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J Theor Biol. 2013 Sep 7;332:203-10. doi: 10.1016/j.jtbi.2013.04.036. Epub 2013 May 7.

Breaking the symmetry: immune enhancement increases persistence of dengue viruses in the presence of asymmetric transmission rates.

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Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, Maryland 21205, USA.


The dengue viruses exist as four antigenically distinct serotypes. These four serotypes co-circulate and interact with each other through multiple immune-mediated mechanisms. Though the majority of previous efforts to understand the transmission dynamics of dengue have assumed identical characteristics for these four serotypes, empirical data suggests that they differ from one another in important ways. Here, we examine dynamics and persistence in models that do not assume symmetry between the dengue viruses. We find that for serotype transmission rates that are only slightly asymmetric, increased transmissibility of secondary infections through immune enhancement increases the persistence of all dengue viruses in opposition to findings in symmetric models. We identify an optimal magnitude of immune enhancement that maximizes the probability of persistence of all four serotypes. In contrast to other pathogen systems where heterogeneity between serotypes in transmissibility facilitates competitive exclusion (Bremmermann and Thieme, 1989), here we find that in the presence of Antibody Dependent Enhancement (ADE) heterogeneity can increase the persistence of multiple serotypes of dengue.


Antibody dependent enhancement; Dengue; Dengue vaccine; Serotypical asymmetry

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