or on an age-neutral perspective. TDBVs thus obtained are 1,986 (committee median perspective) and 1,919 (age neutral perspective).
The distribution of H. influenzae illness is described above. Up to two to three months of age, most infants exhibit maternal antibodies. Although some cases of the disease appear between three and six months, most illness occurs between six and twelve months of age. Hence, the target population for active immunization probably will be all children at about three months of age. An earlier age of initial immunization may be practicable if a vaccine can be developed that induces immunity in younger infants.
H. influenzae generally has not been considered to be associated with outbreaks, but this may change with changing lifestyles in the United States. Studies are underway to determine the risk of primary disease and secondary spread in day care centers (Cochi, personal communication, 1983; Osterholm et al., 1983). Recent studies in Colorado have shown that the relative risk of developing H. influenzae type b disease is up to 12-fold higher in children who attend day care centers than in age matched controls (Istre et al., 1983). Thus, infants and children in day care centers may require special attention.
Invasive disease caused by H. influenzae type b is well suited to control by active immunization because antibody appears to provide protection, and because an opportunity to induce immunity exists between the decline of maternal antibodies (two to three months) and the peak of illness (after six months). Current treatment regimens are not satisfactory because chronic central nervous system sequelae often occur despite antibiotic therapy (Hill, 1983).
Chemoprophylactic agents (e.g., rifampin; Band et al., 1984) and passive immunization (with hyperimmune globulin) are possible post-exposure means of controlling secondary spread of disease. These methods were not considered further because secondary disease probably represents a small proportion of the total disease burden and because the methods are not directly relevant to the committee charge.
Success in vaccine prevention of invasive disease, particularly meningitis, will depend on the development of a vaccine capable of inducing immunity in infants. Progress towards this goal is described below.
Defining the target population is the first step in calculating the benefits that could be produced by a vaccine candidate. This definition can be then translated into an estimate for vaccine