title: Amodiaquine resistance in Plasmodium falciparum malaria in Afghanistan is associated with the pfcrt SVMNT allele at codons 72 to 76.
abstract: Mutations in the Plasmodium falciparum genes pfcrt and pfmdr1 are selected by amodiaquine treatment in Africa. To examine the importance of these mutations in amodiaquine-treated Asian parasites, we determined pre- and posttreatment genotypes for amodiaquine treatment failures from a clinical trial in Afghanistan. The pfcrt codon 72 to 76 haplotype SVMNT was present in all samples tested, both before and after treatment. Amodiaquine did not clearly select for any pfmdr1 genotype, but a novel mutation, pfmdr1 N86F, was detected in four samples. We provide in vivo data to support the in vitro correlation between pfcrt SVMNT and increased resistance to the metabolite of amodiaquine.
authors.affiliation: Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom.
authors.forename: Khalid
authors.initials: K
authors.lastname: Beshir
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Sutherland
authors.forename: Ioannis
authors.initials: I
authors.lastname: Merinopoulos
authors.forename: Naeem
authors.initials: N
authors.lastname: Durrani
authors.forename: Toby
authors.initials: T
authors.lastname: Leslie
authors.forename: Mark
authors.initials: M
authors.lastname: Rowland
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Hallett
mesh_terms: D000346:Afghanistan; D000483:Alleles; D000655:Amodiaquine / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D003062:Codon / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics*; D006239:Haplotypes; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D011110:Polymorphism, Genetic / Q000235:genetics; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000962:Antimalarials; D003062:Codon; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D000655:Amodiaquine