Plasmodium vivax dhfr Mutations among Isolates from Malarious Areas of Iran
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The use of sulfadoxine and pyrimethamine (SP) for treatment of vivax malaria is uncommon in most malarious areas, but Plasmodium vivax isolates are exposed to SP because of mixed infections with other Plasmodium species. As P. vivax is the most prevalent species of human malaria parasites in Iran, monitoring of resistance of the parasite against the drug is necessary. In the present study, 50 blood samples of symptomatic patients were collected from 4 separated geographical regions of south-east Iran. Point mutations at residues 57, 58, 61, and 117 were detected by the PCR-RFLP method. Polymorphism at positions 58R, 117N, and 117T of P. vivax dihydrofolate reductase (Pvdhfr) gene has been found in 12%, 34%, and 2% of isolates, respectively. Mutation at residues F57 and T61 was not detected. Five distinct haplotypes of the Pvdhfr gene were demonstrated. The 2 most prevalent haplotypes were F57S58T61S117 (62%) and F57S58T61N117 (24%). Haplotypes with 3 and 4 point mutations were not found. The present study suggested that P. vivax in Iran is under the pressure of SP and the sensitivity level of the parasite to SP is diminishing and this fact must be considered in development of malaria control programs.
Abstract
The use of sulfadoxine and pyrimethamine (SP) for treatment of vivax malaria is uncommon in most malarious areas, but Plasmodium vivax isolates are exposed to SP because of mixed infections with other Plasmodium species. As P. vivax is the most prevalent species of human malaria parasites in Iran, monitoring of resistance of the parasite against the drug is necessary. In the present study, 50 blood samples of symptomatic patients were collected from 4 separated geographical regions of south-east Iran. Point mutations at residues 57, 58, 61, and 117 were detected by the PCR-RFLP method. Polymorphism at positions 58R, 117N, and 117T of P. vivax dihydrofolate reductase (Pvdhfr) gene has been found in 12%, 34%, and 2% of isolates, respectively. Mutation at residues F57 and T61 was not detected. Five distinct haplotypes of the Pvdhfr gene were demonstrated. The 2 most prevalent haplotypes were F57S58T61S117 (62%) and F57S58T61N117 (24%). Haplotypes with 3 and 4 point mutations were not found. The present study suggested that P. vivax in Iran is under the pressure of SP and the sensitivity level of the parasite to SP is diminishing and this fact must be considered in development of malaria control programs.
참고문헌 (34)
- Mendis K, "Carter R. The neglected burden of Plasmodium vivax malaria", Am J Trop Med Hyg, 64, pp.97~106 (2001)
- Schousboe ML, "Island-wide diversity in single nucleotide polymorphisms of the Plasmodium vivax dihydrofolate reductase and dihydropteroate synthetase genes in Sri Lanka", Malar J, 6, pp.28~ (2007)
- Auliff A, "Amino acid mutations in Plasmodium vivax DHFR and DHPS from several geographical regions and susceptibility to antifolate drugs", Am J Trop Med Hyg, 75, pp.617~621 (2006)
- Kaur S, "Plasmodium vivax dihydrofolate reductase point mutations from the Indian subcontinent", Acta Trop, 97, pp.174~180 (2006)
- Pukrittayakamee S, "Therapeutic responses to antimalarial and antibacterial drugs in vivax malaria", Acta Trop, 89, pp.351~356 (2004)
- Gregson A, "Mechanism of resistance of malaria parasites to antifolates", Pharmacol Rev, 57, pp.117~145 (2005)
- Alam MT, "Similar trends of pyrimethamine resistance-associated mutations in Plasmodium vivax and P. falciparum", Antimicrob Agents Chemother, 51, pp.857~863 (2007)
- Foote SJ, "The mode of action and the mechanism of resistance to antimalarial drugs", Acta Trop, 56, pp.157~171 (1994)
- Thaithong S, "Pyrimethamine resistant mutations in Plasmodium falciparum", Mol Biochem Parasitol, 52, pp.149~158 (1992)
- Volz KW, "Crystal structure of avian dihydrofolate reductase containing phenyltriazine and NADPH", J Biol Chem, 257, pp.2528~2536 (1982)
- Peterson DS, "Molecular basis of differential resistance to cycloguanil and pyrimethamine in Plasmodium falciparum malaria", Proc Natl Acad Sci USA, 87, pp.3018~3022 (1990)
- 김보연, "Molecular characterization of iron binding proteins, transferrin and ferritin heavy chain subunit, from the bumblebee Bombus ignitus", COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY, 152, pp.20~
- de Pecoulas PE, "Sequence variations in the Plasmodium vivax dihydrofolate reductase-thymidylate synthase gene and their relationship with pyrimethamine resistance", Mol Biochem Parasitol, 92, pp.265~273 (1998)
- Hastings MD, "Dihydrofolate reductase mutations in Plasmodium vivax from Indonesia and therapeutic response to sulfadoxine plus pyrimethamine", J Infect Dis, 189, pp.744~750 (2004)
- Kublin JG, "Molecular markers for failure of sulfadoxine-pyrimethamine and chlorproguanil-dapsone treatment of Plasmodium falciparum malaria", J Infect Dis, 185, pp.380~388 (2002)
- Zakeri S, "Detection of malaria parasites by nested PCR in south-eastern, Iran: evidence of highly mixed infections in Chahbahar district", Malar J, 1, pp.2~ (2002)
- Snounou G, "The co-existence of Plasmodium: sidelights from falciparum and vivax malaria in Thailand", Trends Parasitol, 20, pp.333~339 (2004)
- Imwong M, "Association of genetic mutations in Plasmodium vivax dhfr with resistance to sulfadoxine-pyrimethamine: geographical and clinical correlates", Antimicrob Agents Chemother, 45, pp.3122~3127 (2001)
- Imwong M, "Novel point mutations in the dihydrofolate reductase gene of Plasmodium vivax: evidence for sequential selection by drug pressure", Antimicrob Agents Chemother, 47, pp.1514~1521 (2003)
- Tjitra E, "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, pp.3947~3953 (2002)
- Hastings MD, "Novel Plasmodium vivax dhfr alleles from the Indonesian Archipelago and Papua New Guinea: association with pyrimethamine resistance determined by a Saccharomyces cerevisiae expression system", Antimicrob Agents Chemother, 49, pp.733~740 (2005)
- Brega S, "Real-time PCR for dihydrofolate reductase gene single-nucleotide polymorphisms in Plasmodium vivax isolates", Antimicrob Agents Chemother, 48, pp.2581~2587 (2004)
- de Pecoulas PE, "Genetic variation of the dihydrofolate reductase gene in Plasmodium vivax in Snoul, northeastern Cambodia", Acta Trop, 92, pp.1~6 (2004)
- Na BK, "Genetic variations of the dihydrofolate reductase gene of Plasmodium vivax in Mandalay Division, Myanmar", PARASITOLOGY RESEARCH, 96, pp.321~325 (2005), SPRINGER
- Schunk M, "High prevalence of drug-resistance mutations in Plasmodium falciparum and Plasmodium vivax in Southern Ethiopia", Malar J, 5, pp.54~59 (2006)
- 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)
- Leartsakulpanich U, "Molecular characterization of dihydrofolate reductase in relation to antifolate resistance in Plasmodium vivax", Mol Biochem Parasitol, 119, pp.63~73 (2002)
- Tahar R, "Kinetic properties of dihydrofolate reductase from wild-type and mutant Plasmodium vivax expressed in Escherichia coli", Mol Biochem Parasitol, 113, pp.241~249 (2001)
- "Diseases Management Center of MOH, I.R. Iran. Annual Reports of Malaria", ~ (2006)
- Shahbazi A, "Polymorphism of merozoite surface protein-3α gene of Plasmodium vivax in isolates of Iran", Iran J Parasitol, 3, pp.15~20 (2008)
- Shahbazi A, "Diversity of merozoite surface protein-3β gene of Plasmodium vivax isolates from Iran", Iran J Public Health, 36, pp.1~5 (2007)
- Snounou G, "The importance of sensitive detection of malaria parasites in the human and insect hosts in epidemiological studies, as shown by the analysis of field samples from Guinea Bissau", Trans R Soc Trop Med Hyg, 87, pp.649~653 (1993)
- Hawkins VN, "Antifolates can have a role in the treatment of Plasmodium vivax", Trends Parasitol, 23, pp.213~222 (2007)
- Imwong M, "Limited Polymorphism in the dihydropteroate synthetase gene (dhps) of Plasmodium vivax isolates from Thailand", Antimicrob Agents Chemother, 49, pp.4393~4395 (2005)
