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Summary MeninGene study protocol

Background

Meningitis is an inflammation of the membranes covering the brain and spinal cord (the meninges). Each year 22,000 European patients suffer from bacterial meningitis, causing 5000 deaths and leaving 7000 patients disabled. In developing countries, the burden of disease is up to 20 times higher. Streptococcus pneumoniae and Neisseria meningitidis are the most common etiologic agents, accounting for 85% of otal cases.1 Differences in susceptibility and outcome between individuals and populations are poorly understood but genetics of host and pathogen are considered crucial in this host-pathogen interaction. Recent studies have shown that both host and pathogen genetic characteristics influence the risk of acquiring meningitis, the response to treatment in bacterial meningitis patients, and the risk of unfavourable outcome. All of these studies used a candidate single-nucleotide polymorphism approach. Furthermore, genetic factors of the pathogen, which are thought to influence the virulence of the bacterium and thereby disease severity have not been studied. New adjunctive therapies are urgently needed to improve prognosis of bacterial meningitis. Genetic studies can unravel which mechanisms contribute to unfavourable outcome in bacterial meningitis and can be used to identify new treatments.

Objective

The main objective of MeninGene is to identify genetic risk factors in host and pathogen influencing susceptibility to bacterial meningitis, and the rate of complications, unfavourable outcome and death. 

Study-design

We will conduct a prospective observational nation-wide genetic association study in which we will perform massive parallel whole genome sequencing of causative bacteria and sequencing of host genes involved in the immune response in bacterial meningitis. DNA sequences of patients will be compared to healthy controls. Functionality of genes will be determined in leftover cerebrospinal fluid from the diagnostic lumbar puncture.

Study-population

All adult patients with community-acquired bacterial meningitis proven by culture or PCR of cerebrospinal fluid are eligible for the study. Controls consist of patients’ partners of proxies living in the same dwelling, to ensure similar exposure to bacteria, similar age, ethnicity and socio-economic background.

European meningitis database

Data will be entered in a pseudonymized fashion in a European meningitis database and will be made available to European bacterial meningitis researchers upon request if scientific sound and free of direct commercial interest.

Nature and extend of the burden

For the patient and controls, participation will mean that 14 ml of blood will be withdrawn for DNA isolation, preferably together with a scheduled blood withdrawal for diagnostic purposes in the patient.

 

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Collaboration

Neuroinfections Amsterdam collaborates with these companies or institutes:

ERC: European Research Council NWO ZonMw AMC: Academisch Medisch Centrum Stichting Steun Emma Kinderziekenhuis AMC