tetano
Editor, Senior Moderator
Lancet Reg Health Eur
. 2023 Jul 26;32:100682.
doi: 10.1016/j.lanepe.2023.100682. eCollection 2023 Sep. Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study
Priyen Shah[SUP] 1 [/SUP], Marie Voice[SUP] 2 [/SUP], Leonides Calvo-Bado[SUP] 2 [/SUP], Irene Rivero-Calle[SUP] 3 4 [/SUP], Sophie Morris[SUP] 2 [/SUP], Ruud Nijman[SUP] 1 [/SUP], Claire Broderick[SUP] 1 [/SUP], Tisham De[SUP] 1 [/SUP], Irini Eleftheriou[SUP] 5 [/SUP], Rachel Galassini[SUP] 1 [/SUP], Aakash Khanijau[SUP] 6 [/SUP], Laura Kolberg[SUP] 7 [/SUP], Mojca Kolnik[SUP] 8 [/SUP], Aleksandra Rudzate[SUP] 9 [/SUP], Manfred G Sagmeister[SUP] 10 [/SUP], Nina A Schweintzger[SUP] 10 [/SUP], Fatou Secka[SUP] 11 [/SUP], Clare Thakker[SUP] 1 [/SUP], Fabian van der Velden[SUP] 12 [/SUP], Clementien Vermont[SUP] 13 [/SUP], Katarina Vincek[SUP] 8 [/SUP], Philipp K A Agyeman[SUP] 14 [/SUP], Aubrey J Cunnington[SUP] 1 [/SUP], Ronald De Groot[SUP] 15 [/SUP], Marieke Emonts[SUP] 12 16 [/SUP], Katy Fidler[SUP] 17 [/SUP], Taco W Kuijpers[SUP] 18 19 [/SUP], Marine Mommert-Tripon[SUP] 20 [/SUP], Karen Brengel-Pesce[SUP] 20 [/SUP], Francois Mallet[SUP] 20 [/SUP], Henriette Moll[SUP] 21 [/SUP], Stéphane Paulus[SUP] 22 [/SUP], Marko Pokorn[SUP] 8 23 [/SUP], Andrew Pollard[SUP] 22 [/SUP], Luregn J Schlapbach[SUP] 24 [/SUP], Ching-Fen Shen[SUP] 25 26 [/SUP], Maria Tsolia[SUP] 5 [/SUP], Effua Usuf[SUP] 11 [/SUP], Michiel van der Flier[SUP] 15 27 [/SUP], Ulrich von Both[SUP] 7 28 [/SUP], Shunmay Yeung[SUP] 29 [/SUP], Dace Zavadska[SUP] 9 30 [/SUP], Werner Zenz[SUP] 10 [/SUP], Victoria Wright[SUP] 1 [/SUP], Enitan D Carrol[SUP] 6 31 [/SUP], Myrsini Kaforou[SUP] 1 [/SUP], Federico Martinon-Torres[SUP] 3 4 32 [/SUP], Colin Fink[SUP] 2 [/SUP], Michael Levin[SUP] 1 [/SUP], Jethro Herberg[SUP] 1 [/SUP]; PERFORM consortium
Collaborators, Affiliations
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.
Keywords: Bacterial; Diagnostic; Febrile illness; Infectious disease; Molecular diagnostics; Respiratory infection; Viral.
. 2023 Jul 26;32:100682.
doi: 10.1016/j.lanepe.2023.100682. eCollection 2023 Sep. Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study
Priyen Shah[SUP] 1 [/SUP], Marie Voice[SUP] 2 [/SUP], Leonides Calvo-Bado[SUP] 2 [/SUP], Irene Rivero-Calle[SUP] 3 4 [/SUP], Sophie Morris[SUP] 2 [/SUP], Ruud Nijman[SUP] 1 [/SUP], Claire Broderick[SUP] 1 [/SUP], Tisham De[SUP] 1 [/SUP], Irini Eleftheriou[SUP] 5 [/SUP], Rachel Galassini[SUP] 1 [/SUP], Aakash Khanijau[SUP] 6 [/SUP], Laura Kolberg[SUP] 7 [/SUP], Mojca Kolnik[SUP] 8 [/SUP], Aleksandra Rudzate[SUP] 9 [/SUP], Manfred G Sagmeister[SUP] 10 [/SUP], Nina A Schweintzger[SUP] 10 [/SUP], Fatou Secka[SUP] 11 [/SUP], Clare Thakker[SUP] 1 [/SUP], Fabian van der Velden[SUP] 12 [/SUP], Clementien Vermont[SUP] 13 [/SUP], Katarina Vincek[SUP] 8 [/SUP], Philipp K A Agyeman[SUP] 14 [/SUP], Aubrey J Cunnington[SUP] 1 [/SUP], Ronald De Groot[SUP] 15 [/SUP], Marieke Emonts[SUP] 12 16 [/SUP], Katy Fidler[SUP] 17 [/SUP], Taco W Kuijpers[SUP] 18 19 [/SUP], Marine Mommert-Tripon[SUP] 20 [/SUP], Karen Brengel-Pesce[SUP] 20 [/SUP], Francois Mallet[SUP] 20 [/SUP], Henriette Moll[SUP] 21 [/SUP], Stéphane Paulus[SUP] 22 [/SUP], Marko Pokorn[SUP] 8 23 [/SUP], Andrew Pollard[SUP] 22 [/SUP], Luregn J Schlapbach[SUP] 24 [/SUP], Ching-Fen Shen[SUP] 25 26 [/SUP], Maria Tsolia[SUP] 5 [/SUP], Effua Usuf[SUP] 11 [/SUP], Michiel van der Flier[SUP] 15 27 [/SUP], Ulrich von Both[SUP] 7 28 [/SUP], Shunmay Yeung[SUP] 29 [/SUP], Dace Zavadska[SUP] 9 30 [/SUP], Werner Zenz[SUP] 10 [/SUP], Victoria Wright[SUP] 1 [/SUP], Enitan D Carrol[SUP] 6 31 [/SUP], Myrsini Kaforou[SUP] 1 [/SUP], Federico Martinon-Torres[SUP] 3 4 32 [/SUP], Colin Fink[SUP] 2 [/SUP], Michael Levin[SUP] 1 [/SUP], Jethro Herberg[SUP] 1 [/SUP]; PERFORM consortium
Collaborators, Affiliations
- PMID: 37554664
- PMCID: PMC10405323
- DOI: 10.1016/j.lanepe.2023.100682
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.
Keywords: Bacterial; Diagnostic; Febrile illness; Infectious disease; Molecular diagnostics; Respiratory infection; Viral.