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Studies on the noncapsular surface antigens of H. influenzae type b in several laboratories have revealed a number of distinct strains within type b (Hansen et al., 1982a; Loeb and Smith, 1980). The relative prevalence of these different strains as a cause of disease varies with geographic locale. More than 20 different subtypes have been identified, but 5 or 6 account for most H. influenzae type b illness (Hansen et al., 1982a; Loeb and Smith, 1980). Subtyping is primarily of epidemiologic value, because all type b strains are killed by anti-type b polysaccharide antibodies. The type b polysaccharide has been purified and its structure determined. The repeating unit is →3)-β-D-ribose-(1→1)-D-ribitol-5-phosphate.

Host Immune Response

Protection against invasive H. influenzae disease is due primarily to humoral immunity (Solotrovsky and Lynn, 1978). Protective antibodies are induced to both the capsular polysaccharide and major outer membrane surface proteins. Classic studies by Fothergill and Wright (1933) demonstrated an inverse relationship between the development of bactericidal antibodies and the age-related incidence of H. influenzae disease. The same inverse relationship has been demonstrated for antibodies directed against the type b capsular polysaccharide (Anderson et al., 1977).

Following the decline of maternally acquired immunity between two and three months of age, bactericidal antibodies generally are not detectable for about three years. They then rise slowly, reaching adult levels by about age eight. However, there is considerable individual variability in the pattern of antibody changes.

Clinical studies suggest a positive correlation between the presence of anti-type b antibodies and the relative absence of H. influenzae disease in children older than five years of age (Peltola et al., 1977). Passive protection studies in animals, primarily the infant rat, provide further evidence for the protective effects of antibodies against type b polysaccharide (Myerowitz and Norden, 1977).

There is strong evidence from the Finnish studies of the capsular polysaccharide (polyribophosphate) vaccine for the protective role of antibody in older children (Peltola et al., 1984). However, the committee believes the focus should be directed towards a vaccine that would be effective in younger children because of the distribution of the disease described below.

Magnitude of Disease Burden

Estimates of the disease burden imposed by H. influenzae type b are based primarily on information from Cochi (personal communication, 1983), Hill (1983), and Norden (1982). All cases of invasive illness caused by the organism are assumed to fall into generic Morbidity Category C. (Morbidity Categories are defined in Table F.2.)



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