title: Polymorphisms of molecular markers of antimalarial drug resistance and relationship with artesunate-mefloquine combination therapy in patients with uncomplicated Plasmodium falciparum malaria in Thailand.
abstract: The aim of this study was to investigate the association between genetic polymorphisms of Plasmodium falciparum chloroquine resistance transporter (pfcrt), P. falciparum multidrug resistance 1 (pfmdr1), and P. falciparum ATPase (pfatp6) and clinical outcome after a three-day mefloquine-artesunate combination therapy in 134 patients with uncomplicated Plasmodium falciparum malaria in an area with multidrug resistance along the Thailand-Myanmar border. Analysis of gene mutation and amplification were performed by nested real-time polymerase chain reaction and SYBR Green I real-time polymerase chain reaction, respectively. The mutation for pfcrt (codons 76, 220, 271, 326, 356, and 371) was found in all isolates (100%), whereas no mutation of pfmdr1 (codon 86) and pfatp6 (codons 37, 693, 769, 898) was found. The Pfmdr1 copy number was significantly higher in isolates with recrudescence (median number = 2.44) compared with a sensitive response (median number = 1.44). The gene copy number was also found to be significantly higher in paired isolates collected before treatment and at the time of recrudescence. All isolates carried one pfatp6 gene copy.
authors: Thailand Center of Excellence on Drug Discovery and Development, Thammasat University, Rangsit Campus, Klong Luang District, Pathumtani, Thailand; Mae-Sot General Hospital, Mae-Sot, Tak Province, Thailand.
authors: Poonuch
authors: P
authors: Muhamad
authors: Papichaya
authors: P
authors: Phompradit
authors: Wannapa
authors: W
authors: Sornjai
authors: Thunyaluk
authors: T
authors: Maensathian
authors: Wanna
authors: W
authors: Chaijaroenkul
authors: Ronnatrai
authors: R
authors: Rueangweerayut
authors: Kesara
authors: K
authors: Na-Bangchang
mesh_terms: D000962:Antimalarials / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D037621:Artemisinins / Q000008:administration & dosage / Q000627:therapeutic use*; D000077332:Artesunate; D018432:Drug Resistance, Multiple / Q000235:genetics*; D004359:Drug Therapy, Combination; D005819:Genetic Markers; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology; D015767:Mefloquine / Q000008:administration & dosage / Q000627:therapeutic use*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D011110:Polymorphism, Genetic; D013785:Thailand / Q000453:epidemiology
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D005819:Genetic Markers; D000077332:Artesunate; D015767:Mefloquine