Impact of tetravalent dengue vaccination with screening, ADE, and altered infectivity on single-serotype dengue and Zika transmission.

Abstract

Acquired immunity to a dengue virus serotype (whether by infection or the only licensed dengue vaccine) can produce antibody-dependent enhancement (ADE) in later infections with another dengue serotype, resulting in higher viral loads and more severe symptoms such as dengue hemorrhagic fever, unless the person already has immunity to multiple dengue serotypes. Screening to confirm dengue seropositivity is therefore recommended before vaccination. Recent studies suggest that the closely-related Zika virus may also interact with dengue through ADE. This study uses a mathematical model to evaluate the likely impact of imperfect screening and dengue vaccination on the spread of both viruses in a population where only one dengue serotype circulates, although the vaccine may take against any or all of the four recognized serotypes. Analysis focuses on the reproductive numbers of the viruses. Results indicate that vaccination increases the spread of Zika through induced ADE, while its impact on the spread of dengue depends on screening specificity and serotype-specific vaccine efficacies, as well as the intensity of ADE. Numerical analysis identifies the roles played by age-in and catch-up vaccination as well as screening characteristics and prior dengue exposure.