Landscape changes, genetic structure of malaria vectors and their parasites in Senegal: impact on malaria epidemiology and control

Declining malaria incidence offers the opportunity to accelerate toward its elimination, which requires accurate information to target control where it is most needed and will deliver the greatest impact. The impact of environmental adaptation on vector populations, their vectorial capacity and susceptibility to control remain poorly understood. Anopheles arabiensis is common in arid areas, increasing in relative prevalence throughout sub-Saharan Africa, and is the dominant malaria-vector in Senegal. We aim to investigate how natural and anthropogenically-influenced landscape variation influences its genetic diversity, population structure and gene-flow, and how this may impact disease incidence, and aid targeting of vector control. We aim to test the hypothesis that its population structure in Senegal is impacted by both its prevailing environment and recent range expansions toward the more humid parts of the country. Furthermore, local adaptation, especially during this expansion, may have reduced genetic population sizes and genetic diversity, and gene flow between locally-adapted populations.

Expected outcomes are:

– Characterization of An. arabiensis population structure and connectivity to provide predictions for targeted control
– Understanding how genetic diversity, and potential adaptability/vulnerability of its populations depends on environment and range expansion
– Investigation of how the above impact parasite diversity and vector blood feeding, and vectorial capacity. 

Key methodologies

1. Countrywide collections of Anopheles mosquitoes will be made from houses and outbuildings during the first two years of the project with a target of sampling approximately 10,000 female An. arabiensis from 100 locations. 
2. Informative markers suitable for screening such a large collection will be generated from whole genome sequence data generated by the Senegalese Ag1000g Vector Observatory sites by conducting outlier analyses to identify polymorphisms exhibiting maximal differentiation among environmentally-divergent sites. 
3. Approximately 25 putatively selected markers and 75 neutral markers from those identified will be used to design Sequenom multiplex assays. 
4. Following molecular species identification, samples will be screened using these multiplex assays, and pools of DNA tested by qPCR for Plasmodium infection. Plasmodium-positive pools will be separated to identify a set of Plasmodium-infected individual females, the DNA from which will be screened with second Sequenom assays screening approximately 100 available informative markers for P. falciparum diversity. 
5. Blood-fed mosquitoes will be genotyped using a cocktail PCR to identify the species on which they have fed. 
6. Landscape genetic analyses will use environmental variables from publically-available databases of topographical, climatic and land-use variables in an ARCGIS database, generating grids of environmental variation for subsequent comparison with genetic data, with particular, but note sole, focus on least-cost path analysis and canonical correspondence analysis. Data from neutral and putatively adaptive markers will be analyzed separately and results compared to identify key markers for local adaption.

Insecticide Resistance
Measurement of Transmission
Vector Control

Oct 2019 — Jul 2021

$291,453

Senegal

Genetic Epidemiology