title: Pfmdr1 Asn1042Asp and Asp1246Tyr polymorphisms, thought to be associated with chloroquine resistance, are present in chloroquine-resistant and -sensitive Brazilian field isolates of Plasmodium falciparum.
abstract: Parasite resistance to antimalarial drugs, particularly chloroquine, is the most disturbing problem of malaria chemotherapy. There is evidence that the codon 86Tyr polymorphism of the Pfmdr1 gene is associated with chloroquine resistance in West African Plasmodium falciparum. The association of this and four other coding alterations of the Pfmdr1 gene with chloroquine resistance has not been extensively investigated in South American isolates. In this study, we examined 51 Brazilian P. falciparum isolates for the presence or absence of Asn86Tyr, Asn1042Asp, and Asp1246Tyr polymorphisms. While these isolates were all sensitive in vitro to mefloquine, amodiaquine, and quinine, only 2 (4%) were chloroquine-sensitive. The findings reported here provide the first observations of this kind on a large number of field parasite samples from South America. We show that in vitro chloroquine-resistant and -sensitive strains carry the Asn1042Asp and Asp1246Tyr polymorphisms and provide support for earlier suggestions that Asn86Tyr may be rare or absent in South American P. falciparum.
authors.affiliation: Servico de Parasitologia, Instituto Evandro Chagas, FNS, Belém, Pará, Brazil.
authors.forename: M M
authors.initials: MM
authors.lastname: Póvoa
authors.forename: I S
authors.initials: IS
authors.lastname: Adagu
authors.forename: S G
authors.initials: SG
authors.lastname: Oliveira
authors.forename: R L
authors.initials: RL
authors.lastname: Machado
authors.forename: M A
authors.initials: MA
authors.lastname: Miles
authors.forename: D C
authors.initials: DC
authors.lastname: Warhurst
mesh_terms: D000655:Amodiaquine / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology*; D004351:Drug Resistance / Q000235:genetics; D006801:Humans; D015767:Mefloquine / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011803:Quinine / Q000494:pharmacology
chemical_list: D000962:Antimalarials; D000655:Amodiaquine; D002738:Chloroquine; D011803:Quinine; D015767:Mefloquine