Meningococcal Meningitis

Meningococcal meningitis and septicaemia are caused by various serogroups of Neisseria meningitidis (meningococcus) which is an aerobic Gram-negative encapsulated bacteria. At least 12 serotypes of meningococcus have been characterized by differences in the polysaccharide capsule, of which groups A, B and C account for about 90% of meningococcal disease. Recent outbreaks of group Y and W135 strains suggest that these serotypes are gaining in importance. N. meningitidis is one of the most common causes of bacterial meningitis in the world and the only bacterium capable of generating large epidemics of meningitis. Explosive epidemics with incidence rates of up to 1000 cases per 100,000 inhabitants have been reported, particularly in sub-Saharan Africa.

Meningococcus is transmitted by aerosol or direct contact with respiratory secretions of patients or healthy human carriers. As a rule, endemic disease occurs primarily in children and adolescents, with highest attack rates in infants aged 3-12 months, whereas in epidemics older children and young adults may be more involved. Nasopharyngeal carriage of meningococci is most common among adolescents and young adults, less so among young children and relatively rare in adult populations. Transient nasopharyngeal carriage rather than disease is the normal outcome of meningococcal colonization. However, the rapid progression of meningococcal disease frequently results in death within 1-2 days after onset. 5-15% of children and young adults carry meningococci in the nose and throat, so chemoprophylaxis is of little value for the control of most endemic and epidemic disease. Immunization is the only rational approach to the control of meningococcal disease.

Meningococcal Vaccines

Meningococcal vaccines containing unconjugated purified capsular polysaccharides (A, C, Y and W) have been available since the 1970s and are still used to immunise travellers and at risk individuals. Conjugated vaccine containing polysaccharide chemically conjugated to a protein carrier such as the non-toxic diphtheria toxin CRM 197 or tetanus toxoid are also now available. Vaccines can be formulated as bivalent (groups A and C) or tetravalent (groups A, C, Y, and W135). Meningitis B vaccines have been developed to combat strains endemic in certain areas, such as the disease outbreaks in New Zealand. Efforts involving joint collaborations between WHO, PATH, and other organizations are under way to develop group A conjugate vaccines to control epidemics of meningitis in sub-Saharan Africa. Protection is usually group-specific, and for groups A, C, Y and W135 protection appears largely to be due to anti-polysaccharide antibodies.

Meningococcal Vaccine Standardization

Written Standards

Meningococcal A vaccines

The recommendations include provisions for the production and quality control of meningococcal A conjugate vaccines were adopted in 2006.

Recommendations to assure the quality, safety and efficacy of group A meningococcal conjugate vaccines, TRS 962, Annex 2

Meningococcal C vaccines

The Recommendations for the production and control of Meningococcal group C conjugate vaccines were updated in 2001. An addendum was developed in 2003 which included for serological assays to evaluate the immune response to meningococcal conjugate vaccines. The clinical evaluation of group C meningococcal conjugate vaccines was further updated in 2007.

Meningococcal polysaccharides vaccines (unconjugated)

WHO recommendations for meningococcal vaccines which were first adopted in 1975 described the production and quality control of A and C polysaccharide vaccine preparations. These were updated in 1980 to include provisions for the increased potency attainable through reduction in the endotoxin content, the use of lactose as a thermal stabilizer, and to include the Y, 29E, and W135 strains. Another amendment in the 1999 reduced the number of guinea pigs required for the abnormal toxicity test.