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Influence of the pfmdr1 Gene on In Vitro Sensitivities of Piperaquine in Thai Isolates of Plasmodium falciparum

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  • 1 Department of Parasitology, Phramongkutklao College of Medicine, Bangkok, Thailand.
  • 2 Mahidol University International College, Nakhon Pathom, Thailand.
  • 3 Division of Molecular and Biochemical Parasitology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.

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 Thai Plasmodium falciparum isolates against piperaquine and the influence of the pfmdr1 gene on in vitro response. One hundred and thirty-seven standard laboratory and adapted Thai isolates of P. falciparum were assessed for in vitro piperaquine sensitivity. Polymorphisms of the pfmdr1 gene were determined by polymerase chain reaction methods. The mean and standard deviation of the piperaquine IC50 in Thai isolates of P. falciparum were 16.7 ± 6.3 nM. The parasites exhibiting chloroquine IC50 of ≥ 100 nM were significantly less sensitive to piperaquine compared with the parasite with chloroquine IC50 of < 100 nM. No significant association between the pfmdr1 copy number and piperaquine IC50 values was found. In contrast, the parasites containing the pfmdr1 86Y 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 the pfmdr1 86Y allele are predominant such as the Thai–Malaysian border.

Author Notes

* Address correspondence to Mathirut Mungthin, Department of Parasitology, Phramongkutklao College of Medicine, Ratchawithi Road, Bangkok 10400, Thailand. E-mail: mathirut@hotmail.com

Financial support: This study was financially supported by the Health System Research Institute/National Science and Technology Development Agency (P-13-50112) and the Phramongkutklao Research Fund.

Authors' addresses: Mathirut Mungthin, Naruemon Sitthichot, Nantana Suwandittakul, and Rommanee Khositnithikul, Department of Parasitology, Phramongkutklao College of Medicine, Bangkok, Thailand, E-mails: mathirut@hotmail.com, mude_143@hotmail.com, suwanna_b@hotmail.com, and kik_kuru@yahoo.com. Ekularn Watanatanasup, Mahidol University International College, Nakhon Pathom, Thailand, E-mail: ekularn.wat@mahidol.ac.th. Stephen A. Ward, Division of Molecular and Biochemical Parasitology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom, E-mail: steve.ward@lstmed.ac.uk.

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