Determining the risks of mosquito-borne viral zoonoses emerging and spreading from East African forests

Many diseases are transmitted to humans by mosquitoes. For example, the well-known and widespread tropical diseases yellow fever and dengue fever, are caused by viruses spread by the mosquito, Aedes aegypti. These were originally animal diseases and the viruses and mosquito originated from the tropical forests of Africa. These forests are rich in animal wildlife and also have large numbers of associated animal-feeding mosquito species and the viruses these mosquitoes transmit. These viruses sometimes spill over into human populations resulting in localised outbreaks of what are normally animal diseases e.g. Chikungunya and Zika. As humans encroach increasingly on these forests, they expose themselves to greater and greater risk of being infected by these primarily animal-infecting viruses. Because of this vast array of viruses (some of which may even be unknown to science), and the large number of mosquito species that could spread them, these old tropical African forests are a high risk as a source of new diseases in humans. We aim to predict these risks and to identify viruses or mosquitoes likely to be involved in future human disease. This information can be used to prevent the spread of new human diseases. For example, surveillance strategies could be put in place to detect changes in viruses or mosquitoes that are early warning signs of a new disease emerging in humans. In addition, changes could be made to how land is used, e.g. for agriculture, in and around forests.

We will study the interactions that occur between mosquitoes, viruses, the environment (forest and surrounding villages) and humans to assess what changes could occur to result in the emergence of new human diseases. For example, we want to know: How often humans enter the forest and why? How might increased human mobility affect disease spread? What is the potential for viruses to infect humans by switching from animal-feeding into human-feeding mosquitoes? May mosquito species that normally live in the forest move to human habitats so bringing humans into contact with the viruses these mosquitoes normally transmit to animals? Because this will be a large and complex project we will first have a planning phase. This will involve discussions between UK and African scientists, social scientists and agencies involved in health and policy making, e.g. the World Health Organisation, to enable us to design an integrated research plan that will deliver the information needed to prevent or minimize new human disease.

Our long-term study will make predictions of the likelihood of viral zoonotic diseases emerging in humans from a key forest ecosystem: the old, tropical forests of Africa. These ancient forests have accumulated rich biodiversity, not only of animal wildlife but also their associated vector mosquitoes and a diverse array of arboviruses. Humans are increasingly interacting with this ecosystem and are already widely affected by several, originally zoonotic, viruses such as yellow fever and dengue. Other zoonotic viruses are also capable of infecting humans, e.g. Zika and Chikungunya, sometimes emerging as localized epidemics. This high viral diversity, coupled with the large number of potential vector species ( 100 species of Aedes mosquitoes in East Africa), make this ecosystem an extremely high risk for emerging zoonoses. The greatest risk is probably transfer of a novel virus into the mosquito Aedes aegypti because of this mosquito?s adaptation to domestic habitat and global distribution. For this reason, and because of their high diversity in African forests, our study will focus on Aedes mosquitoes and the viruses they transmit.

We will use a multi-disciplinary approach to study the range of biological, socio-economic, and environmental factors that interact to affect risks of zoonotic viral emergence. This will involve studies of human behaviour, vector ecology, the genomics of vector adaptation to domestic habitat, vector feeding preference, viral specificity to different mosquito species, etc. We will integrate the information across the levels, from molecular evolution to social change, towards a predictive framework using mathematical and computer modelling techniques. As well as providing an integrative understanding of the system, the modelling will be able to identify and quantify particular risks. Socio-economic data will be used to enable different interaction scenarios to be explored within the model. As such our approach is a system biology approach in the broadest sense, integrating high throughput data with bio-informatics and mechanistic models of the predictive outcomes.

The catalyst grant will enable us to develop a detailed, practicable, integrated research strategy, iterated through a series of network meetings. We will make a brief visit to potential field sites in Tanzania to formulate appropriate and realistic research methodologies. A key meeting will be a workshop in Tanzania aimed at identifying the research needs of diverse stakeholders (from health, forestry, national parks, land use planners, etc) to ensure maximal use of project output, for example, for better surveillance systems or informing land use policy.