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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study
The Lancet Regional Health - Europe, Volume 32, Article 100682, Year 2023
Notification
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Description
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. © 2023 The Authors
Authors & Co-Authors
Shah, Priyen
United Kingdom, London
Imperial College London
Voice, Marie
United Kingdom, Coventry
University of Warwick
Calvo-Bado, Leo A.
United Kingdom, Coventry
University of Warwick
Rivero, Irene
Spain, Santiago de Compostela
Hospital Clínico Universitario de Santiago
Spain, Santiago de Compostela
Universidad de Santiago de Compostela
Morris, Sophie
United Kingdom, Coventry
University of Warwick
Nijman, Ruud Gerard
United Kingdom, London
Imperial College London
Broderick, Claire
United Kingdom, London
Imperial College London
De, Tisham
United Kingdom, London
Imperial College London
Eleftheriou, Irini
Unknown Affiliation
Galassini, Rachel
United Kingdom, London
Imperial College London
Khanijau, Aakash
United Kingdom, Liverpool
University of Liverpool
Kolberg, Laura
Germany, Munich
Ludwig-maximilians-universität München
Kolnik, Mojca
Slovenia, Ljubljana
Univerzitetni Klinični Center Ljubljana
Rudzate, Aleksandra
Latvia, Riga
Bērnu Klīniskā Universitātes Slimnīca
Sagmeister, Manfred G.
Austria, Graz
Medizinische Universität Graz
Schweintzger, Nina Alexandra
Austria, Graz
Medizinische Universität Graz
Secka, Fatou
Gambia, Fajara
Medical Research Council Unit the Gambia at Lshtm
Thakker, Clare
United Kingdom, London
Imperial College London
van der Velden, Fabian Johannes Stanislaus
United Kingdom, Newcastle
The Newcastle Upon Tyne Hospitals Nhs Foundation Trust
Vermont, Clementien L.
Netherlands, Rotterdam
Erasmus Mc
Vincek, Katarina
Slovenia, Ljubljana
Univerzitetni Klinični Center Ljubljana
Agyeman, Philipp Kwame Abayie
Switzerland, Bern
University of Bern
Cunnington, Aubrey J.
United Kingdom, London
Imperial College London
de Groot, Ronald C.A.
Netherlands, Nijmegen
Radboud University Medical Center
Emonts, Marieke
United Kingdom, Newcastle
The Newcastle Upon Tyne Hospitals Nhs Foundation Trust
United Kingdom, Newcastle
Newcastle University
Fidler, Katy J.
United Kingdom, Brighton
The Royal Alex Children’s Hospital
Kuijpers, Taco W.
Netherlands, Amsterdam
Universiteit Van Amsterdam
Netherlands, Amsterdam
Sanquin Research
Mommert-Tripon, Marine
France, Marcy-l'etoile
Biomérieux sa
Brengel-Pesce, Karen
France, Marcy-l'etoile
Biomérieux sa
Mallet, François
France, Marcy-l'etoile
Biomérieux sa
Moll, Henriëtte A.
Netherlands, Rotterdam
Erasmus Mc
Paulus, Stéphane C.
United Kingdom, Oxford
University of Oxford
Pokorn, Marko
Slovenia, Ljubljana
Univerzitetni Klinični Center Ljubljana
Slovenia, Ljubljana
Univerza V Ljubljani
Pollard, Andrew J.
United Kingdom, Oxford
University of Oxford
Schlapbach, Luregn J.
Switzerland, Zurich
Universität Zürich
Shen, Chingfen
Taiwan, Tainan
National Cheng Kung University
Tsolia, Maria N.
Unknown Affiliation
Usuf, Effua Abigail
Gambia, Fajara
Medical Research Council Unit the Gambia at Lshtm
van der Flier, Michiel
Netherlands, Nijmegen
Radboud University Medical Center
Netherlands, Utrecht
University Medical Center Utrecht
von Both, Ulrich
Germany, Munich
Ludwig-maximilians-universität München
Yeung, Shunmay M.
United Kingdom, London
London School of Hygiene & Tropical Medicine
Zavadska, Dace
Latvia, Riga
Bērnu Klīniskā Universitātes Slimnīca
Latvia, Riga
Riga Stradins University
Zenz, Werner M.
Austria, Graz
Medizinische Universität Graz
Wright, Victoria J.
United Kingdom, London
Imperial College London
Carrol, Enitan D.
United Kingdom, Liverpool
University of Liverpool
United Kingdom, Liverpool
Alder Hey Children's Hospital
Kaforou, Myrsini
United Kingdom, London
Imperial College London
Martinón-Torres, Federico
Spain, Santiago de Compostela
Hospital Clínico Universitario de Santiago
Spain, Santiago de Compostela
Universidad de Santiago de Compostela
Spain, Madrid
Instituto de Salud Carlos Iii
Fink, Colin G.
United Kingdom, Coventry
University of Warwick
Levin, Michael L.
United Kingdom, London
Imperial College London
Herberg, Jethro Adam
United Kingdom, London
Imperial College London
Calle, Irene Rivero
Unknown Affiliation
Sagmeister, Manfred
Unknown Affiliation
Schweintzger, Nina
Unknown Affiliation
Kuijpers, T. W.
Unknown Affiliation
Baumard, Lucas
Unknown Affiliation
Bellos, Evangelos
Unknown Affiliation
Coin, Lachlan J.M.
Unknown Affiliation
D'Souza, Giselle
Unknown Affiliation
Habgood-Coote, Dominic
Unknown Affiliation
Hamilton, Shea
Unknown Affiliation
Hoggart, Clive J.
Unknown Affiliation
Hourmat, Sara
Unknown Affiliation
Jackson, Heather R.
Unknown Affiliation
Lin, Naomi
Unknown Affiliation
Menikou, Stephanie
Unknown Affiliation
Nichols, Samuel J.
Unknown Affiliation
Paz, Ivonne Pena
Unknown Affiliation
Powell, Oliver
Unknown Affiliation
Vito, Ortensia
Unknown Affiliation
Wilson, Clare M.
Unknown Affiliation
Abdulla, Amina F.
Unknown Affiliation
Ali, Ladan
Unknown Affiliation
Darnell, Sarah
Unknown Affiliation
Jorgensen, Rikke
Unknown Affiliation
Maconochie, Ian
Unknown Affiliation
Mustafa, Sobia
Unknown Affiliation
Persand, Salina
Unknown Affiliation
Walsh, Ben
Unknown Affiliation
Stevens, Molly M.
Unknown Affiliation
Kim, Nayoung
Unknown Affiliation
Kim, Eunjung
Unknown Affiliation
Pierce, Benjamin
Unknown Affiliation
Dudley, Julia R.
Unknown Affiliation
Richmond, Vivien
Unknown Affiliation
Tavliavini, Emma
Unknown Affiliation
Liu, Chingchuan
Unknown Affiliation
Wang, Shihmin
Unknown Affiliation
González, Fernando Álves
Unknown Affiliation
Farto, Cristina Balo
Unknown Affiliation
Barral-Arca, Ruth
Unknown Affiliation
Castro, María Barreiro
Unknown Affiliation
Bello, Xabier
Unknown Affiliation
Ben García, Mirian
Unknown Affiliation
Carnota, Sandra
Unknown Affiliation
Cebey-López, Miriam
Unknown Affiliation
Currás-Tuala, María José
Unknown Affiliation
Suárez, Carlos Durán
Unknown Affiliation
Vicente, Luisa García
Unknown Affiliation
Gõmez-Carballa, Alberto
Unknown Affiliation
Rial, Jose Gómez
Unknown Affiliation
Iglesias, Pilar Leboráns
Unknown Affiliation
Martinón-Torres, Nazareth
Unknown Affiliation
Martinón-Sánchez, José María
Unknown Affiliation
Pérez, Belén Mosquera
Unknown Affiliation
Pardo-Seco, Jacobo
Unknown Affiliation
Pischedda, Sara
Unknown Affiliation
Rodríguez-Tenreiro, Carmen
Unknown Affiliation
Redondo Collazo, Lorenzo
Unknown Affiliation
Fernández, Sonia Serén
Unknown Affiliation
Gardovska, Dace Kh
Unknown Affiliation
Bojang, Kalifa A.
Unknown Affiliation
Zaman, Syed M.A.
Unknown Affiliation
Anderson, Suzanne T.B.
Unknown Affiliation
Roca, Anna
Unknown Affiliation
Sarr, Isatou
Unknown Affiliation
Darboe, Saffiatou
Unknown Affiliation
Ceesay, Samba
Unknown Affiliation
D'Alessandro, Umberto
Unknown Affiliation
Hagedoorn, Nienke N.
Unknown Affiliation
Dik, Willem Arnout
Unknown Affiliation
Berger, Christoph Tobias
Unknown Affiliation
Pósfay-Barbe, Klara Maria
Unknown Affiliation
Heininger, Ulrich
Unknown Affiliation
Kahlert, Christian R.
Unknown Affiliation
Riedel, Thomas
Unknown Affiliation
Jennings, Rebecca J.
Unknown Affiliation
Romaine, Sam T.
Unknown Affiliation
Spyridis, Nikos P.
Unknown Affiliation
Kohlmaier, Benno
Unknown Affiliation
Kohlfürst, Daniela S.
Unknown Affiliation
Binder, Alexander
Unknown Affiliation
Benesch, Martin
Unknown Affiliation
Eber, Ernst
Unknown Affiliation
Sperl, Matthias
Unknown Affiliation
Till, Holger Karl H.
Unknown Affiliation
Trobisch, Andreas
Unknown Affiliation
Dewez, Juan Emmanuel
Unknown Affiliation
Hibberd, Martin Lloyd
Unknown Affiliation
Bath, David
Unknown Affiliation
Fitchett, Elizabeth J.A.
Unknown Affiliation
Wedderburn, Catherine J.
Unknown Affiliation
Leurent, Baptiste
Unknown Affiliation
de Jonge, Marien Isaäk
Unknown Affiliation
van Aerde, Koen J.
Unknown Affiliation
Alkema, Wynand B.L.
Unknown Affiliation
Philipsen, Ria La
Unknown Affiliation
Obihara, Charlie C.C.
Unknown Affiliation
Kandasamy, Rama
Unknown Affiliation
Carter, Michael J.
Unknown Affiliation
Bibi, Sagida
Unknown Affiliation
Kelly, Dominic F.
Unknown Affiliation
Gurung, Meeru
Unknown Affiliation
Murdoch, David Roger
Unknown Affiliation
Shrestha, Shrijana R.
Unknown Affiliation
Lim, Emma J.
Unknown Affiliation
Agbeko, Rachel Sarah
Unknown Affiliation
Martin, Alexander James
Unknown Affiliation
de Vries, Gabriella
Unknown Affiliation
Bidlingmaier, Christoph M.
Unknown Affiliation
Danhauser, Katharina
Unknown Affiliation
Griese, Matthias
Unknown Affiliation
Lurz, Eberhard
Unknown Affiliation
Reiter, Karl
Unknown Affiliation
Pachot, Alexandre
Unknown Affiliation
Mommert, Marine
Unknown Affiliation
van den Berg, J. Merlijn
Unknown Affiliation
Barendregt, Anouk Marinke
Unknown Affiliation
Pajkrt, Dasja
Unknown Affiliation
van der Kuip, Martijn
Unknown Affiliation
Van Furth, A. M.
Unknown Affiliation
van Mierlo, Gerard J.
Unknown Affiliation
Statistics
Citations: 5
Authors: 171
Affiliations: 28
Identifiers
Doi:
10.1016/j.lanepe.2023.100682
ISSN:
26667762
Research Areas
Health System And Policy
Maternal And Child Health
Study Design
Cohort Study