 (0·79-1·55) in the ≤4 spots stratum to 12·73 (8·74-18·57) for ≥50 spots. For BCG-adjusted TST, rates increased from 1·07 (0·76-1·54) in the &lt;5mm stratum to 10·95 (7·71-15·58) for ≥15mm. Over three years’ follow-up, there was a modest increase in positive predictive value (PPV) with the higher thresholds (3·0% for QFT-GIT ≥0·35 IU/mL vs. 3·6% for ≥4·00 IU/mL; 3·4% for T-SPOT.TB ≥5 spots vs. 5·0% for ≥50 spots; and 3·1% for BCG-adjusted TST ≥5mm vs. 4·3% for ≥15mm). Sensitivity for incident TB declined as thresholds increased (61·0% for QFT-GIT ≥0·35 IU/mL vs. 23·2% for ≥4·00 IU/mL; 65·4% for T-SPOT.TB ≥5 spots vs. 27·2% for ≥50 spots; 69·7% for BCG-adjusted TST ≥5mm vs. 28·1% for ≥15mm). <b>Conclusions:</b> Higher thresholds lead to marginal improvement in PPV, but a marked loss of sensitivity. Novel biomarkers are required to better predict incident TB.