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Geographical Distribution of Amino Acid Mutations in Plasmodium vivax DHFR and DHPS from Malaria Endemic Areas of Thailand

Both malaria treatment and prophylaxis target the parasite dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR) enzymes. Specific point mutations in these genes confer resistance to sulfadoxine-pyrimethamine (SP) in both Plasmodium falciparum and P. vivax. We used direct sequencing to examine the prevalence of point mutations in pvdhps and pvdhfr in 160 P. vivax isolates collected from areas along the international borders of Thailand. Results show that the majority of the isolates harbored a quadruple mutant allele of pvdhfr and a double mutant allele of pvdhps, but the distribution was not uniform. The highly mutant allele combination was especially prevalent along the Thai-Myanmar border, whereas the majority of the isolates from areas along the Thai-Cambodian and Thai-Malaysian borders carried double mutant alleles of pvdhfr and single mutant alleles of pvdhps. Novel mutations that have not been identified previously at codon 512 of pvdhps (K512M, K512E, K512T) were also found.

Received August 27, 2007. Accepted for publication November 21, 2007.

Acknowledgments: The authors thank the patients who participated in this study and the staff of Malaria Clinic for their kind assistance during blood sample collection.

Financial support: This work was supported by Thailand Research Fund through The Royal Golden Jubilee PhD program.

^* Address correspondence to Kesara Na-Bangchang, Faculty of Allied Health Sciences, Thammasat University, Pathumtani, Thailand, 12121. E-mail: kesaratmu{at}yahoo.com

Authors’ addresses: Kanchana Rungsihirunrat and Kesara Na-Bangchang, Faculty of Allied Health Sciences, Thammasat University, Pathumtani 12121, Thailand, E-mail: kesaratmu{at}yahoo.com. Carol Hopkins Sibley, Department of Genome Sciences, University of Washington, Seattle, WA 98195-5065. Mathirut Mungthin, Department of Parasitology, Phramongkutklao College of Medicine, Bangkok, Thailand.

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