Evaluation of QuantiFERON-TB Gold-Plus in Health Care Workers in a Low-Incidence Setting.

Although launched in 2015, little is known about the accuracy of QuantiFERON-TB Gold-Plus (QFT-Plus) for diagnosis of latent infection (LTBI). Unlike its predecessor, QFT-Plus utilizes two antigen tubes to elicit an immune response from CD4 and CD8 T lymphocytes. We conducted a cross-sectional study in low-risk health care workers (HCWs) at a single U.S. center to compare QFT-Plus to QuantiFERON-TB Gold in-tube (QFT). A total of 989 HCWs were tested with both QFT and QFT-Plus. Risk factors for LTBI were obtained from a questionnaire. QFT-Plus was considered positive if either antigen tube 1 (TB1) or TB2 tested positive, per the manufacturer's recommendations, or if both TB1 and TB2 tested positive, using a conservative definition. Results were compared using Cohen's kappa and linear regression, respectively. Agreement of QFT with QFT-Plus was high, at 95.6% (95% confidence interval [CI], 94.3 to 96.9; kappa, 0.57). The majority of discordant results between QFT and QFT-Plus TB1 (84.8%) and QFT and QFT-Plus TB2 (88.6%) fell within the range of 0.2 to 0.7 IU/ml. The positivity rate in 626 HCWs with no identifiable risk factors and no self-reported history of positive LTBI tests was 2.1% (CI, 1.0 to 3.2) and 3.0% (CI, 1.7 to 4.3) with QFT and QFT-Plus, respectively. A conservative definition of a QFT-Plus-positive result yielded a positivity rate of 1.0% (CI, 0.2 to 1.7; value of 0.0002 versus QFT-Plus and 0.07 versus QFT). On follow-up testing, of 11 HCWs with discordant QFT-Plus results, 90.9% (10/11) had a negative QFT result. The QFT-Plus assay showed a high degree of agreement with QFT in U.S. HCWs. A conservative interpretation of QFT-Plus eliminated nearly all nonreproducible positive results in low-risk HCWs. Larger studies are needed to validate the latter finding and to more clearly define conditions under which a conservative interpretation can be used to minimize nonreproducible positive results in low-risk populations.