title: Influence of thepfmdr1Gene on In Vitro Sensitivities of Piperaquine in Thai Isolates ofPlasmodium falciparum.
abstract: Piperaquine combined with dihydroartemisinin is one of the artemisinin derivative combination therapies, which can replace artesunate-mefloquine in treating uncomplicated falciparum malaria in Thailand. The aim of this study was to determine the in vitro sensitivity of ThaiPlasmodium falciparumisolates against piperaquine and the influence of thepfmdr1gene on in vitro response. One hundred and thirty-seven standard laboratory and adapted Thai isolates ofP. falciparumwere assessed for in vitro piperaquine sensitivity. Polymorphisms of thepfmdr1gene were determined by polymerase chain reaction methods. The mean and standard deviation of the piperaquine IC50in Thai isolates ofP. falciparumwere 16.7 ± 6.3 nM. The parasites exhibiting chloroquine IC50of ≥ 100 nM were significantly less sensitive to piperaquine compared with the parasite with chloroquine IC50of < 100 nM. No significant association between thepfmdr1copy number and piperaquine IC50values was found. In contrast, the parasites containing thepfmdr186Y allele exhibited significantly reduced piperaquine sensitivity. Before nationwide implementation of dihydroartemisinin-piperaquine as the first-line treatment in Thailand, in vitro and in vivo evaluations of this combination should be performed especially in areas where parasites containing thepfmdr186Y allele are predominant such as the Thai-Malaysian border.
authors.affiliation: Department of Parasitology, Phramongkutklao College of Medicine, Bangkok, Thailand.
authors.forename: Mathirut
authors.initials: M
authors.lastname: Mungthin
authors.affiliation: Mahidol University International College, Nakhon Pathom, Thailand.
authors.forename: Ekularn
authors.initials: E
authors.lastname: Watanatanasup
authors.affiliation: Department of Parasitology, Phramongkutklao College of Medicine, Bangkok, Thailand.
authors.forename: Naruemon
authors.initials: N
authors.lastname: Sitthichot
authors.affiliation: Department of Parasitology, Phramongkutklao College of Medicine, Bangkok, Thailand.
authors.forename: Nantana
authors.initials: N
authors.lastname: Suwandittakul
authors.affiliation: Department of Parasitology, Phramongkutklao College of Medicine, Bangkok, Thailand.
authors.forename: Rommanee
authors.initials: R
authors.lastname: Khositnithikul
authors.affiliation: Division of Molecular and Biochemical Parasitology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Ward
mesh_terms: D000483:Alleles; D000962:Antimalarials / Q000494:pharmacology; D037621:Artemisinins / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics*; D018628:Gene Dosage; D060005:Genotyping Techniques; D020128:Inhibitory Concentration 50; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics* / Q000378:metabolism; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology*; D013785:Thailand; D010879:Piperazines
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D002738:Chloroquine; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015800:Protozoan Proteins; D011804:Quinolines; C513498:Mdr1 protein, Plasmodium falciparum; C416369:PfCRT protein, Plasmodium falciparum; C039060:artenimol; C031327:artemisinin; C034759:piperaquine; D010879:Piperazines