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.

Keywords: Bacterial meningitis; Diagnostic biomarker; Meta-analysis; Paediatric; Systematic review.