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

Nina S Groeneveld; Merijn W Bijlsma; Diederik van de Beek; Matthijs C Brouwer

doi:10.1016/j.cmi.2024.12.009

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

Clin Microbiol Infect. 2024 Dec 11:S1198-743X(24)00595-0. doi: 10.1016/j.cmi.2024.12.009. Online ahead of print.

Authors

Nina S Groeneveld¹, Merijn W Bijlsma², Diederik van de Beek¹, Matthijs C Brouwer³

Affiliations

¹ Amsterdam UMC, University of Amsterdam, Department of Neurology, Amsterdam Neuroscience, Meibergdreef, Amsterdam, The Netherlands.
² Amsterdam UMC, University of Amsterdam, Department of Neurology, Amsterdam Neuroscience, Meibergdreef, Amsterdam, The Netherlands; Amsterdam UMC, University of Amsterdam, Department of Paediatrics, Amsterdam Neuroscience, Meibergdreef, Amsterdam, The Netherlands.
³ Amsterdam UMC, University of Amsterdam, Department of Neurology, Amsterdam Neuroscience, Meibergdreef, Amsterdam, The Netherlands. Electronic address: m.c.brouwer@amsterdamumc.nl.

PMID: 39672463
DOI: 10.1016/j.cmi.2024.12.009

Abstract

Background: Biomarkers for paediatric bacterial meningitis are essential for 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 QUADAS-2 tool was used to assess risk of bias.

Methods of data synthesis: Difference in biomarker concentrations were assessed by calculating standardised and weighted mean differences. A random-effects meta-analysis model was used. Hierarchical summary receiver-operating characteristic curves were constructed.

Results: We identified 3,435 studies, of which 112 articles on 113 individual biomarkers (CSF n=90, blood n=23) were included. In CSF, CRP, IL-6, TNF-α and 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 non-bacterial 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).

Conclusions: 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.

Prospero id: CRD42022361785.

Keywords: bacterialmeningitis; diagnostic biomarker; meta-analysis; paediatric; systematic review.

Publication types

Review