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.

Population-based study of non-typable Haemophilus influenzae invasive disease in children and neonates.

The extent of non-capsulate, non-serotypable Haemophilus influenzae (NST) as a cause of serious invasive disease in children has not been fully defined. We describe the epidemiology of these childhood infections from cases identified during a continuing prospective survey of invasive H influenzae disease in the Oxford region, UK. 408 strains of H influenzae were isolated from cases of invasive disease. 383 (94%) were H influenzae type b (Hib), 24 (6%) were NST strains, and 1 was a type f strain. 3 of the NST strains were non-capsulate type b mutants (b-), but the remaining 21 strains were from the phylogenetically distinct and heterogeneous population of non-capsulate H influenzae (NC). 10 of the NC strains were isolated from neonates with sepsis; crude mortality rate was 40%, with an incidence of 4.6 cases per 100,000 livebirths. 11 NC strains were isolated from children after the neonatal period and under 10 years of age, 4 (36%) of which had severe, unrelated, predisposing conditions. The incidence of NC invasive diseases in these children was 0.5 per 100,000 per year. The attributable mortality for these infections was 10%. Infections due to these H influenzae strains are, after the implementation of Hib vaccines, likely to persist and represent a substantial proportion of the serious infections caused by this species.