Infection severity across scales in multi-strain immuno-epidemiological Dengue model structured by host antibody level

TL;DR

This paper develops a multi-scale model linking within-host immune responses to population-level Dengue spread, capturing antibody dynamics and severity, to better understand disease transmission and hemorrhagic fever risk.

Contribution

It introduces a novel coupled within-host and epidemiological model structured by host antibody levels, incorporating antibody-dependent enhancement effects.

Findings

Model captures antibody waning and cross-reactivity effects.

Reproduction numbers depend on immunological variables.

Numerical simulations reveal parameter impacts on disease spread.

Abstract

Infection by distinct Dengue virus serotypes and host immunity are intricately linked. In particular, certain levels of cross-reactive antibodies in the host may actually enhance infection severity leading to Dengue hemorrhagic fever (DHF). The coupled immunological and epidemiological dynamics of Dengue calls for a multi-scale modeling approach. In this work, we formulate a within-host model which mechanistically recapitulates characteristics of antibody dependent enhancement (ADE) in Dengue infection. The within-host scale is then linked to epidemiological spread by a vector-host partial differential equation model structured by host antibody level. The coupling allows for dynamic population-wide antibody levels to be tracked through primary and secondary infections by distinct Dengue strains, along with waning of cross-protective immunity after primary infection. Analysis of both the within-host and between-host systems are conducted. Stability results in the epidemic model are formulated via basic and invasion reproduction numbers as a function of immunological variables. Additionally, we develop numerical methods in order to simulate the multi-scale model and assess the influence of parameters on disease spread and DHF prevalence in the population.