Zika virus is an example of a mosquito transmitted virus that rapidly emerged out of Africa and spread across South and Central America, as well as the Caribbean Islands. While the effects of Zika infection can be shattering (e.g. microcephaly, neurological disease), we lack therapeutics or a viable vaccine to control transmission. Killing mosquitoes and reducing mosquito-human contact rates are the only mechanisms to mitigate disease risk. Developing tools that will allow us to successfully predict outbreaks of these viruses and efficiently target current and future interventions to specific times and locations will aid effective mosquito and disease control. Yet, these efforts are often limited by several key knowledge gaps.

This research addressed these knowledge gaps that presently curtail our ability to predict ZIKV disease transmission. These included (but are not limited to): 1) a very poor understanding of the ability of the virus to establish and replicate within the mosquito after feeding on humans that can vary widely in the amount of virus present in the blood, and 2) how key environmental variables like temperature affect this ability in the cold-blooded mosquito, whose small body quickly tracks changes in environmental temperature, as well as potential disease intervention strategies (for example, vaccination, drug treatment, mosquito control).

Our research demonstrated that when mosquitoes are exposed to an increasing concentration of virus in the blood-meal they experience increases in the probability of becoming infected and infectious, as well as the rate at which virus spreads to the saliva. This in turn translated into a predicted increase in overall risk of transmission by 3.8-fold. We also demonstrated that temperature is a strong driver of the ability of mosquitoes to become infected, infectious, and overall risk of transmission. Zika virus transmission was optimized at 29°C and was constrained at temperatures below 22.7°C and above 34.7°C.  Thus, as mean temperatures move toward the predicted thermal optimum (29^oC) due to climate change, urbanization, or seasonality, Zika could expand north and into longer seasons. In fact, we would predict that an additional 1.3 billion new people could be at risk for future Zika virus exposure with global warming. Finally, we demonstrated that common disease intervention efforts that focus on reducing the probability of transmission to the human host (vaccination), the time a human host is infectious (drug treatment), and how long mosquitoes survive in the field (insecticide applications) are all highly sensitive to variation in environmental temperature. This result suggests that the ability of common strategies to control virus transmission could vary with temperature across geographic region, land use, and season.

Intellectual merit and broader impacts: The funded research has produced a comprehensive framework for integrating and assessing how relevant sources of variation introduced by the human host, the surrounding environment, and our disease control strategies influence mosquito-borne disease transmission. While this project focused on the Zika virus system, the implications of this work will extend to other systems and geographic regions that involve the highly invasive and human tolerant yellow fever mosquito, such as dengue and chikungunya viruses.  The project also materially and intellectually supported inter-institution relationships between Harvard, Stanford, PIVOT, and the University of Georgia. Finally, the funded research provided research opportunities and training for two Ph.D. students, one post-doctoral researcher, one technician, and three undergraduate researchers.

Last Modified: 12/05/2018
Modified by: Courtney Murdock