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

Authors :
Priyen Shah
Marie Voice
Leonides Calvo-Bado
Irene Rivero-Calle
Sophie Morris
Ruud Nijman
Claire Broderick
Tisham De
Irini Eleftheriou
Rachel Galassini
Aakash Khanijau
Laura Kolberg
Mojca Kolnik
Aleksandra Rudzate
Manfred G. Sagmeister
Nina A. Schweintzger
Fatou Secka
Clare Thakker
Fabian van der Velden
Clementien Vermont
Katarina Vincek
Philipp K.A. Agyeman
Aubrey J. Cunnington
Ronald De Groot
Marieke Emonts
Katy Fidler
Taco W. Kuijpers
Marine Mommert-Tripon
Karen Brengel-Pesce
Francois Mallet
Henriette Moll
Stéphane Paulus
Marko Pokorn
Andrew Pollard
Luregn J. Schlapbach
Ching-Fen Shen
Maria Tsolia
Effua Usuf
Michiel van der Flier
Ulrich von Both
Shunmay Yeung
Dace Zavadska
Werner Zenz
Victoria Wright
Enitan D. Carrol
Myrsini Kaforou
Federico Martinon-Torres
Colin Fink
Michael Levin
Jethro Herberg
Irene Rivero Calle
Manfred Sagmeister
Nina Schweintzger
Fabian Van der Velden
Taco Kuijpers
Michiel Van der Flier
Ulrich Von Both
Lucas Baumard
Evangelos Bellos
Lachlan Coin
Giselle D'Souza
Dominic Habgood-Coote
Shea Hamilton
Cllive Hoggart
Sara Hourmat
Heather Jackson
Naomi Lin
Stephanie Menikou
Samuel Nichols
Ivonne Pena Paz
Oliver Powell
Ortensia Vito
Clare Wilson
Amina Abdulla
Ladan Ali
Sarah Darnell
Rikke Jorgensen
Ian Maconochie
Sobia Mustafa
Salina Persand
Ben Walsh
Molly Stevens
Nayoung Kim
Eunjung Kim
Benjamin Pierce
Julia Dudley
Vivien Richmond
Emma Tavliavini
Ching-Chuan Liu
Shih-Min Wang
Fernando Álves González
Cristina Balo Farto
Ruth Barral-Arca
María Barreiro Castro
Xabier Bello
Mirian Ben García
Sandra Carnota
Miriam Cebey-López
María José Curras-Tuala
Carlos Durán Suárez
Luisa García Vicente
Alberto Gómez-Carballa
Jose Gómez Rial
Pilar Leboráns Iglesias
Nazareth Martinón-Torres
José María Martinón Sánchez
Belén Mosquera Pérez
Jacobo Pardo-Seco
Lidia Piñeiro Rodríguez
Sara Pischedda
Sara Ray Vázquez
Carmen Rodríguez-Tenreiro
Lorenzo Redondo-Collazo
Miguel Sadiki Ora
Antonio Sallas
Sonia Serén Fernández
Cristina Serén Trasorras
Marisol Vilas Iglesias
Anda Balode
Arta Bãrdzdina
Dãrta Deksne
Dace Gardovska
Dagne Grãvele
Ilze Grope
Anija Meiere
Ieve Nokalna
Jana Pavãre
Zanda Pučuka
Katrīna Selecka
Dace Svile
Urzula Nora Urbãne
Kalifa Bojang
Syed M.A. Zaman
Suzanne Anderson
Anna Roca
Isatou Sarr
Momodou Saidykhan
Saffiatou Darboe
Samba Ceesay
Umberto D'alessandro
Dorine M. Borensztajn
Nienke N. Hagedoorn
Chantal Tal
Joany Zachariasse
W. Dik
Christoph Aebi
Christoph Berger
Verena Wyss
Mariama Usman
Eric Giannoni
Martin Stocker
Klara M. Posfay-Barbe
Ulrich Heininger
Sara Bernhard-Stirnemann
Anita Niederer-Loher
Christian Kahlert
Giancarlo Natalucci
Christa Relly
Thomas Riedel
Elizabeth Cocklin
Rebecca Jennings
Joanne Johnson
Simon Leigh
Karen Newall
Sam Romaine
Maria Tambouratzi
Antonis Marmarinos
Marietta Xagorari
Kelly Syggelou
Nikos Spyridis
Jennifer Blackmore
Rebekah Harrison
Benno Kohlmaier
Daniela S. Kohlfürst
Christoph Zurl
Alexander Binder
Susanne Hösele
Manuel Leitner
Lena Pölz
Glorija Rajic
Sebastian Bauchinger
Hinrich Baumgart
Martin Benesch
Astrid Ceolotto
Ernst Eber
Siegfried Gallisti
Gunther Gores
Harald Haidl
Almuthe Hauer
Christa Hude
Markus Keldorfer
Larissa Krenn
Heidemarie Pilch
Andreas Pfleger
Klaus Pfurtscheller
Gudrun Nordberg
Tobias Niedrist
Siegfried Rödl
Andrea Skrabl-Baumgartner
Matthias Sperl
Laura Stampfer
Volker Strenger
Holger Till
Andreas Trobisch
Sabine Löffler
Juan Emmanuel Dewez
Martin Hibberd
David Bath
Alec Miners
Elizabeth Fitchett
Catherine Wedderburn
Anne Meierford
Baptiste Leurent
Marien I. De Jonge
Koen van Aerde
Wynand Alkema
Bryan van den Broek
Jolein Gloerich
Alain J. Van Gool
Stefanie Henriet
Martijn Huijnen
Ria Philipsen
Esther Willems
G.P.J.M. Gerrits
M. Van Leur
J. Heidema
L. De Haan
C.J. Miedema
C. Neeleman
C.C. Obihara
G.A. Tramper-Stranders
Rama Kandasamy
Michael J. Carter
Daniel O'Connor
Sagida Bibi
Dominic F. Kelly
Meeru Gurung
Stephen Throson
Imran Ansari
David R. Murdoch
Shrijana Shrestha
Zoe Oliver
Emma Lim
Lucille Valentine
Karen Allen
Kathryn Bell
Adora Chan
Stephen Crulley
Kirsty Devine
Daniel Fabian
Sharon King
Paul McAlinden
Sam McDonald
Anne McDonell
Alisa Pickering
Evelyn Thomson
Amanda Wood
Diane Wallia
Phil Woodsford
Frances Baxter
Ashley Bell
Mathew Rhodes
Rachel Agbeko
Christine Mackerness
Bryan Baas
Lieke Kloosterhuis
Wilma Oosthoek
Tasnim Arif
Joshua Bennet
Kalvin Collings
Ilona Van der Giessen
Alex Martin
Aqeela Rashid
Emily Rowlands
Joshua Soon
Gabriella De Vries
Mike Martin
Ravi Mistry
Manuela Zwerenz
Judith Buschbeck
Christoph Bidlingmaier
Vera Binder
Katharina Danhauser
Nikolaus Haas
Matthias Griese
Matthias Kappler
Eberhard Lurz
Georg Muench
Karl Reiter
Carola Schoen
Alexandre Pachot
Marine Mommert
Tina Plankar Srovin
Natalija Bahovec
Petra Prunk
Veronika Osterman
Tanja Avramoska
Ilse Jongerius
J.M. van den Berg
D. Schonenberg
A.M. Barendregt
D. Pajkrt
M. van der Kuip
A.M. van Furth
Evelien Sprenkeler
Judith Zandstra
G. van Mierlo
J. Geissler
Source :
The Lancet Regional Health. Europe, Vol 32, Iss , Pp 100682- (2023)
Publication Year :
2023
Publisher :
Elsevier, 2023.

Abstract

Summary: 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.

Details

Language :
English
ISSN :
26667762
Volume :
32
Issue :
100682-
Database :
Directory of Open Access Journals
Journal :
The Lancet Regional Health. Europe
Publication Type :
Academic Journal
Accession number :
edsdoj.385b84aa34944e70970397e2518aaf4f
Document Type :
article
Full Text :
https://doi.org/10.1016/j.lanepe.2023.100682