Impact of insecticide control measures and temperature on Dengue Virus transmission by Aedes aegypti mosquitoes - Dengue is a human disease caused by the dengue virus (DENV) and transmitted by Aedes aegypti and Aedes albopictus mosquitoes that afflicts hundreds of millions of humans, causes 20,000 confirmed human deaths annually, and puts >3.6 billion people at risk. Temperature varies profoundly spatially and temporally across transmission regions, and transmission-linked traits such as mosquito survival, reproduction, biting, and vectorial capacity are highly sensitive to temperature. Therefore, the R0, an important proxy of the population growth rate of pathogens and thus transmission, of dengue also varies profoundly with temperature. In recent years, my sponsor, co-sponsor, and colleagues have developed temperature-dependent, trait-based transmission models for mosquito-borne diseases (including dengue), using a generalized R0 equation derived from the classic Ross-Macdonald model. This predictive equation, however, is limited by the fact that temperature is the sole abiotic factor considered, despite other widespread abiotic factors, such as insecticides, being well known to impact traits of mosquitoes that affect transmission. My objective for this application is to develop and parameterize this model for DENV transmission by Ae. aegypti with commonly deployed insecticides with an overall goal of reducing DENV transmission. My central hypothesis is that insecticides and temperature interact synergistically or antagonistically, rather than additively, to affect the R0 of DENV. To test this hypothesis, I will conduct response surface experiments crossing 5 insecticide doses of both the larvicide temephos and the adulticide deltamethrin and 7 temperatures on juvenile and adult Ae. aegypti and DENV, and I will measure all eight temperature-dependent parameters in the generalized R0 equation. Using Bayesian inference, I will fit thermal performance curves to each trait across insecticide doses and implement these into the R0 equation. Once these aims have been completed, I will have developed the first fully parameterized insecticide- and temperaturedependent R0 model for dengue. The aim of this R0 model is to more accurately predict disease incidence, identify the extent to which temperature impacts the efficacy of common insecticides, determine the ideal seasonal conditions to deploy insecticides in, and determine minimum insecticide concentrations to prevent dengue transmission across thermally variable landscapes. Public Health Statement Temperature-dependent, trait-based transmission models are essential to informing control of dengue virus (DENV) transmission by Aedes aegpyti and Aedes albopictus mosquitoes. They are limited, however, by temperature being the sole abiotic factor considered, despite other widespread abiotic factors, such as insecticides, being well known to impact transmission-linked mosquito and pathogen traits. Through experiments crossing common insecticides with temperature treatments, this application will develop and parameterize an insecticide- and temperature-dependent, trait-based transmission model for DENV. This is expected to predict dengue incidence more accurately than current temperature-alone models, identify the extent to which temperature impacts the efficacy of common insecticides, and determine the most effective environmental conditions to deploy insecticides in to reduce transmission.
