Research Article: Epidemiological significance of dengue virus genetic variation in mosquito infection dynamics

Date Published: July 13, 2018

Publisher: Public Library of Science

Author(s): Albin Fontaine, Sebastian Lequime, Isabelle Moltini-Conclois, Davy Jiolle, Isabelle Leparc-Goffart, Robert Charles Reiner, Louis Lambrechts, Neil M. Ferguson.


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.

Partial Text

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]. Transmission of arboviruses is governed by a complex set of biotic and abiotic factors [2], the majority of which relate to the vector biology [3]. Individual, temporal and spatial variability in these factors results in considerable heterogeneities in arbovirus transmission dynamics, but the relative contribution of each factor is still poorly understood [4–7].

Building on earlier studies that showed EIP variation between DENV genotypes [23] and possibly serotypes [19, 20, 25], we have demonstrated that viral genetic variation in the kinetics of mosquito infection may contribute to heterogeneity in DENV transmission dynamics. Such temporal variation in the transmission process has generally been ignored in models of mosquito-borne pathogen epidemiology [9], with the exception of temperature-dependent models [10–12]. We experimentally compared field-derived DENV isolates representing the worldwide genetic diversity of recently circulating strains. We found significant variation in the dynamics of systemic infection of Ae. aegypti among the DENV isolates, which was poorly predicted by midgut infection patterns. Using large-scale simulations with a stochastic agent-based model, we illustrated how the empirical variation in systemic infection dynamics may translate into sizeable differences in epidemiological outcome (risk and magnitude of dengue outbreak in the human population).