The impact of borderline Quantiferon-Plus results for latent tuberculosis screening under routine conditions in a low endemic setting

Quantiferon-TB Gold Plus (QFT-Plus) is an interferon gamma release assay used to diagnose latent tuberculosis (LTB). A borderline range (0.20-0.99 IU/mL) around the cut off (0.35 IU/ml) has been suggested for the earlier QFT version. Our aims were to evaluate the borderline range for QFT-Plus and the contribution of the new TB2 antigen tube. QFT-Plus results were collected from clinical laboratories in Sweden and linked to incident active TB within 3-24 months using the national TB registry. Among QFT-Plus results from 58539 patients, 83% were negative (<0.20 IU/ml), 2.4% borderline negative (0.20-0.34 IU/ml), 3.4% borderline positive (0.35-0.99 IU/ml), 9.6% positive (≥1.0 IU/ml) and 1.6% indeterminate. Follow-up tests after initial borderline results were negative (<0.20 IU/ml) in 38.3% without any cases of incident active TB within 2 years. Applying the 0.35 IU/ml cut-off, 1.5% of TB1 and TB2 results were discrepant whereof 52% within borderline range. A TB2≥0.35 IU/ml with TB1<0.20 IU/ml was found in 0.4% (231/58539) of all included baseline QFT-Plus test results, including 1.8% (1/55) of incident TB cases. A borderline range for QFT-Plus is clinically useful as more than one third of those with borderline results are convincingly negative upon retesting, without developing incident active TB. The TB2 tube contribution for LTB diagnosis appears limited.