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Paediatric Meningitis in the Conjugate Vaccine Era and Development of a Novel Clinical Decision Model to Predict Bacterial Aetiology in 3,002 Children with Suspected Meningitis
42 Pages Posted: 17 Jul 2023
More...Abstract
Background: Implementation of bacterial conjugate vaccines have resulted in dramatic reductions in bacterial meningitis globally. The aetiology of childhood meningitis in the conjugate vaccine era is not well-defined, and differentiating bacterial meningitis from other similar childhood illnesses is a major challenge. 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. Meningitis was defined as identification of bacteria/viruses from CSF and/or a CSF WBC>5/μL. Aetiology and clinical and laboratory features were analysed. Two new clinical decision rules were developed to distinguish bacterial meningitis from aseptic or suspected meningitis.
Findings: 3,002 children (median age 2·4 months, IQR: 1·0-12·7) were prospectively recruited at 31 UK hospitals. Overall 1,101/3,002 (36·7%) had meningitis, including 203 with a bacterial aetiology, 423 viral and 280 with no pathogen identified. Enterovirus was the most common pathogen in those aged < six months and 10-16 years, with N. meningitidis and/or S. pneumoniae commonest at age six months–nine 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 LP (sensitivity 84%, specificity 93%), to determine risk of bacterial meningitis.
Interpretation: Bacterial meningitis comprised only 6% of children presenting to hospital with suspected meningitis/encephalitis. Our clinical decision rules provide important novel approaches to identify the children with bacterial meningitis.
Funding: This independent research was supported by the UK Meningitis Research Foundation, Pfizer, and the National Institute for Health Research Programme Grants for Applied Research Programme (Understanding and improving the outcome of viral encephalitis, RP-PG-0108- 10048). MS is supported via salary awards from the BC Children’s Hospital Foundation and Michael Smith Health Research BC. TS is supported by the National Institute for Health and Care Research (NIHR) Health Protection Research Unit in Emerging and Zoonotic Infections (Grant Nos. IS-HPU- 1112-10117 and NIHR200907).
Declaration of Interest: MS has been an investigator on projects funded by GlaxoSmithKline, Merck, Moderna, Pfizer, Sanofi-Pasteur, Seqirus, Symvivo and VBI Vaccines. All funds have been paid to his institute, and he has not received any personal payments. AJP was a member of the World Health Organization’s Strategic Advisory Group of Experts on Immunization until January 2022 and remains chair of the UK Department of Health and Social Care's Joint Committee on Vaccination and Immunisation (JCVI). AJP also reports providing advice to Shionogi on COVID-19, and funding from the National Institute for Health Research (NIHR), AstraZeneca, the Bill & Melinda Gates Foundation, Wellcome, the Medical Research Council, and the Coalition for Epidemic Preparedness Innovations (CEPI). Oxford University has entered into a partnership with AstraZeneca for the development of COVID-19 vaccines. TS is Director of The Pandemic Institute, which has received funding from Innova, CSL Seqirus, Aviva and DAM Health; was an advisor to the GSK Ebola Vaccine programme and the Siemens Diagnostic Programme; Co-Chaired the WHO Neuro-COVID task force and sat on the UK Government’s Advisory Committee on Dangerous Pathogens, and the Medicines and Healthcare Products Regulatory Agency (MHRA) Expert Working Group on Covid-19 vaccines. PH has been an investigator on projects funded by GlaxoSmithKline, Merck, Moderna, Pfizer, Sanofi- Pasteur, Novavax, Valneva, Minervax and AZ. All funds have been paid to his institute, and he has not received any personal payments. He is a member of the UK JCVI. All other authors have no COI to disclose.
Ethical Approval: The study was approved by NRES Committee East Midlands - Nottingham 1 (Ref: 11/EM/0442).
Keywords: meningitis, encephalitis, paediatrics, vaccines, Neisseria meningitidis, Streptococcus pneumoniae, group B Streptococcus, clinical decision rule, enterovirus, lumbar puncture
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