Mathematical modeling of sequential Dengue–Zika infections: dynamic insights into antibody-dependent enhancement and neutralization effects

Human infections caused by viruses of the Flavivirus genus, such as dengue virus and Zika virus, are developing global concern. The phenomenon of antibody-dependent enhancement (ADE) indicates that secondary infection with one flavivirus after a primary infection with another can lead to a larger viral load. This poses challenges for existing dengue vaccines and presents obstacles to the development of future Zika vaccines. This study aims to shed light on a distinct aspect of ADE, known as antibody-dependent neutralization (ADN). A sequential infection model for dengue and Zika is proposed, capturing the joint dynamics of both diseases. A qualitative analysis is conducted, examining a disease-free state and four boundary equilibrium points, with two strains representing sequential dengue and Zika infections. The model is calibrated using weekly case data on dengue and Zika infections from Espirito Santo, Brazil, from January 3, 2021, to September 11, 2021. To identify the key drivers of disease dynamics, we apply global sensitivity analysis techniques, including partial rank correlation coefficient (PRCC) and Latin hypercube sampling (LHS). Analysis reveals that although ADE has an obstructive impact on sequential cases, it can contribute to neutralizing infection status when it exceeds a threshold due to ADN.