Molecular monitoring of dihydrofolatereductase (dhfr) and dihydropteroatesynthetase (dhps) associated with sulfadoxine-pyrimethamine resistance in Plasmodium vivax isolates of Palawan, Philippines.

Acta Trop

Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat University, Pathumthani 12121, Thailand. Electronic address:

Published: April 2018

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The emergence of drug-resistant Plasmodium vivax poses problems for malaria control and elimination in some parts of the world, especially in developing countries where individuals are routinely exposed to the infection. The aim of this study was to determine the single nucleotide polymorphisms (SNPs) in dihydropteroate synthase (pvdhps) and dihydrofolate reductase (pvdhfr) genes associated with sulfadoxine-pyrimethamine (SP) drug resistance among P. vivax isolates collected in Palawan, Philippines. Genetic polymorphisms of pvdhps and pvdhfr were analysed by nested PCR. Analysis at specific codons IPFSTSI associated with pyrimethamine resistance in the pvdhfr gene revealed that most of the samples (66/87, 75.9%) carried double mutation at positions IPFRTNI, while only 18.4% (16/87) of the isolates carried the wild-type haplotype (IPFSTSI). For the pvdhps gene, the codons involved in sulfadoxine resistance SAKAV were investigated. Single mutation at position SGKAV was most observed in 68.0% (68/100) of the samples, whereas wild-type haplotype was found in 26.0% (26/100) of samples. The pvdhps and pvdhfr combination SAKAV/IPFSTSI (wild-type), SGKAV/IPFRTNI, and SAKAV-IPFRTNI were the most frequently observed combination haplotypes from the three study sites. The information on molecular markers associated with antifolate drug-resistance could help better understanding ofthe molecular epidemiology and situation of SP resistant P. vivax malaria in the country. Continuous surveillance of these genetic markers is necessary to monitor the evolution of SP resistance in the Philippines.

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http://dx.doi.org/10.1016/j.actatropica.2018.01.006DOI Listing

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