title: Haemophilus influenzae serotype b conjugate vaccine failure in twelve countries with established national childhood immunization programmes.
abstract: The present study describes the clinical and immunological features of children with Hib vaccine failure, who were identified through national surveillance between 1996 and 2001 in Europe, Israel and Australia. True vaccine failure was defined as invasive Hib disease occurring ≥2 weeks after one dose, given after the first birthday, or ≥1 week after ≥2 doses, given at <1 year of age. Of the 423 cases (representing 0.2 cases per 100,000 child-years at risk) reported, 330 (78%) had received three doses in the first year of life and developed disease at a median age of 28 months. Of the remaining 93, 48 had received two doses in infancy, 34 had received four doses including a booster, and 11 had received a single dose after 12 months of age. These children developed disease at a median age of 12, 33 and 71 months, respectively. In total, 47 out of 258 children (18%) with available information had an underlying medical problem (including prematurity) and 53 out of 161 (33%) had immunoglobulin deficiency. Convalescent Hib antibody concentrations were above the putative protective concentration of 1.0 mg/L in 147/194 (76%) children; low concentrations were associated with both the presence of an underlying medical problem and young age at the time of Hib disease. Almost all children who received an additional vaccine dose developed antibodies at protective concentrations. Thus, Hib vaccine failure is rare, but can occur with any immunization schedule. Children with Hib vaccine failure should have immunoglobulin and convalescent Hib antibody concentrations measured after infection and receive additional vaccination, if required.
authors.affiliation: Immunisation Department, Centre for Infections, Health Protection Agency, London, UK. shamez.ladhani@hpa.org.uk
authors.forename: S
authors.initials: S
authors.lastname: Ladhani
authors.forename: P T
authors.initials: PT
authors.lastname: Heath
authors.forename: M P E
authors.initials: MP
authors.lastname: Slack
authors.forename: P B
authors.initials: PB
authors.lastname: McIntyre
authors.forename: J
authors.initials: J
authors.lastname: Diez-Domingo
authors.forename: J
authors.initials: J
authors.lastname: Campos
authors.forename: R
authors.initials: R
authors.lastname: Dagan
authors.forename: M E
authors.initials: ME
authors.lastname: Ramsay
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood*; D001315:Australia / Q000453:epidemiology; D016667:Bacterial Capsules / Q000008:administration & dosage* / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005060:Europe / Q000453:epidemiology; D006192:Haemophilus Infections / Q000453:epidemiology / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D018073:Haemophilus Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D019741:Haemophilus influenzae type b / Q000276:immunology*; D006801:Humans; D017589:Immunization Programs; D007115:Immunization Schedule; D007557:Israel / Q000453:epidemiology; D011159:Population Surveillance; D017211:Treatment Failure; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D018073:Haemophilus Vaccines; C044237:Haemophilus influenzae type b polysaccharide vaccine; D018074:Vaccines, Conjugate