We hypothesize that dengue virus (DENV) infected humans vary in their infectiousness to Aedes aegypti and, thus, in their potential for involvement in virus transmission dynamics. We expect that the relative contribution of different people can be predicted by the magnitude and duration of their viremia, which are positively associated with the severity of their disease. We will test the following three assumptions of our hypothesis by directly feeding Ae. aegypti on DENV-viremic people: 1) mosquito infection is positively associated with magnitude of viremia, 2) human to mosquito transmission is a function of temporal heterogeneity in viremic profiles, and 3) although their infectiousness is relatively low, people with inapparent and mild infections can infect mosquitoes and contribute to DENV transmission.
In Aim 1 we will characterize the relationship between magnitude of human DENV viremia and infectiousness to Ae. aegypti. We will test the prediction that there is a positive relationship between increasing magnitude of viremia, severity of disease, and mosquito infection by measuring infectiousness of naturally infected people to mosquitoes. We expect there to be a threshold below which virus transmission to mosquitoes does not occur and a negative relationship between viremia titer and duration of extrinsic incubation in mosquitoes.
In Aim 2 we will describe temporal dynamics of human DENV infectiousness to Ae. aegypti and determine whether the potential for humans to transmit DENV to mosquitoes changes over the course of a person's viremia. We will sequentially measure infectiousness of the same naturally viremic individuals to monitor temporal dynamics in mosquito infection. We expect that potential for mosquito infection will be the product of duration and varying magnitudes of viremia, which will be positively associated with disease severity.
In Aim 3 we will determine the relative capacity of people with inapparent/mild DENV infections to transmit virus to Ae. aegypti. We expect that viremia during inapparent/mild infections is sufficiently high and long-lasting to infect mosquitoes and contribute to DENV transmission. By characterizing a robust sample, we will provide the first quantitative estimates of critical transmission parameters for people with inapparent/mild dengue infections.
In as natural as way as is possible, Project 1 will quantitatively define heterogeneity in the capacity of people across the spectrum of dengue disease severity to infect mosquitoes. Clarifying this enigma will facilitate application and evaluation of disease prevention strategies, define surveillance and intervention priorities, and refine the theory of DENV transmission dynamics.
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