Resurgence of invasive Haemophilus influenzae type b disease in France, 2017-2024: epidemiological, genomic, and immunological insights.

Abstract

Haemophilus influenzae type b (Hib) conjugate vaccines have markedly reduced global invasive Hib disease. However, surveillance in France has shown a resurgence of Hib infections in children despite >90% vaccination coverage, coinciding with the shift from a 3 + 1 to a 2 + 1 schedule. All laboratory-confirmed Hib cases reported to the French National Reference Centre for Meningococci and Haemophilus influenzae (NRCMHi) between 2017 and 2024 were analysed. Vaccine failure was defined as invasive Hib disease at least 2 weeks after completion of the age-appropriate schedule. Clinical, microbiological, and immunological data were collected, including whole-genome sequencing (WGS), anti-polyribosylribitol phosphate (PRP) IgG levels, and complement deposition assays. Among 1663 invasive H. influenzae cases, 268 (16.1%) were due to Hib, with annual proportions rising from 6.9% in 2017 to 16.8% in 2024. Of 197 cases in children under 5 years, 174 had known vaccination status; 55 (31.6%) met criteria for vaccine failure after completing the 2 + 1 schedule. All isolates were ST-6 clonal complex, without genotype linked to failure. Capsule locus duplication was found in 37% of isolates but unrelated to vaccination status. Acute-phase sera from failure cases showed anti-PRP IgG < 1 µg/mL, with convalescent titres rising above1 µg/mL; complement C3b and C5b-9 deposition correlated with antibody levels. The resurgence of Hib among fully vaccinated children highlights the need to reassess the 2 + 1 schedule and strengthen serological monitoring to sustain herd protection.