1921
Volume 83, Issue 3
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract.

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 dihydrofolate reductase () and dihydropteroate synthase () 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 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 point mutations correlated strongly with the 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 and in isolates from different malaria-endemic countries is associated with selection pressure imposed by sulfadoxine-pyrimethamine.

Loading

Article metrics loading...

The graphs shown below represent data from March 2017
/content/journals/10.4269/ajtmh.2010.10-0004
2010-09-07
2019-11-18
Loading full text...

Full text loading...

/deliver/fulltext/14761645/83/3/474.html?itemId=/content/journals/10.4269/ajtmh.2010.10-0004&mimeType=html&fmt=ahah

References

  1. Mendis K, Sina BJ, Marchesini P, Carter R, , 2001. The neglected burden of Plasmodium vivax malaria. Am J Trop Med Hyg 64: 97106. [Google Scholar]
  2. 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: 105113.[Crossref] [Google Scholar]
  3. 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: 555566.[Crossref] [Google Scholar]
  4. Thimasarn K, Malikul S, , 1999. Malaria Control Program in Thailand. , ed. Bangkok, Thailand: Malaria Division, Department of Communicable Disease Control, Ministry of Public Health, Thailand, 88102. [Google Scholar]
  5. 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: 15141521.[Crossref] [Google Scholar]
  6. 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: 468472.[Crossref] [Google Scholar]
  7. 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: 11841190.[Crossref] [Google Scholar]
  8. 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: 9198.[Crossref] [Google Scholar]
  9. 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: 26572659.[Crossref] [Google Scholar]
  10. 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: 175176. [Google Scholar]
  11. 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: 321325.[Crossref] [Google Scholar]
  12. 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: 827834.[Crossref] [Google Scholar]
  13. 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: 582588.[Crossref] [Google Scholar]
  14. Young MD, Burgess RW, , 1959. Pyrimethamine resistance in Plasmodium vivax malaria. Bull World Health Organ 20: 2736. [Google Scholar]
  15. 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: 617621. [Google Scholar]
  16. 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: 10571065. [Google Scholar]
  17. 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: 565568. [Google Scholar]
  18. 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: 39473953.[Crossref] [Google Scholar]
  19. 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: 22142222.[Crossref] [Google Scholar]
  20. 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: 213222.[Crossref] [Google Scholar]
  21. 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: 6373.[Crossref] [Google Scholar]
  22. 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: 265273.[Crossref] [Google Scholar]
  23. 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: 215217. [Google Scholar]
  24. 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: 25812587.[Crossref] [Google Scholar]
  25. 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: 3542.[Crossref] [Google Scholar]
  26. 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: 409417.[Crossref] [Google Scholar]
  27. 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: 247252. [Google Scholar]
  28. Triglia T, Cowman AF, , 1994. Primary structure and expression of the dihydropteroate synthetase gene of Plasmodium falciparum . Proc Natl Acad Sci USA 91: 71497153.[Crossref] [Google Scholar]
  29. Triglia T, Cowman AF, , 1999. The mechanism of resistance to sulfa drugs in Plasmodium falciparum . Drug Resist Updat 2: 1519.[Crossref] [Google Scholar]
  30. 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: 38073815.[Crossref] [Google Scholar]
  31. 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: 462467. [Google Scholar]
  32. Menegon M, Majori G, Severini C, , 2006. Genetic variations of the Plasmodium vivax dihydropteroate synthase gene. Acta Trop 98: 196199.[Crossref] [Google Scholar]
  33. 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: 348355. [Google Scholar]
  34. 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: 43934395.[Crossref] [Google Scholar]
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.2010.10-0004
Loading
/content/journals/10.4269/ajtmh.2010.10-0004
Loading

Data & Media loading...

  • Received : 03 Jan 2010
  • Accepted : 15 May 2010
  • Published online : 07 Sep 2010

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error