QFT-Plus: a plus in variability? – Evaluation of new generation IGRA in serial testing of students with a migration background in Germany

Abstract

BackgroundCurrently available Interferon-gamma release assays (IGRAs) show a considerable variability in serial testing for latent tuberculosis infection (LTBI).This study offers first results for the new generation IGRA QuantiFERON-TB Gold Plus (QFT-Plus) introduced in 2015 in comparison with its predecessor QuantiFERON-TB Gold In-Tube (QFT-GIT) from serial testing of students with a migration background at German universities.MethodsForty-one students were selected from a previous study. All students with a positive IGRA were asked and 11 agreed to participate in this cohort study. Additionally 30 students with negative IGRA results were selected by chance. Weekly testing with QFT-Plus and QFT-GIT was performed in all individuals over a 4-week period. IGRA variability was evaluated by calculating conversion and reversion rates.ResultsFrom 41 participants a total number of 163 serial measurements were analyzed for each IGRA, leading to 122 possible IGRA changes each. QFT-Plus had four conversions and two reversions leading to a conversion rate of 4.3% (4 of 93 possible conversions, 95% CI 1.4–11.3%) and reversion rate of 6.9% (2 of 29 possible reversions, 95% CI 1.2–24.2%). QFT-GIT had 2 conversions and 1 reversion causing slightly lower rates with 2.2% conversions (2 of 91, 95% CI 0.4–8.5%) and 3.2% reversions (1 of 31, 95% CI 0.2–18.5%). Inconsistent IGRA results occurred in 4 subjects for QFT-Plus (8 stable positives, 29 stable negatives) and in 2 subjects for QFT-GIT (9 stable positives, 30 stable negatives). Agreement between the two IGRAs was 95.1% (κ = 0.89). Variance attributed to the individuals was low (QFT-Plus: ICC = 0.88).ConclusionThis study confirms occurrence of conversions and reversions for the new QFT-Plus in serial testing of a high-risk cohort in a low-incidence setting with improbable new TB contact during the study. QFT-Plus conversion and reversion rates were slightly higher than for the QFT-GIT but overall they were lower for both IGRAs than in other studies that investigated IGRA variability.Electronic supplementary materialThe online version of this article (doi:10.1186/s12995-016-0148-z) contains supplementary material, which is available to authorized users.

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

“…They suggested that the conversion and reversion rates for QFT-Plus were slightly higher than those for QFT-GIT, but the increase in variability was not significant due to the high rate of agreement between QFT-GIT and QFT-Plus (40). Based on the results reported by Knierer et al (40) and our studies, the assay variability of QFT-Plus near the cutoff level remained the same as that with QFT-GIT. Currently, the QFT-Plus results are interpreted by applying the same cutoff applied to QFT-GIT and are based on the positivity of either TB1 or TB2; however, more data are needed to validate the interpretation criteria in different cohorts with different risks of M. tuberculosis infection or different clinical conditions.…”

“…Knierer et al confirmed the occurrence of conversions and reversions for QFT-Plus in serial testing of a high-risk cohort in a low-incidence setting (40). They suggested that the conversion and reversion rates for QFT-Plus were slightly higher than those for QFT-GIT, but the increase in variability was not significant due to the high rate of agreement between QFT-GIT and QFT-Plus (40). Based on the results reported by Knierer et al (40) and our studies, the assay variability of QFT-Plus near the cutoff level remained the same as that with QFT-GIT.…”

“…Except for one patient who showed conversion in both tests, probably due to the effect of G-CSF in the first test (39), there were no significant factors affecting the M. tuberculosis risk identified in the other two patients, who showed conversion in each QFT-GIT and QFT-Plus assay. Knierer et al confirmed the occurrence of conversions and reversions for QFT-Plus in serial testing of a high-risk cohort in a low-incidence setting (40). They suggested that the conversion and reversion rates for QFT-Plus were slightly higher than those for QFT-GIT, but the increase in variability was not significant due to the high rate of agreement between QFT-GIT and QFT-Plus (40).…”

Prevalence of latent tuberculosis infection among foreign students in Lübeck, Germany tested with QuantiFERON-TB Gold In-Tube and QuantiFERON-TB Gold Plus

“…Repetition of the IGRA was performed one week after the first positive test was performed in the scope of a four week variability study. Results of this study are reported else were [14]. Participants who had had prior contact with a person with active TB during the last 2 years were offered specialist advice.…”

QuantiFERON-TB Gold Plus Is a More Sensitive Screening Tool than QuantiFERON-TB Gold In-Tube for Latent Tuberculosis Infection among Older Adults in Long-Term Care Facilities

“…Furthermore, positive TB2 test results significantly increased the sensitivity of QFT-Plus, from 86.4% to 100.0% (P ϭ 0.004), leading to a higher overall sensitivity than that of QFT-GIT (100.0% versus 89.4%, respectively, P ϭ 0.003). Previous studies have found that IGRAs tend to have a high variability with high rates of conversions and reversions in serial testing (26). The elevated test variability leads to uncertainty over whether the positive result is "transient" or "stable," with treatment being beneficial to those subjects with transient-positive QFTs.…”