Etiology

Meningococcal infections are caused by Neisseria meningitidis, an aerobic gram-negative diplococcus found exclusively in the human nasopharynx.

Meningococci colonize the human nasopharynx by adhering to nonciliated columnar epithelial cells.[12] Transmission occurs by inhalation of respiratory droplets or by direct contact with infected secretions.[13]

Approximately 10% of people are colonized at any given time, with peak rates in adolescents and young adults (10% to 35%) and the lowest prevalence in young children.[14][15] Carriage may be transient or persist for months. Many colonizing strains of N meningitidis are not pathogenic. Rarely, however, pathogenic strains may invade the bloodstream, causing systemic illness and hematogenous infections, or spread to the lower respiratory tract.[1] Disease typically occurs within 10 days after colonization of a susceptible host by pathogenic strains.[4]

Virulence factors expressed by pathogenic strains include the capsular polysaccharide, lipooligosaccharide, pili, and other outer membrane proteins.[4]

Whereas N meningitidis strains that colonize the nasopharynx are diverse, most invasive disease is caused by a relatively small group of genetically related bacteria, suggesting these organisms have increased pathogenicity.[16]

Pathophysiology

Sepsis caused by meningococci is multifactorial.[17] Bacterial factors, chiefly lipooligosaccharide, stimulate a proinflammatory cytokine response.[18][19]

The signs and symptoms of meningitis are a result of local inflammatory responses leading to cerebral edema, elevated intracranial pressure, and vascular thrombosis.

Hypotension results from increased vascular permeability and, in later stages of the illness, dysregulation of vascular tone. Both myocarditis and myocardial depression may contribute to poor tissue perfusion.

Bacteria release endotoxin, which triggers the inflammatory response; this in turn leads to activation of the coagulation cascade and downregulation of anticoagulant and fibrinolytic pathways. Disseminated intravascular coagulation is caused by these acquired deficiencies of protein C, protein S, and antithrombin III, increases in plasminogen activator inhibitor and thrombin-activatable fibrinolysis inhibitor, and reduced activation of protein C on endothelial cells. Resulting small-vessel thrombosis and skin necrosis cause purpura fulminans.

More rarely, thrombosis of larger blood vessels results in ischemia or infarction of digits or extremities.

Waterhouse-Friderichsen syndrome is caused by bilateral adrenal hemorrhage and necrosis with acute adrenal insufficiency.

Classification

Serologic classification[2]

Phenotypic classifications of the bacteria are based on the surface structures they elaborate. The most clinically relevant classification is serogrouping. Most pathogenic strains of N meningitidis possess 1 of 12 structurally and serologically distinct polysaccharide capsules:[2]

  • Serogroups A, B, C, Y, and W-135 cause >95% of invasive infections

  • Strains can be further distinguished by serotyping of major and minor outer membrane proteins and by immunotyping of lipooligosaccharides.

Genomic typing[3]

Multilocus or whole-genome sequencing can classify distinct strains of N meningitidis and is useful for epidemiologic studies.

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