Parasites, Hosts and Diseases

The Korea Society for Parasitology and Tropical Medicine (대한기생충학·열대의학회)
권호 표지
DOI QR코드

DOI QR Code

Genetic Polymorphisms in Plasmodium vivax Dihydrofolate Reductase and Dihydropteroate Synthase in Isolates from the Philippines, Bangladesh, and Nepal

  • Thongdee, Pimwan (Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University) ;
  • Kuesap, Jiraporn (Graduate Program in Biomedical Sciences, Faculty of Allied Health Sciences, Thammasat University) ;
  • Rungsihirunrat, Kanchana (Malaria Research Program, College of Public Health Sciences, Chulalongkorn University) ;
  • Dumre, Shyam Prakash (World Health Organization-Nepal/Epidemiology and Disease Control Division (EDCD), DoHS) ;
  • Espino, Effie (Research Institute for Tropical Medicine (RITM), Department of Health (DOH)) ;
  • Noedl, Harald (Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna) ;
  • Na-Bangchang, Kesara (Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University)
  • Received : 2014.11.24
  • Accepted : 2015.01.25
  • Published : 2015.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

Genetic polymorphisms of pvdhfr and pvdhps genes of Plasmodium vivax were investigated in 83 blood samples collected from patients in the Philippines, Bangladesh, and Nepal. The SNP-haplotypes of the pvdhfr gene at the amino acid positions 13, 33, 57, 58, 61, 117, and 173, and that of the pvdhps gene at the positions 383 and 553 were analyzed by nested PCR-RFLP. Results suggest diverse polymorphic patterns of pvdhfr alone as well as the combination patterns with pvdhps mutant alleles in P. vivax isolates collected from the 3 endemic countries in Asia. All samples carried mutant combination alleles of pvdhfr and pvdhps. The most prevalent combination alleles found in samples from the Philippines and Bangladesh were triple mutant pvdhfr combined with single mutant pvdhps allele and triple mutant pvdhfr combined with double wild-type pvdhps alleles, respectively. Those collected from Nepal were quadruple mutant pvdhfr combined with double wild-type pvdhps alleles. New alternative antifolate drugs which are effective against sulfadoxine-pyrimethamine (SP)-resistant P. vivax are required.

Keywords

References

  1. Mint Lekweiry K, Ould Mohamed Salem Boukhary A, Gaillard T, Wurtz N, Bogreau H, Hafid JE, Trape JF, Bouchiba H, Ould Ahmedou Salem MS, Pradines B, Rogier C, Basco LK, Briolant S. Molecular surveillance of drug-resistant Plasmodium vivax using pvdhfr, pvdhps and pvmdr1 markers in Nouakchott, Mauritania. J Antimicrob Chemother 2012; 67: 367-374. https://doi.org/10.1093/jac/dkr464
  2. Rahman MM, Ortega L, Rastogi RM, Thimasarn K. Antimalarial drug resistance. Regional Health Forum 2011; 15: 52-56.
  3. Annual Epidemiological Surveillance Report 2012. Available from: http://www.who.int/malaria/publications/.../profile_phl_en.pdf. 2012.
  4. Wijeyaratne PM, Valecha N, Joshi AB, Singh D, Pandey S. An inventory on malaria drug resistance in Bangladesh, Bhutan, India and Nepal. Environmental Health Project 2004. p 1-43.
  5. Gregson A, Plowe CV. Mechanisms of resistance of malaria parasites to antifolates. Pharmacol Rev 2005; 57: 117-145. https://doi.org/10.1124/pr.57.1.4
  6. Kaur S, Prajapati SK, Kalyanaraman K, Mohmmed A, Joshi H, Chauhan VS. Plasmodium vivax dihydrofolate reductase point mutations from the Indian subcontinent. Acta Trop 2006; 97: 174-180. https://doi.org/10.1016/j.actatropica.2005.10.003
  7. Mayxay M, Pukrittayakamee S, Newton PN, White NJ. Mixed-species malaria infections in humans. Trends Parasitol 2004; 20: 233-240. https://doi.org/10.1016/j.pt.2004.03.006
  8. Snounou G, White NJ. The co-existence of Plasmodium: sidelights from falciparum and vivax malaria in Thailand. Trends Parasitol 2004; 20: 333-339. https://doi.org/10.1016/j.pt.2004.05.004
  9. Zakeri S, Najafabadi ST, Zare A, Djadid ND. Detection of malaria parasites by nested PCR in south-eastern, Iran: evidence of highly mixed infections in Chahbahar district. Malar J 2002; 1: 2. https://doi.org/10.1186/1475-2875-1-2
  10. Mehlotra RK, Lorry K, Kastens W, Miller SM, Alpers MP, Bockarie M, Kazura JW, Zimmerman PA. Random distribution of mixed species malaria infections in Papua New Guinea. Am J Trop Med Hyg 2000; 62: 225-231. https://doi.org/10.4269/ajtmh.2000.62.225
  11. Imwong M, Pukrittayakamee S, Renia L, Letourneur F, Charlieu JP, Leartsakulpanich U, Looareesuwan S, White NJ, Snounou G. Novel point mutations in the dihydrofolate reductase gene of Plasmodium vivax: evidence for sequential selection by drug pressure. Antimicrob Agents Chemother 2003; 47: 1514-1521. https://doi.org/10.1128/AAC.47.5.1514-1521.2003
  12. Thongdee P, Kuesap J, Rungsihirunrat K, Tippawangkosol P, Mungthin M, Na-Bangchang K. Distribution of dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) mutant alleles in Plasmodium vivax isolates from Thailand. Acta Trop 2013; 128: 137-143. https://doi.org/10.1016/j.actatropica.2013.07.005
  13. Kuesap J, Rungsrihirunrat K, Thongdee P, Ruangweerayut R, Na-Bangchang K. 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 2011; 106 (Suppl 1): 130-133.
  14. Hastings MD, Porter KM, Maguire JD, Susanti I, Kania W, Bangs MJ, Sibley CH, Baird JK. Dihydrofolate reductase mutations in Plasmodium vivax from Indonesia and therapeutic response to sulfadoxine plus pyrimethamine. J Infect Dis 2004; 189: 744-750. https://doi.org/10.1086/381397
  15. Ranjitkar S, Schousboe ML, Thomsen TT, Adhikari M, Kapel CM, Bygbjerg IC, Alifrangis M. Prevalence of molecular markers of anti-malarial drug resistance in Plasmodium vivax and Plasmodium falciparum in two districts of Nepal. Malar J 2011; 10: 75. https://doi.org/10.1186/1475-2875-10-75
  16. Imwong M, Pukrittakayamee S, Looareesuwan S, Pasvol G, Poirriez J, White NJ, Snounou G. Association of genetic mutations in Plasmodium vivax dhfr with resistance to sulfadoxine-pyrimethamine: geographical and clinical correlates. Antimicrob Agents Chemother 2001; 45: 3122-3127. https://doi.org/10.1128/AAC.45.11.3122-3127.2001
  17. Zakeri S, Afsharpad M, Ghasemi F, Raeisi A, Safi N, Butt W, Atta H, Djadid ND. Molecular surveillance of Plasmodium vivax dhfr and dhps mutations in isolates from Afghanistan. Malar J 2010; 9: 75. https://doi.org/10.1186/1475-2875-9-75
  18. Afsharpad M, Zakeri S, Pirahmadi S, Djadid ND. Molecular assessment of dhfr/dhps mutations among Plasmodium vivax clinical isolates after introduction of sulfadoxine/pyrimethamine in combination with artesunate in Iran. Infect Genet Evol 2012; 12: 38-44. https://doi.org/10.1016/j.meegid.2011.10.003
  19. Barnadas C, Kent D, Timinao L, Iga J, Gray LR, Siba P, Mueller I, Thomas PJ, Zimmerman PA. A new high-throughput method for simultaneous detection of drug resistance associated mutations in Plasmodium vivax dhfr, dhps and mdr1 genes. Malar J 2011; 10; 282. https://doi.org/10.1186/1475-2875-10-282
  20. Barnadas C, Tichit M, Bouchier C, Ratsimbasoa A, Randrianasolo L, Raherinjafy R, Jahevitra M, Picot S, Menard D. Plasmodium vivax dhfr and dhps mutations in isolates from Madagascar and therapeutic response to sulphadoxine-pyrimethamine. Malar J 2008; 7: 35. https://doi.org/10.1186/1475-2875-7-35
  21. Zakeri S, Motmaen SR, Afsharpad M, Djadid ND. Molecular characterization of antifolates resistance-associated genes (dhfr and dhps) in Plasmodium vivax isolates from the Middle East. Malar J 2009; 8: 20. https://doi.org/10.1186/1475-2875-8-20
  22. Rungsihirunrat K, Sibley CH, Mungthin M, Na-Bangchang K. Geographical distribution of amino acid mutations in Plasmodium vivax DHFR and DHPS from malaria endemic areas of Thailand. Am J Trop Med Hyg 2008; 78: 462-467.
  23. Auliff A, Wilson DW, Russell B, Gao Q, Chen N, Anh LN, Maguire J, Bell D, O'Neil MT, Cheng Q. Amino acid mutations in Plasmodium vivax DHFR and DHPS from several geographical regions and susceptibility to antifolate drugs. Am J Trop Med Hyg 2006; 75: 617-621.
  24. Almeidaa AD, do Rosariob VE, Henriquesb G, Arezb AP, Cravob P. Plasmodium vivax in the democratic Republic of East Timor: parasite prevalence and antifolate resistance-associated mutations. Acta Trop 2010; 115: 288-292. https://doi.org/10.1016/j.actatropica.2010.04.008
  25. Lu F, Lim CS, Nam DH, Kim K, Lin K, Kim TS. Mutations in the antifolate resistance-associated genes dihydrofolate reductase and dihydropteroate synthase in Plasmodium vivax isolates from malaria-endemic countries. Am J Trop Med Hyg 2010; 83: 474-479. https://doi.org/10.4269/ajtmh.2010.10-0004
  26. Zakeri S, Afsharpad M, Ghasemi F, Raeisi A, Kakar Q, Atta H, Djadid ND. Plasmodium vivax: prevalence of mutations associated with sulfadoxine-pyrimethamine resistance in Plasmodium vivax clinical isolates from Pakistan. Exp Parasitol 2011; 127: 167-172. https://doi.org/10.1016/j.exppara.2010.07.011
  27. Imwong M, Pukrittayakamee S, Gruner AC, Renia L, Letourneur F, Looareesuwan S, White NJ, Snounou G. Practical PCR genotyping protocols for Plasmodium vivax using pvcs and pvmsp1. Malar J 2005; 4: 20. https://doi.org/10.1186/1475-2875-4-20

Cited by

  1. Mutations of pvdhfr and pvdhps genes in vivax endemic-malaria areas in Kota Marudu and Kalabakan, Sabah vol.15, pp.None, 2016, https://doi.org/10.1186/s12936-016-1109-9
  2. Geographic distribution of amino acid mutations in DHFR and DHPS in Plasmodium vivax isolates from Lao PDR, India and Colombia vol.15, pp.None, 2016, https://doi.org/10.1186/s12936-016-1543-8