Abstract
The kinetics of arthropod-borne virus (arbovirus) transmission by their vectors have long been recognized as a powerful determinant of arbovirus epidemiology. The time interval between virus acquisition and transmission by the vector, termed extrinsic incubation period (EIP), combines with vector mortality rate and vector competence to determine the proportion of infected vectors that eventually become infectious. However, the dynamic nature of this process, and the amount of natural variation in transmission kinetics among arbovirus strains, are poorly documented empirically and are rarely considered in epidemiological models. Here, we combine newly generated empirical measurements in vivo and outbreak simulations in silico to assess the epidemiological significance of genetic variation in dengue virus (DENV) transmission kinetics by Aedes aegypti mosquitoes. We found significant variation in the dynamics of systemic mosquito infection, a proxy for EIP, among eight field-derived DENV isolates representing the worldwide diversity of recently circulating type 1 strains. Using a stochastic agent-based model to compute time-dependent individual transmission probabilities, we predict that the observed variation in systemic mosquito infection kinetics may drive significant differences in the probability of dengue outbreak and the number of human infections. Our results demonstrate that infection dynamics in mosquitoes vary among wild-type DENV isolates and that this variation potentially affects the risk and magnitude of dengue outbreaks. Our quantitative assessment of DENV genetic variation in transmission kinetics contributes to improve our understanding of heterogeneities in arbovirus epidemiological dynamics.
Highlights
In the last few decades, arthropod-borne viruses have become major contributors of global mortality and disability, calling for an improved understanding of their transmission dynamics [1]
Due to the lack of available data, epidemiological models rarely account for the dynamic nature of this process and its natural variation among arbovirus strains
We experimentally monitored the dynamics of mosquito infection by eight strains of dengue virus and found significant differences between them
Summary
In the last few decades, arthropod-borne viruses (arboviruses) have become major contributors of global mortality and disability, calling for an improved understanding of their transmission dynamics [1]. In classic models of mosquito-borne pathogen transmission, one of the most influential parameters is the extrinsic incubation period (EIP), defined as the time interval between pathogen acquisition and pathogen transmission by the vector [8]. Current approaches to assess the epidemiological significance of variation in arbovirus transmission kinetics rely on temperaturedependent models developed from limited empirical data [10,11,12]. These models generally assume that the only factor affecting transmission kinetics is ambient temperature
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