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serogroups B, C, Y, and W135 account for almost all cases. It is unknown whether a similar distribution of serogroups accounts for endemic disease in developing countries.

Epidemic meningococcal disease occurs both as focal outbreaks and diffuse epidemics. Outbreaks are usually caused by strains of a single serogroup or serotype (the epidemic strain) or both. Epidemic disease often occurs in older children and young adults (as well as in infants and young children) and is geographically restricted. In the developed world prior to World War II, most outbreaks were caused by strains of serogroup A; this remains the case in most developing countries today. Epidemics of group A disease occur at roughly 10-year intervals in the African meningitis belt and may be associated with periods of warfare or economic decline. Group B and group C strains are also capable of causing epidemics, although the epidemics are usually less severe than those caused by group A strains. Group W135 has only a limited epidemic potential, and group Y is not known to have caused outbreaks.

Previous Efforts at Vaccination

Six purified capsular polysaccharides have been tested as vaccines in man. In individuals over 2 years of age, vaccines from strains of groups A, C, Y, and W135 reliably induce bactericidal antibodies that provide protection. The group C polysaccharide is not effectively immunogenic in children under 2 years of age. The group A polysaccharide induces low but protective levels of antibody in this age group. Protection as predicted by antibody levels afforded by the group C vaccine is long-lived in those who respond. The duration of protection against group A meningococcal disease appears to be related to world geography and age at time of immunization. Children under 4 years of age have a rapid fall off in antibody. In comparing the African and Finnish experience, the duration of protective efficacy appeared shorter in Africa. One contributing factor may be the presence of endemic malaria; Williamson and Greenwood (1978) observed a rapid decline in group A polysaccharide antibodies in individuals with malaria. Studies have not been conducted of the kinetics of antibodies to the polysaccharides of groups Y and W135.

The group B capsule is a homopolymer of alpha 2–8 linked sialic acid and, as such, closely resembles the terminal sialic acid residues on a number of gangliosides, and on polysialyl glycopeptides found in fetal brains. The polysaccharide is also found on the common gut organism E. coli K1; and, as a result, most individuals have primarily IgM antibodies to the B polysaccharide. These antibodies apparently do not facilitate bactericidal killing of the group B organisms.

In assessing the effectiveness of the current A, C, Y, and W135 tetravalent vaccine, it is imperative to distinguish between efficacy in the individual vaccinee and efficacy as a public health policy. in vaccinees older than 2 years of age, these four polysaccharides are highly immunogenic (about 85 to 95 percent) with no significant adverse reactions. Administration of the tetravalent vaccine may be less than optimally effective as a public health policy, however, for at least two reasons:



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