Optimal trial design for a confined release of malaria-refractory transgenic mosquitoes

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Malaria is an infectious disease caused by a parasite spread between people by mosquitoes. In sub-Saharan Africa, it causes an estimated 800,000 deaths per year, most of whom are children under the age of five. The disease is proving very difficult to control in many parts of Africa using tools that are currently available. These include bed nets, insecticides and antimalarial drugs. It is thought that, even if these tools are widespread, elimination may not be possible in some areas. Consequently, new strategies are being considered that will complement existing ones. One such strategy is the use of genetically modified (GM) mosquitoes. Strategies using GM mosquitoes can be grouped into two categories - those aiming to reduce mosquito population size, and those aiming to replace mosquito populations with varieties unable to transmit diseases. The former strategy has been tested in the Cayman Islands, Malaysia and Brazil to control dengue fever. The latter strategy is being considered for malaria control because it is more promising on a wider scale. Here, mosquitoes would be engineered with a gene that prevents them from transmitting malaria. This would be linked to a gene that favors its inheritance across generations. Mosquitoes have a short generation time - just a few weeks - and so the antimalarial gene could quickly increase in frequency, spreading into one population and then into another. This is promising for wide-scale malaria control, but draws into question the ability to conduct a confined field trial.In this project, Dr John Marshall, a researcher in the Department of Infectious Disease Epidemiology at Imperial College London, will develop a computer simulation to determine the optimal strategy for conducting a field trial of GM mosquitoes for malaria control. One major requirement for a field trial is that transgenes remain confined to their release site while also causing a significant reduction in local malaria transmission. Field trials are being considered on islands off the coast of Africa, including the Comoros Islands, Bioko Island, and Sao Tome and Principe. Dr Marshall will tailor his models to these locations using available mosquito and malaria prevalence data. He will then use his model to determine whether transgenes can be confined to these field sites, and under what release scenarios they will cause a maximal reduction in malaria transmission.If a confined field trial is eventually successful, this will provide an important mandate for more invasive GM mosquito strategies with the potential to control malaria on a much wider scale. The malaria modelling group at Imperial College London, led by Professor Azra Ghani, has developed a model of malaria transmission covering the African continent. Dr Marshall will use this model to explore the role that GM mosquitoes could play as part of a combined, Africa-wide malaria control program. GM mosquitoes hold great promise for malaria control because they can spread beyond their release site and reduce disease transmission without requiring human compliance. This modelling work will allow the public health impact of GM mosquitoes to be predicted and compared against other combinations of malaria interventions.