TY - JOUR
T1 - A Novel Combination of Host Protein Biomarkers to Distinguish Bacterial from Viral Infections in Febrile Children in Emergency Care
AU - Tan, Chantal D.
AU - Van Den Broek, Bryan
AU - Womersley, Rebecca S.
AU - Kaforou, Myrsini
AU - Hagedoorn, Nienke N.
AU - Van Der Flier, Michiel
AU - Jackson, Heather
AU - Moll, Henriette A.
AU - Snijder, Rozemarijn
AU - De Jonge, Marien I.
AU - Vermont, Clementien L.
N1 - Funding Information:
This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 668303. The Research was supported by the National Institute for Health Research Biomedical Research Centres at Imperial College London, Newcastle Hospitals NHS Foundation Trust and Newcastle University. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. For the remaining authors no sources of funding were declared. The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the article; and decision to submit the article for publication.
Publisher Copyright:
© 2023 Lippincott Williams and Wilkins. All rights reserved.
PY - 2023/7
Y1 - 2023/7
N2 - Background: Distinguishing bacterial and viral infections based on clinical symptoms in febrile children attending the emergency department (ED) is challenging. The aim of this study is to determine a novel combination of host protein biomarkers and to assess its performance in distinguishing between bacterial and viral infection in febrile children attending EDs. Methods: A literature search was performed to identify blood protein biomarkers able to distinguish bacterial and viral infections (May 2015-May 2019). We selected 7 protein biomarkers: Procalcitonin, TNF-related apoptosis-inducing ligand (TRAIL), interleukin (IL)-4, IL-6, Interferon gamma-induced protein-10 (CXCL-10), interferon-gamma and lipocalin 2 (LCN2). These were measured in blood plasma using a bead-based immunoassay in children with a confirmed bacterial or viral infection attending EDs in the Netherlands. We used generalized linear modeling to classify bacterial and viral infections and applied a previously developed feature selection algorithm to select the optimal combination of proteins. We performed a subgroup analysis of this protein signature in patients with C-reactive protein <60 mg/L, representing a clinically challenging diagnostic group. Results: In total 102 children were included (N = 67 bacterial; N = 35 viral). Individual performance of the 7 biomarkers in classifying bacterial versus viral infections ranged from 60.8%-74.5% area under the receiver operator curve (AUC). TRAIL, LCN2 and IL-6 were identified as the best 3-protein signature with an AUC of 86% (95% CI: 71.3%-100%). In 57 patients with C-reactive protein levels <60 mg/L, the 3-protein signature had an AUC of 85.1% (95% CI: 75.3%-94.9%). Conclusion: We demonstrate a promising novel combination of 3 host protein biomarkers; TRAIL, LCN2 and IL-6, which performs well in classifying bacterial and viral infections in febrile children in emergency care.
AB - Background: Distinguishing bacterial and viral infections based on clinical symptoms in febrile children attending the emergency department (ED) is challenging. The aim of this study is to determine a novel combination of host protein biomarkers and to assess its performance in distinguishing between bacterial and viral infection in febrile children attending EDs. Methods: A literature search was performed to identify blood protein biomarkers able to distinguish bacterial and viral infections (May 2015-May 2019). We selected 7 protein biomarkers: Procalcitonin, TNF-related apoptosis-inducing ligand (TRAIL), interleukin (IL)-4, IL-6, Interferon gamma-induced protein-10 (CXCL-10), interferon-gamma and lipocalin 2 (LCN2). These were measured in blood plasma using a bead-based immunoassay in children with a confirmed bacterial or viral infection attending EDs in the Netherlands. We used generalized linear modeling to classify bacterial and viral infections and applied a previously developed feature selection algorithm to select the optimal combination of proteins. We performed a subgroup analysis of this protein signature in patients with C-reactive protein <60 mg/L, representing a clinically challenging diagnostic group. Results: In total 102 children were included (N = 67 bacterial; N = 35 viral). Individual performance of the 7 biomarkers in classifying bacterial versus viral infections ranged from 60.8%-74.5% area under the receiver operator curve (AUC). TRAIL, LCN2 and IL-6 were identified as the best 3-protein signature with an AUC of 86% (95% CI: 71.3%-100%). In 57 patients with C-reactive protein levels <60 mg/L, the 3-protein signature had an AUC of 85.1% (95% CI: 75.3%-94.9%). Conclusion: We demonstrate a promising novel combination of 3 host protein biomarkers; TRAIL, LCN2 and IL-6, which performs well in classifying bacterial and viral infections in febrile children in emergency care.
KW - bacterial infection
KW - biomarker
KW - emergency department
KW - viral infection
UR - http://www.scopus.com/inward/record.url?scp=85162837896&partnerID=8YFLogxK
U2 - 10.1097/INF.0000000000003952
DO - 10.1097/INF.0000000000003952
M3 - Article
C2 - 37200500
AN - SCOPUS:85162837896
SN - 0891-3668
VL - 42
SP - E235-E242
JO - Pediatric Infectious Disease Journal
JF - Pediatric Infectious Disease Journal
IS - 7
ER -