Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study.
Details
Serval ID
serval:BIB_C651D276B57B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study.
Journal
The Lancet regional health. Europe
Working group(s)
PERFORM consortium
Contributor(s)
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.
ISSN
2666-7762 (Electronic)
ISSN-L
2666-7762
Publication state
Published
Issued date
09/2023
Peer-reviewed
Oui
Volume
32
Pages
100682
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
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.
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.
Keywords
Bacterial, Diagnostic, Febrile illness, Infectious disease, Molecular diagnostics, Respiratory infection, Viral
Pubmed
Web of science
Publisher's website
Open Access
Yes
Create date
28/08/2024 9:22
Last modification date
30/10/2024 7:18
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