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Candidate Biomarkers for the Detection of Serious Infections in Children: A Prospective Clinical Study
Maria Chiara Pellegrin1, Arturo Penco2, Leonardo Amadio1
1Institute for Maternal and Child Health-IRCCS Burlo Garofolo, 34137 Trieste, Italy.
Insights
Early diagnosis of serious bacterial infections (SBI) in children is difficult. While C-reactive protein (CRP) and Intercellular Adhesion Molecule-1 (ICAM-1) showed some predictive value, blood biomarkers have limited usefulness for detecting SBI in pediatric patients.
Area of Science:
- Pediatric Infectious Diseases
- Clinical Diagnostics
- Biomarker Research
Background:
- Serious bacterial infections (SBI) in children present significant morbidity and mortality risks.
- Early and accurate identification of SBI in pediatric patients remains a clinical challenge.
- The diagnostic utility of existing laboratory tests and novel biomarkers for SBI requires further investigation.
Purpose of the Study:
- To prospectively evaluate the diagnostic performance of a panel of blood biomarkers for detecting SBI in children with systemic inflammatory response syndrome (SIRS).
- To identify reliable laboratory markers for the early diagnosis of serious bacterial infections in pediatric populations.
Main Methods:
- A prospective, observational, single-center study involving 103 pediatric patients with signs of SIRS.
- Measurement of C-reactive protein (CRP), procalcitonin (PCT), white blood cell count (WBC), absolute neutrophil count (ANC), interleukins (IL-6, IL-8, IL-10), complement complex (C5b-9), PV-1, ICAM-1, and PLA2.
- Statistical analysis including logistic regression and Receiver Operating Characteristic (ROC) curve analysis to assess diagnostic accuracy.
Main Results:
- Serious bacterial infections (SBI) were diagnosed in 38% of the patients.
- C-reactive protein (CRP) and Intercellular Adhesion Molecule-1 (ICAM-1) were significant predictors of SBI.
- White blood cell count (WBC), absolute neutrophil count (ANC), and ANC/WBC ratio showed association with SBI in non-neutropenic children.
- A combined model of CRP and ANC/WBC ratio demonstrated improved diagnostic accuracy compared to individual markers, though overall performance was suboptimal.
Conclusions:
- This study highlights the limited diagnostic utility of most blood biomarkers for the early detection of SBI in children.
- CRP, ICAM-1, WBC, ANC, and ANC/WBC ratio demonstrated moderate diagnostic accuracy, with a combined CRP and ANC/WBC ratio model showing potential.
- Further research is needed to develop more effective biomarkers for timely SBI diagnosis in pediatric patients.
Abstract:
Serious bacterial infections (SBI) in children are associated with considerable morbidity and mortality, and their early identification remains challenging. The role of laboratory tests in this setting is still debated, and new biomarkers are needed. This prospective, observational, single-center study aims to evaluate the diagnostic role of blood biomarkers in detecting SBI in children presenting with signs of systemic inflammatory response syndrome (SIRS). A panel of biomarkers was performed, including C-reactive protein (CRP), procalcitonin (PCT), white blood cell count (WBC), absolute neutrophil count (ANC), interleukin (IL)-6, IL-8, IL-10, human terminal complement complex (C5b-9), Plasmalemma-Vesicle-associated protein 1 (PV-1), Intercellular Adhesion Molecule-1 (ICAM-1), and Phospholipase A2 (PLA2). Among 103 patients (median age 2.9 years, 60% males), 39 had a diagnosis of SBI (38%). Significant predictors of SBI were CRP (p = 0.001) and ICAM-1 (p = 0.043). WBC (p = 0.035), ANC (p = 0.012) and ANC/WBC ratio (p = 0.015) were also significantly associated with SBI in children without pre-existing neutropenia. ROC curves, however, revealed suboptimal performance for all variables. Nevertheless, a model that combined CRP and ANC/WBC ratio had more in-depth diagnostic accuracy than either of the two variables. Overall, this study confirms the limited usefulness of blood biomarkers for the early diagnosis of SBI. WBC, ANC, ANC/WBC ratio, CRP, and ICAM-1 showed the best, albeit moderate, diagnostic accuracy.
