# A detailed analysis of borderline results in the QuantiFERON-TB Gold-Plus assay incorporating longitudinal follow-up: intermediate-burden setting

## TL;DR

This study examines how borderline results from a TB test change over time, showing that follow-up testing is important for accurate interpretation.

## Contribution

This is the first longitudinal study of borderline QuantiFERON-TB Gold Plus results in an intermediate TB burden setting.

## Key findings

- Borderline TB1 and TB2 results showed weak agreement and moderate correlation.
- TB2 results had the highest variability during the first follow-up.
- Borderline results in both TB1 and TB2 showed higher reversion and conversion rates.

## Abstract

The QuantiFERON-TB Gold Plus (QFT-Plus; Qiagen, Hilden, Germany) assay is widely used for latent TB infection (LTBI) screening; however, borderline results often show variability during follow-up. We investigated the longitudinal variability of borderline TB1 and TB2 results throughout the follow-up period. A total of 770 individuals with initial borderline results (0.2–0.7 IU/mL) in either the TB1 or TB2 tube were retrospectively collected over a 5-year period. Agreement and correlation between the initial TB1 and TB2 results were analyzed. Trends in reversion and conversion were evaluated separately for each tube and for combined results among individuals with available follow-up tests. Initial TB1 and TB2 borderline results showed weak agreement (Cohen’s κ = 0.441, 95% CI 0.401–0.480) and moderate correlation (Spearman’s ρ = 0.640, 95% CI 0.596–0.680; P < 0.001). TB2 exhibited the highest variability during the first follow-up (33.8%, 47/139), which decreased with subsequent testing. Among those with ≥2 follow-ups, 30.2% (13/43) showed result changes. Cases with borderline values in both TB1 and TB2 showed higher rates of reversion and conversion, whereas having a low-negative result (<0.2 IU/mL) in at least one tube was associated with minimal variability. The QFT-Plus assay provides separate TB1 and TB2 values, and integrating these results may improve interpretation. Follow-up testing is particularly warranted when borderline results occur in both tubes. Further studies are needed to define appropriate criteria and optimal retesting intervals.

This is the first study to longitudinally assess borderline QuantiFERON-TB Gold Plus (QFT-Plus) results in an intermediate TB burden setting, highlighting the need for defined criteria and retesting intervals.