Biomarkers in paediatric bacterial meningitis: a systematic review and meta-analysis of diagnostic test accuracy

Abstract

Background

Biomarkers for paediatric bacterial meningitis are essential for an accurate diagnosis.

Objectives

To perform a systematic review of diagnostic accuracy on cerebrospinal fluid (CSF) and blood biomarkers for paediatric bacterial meningitis.

Data sources

Databases Medline, Excerpta Medica Database, Scopus, and Web of Science were used.

Study eligibility criteria

Eligible studies were those on novel diagnostic CSF and blood biomarkers from which data on biomarker concentration or diagnostic accuracy could be abstracted.

Participants

Paediatric patients (0–18 years) suspected of a central nervous system (CNS) infection.

Assessment of risk of bias

The Quality Assessment tool for Diagnostic Accuracy Studies (QUADAS)-2 tool was used to assess risk of bias.

Methods of data synthesis

The difference in biomarker concentrations were assessed by calculating standardized and weighted mean differences. A random-effects meta-analysis model was used. Hierarchical summary receiver-operating characteristic curves were constructed.

Results

We identified 3435 studies, of which 112 articles on 113 individual biomarkers (CSF n = 90 and blood n = 23) were included. In CSF, C-reactive protein (CRP), Interleukin (IL)-6, Tumor necrosis factor (TNF)-α, and Interleukin (IL)-8 showed the largest mean differences between bacterial meningitis and viral meningitis and IL-6, TNF-α, and IL-8 between bacterial meningitis and no CNS infection/inflammation. CSF CRP and ferritin showed excellent discrimination for bacterial versus viral meningitis (summary area under the curve [sAUC] 0.94; 95% CI, 0.92–0.97, sAUC 0.94; 95% CI, 0.90–1.0). CSF IL-6 and procalcitonin showed excellent discrimination for bacterial versus nonbacterial meningitis and versus no CNS infection/inflammation (sAUC IL-6: 0.98; 95% CI, 0.96–1.00, sAUC procalcitonin: 0.96; 95% CI, 0.94–0.99). Procalcitonin in blood showed good discrimination (AUC, 0.89; 95% CI, 0.68–1.00).

Discussion

We identified several CSF biomarkers with high diagnostic accuracy for the diagnosis of bacterial meningitis, including IL-6, procalcitonin, CRP, and ferritin. None of the blood biomarkers exhibited excellent discrimination for paediatric bacterial meningitis. Validation of these biomarkers in prospective, well-designed studies of diagnostic accuracy performed in children with suspected meningitis is needed.