Are children with prolonged fever at a higher risk for serious illness? A prospective observational study

Ruud G. Nijman*, Chantal D. Tan, The PERFORM consortium (Personalized Risk assessment in febrile children to optimize Real-life Management across the European Union), Nienke N. Hagedoorn, Daan Nieboer, Jethro Adam Herberg, Anda Balode, Ulrich Von Both, Enitan D. Carrol, Irini Eleftheriou, Marieke Emonts, Michiel Van Der Flier, Ronald De Groot, Benno Kohlmaier, Emma Lim, Federico Martinón-Torres, Marko Pokorn, Franc Strle, Maria Tsolia, Shunmay YeungJoany M. Zachariasse, Dace Zavadska, Werner Zenz, Michael Levin, Clementien L. Vermont, Henriette A. Moll, Ian K. MacOnochie

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)


Objectives: To describe the characteristics and clinical outcomes of children with fever ≥5 days presenting to emergency departments (EDs). Design: Prospective observational study. Setting: 12 European EDs. Patients: Consecutive febrile children <18 years between January 2017 and April 2018. Interventions: Children with fever ≥5 days and their risks for serious bacterial infection (SBI) were compared with children with fever <5 days, including diagnostic accuracy of non-specific symptoms, warning signs and C-reactive protein (CRP; mg/L). Main outcome measures: SBI and other non-infectious serious illness. Results: 3778/35 705 (10.6%) of febrile children had fever ≥5 days. Incidence of SBI in children with fever ≥5 days was higher than in those with fever <5 days (8.4% vs 5.7%). Triage urgency, life-saving interventions and intensive care admissions were similar for fever ≥5 days and <5 days. Several warning signs had good rule in value for SBI with specificities >0.90, but were observed infrequently (range: 0.4%-17%). Absence of warning signs was not sufficiently reliable to rule out SBI (sensitivity 0.92 (95% CI 0.87-0.95), negative likelihood ratio (LR) 0.34 (0.22-0.54)). CRP <20 mg/L was useful for ruling out SBI (negative LR 0.16 (0.11-0.24)). There were 66 cases (1.7%) of non-infectious serious illnesses, including 21 cases of Kawasaki disease (0.6%), 28 inflammatory conditions (0.7%) and 4 malignancies. Conclusion: Children with prolonged fever have a higher risk of SBI, warranting a careful clinical assessment and diagnostic workup. Warning signs of SBI occurred infrequently but, if present, increased the likelihood of SBI. Although rare, clinicians should consider important non-infectious causes of prolonged fever.

Original languageEnglish
Article numberarchdischild-2023-325343
Pages (from-to)632-639
Number of pages8
JournalArchives of Disease in Childhood
Issue number8
Early online date25 Apr 2023
Publication statusPublished - 1 Aug 2023

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