Mendis K, Sina BJ, Marchesini P, Carter R, 2001. The neglected burden of Plasmodium vivax malaria. Am J Trop Med Hyg 64: 97–106.
Yeshiwondim AK, Tekle AH, Dengela DO, Yohannes AM, Teklehaimanot A, 2010. Therapeutic efficacy of chloroquine and chloroquine plus primaquine for the treatment of Plasmodium vivax in Ethiopia. Acta Trop 113: 105–113.
Mueller I, Galinski MR, Baird JK, Carlton JM, Kochar DK, Alonso PL, del Portillo HA, 2009. Key gaps in the knowledge of Plasmodium vivax, a neglected human malaria parasite. Lancet Infect Dis 9: 555–566.
Thimasarn K, 1999. Malaria Control Program in Thailand. Malikul S, ed. Bangkok, Thailand: Malaria Division, Department of Communicable Disease Control, Ministry of Public Health, Thailand, 88–102.
Imwong M, Pukrittayakamee S, Renia L, Letourneur F, Charlieu JP, Leartsakulpanich U, Looareesuwan S, White NJ, Snounou G, 2003. Novel point mutations in the dihydrofolate reductase gene of Plasmodium vivax: evidence for sequential selection by drug pressure. Antimicrob Agents Chemother 47: 1514–1521.
Smithuis FM, Monti F, Grundl M, Oo AZ, Kyaw TT, Phe O, White NJ, 1997. Plasmodium falciparum: sensitivity in vivo to chloroquine, pyrimethamine/sulfadoxine and mefloquine in western Myanmar. Trans R Soc Trop Med Hyg 91: 468–472.
Smithuis F, Shahmanesh M, Kyaw MK, Savran O, Lwin S, White NJ, 2004. Comparison of chloroquine, sulfadoxine/pyrimethamine, mefloquine and mefloquine-artesunate for the treatment of falciparum malaria in Kachin State, North Myanmar. Trop Med Int Health 9: 1184–1190.
Guthmann JP, Pittet A, Lesage A, Imwong M, Lindegardh N, Min Lwin M, Zaw T, Annerberg A, de Radigues X, Nosten F, 2008. Plasmodium vivax resistance to chloroquine in Dawei, southern Myanmar. Trop Med Int Health 13: 91–98.
Imwong M, Pukrittayakamee S, Pongtavornpinyo W, Nakeesathit S, Nair S, Newton P, Nosten F, Anderson TJ, Dondorp A, Day NP, White NJ, 2008. Gene amplification of the multidrug resistance 1 gene of Plasmodium vivax isolates from Thailand, Laos, and Myanmar. Antimicrob Agents Chemother 52: 2657–2659.
Liang GL, Sun XD, Wang J, Zhang ZX, 2009. Sensitivity of Plasmodium vivax to chloroquine in Laza City, Myanmar. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi 27: 175–176.
Na BK, Lee HW, Moon SU, In TS, Lin K, Maung M, Chung GT, Lee JK, Kim TS, Kong Y, 2005. Genetic variations of the dihydrofolate reductase gene of Plasmodium vivax in Mandalay Division, Myanmar. Parasitol Res 96: 321–325.
Kim C, Shin DC, Yong TS, Oh DK, Kim RK, Park K, Suh IL, 2006. Chemoprophylaxis and the epidemiological characteristics of re-emergent P. vivax malaria in the Republic of Korea. Bull World Health Organ 84: 827–834.
Sibley CH, Hyde JE, Sims PF, Plowe CV, Kublin JG, Mberu EK, Cowman AF, Winstanley PA, Watkins WM, Nzila AM, 2001. Pyrimethamine-sulfadoxine resistance in Plasmodium falciparum: what next? Trends Parasitol 17: 582–588.
Young MD, Burgess RW, 1959. Pyrimethamine resistance in Plasmodium vivax malaria. Bull World Health Organ 20: 27–36.
Auliff A, Wilson DW, Russell B, Gao Q, Chen N, Anh le N, Maguire J, Bell D, O'Neil MT, Cheng Q, 2006. Amino acid mutations in Plasmodium vivax DHFR and DHPS from several geographical regions and susceptibility to antifolate drugs. Am J Trop Med Hyg 75: 617–621.
Rungsihirunrat K, Na-Bangchang K, Hawkins VN, Mungthin M, Sibley CH, 2007. Sensitivity to antifolates and genetic analysis of Plasmodium vivax isolates from Thailand. Am J Trop Med Hyg 76: 1057–1065.
Plowe CV, Djimde A, Bouare M, Doumbo O, Wellems TE, 1995. Pyrimethamine and proguanil resistance-conferring mutations in Plasmodium falciparum dihydrofolate reductase: polymerase chain reaction methods for surveillance in Africa. Am J Trop Med Hyg 52: 565–568.
Tjitra E, Baker J, Suprianto S, Cheng Q, Anstey NM, 2002. Therapeutic efficacies of artesunate-sulfadoxine-pyrimethamine and chloroquine-sulfadoxine-pyrimethamine in vivax malaria pilot studies: relationship to Plasmodium vivax dhfr mutations. Antimicrob Agents Chemother 46: 3947–3953.
Korsinczky M, Fischer K, Chen N, Baker J, Rieckmann K, Cheng Q, 2004. Sulfadoxine resistance in Plasmodium vivax is associated with a specific amino acid in dihydropteroate synthase at the putative sulfadoxine-binding site. Antimicrob Agents Chemother 48: 2214–2222.
Hawkins VN, Joshi H, Rungsihirunrat K, Na-Bangchang K, Sibley CH, 2007. Antifolates can have a role in the treatment of Plasmodium vivax. Trends Parasitol 23: 213–222.
Leartsakulpanich U, Imwong M, Pukrittayakamee S, White NJ, Snounou G, Sirawaraporn W, Yuthavong Y, 2002. Molecular characterization of dihydrofolate reductase in relation to antifolate resistance in Plasmodium vivax. Mol Biochem Parasitol 119: 63–73.
de Pecoulas PE, Tahar R, Ouatas T, Mazabraud A, Basco LK, 1998. Sequence variations in the Plasmodium vivax dihydrofolate reductase-thymidylate synthase gene and their relationship with pyrimethamine resistance. Mol Biochem Parasitol 92: 265–273.
Lee KS, Kim TH, Kim ES, Lim HS, Yeom JS, Jun G, Park JW, 2009. Short report: chloroquine-resistant Plasmodium vivax in the Republic of Korea. Am J Trop Med Hyg 80: 215–217.
Brega S, de Monbrison F, Severini C, Udomsangpetch R, Sutanto I, Ruckert P, Peyron F, Picot S, 2004. Real-time PCR for dihydrofolate reductase gene single-nucleotide polymorphisms in Plasmodium vivax isolates. Antimicrob Agents Chemother 48: 2581–2587.
Li J, Collins WE, Wirtz RA, Rathore D, Lal A, McCutchan TF, 2001. Geographic subdivision of the range of the malaria parasite Plasmodium vivax. Emerg Infect Dis 7: 35–42.
Marfurt J, de Monbrison F, Brega S, Barbollat L, Muller I, Sie A, Goroti M, Reeder JC, Beck HP, Picot S, Genton B, 2008. Molecular markers of in vivo Plasmodium vivax resistance to amodiaquine plus sulfadoxine-pyrimethamine: mutations in pvdhfr and pvmdr1. J Infect Dis 198: 409–417.
Kyabayinze D, Cattamanchi A, Kamya MR, Rosenthal PJ, Dorsey G, 2003. Validation of a simplified method for using molecular markers to predict sulfadoxine-pyrimethamine treatment failure in African children with falciparum malaria. Am J Trop Med Hyg 69: 247–252.
Triglia T, Cowman AF, 1994. Primary structure and expression of the dihydropteroate synthetase gene of Plasmodium falciparum. Proc Natl Acad Sci USA 91: 7149–7153.
Triglia T, Cowman AF, 1999. The mechanism of resistance to sulfa drugs in Plasmodium falciparum. Drug Resist Updat 2: 15–19.
Triglia T, Wang P, Sims PF, Hyde JE, Cowman AF, 1998. Allelic exchange at the endogenous genomic locus in Plasmodium falciparum proves the role of dihydropteroate synthase in sulfadoxine-resistant malaria. EMBO J 17: 3807–3815.
Rungsihirunrat K, Sibley CH, Mungthin M, Na-Bangchang K, 2008. Geographical distribution of amino acid mutations in Plasmodium vivax DHFR and DHPS from malaria endemic areas of Thailand. Am J Trop Med Hyg 78: 462–467.
Menegon M, Majori G, Severini C, 2006. Genetic variations of the Plasmodium vivax dihydropteroate synthase gene. Acta Trop 98: 196–199.
Hawkins VN, Suzuki SM, Rungsihirunrat K, Hapuarachchi HC, Maestre A, Na-Bangchang K, Sibley CH, 2009. Assessment of the origins and spread of putative resistance-conferring mutations in Plasmodium vivax dihydropteroate synthase. Am J Trop Med Hyg 81: 348–355.
Imwong M, Pukrittayakamee S, Cheng Q, Moore C, Looareesuwan S, Snounou G, White NJ, Day NP, 2005. Limited polymorphism in the dihydropteroate synthetase gene (dhps) of Plasmodium vivax isolates from Thailand. Antimicrob Agents Chemother 49: 4393–4395.
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Parasite dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) are known target enzymes of antifolate drugs used for the treatment and prophylaxis of persons with malaria. We sequenced the Plasmodium vivax dihydrofolate reductase (pvdhfr) and dihydropteroate synthase (pvdhps) genes to examine the prevalence and extent of point mutations in isolates from malaria-endemic countries. Double mutations (S58R and S117N) or quadruple mutations (F57L/I, S58R, T61M, and S117T) in the pvdhfr gene were found in isolates from Thailand (96.4%) and Myanmar (71.4%), but in only one isolate (1.0%) from Korea, where sulfadoxine-pyrimethamine has never been used. The pvdhfr point mutations correlated strongly with the pvdhps point mutations and ranged from single to triple mutations (S382A, A383G, and A553G), among isolates from Thailand, Myanmar, and Korea. These findings suggests that the prevalence of mutations in pvdhfr and pvdhps in P. vivax isolates from different malaria-endemic countries is associated with selection pressure imposed by sulfadoxine-pyrimethamine.
Financial support: This study was supported by a National Research Foundation of Korea grant funded by the Korean Government (KRF-2008-314-E00075).
Disclosure: The view of the authors do not purport to reflect the position of the U.S. Department of the Army or Department of Defense.
Authors' addresses: Feng Lu, Department of Parasitology, Kangwon National University College of Medicine, Chuncheon, Gangwon-do, Republic of Korea and Jiangsu Institute of Parasitic Diseases, Wuxi, People's Republic of China, E-mail: email@example.com. Chae Seung Lim and Deok-Hwa Nam, Department of Laboratory Medicine, College of Medicine, Korea University, Seoul, Republic of Korea, E-mails: firstname.lastname@example.org and email@example.com. Kwonkee Kim, Department of Internal Medicine, Gachon University Cheorwon Gil Hospital, Cheorwon, Gangwon-do, Republic of Korea, E-mail: firstname.lastname@example.org. Khin Lin, Vector-Borne Diseases Control Project, Department of Health, Ministry of Health, Mandalay, Myanmar. Tong-Soo Kim, Department of Parasitology, Inha University School of Medicine, Incheon, Republic of Korea, E-mail: email@example.com. Hyeong-Woo Lee, Department of Malaria and Parasite Disease, National Institute of Health, Korea Centers for Disease Control and Prevention, Seoul, Republic of Korea and Department of Pathology, University of Florida, Gainesville, FL, E-mail: firstname.lastname@example.org. Jun-Hu Chen and Yue Wang, Department of Parasitology, Kangwon National University College of Medicine, Chuncheon, Gangwon-do, Republic of Korea and Institute of Parasitic Diseases, Zhejiang Academy of Medical Sciences, Hangzhou, People's Republic of China, E-mails: email@example.com and firstname.lastname@example.org. Jetsumon Sattabongkot, Department of Entomology, Armed Forces Research Institute of Medical Science, Bangkok, Thailand, E-mail: email@example.com. Eun-Taek Han, Department of Parasitology, Kangwon National University College of Medicine, Chuncheon, Gangwon-do, Republic of Korea, E-mail: firstname.lastname@example.org.