TY - JOUR
T1 - Febrile illness in high-risk children
T2 - a prospective, international observational study
AU - van der Velden, Fabian J. S.
AU - de Vries, Gabriella
AU - Martin, Alexander
AU - Lim, Emma
AU - von Both, Ulrich
AU - Kolberg, Laura
AU - Carrol, Enitan D.
AU - Khanijau, Aakash
AU - Herberg, Jethro A.
AU - de, Tisham
AU - Galassini, Rachel
AU - Kuijpers, Taco W.
AU - PERFORM consortium
AU - Martinón-Torres, Federico
AU - Rivero-Calle, Irene
AU - Vermont, Clementien L.
AU - Hagedoorn, Nienke N.
AU - Pokorn, Marko
AU - Pollard, Andrew J.
AU - Schlapbach, Luregn J.
AU - Tsolia, Maria
AU - Elefhteriou, Irini
AU - Yeung, Shunmay
AU - Zavadska, Dace
AU - Fink, Colin
AU - Voice, Marie
AU - Zenz, Werner
AU - Kohlmaier, Benno
AU - Agyeman, Philipp K. A.
AU - Usuf, Effua
AU - Secka, Fatou
AU - de Groot, Ronald
AU - Levin, Michael
AU - van der Flier, Michiel
AU - Emonts, Marieke
AU - PERFORM consortium (Personalised Risk assessment in febrile children to optimize Real-life Management across the European Union)
AU - Tutu-van Furth, A.M.
N1 - Funding Information: This project received funding under the European Union’s Horizon2020 research and innovation programme, grant agreement number 668303. UK enrolment was supported by NIHR Biomedical Research Centres at Imperial College London, and Newcastle. Publisher Copyright: © 2022, The Author(s).
PY - 2023
Y1 - 2023
N2 - To assess and describe the aetiology and management of febrile illness in children with primary or acquired immunodeficiency at high risk of serious bacterial infection, as seen in emergency departments in tertiary hospitals. Prospective data on demographics, presenting features, investigations, microbiology, management, and outcome of patients within the ‘Biomarker Validation in HR patients’ database in PERFORM, were analysed. Immunocompromised children (< 18 years old) presented to fifteen European hospitals in nine countries, and one Gambian hospital, with fever or suspected infection and clinical indication for blood investigations. Febrile episodes were assigned clinical phenotypes using the validated PERFORM algorithm. Logistic regression was used to assess the effect size of predictive features of proven/presumed bacterial or viral infection. A total of 599 episodes in 482 children were analysed. Seventy-eight episodes (13.0%) were definite bacterial, 67 episodes probable bacterial (11.2%), and 29 bacterial syndrome (4.8%). Fifty-five were definite viral (9.2%), 49 probable viral (8.2%), and 23 viral syndrome (3.8%). One hundred ninety were unknown bacterial or viral infections (31.7%), and 108 had inflammatory or other non-infectious causes of fever (18.1%). Predictive features of proven/presumed bacterial infection were ill appearance (OR 3.1 (95% CI 2.1–4.6)) and HIV (OR 10.4 (95% CI 2.0–54.4)). Ill appearance reduced the odds of having a proven/presumed viral infection (OR 0.5 (95% CI 0.3–0.9)). A total of 82.1% had new empirical antibiotics started on admission (N = 492); 94.3% proven/presumed bacterial (N = 164), 66.1% proven/presumed viral (N = 84), and 93.2% unknown bacterial or viral infections (N = 177). Mortality was 1.9% (N = 11) and 87.1% made full recovery (N = 522). Conclusion: The aetiology of febrile illness in immunocompromised children is diverse. In one-third of cases, no cause for the fever will be identified. Justification for standard intravenous antibiotic treatment for every febrile immunocompromised child is debatable, yet effective. Better clinical decision-making tools and new biomarkers are needed for this population.What is Known:• Immunosuppressed children are at high risk for morbidity and mortality of serious bacterial and viral infection, but often present with fever as only clinical symptom.• Current diagnostic measures in this group are not specific to rule out bacterial infection, and positivity rates of microbiological cultures are low.What is New:• Febrile illness and infectious complications remain a significant cause of mortality and morbidity in HR children, yet management is effective.• The aetiology of febrile illness in immunocompromised children is diverse, and development of pathways for early discharge or cessation of intravenous antibiotics is debatable, and requires better clinical decision-making tools and biomarkers.
AB - To assess and describe the aetiology and management of febrile illness in children with primary or acquired immunodeficiency at high risk of serious bacterial infection, as seen in emergency departments in tertiary hospitals. Prospective data on demographics, presenting features, investigations, microbiology, management, and outcome of patients within the ‘Biomarker Validation in HR patients’ database in PERFORM, were analysed. Immunocompromised children (< 18 years old) presented to fifteen European hospitals in nine countries, and one Gambian hospital, with fever or suspected infection and clinical indication for blood investigations. Febrile episodes were assigned clinical phenotypes using the validated PERFORM algorithm. Logistic regression was used to assess the effect size of predictive features of proven/presumed bacterial or viral infection. A total of 599 episodes in 482 children were analysed. Seventy-eight episodes (13.0%) were definite bacterial, 67 episodes probable bacterial (11.2%), and 29 bacterial syndrome (4.8%). Fifty-five were definite viral (9.2%), 49 probable viral (8.2%), and 23 viral syndrome (3.8%). One hundred ninety were unknown bacterial or viral infections (31.7%), and 108 had inflammatory or other non-infectious causes of fever (18.1%). Predictive features of proven/presumed bacterial infection were ill appearance (OR 3.1 (95% CI 2.1–4.6)) and HIV (OR 10.4 (95% CI 2.0–54.4)). Ill appearance reduced the odds of having a proven/presumed viral infection (OR 0.5 (95% CI 0.3–0.9)). A total of 82.1% had new empirical antibiotics started on admission (N = 492); 94.3% proven/presumed bacterial (N = 164), 66.1% proven/presumed viral (N = 84), and 93.2% unknown bacterial or viral infections (N = 177). Mortality was 1.9% (N = 11) and 87.1% made full recovery (N = 522). Conclusion: The aetiology of febrile illness in immunocompromised children is diverse. In one-third of cases, no cause for the fever will be identified. Justification for standard intravenous antibiotic treatment for every febrile immunocompromised child is debatable, yet effective. Better clinical decision-making tools and new biomarkers are needed for this population.What is Known:• Immunosuppressed children are at high risk for morbidity and mortality of serious bacterial and viral infection, but often present with fever as only clinical symptom.• Current diagnostic measures in this group are not specific to rule out bacterial infection, and positivity rates of microbiological cultures are low.What is New:• Febrile illness and infectious complications remain a significant cause of mortality and morbidity in HR children, yet management is effective.• The aetiology of febrile illness in immunocompromised children is diverse, and development of pathways for early discharge or cessation of intravenous antibiotics is debatable, and requires better clinical decision-making tools and biomarkers.
KW - Antibiotics
KW - Fever
KW - Immunocompromised
KW - Infection
KW - Paediatric
UR - http://www.scopus.com/inward/record.url?scp=85139972595&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/s00431-022-04642-1
DO - https://doi.org/10.1007/s00431-022-04642-1
M3 - Article
C2 - 36243780
SN - 0340-6199
VL - 182
SP - 543
JO - European journal of pediatrics
JF - European journal of pediatrics
ER -