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http://dx.doi.org/10.3347/kjp.2022.60.2.109

Molecular Markers for Sulfadoxine/Pyrimethamine and Chloroquine Resistance in Plasmodium falciparum in Thailand  

Kuesap, Jiraporn (Faculty of Allied Health Sciences, Thammasat University)
Suphakhonchuwong, Nutnicha (Faculty of Allied Health Sciences, Thammasat University)
Kalawong, Lertluk (Faculty of Allied Health Sciences, Thammasat University)
Khumchum, Natthaya (Faculty of Allied Health Sciences, Thammasat University)
Publication Information
Parasites, Hosts and Diseases / v.60, no.2, 2022 , pp. 109-116 More about this Journal
Abstract
Drug resistance is an important problem hindering malaria elimination in tropical areas. Point mutations in Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes confer resistance to antifolate drug, sulfadoxine-pyrimethamine (SP) while P. falciparum chloroquine-resistant transporter (Pfcrt) genes caused resistance to chloroquine (CQ). Decline in Pfdhfr/Pfdhps and Pfcrt mutations after withdrawal of SP and CQ has been reported. The aim of present study was to investigate the prevalence of Pfdhfr, Pfdhps, and Pfcrt mutation from 2 endemic areas of Thailand. All of 200 blood samples collected from western area (Thai-Myanmar) and southern area (Thai-Malaysian) contained multiple mutations in Pfdhfr and Pfdhps genes. The most prevalent haplotypes for Pfdhfr and Pfdhps were quadruple and double mutations, respectively. The quadruple and triple mutations of Pfdhfr and Pfdhps were common in western samples, whereas low frequency of triple and double mutations was found in southern samples, respectively. The Pfcrt 76T mutation was present in all samples examined. Malaria isolated from 2 different endemic regions of Thailand had high mutation rates in the Pfdhfr, Pfdhps, and Pfcrt genes. These findings highlighted the fixation of mutant alleles causing resistance of SP and CQ in this area. It is necessary to monitor the re-emergence of SP and CQ sensitive parasites in this area.
Keywords
Plasmodium falciparum; dihydropteroate synthase; dihydrofolate reductase; chloroquine-resistant transporter; molecular marker;
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1 Maguire JD, Susanti AI Krisin, Sismadi P, Fryauff DJ, Baird JK. The T76 mutation in the pfcrt gene of Plasmodium falciparum and clinical chloroquine resistance phenotypes in Papua, Indonesia. Ann Trop Med Parasitol 2001; 95: 559-572. https://doi.org/10.1080/00034980120092516   DOI
2 Sugaram R, Suwannasin K, Kunasol C, Mathema VB, Day NPJ, Sudathip P, Prempree P, Dondorp AM, Imwong M. Molecular characterization of Plasmodium falciparum antifolate resistance markers in Thailand between 2008 and 2016. Malar J 2020; 19: 107. https://doi.org/10.1186/s12936-020-03176-x   DOI
3 Holmgren G, Gil JP, Ferreira PM, Veiga MI, Obonyo CO, Bjorkman A. Amodiaquine resistant Plasmodium falciparum malaria in vivo is associated with selection of pfcrt 76T and pfmdr1 86Y. Infect Genet Evol 2006; 6: 309-314. https://doi.org/10.1016/j.meegid.2005.09.001   DOI
4 Pearce RJ, Ord R, Kaur H, Lupala C, Schellenberg J, Shirima K, Manzi F, Alonso P, Tanner M, Mshinda H, Roper C, Schellenberg D. A community-randomized evaluation of the effect of intermittent preventive treatment in infants on antimalarial drug resistance in southern Tanzania. J Infect Dis 2013; 207: 848-859. https://doi.org/10.1093/infdis/jis742   DOI
5 Lau TY, Sylvi M, William T. Mutational analysis of Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase genes in the interior division of Sabah, Malaysia. Malar J 2013; 12: 445. https://doi.org/10.1186/1475-2875-12-445   DOI
6 Alam MT, Vinayak S, Congpuong K, Wongsrichanalai C, Satimai W, Slutsker L, Escalante AA, Barnwell JW, Udhayakumar V. Tracking origins and spread of sulfadoxine-resistant Plasmodium falciparum dhps alleles in Thailand. Antimicrob Agents Chemother 2011; 155-164. https://doi.org/10.1128/AAC.00691-10   DOI
7 Na-Bangchang K, Congpuong K. Current malaria status and distribution of drug resistance in East and Southeast Asia with special focus to Thailand. Tohoku J Exp Med 2007; 211: 99-113. https://doi.org/10.1620/tjem.211.99   DOI
8 Krudsood S, Imwong M, Wilairatana P, Pukrittayakamee S, Nonprasert A, Snounou G, White NJ, Looareesuwan S. Artesunate-dapsone-proguanil treatment of falciparum malaria: genotypic determinants of therapeutic response. Trans R Soc Trop Med Hyg 2005; 99: 142-149. https://doi.org/10.1016/j.trstmh.2004.07.001   DOI
9 Chen N, Kyle DE, Pasay C, Fowler EV, Baker J, Peters JM, Cheng Q. pfcrt allelic types with two novel amino acid mutations in chloroquine-resistant Plasmodium falciparum isolates from the Philippines. Antimicrob Agents Chemother 2003; 47: 3500-3505. https://doi.org/10.1128/AAC.47.11.3500-3505.2003   DOI
10 Wongsrichanalai C, Pickard AL, Wernsdorfer WH, Meshnick SR. Epidemiology of drug-resistant malaria. Lancet Infect Dis 2002; 2: 209-218. https://doi.org/10.1016/s1473-3099(02)00239-6   DOI
11 McCollum AM, Mueller K, Villegas L, Udhayakumar V, Escalante AA. Common origin and fixation of Plasmodium falciparum dhfr and dhps mutations associated with sulfadoxine-pyrimethamine resistance in a low-transmission area in South America. Antimicrob Agents Chemother 2007; 51: 2085-2091. https://doi.org/10.1128/AAC.01228-06   DOI
12 Imwong M, Jindakhad T, Kunasol C, Sutawong K, Vejakama P, Dondorp AM. An outbreak of artemisinin resistant falciparum malaria in Eastern Thailand. Sci Rep 2015; 5: 17412. https://doi.org/10.1038/srep17412   DOI
13 Setthaudom C, Tan-ariya P, Sitthichot N, Khositnithikul R, Suwandittakul N, Leelayoova S, Mungthin M. Role of Plasmodium falciparum chloroquine resistance transporter and multidrug resistance 1 genes on in vitro chloroquine resistance in isolates of Plasmodium falciparum from Thailand. Am J Trop Med Hyg 2011; 85: 606-611. https://doi.org/10.4269/ajtmh.2011.11-0108   DOI
14 Jiang T, Chen J, Fu H, Wu K, Yao Y, Eyi JUM, Matesa RA, Obono MMO, Du W, Tan H, Lin M, Li J. High prevalence of Pfdhfr- Pfdhps quadruple mutations associated with sulfadoxine-pyrimethamine resistance in Plasmodium falciparum isolates from Bioko Island, Equatorial Guinea. Malar J 2019; 18: 101. https://doi.org/10.1186/s12936-019-2734-x   DOI
15 Zhao Y, Liu Z, Soe MT, Wang L, Soe TN, Wei H, Than A, Aung PL, Li Y, Zhang X, Hu Y, Wei H, Zhang Y, Burgess J, Siddiqui FA, Menezes L, Wang Q, Kyaw MP, Cao Y, Cui L. Genetic variations associated with drug resistance markers in asymptomatic Plasmodium falciparum infections in Myanmar. Genes 2019; 10: 692. https://doi.org/10.3390/genes10090692   DOI
16 Noedl H, Socheat D, Satimai W. Artemisinin-resistant malaria in Asia. N Engl J Med 2009; 361: 540-541. https://doi.org/10.1056/NEJMc0900231   DOI
17 Harinasuta T, Suntharasamai P, Viravan C. Chloroquine resistant falciparum malaria in Thailand. Lancet 1965; 286: 657-660. https://doi.org/10.1016/s0140-6736(65)90395-8   DOI
18 Young MD, Contacos PG, Stitcher JE, Millar JW. Drug resistance in Plasmodium falciparum from Thailand. Am J Trop Med Hyg 1963; 12: 305-314. https://doi.org/10.4269/ajtmh.1963.12.305   DOI
19 Chin W, Bear DM, Colwell EJ, Kosakal S. A comparative evaluation of sulfalene-trimethoprim and sulphormethoxine-pyrimethamine against falciparum malaria in Thailand. Am J Trop Med Hyg 1973; 22: 308-312. https://doi.org/10.4269/ajtmh.1973.22.308   DOI
20 Plowe CV, Cortese JF, Djimde A, Nwanyanwu OC, Watkins WM, Winstanley PA, Estrada-Franco JG, Mollinedo RE, Avila JC, Cespedes JL, Carter D, Doumbo OK. Mutations in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase and epidemiologic patterns of pyrimethamine-sulfadoxine use and resistance. J Infect Dis 1997; 176: 1590-1596. https://doi.org/10.1086/514159   DOI
21 Raman J, Sharp B, Kleinschmidt I, Roper C, Streat E, Kelly V, Barnes KI. Differential effect of regional drug pressure on dihydrofolate reductase and dihydropteroate synthetase mutations in southern Mozambique. Am J Trop Med Hyg 2008; 78: 256-261. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3748784   DOI
22 Duraisingh MT, Curtis J, Warhurst DC. Plasmodium falciparum: detection of polymorphisms in the dihydrofolate reductase and dihydropteroate synthetase genes by PCR and restriction digestion. Exp Parasitol 1998; 89: 1-8. https://doi.org/10.1006/expr.1998.4274   DOI
23 Kublin JG, Cortese JF, Njunju EM, Mukadam RA, Wirima JJ, Kazembe PN, Djimde AA, Kouriba B, Taylor TE, Plowe CV. Reemergence of chloroquine-sensitive Plasmodium falciparum malaria after cessation of chloroquine use in Malawi. J Infect Dis 2003; 187: 1870-1875. https://doi.org/10.1086/375419   DOI
24 Golassa L, Enweji N, Erko B, Aseffa A, Swedberg G. Detection of a substantial number of submicroscopic Plasmodium falciparum infections by polymerase chain reaction: a potential threat to malaria control and diagnosis in Ethiopia. Malar J 2013; 12: 352. https://doi.org/10.1186/1475-2875-12-352   DOI
25 Basuki S, Fitriah, Riyanto S, Budiono, Dachlan YP, Uemura H. Two novel mutations of pfdhps K540T and I588F, affecting sulphadoxine-pyrimethamine-resistant response in uncomplicated falciparum malaria at Banjar district, South Kalimantan Province, Indonesia. Malar J 2014; 13: 135. https://doi.org/10.1186/1475-2875-13-135   DOI
26 Babiker HA, Pringle SJ, Abdel-Muhsin A, Mackinnon M, Hunt P, Walliker D. High-level chloroquine resistance in Sudanese isolates of Plasmodium falciparum is associated with mutations in the chloroquine resistance transporter gene pfcrt and the multidrug resistance gene pfmdr1. J Infect Dis 2001;183: 1535-1538. https://doi.org/10.1086/320195   DOI
27 Hailemeskel E, Kassa M, Taddesse G, Mohammed H, Woyessa A, Tasew G, Sleshi M, Kebede A, Petros B. Prevalence of sulfadoxine-pyrimethamine resistance-associated mutations in dhfr and dhps genes of Plasmodium falciparum three years after SP withdrawal in Bahir Dar, Northwest Ethiopia. Acta Trop 2013; 128: 636-641. https://doi.org/10.1016/j.actatropica.2013.09.010   DOI
28 McCollum AM, Mueller K, Villegas L, Udhayakumar V, Escalante AA. Common origin and fixation of Plasmodium falciparum dhfr and dhps mutations associated with sulfadoxine-pyrimethamine resistance in a low-transmission area in South America. Antimicrob Agents Chemother 2007; 51: 2085-2091. https://doi.org/10.1128/AAC.01228-06   DOI
29 Mwai L, Ochong E, Abdirahman A, Kiara SM, Ward S, Kokwaro G, Sasi P, Marsh K, Borrmann S, Mackinnon M, Nzila A. Chloroquine resistance before and after its withdrawal in Kenya. Malaria J 2009; 8: 106. https://doi.org/10.1186/1475-2875-8-106   DOI
30 Wang X, Mu J, Li G, Chen P, Guo X, Fu L, Chen L, Su X, Wellems TE. Decreased prevalence of the Plasmodium falciparum chloroquine resistance transporter 76T marker associated with cessation of chloroquine use against P. falciparum malaria in Hainan, People's Republic of China. Am J Trop Med Hyg 2005; 72: 410-414.   DOI
31 Basco LK, Eldin de Pecoulas P, Wilson CM, Le Bras J, Mazabraud A. Point mutations in the dihydrofolate reductase-thymidylate synthase gene and pyrimethamine and cycloguanil resistance in Plasmodium falciparum. MolBiochem Parasitol 1995; 69: 135-138. https://doi.org/10.1016/0166-6851(94)00207-4   DOI
32 Khim N, Bouchier C, Ekala MT, Incardona S, Lim P, Legrand E, Jambou R, Doung S, Puijalon OM, Fandeur T. Countrywide survey shows very high prevalence of Plasmodium falciparum multilocus resistance genotypes in Cambodia. Antimicrob Agents Chemother 2005; 49: 3147-3152. https://doi.org/10.1128/AAC.49.8.3147-3152.2005   DOI
33 Djimde A, Doumbo OK, Cortese JF, Kayentao K, Doumbo S, Diourte Y, Coulibaly D, Dicko A, Su XZ, Nomura T, Fidock DA, Wellems TE, Plowe CV. A molecular marker for chloroquine-resistant falciparum malaria. N Engl J Med 2001; 344: 257-263. https://doi.org/10.1056/NEJM200101253440403   DOI
34 Mohammed A, Ndaro A, Kalinga A, Manjurano A, Mosha JF, Mosha DF, van Zwetselaar M, Koenderink JB, Mosha FW, Alifrangis M, Reyburn H, Roper C, Kavishe RA. Trends in chloroquine resistance marker, Pfcrt-K76T mutation ten years after chloroquine withdrawal in Tanzania. Malar J 2013; 12: 415. https://doi.org/10.1186/1475-2875-12-415   DOI
35 Lopes D, Rungsihirunrat K, Nogueira F, Seugorn A, Gil JP, do Rosario VE, Cravo P. Molecular characterisation of drug-resistant Plasmodium falciparum from Thailand. Malaria J 2002; 1: 12. https://doi.org/10.1186/1475-2875-1-12   DOI
36 Congpuong K, Na Bangchang K, Mungthin M, Bualombai P, Wernsdorfer WH. Molecular epidemiology of drug resistance markers of Plasmodium falciparum malaria in Thailand. Trop Med Int Health 2005; 8: 717-722. https://doi.org/10.1111/j.1365-3156.2005.01450.x   DOI
37 Rungsihirunrat K, Chaijareonkul W, Seugorn A, Na-Bangchang K, Thaithong S. Association between chloroquine resistance phenotypes and point mutations in pfcrt and pfmdr1 in Plasmodium falciparum isolates from Thailand. Acta Trop 2009; 109: 37-40. https://doi.org/10.1016/j.actatropica.2008.09.011   DOI
38 Johnson DE, Roendej P, Williams RG. Falciparum malaria acquired in the area of the Thai-Khmer border resistant to treatment with Fansidar. Am J Trop Med Hyg 1982; 31: 907-912. https://doi.org/10.4269/ajtmh.1982.31.907   DOI
39 WHO Mekong Malaria Programme. Malaria in the Greater Mekong Subregion: Regional and Country Profiles. World Health Organization. Geneva, Switzerland. 2008. http: //www.whothailand.org/EN/Section3/Section113.htm.
40 Reeder JC, Rieckmann KH, Genton B, Lorry K, Wines B, Cowman AF. Point mutations in the dihydrofolate reductase and dihydropteroate synthetase genes and in vitro susceptibility to pyrimethamine and cycloguanil of Plasmodium falciparum isolates from Papua New Guinea. Am J Trop Med Hyg 1996; 55: 209-213. https://doi.org/10.4269/ajtmh.1996.55.209   DOI
41 Wongsrichanalai C, Sirichaisinthop J, Karwacki JJ, Congpuong K, Miller RS, Pang L, Thimasarn K. Drug resistant malaria on the Thai-Myanmar and Thai-Cambodian borders. Southeast Asian J Trop Med Public Health 2001; 32: 41-49.