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Performance of QuantiFERON-TB Gold Plus assays in children and adolescents at risk of tuberculosis: a cross-sectional multicentre study
  1. Aleix Soler-Garcia1,
  2. Anna Gamell1,
  3. Tomàs Pérez-Porcuna2,3,
  4. Antonio Soriano-Arandes4,
  5. Begoña Santiago5,
  6. Teresa Tórtola6,
  7. María Jesús Ruiz-Serrano7,
  8. José Javier Korta Murua8,9,
  9. Matilde Bustillo-Alonso10,
  10. María Isabel Garrote-Llanos11,
  11. Paula Rodríguez-Molino12,
  12. Ana Isabel Piqueras13,
  13. Alfredo Tagarro14,15,16,
  14. Manuel Monsonís17,
  15. Marc Tebruegge18,19,
  16. Antoni Noguera-Julian1,16,20,21
  17. On behalf of the QFT-Plus Study Group of the Spanish Pediatric TB Research Network
  1. 1Malalties Infeccioses i Resposta Inflamatòria Sistèmica en Pediatria, Unitat d'Infeccions, Servei de Pediatria, Institut de Recerca Pediàtrica, Hospital Sant Joan de Déu, Barcelona, Spain
  2. 2Atenció Primària, Fundació Assistencial Mútua de Terrassa, Terrassa, Spain
  3. 3Unitat de Salut Internacional, Departament de Pediatria, Fundació Recerca Hospital Universitari Mútua de Terassa, Universitat de Barcelona, Terrassa, Spain
  4. 4Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Vall d'Hebron, Barcelona, Spain
  5. 5Paediatric Infectious Diseases Unit, Gregorio Marañón Mother and Child Hospital, Madrid, Spain
  6. 6Unitat de Micobactèries, Laboratori Supranacional de Referència de l'OMS per a la Tuberculosi, Hospital Vall d'Hebron, Barcelona, Spain
  7. 7Clinical Microbiology and Infectious Diseases Department, Gregorio Marañón Mother and Child Hospital, Madrid, Spain
  8. 8Servicio de Pediatría, Hospital Universitario Donostia-Instituto BioDonostia, Donostia Ospitalea, San Sebastian, Spain
  9. 9Departamento de Pediatría, Facultad de Medicina, EHU-UPV, Donostia University Hospital Gipuzkoa Building, San Sebastian, Spain
  10. 10Pediatrics Department, Miguel Servet University Hospital, Zaragoza, Spain
  11. 11Pediatric Infectious Diseases Unit, Department of Pediatrics, Hospital de Basurto, Basurto, Spain
  12. 12Pediatric Infectious and Tropical Diseases Department, Hospital Universitario La Paz, Madrid, Spain
  13. 13Pediatric Infectious Diseases Unit, Hospital Universitario y Politécnico La Fe, Hospital La Fe, Valencia, Spain
  14. 14Servicio de Pediatría, Hospital Universitario Infanta Sofía, San Sebastian de los Reyes, Spain
  15. 15Fundación para la Investigación Biomédica del Hospital 12 de Octubre, Universidad Europea de Madrid, Hospital Universitario 12 de Octubre, Madrid, Spain
  16. 16Red de Investigación Translacional en Infectología Pediátrica, RITIP, Madrid, Spain
  17. 17Servei de Microbiologia, Hospital Sant Joan de Déu, Barcelona, Spain
  18. 18Department of Pediatrics, University of Melbourne, Parkville, Victoria, Australia
  19. 19Department of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, University College London, London, UK
  20. 20CIBERESP, Madrid, Spain
  21. 21Departament de Pediatria, Universitat de Barcelona Facultat de Medicina, Barcelona, Spain
  1. Correspondence to Dr Antoni Noguera-Julian, Malalties Infeccioses i Resposta Inflamatòria Sistèmica en Pediatria, Unitat d'Infeccions, Servei de Pediatria, Institut de Recerca Pediàtrica, Hospital Sant Joan de Déu, 08950 Barcelona, Spain; ton{at}sjdhospitalbarcelona.org

Abstract

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.

  • tuberculosis

Data availability statement

Data are available upon reasonable request. Data are available upon reasonable request to the corresponding author.

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Data availability statement

Data are available upon reasonable request. Data are available upon reasonable request to the corresponding author.

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Footnotes

  • 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.