title: In vitro susceptibility and genetic variations for chloroquine and mefloquine in Plasmodium falciparum isolates from Thai-Myanmar border.
abstract: In vitro drug susceptibility to chloroquine (CQ) and mefloquine (MF) were assessed in 39 P. falciparum isolates from the Thai-Myanmar border area. To further characterize CQ- and MF-resistance profiles in this area, we also analyzed pfcrt K76T mutation that is critical for CQ resistance, and pfmdr1 polymorphism that has an association with MF resistance. Eighteen isolates were successfully examined by in vitro tests for CQ, and 17 of them had resistance to the drug. Geometric mean concentration of CQ that inhibited the growth of parasites at 50% (IC50) was 371 +/- 227 nM (105-971 nM). Sixteen isolates were successfully examined by in vitro tests for MF, and 8 of them were resistant to the drug. Geometric mean of IC50 for MF was 41 +/- 31 nM (4-125 nM). Genotypes of drug resistance, such as pfcrt and pfmdr1 mutations, were also analyzed. All the 39 isolates had the same haplotype (CVIET) for PfCRT at its 72-76th amino acids. A pfmdr1 Y86 mutation was found in 95% of isolates. A pfmdr1 D1042 mutation was also present in 7 isolates, while no pfmdr1 Y1246 mutation was observed. These results indicated a correlation between CQ resistance and the pfcrt T76 and pfmdr1 Y86 mutations.
authors.affiliation: Research Institute, International Medical Center of Japan, Tokyo, Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Hatabu
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Kawazu
authors.forename: Somei
authors.initials: S
authors.lastname: Kojima
authors.forename: Kumiko
authors.initials: K
authors.lastname: Sato
authors.forename: Pratap
authors.initials: P
authors.lastname: Singhasivanon
authors.forename: Sornchai
authors.initials: S
authors.lastname: Looareesuwan
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kano
mesh_terms: D000818:Animals; D002738:Chloroquine / Q000494:pharmacology* / Q000627:therapeutic use; D004198:Disease Susceptibility; D004352:Drug Resistance, Microbial / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D066298:In Vitro Techniques; D008288:Malaria / Q000188:drug therapy / Q000235:genetics* / Q000469:parasitology; D015767:Mefloquine / Q000494:pharmacology* / Q000627:therapeutic use; D009154:Mutation; D002052:Myanmar; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013785:Thailand
chemical_list: D002738:Chloroquine; D015767:Mefloquine