ABSTRACT
We describe an analysis of genome variation in 825 P. falciparum samples from Asia and Africa that identifies an unusual pattern of parasite population structure at the epicenter of artemisinin resistance in western Cambodia. Within this relatively small geographic area, we have discovered several distinct but apparently sympatric parasite subpopulations with extremely high levels of genetic differentiation. Of particular interest are three subpopulations, all associated with clinical resistance to artemisinin, which have skewed allele frequency spectra and high levels of haplotype homozygosity, indicative of founder effects and recent population expansion. We provide a catalog of SNPs that show high levels of differentiation in the artemisinin-resistant subpopulations, including codon variants in transporter proteins and DNA mismatch repair proteins. These data provide a population-level genetic framework for investigating the biological origins of artemisinin resistance and for defining molecular markers to assist in its elimination.
Subject(s)
Antimalarials/pharmacology , Artemisinins/pharmacology , Genes, Protozoan , Malaria, Falciparum/parasitology , Plasmodium falciparum/genetics , Cambodia/epidemiology , Chromosome Painting , Cluster Analysis , Drug Resistance , Founder Effect , Genetic Association Studies , Homozygote , Humans , Malaria, Falciparum/drug therapy , Malaria, Falciparum/epidemiology , Models, Genetic , Plasmodium falciparum/drug effects , Polymorphism, Single Nucleotide , Principal Component AnalysisABSTRACT
Despite the recognition of its importance, guidance on community engagement practices for researchers remains underdeveloped, and there is little empirical evidence of what makes community engagement effective in biomedical research. We chose to study the Navrongo Health Research Centre in northern Ghana because of its well-established community engagement practices and because of the opportunity it afforded to examine community engagement in a traditional African setting. Our findings suggest that specific preexisting features of the community have greatly facilitated community engagement and that using traditional community engagement mechanisms limits the social disruption associated with research conducted by outsiders. Finally, even in seemingly ideal, small, and homogeneous communities, cultural issues exist, such as gender inequities, that may not be effectively addressed by traditional practices alone.
