title: Genetic structure of Plasmodium falciparum populations between lowland and highland sites and antimalarial drug resistance in Western Kenya.
abstract: Human travel to malaria endemic lowlands from epidemic highlands has been shown to increase the risk of malaria infections in the highlands. In order to gain insight on the impact of human travel, we examined prevalence, genetic variability and population genetic structure of Plasmodium falciparum in asymptomatic children from one highland site and three surrounding malaria endemic lowland sites in Western Kenya, using multilocus microsatellite genotyping. We further analyzed the frequencies of mutations at the genes conferring resistance to chloroquine and sulfadoxine-pyrimethamine. We found a significant decrease in malaria prevalence in the highland site from 2006 to 2007, 1 year after the introduction of the artemisinin-based combination therapy as first-line treatment for uncomplicated malaria and the scale-up of insecticide-treated bed nets. Population genetic diversity, measured by the number of observed and effective microsatellite alleles and Nei's unbiased genetic diversity, was high and comparable for both highland and lowland populations. Analysis of molecular variance did not detect a significant genetic structure across highland and lowland regions. Similarly, mutations at key antimalarial-resistance codons of the pfcrt, pfmdr1, pfdhfr and pfdhps genes were found at comparable high frequencies in all four sites. High level of gene flow and lack of significant genetic structure in malaria parasites between highland and lowland areas suggest the importance of human travel in shaping parasite population structure.
authors.affiliation: Program in Public Health, College of Health Sciences, University of California, Irvine 92697, USA. mbonizzo@uci.edu
authors.forename: Mariangela
authors.initials: M
authors.lastname: Bonizzoni
authors.forename: Yaw
authors.initials: Y
authors.lastname: Afrane
authors.forename: Frederick N
authors.initials: FN
authors.lastname: Baliraine
authors.forename: Dolphine A
authors.initials: DA
authors.lastname: Amenya
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Githeko
authors.forename: Guiyun
authors.initials: G
authors.lastname: Yan
mesh_terms: D000293:Adolescent; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D002648:Child; D002738:Chloroquine / Q000494:pharmacology / Q000627:therapeutic use; D004338:Drug Combinations; D004351:Drug Resistance; D019353:Endemic Diseases; D005828:Genetics, Population; D006239:Haplotypes; D006801:Humans; D007630:Kenya / Q000453:epidemiology; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000453:epidemiology / Q000469:parasitology*; D026901:Membrane Transport Proteins / Q000235:genetics; D018895:Microsatellite Repeats; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000235:genetics; D011739:Pyrimethamine / Q000494:pharmacology / Q000627:therapeutic use; D013413:Sulfadoxine / Q000494:pharmacology / Q000627:therapeutic use; D014195:Travel
chemical_list: D000962:Antimalarials; D002738:Chloroquine; D004338:Drug Combinations; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015800:Protozoan Proteins; D011739:Pyrimethamine; D013413:Sulfadoxine; C513498:Mdr1 protein, Plasmodium falciparum; C416369:PfCRT protein, Plasmodium falciparum; C001205:fanasil, pyrimethamine drug combination