Mathematical models of Haemophilus influenzae type b.

A review of empirical studies and the development of a simple theoretical framework are used to explore the relationship between Haemophilus influenzae type b (Hib) carriage and disease within populations. The models emphasize the distinction between asymptomatic and symptomatic infection. Maximum likelihood methods are used to estimate parameter values of the models and to evaluate whether models of infection and disease are satisfactory. The low incidence of carriage suggests that persistence of infection is only compatible with the absence of acquired immunity to asymptomatic infection. The slight decline in carriage rates amongst adults is compatible with acquired immunity, but could be a consequence of reduced contacts. The low rate of disease observed in adulthood cannot be explained if protection from disease is a product of previous detectable exposure to Hib alone. We estimate an R0 of 3.3 for Hib in developed countries, which suggests that current immunization programmes may eliminate the infection. Analysis of the disease data set suggests the absence of maternal immunity and increased susceptibility to disease in the oldest age classes.

Conjugate vaccines and the carriage of Haemophilus influenzae type b.

Pharyngeal carriage of Haemophilus influenzae type b (Hib) is important in the transmission of Hib organisms, the pathogenesis of Hib disease, and the development of immunity to the bacterium. The remarkable success of current vaccination programs against Hib has been due in part to the effect of conjugate Hib vaccines in decreasing carriage of Hib. This review explores evidence for this effect, and discusses the possible mechanisms of the mucosal influence of Hib conjugate vaccines.

The impact of conjugate vaccine on carriage of Haemophilus influenzae type b.

Conjugate vaccines against Haemophilus influenzae type b (Hib) may modify Hib pharyngeal colonization. Hib colonization was compared in 371 infants and their families. In Oxfordshire, infants received PRP-T (polyribosylribitol phosphate conjugated to tetanus toxoid) and in Buckinghamshire they did not (controls). Infants were followed at 6, 9, and 12 months of age. Also, 6 unvaccinated Hib carriers were vaccinated and followed for 6 weeks. Hib acquisition was lower in vaccinees than controls (P < .01). During surveillance, 1.5% of vaccinees and 6.3% of controls carried Hib (P = .04). Among those with family Hib exposure, the carriage rates were 8.7% and 38.5% (P = .07), respectively. Hiv carriage rates were lower among vaccinees' unvaccinated siblings. Giving conjugate vaccine to a child carrying Hib did not rapidly terminate carriage. Thus, a primary means by which herd immunity to Hib is induced in a vaccinated population may be through reduction or delay in the initial acquisition of Hib.

Haemophilus influenzae type b carriage and immunity four years after receiving the Haemophilus influenzae oligosaccharide-CRM197 (HbOC) conjugate vaccine.

Late in 1991, before the implementation of a national immunization program against Haemophilus influenzae type b (Hib) in the United Kingdom, we performed a 4-year follow-up of 120 children who in 1987 had been enrolled in an immunogenicity trial in which 60 of them (vaccinees) received an Hib conjugate vaccine (HbOC) at the same time as diphtheria-tetanus toxoid-pertussis vaccine at the ages of 3, 5 and 9 months. Sixty others (controls) received only diphtheria-tetanus toxoid-pertussis vaccine at the same ages and were not subsequently immunized against Hib. We investigated Hib pharyngeal colonization using the antiserum agar method and the concentrations of serum IgG antibody to the type b capsule by enzyme-linked immunosorbent assay. At 4 years of age the Hib colonization rates in vaccinees and controls were 8% (5 of 60) and 5% (3 of 60), respectively. The children colonized with Hib had greater serum anti-capsular IgG concentrations than did noncolonized children (P < 0.001), and colonized vaccinees tended to have higher concentrations than colonized controls (P = 0.053). Regardless of Hib colonization status vaccinees had greater antibody concentrations than controls (P < 0.001). Forty-nine percent of vaccinees had an antibody concentration > 1 microgram/ml. There was an inverse relationship between the Hib colony count on culture and the serum IgG concentration. These data indicate that the increase in serum antibody concentration after immunization with an Hib conjugate vaccine is sustained and that immunization primes for a booster response on exposure to Hib. There may be a relationship between previous Hib conjugate immunization and the density of Hib colonization in children.

An improved antiserum agar method for detecting carriage of Haemophilus influenzae type b.

Enriched Columbia medium was tested against Levinthal medium for the isolation of Haemophilus influenzae type b. In both media, Haemophilus influenzae type b recovery and antigen-antibody precipitation halos were equivalent. Haemophilus influenzae type b colony size and iridescence were superior on enriched Columbia medium. Enriched Columbia medium is inexpensive, simply prepared and easily standardised.