Blood biomarkers in early bacterial infection and sepsis diagnostics in feverish young children

Abstract

Background and objectives: While most feverish children have self-limiting diseases, 5-10% develop a serious and potentially life-threatening bacterial infection (BI). Due to potential risk, prompt recognition of BI and sepsis in the pediatric emergency department (PED) remains a clinical priority. The aim of the study was to evaluate the role of certain cytokines and chemokines separately and in combination with routine blood tests in early BI and sepsis diagnostics at PED.

Materials and methods: We prospectively studied children younger than 5 presenting to the PED with fever lasting for under 12 hours with high risk for serious illness. Clinical data, routine blood analysis, and inflammatory cytokine and chemokine panels were evaluated for their diagnostic abilities. Two separate analyses were carried out on the patients' data: one contrasting BI and viral infection (VI) groups, the other comparing septic and non-septic patients.

Results: The sample comprised 70 patients (40% with BI). IL-2 was found to be the most specific biomarker to identify BI with specificity of 100%. The best discriminative ability was demonstrated by combining IL-2, IL-6, CRP, WBC, and neutrophil count: AUC 0.942 (95% Cl 0.859-0.984). IL-10 exhibited a greater AUC (0.837. 95% CI: 0.730-0.915 p<0.05) than CRP (0.807. 95% CI: 0.695-0.895 p<0.05) when predicting sepsis and showed high specificity (98%) and moderate sensitivity (75%).

Conclusions: IL-6 and IL-2 could increase the diagnostic ability of routine blood tests for predicting BI, as IL-10 raises specificity for recognizing sepsis in the early hours of disease onset.

Keywords: blood biomarkers; chemokine; cytokine; pediatric emergency department; sepsis, bacterial infection.

Figure 1

Traffic light system for identifying risk of serious illness, NICE. Adapted from “Assessment and initial management of feverish illness in children younger than 5 years: summary of updated NICE guidance” by E. Fields, J. Chard, S. M. Murphy and M. Richardson, 2013, BMJ, 346:f2866. Copyright 2013 by BMJ .

Figure 2

Comparison of CRP (mg/l) levels (a) WBC and NC (pg/ml) levels (b) and Il-2, IL-6 and sTREM-1 levels (c) in the two groups. ROC analysis of different combinations of biomarkers for predicting BI (d). IL - interleukin; CRP - C reactive protein; WBC - white blood cells; NC - neutrophil count. VI -viral infection, BI - bacterial infection, sTREM-1- soluble triggering receptor expressed on myelocytes 1, ROC - receiver operating characteristic curve.

Figure 3

Distribution of levels of CRP (mg/l) (a) and IL-10 (pg/ml) (b) in two groups. ROC analysis of CRP, IL-10 and combination of both biomarkers in predicting sepsis (c). IL, interleukin; CRP, C reactive protein; WBC, white blood cells; NC, neutrophil count.