Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study
Abstract
The PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice. 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. 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. 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. EU Horizon 2020 grant 668303.
Related
- DWI-FLAIR mismatch for the identification of patients with acute ischaemic stroke within 4·5 h of symptom onset (PRE-FLAIR): a multicentre observational study
- Nasopharyngeal metatranscriptome profiles of infants with bronchiolitis and risk of childhood asthma: a multicentre prospective study
- Prospective multicentre study evaluating ctDNA as a biomarker of residual disease after chemoradiotherapy for locally advanced head and neck squamous cell carcinoma: NeckTAR-IN protocol
- Plasma Dimethylarginine Concentrations in Dogs With Large Cell Lymphoma or Hemangiosarcoma: A Prospective Observational Study
- Safety of lecanemab in real-world patients with Alzheimer’s disease: a prospective, observational case series supported by FAERS signal analysis
BibTeX
@article{shah2026relationship,
title = {{Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study}},
author = {Priyen Shah and Marie Voice and Leonides Calvo-Bado and Irene Rivero-Calle and Sophie Morris and Ruud G Nijman and Claire Broderick and Tisham De and Irini Eleftheriou and Rachel Galassini and Aakash Khanijau and Laura Kolberg and Mojca Kolnik and Aleksandra Rudzate and Manfred Sagmeister and Nina Schweintzger and Fatou Secka and Clare Thakker and Fabian van der Velden and Clementien Vermont and Katarina Vincek and Philipp K.A. Agyeman and Aubrey Cunnington and Ronald de Groot and Marieke Emonts and Katy Fidler and Taco Kuijpers and Marine Mommert-Tripon and Karen Brengel-Pesce and Francois Mallet and Henriette Moll and Stéphane Paulus and Marko Pokorn and Andrew Pollard and Luregn Schlapbach and Ching-Fen Shen and Maria Tsolia and Effua Usuf and Michiel van der Flier and Ulrich von Both and Shunmay Yeung and Dace Zavadska and Werner Zenz and Victoria Wright and Enitan Carrol and Myrsini Kaforou and Federico Martinon-Torres and Colin Fink and Michael Levin and Jethro Herberg and Priyen Shah and Marie Voice and Leonides Calvo-Bado and Irene Rivero Calle and Sophie Morris and Ruud G Nijman and Claire Broderick and Tisham De and Irini Eleftheriou and Rachel Galassini},
journal = {The Lancet Regional Health - Europe},
year = {2026},
month = oct,
doi = {10.1016/j.lanepe.2023.100682},
url = {https://hal.science/hal-05793067v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study
AU - Priyen Shah
AU - Marie Voice
AU - Leonides Calvo-Bado
AU - Irene Rivero-Calle
AU - Sophie Morris
AU - Ruud G Nijman
AU - Claire Broderick
AU - Tisham De
AU - Irini Eleftheriou
AU - Rachel Galassini
AU - Aakash Khanijau
AU - Laura Kolberg
AU - Mojca Kolnik
AU - Aleksandra Rudzate
AU - Manfred Sagmeister
AU - Nina Schweintzger
AU - Fatou Secka
AU - Clare Thakker
AU - Fabian van der Velden
AU - Clementien Vermont
AU - Katarina Vincek
AU - Philipp K.A. Agyeman
AU - Aubrey Cunnington
AU - Ronald de Groot
AU - Marieke Emonts
AU - Katy Fidler
AU - Taco Kuijpers
AU - Marine Mommert-Tripon
AU - Karen Brengel-Pesce
AU - Francois Mallet
AU - Henriette Moll
AU - Stéphane Paulus
AU - Marko Pokorn
AU - Andrew Pollard
AU - Luregn Schlapbach
AU - Ching-Fen Shen
AU - Maria Tsolia
AU - Effua Usuf
AU - Michiel van der Flier
AU - Ulrich von Both
AU - Shunmay Yeung
AU - Dace Zavadska
AU - Werner Zenz
AU - Victoria Wright
AU - Enitan Carrol
AU - Myrsini Kaforou
AU - Federico Martinon-Torres
AU - Colin Fink
AU - Michael Levin
AU - Jethro Herberg
AU - Priyen Shah
AU - Marie Voice
AU - Leonides Calvo-Bado
AU - Irene Rivero Calle
AU - Sophie Morris
AU - Ruud G Nijman
AU - Claire Broderick
AU - Tisham De
AU - Irini Eleftheriou
AU - Rachel Galassini
PY - 2026
DA - 2026/10/11
JO - The Lancet Regional Health - Europe
DO - 10.1016/j.lanepe.2023.100682
UR - https://hal.science/hal-05793067v1
AB - The PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice. 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. 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. 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. EU Horizon 2020 grant 668303.
SN - 2666-7762
ER -