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

Abstract

Although launched in 2015, little is known about the accuracy of QuantiFERON-TB Gold-Plus (QFT-Plus) for diagnosis of latent M. tuberculosis infection (LTBI). Unlike its predecessor, QFT-Plus utilizes two antigen tubes to elicit an immune response from CD4 ϩ and CD8 ϩ T lymphocytes. We conducted a crosssectional 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; P 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.

Comparative Evaluation of QuantiFERON-TB Gold In-Tube and QuantiFERON-TB Gold Plus in Diagnosis of Latent Tuberculosis Infection in Immunocompromised Patients

“…Thus, the discrepancy between QFT-GIT and QFT-Plus might be affected not only by the differences in the antigenic stimulants (the absence of TB7.7 in the TB1 tube and addition of the TB2 tube) but also by the populations examined and the underlying conditions of the patients as well. However, as observed in previous IGRA studies (9,24,25,32), most of the discordant results (77.8%) were scattered within IFN-␥ levels of 0.30 to 1.00 IU/ml, which cross the assay cutoff ( Fig. 1).…”

“…Yi et al reported sensitivities of 98.6% and 97.6% for QFT-GIT and QFT-Plus, respectively, for the diagnosis of active tuberculosis in a Japanese population (26). In particular, the higher positivity rate with QFT-Plus in the study conducted by Moon et al was due to more frequent positive results with TB2 than TB1 (24). In this study, we observed a higher positivity rate with QFT-GIT (29.0%) than with QFT-Plus (27.8%), although we observed more TB1 Ϫ TB2 ϩ results with QFT-Plus.…”

“…However, among the three patient groups, the SOT group showed the lowest degree of agreement between the two assays (90.5%; value, 0.808), followed by the HSCT group (97.1%; value, 0.919) and the TNF-␣ inhibitor therapy group (97.7%; value, 0.939). In recent comparative studies, Moon et al reported that low-risk health care workers in the United States showed 2.1% and 3.0% positivity rates by QFT-GIT and QFT-Plus, respectively (24). Hoffman et al reported 94.5% agreement between the two assays within various populations, including health care workers and patients with suspicion of active tuberculosis in a German hospital (25).…”

“…TB1 contains the long peptides of ESAT-6 and CFP-10 but not TB7.7, while TB2 contains six short peptides, in addition to same components in TB1, thus inducing both CD4 ϩ and CD8 ϩ T-cell immune responses (23). There have been recent reports on the performance of the QFT-Plus assay in the diagnosis of active tuberculosis in high-risk patients and LTBI in low-risk populations (24)(25)(26); however, the performance evaluation of the QFT-Plus assay in immunocompromised patients has rarely been reported. The Republic of Korea is a country with an intermediate M. tuberculosis burden, and BCG vaccination is mandatory at birth.…”

Higher Positivity Rate with Fourth-Generation QuantiFERON-TB Gold Plus Assay in Low-Risk U.S. Health Care Workers

“…The QFT-Plus assay was introduced on the IGRA market with the touted advantage of better sensitivity than its predecessor in immunocompromised hosts and after recent exposure. However, studies that have compared the QFT-Plus assay to the QFT assay have shown similar sensitivity in patients with active TB and similar test performance in HCW (1,5). As reported here, similarly to the implementation of the original QFT (3), we are seeing an increase in nonreproducible positive results in low-risk serially tested HCW (Fig.…”