Haemophilus influenzae type b (Hib) seroprevalence in France: impact of vaccination schedules

BackgroundHaemophilus influenzae serotype b (Hib) conjugate vaccine was introduced in France in 1992 as a 3+1 scheme at 2, 3, and 4months (primary vaccination) with a booster at the age of 16-18months. The vaccination was simplified in 2013 to a 2+1 scheme at 2 and 4months (primary immunization) and a booster at the age of 11months. The coverage was 95.4% in France at 24months in 2017. During the period 2017-2019 the number of Hib invasive infections increased with several cases of vaccine failure.MethodsThe numbers and proportions of Hib invasive isolates during the period 2017-2019 were compared and vaccine failure cases were explored. A seroprevalence study was performed by measuring anti-polyribosyl-ribitol phosphate (PRP) IgG concentrations by ELISA among children <5years of age at the time of sampling covering the periods of the 3+1 or 2+1 schemes of Hib vaccination. A collection of residual 232 sera was tested (group 3+1 n=130) and (group 2+1, n=102) was used.ResultsAnti-PRP IgG concentrations were significantly higher in toddlers of 2years (median 2.9 mu g/ml) in the 3+1 group while these concentrations showed a median of 0.58 mu g/ml among children in 2+1 group. The proportion of children of 2years of age who achieved 1 mu g/ml threshold (56%) was higher in the 3+1 group than that observed in the 2+1 group (25%). All the detected cases of vaccine failure received the 2+1 scheme and anti-PRP IgG levels were less than 1 mu g/ml at the admission. However, these levels increased significantly 1 month after the admission suggesting a secondary immune response to the Hib infection.ConclusionsThe simplification of the vaccination to a 2+1 scheme seems to reduce the level of anti PRP IgG. Hib antibodies wane rapidly after the 11months booster and may not be enough to ensure long term protection. Surveillance of cases and monitoring of titres need to be continued to inform future vaccination policy.