DOI: 10.5061/dryad.gxd2547s8
title: Host biomarkers and combinatorial scores for the detection of serious and invasive bacterial infection in pediatric patients with fever without source

description: Background  Improved tools are required to detect bacterial
 infection in children with fever without source (FWS), especially when
 younger than 3 years old. The aim of the present study was to investigate
 the diagnostic accuracy of a host signature combining for the first time
 two viral-induced biomarkers, tumor necrosis factor-related
 apoptosis-inducing ligand (TRAIL) and interferon γ-induced
 protein-10 (IP-10), with a bacterial-induced one, C-reactive protein
 (CRP), to reliably predict bacterial infection in children with fever
 without source (FWS) and to compare its performance to routine individual
 biomarkers (CRP, procalcitonin (PCT), white blood cell and absolute
 neutrophil counts, TRAIL, and IP-10) and to the Labscore. Methods This was
 a prospective diagnostic accuracy study conducted in a single tertiary
 center in children aged less than 3 years old presenting with FWS.
 Reference standard etiology (bacterial or viral) was assigned by a panel
 of three independent experts. Diagnostic accuracy (AUC, sensitivity,
 specificity) of host individual biomarkers and combinatorial scores was
 evaluated in comparison to reference standard outcomes (expert panel
 adjudication and microbiological diagnosis).  Results 241
 patients were included. 68 of them (28%) were diagnosed with a bacterial
 infection and 5 (2%) with invasive bacterial infection (IBI). Labscore,
 ImmunoXpert, and CRP attained the highest AUC values for the detection of
 bacterial infection, respectively 0.854 (0.804–0.905), 0.827
 (0.764–0.890), and 0.807 (0.744–0.869). Labscore and ImmunoXpert
 outperformed the other single biomarkers with higher sensitivity and/or
 specificity and showed comparable performance to one another although
 slightly reduced sensitivity in children &lt; 90 days of age.
 Conclusion Labscore and ImmunoXpert demonstrate high diagnostic accuracy
 for safely discriminating bacterial infection in children with FWS aged
 under and over 90 days, supporting their adoption in the assessment of
 febrile patients.
description: <strong>Study Design</strong>:
 Prospective diagnostic accuracy study in children with FWS aged less than
 3 years old (consecutive sample), performed in the pediatric emergency
 department (PED) of a single Swiss tertiary center from November 2015 to
 January 2018, using expert panel adjudication and microbiological
 diagnosis as diagnostic reference standards.  Primary
 objective: To prospectively investigate the diagnostic accuracy of a host
 signature (TRAIL, IP-10, and CRP) to reliably predict bacterial infections
 and to compare its performance to routine individual biomarkers (CRP, PCT,
 WBC, ANC, TRAIL, and IP-10) and to the Labscore. 
 Secondary
 objectives: To compare the diagnostic accuracy of the ImmunoXpert, the
 Labscore, and individual biomarkers to reliably predict IBI.
 <strong>Participants</strong>:
 Patients aged less than 3 years old presenting to the PED with FWS after a
 thorough history and physical exam were eligible.  Exclusion criteria were
 comorbidities predisposing to infections such as cancer, primary or
 secondary immunodeficiency, and iatrogenic immunosuppression.
 <strong>Study Procedure</strong>:
 After informed consent was obtained, patients’ clinical characteristics
 were recorded (age, sex, delay between fever onset and presentation,
 maximum temperature before presentation). Patients were assessed with
 white blood cell count (WBC), absolute neutrophil count (ANC), band count,
 CRP, PCT, urinary dipstick and culture, and blood culture. Additional
 testing (CSF culture, chest X-ray, synovial fluid
 or stool culture, etc.) was optional. An additional 0.6 mL sample was
 drawn, dedicated to the determination of CRP, TRAIL and IP-10 and the
 ImmunoXpert score. A group of 50 healthy Canadian children from trauma and
 dental clinics served as control patients to assess the differential
 expression of biomarkers and combinatorial scores between patients with
 fever without source and children with no fever and no current infection.
 The study was approved by the Institutional Ethics Committee (Cantonal
 Committee on Ethics in Scientific Research of Geneva, CCER), adheres to
 STARD 2015 guidelines, and
 is registered under ClinicalTrials.gov (NCT03224026). No
 investigation was performed before signature of a written informed
 consent. The use of sera from control patients was approved by Toronto’s
 Hospital for Sick Children Ethics Committee.  <strong>Blinding
 process</strong>: Experts had access to full medical records but
 were blinded to the diagnosis of their peers and to TRAIL, IP-10 and
 ImmunoXpert results; CRP, PCT and urinary dipstick data were available to
 the experts. The ImmunoXpert test was performed on anonymized samples, and
 performers/readers of the index tests had no access to clinical
 information and reference standard results. The index test and panel
 expert reference standard outcomes were locked prior to unblinding at the
 end of the recruitment phase.
description: # Host biomarkers and combinatorial scores for the detection of serious
 and invasive bacterial infection in pediatric patients with fever without
 source
 [https://doi.org/10.5061/dryad.gxd2547s8](https://doi.org/10.5061/dryad.gxd2547s8) The data set contains results from a study on host biomarkers and combinatorial scores for the detection of serious and invasive bacterial infection in pediatric patients aged 0-3 years old presenting with fever without source. ## Description of the data and file structure Data include clinical characteristics of the patient (patient type, ie study or control patient, age, sex, duration of fever), reference standard diagnosis (expert panel adjudication and microbiological diagnosis) and results from biomarkers and combinatorial scores. They are included in the file named "VirEF Dataset". Explanations on coding (abbreviations, corresponding values and units of measure) of the variables included in the main dataset are detailed in the second uploaded excel file named "VirEF Dataset Coding". ## Sharing/Access information Broader information on the topic can be found in the related article. ## Code/Software Codes are detailed in the file named "VirEF Dataset Coding". n/a indicates no value is available in the corresponding cell (missing data due to absent or insufficient blood sample or value not applicable to the type of patient, i.e. control vs study patients).