Immune-mediated protection and enhancement of dengue drives patterns of infant cases in Brazil

Infants represent a vulnerable population for severe outcomes from infectious diseases. For dengue virus, maternal antibodies can cause severe disease in infants aged 5-12 months through antibody-dependent enhancement, but the role of maternal immunity in neonates aged 0-30 days has not been quantified. Our study leverages the re-emerging setting of Brazil, where the proportion of mothers with anti-dengue antibodies varies across space and time. Infant dengue burden has risen 11-fold from 2000-2024, in line with expansion in the general population. We fit mechanistic models to infant dengue and severe dengue cases reported through surveillance to disentangle the competing roles of maternal immunity, transmission, and age on the risk of dengue and severe dengue in infants across the first year of life. We observed peaks in severe dengue risk in neonates and at 7-8 months of age. These two peaks were explained by competing mechanisms. Infants born to seropositive mothers had lower overall risk of dengue, but increased risk of severe disease from 5-12 months, than those born to seronegative mothers. As dengue incidence increases, and vaccination becomes available, maternal antibodies may decrease infant burden but increase the risk of severe disease.