Introduction The QuantiFERON-TB Gold Plus (QFT-Plus) assay, which features two antigen-stimulated tubes (TB1 and TB2) instead of a single tube used in previous-generation interferon-gamma release assays (IGRAs), was launched in 2016. Despite this, data regarding the assay’s performance in the paediatric setting remain scarce. This study aimed to determine the performance of QFT-Plus in a large cohort of children and adolescents at risk of tuberculosis (TB) in a low-burden setting.
Methods Cross-sectional, multicentre study at healthcare institutions participating in the Spanish Paediatric TB Research Network, including patients <18 years who had a QFT-Plus performed between September 2016 and June 2020.
Results Of 1726 patients (52.8% male, median age: 8.4 years), 260 (15.1%) underwent testing during contact tracing, 288 (16.7%) on clinical/radiological suspicion of tuberculosis disease (TBD), 649 (37.6%) during new-entrant migrant screening and 529 (30.6%) prior to initiation of immunosuppressive treatment. Overall, the sensitivity of QFT-Plus for TBD (n=189) and for latent tuberculosis infection (LTBI, n=195) was 83.6% and 68.2%, respectively. The agreement between QFT-Plus TB1 and TB2 antigen tubes was excellent (98.9%, κ=0.961). Only five (2.5%) patients with TBD had discordance between TB1 and TB2 results (TB1+/TB2−, n=2; TB1−/TB2+, n=3). Indeterminate assay results (n=54, 3.1%) were associated with young age, lymphopenia and elevated C reactive protein concentrations.
Conclusions Our non-comparative study indicates that QFT-Plus does not have greater sensitivity than previous-generation IGRAs in children in both TBD and LTBI. In TBD, the addition of the second antigen tube, TB2, does not enhance the assay’s performance substantially.
Data availability statement
Data are available upon reasonable request. Data are available upon reasonable request to the corresponding author.
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MT and AN-J are joint senior authors.
Collaborators On behalf of the QFT-Plus Study Group of the Spanish Pediatric TB Research Network (pTBred; see online supplemental appendix 1).
Contributors TP-P, AS-A, AN-J and MT conceived the original idea and supervised the development of the project. AS-G, AG, TP-P, AS-A, BS, MJR-S, JJKM, MB-A, MIG-L, PR-M, AIP, AT and AN-J collaborated on the enrolment of patients and the clinical interpretation of individual results. MM and TT supervised the development of the immunological experiments. AS-G, AG, MT and AN-J performed the analysis of the data and designed the figures. AS-G and AG wrote the first draft of the manuscript, with support from AN-J and MT. All authors discussed the results and commented on and approved the final version of the manuscript.
AN-J accepts full responsibility for the work and the conduct of the study, had access to the data, and controlled the decision to publish.
Funding This work was partially supported by a research grant from the Carlos III Institute of Health, Ministry of Economy and Competitiveness (Spain), reference PI16/00314, and by the Spanish Society of Pneumology and Thoracic Surgery, grant number 90/2015. Tomàs PÉREZ-PORCUNA and Antoni NOGUERA-JULIAN were supported by “Subvencions per a la Intensificació de Facultatius Especialistes” (Departament de Salut de la Generalitat de Catalunya, Programa PERIS 2016–2020) [SLT006/17/00144 and SLT008/18/00193, respectively].
Competing interests MT has received QuantiFERON assays at reduced pricing or free of charge for tuberculosis diagnostics projects from the manufacturer (Cellestis/Qiagen) in the past and has received support for conference attendance from Cepheid. The manufacturers had no influence on the study design, data collection, analysis or interpretation, writing of the manuscript or decision to submit the data for publication.
Provenance and peer review Not commissioned; externally peer reviewed.
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