Within-host models unravelling the dynamics of dengue reinfections

Dengue fever is a major public health concern in tropical regions, caused by four distinct serotypes. Sequential infection with a different serotype increases the risks of severe disease through antibody-dependent enhancement (ADE). Huge modeling efforts have focused on primary and heterologous secondary infections, while the dynamics of homologous secondary infections were overlooked due to the assumption of lifelong immunity preventing reinfections by the same serotype. Recent findings challenge the current understanding of dengue immunity. To explore immunological responses in various dengue infection scenarios, we use a within-host modeling framework that considers individual immunological variations. These models are validated using empirical data. In addition to successfully capturing primary and heterologous secondary infection dynamics facilitated by ADE, this framework provides, for the first time, insights into homotypic reinfection dynamics and discusses its relevance in dengue transmission at the population level, with potential implications for disease prevention and control strategies.