The Impact of Borderline Quantiferon-TB Gold Plus Results for Latent Tuberculosis Screening under Routine Conditions in a Low-Endemicity Setting

Abstract

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.

The Value of the Second QuantiFERON-TB Gold-Plus Antigen Tube at Diagnosis and at Treatment Completion in Spanish Children With Tuberculosis

“…Notably, in a Swedish study that included 58,539 patients, follow-up tests after initial borderline QFT-Plus results were negative in 38% of cases, and there were no cases of incident TBD within 2 years. 11…”

A protein signature associated with active tuberculosis identified by plasma profiling and network-based analysis

“…Of the 10 healthy controls, 1 had a QFT-Gold Plus result in the low range of the borderline interval (0.35–0.99 IU/mL) but with no known TB exposure, potentially indicating a false-positive result. 20 , 21 All groups had a similar gender distribution, but the healthy controls were significantly younger than the active and latent TB groups ( Table 1 ).…”

A protein signature associated with active tuberculosis identified by plasma profiling and network-based analysis

“…From the 10 healthy controls, 1 had a QFT-Gold Plus result in the low range of the borderline interval (0.35-0.99 IU/ml) but with no known exposure, potentially indicating a false positive result (18, 19).…”

“…From the 10 healthy controls, 1 had a QFT-Gold Plus result in the low range of the borderline interval (0.35-0.99 IU/ml) but with no known exposure, potentially indicating a false positive result (18,19). Patient origins; Active TB: Somalia (4) Eritrea (3), Sweden (3), Philippines (2), Peru, Bangladesh, Pakistan, Mongolia, Poland, China, Afghanistan.…”