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Original research
Update of a clinical prediction model for serious bacterial infections in preschool children by adding a host-protein-based assay: a diagnostic study
  1. Chantal van Houten1,
  2. Josephine Sophia van de Maat2,
  3. Christiana Naaktgeboren3,
  4. Louis Bont1,
  5. R Oostenbrink2
  1. 1 Paediatric infectious diseases, University Medical Centre Utrecht, Utrecht, The Netherlands
  2. 2 General Paediatrics, Erasmus MC Sophia Childrens Hospital, Rotterdam, The Netherlands
  3. 3 Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, The Netherlands
  1. Correspondence to Professor Louis Bont; l.bont{at}


Objective To determine whether updating a diagnostic prediction model by adding a combination assay (tumour necrosis factor-related apoptosis-inducing ligand, interferon γ induced protein-10 and C reactive protein (CRP)) can accurately identify children with pneumonia or other serious bacterial infections (SBIs).

Design Observational double-blind diagnostic study.

Setting Two hospitals in Israel and four hospitals in the Netherlands.

Patients 591 children, aged 1–60 months, presenting with lower respiratory tract infections or fever without source. 96 of them had SBIs. The original Feverkidstool, a polytomous logistic regression model including clinical variables and CRP, was recalibrated and thereafter updated by using the assay.

Main outcome measures Pneumonia, other SBIs or no SBI.

Results The recalibrated original Feverkidstool discriminated well between SBIs and viral infections, with a c-statistic for pneumonia of 0.84 (95% CI 0.77 to 0.92) and 0.82 (95% CI 0.77 to 0.86) for other SBIs. The discriminatory ability increased when CRP was replaced by the combination assay; c-statistic for pneumonia increased to 0.89 (95% CI 0.82 to 0.96) and for other SBIs to 0.91 (95% CI 0.87 to 0.94). This updated Feverkidstool improved diagnosis of SBIs mainly in children with low–moderate risk estimates of SBIs.

Conclusion We improved the diagnostic accuracy of the Feverkidstool by replacing CRP with a combination assay to predict pneumonia or other SBIs in febrile children. The updated Feverkidstool has the largest potential to rule out bacterial infections and thus to decrease unnecessary antibiotic prescription in children with low-to-moderate predicted risk of SBIs.

  • infectious diseases
  • accident & emergency
  • epidemiology

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  • Contributors CvH was responsible for protocol development, data analyses and was the main author of the paper; JSvdM was responsible for protocol development and writing of the manuscript; CN was responsible for data analyses and revision of the manuscript; LB supervised protocol development, analyses and writing of the manuscript; RO was responsible for protocol development and supervised the analyses and writing of the manuscript.

  • Funding The OPPORTUNITY Study was supported by an unrestricted grant from MeMed Diagnostics to the University Medical Centre Utrecht. The sponsor of the OPPORTUNITY Study had no role in study design, data collection, data analysis, data interpretation, writing of the manuscript or the decision to submit the manuscript for publication.

  • Competing interests None declared.

  • Patient consent for publication Parents gave written informed consent.

  • Ethics approval The OPPORTUNITY Study was approved by the ethics committees in the participating countries.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.

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