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Appendix D-8: The Prospects for Immunizing Against Neisseria meningitidis
Pages 251-266

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From page 251...
... Meningococcal disease, the associated immunological phenomena, and vaccination strategies have been recently reviewed (Frasch, 1983, 1985; Griffiss, 1982; Peltola, 1983) D ISEASE DESCRIPTION Neisseria meningitidis causes about one-third of all cases of bacterial meningitis worldwide.
From page 252...
... 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.
From page 253...
... Endemic disease, in contrast, is caused by strains of much greater serotype diversity. However, vaccines containing noncapsular surface antigens are the only practical option for a group B vaccine.
From page 254...
... They are also able to survive in individuals with isolated deficiencies of immunoglobulins, particularly IgM, and complement components, and in those in whom circulating IgA blocks bactericidal activity (Griffiss, personal communication, 1985~@ Griffiss (1982) has theorized that the first two mechanisms could account for endemic disease, the third for epidemic disease.
From page 255...
... Endemic meningococcal disease is presumed to be distributed worldwide, although data are not available from most areas. Disease Burden Estimates Little reliable data are available on the worldwide incidence of meningococcal meningitis from which to estimate the disease burden arising from endemic and epidemic disease caused by N
From page 256...
... . Benin Burkina Faso Cameroon Central African Republic Chad Ethiopia Ghana Guinea Ivory Coast Kenya Mali Mauritania Niger Nigeria Senegal Sudan Tanzania The Gambia Uganda Total 3.9 6.7 9.4 2.6 5 32 14.3 5.6 9.2 19.4 7.6 1.8 6.3 88.1 6.5 21.1 21.2 0.7 14.3 275.7 SOURCE: Population Reference Bureau (1984)
From page 257...
... Deaths Under 5 5.4 498,559,000 26,922 20 5,384 5-14 6.1 909,366,000 55,471 10 5,547 15-59 2.4 1,954,728,000 46,913 25 11,728 60 and over 0.8 232,347,000 1,859 80 1,487 Endemic Meningococcal Meningitis Incidence rates for endemic meningococcal meningitis can be derived from the data reported by Cadoz et al.
From page 258...
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From page 259...
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From page 260...
... , the vaccine target population for endemic disease is considered to be the birth cohort in developing countries. Epidemic disease most often occurs in young children, but it also may occur in older children and young adults.
From page 261...
... However, relatively little disease occurs in children under 6 months of age. Based on the above considerations, it is estimated that 95 percent of meningococcal meningitis is theoretically preventable with a hypothetical fully effective improved vaccine for groups A, C, Y
From page 262...
... has comprehensively reviewed the development of existing meningococcal vaccines and their characteristics. The principal drawback of the existing polysaccharide vaccines against _ meningitidis (groups A, C, Y
From page 263...
... meningitidis and to identify bacterial strains will increase the usefulness of future clinical trials. Obstacles to Development of Vaccines Against Group B Strains The major obstacle to preparation of a vaccine against this important cause of meningococcal meningitis is that the group B capsular polysaccharide is not an effective immunogen in mice or in humans (Frasch, personal communication, 1984; Wyle et al., 1972~.
From page 264...
... Efforts to improve the polysaccharide's immunogenicity by using adjuvants or covalent linkage to proteins must be pursued with caution because certain structures in the human fetal and newborn brain contain short oligosaccharides of sialic acid with the same alpha 2-8 linkage {Finne et al., 1983; Soderstrom et al., 1984; Zollinger et al., 1979~. This potential cross-reactivity may explain, in part, the poor immunogenicity of the group B polysaccharide.
From page 265...
... 1981. Antibody response to capsular polysaccharides of groups A and C Neisseria meningitidis and Haemophilus influenzae type b during bacteremic disease.
From page 266...
... 1980. Type-specific antigens of group A Neisseria meningitidis: Lipopolysaccharide and heatmodifiable outer membrane proteins.


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