Long-term immunological follow-up of children with haemophilus influenzae serotype b vaccine failure in the United Kingdom

Background. It is not known how long children with Haemophilus influenzae serotype b (Hib) vaccine failure retain protective Hib antibody concentrations after infection. The objective of this study was to determine Hib antibody concentrations in children several years after infection and to identify risk factors for low antibody concentrations. Methods. The families of children from the United Kingdom who developed invasive Hib disease after prior immunization with Hib conjugate vaccine (i.e., Hib vaccine failure) from October 1992 through December 2005 were asked to complete a questionnaire. A blood sample was also obtained from each child. Results. Of 323 families approached, 260 (80.5%) returned a completed questionnaire, and 175 (54.2%) children provided a blood sample. The median age at follow-up was 8.4 years (interquartile range [IQR], 6.2-15.4 years), and the median duration of follow-up was 4.1 years (IQR, 3.5-9.7 years). Twenty-seven children (16.1%) had been born prematurely and/or had an underlying medical condition, and 18 (10.8%) had immunoglobulin deficiency. The median Hib antibody concentration was 0.70 μg/mL (IQR, 0.22-5.8 μg/mL). Overall, 95 children (56.9%) had antibody concentrations <1.0 μg/mL, and 27 (16.2%) had antibody concentrations <0.15 μg/mL. All 3 children with Down syndrome and 10 (42%) of 24 children aged <5 years at follow-up had Hib antibody concentrations <0.15 μg/mL. An antibody concentration <0.15 μg/mL was independently associated with underlying conditions, young age at onset of Hib disease, and shorter time from Hib disease to follow-up. Conclusions. More than one-half of the children with Hib vaccine failure had antibody concentrations below those considered to confer long-term protection, which suggests that these children might be at further risk of invasive Hib disease and would benefit from another dose of Hib vaccine.