[Seminar Blog] How researchers use genomic monitoring to fight mosquitoes spreading malaria

Anopheles gambiae mosquito. Photo from James Gathany, CDC/Wikimedia Commons

written by: Allison Elizabeth Huysman
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​Mosquitoes are well known as both irritating and as vectors of dangerous diseases. In parts of the world like Africa, southeast Asia, and South America, mosquitoes in the genus Anopheles spread the life-threatening disease malaria. Public health measures to control disease transmission by mosquitoes include physical prevention with bed nets and chemical prevention using insect repellents. However, the effectiveness of chemical measures depends on the mosquitoes not developing a resistance to them.

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In a recent seminar, Dr. Alistair Miles, the Malaria Vector Surveillance Lead for the Wellcome Sanger Institute in the UK, shared current research on insecticide resistance by mosquitoes throughout Africa. Dr. Miles is part of a large collaboration of many groups in Africa, Europe, and the United States. Through the example of many genetic markers, he showcased the vast amount of genetic diversity and molecular mechanisms that may cause insecticide resistance to evolve. Some of the ways that Dr. Miles and collaborators have identified occurrences of resistance include scanning the entire genome for regions that have patterns across a population (The Anopheles gambiae 1000 Genomes Consortium, 2017) and identifying mutations particular genes of interest (Clarkson et al., 2021). These tools can be used together to identify how resistance arises and develop ways to improve Anopheles mosquito control.
 
The approach of finding patterns across the whole genome, or all the genetic material in an organism, is called genome-wide selection scans (GWSS). Researchers sequence genetic diversity within many samples to identify selective sweeps, or genetic regions that have very low diversity indicating that most or all individuals in the population carry that mutation. When a population is under strain from a particular insecticide, there will be survival pressure for all individuals to carry mutations which provide some measure of resistance to the insecticide. This can be identified by scanning for consistent regions of the genome with low diversity across many individuals. Dr. Miles and collaborators have used this method to determine regions of the genome in multiple species of Anopheles mosquitoes that indicate resistance to common insecticides (The Anopheles gambiae 1000 Genomes Consortium, 2017). The identified regions then can be targeted for future research into genes that may have developed resistance to a chemical insecticide.
 
Synthetic pyrethroids are commonly used and are therefore important to study for the evolution of resistance. Dr. Miles and collaborators have found mutations causing resistance to pyrethroids that have spread across Anopheles mosquito populations throughout Africa (Kamau et al. 2024). The researchers suggested methods to target mutations that cause resistance when monitoring populations for new outbreaks (Clarkson et al. 2021). In another study, the research team unexpectedly found evidence of resistance to DDT in an isolated location even though DDT has long been banned worldwide (Odero et al. 2024). Investigations that followed identified leftover stockpiles of DDT that were leaking into soil. While this was not confirmed as the source of the mutation, the World Bank removed the contaminated soils by DDT. As resistance to insecticides rapidly evolves, monitoring of genes that cause resistance to pyrethroids and other chemical insecticides has become a necessary tool for controlling outbreaks.
 
Dr. Miles and his collaborators are working to make the data they have generated accessible to the general public and other researchers. Together, they have sequenced the genomes of over 22,000 samples of the species Anopheles gambiae and almost 4,000 samples of Anopheles funestus, both of which are important vectors of malaria. The Malaria Vector Genome Observatory houses data for surveillance of malaria vectors and an online training course provides researchers with the tools to analyze and learn from the data. These efforts to collaborate, generate data, and provide training are important tools in efforts to control the spread of malaria.
 
References:
Clarkson, C.S., A. Miles, N.J. Harding, A.O. O'Reilly, D. Weetman, D. Kwiatkowski, M.J. Donnelly. Anopheles gambiae 1000 Genomes Consortium. The genetic architecture of target-site resistance to pyrethroid insecticides in the African malaria vectors Anopheles gambiae and Anopheles coluzzii. Molecular Ecology 30(21), 5303-5317 (2021). https://doi.org/10.1111/mec.15845. 
 
Kamau, L., K.L. Bennett, E. Ochomo, et al. The Anopheles coluzzii range extends into Kenya: detection, insecticide resistance profiles and population genetic structure in relation to conspecific populations in West and Central Africa. Malaria Journal  23, 122 (2024). https://doi.org/10.1186/s12936-024-04950-x.
 
Odero, J.O., T.P.W. Dennis, B. Polo, et al. Discovery of Knock-Down Resistance in the Major African Malaria Vector Anopheles funestus. Molecular Ecology 33(22), e17542 (2024). https://doi.org/10.1111/mec.17542
 
The Anopheles gambiae 1000 Genomes Consortium. Genetic diversity of the African malaria vector Anopheles gambiae. Nature 552, 96–100 (2017). https://doi-org.proxy-um.researchport.umd.edu/10.1038/nature24995.