TY - JOUR
T1 - Relationship between molecular pathogen detection and clinical disease in febrile children across Europe
T2 - a multicentre, prospective observational study
AU - Shah, Priyen
AU - Voice, Marie
AU - The PERFORM consortium (Personalized Risk assessment in febrile children to optimize Real-life Management across the European Union)
AU - Calvo-Bado, Leonides
AU - Rivero-Calle, Irene
AU - Morris, Sophie
AU - Nijman, Ruud
AU - Broderick, Claire
AU - De, Tisham
AU - Eleftheriou, Irini
AU - Galassini, Rachel
AU - Khanijau, Aakash
AU - Kolberg, Laura
AU - Kolnik, Mojca
AU - Rudzate, Aleksandra
AU - Sagmeister, Manfred
AU - Schweintzger, Nina
AU - Secka, Fatou
AU - Thakker, Clare
AU - van der Velden, Fabian
AU - Vermont, Clementien
AU - Vincek, Katarina
AU - Agyeman, Philipp K.A.
AU - Cunnington, Aubrey J.
AU - De Groot, Ronald
AU - Emonts, Marieke
AU - Fidler, Katy
AU - Kuijpers, Taco
AU - Mommert-Tripon, Marine
AU - Brengel-Pesce, Karen
AU - Mallet, Francois
AU - Moll, Henriette
AU - Paulus, Stéphane
AU - Pokorn, Marko
AU - Pollard, Andrew
AU - van der Flier, Michiel
AU - Borensztajn, Dorine M.
AU - Hagedoorn, Nienke N.
AU - Zachariasse, Joany
AU - Dik, W.
AU - Stocker, Martin
AU - Willems, Esther
AU - De Haan, L.
AU - Neeleman, C.
AU - Tramper-Stranders, G. A.
AU - Baas, Bryan
AU - Kloosterhuis, Lieke
AU - Oosthoek, Wilma
AU - De Vries, Gabriella
AU - van den Berg, J. M.
AU - Barendregt, A. M.
N1 - Acknowledgements
We are grateful to all patients and families that contributed towards this
study. This project received funding under the European Union’s Horizon 2020 Research and Innovation program under grant agreement
number 668303. PERFORM consortium activities included obtaining
study funding, patient recruitment, clinical data collection and entry,
assignment of patient phenotypes, processing and storage of research
samples used in this analysis, and molecular pathogen testing.
Publisher Copyright: © 2023 The Authors
PY - 2023/9
Y1 - 2023/9
N2 - Background: The PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice. Methods: Febrile children and controls were recruited on presentation to hospital in 9 European countries 2016–2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed. Findings: Of 4611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3477 (75%) had uncertain aetiology. 1061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N. meningitidis (OR: 3.37, 95% CI: 1.92–5.99), S. pneumoniae (OR: 3.89, 95% CI: 2.07–7.59), Group A streptococcus (OR 2.73, 95% CI 1.13–6.09) and E. coli (OR 2.7, 95% CI 1.02–6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11–0.46), influenza B (OR 0.12, 95% CI 0.02–0.37) and RSV (OR 0.16, 95% CI: 0.06–0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23–0.72) and EBV (OR 0.71, 95% CI 0.56–0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively. Interpretation: Most febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics. Funding: EU Horizon 2020 grant 668303.
AB - Background: The PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice. Methods: Febrile children and controls were recruited on presentation to hospital in 9 European countries 2016–2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed. Findings: Of 4611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3477 (75%) had uncertain aetiology. 1061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N. meningitidis (OR: 3.37, 95% CI: 1.92–5.99), S. pneumoniae (OR: 3.89, 95% CI: 2.07–7.59), Group A streptococcus (OR 2.73, 95% CI 1.13–6.09) and E. coli (OR 2.7, 95% CI 1.02–6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11–0.46), influenza B (OR 0.12, 95% CI 0.02–0.37) and RSV (OR 0.16, 95% CI: 0.06–0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23–0.72) and EBV (OR 0.71, 95% CI 0.56–0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively. Interpretation: Most febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics. Funding: EU Horizon 2020 grant 668303.
UR - http://www.scopus.com/inward/record.url?scp=85165624641&partnerID=8YFLogxK
U2 - 10.1016/j.lanepe.2023.100682
DO - 10.1016/j.lanepe.2023.100682
M3 - Article
C2 - 37554664
AN - SCOPUS:85165624641
SN - 2666-7762
VL - 32
JO - The Lancet Regional Health - Europe
JF - The Lancet Regional Health - Europe
M1 - 100682
ER -
