title: Selective sweeps and genetic lineages of Plasmodium falciparum drug -resistant alleles in Ghana.
abstract: BACKGROUND
  In 2005, Ghana adopted artemisinin-based combination therapy (ACT) for primary treatment of falciparum malaria. A comprehensive study of the drug-resistance-associated mutations and their genetic lineages will lead to a better understanding of the evolution of antimalarial drug resistance in this region.
  
  
  METHODS
  The pfcrt, pfmdr1, dhps, and dhfr mutations associated with chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) resistance and the microsatellite loci flanking these genes were genotyped in Plasmodium falciparum isolates from Ghana.
  
  
  RESULTS
  The prevalence of mutations associated with both CQ and SP resistance was high in Ghana. However, we observed a decrease in prevalence of the pfcrt K76T mutation in northern Ghana after the change in drug policy from CQ to ACT. Analysis of genetic diversity and differentiation at microsatellite loci flanking all 4 genes indicated that they have been under strong selection, because of CQ and SP use. The triple-mutant pfcrt and dhfr alleles in Ghana were derived from Southeast Asia, whereas the double-mutant dhfr, dhps, and pfmdr1 alleles were of African lineage.
  
  
  CONCLUSIONS
  Because of the possible role of pfmdr1 in amodiaquine and mefloquine resistance, demonstrating selection on pfmdr1 and defining lineages of resistant alleles in an African population holds great importance.
authors.affiliation: Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA. hsf1@cdc.gov
authors.forename: Md Tauqeer
authors.initials: MT
authors.lastname: Alam
authors.forename: Dziedzom K
authors.initials: DK
authors.lastname: de Souza
authors.forename: Sumiti
authors.initials: S
authors.lastname: Vinayak
authors.forename: Sean M
authors.initials: SM
authors.lastname: Griffing
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Poe
authors.forename: Nancy O
authors.initials: NO
authors.lastname: Duah
authors.forename: Anita
authors.initials: A
authors.lastname: Ghansah
authors.forename: Kwame
authors.initials: K
authors.lastname: Asamoa
authors.forename: Laurence
authors.initials: L
authors.lastname: Slutsker
authors.forename: Michael D
authors.initials: MD
authors.lastname: Wilson
authors.forename: John W
authors.initials: JW
authors.lastname: Barnwell
authors.forename: Venkatachalam
authors.initials: V
authors.lastname: Udhayakumar
authors.forename: Kwadwo A
authors.initials: KA
authors.lastname: Koram
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D000962:Antimalarials / Q000494:pharmacology*; D005075:Biological Evolution; D002675:Child, Preschool; D002738:Chloroquine / Q000494:pharmacology; D016054:DNA, Protozoan / Q000235:genetics; D004094:Dihydropteroate Synthase / Q000235:genetics; D004338:Drug Combinations; D004351:Drug Resistance; D019143:Evolution, Molecular; D005838:Genotype; D005869:Ghana; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016778:Malaria, Falciparum / Q000469:parasitology*; D026901:Membrane Transport Proteins / Q000235:genetics; D018895:Microsatellite Repeats; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D020125:Mutation, Missense; D010963:Plasmodium falciparum / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D015800:Protozoan Proteins / Q000235:genetics; D011739:Pyrimethamine / Q000494:pharmacology; D013413:Sulfadoxine / Q000494:pharmacology; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics
chemical_list: D000962:Antimalarials; D002738:Chloroquine; D016054:DNA, Protozoan; D004094:Dihydropteroate Synthase; D004338:Drug Combinations; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015800:Protozoan Proteins; D011739:Pyrimethamine; D013413:Sulfadoxine; D013762:Tetrahydrofolate Dehydrogenase; C513498:Mdr1 protein, Plasmodium falciparum; C416369:PfCRT protein, Plasmodium falciparum; C001205:fanasil, pyrimethamine drug combination