New haplotypes of the Plasmodium falciparum chloroquine resistance transporter (pfcrt) gene among chloroquine-resistant parasite isolates.
Mutations in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) gene were examined to assess their associations with chloroquine resistance in clinical samples from Armopa (Papua) and Papua New Guinea. In Papua, two of the five pfcrt haplotypes found were new: SVIET from Armopa and CVIKT from an isolate in Timika. There was also a strong association (P < 0.0001) between the pfcrt 76T allele and chloroquine resistance in 50 samples. In Papua New Guinea, mutations in the pfcrt gene were observed in 15 isolates with chloroquine minimum inhibitory concentrations (MICs) of 16-64 pmol, while the remaining six isolates, which had a wild-type pfcrt gene at codon 76, had MICs of 2-8 pmol. These observations confirm that mutations at codon 76 in the pfcrt gene are present in both in vivo and in vitro cases of chloroquine resistance, and that detection of the pfcrt 76T allele could predict potential chloroquine treatment failures.
Nagesha
Hadya S
HS
The Walter and Eliza Hall Institute for Medical Research, Melbourne, Australia. hadya@wehi.edu.au
Casey
Gerard J
GJ
Rieckmann
Karl H
KH
Fryauff
David J
DJ
Laksana
Budi S
BS
Reeder
John C
JC
Maguire
Jason D
JD
Baird
J Kevin
JK
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D002738:Chloroquine / Q000494:pharmacology* / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D016054:DNA, Protozoan / Q000737:chemistry; D004351:Drug Resistance / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007214:Indonesia; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology*; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D009154:Mutation; D010219:Papua New Guinea; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D015800:Protozoan Proteins
D000962:Antimalarials; D016054:DNA, Protozoan; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D002738:Chloroquine