PLoS ONE (Jan 2023)

Host biomarkers and combinatorial scores for the detection of serious and invasive bacterial infection in pediatric patients with fever without source.

  • Laurence Lacroix,
  • Sebastien Papis,
  • Chiara Mardegan,
  • Fanny Luterbacher,
  • Arnaud L'Huillier,
  • Cyril Sahyoun,
  • Kristina Keitel,
  • Niv Mastboim,
  • Liat Etshtein,
  • Liran Shani,
  • Einav Simon,
  • Eran Barash,
  • Roy Navon,
  • Tanya M Gottlieb,
  • Kfir Oved,
  • Eran Eden,
  • Christophe Combescure,
  • Annick Galetto-Lacour,
  • Alain Gervaix

DOI
https://doi.org/10.1371/journal.pone.0294032
Journal volume & issue
Vol. 18, no. 11
p. e0294032

Abstract

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BackgroundImproved 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.MethodsThis 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).Results241 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 ConclusionLabscore 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.