Rationale In 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).
Objectives This 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.
Methods Multicentre, 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 results 1001 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.TB in 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.TB 77.6% (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).
Conclusions The 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.
Data availability statement
Data are available on reasonable request.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.
DB and AN-J are joint first authors.
Twitter @surf4children, @tonisoriano66
Correction notice This article has been corrected since it was published Online First. Changes have been made to some affiliations and the funding statement. Minor changes have also been applied to the tables and text.
Collaborators Laura Minguell (Hospital Universitari Arnau de Vilanova. Lleida, Spain), Estrella Peromingo (Department of Paediatrics, Hospital Universitario Puerta del Mar, Cádiz, Spain), David Gomez Pastrana (Department of Paediatrics, Hospital Universitario de Jerez, Jerez de la Frontera, Spain), Tomas Pérez-Porcuna (Unitat de Salut Internacional, Departament de Pediatria, Fundació Recerca Mútua Terrassa, Atenció Primària, Hospital Universitari Mútua de Terrassa, Universitat de Barcelona, Terrassa, Spain), Beatriz Soto (Hospital Universitario de Getafe, Madrid, Spain), Elena Colino Gil (Department of Paediatrics, Complejo Hospitalario Universitario Insular Materno—Infantil de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain), Mercedes Herranz-Aguirre (Sección de Enfermedades Infecciosas Pediátricas, Servicio de Pediatría, Complejo Hospitalario de Navarra, Pamplona, Spain), Cesar Gavilan Martin (Servicio de Pediatría, Hospital Universitario San Juan de Alicante, Spain), Eva María López-Medina (Pediatric infectious Disease Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain), Christine Bell (Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK), Frances Child (Royal Manchester Children’s Hospital, UK), Inga Ivaškevičienė (Clinic of Children’s Diseases, Institute of Clinical Medicine, Vilnius University, Vilnius, Lithuania), Zulema Lobato (Department of Paediatrics, Hospital Sant Joan de Déu—Fundació Althaia, Manresa, Spain), Neus Rius (Hospital Universitari Sant Joan de Reus, Spain), Olga Calavia (Department of Paediatrics, Hospital Joan XXIII, Tarragona, Spain), Daniel Blázquez-Gamero (Pediatric Infectious Diseases Unit, Hospital Universitario 12 de Octubre, Madrid, Spain), Begoña Carazo (Pediatric Infectious Diseases Unit, Pediatrics Department, Hospital Materno Infantil de Málaga, Málaga, Spain), Maria Queralt Soler Campins (Department of Paediatrics, Consorci Sanitari de Terrassa, Terrassa, Spain), Cristina Calvo (Pediatric and Infectious Diseases Department Hospital Universitario La Paz, Madrid, Spain), Javier Korta Murua (Department of Paediatrics, Hospital Universitario Donostia, San Sebastián, Spain), Charlotte Buxbaum (Astrid Lindgren Children’s Hospital, Karolinska University Hospital Huddinge, Stockholm, Sweden), Ivan Pavić (Department of Paediatric Allergology, Pulmonology, Rheumatology and Clinical Immunology, Children’s Hospital Zagreb, Zagreb, Croatia), Cristina Alvarez (Department of Paediatrics, Hospital Universitario Marqués de Valdecillas, Santander, Spain), Elvira Cobo-Vazquez (Hospital Universitario Fundación de Alcorcón, Madrid, Spain), Beatriz Perez Gorricho (Pediatric Infectious Diseases Unit, Department of Pediatrics, Hospital Infantil Universitario Niño Jesús, Madrid, Spain), Sonia Rodriguez (Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Spain), Ana Menasalvas (Department of Paediatrics, Hospital Virgen de la Arrixaca, Murcia, Spain), Maria Isabel Garrote Llanos (Pediatric Infectious Diseases Department, Hospital Universitario de Basurto, Bilbao, Spain), Sara Berhard-Stirnemann (Department of Paediatrics, Cantonal Hospital Aarau Children’s Hospital, Aarau, Switzerland), Marie Rohr (Department of Paediatrics, Hôpitaux Universitaires de Genève, Geneva, Switzerland), Christa Relly (Division of Infectious Diseases and Hospital Epidemiology, University Children’s Hospital Zurich, Zurich, Switzerland), Lourdes Garcia Rodriguez (Pediatria, Hospital de Mataró—Consorci Sanitari del Maresme, Barcelona, Spain), Maria del Pozo (Pediatrics Department, Hospital General Universitario de Albacete, Albacete, Spain), Irene Rivero-Calle (Translational Pediatrics and Infectious Diseases Section, Hospital Clínico Universitario de Santiago de Compostela, Spain), Alfredo Tagarro (Pediatrics Department, Hospital Universitario Infanta Sofía, San Sebastián de los Reyes, Madrid, Spain), Andrea Duppenthaler (Department of Paediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland), Isabelle Rochat Guignard (Service of Paediatrics, Department of Woman, Mother, Child, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland), Michael Buettcher (Paediatric Infectious Diseases, Department of Paediatrics, Lucerne Children’s Hospital, Switzerland), Elizabeth Whittaker (Section of Paediatric Infectious Diseases, Imperial College, London, UK), Paddy McMaster (Department of Paediatric Infectious Diseases, Northern Care Alliance NHS Group, Manchester, UK), Verdiana Vigliano (Catholic University of Rome, Italy), Cristina Russo (Bambino Gesù Children Hospital, Rome, Italy).
Contributors DB, MT, BS-G, AN-J conceptualised the study, wrote the first draft and the last version of the manuscript. All authors contributed to methodology, data collection, revision of initial draft and final version of the manuscript. MT and BS-G are joint last authors. DB is the author acting as guarantor.
Funding AN-J was supported by “Subvencions per a la Intensificació de Facultatius Especialistes” (Departament de Salut de la Generalitat de Catalunya, Programa PERIS 2016-2020) [SLT008/18/00193]. AHL is funded by the Spanish Ministry of Science and Innovation—Instituto de Salud Carlos III and Fondos FEDER (Contrato Río Hortega CM20/00128).
Competing interests DB participated in a Qiagen advisory board meeting on the use of IGRAs in children <5 years of age. The manufacturers had no influence on the study design, data collection, analysis or interpretation, writing of the manuscript or the decision to submit the data for publication. BS-G and MT have received support from Cepheid for a project on molecular TB diagnostics unrelated to the study reported here. MT has received QuantiFERON-TB assays at reduced pricing or free of charge for TB diagnostics projects from the manufacturer (Cellestis/Qiagen) in the past, and has received support for conference attendance from Cepheid.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.