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INTRODUCTION

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Neisseria meningitidis is a common commensal bacterium of the human upper respiratory tract. Colonization infrequently leads to disseminated disease, but the resulting meningitis and sepsis can be fulminant and rapidly fatal in healthy children and adults. Among survivors, 11% to 19% are left with disabilities such as neurologic deficit, hearing loss, or limb amputation. Despite advances in vaccine technology, N meningitidis remains a significant worldwide pathogen and the cause of epidemic meningitis. Children and young adults bear most of the burden of disease.

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PATHOGENESIS AND EPIDEMIOLOGY

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N meningitidis are gram-negative, aerobic diplococci that grow well on enriched medium such as chocolate or Mueller-Hinton agar in an atmosphere of 5% to 10% carbon dioxide. Organisms are divided into 13 serogroups based on the structure of their capsular polysaccharide, but only 6 (A, B, C, Y, W-135, and X) account for most of the disease, with groups A, B, C, and Y predominating. Molecular subtyping methods (eg, multilocus enzyme electrophoresis, pulsed-field gel electrophoresis, or DNA sequence analysis) are useful for the characterization of outbreaks and the identification of disease-causing clones.

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Meningococci are transmitted by aerosol or contact with secretions and colonize the respiratory mucosa. Focal spread can lead to respiratory tract infection, including pneumonia. Invasion through epithelial surfaces leads to bloodstream dissemination, allowing the bacteria to seed the meninges, pericardium, or large joints. The loss of protective maternal antibody renders the infant susceptible until endogenous antibody is induced by carriage of N meningitidis and Neisseria lactamica, a nonpathogenic species, as well as cross-reactive antibody induced by normal enteric organisms.

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N meningitidis enters the nasopharynx and attaches to nonciliated epithelial cells, probably through the binding of the pili to the CD46 receptor (a membrane cofactor protein) and the subsequent binding of opacity-associated proteins, Opa and Opc, to the CD66e (carcinoembryonic antigen) and heparan sulfate proteoglycan receptors, respectively (Fig. 270-1). The attached organisms are engulfed by the cells, enter phagocytic vacuoles, and may then pass through the cells. IgA1 protease (an outer-membrane protein) cleaves lysosome-associated membrane protein and may promote the survival of N meningitidis in epithelial cells. PorB (another outer-membrane protein) crosses the cell membrane and arrests the maturation of the phagosome. In the bloodstream, the organisms release endotoxin in the form of blebs (vesicular outer-membrane structures) that contain 50% lipooligosaccharide and 50% outer-membrane proteins, phospholipids, and capsular polysaccharide. The endotoxin and probably other components stimulate cytokine production and the alternative complement pathway. N meningitidis crosses the blood-brain barrier endothelium by entering the subarachnoid space, possibly through the choroid plexus of the lateral ventricles.

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Figure 270-1

Colonization of Neisseria meningitidis in the nasopharynx and entry into the bloodstream and cerebrospinal fluid.

Graphic Jump Location
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Humans are the only reservoir for N meningitidis. Approximately 10% of the general population are asymptomatic, nasopharyngeal carriers. ...

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