Paediatric meningitis in the conjugate vaccine era and a novel clinical decision model to predict bacterial aetiology

N G Martin; S Defres; L Willis; R Beckley; H Hardwick; A Coxon; S Kadambari; L-M Yu; X Liu; U Galal; K Conlin; M J Griffiths; R Kneen; S Nadel; P T Heath; D E Kelly; T Solomon; M Sadarangani; A J Pollard; UK-ChiMES and ENCEPH-UK study groups

doi:10.1016/j.jinf.2024.106145

Paediatric meningitis in the conjugate vaccine era and a novel clinical decision model to predict bacterial aetiology

J Infect. 2024 May;88(5):106145. doi: 10.1016/j.jinf.2024.106145. Epub 2024 Mar 27.

Authors

N G Martin¹, S Defres², L Willis³, R Beckley³, H Hardwick², A Coxon³, S Kadambari⁴, L-M Yu⁵, X Liu³, U Galal³, K Conlin³, M J Griffiths⁶, R Kneen⁷, S Nadel⁸, P T Heath⁹, D E Kelly³, T Solomon¹⁰, M Sadarangani¹¹, A J Pollard³; UK-ChiMES and ENCEPH-UK study groups

Affiliations

¹ Department of Paediatrics, University of Oxford and the Oxford University Hospitals NHS Foundation Trust, Level 2, Children's Hospital, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK; Department of Paediatrics, University of Otago Christchurch, 2 Riccarton Avenue, Christchurch Central City, Christchurch 8011, New Zealand.
² Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool L69 3BX, UK.
³ Department of Paediatrics, University of Oxford and the Oxford University Hospitals NHS Foundation Trust, Level 2, Children's Hospital, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK.
⁴ Department of Paediatric Infectious Diseases, Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK; Infection, Immunity & Inflammation Department, University College London, Great Ormond Street Institute of Child Health, 30 Guilford St, London WC1N 1EH, UK.
⁵ Nuffield Department of Primary Health Sciences, University of Oxford, Radcliffe Primary Care Building, Radcliffe Observatory Quarter, Woodstock Rd, Oxford OX2 6GG, UK.
⁶ Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool L69 3BX, UK; Department of Neurology, Alder Hey Children's NHS Trust, E Prescot Rd, Liverpool L14 5AB, UK.
⁷ Department of Neurology, Alder Hey Children's NHS Trust, E Prescot Rd, Liverpool L14 5AB, UK.
⁸ Department of Paediatrics, St. Mary's Hospital, Praed St, London W2 1NY, UK.
⁹ Centre for Neonatal and Paediatric Infection & Vaccine Institute, St. George's, University of London, Cranmer Terrace, London SW17 0RE, UK.
¹⁰ Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool L69 3BX, UK; Department of Neurology, Walton Centre NHS Foundation Trust, Lower Ln, Fazakerley, Liverpool L9 7LJ, UK.
¹¹ Vaccine Evaluation Center, BC Children's Hospital Research Institute, 950 West 28th Ave, Vancouver, BC V5Z 4H4, Canada; Department of Pediatrics, University of British Columbia, 4480 Oak Street, Vancouver, BC V5Z 4H4, Canada. Electronic address: [email protected].

PMID: 38552719
DOI: 10.1016/j.jinf.2024.106145

Abstract

Objectives: The aims of this study were to assess aetiology and clinical characteristics in childhood meningitis, and develop clinical decision rules to distinguish bacterial meningitis from other similar clinical syndromes.

Methods: Children aged <16 years hospitalised with suspected meningitis/encephalitis were included, and prospectively recruited at 31 UK hospitals. Meningitis was defined as identification of bacteria/viruses from cerebrospinal fluid (CSF) and/or a raised CSF white blood cell count. New clinical decision rules were developed to distinguish bacterial from viral meningitis and those of alternative aetiology.

Results: The cohort included 3002 children (median age 2·4 months); 1101/3002 (36·7%) had meningitis, including 180 bacterial, 423 viral and 280 with no pathogen identified. Enterovirus was the most common pathogen in those aged <6 months and 10-16 years, with Neisseria meningitidis and/or Streptococcus pneumoniae commonest at age 6 months to 9 years. The Bacterial Meningitis Score had a negative predictive value of 95·3%. We developed two clinical decision rules, that could be used either before (sensitivity 82%, specificity 71%) or after lumbar puncture (sensitivity 84%, specificity 93%), to determine risk of bacterial meningitis.

Conclusions: Bacterial meningitis comprised 6% of children with suspected meningitis/encephalitis. Our clinical decision rules provide potential novel approaches to assist with identifying children with bacterial meningitis.

Funding: This study was funded by the Meningitis Research Foundation, Pfizer and the NIHR Programme Grants for Applied Research.

Keywords: Bacteria; Cerebrospinal fluid; Children; Diagnostics; Meningitis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Child
Child, Preschool
Clinical Decision Rules
Decision Support Techniques
Female
Humans
Infant
Male
Meningitis, Bacterial* / cerebrospinal fluid
Meningitis, Bacterial* / diagnosis
Meningitis, Bacterial* / microbiology
Meningitis, Viral* / cerebrospinal fluid
Meningitis, Viral* / diagnosis
Neisseria meningitidis / isolation & purification
Prospective Studies
Streptococcus pneumoniae / isolation & purification
United Kingdom / epidemiology
Vaccines, Conjugate*

Substances

Vaccines, Conjugate