Genetic Polymorphisms in the pvdhfr, pvmdr1, and pvdhps Genes of Plasmodium vivax in Patients at a Secondary Hospital in South Korea
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Background: Plasmodium vivax is a major pathogen that causes malaria in South Korea. Several genetic polymorphisms in dihydrofolate reductase (pvdhfr ), P. vivax multidrugresistance protein 1 (pvmdr1 ), and P. vivax hydroxymethylpterin pyrophosphokinasedihydropteroatesynthetase (pvdhps) genes are known to be associated with drug resistancein P. vivax. The objective of this study was to profile the known polymorphisms of P. vivaxresistance genes in patients at a secondary hospital in South Korea. Methods: A total of 12 patients with confirmed P. vivax infections were enrolled for thisstudy. Sanger sequencing was performed for the pvdhfr, pvmdr1, and pvdhps genes to detectpolymorphisms of these drug resistance genes. Results: Each specimen had single or double polymorphism in pvdhfr. One specimen had apolymorphism in pvdhps. However, no specimen had any polymorphisms in pvmdr1. Therewas no strain with multi-polymorphisms exceeding double polymorphisms, which reportedthe geographic location of treatment failure. Conclusion: No specimen showed chloroquine-resistance polymorphism in pvmdr1. Treatment with first-line therapy was successful. The prevalence of F57L in pvdhfr was higherthan that reported previously. This change must be confirmed by further monitoring andsurveillance of the strains with multi-polymorphisms.
Abstract
Background: Plasmodium vivax is a major pathogen that causes malaria in South Korea. Several genetic polymorphisms in dihydrofolate reductase (pvdhfr ), P. vivax multidrugresistance protein 1 (pvmdr1 ), and P. vivax hydroxymethylpterin pyrophosphokinasedihydropteroatesynthetase (pvdhps) genes are known to be associated with drug resistancein P. vivax. The objective of this study was to profile the known polymorphisms of P. vivaxresistance genes in patients at a secondary hospital in South Korea. Methods: A total of 12 patients with confirmed P. vivax infections were enrolled for thisstudy. Sanger sequencing was performed for the pvdhfr, pvmdr1, and pvdhps genes to detectpolymorphisms of these drug resistance genes. Results: Each specimen had single or double polymorphism in pvdhfr. One specimen had apolymorphism in pvdhps. However, no specimen had any polymorphisms in pvmdr1. Therewas no strain with multi-polymorphisms exceeding double polymorphisms, which reportedthe geographic location of treatment failure. Conclusion: No specimen showed chloroquine-resistance polymorphism in pvmdr1. Treatment with first-line therapy was successful. The prevalence of F57L in pvdhfr was higherthan that reported previously. This change must be confirmed by further monitoring andsurveillance of the strains with multi-polymorphisms.
참고문헌 (19)
- Kim YK, "Therapeutic efficacy of chloroquine in Plasmodium vivax and the pvmdr1 polymorphisms in the Republic of Korea under mass chemoprophylaxis", Am J Trop Med Hyg, 84, pp.532~534 (2011)
- Rieckmann KH, "Plasmodium vivax resistance to chloroquine?", Lancet, 2, pp.1183~1184 (1989)
- Schwartz IK, "Chloroquine-resistant Plasmodium vivax from Indonesia", N Engl J Med, 324, pp.927~ (1991)
- Tjitra E, "Therapeutic efficacies of artesunatesulfadoxine-pyrimethamine and chloroquine-sulfadoxine-pyrimethamine in vivax malaria pilot studies : relationship to Plasmodium vivax dhfr mutations", Antimicrob Agents Chemother, 46, pp.3947~3953 (2002)
- Barnadas C, "Plasmodium vivax resistance to chloroquine in Madagascar : clinical efficacy and polymorphisms in pvmdr1and pvcrt-o genes", Antimicrob Agents Chemother, 52, pp.4233~4240 (2008)
- Orjuela-Sánchez P, "Analysis of single-nucleotide polymorphisms in the crt-o and mdr1 genes of Plasmodium vivax among chloroquine-resistant isolates from the Brazilian Amazon region", Antimicrob Agents Chemother, 53, pp.3561~3564 (2009)
- Vargas-Rodríguez Rdel C, "Single-nucleotide polymorphism and copy number variation of the multidrug resistance-1locus of Plasmodium vivax : local and global patterns", Am J Trop Med Hyg, 87, pp.813~821 (2012)
- Feng Lu, "Prevalence of Drug Resistance-Associated Gene Mutations in Plasmodium vivax in Central China", Parasites, Hosts and Diseases, 50(4), pp.379~384 (2012), 대한기생충학ㆍ열대의학회
- Khattak AA, "Prevalence and patterns of antifolate and chloroquine drug resistance markers in Plasmodium vivax across Pakistan", Malar J, 12, pp.310~ (2013)
- WHO, "WHO guidelines approved by the guidelines review committee. In: Guidelines for the treatment of malaria", World Health Organization, ~ (2015)
- Barnadas C, "High prevalence and fixation of Plasmodium vivax dhfr", dhps mutations related to sulfadoxine, Am J Trop Med Hyg, pp.2009, 81[DOI]
- Hawkins VN, "Antifolates can have a role in the treatment of Plasmodium vivax", Trends Parasitol, 23, pp.213~222 (2007)
- Marques MM, "Plasmodium vivax chloroquine resistance and anemia in the western Brazilian Amazon", Antimicrob Agents Chemother, 58, pp.342~347 (2014)
- Kuesap J, "Change in mutation patterns of Plasmodium vivax dihydrofolate reductase (Pvdhfr) and dihydropteroate synthase (Pvdhps) in P. vivax isolates from malaria endemic areas of Thailand", Mem Inst Oswaldo Cruz, 106(S), pp.130~133 (2011)
- Mint Lekweiry K, "Molecular surveillance of drug-resistant Plasmodium vivax using pvdhfr, pvdhps and pvmdr1 markers in Nouakchott, Mauritania", J Antimicrob Chemother, 67, pp.367~374 (2012)
- Gama BE, "Characterisation of pvmdr1 and pvdhfr genes associated with chemoresistance in Brazilian Plasmodium vivax isolates", Mem Inst Oswaldo Cruz, 104, pp.1009~1011 (2009)
- Valecha N, "Therapeutic efficacy of chloroquine in Plasmodium vivax from areas with different epidemiological patterns in India and their Pvdhfr gene mutation pattern", Trans R Soc Trop Med Hyg, 100, pp.831~837 (2006)
- Lu F, "Mutations in the antifolate-resistanceassociated genes dihydrofolate reductase and dihydropteroate synthase in Plasmodium vivax isolates from malaria-endemic countries", Am J Trop Med Hyg, 83, pp.474~479 (2010)
- Choi YK, "Genetic diversity and antimalarial drug resistance of Plasmodium vivax in Korea", pp.2010