Prior to the development and use of Hib conjugate vaccines, Hib was the most common cause of invasive bacterial infection and bacterial meningitis in children in the United States; 3 to 6% died, and permanent sequelae, ranging from mild hearing loss to mental retardation, were seen in 20 to 30% of survivors. The conjugate vaccines induce bactericidal antibodies to capsular polysaccharide (polyribitol ribose phosphate [PRP]), a critical virulence factor that facilitates hematogenous dissemination. A key step in the development of the vaccines was the conjugation of PRP to a protein carrier, enabling the induction of antibody responses in infants at the peak age incidence of Hib infection. An unexpected finding was that vaccination reduced or eliminated nasopharyngeal carriage of Hib. In the pre-Hib vaccine era, the colonization rate of Hib in infants and children was 3 to 5%. The rate is close to zero in countries that employ widespread Hib vaccination. The reduction of circulating strains in the population results in a herd effect, contributing importantly to the efficacy of the vaccine.
Despite the immunogenicity and high efficacy of Hib conjugate vaccines in infants, a small number of Hib infections occur in vaccinated children. Children who experience Hib disease despite vaccination appear to have a defect in immunological priming, resulting in lower-avidity antibodies to Hib capsular polysaccharide (5
Higher rates of invasive Hib disease were observed in the prevaccine era among some indigenous populations, including Native Americans in the southwest United States, Alaska Native children, and Australian aboriginal populations. Immunization programs have resulted in marked reduction in invasive Hib disease in these populations. However, despite high rates of immunization, the incidence of invasive Hib disease remains higher in native populations than in nonnative populations (29
). The ability to respond to an Hib conjugate vaccine with protective immune responses appears to have both genetic and acquired components (46
). The presence of low-response groups in a population will influence the efficacy of vaccine programs, emphasizing the importance of continued surveillance of invasive H. influenzae
infection with careful attention to the distribution of capsular serotypes of disease-causing strains. The importance of continued surveillance is further emphasized by the potential for reservoirs for continued circulation of Hib under selected circumstances in selected populations (33
While Hib conjugate vaccines have nearly eradicated Hib disease in developed countries that have adopted widespread use, a substantial global burden of Hib infection persists. Watt et al. (48
) estimated that Hib caused ~8 million serious illnesses and ~371,000 deaths worldwide in 2000. These infections are almost entirely vaccine preventable.