This Seminar is based on the collective experience of all the authors with meningococcal disease and the meningococcal disease published work. We also searched Medline and PubMed. We used the search terms “Neisseria meningitidis”, “meningococci” or “meningococcal meningococcemia”, or “epidemic meningitis”. We largely selected publications in the past 5 years, but did not exclude important and highly regarded older publications. We also searched reference lists of articles identified by
SeminarEpidemic meningitis, meningococcaemia, and Neisseria meningitidis
Section snippets
Biology and microbiology
N meningitidis is a gram-negative β-proteobacterium and member of the bacterial family Neisseriaceae.4, 9, 10 There are 13 serogroups of N meningitidis based on different capsular polysaccharide structures, but only six serogroups (A, B, C, W-135, X, and Y) cause most life-threatening disease.1, 4, 11 These pathogenic bacteria occur in a few genetically defined clonal complexes that can emerge and spread worldwide.12, 13, 14, 15, 16 Meningococcal virulence is related to both capsule expression,
Epidemiology
Meningococcal disease can vary in incidence from very rare to over 1000 cases per 100 000 population every year.1, 4, 21, 31, 32 Serogroup A N meningitidis causes the highest incidence of disease. Repeated pandemics of serogroup A disease have taken place in Sahelian and sub-Sahelian countries of Africa, known as the African meningitis belt, every 5–10 years since 1905, and to a lesser extent in China and Russia over the past 25 years (figure 1).12, 14, 33, 34, 35 Outbreaks of serogroup A
Transmission and carriage
Acquisition of meningococci through very close contact with respiratory secretions or saliva can be transient, lead to colonisation (carriage), or result in invasive disease.49, 50, 51, 52, 53, 54 The inoculum size needed for transmission is unknown. Once meningococci penetrate the mucus barrier of the upper respiratory tract and attach to human epithelial cells, a series of interactions take place that result in effacement of the epithelial surface and microcolony formation (figure 4).50
Host susceptibility
Absence of protective bactericidal antibodies is the most important single predisposing factor for systemic meningococcal disease, but genetic polymorphisms and other host co-factors contribute to disease.43, 44, 61 Disappearance of antibody acquired from the mother increases the risk for infants and young children. Congenital and acquired antibody deficiencies, and possibly blocking of IgA immunoglobulin, also increase risk. Opsonisation and phagocytic function are important host defence
Pathophysiology
Different biological processes contribute to the pathogenesis and pathophysiology of meningococcal disease.2, 3, 71 Lipo-oligosaccharide is one of the most potent molecules activating various immune cells.2, 28, 72, 73 Lipo-oligosaccharides in whole and disintegrated bacteria and in outer membrane vesicles (figure 2) released by growing meningococci, are biologically very potent. They are abundantly present in shock plasma and in cerebrospinal fluid obtained from patients with meningcoccal
Clinical presentations
Although the overall clinical pattern of meningococcal disease is similar in all epidemiological situations, the number of patients who present with specific clinical features can vary from outbreak to outbreak for reasons that are not well understood. Fulminant septicaemia is recorded less frequently during African epidemics than it is for patients in industrialised countries.
In endemic and epidemic disease outbreaks in industrialised countries, haemorrhagical skin lesions are present in
Diagnosis
The clinical diagnosis of meningococcal meningitis relies on the recognition of fever, rash, meningeal signs, and altered mental status, and is confirmed by pleocytosis, gram stain with or without culture of cerebrospinal fluid, or blood or skin lesions.1, 4 The early diagnosis of meningococcaemia is a challenge because rash and meningeal signs might not be present. A retrospective study118 suggested that general symptoms of sepsis (leg pains, cold hands and feet, abnormal skin colour)
Treatment
Before passive immune or antibiotic treatment was available, the mortality of systemic meningococcal disease was 70–90%.124 The case fatality rate is now around 10% in many countries, including the UK.125 However, early recognition by parents and health professionals of the importance of fever and headache with a non-blanching rash (the glass test; figure 6B), prehospital antibiotic treatment, rapid transportation to a local hospital, and stabilisation in an intensive-care unit has
Prevention
Chemoprophylaxis to eliminate meningococci from carriers, and thus protect other susceptible individuals, is recommended for close contacts of patients. The occurrence of meningococcal disease in household contacts is 100-fold higher than in the normal population.1 Chemoprophylaxis can be helpful in the control of localised outbreaks in residential schools, barracks, etc, but is generally not recommended for the control of epidemics because of cost and drug resistance. For example, widespread
Future perspectives
N meningitidis has become a model organism for understanding bacterial pathogens that colonise and infect only human beings. Further dissection of the genetics and pathogenicity of the Neisseriaceae family should continue to reveal much about how meningococcus evolved, spread worldwide, and causes disease. This research is important in the quest for definition of basic mechanisms of microbial pathogenesis and for the design of strategies to deal with emerging or re-emerging microbial threats.
Search strategy and selection criteria
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