Partial cross-enhancement in models for dengue epidemiology

Four distinct serotypes of dengue virus co-circulate in many parts of the world. Antibodies to one serotype prevent infection with the homologous serotype, but may enhance infections with heterologous serotypes. Enhanced secondary infections have been implicated in the majority of severe cases, termed dengue hemorrhagic fever. Conventionally, mathematical models assume that all heterologous secondary infections are subject to enhanced susceptibility or transmissibility. However, empirical data show that only a minority of secondary infections lead to severe disease, which suggests that only a minority of secondary infections are subject to enhancement. We present a new modelling framework in which the population susceptible to secondary infection is split into a group prone to enhanced infection and a group with some degree of cross-protection. We use this framework to re-evaluate the role of enhanced infections in several well known dengue models that exhibit multi-annual epidemiological oscillations. We show that enhancement is unlikely to be driving such oscillations but may be modifying the effects of other drivers.