Aetiology
Meningococcal infections are caused by Neisseria meningitidis, an aerobic gram-negative diplococcus found exclusively in the human nasopharynx.
Meningococci colonise the human nasopharynx by adhering to non-ciliated columnar epithelial cells.[17] Transmission occurs by inhalation of respiratory droplets or by direct contact with infected secretions.[18]
Carriage prevalence increases through childhood, from around 5% in infants to a peak of 24% in 19-year olds; it decreases in adulthood to around 8%.[7][19] Carriage may be transient or persist for months. The mean duration of carriage in settings where prevalence is stable has been estimated at about 21 months.[7]
Many colonising strains of N meningitidis are not pathogenic. Rarely, however, pathogenic strains may invade the bloodstream, causing systemic illness and haematogenous infections, or spread to the lower respiratory tract. Disease typically occurs within 10 days after colonisation of a susceptible host by pathogenic strains.[4]
Virulence factors expressed by pathogenic strains include the capsular polysaccharide, lipo-oligosaccharide, pili, and other outer membrane proteins.[4]
Whereas N meningitidis strains that colonise the nasopharynx are diverse, most invasive disease is caused by a relatively small group of genetically related bacteria, suggesting that these organisms have increased pathogenicity.[20]
Pathophysiology
Sepsis caused by meningococci is multifactorial.[21] Bacterial factors, chiefly lipo-oligosaccharide, stimulate a pro-inflammatory cytokine response.[22][23]
The signs and symptoms of meningitis are a result of local inflammatory responses leading to cerebral oedema, raised 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 ischaemia or infarction of digits or extremities.
Waterhouse-Friderichsen's syndrome is caused by bilateral adrenal haemorrhage and necrosis with acute adrenal insufficiency.
Classification
Serological 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 Neisseria meningitidis possess 1 of 13 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 lipo-oligosaccharides.
Genomic typing[3]
Multi-locus or whole genome sequencing can classify distinct strains of N meningitidis and is useful for epidemiological studies.
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