Performance of QuantiFERON-TB Gold Plus assays in paediatric tuberculosis: a multicentre PTBNET study

Abstract

RationaleIn 2016, a new interferon-gamma release assay (IGRA) was introduced, QuantiFERON-TB Gold Plus (QFT-Plus), claimed to have improved sensitivity in active tuberculosis (TB).ObjectivesThis study aimed to determine the performance of QFT-Plus, compared with previous generation IGRAs and the tuberculin skin test (TST), in children with TB in Europe.MethodsMulticentre, ambispective cohort study within the Paediatric Tuberculosis Network European Trials Group (ptbnet), a dedicated paediatric TB research network comprising >300 members, capturing TB cases <18 years-of-age diagnosed between January 2009 and December 2019.Measurements and main results1001 TB cases from 16 countries were included (mean age (IQR) 5.6 (2.4–12.1) years). QFT-Plus was performed in 358, QFT Gold in-Tube (QFT-GIT) in 600, T-SPOT.TBin 58 and TST in 636 cases. The overall test sensitivities were: QFT-Plus 83.8% (95% CI 80.2% to 87.8%), QFT-GIT 85.5% (95% CI 82.7% to 88.3%), T-SPOT.TB77.6% (95% CI 66.9% to 88.3%) and TST (cut-off ≥10 mm) 83.3% (95% CI 83.3% to 86.2%). There was a trend for tests to have lower sensitivity in patients with miliary and/or central nervous system (CNS) TB (73.1%, 70.9%, 63.6% and 43.5%, respectively), and in immunocompromised patients (75.0%, 59.6%, 45.5% and 59.1%, respectively).ConclusionsThe results indicate that the latest generation IGRA assay, QFT-Plus, does not perform better than previous generation IGRAs or the TST in children with TB disease. Overall, tests performed worse in CNS and miliary TB, and in immunocompromised children. None of the tests evaluated had sufficiently high sensitivity to be used as a rule-out test in children with suspected TB.

Tuberculosis Case Detection and Guideline Adherence among Child Contacts in Switzerland: A Retrospective Observational Study

“…Half of the children 5–11 years of age and the majority of children 12–16 years of age were tested with an IGRA. IGRA is considered more specific in children with previous BCG immunisation but sensitivity is comparable as shown in a recent multicentre study from Europe [19]. As known from other Swiss studies, most of the children with TB disease in Switzerland are of foreign origin [8] and many of them have been vaccinated with Bacillus Calmette-Guérin, which is associated with the risk of a false-positive TST [20].…”

QuantiFERON-TB Gold Plus Performance in Children: A Narrative Review

“…This study reported that QFT-Plus did not have improved sensitivity compared with QFT-GIT in the overall population or in children less than 1 year of age but did have improved sensitivity in immunocompromised children (75.0% vs. 59.6%, respectively). 40 Further evidence is needed to better define the sensitivity of QFT-Plus versus QFT-GIT in different pediatric populations.…”

IP-10 for the diagnosis and treatment monitoring of tuberculosis in children.

“…Neither test discriminates ATB from LTBI, nor are they licensed for ATB diagnosis. Yet, they are widely used to facilitate the diagnosis of ATB with sensitivity reaching 77-85% 10 . The new version of QFT test, QuantiFERON-TB Gold Plus, has so far exhibited similar properties to previous-generation IGRAs in children in both ATB and LTBI 10 .…”