Mosquito in close up. Image credit: CDC/Dr Paul Howell
Categories: Sanger Science21 September 20186.2 min read

Building capacity for genomic surveillance of malaria mosquitoes in Africa

By: Alistair Miles
Date: 21/09/2018

In 2009, a group of African entomologists and public health professionals founded the Pan-African Mosquito Control Association (PAMCA). The aim was to bring together mosquito control professionals from across the continent, and provide a platform to build capacity and coordinate efforts to improve mosquito control and prevent diseases like malaria. A few years later, in 2013, we began work at the Sanger Institute on a new project to sequence the genomes of more than 1,000 malaria mosquitoes collected from across Africa. It’s taken time for that work to bear fruit, but the project has now generated a wealth of new data that could be put to practical use.

Children sleeping under an insecticide-treated bednet. Photo credit: Martin Donnelly

Thanks to new funding from the Bill and Melinda Gates Foundation, these efforts are now coming together, and PAMCA has recently invited researchers to propose new projects on mosquito genomics in Africa. Our mosquito team at the Sanger institute is excited to be supporting those projects, and will sequence the whole genomes of thousands of new mosquitoes collected from locations where we currently have little or no data.

Mosquito-borne diseases, particularly malaria, still have a devastating impact on public health in Africa, and massive efforts are made each year to control mosquitoes. For example, in 2017 the Global Fund paid for 197 million insecticide-treated bednets to be distributed in Africa. This approach has led to major reductions in disease, but brute force can only get you so far. Under this intense and uniform pressure, mosquito populations are rapidly evolving, and insecticide resistance has spread across the continent. As we struggle now to gain the upper hand, those working at the front line of mosquito population monitoring and control have a pivotal role to play.

In an ideal world, every province in every malaria-endemic country would have a well-trained, well-resourced, dedicated team of medical entomologists. Those teams would regularly collect data on local mosquito populations and run experiments to compare different tools and tactics for mosquito control. They would assess whether current mosquito control efforts are still effective, give advice on the best plan of attack for the next season, and raise the alert about any changes in local mosquitoes, such as the emergence or spread of a new form of insecticide resistance.

In some parts of Africa, this vision is not so far from reality. But there is a broad consensus that much more could be done to build capacity for mosquito population monitoring and surveillance. With recent advances in genomics, there is also now an opportunity to equip teams with new tools to collect richer and more relevant data, and to join up data and coordinate efforts across countries. This is why the Gates Foundation and the Sanger Institute are partnering with PAMCA and supporting this new funding call.

Training session in sampling mosquito larvae for community volunteers. Photo credit: Prosper Chaki

The Sanger Institute has committed to provide genome sequencing for all of the new PAMCA projects. The call will fund nine projects in total, each lasting 12 months, and our aim is to sequence whole genomes of 500 mosquitoes from each project. A particular focus of this call is to fund projects working in locations where little or no data on mosquito populations has so far been collected. Ironically, these are often areas with high rates of malaria, and so filling in these gaps in our continental map of mosquito populations is vital.

Last year we published results from the largest ever genomic study of mosquitoes, which sequenced Anopheles gambiae mosquitoes, the species primarily responsible for transmitting malaria, collected from eight African countries. We found evidence that insecticide resistance is emerging locally in a number of geographically distinct mosquito populations, but it is also spreading between mosquito populations in different countries, in some cases separated by thousands of kilometres. These findings show that how insecticides are used in one location can have an impact on many other locations, and that mosquitoes, of course, do not respect political borders. The management of insecticide use, therefore, has to be coordinated.

Unlike the Aedes mosquitoes that transmit dengue and zika, which can travel over large distances by laying their eggs in car tyres, it is more likely that insecticide resistance spreads between Anopheles mosquito populations by adult mosquitoes flying to find new food and breeding grounds. But although we know that an insecticide resistance gene can find its way into populations as distant as Guinea and Angola, for example, we still don’t know where resistance is emerging, or what routes it can take as it spreads outwards from any given origin. Filling in these gaps in our understanding of mosquito movement and gene flow is a major goal of the new PAMCA projects.

Mosquito larvae. Photo credit: Martin Donnelly

Insecticides are likely to remain an essential component of mosquito control for the foreseeable future. But because of the challenges of resistance, and the significant costs and logistical issues involved in distributing millions of nets and spraying hundreds of thousands of homes each year, efforts are being made to develop alternative methods of mosquito control. New methods based on gene drive, where a selfish gene is introduced into a mosquito population and then spreads to cause the population to crash or become unable to transmit disease, have been proven to work in the lab, and are now being developed for use in the field. There are considerable technical, regulatory and logistical hurdles still to be overcome, but the technology has the potential to transform mosquito control in Africa. Understanding how mosquito populations are connected across Africa is obviously a prerequisite to planning any kind of deployment of gene drive, so sequencing mosquito genomes from across the complete geographical range of the species is all the more important.

Since its inception, PAMCA has established chapters in 8 countries, formed strategic partnerships with regional bodies and academic institutions, performed an Africa-wide assessment of entomological capacity, and run training workshops on gene drive. PAMCA has also held annual conferences in Kenya, Tanzania, Nigeria and Burkina Faso, bringing together entomologists, researchers, health professionals and members of governmental and non-governmental organisations. From 24-26 September, the 5th annual conference will be held in Victoria Falls, Zimbabwe. I’m excited to be attending the conference for the first time this year, and to be participating in a symposium on mosquito genomics, alongside colleagues from Sanger, the Liverpool School of Tropical Medicine, and PAMCA. It should be a great opportunity to discuss the new funding call. Hopefully the new PAMCA projects will go some way towards increasing capacity both for basic medical entomology and for the analysis and interpretation of genomic data, as well as generating a wealth of new data from contemporary mosquito populations in understudied locations.

Applying for PAMCA funding

Researchers interested in applying for the PAMCA funding, please see the PAMCA request for proposals document for more information. The closing date for the first round of applications is 3rd October.

About the author:

Alistair Miles is Head of Epidemiological Informatics in the group of Dominic Kwiatkowski, at the University of Oxford, and the Wellcome Trust Sanger Institute.

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