20.500.12556/DiRROS-24142 Relationship between molecular pathogen detection and clinical disease in febrile children across Europe a multicentre, prospective observational study 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. molecular diagnostics diagnostic febrile illness infectious disease bacterial infection viral infection respiratory infection true false true Angleški jezik Ni določen Neznano 2025-11-17 15:30:28 2025-11-17 15:30:28 2025-11-18 03:43:33 0000-00-00 00:00:00 2023 0 0 Nasl. z nasl. zaslona; Opis vira z dne 23. 7. 2025; str. 1-17 [article no.] 100682 Vol. 32 Sep. 2023 0000-00-00 Zaloznikova Objavljeno apc 0000-00-00 0000-00-00 0000-00-00 616-053.2 2666-7762 10.1016/j.lanepe.2023.100682 243502595 RAZ_Shah_Priyen_2023.pdf RAZ_Shah_Priyen_2023.pdf 1 C5156203130E3004EA0941DA327186A2 3a19cb8aa7ff6bd3f4f9ce4f9758e58b1db308827f3631c4c3954bb3ab32de08 24029f07-c3c2-11f0-94a7-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=35934 https://www.thelancet.com/journals/lanepe/article/PIIS2666-7762(23)00101-1/fulltext 0 2f1a1126-c3c2-11f0-94a7-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=35935 Univerzitetni klinični center Ljubljana 0 0 0