Spatial Patterns of Malaria in the Democratic Republic of Congo: A Landscape Genetics Approach
How does malaria spread from place to place? Malaria parasites can be carried over short distances by mosquitoes and over any distance by people. Geographic spread (diffusion) can lead to outbreaks in previously malaria-free areas and the introduction of drug resistance into zones where drug resistance had not previously existed. This project uses a landscape genetics approach to understanding malaria diffusion. Landscape genetics incorporates methods of population genetics, ecology and spatial statistics. Population movements are inferred from the measurement of movement of genetic markers (gene flow). The goal of this study is to measure the movement of genetic markers (gene flow) to understand the factors which prevent transmission (barriers) or promote it (corridors). Barriers can be caused by humans such as malaria control programs or they can be natural such as mountains that restrict mosquito vector habitat because of cool temperatures. Corridors can also be created by humans such as roads or they can be natural such as rivers used for transportation. To achieve the goals of this project we use data and specimens from the Democratic Republic of the Congo (DRC), a country with high but spatially variable malaria endemicity. The project takes advantage of DNA samples from the large population-based 2007 Demographic Health Survey (DHS), which includes >10,000 people in 300 geocoded survey clusters. We measured 7 neutral microsatellite markers for 82 P. falciparum infected patients in 7 sample clusters from the 2007 DRC DHS using nested PCR. Genetic relatedness between DRC parasites was analyzed using measures of genetic distance including Nei's genetic distance (Gst) and Rst. We also compared the genetic distance of the DRC parasites to West African (Ghanaian) East African (Kenyan) parasites. Findings show that the genetic distance was greater when clusters were further apart (i.e., isolation by distance) at a national-level but within DRC there is a complex substructure. Samples to the West and South are more related to West African parasites, while the clusters in the North are more related to East African parasites. We also investigated genetic relatedness and geographic clustering of sulfadoxine resistance in falciparum parasites in the DRC. We found that resistant haplotypes were clustered into subpopulations: one in northeastern DRC, and the other in the balance of the DRC. This likely indicates that geographically-distinct mutant haplotypes derive from separate lineages. Thus, the DRC may be a watershed for haplotypes associated with resistance. This research demonstrates the contributions that geography can make to understanding the evolutionary dynamics of infectious diseases.
