Author:
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Wellems TE, Plowe CV, 2001. Chloroquine-resistant malaria. J Infect Dis 184: 770–776.
-
2.
Wongsrichanalai C, Pickard AL, Wernsdorfer WH, Meshnick SR, 2002. Epidemiology of drug-resistant malaria. Lancet Infect Dis 2: 209–218.
-
3.
Fidock DA et al. 2000. Mutations in the P. falciparum digestive vacuole transmembrane protein PfCRT and evidence for their role in chloroquine resistance. Mol Cell 6: 861–871.
-
4.
Ecker A, Lehane AM, Clain J, Fidock DA, 2012. PfCRT and its role in antimalarial drug resistance. Trends Parasitol 28: 504–514.
-
5.
Petersen I et al. 2015. Balancing drug resistance and growth rates via compensatory mutations in the Plasmodium falciparum chloroquine resistance transporter. Mol Microbiol 97: 381–395.
-
6.
Gabryszewski SJ et al. 2016. Evolution of fitness cost-neutral mutant PfCRT conferring P. falciparum 4-aminoquinoline drug resistance is accompanied by altered parasite metabolism and digestive vacuole physiology. PLoS Pathog 12: e1005976.
-
7.
Callaghan PS, Hassett MR, Roepe PD, 2015. Functional comparison of 45 naturally occurring isoforms of the Plasmodium falciparum chloroquine resistance transporter (PfCRT). Biochemistry 54: 5083–5094.
-
8.
Agrawal S et al. 2017. Association of a novel mutation in the Plasmodium falciparum chloroquine resistance transporter with decreased piperaquine sensitivity. J Infect Dis 216: 468–476.
-
9.
Parker D, Lerdprom R, Srisatjarak W, Yan G, Sattabongkot J, Wood J, Sirichaisinthop J, Cui L, 1994. Longitudinal in vitro surveillance of Plasmodium falciparum sensitivity to common anti-malarials in Thailand between 1994 and 2010. Malar J 11: 290.
-
10.
Chaijaroenkul W, Ward SA, Mungthin M, Johnson D, Owen A, Bray PG, Na-Bangchang K, 2011. Sequence and gene expression of chloroquine resistance transporter (Pfcrt) in the association of in vitro drugs resistance of Plasmodium falciparum. Malar J 10: 42.
-
11.
Takahashi N et al. 2012. Large-scale survey for novel genotypes of Plasmodium falciparum chloroquine-resistance gene Pfcrt. Malar J 11: 92.
-
12.
Harinasuta T, Suntharasamai P, Viravan C, 1965. Chloroquine-resistant falciparum malaria in Thailand. Lancet 2: 657–660.
-
13.
Malikul S, 2000. Malariology 1999 in Commemoration of 50 Years of Malaria Control in Thailand. Bangkok, Thailand: The Agricultural Co-operative Federation of Thailand Press (in Thai).
-
14.
Thimasarn K, Sirichaisinthop J, Vijaykadga S, Tansophalaks S, Yamokgul P, Laomiphol A, Palananth C, Thamewat U, Tháithong S, Rooney W, 1995. In vivo study of the response of Plasmodium falciparum to standard mefloquine/sulfadoxine/pyrimethamine (MSP) treatment among gem miners returning from Cambodia. Southeast Asian J Trop Med Public Health 26: 204–212.
-
15.
Wongsrichanalai C, Prajakwong S, Meshnick SR, Shanks GD, Thimasarn K, 2004. Mefloquine-its 20 years in the Thai malaria control program. Southeast Asian J Trop Med Public Health 35: 300–308.
-
16.
Zhou G, Sirichaisinthop J, Sattabongkot J, Jones J, Bjørnstad ON, Yan G, Cui L, 2005. Spatio-temporal distribution of Plasmodium falciparum and P. vivax malaria in Thailand. Am J Trop Med Hyg 72: 256–262.
-
17.
World Health Organisation, 2014. Status Report on Artemisinin Resistance: September 2014. Geneva, Switzerland: WHO.
-
18.
Putaporntip C, Kuamsab N, Kosuwin R, Tantiwattanasub W, Vejakama P, Sueblinvong T, Seethamchai S, Jongwutiwes S, Hughes AL, 2016. Natural selection of K13 mutants of Plasmodium falciparum in response to artemisinin combination therapies in Thailand. Clin Microbiol Infect 285: e1–e8.
-
19.
Jongwutiwes S, Buppan P, Kosuvin R, Seethamchai S, Pattanawong U, Sirichaisinthop J, Putaporntip C, 2011. Plasmodium knowlesi malaria in humans and macaques, Thailand. Emerg Infect Dis 17: 1799–1806.
-
20.
Sidhu AB, Verdier-Pinard D, Fidock DA, 2002. Chloroquine resistance in Plasmodium falciparum malaria parasites conferred by Pfcrt mutations. Science 298: 210–213.
-
21.
Johnson DJ, Fidock DA, Mungthin M, Lakshmanan V, Sidhu AB, Bray PG, Ward SA, 2004. Evidence for a central role for PfCRT in conferring Plasmodium falciparum resistance to diverse antimalarial agents. Mol Cell 15: 867–877.
-
22.
Dhingra SK et al. 2017. A variant PfCRT isoform can contribute to Plasmodium falciparum resistance to the first-line partner drug piperaquine. MBio 8: e00303–e00317.
-
23.
Conrad MD et al. 2014. Comparative impacts over 5 years of artemisinin-based combination therapies on Plasmodium falciparum polymorphisms that modulate drug sensitivity in Ugandan children. J Infect Dis 210: 344–353.
-
24.
Hemming-Schroeder E et al. 2018. Impacts of antimalarial drugs on Plasmodium falciparum drug resistance markers, western Kenya, 2003–2015. Am J Trop Med Hyg 98: 692–699.
-
25.
Tumwebaze P et al. 2017. Changing antimalarial drug resistance patterns identified by surveillance at three sites in Uganda. J Infect Dis 215: 631–635.
-
26.
Putaporntip C, Buppan P, Jongwutiwes S, 2011. Improved performance with saliva and urine as alternative DNA sources for malaria diagnosis by mitochondrial DNA-based PCR assays. Clin Microbiol Infect 17: 1484–1491.
-
27.
Librado P, Rozas J, 2009. DnaSP v5: a software for comprehensive analysis of DNA polymorphism data. Bioinformatics 25: 1451–1452.
-
28.
Tamura K, Stecher G, Peterson D, Filipski A, Kumar S, 2013. MEGA6: molecular evolutionary genetics analysis version 6.0. Mol Biol Evol 30: 2725–2729.
-
29.
Martin DP, Murrell B, Khoosal A, Muhire B, 2017. Detecting and analyzing genetic recombination using RDP4. Methods Mol Biol 1525: 433–460.
-
30.
Tajima F, 1983. Evolutionary relationship of DNA sequences in finite populations. Genetics 105: 437–460.
-
31.
Excoffier L, Lischer HE, 2010. Arlequin suite ver 3.5: a new series of programs to perform population genetics analyses under Linux and Windows. Mol Ecol Resour 10: 564–567.
-
32.
Looareesuwan S, Viravan C, Webster HK, Kyle DE, Hutchinson DB, Canfield CJ, 1996. Clinical studies of atovaquone, alone or in combination with other antimalarial drugs, for treatment of acute uncomplicated malaria in Thailand. Am J Trop Med Hyg 54: 62–66.
-
33.
Thaithong S, Beale GH, 1981. Resistance of ten Thai isolates of Plasmodium falciparum to chloroquine and pyrimethamine by in vitro tests. Trans R Soc Trop Med Hyg 75: 271–273.
-
34.
Foote SJ, Kyle DE, Martin RK, Oduola AM, Forsyth K, Kemp DJ, Cowman AF, 1990. Several alleles of the multidrug-resistance gene are closely linked to chloroquine resistance in Plasmodium falciparum. Nature 345: 255–258.
-
35.
Durrand V, Berry A, Sem R, Glaziou P, Beaudou J, Fandeur T, 2004. Variations in the sequence and expression of the Plasmodium falciparum chloroquine resistance transporter (Pfcrt) and their relationship to chloroquine resistance in vitro. Mol Biochem Parasitol 136: 273–285.
-
36.
Jongwutiwes S, Putaporntip C, Hughes AL, 2010. Bottleneck effects on vaccine-candidate antigen diversity of malaria parasites in Thailand. Vaccine 28: 3112–3117.
-
37.
Kublin JG, Cortese JF, Njunju EM, Mukadam RA, Wirima JJ, Kazembe PN, Djimdé AA, Kouriba B, Taylor TE, Plowe CV, 2003. Reemergence of chloroquine-sensitive Plasmodium falciparum malaria after cessation of chloroquine use in Malawi. J Infect Dis 187: 1870–1875.
-
38.
Hughes AL, 2008. Near neutrality: leading edge of the neutral theory of molecular evolution. Ann N Y Acad Sci 1133: 162–179.
-
39.
Nash D, Nair S, Mayxay M, Newton PN, Guthmann JP, Nosten F, Anderson TJ, 2005. Selection strength and hitchhiking around two anti-malarial resistance genes. Proc Biol Sci 272: 1153–1161.
-
40.
Hughes AL, Packer B, Welch R, Bergen AW, Chanock SJ, Yeager M, 2003. Widespread purifying selection at polymorphic sites in human protein-coding loci. Proc Natl Acad Sci USA 100: 15754–15757.
-
41.
Price MN, Arkin AP, 2015. Weakly deleterious mutations and low rates of recombination limit the impact of natural selection on bacterial genomes. MBio 6: e01302–e01315.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 1515 | 1317 | 72 |
| Full Text Views | 580 | 11 | 0 |
| PDF Downloads | 140 | 12 | 0 |
Multiple Novel Mutations in Plasmodium falciparum Chloroquine Resistance Transporter Gene during Implementation of Artemisinin Combination Therapy in Thailand
Pattakorn Buppan
Pattakorn Buppan
Molecular Biology of Malaria and Opportunistic Parasites Research Unit, Department of Parasitology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand;
Inter-Department Program of Biomedical Sciences, Faculty of Graduate School, Chulalongkorn University, Bangkok, Thailand;
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Inter-Department Program of Biomedical Sciences, Faculty of Graduate School, Chulalongkorn University, Bangkok, Thailand;
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Sunee Seethamchai
Sunee Seethamchai
Department of Biology, Faculty of Science, Naresuan University, Pitsanulok Province, Thailand;
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Napaporn Kuamsab
Napaporn Kuamsab
Molecular Biology of Malaria and Opportunistic Parasites Research Unit, Department of Parasitology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand;
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Pongchai Harnyuttanakorn
Pongchai Harnyuttanakorn
Department of Biology, Faculty of Science, Chulalongkorn University, Bangkok, Thailand
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Chaturong Putaporntip
Chaturong Putaporntip
Molecular Biology of Malaria and Opportunistic Parasites Research Unit, Department of Parasitology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand;
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Somchai Jongwutiwes
Somchai Jongwutiwes
Molecular Biology of Malaria and Opportunistic Parasites Research Unit, Department of Parasitology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand;
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Mutations in the chloroquine resistance transporter gene of Plasmodium falciparum (Pfcrt) are associated with drug susceptibility status of chloroquine and other antimalarials that interfere with heme detoxification process including artemisinin. We aim to investigate whether an increase in duration of artemisinin combination therapy (ACT) in Thailand could affect mutations in Pfcrt. The complete coding sequences of Pfcrt and dihydrofolate reductase (Pfdhfr), and size polymorphisms of the merozoite surface proteins-1 and 2 (Pfmsp-1 and Pfmsp-2) of 189 P. falciparum isolates collected during 1991 and 2016 were analyzed. In total, 12 novel amino acid substitutions and 13 novel PfCRT haplotypes were identified. The most prevalent haplotype belonged to the Dd2 sequence and no wild type was found. A significant positive correlation between the frequency of Pfcrt mutants and the year of sample collection was observed during nationwide ACT implementation (r = 0.780; P = 0.038). The number of haplotypes and nucleotide diversity of isolates collected during 3-day ACT (2009–2016) significantly outnumbered those collected before this treatment regimen. Positive Darwinian selection occurred in the transmembrane domains only among isolates collected during 3-day ACT but not among those collected before this period. No remarkable change was observed in the molecular indices for other loci analyzed when similar comparisons were performed. An increase in the duration of artesunate in combination therapy in Thailand could exert selective pressure on the Pfcrt locus, resulting in emergence of novel variants. The impact of these novel haplotypes on antimalarial susceptibilities requires further study.
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Author Notes
Financial support: The Thai Government Research Budgets (GRB-APS-12593011 and GBA-600093004) and Chulalongkorn University Research Grants (Fiscal Years 2006–2008) to S. J., C. P., and S. S.; The Thailand Research Fund (RSA5980054) to C. P.; and Ratchadapiseksompotch Fund, Faculty of Medicine, Chulalongkorn University (RA60/109) to C. P., S. J., and P. B.
Authors’ addresses: Pattakorn Buppan, Molecular Biology of Malaria and Opportunistic Parasites Research Unit, Department of Parasitology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand and Inter-Department Program of Biomedical Sciences, Faculty of Graduate School, Chulalongkorn University, Bangkok, Thailand, E-mail: pattakorn.b@gmail.com. Napaporn Kuamsab, Chaturong Putaporntip, and Somchai Jongwutiwes, Molecular Biology of Malaria and Opportunistic Parasites Research Unit, Department of Parasitology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, E-mails: kuamsab@gmail.com, p.chaturong@gmail.com, and jongwutiwes@gmail.com. Sunee Seethamchai, Department of Biology, Faculty of Science, Naresuan University, Pitsanulok Province, Thailand, E-mail: sunoat@gmail.com. Pongchai Harnyuttanakorn, Department of Biology, Faculty of Science, Chulalongkorn University, Bangkok, Thailand, E-mail: hpongchai@gmail.com.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Wellems TE, Plowe CV, 2001. Chloroquine-resistant malaria. J Infect Dis 184: 770–776.
-
2.
Wongsrichanalai C, Pickard AL, Wernsdorfer WH, Meshnick SR, 2002. Epidemiology of drug-resistant malaria. Lancet Infect Dis 2: 209–218.
-
3.
Fidock DA et al. 2000. Mutations in the P. falciparum digestive vacuole transmembrane protein PfCRT and evidence for their role in chloroquine resistance. Mol Cell 6: 861–871.
-
4.
Ecker A, Lehane AM, Clain J, Fidock DA, 2012. PfCRT and its role in antimalarial drug resistance. Trends Parasitol 28: 504–514.
-
5.
Petersen I et al. 2015. Balancing drug resistance and growth rates via compensatory mutations in the Plasmodium falciparum chloroquine resistance transporter. Mol Microbiol 97: 381–395.
-
6.
Gabryszewski SJ et al. 2016. Evolution of fitness cost-neutral mutant PfCRT conferring P. falciparum 4-aminoquinoline drug resistance is accompanied by altered parasite metabolism and digestive vacuole physiology. PLoS Pathog 12: e1005976.
-
7.
Callaghan PS, Hassett MR, Roepe PD, 2015. Functional comparison of 45 naturally occurring isoforms of the Plasmodium falciparum chloroquine resistance transporter (PfCRT). Biochemistry 54: 5083–5094.
-
8.
Agrawal S et al. 2017. Association of a novel mutation in the Plasmodium falciparum chloroquine resistance transporter with decreased piperaquine sensitivity. J Infect Dis 216: 468–476.
-
9.
Parker D, Lerdprom R, Srisatjarak W, Yan G, Sattabongkot J, Wood J, Sirichaisinthop J, Cui L, 1994. Longitudinal in vitro surveillance of Plasmodium falciparum sensitivity to common anti-malarials in Thailand between 1994 and 2010. Malar J 11: 290.
-
10.
Chaijaroenkul W, Ward SA, Mungthin M, Johnson D, Owen A, Bray PG, Na-Bangchang K, 2011. Sequence and gene expression of chloroquine resistance transporter (Pfcrt) in the association of in vitro drugs resistance of Plasmodium falciparum. Malar J 10: 42.
-
11.
Takahashi N et al. 2012. Large-scale survey for novel genotypes of Plasmodium falciparum chloroquine-resistance gene Pfcrt. Malar J 11: 92.
-
12.
Harinasuta T, Suntharasamai P, Viravan C, 1965. Chloroquine-resistant falciparum malaria in Thailand. Lancet 2: 657–660.
-
13.
Malikul S, 2000. Malariology 1999 in Commemoration of 50 Years of Malaria Control in Thailand. Bangkok, Thailand: The Agricultural Co-operative Federation of Thailand Press (in Thai).
-
14.
Thimasarn K, Sirichaisinthop J, Vijaykadga S, Tansophalaks S, Yamokgul P, Laomiphol A, Palananth C, Thamewat U, Tháithong S, Rooney W, 1995. In vivo study of the response of Plasmodium falciparum to standard mefloquine/sulfadoxine/pyrimethamine (MSP) treatment among gem miners returning from Cambodia. Southeast Asian J Trop Med Public Health 26: 204–212.
-
15.
Wongsrichanalai C, Prajakwong S, Meshnick SR, Shanks GD, Thimasarn K, 2004. Mefloquine-its 20 years in the Thai malaria control program. Southeast Asian J Trop Med Public Health 35: 300–308.
-
16.
Zhou G, Sirichaisinthop J, Sattabongkot J, Jones J, Bjørnstad ON, Yan G, Cui L, 2005. Spatio-temporal distribution of Plasmodium falciparum and P. vivax malaria in Thailand. Am J Trop Med Hyg 72: 256–262.
-
17.
World Health Organisation, 2014. Status Report on Artemisinin Resistance: September 2014. Geneva, Switzerland: WHO.
-
18.
Putaporntip C, Kuamsab N, Kosuwin R, Tantiwattanasub W, Vejakama P, Sueblinvong T, Seethamchai S, Jongwutiwes S, Hughes AL, 2016. Natural selection of K13 mutants of Plasmodium falciparum in response to artemisinin combination therapies in Thailand. Clin Microbiol Infect 285: e1–e8.
-
19.
Jongwutiwes S, Buppan P, Kosuvin R, Seethamchai S, Pattanawong U, Sirichaisinthop J, Putaporntip C, 2011. Plasmodium knowlesi malaria in humans and macaques, Thailand. Emerg Infect Dis 17: 1799–1806.
-
20.
Sidhu AB, Verdier-Pinard D, Fidock DA, 2002. Chloroquine resistance in Plasmodium falciparum malaria parasites conferred by Pfcrt mutations. Science 298: 210–213.
-
21.
Johnson DJ, Fidock DA, Mungthin M, Lakshmanan V, Sidhu AB, Bray PG, Ward SA, 2004. Evidence for a central role for PfCRT in conferring Plasmodium falciparum resistance to diverse antimalarial agents. Mol Cell 15: 867–877.
-
22.
Dhingra SK et al. 2017. A variant PfCRT isoform can contribute to Plasmodium falciparum resistance to the first-line partner drug piperaquine. MBio 8: e00303–e00317.
-
23.
Conrad MD et al. 2014. Comparative impacts over 5 years of artemisinin-based combination therapies on Plasmodium falciparum polymorphisms that modulate drug sensitivity in Ugandan children. J Infect Dis 210: 344–353.
-
24.
Hemming-Schroeder E et al. 2018. Impacts of antimalarial drugs on Plasmodium falciparum drug resistance markers, western Kenya, 2003–2015. Am J Trop Med Hyg 98: 692–699.
-
25.
Tumwebaze P et al. 2017. Changing antimalarial drug resistance patterns identified by surveillance at three sites in Uganda. J Infect Dis 215: 631–635.
-
26.
Putaporntip C, Buppan P, Jongwutiwes S, 2011. Improved performance with saliva and urine as alternative DNA sources for malaria diagnosis by mitochondrial DNA-based PCR assays. Clin Microbiol Infect 17: 1484–1491.
-
27.
Librado P, Rozas J, 2009. DnaSP v5: a software for comprehensive analysis of DNA polymorphism data. Bioinformatics 25: 1451–1452.
-
28.
Tamura K, Stecher G, Peterson D, Filipski A, Kumar S, 2013. MEGA6: molecular evolutionary genetics analysis version 6.0. Mol Biol Evol 30: 2725–2729.
-
29.
Martin DP, Murrell B, Khoosal A, Muhire B, 2017. Detecting and analyzing genetic recombination using RDP4. Methods Mol Biol 1525: 433–460.
-
30.
Tajima F, 1983. Evolutionary relationship of DNA sequences in finite populations. Genetics 105: 437–460.
-
31.
Excoffier L, Lischer HE, 2010. Arlequin suite ver 3.5: a new series of programs to perform population genetics analyses under Linux and Windows. Mol Ecol Resour 10: 564–567.
-
32.
Looareesuwan S, Viravan C, Webster HK, Kyle DE, Hutchinson DB, Canfield CJ, 1996. Clinical studies of atovaquone, alone or in combination with other antimalarial drugs, for treatment of acute uncomplicated malaria in Thailand. Am J Trop Med Hyg 54: 62–66.
-
33.
Thaithong S, Beale GH, 1981. Resistance of ten Thai isolates of Plasmodium falciparum to chloroquine and pyrimethamine by in vitro tests. Trans R Soc Trop Med Hyg 75: 271–273.
-
34.
Foote SJ, Kyle DE, Martin RK, Oduola AM, Forsyth K, Kemp DJ, Cowman AF, 1990. Several alleles of the multidrug-resistance gene are closely linked to chloroquine resistance in Plasmodium falciparum. Nature 345: 255–258.
-
35.
Durrand V, Berry A, Sem R, Glaziou P, Beaudou J, Fandeur T, 2004. Variations in the sequence and expression of the Plasmodium falciparum chloroquine resistance transporter (Pfcrt) and their relationship to chloroquine resistance in vitro. Mol Biochem Parasitol 136: 273–285.
-
36.
Jongwutiwes S, Putaporntip C, Hughes AL, 2010. Bottleneck effects on vaccine-candidate antigen diversity of malaria parasites in Thailand. Vaccine 28: 3112–3117.
-
37.
Kublin JG, Cortese JF, Njunju EM, Mukadam RA, Wirima JJ, Kazembe PN, Djimdé AA, Kouriba B, Taylor TE, Plowe CV, 2003. Reemergence of chloroquine-sensitive Plasmodium falciparum malaria after cessation of chloroquine use in Malawi. J Infect Dis 187: 1870–1875.
-
38.
Hughes AL, 2008. Near neutrality: leading edge of the neutral theory of molecular evolution. Ann N Y Acad Sci 1133: 162–179.
-
39.
Nash D, Nair S, Mayxay M, Newton PN, Guthmann JP, Nosten F, Anderson TJ, 2005. Selection strength and hitchhiking around two anti-malarial resistance genes. Proc Biol Sci 272: 1153–1161.
-
40.
Hughes AL, Packer B, Welch R, Bergen AW, Chanock SJ, Yeager M, 2003. Widespread purifying selection at polymorphic sites in human protein-coding loci. Proc Natl Acad Sci USA 100: 15754–15757.
-
41.
Price MN, Arkin AP, 2015. Weakly deleterious mutations and low rates of recombination limit the impact of natural selection on bacterial genomes. MBio 6: e01302–e01315.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 1515 | 1317 | 72 |
| Full Text Views | 580 | 11 | 0 |
| PDF Downloads | 140 | 12 | 0 |