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Meningococcal infections 

Meningococcal infections

Chapter:
Meningococcal infections
Author(s):

Petter Brandtzaeg

DOI:
10.1093/med/9780199204854.003.070605_update_004

Update: Prevention – (1) large scale vaccination in sub-Saharan Africa with serogroup A conjugate vaccine (MenAfriVac®) has proven very effective; (2) discussion of new vaccine containing factor H binding protein (fHbp) subfamily A and B.

Treatment – recommendations for pre-hospital use of ceftriaxone.

Updated on 30 Jul 2015. The previous version of this content can be found here.
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date: 25 March 2017

Neisseria meningitidis is an obligate human Gram-negative diplococcus. It is carried in the nasopharynx by about 10% of people, with most strains being harmless and inducing immunity. Pathogenic strains usually belong to specific clones that are encapsulated, express pili and the major porin, PorA. Serogroups A, B, and C usually account for more than 90% of all invasive isolates.

Epidemiology

Young asymptomatic adults are the main reservoir. Meningococci are transmitted by droplets and susceptible people usually develop the first symptoms within 2 to 4 days. The incidence of disease is highest during the first 4 years of life, with a secondary lower peak in adolescents. Pathogenic strains tend to cause single cases or small clusters in industrialized countries, whereas they cause large outbreaks in developing countries, particularly in the meningitis belt of Africa. Host factors predisposing to invasive disease include (1) lack of protective antibodies, (2) defects in the complement system, (3) HIV infection, and (4) polymorphisms of complement factor H, and possibly tumour necrosis factor.

Clinical features and prognosis

Initially, N. meningitidis induces bacteraemia, with growth velocity in the circulation a major determinant of the clinical presentation and outcome. The two major clinical presentations are meningitis and septic shock.

Meningitis—the commonest presentation (40–50%), preceded by low-grade meningococcaemia (<103/ml). After transition to the subarachnoid space, the meningococci proliferate to high levels (106–109/ml) in the cerebrospinal fluid. Clinically, the patients develop fever, and subsequently a petechial rash (30–80% of cases) and increasing symptoms of meningitis. If adequately treated with antibiotics, case fatality is <1% in industrialized countries, but higher in developing countries. Brain oedema leading to herniation of the cerebellum is the main cause of death. Neurosensory hearing loss is the major complication.

Septic shock—symptoms develop in 30% of European patients. The septic shock is preceded by high-grade meningococcaemia (106–108/ml). The massive bacterial proliferation leads to rapidly escalating endotoxin levels in plasma. Endotoxin triggers the innate immune system inappropriately. Within 12 h of initial symptoms, the patient may have persistent circulatory failure and severe coagulopathy leading to extensive skin haemorrhages, thrombosis of the extremities leading to gangrene, and impaired renal, adrenal, and pulmonary function. Mortality is high (16–52%).

Mild meningococcaemia—in industrialized countries, 20 to 30% of cases present with fever and petechial or macular rash, but without marked signs of meningitis or shock. The meningococcaemia is low-grade (<104/ml) and often transient. Occasional complications include pericarditis, arthritis, ocular infection or chronic meningococcaemia. Prognosis is good (with appropriate antibiotic treatment).

Diagnosis

Intra- and extracellular diplococci can be observed in the cerebrospinal fluid, peripheral blood buffy coat (fulminant septicaemia), and biopsies of haemorrhagic skin lesions using Gram or acridine orange stains. N. meningitidis can be grown from blood culture and swabs from the nasopharynx/tonsils. Polymerase chain reaction (PCR) methods are increasingly used to detect and classify N. meningitidis in blood, cerebrospinal fluid, other bodily fluids, and skin biopsies.

Treatment

Aside from supportive care, appropriate antibiotic treatment should be started immediately in suspected cases of meningococcal infection: this should not be delayed while the patient is transferred to hospital, or for the results of investigations to become available. Ceftriaxone or benzylpenicillin (intravenously or intramuscularly) remain the drugs of choice in most countries; chloramphenicol is also effective.

Prevention

Vaccination—conjugate vaccines comprising serogroups A, C, Y, and W polysaccharide are effective from 2 months of age. Two vaccines covering most serogroup B strains are presently marketed, one in Europe, Canada, and Australia, the other in the US.

Secondary prophylaxis—health authorities in most countries advise that close contacts of cases of meningococcal disease have eradication treatment, e.g. with a single dose of ciprofloxacin 500 mg or ofloxacin 400 mg. During pregnancy, a single dose of 250 mg ceftriaxone intramuscularly, and, for children below 12 years of age 125 mg intramuscularly, is effective.

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