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Many people are nasopharyngeal carriers of Neisseria meningitidis but few develop invasive disease. Factors associated with invasion include viral infection, dry dusty air, and passive smoking. Bacterial factors related to invasiveness in the nasopharynx include adhesion factors, IgA protease production, ciliary inhibiting factors, the polysaccharide capsule, and surface antigens which may vary in expression or structure. The polysaccharide of group B meningococci is non-immunogenic because of its similarity to the human neural cell adhesion molecule. Host factors that limit survival of meningococci in the circulation include both the innate immune system and acquired immunity but specific antibodies are the most important mechanism. Deficiency in the terminal components of the complement pathway and properdin deficiency both lead to recurrent infection and mutations in the mannose binding lectin gene increase the risk of meningococcal disease.
Tissue damage in meningococcal disease is often caused by host immune mechanisms activated by endotoxin. Endotoxin binds to plasma endotoxin binding protein and to the cellular receptor, CD14 and other cellular receptors triggering an intense inflammatory response. Activated macrophages produce a range of proinflammatory cytokines the concentrations of which are related to disease severity and mortality. Microvascular injury in meningococcal sepsis manifests as increased vascular permeability leading to massive proteinuria and hypovolaemia, vasoconstriction or vasodilatation, intravascular thrombosis, and myocardial dysfunction. Renal failure, pulmonary oedema, gastrointestinal ischaemia, and brain impairment may follow. Central nervous system involvement may also be due to meningitis.
Treatment includes management of shock with restoration of blood volume. A variety of treatments aimed at reducing the inflammatory response have been tried with mixed results. Controlled trials of bactericidal permeability increasing protein (rBPI21) and activated protein C in childhood sepsis are being planned or under consideration.
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