Titre
Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Shah, P.
Auteure/Auteur
Voice, M.
Auteure/Auteur
Calvo-Bado, L.
Auteure/Auteur
Rivero-Calle, I.
Auteure/Auteur
Morris, S.
Auteure/Auteur
Nijman, R.
Auteure/Auteur
Broderick, C.
Auteure/Auteur
De, T.
Auteure/Auteur
Eleftheriou, I.
Auteure/Auteur
Galassini, R.
Auteure/Auteur
Khanijau, A.
Auteure/Auteur
Kolberg, L.
Auteure/Auteur
Kolnik, M.
Auteure/Auteur
Rudzate, A.
Auteure/Auteur
Sagmeister, M.G.
Auteure/Auteur
Schweintzger, N.A.
Auteure/Auteur
Secka, F.
Auteure/Auteur
Thakker, C.
Auteure/Auteur
van der Velden, F.
Auteure/Auteur
Vermont, C.
Auteure/Auteur
Vincek, K.
Auteure/Auteur
Agyeman, PKA
Auteure/Auteur
Cunnington, A.J.
Auteure/Auteur
De Groot, R.
Auteure/Auteur
Emonts, M.
Auteure/Auteur
Fidler, K.
Auteure/Auteur
Kuijpers, T.W.
Auteure/Auteur
Mommert-Tripon, M.
Auteure/Auteur
Brengel-Pesce, K.
Auteure/Auteur
Mallet, F.
Auteure/Auteur
Moll, H.
Auteure/Auteur
Paulus, S.
Auteure/Auteur
Pokorn, M.
Auteure/Auteur
Pollard, A.
Auteure/Auteur
Schlapbach, L.J.
Auteure/Auteur
Shen, C.F.
Auteure/Auteur
Tsolia, M.
Auteure/Auteur
Usuf, E.
Auteure/Auteur
van der Flier, M.
Auteure/Auteur
von Both, U.
Auteure/Auteur
Yeung, S.
Auteure/Auteur
Zavadska, D.
Auteure/Auteur
Zenz, W.
Auteure/Auteur
Wright, V.
Auteure/Auteur
Carrol, E.D.
Auteure/Auteur
Kaforou, M.
Auteure/Auteur
Martinon-Torres, F.
Auteure/Auteur
Fink, C.
Auteure/Auteur
Levin, M.
Auteure/Auteur
Herberg, J.
Auteure/Auteur
Contributrices/contributeurs
Shah, P.
Voice, M.
Calvo-Bado, L.
Calle, I.R.
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.K.
Cunnington, A.J.
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.J.
Shen, C.F.
Tsolia, M.
Usuf, E.
Van der Flier, M.
Von Both, U.
Yeung, S.
Zavadska, D.
Zenz, W.
Wright, V.
Carrol, E.D.
Kaforou, M.
Martinon-Torres, F.
Fink, C.
Levin, M.
Herberg, J.
Baumard, L.
Bellos, E.
Coin, L.
D'Souza, G.
Habgood-Coote, D.
Hamilton, S.
Hoggart, C.
Hourmat, S.
Jackson, H.
Lin, N.
Menikou, S.
Nichols, S.
Paz, I.P.
Powell, O.
Vito, O.
Wilson, C.
Abdulla, A.
Ali, L.
Darnell, S.
Jorgensen, R.
Maconochie, I.
Mustafa, S.
Persand, S.
Walsh, B.
Stevens, M.
Kim, N.
Kim, E.
Pierce, B.
Dudley, J.
Richmond, V.
Tavliavini, E.
Liu, C.C.
Wang, S.M.
González, F.Á.
Farto, C.B.
Barral-Arca, R.
Castro, M.B.
Bello, X.
Ben García, M.
Carnota, S.
Cebey-López, M.
Curras-Tuala, M.J.
Suárez, C.D.
Vicente, L.G.
Gómez-Carballa, A.
Rial, J.G.
Iglesias, P.L.
Martinón-Torres, N.
Martinón Sánchez, J.M.
Pérez, B.M.
Pardo-Seco, J.
Rodríguez, L.P.
Pischedda, S.
Vázquez, S.R.
Rodríguez-Tenreiro, C.
Redondo-Collazo, L.
Ora, M.S.
Sallas, A.
Fernández, S.S.
Trasorras, C.S.
Iglesias, M.V.
Balode, A.
Bãrdzdina, A.
Deksne, D.
Gardovska, D.
Grãvele, D.
Grope, I.
Meiere, A.
Nokalna, I.
Pavãre, J.
Pučuka, Z.
Selecka, K.
Svile, D.
Urbãne, U.N.
Bojang, K.
Zaman, S.M.
Anderson, S.
Roca, A.
Sarr, I.
Saidykhan, M.
Darboe, S.
Ceesay, S.
D'alessandro, U.
Borensztajn, D.M.
Hagedoorn, N.N.
Tal, C.
Zachariasse, J.
Dik, W.
Aebi, C.
Berger, C.
Wyss, V.
Usman, M.
Giannoni, E.
Stocker, M.
Posfay-Barbe, K.M.
Heininger, U.
Bernhard-Stirnemann, S.
Niederer-Loher, A.
Kahlert, C.
Natalucci, G.
Relly, C.
Riedel, T.
Cocklin, E.
Jennings, R.
Johnson, J.
Leigh, S.
Newall, K.
Romaine, S.
Tambouratzi, M.
Marmarinos, A.
Xagorari, M.
Syggelou, K.
Spyridis, N.
Blackmore, J.
Harrison, R.
Kohlmaier, B.
Kohlfürst, D.S.
Zurl, C.
Binder, A.
Hösele, S.
Leitner, M.
Pölz, L.
Rajic, G.
Bauchinger, S.
Baumgart, H.
Benesch, M.
Ceolotto, A.
Eber, E.
Gallisti, S.
Gores, G.
Haidl, H.
Hauer, A.
Hude, C.
Keldorfer, M.
Krenn, L.
Pilch, H.
Pfleger, A.
Pfurtscheller, K.
Nordberg, G.
Niedrist, T.
Rödl, S.
Skrabl-Baumgartner, A.
Sperl, M.
Stampfer, L.
Strenger, V.
Till, H.
Trobisch, A.
Löffler, S.
Dewez, J.E.
Hibberd, M.
Bath, D.
Miners, A.
Fitchett, E.
Wedderburn, C.
Meierford, A.
Leurent, B.
De Jonge, M.I.
van Aerde, K.
Alkema, W.
van den Broek, B.
Gloerich, J.
Van Gool, A.J.
Henriet, S.
Huijnen, M.
Philipsen, R.
Willems, E.
Gerrits, GPJM
Van Leur, M.
Heidema, J.
De Haan, L.
Miedema, C.J.
Neeleman, C.
Obihara, C.C.
Tramper-Stranders, G.A.
Kandasamy, R.
Carter, M.J.
O'Connor, D.
Bibi, S.
Kelly, D.F.
Gurung, M.
Throson, S.
Ansari, I.
Murdoch, D.R.
Shrestha, S.
Oliver, Z.
Lim, E.
Valentine, L.
Allen, K.
Bell, K.
Chan, A.
Crulley, S.
Devine, K.
Fabian, D.
King, S.
McAlinden, P.
McDonald, S.
McDonell, A.
Pickering, A.
Thomson, E.
Wood, A.
Wallia, D.
Woodsford, P.
Baxter, F.
Bell, A.
Rhodes, M.
Agbeko, R.
Mackerness, C.
Baas, B.
Kloosterhuis, L.
Oosthoek, W.
Arif, T.
Bennet, J.
Collings, K.
Van der Giessen, I.
Martin, A.
Rashid, A.
Rowlands, E.
Soon, J.
De Vries, G.
van der Velden, F.
Martin, M.
Mistry, R.
Zwerenz, M.
Buschbeck, J.
Bidlingmaier, C.
Binder, V.
Danhauser, K.
Haas, N.
Griese, M.
Kappler, M.
Lurz, E.
Muench, G.
Reiter, K.
Schoen, C.
Brengel-Pesce, K.
Pachot, A.
Mommert, M.
Vincek, K.
Srovin, T.P.
Bahovec, N.
Prunk, P.
Osterman, V.
Avramoska, T.
Jongerius, I.
van den Berg, J.M.
Schonenberg, D.
Barendregt, A.M.
Pajkrt, D.
van der Kuip, M.
van Furth, A.M.
Sprenkeler, E.
Zandstra, J.
van Mierlo, G.
Geissler, J.
Groupes de travail
PERFORM consortium
Liens vers les personnes
Liens vers les unités
ISSN
2666-7762
Statut éditorial
Publié
Date de publication
2023-09
Volume
32
Première page
100682
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Résumé
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.
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.
PID Serval
serval:BIB_C651D276B57B
PMID
URL éditeur
Open Access
Oui
Date de création
2024-08-28T08:22:51.863Z
Date de création dans IRIS
2025-05-21T01:55:51Z
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PID Serval
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URN
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