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Classification and Pathogenesis of Meningococcal Infections

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Neisseria meningitidis

Part of the book series: Methods in Molecular Biology ((MIMB,volume 799))

Abstract

The clinical symptoms induced by Neisseria meningitidis reflect compartmentalized intravascular and intracranial bacterial growth and inflammation. In this chapter, we describe a classification system for meningococcal disease based on the nature of the clinical symptoms. Meningococci invade the subarachnoid space and cause meningitis in as many as 50–70% of patients. The bacteremic phase is moderate in patients with meningitis and mild systemic meningococcemia but graded high in patients with septic shock. Three landmark studies using this classification system and comprising 862 patients showed that 37–49% developed meningitis without shock, 10–18% shock without meningitis, 7–12% shock and meningitis, and 18–33% had mild meningococcemia without shock or meningitis. N. meningitidis lipopolysaccharide (LPS) is the principal trigger of the innate immune system via activation of the Toll-like receptor 4-MD2 cell surface receptor complex on myeloid and nonmyeloid human cells. The intracellular signals are conveyed via MyD88-dependent and -independent pathways altering the expression of >4,600 genes in target cells such as monocytes. However, non-LPS molecules contribute to inflammation, but 10–100-fold higher concentrations are required to reach the same responses as induced by LPS. Activation of the complement and coagulation systems is related to the bacterial load in the circulation and contributes to the development of shock, organ dysfunction, thrombus formation, bleeding, and long-term complications in patients. Despite rapid intervention and advances in patient intensive care, why as many as 30% of patients with systemic meningococcal disease develop massive meningococcemia leading to shock and death is still not understood.

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Acknowledgments

Peter Kierulf, Reidun Övstebö, Berit Brusletto, Tom Eirik Mollnes, Bernt Christian Hellerud, Arne Höiby, Anne Marie Siebke Tröseid, Tom Sprong, Chris Neeleman, and Sabine de Greeff have all contributed extensively to the studies.

The studies have been financed by Ullevål University Hospital, Oslo, the Reginal Health Authority Helse Söröst, Norway, and the Dutch Organisation for Scientific Research, the Netherlands. A particular thank you to all patients, parents, and relatives who consented to participate in the studies.

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Authors and Affiliations

  1. Departments of Pediatrics and Medical Biochemistry, University of Oslo, Oslo, Norway

    Petter Brandtzaeg

  2. Department of Internal Medicine and Nijmegen Institute for Infection, Inflammation and Immunity, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

    Marcel van Deuren

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  1. Petter Brandtzaeg
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  2. Marcel van Deuren
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Correspondence to Petter Brandtzaeg .

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Editors and Affiliations

  1. Medical School, Molecular Microbiology and Infection, University of Southampton, Tremona Road, Southampton, SO16 6YD, Hampshire, United Kingdom

    Myron Christodoulides

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Brandtzaeg, P., van Deuren, M. (2012). Classification and Pathogenesis of Meningococcal Infections. In: Christodoulides, M. (eds) Neisseria meningitidis. Methods in Molecular Biology, vol 799. Humana, Totowa, NJ. https://doi.org/10.1007/978-1-61779-346-2_2

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  • DOI: https://doi.org/10.1007/978-1-61779-346-2_2

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  • Publisher Name: Humana, Totowa, NJ

  • Print ISBN: 978-1-61779-345-5

  • Online ISBN: 978-1-61779-346-2

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