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Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study

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Title: Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study
Authors: Herberg, J
Shah, P
Voice, M
Calvo-Bado, L
Rivero Calle, I
Morris, S
Nijman, R
Broderick, C
De, T
Eleftheriou, I
Galassini, R
Khanijau, A
Kolberg, L
Kolnik, M
Rudzate, A
Sagmeister, M
Schweintzger, N
Secka, F
Thakker, C
Van der Velden, F
Vermont, C
Vincek, K
Agyeman, P
Cunnington, A
De Groot, R
Emonts, M
Fidler, K
Kuijpers, T
Mommert-Tripon, M
Brengel-Pesce, K
Mallet, F
Moll, H
Paulus, S
Pokorn, M
Pollard, A
Schlapbach, L
Shen, C-F
Tsolia, M
Usuf, E
Van Der Flier, M
Von Both, U
Yeung, S
Zavadska, D
Zenz, W
Wright, V
Carrol, E
Kaforou, M
Martinon-Torres, F
Fink, C
Levin, M
PERFORM consortium
Item Type: Journal Article
Abstract: 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 4,611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3,477 (75%) had uncertain aetiology. 1,061 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.
Issue Date: Sep-2023
Date of Acceptance: 28-Jun-2023
URI: http://hdl.handle.net/10044/1/105381
DOI: 10.1016/j.lanepe.2023.100682
ISSN: 2666-7762
Publisher: Elsevier
Start Page: 1
End Page: 17
Journal / Book Title: The Lancet Regional Health. Europe
Volume: 32
Copyright Statement: © 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Publication Status: Published
Article Number: 100682
Online Publication Date: 2023-07-26
Appears in Collections:Department of Infectious Diseases
Faculty of Medicine

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