Infection severity across scales in multi-strain immuno-epidemiological Dengue model structured by host antibody level
- 1 May 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Journal of Mathematical Biology
- Vol. 80 (6), 1803-1843
- https://doi.org/10.1007/s00285-020-01480-3
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 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.Funding Information
- Division of Mathematical Sciences (1815095)
- Simons Foundation (SFARI 638193)
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