Largest genetic study of mosquitoes reveals spread of insecticide resistance across Africa

November 29, 2017

The largest ever genetic study of mosquitoes reveals the movement of insecticide resistance between different regions of Africa and finds several rapidly evolving insecticide resistance genes. Reported today (29 November) in Nature, this genetic resource will be used to develop new tools for monitoring resistance and managing insecticide use, and for designing novel control methods.

Malaria is transmitted by mosquitoes and rising resistance to insecticides is hampering efforts to control the disease. The study by researchers from the Wellcome Trust Sanger Institute and their collaborators also discovered that wild mosquitoes collected in Africa were genetically far more diverse than had been thought. This helps to explain how mosquitoes evolve insecticide resistance so quickly.

More than 200 million people are infected with the malaria parasite worldwide each year, which is transmitted by blood-sucking Anopheles mosquitoes. Malaria caused the deaths of around 429,000 people in 2015* with the majority of cases in sub-Saharan Africa.

Public health measures in Africa such as insecticide-treated bed nets and insecticide-spraying have helped reduce the numbers of malaria cases since 2000, but many mosquitoes have evolved resistance to insecticides. This is now threatening to derail malaria control in Africa.

To understand how mosquitoes are evolving, researchers working with the Anopheles gambiae 1000 genomes project sequenced the DNA of 765 wild Anopheles mosquitoes. These were taken from 15 locations across eight African countries, creating the largest data resource on natural genetic variation for any species of insect. They then examined each of the mosquito genomes.

The researchers revealed that the Anopheles gambie mosquitoes are extremely genetically diverse compared with most other animal species. High genetic diversity enables rapid evolution and the study found 52 million small differences amongst the mosquito genomes.

Dr Mara Lawniczak, a corresponding author on the paper and Faculty at the Wellcome Trust Sanger Institute, said: "The diversity of mosquito genomes was far greater than we expected. Such high levels of genetic variation poise mosquito populations to rapidly evolve in response to our efforts to control them whether that be with insecticides or any other control measure, including gene drive."

New strategies to control mosquitoes are being developed that use 'gene drive'- using the latest Crispr/Cas 9 genetic tools to make mosquitoes infertile or unable to carry the malaria parasite. However, this technology requires an exact match with any targeted gene. The researchers found that gene drive is unlikely to work for most mosquito genes because they are too variable in nature, however they also used the data to highlight less variable targets that are potentially more suitable for gene drive based methods to control mosquitoes.

The mosquito genomes also revealed rapid evolution of several genes that had previously been implicated in insecticide resistance. Unexpectedly, the researchers discovered many previously-unknown genetic variants within those genes that could be causing insecticide resistance. Worryingly, they showed that these genetic variants for insecticide resistance were not only emerging independently in different parts of Africa, but were also being spread across the continent by mosquito migration.

Professor Martin Donnelly, a corresponding author from the Liverpool School of Tropical Medicine and Honorary Faculty at the Wellcome Trust Sanger Institute, said: "We know that mosquito populations are rapidly evolving resistance to insecticides, which is a serious threat to the future of malaria control in Africa. We have been able to see that a diverse array of genes linked to insecticide resistance are under very strong selection, confirming that they are playing an important role in the evolution of insecticide resistance in natural mosquito populations. Our study highlights the severe challenges facing public efforts to control mosquitoes and to manage and limit insecticide resistance."

Alistair Miles, lead author from the University of Oxford and the Wellcome Trust Sanger Institute, said: "The data we have generated are a unique resource for studying how mosquito populations are responding to our current control efforts, and for designing better technologies and strategies for mosquito control in the future. More data will be needed to fill in the geographical gaps and study how mosquito populations change over time and in response to specific control interventions. However, this study demonstrates a clear path towards building a new and much-needed source of intelligence to support the campaign to eradicate malaria in Africa."
-end-
Contact

Dr Samantha Wynne,
Wellcome Trust Sanger Institute
Hinxton, Cambridge, CB10 1SA, UK
Tel +44 (0)1223 492368
Email press.office@sanger.ac.uk

Notes to editors

*WHO stats on malaria http://www.who.int/features/factfiles/malaria/en/

For more information about malaria please see http://www.yourgenome.org/facts/what-is-malaria

Funding:

This work was supported by the Wellcome Trust, Medical Research Council UK, the Department for International Development, the Foundation for the National Institutes of Health through the Vector-Based Control of Transmission: Discovery Research (VCTR) program of the Grand Challenges in Global Health initiative of the Bill & Melinda Gates Foundation and the National Institute of Allergy and Infectious Diseases (NIAID).

Participating Centres:Selected Websites:

About the Ag1000G project


The Anopheles gambiae 1000 genomes project (Ag1000G) was established in 2014 to sequence the genomes of mosquitoes collected from natural populations across Africa. Led by the Wellcome Trust Sanger Institute, the Ag1000G project is supported by an international consortium of 20 research institutions.

The primary goal of the Ag1000G project is to generate data on natural genetic variation within and between mosquito populations in different parts of Africa. Data on genetic variation are a fundamental tool for many fields of biological research, including basic research in fundamental areas such as evolution and ecology, and applied research into new tools for mosquito control. http://www.malariagen.net/ag1000g

Liverpool School of Tropical Medicine (LSTM)

Liverpool School of Tropical Medicine (LSTM) is the world's oldest centre of excellence in tropical medicine and international public health. It has been engaged in the fight against infectious, debilitating and disabling diseases since 1898 and continues to break the cycle of poor health and poverty with a research portfolio in excess of well over £210 million and a teaching programme attracting students from over 65 countries. For further information please visit http://www.lstmed.ac.uk

Big Data Institute, University of Oxford

The Big Data Institute is located in the Li Ka Shing Centre for Health Informatics and Discovery at the University of Oxford. It is an interdisciplinary research centre that focuses on the analysis of large, complex data sets for research into the causes, consequences, prevention and treatment of disease. Research is conducted in areas such as genomics, population health, infectious disease surveillance and the development of new analytic methods. The Big Data Institute is supported by funding from the Medical Research Council, the UK Research Partnership Investment Fund, the National Institute for Health Research Oxford Biomedical Research Centre, and philanthropic donations from the Li Ka Shing and Robertson Foundations. Further details are available at http://www.bdi.ox.ac.uk

The Wellcome Trust Sanger Institute

The Wellcome Trust Sanger Institute is one of the world's leading genome centres. Through its ability to conduct research at scale, it is able to engage in bold and long-term exploratory projects that are designed to influence and empower medical science globally. Institute research findings, generated through its own research programmes and through its leading role in international consortia, are being used to develop new diagnostics and treatments for human disease. To celebrate its 25th year in 2018, the Institute is sequencing 25 new genomes of species in the UK. Find out more at http://www.sanger.ac.uk or follow @sangerinstitute

Wellcome

Wellcome exists to improve health for everyone by helping great ideas to thrive. We're a global charitable foundation, both politically and financially independent. We support scientists and researchers, take on big problems, fuel imaginations and spark debate. http://www.wellcome.ac.uk

Wellcome Trust Sanger Institute

Related Malaria Articles from Brightsurf:

Clocking in with malaria parasites
Discovery of a malaria parasite's internal clock could lead to new treatment strategies.

Breakthrough in malaria research
An international scientific consortium led by the cell biologists Volker Heussler from the University of Bern and Oliver Billker from the UmeƄ University in Sweden has for the first time systematically investigated the genome of the malaria parasite Plasmodium throughout its life cycle in a large-scale experiment.

Scientists close in on malaria vaccine
Scientists have taken another big step forward towards developing a vaccine that's effective against the most severe forms of malaria.

New tool in fight against malaria
Modifying a class of molecules originally developed to treat the skin disease psoriasis could lead to a new malaria drug that is effective against malaria parasites resistant to currently available drugs.

Malaria expert warns of need for malaria drug to treat severe cases in US
The US each year sees more than 1,500 cases of malaria, and currently there is limited access to an intravenously administered (IV) drug needed for the more serious cases.

Monkey malaria breakthrough offers cure for relapsing malaria
A breakthrough in monkey malaria research by two University of Otago scientists could help scientists diagnose and treat a relapsing form of human malaria.

Getting to zero malaria cases in zanzibar
New research led by the Johns Hopkins Center for Communication Programs, Ifakara Health Institute and the Zanzibar Malaria Elimination Program suggests that a better understanding of human behavior at night -- when malaria mosquitoes are biting -- could be key to preventing lingering cases.

Widely used malaria treatment to prevent malaria in pregnant women
A global team of researchers, led by a research team at the Liverpool School of Tropical Medicine (LSTM), are calling for a review of drug-based strategies used to prevent malaria infections in pregnant women, in areas where there is widespread resistance to existing antimalarial medicines.

Protection against Malaria: A matter of balance
A balanced production of pro and anti-inflammatory cytokines at two years of age protects against clinical malaria in early childhood, according to a study led by ISGlobal, an institution supported by ''la Caixa'' Foundation.

The math of malaria
A new mathematical model for malaria shows how competition between parasite strains within a human host reduces the odds of drug resistance developing in a high-transmission setting.

Read More: Malaria News and Malaria Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.