BACKGROUND: Amidst a global resurgence of diphtheria cases with numerous outbreaks recorded worldwide since 2000, a better understanding of this vaccine-preventable disease's circulation is needed. METHODS: We retrospectively analyzed sera from 2 sero-epidemiological cross-sectional studies in Madagascar and Cambodia on fully primo-vaccinated 3- to 15-year-olds. Using enzyme-linked immunosorbent assay (ELISA) and seroneutralization (Vero Cell TNT) for the 3- to 8-year-olds with low ELISA titration values (<
0.01 IU/mL), we assessed (i) the duration of protection by primary vaccination for 3- to 8-year-olds and (ii) the level of diphtheria in children and adolescents. Seropositivity was defined as a titration value (by ELISA or TNT) of at least 0.1 IU/mL and was used as a proxy for diphtheria infection among individuals >
6 years postvaccination. RESULTS: Seven hundred forty-five children in Cambodia and 949 children in Madagascar were included. Our results show significantly more unprotected children among the 5- to 6-year-olds than among the 3- to 4-year-olds, with 41.1% (39/95) vs 26.7% (27/101
CONCLUSIONS: Our data show that the disease is present at high levels in Cambodia and Madagascar and that the national recommendation-primary vaccination-is not sufficient: Booster doses appear necessary at around 6 years of age and for adolescents, as recommended by the World Health Organization.