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RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
World Health Organization, 2012. World Malaria Report 2012. Geneva, Switzerland: World Health Organization.
-
2.
Takala-Harrison S et al. 2013. Genetic loci associated with delayed clearance of Plasmodium falciparum following artemisinin treatment in southeast Asia. Proc Natl Acad Sci USA 110: 240–245.
-
3.
Dondorp AM et al. 2009. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 361: 455–467.
-
4.
Ashley EA et al..; Tracking Resistance to Artemisinin Collaboration, 2014. Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 371: 411–423.
-
5.
Price RN et al. 2004. Mefloquine resistance in Plasmodium falciparum and increased pfmdr1 gene copy number. Lancet 364: 438–447.
-
6.
Chavchich M, Gerena L, Peters J, Chen N, Cheng Q, Kyle DE, 2010. Role of pfmdr1 amplification and expression in induction of resistance to artemisinin derivatives in Plasmodium falciparum. Antimicrob Agents Chemother 54: 2455–2464.
-
7.
Slater HC, Griffin JT, Ghani AC, Okell LC, 2016. Assessing the potential impact of artemisinin and partner drug resistance in sub-Saharan Africa. Malar J 15: 10.
-
8.
Croft SL, Duparc S, Arbe-Barnes SJ, Craft JC, Shin CS, Fleckenstein L, Borghini-Fuhrer I, Rim HJ, 2012. Review of pyronaridine anti-malarial properties and product characteristics. Malar J 11: 270.
-
9.
Rueangweerayut R et al. Pyronaridine-Artesunate Study Team, 2012. Pyronaridine-artesunate versus mefloquine plus artesunate for malaria. N Engl J Med 366: 1298–1309.
-
10.
Kayentao K et al. 2012. Pyronaridine-artesunate granules versus artemether-lumefantrine crushed tablets in children with Plasmodium falciparum malaria: a randomized controlled trial. Malar J 11: 364.
-
11.
Poravuth Y et al. 2011. Pyronaridine-artesunate versus chloroquine in patients with acute Plasmodium vivax malaria: a randomized, double-blind, non-inferiority trial. PLoS One 6: e14501.
-
12.
Tshefu AK et al..; Pyronaridine-artesunate Study Team, 2010. Efficacy and safety of a fixed-dose oral combination of pyronaridine-artesunate compared with artemether-lumefantrine in children and adults with uncomplicated Plasmodium falciparum malaria: a randomised non-inferiority trial. Lancet 375: 1457–1467.
-
13.
Duparc S, Borghini-Fuhrer I, Craft CJ, Arbe-Barnes S, Miller RM, Shin CS, Fleckenstein L, 2013. Safety and efficacy of pyronaridine-artesunate in uncomplicated acute malaria: an integrated analysis of individual patient data from six randomized clinical trials. Malar J 12: 70.
-
14.
Ramharter M et al. 2008. Fixed-dose pyronaridine-artesunate combination for treatment of uncomplicated falciparum malaria in pediatric patients in Gabon. J Infect Dis 198: 911–919.
-
15.
Pradines B, Tall A, Fusai T, Spiegel A, Hienne R, Rogier C, Trape JF, Le Bras J, Parzy D, 1999. In vitro activities of benflumetol against 158 Senegalese isolates of Plasmodium falciparum in comparison with those of standard antimalarial drugs. Antimicrob Agents Chemother 43: 418–420.
-
16.
Pradines B, Tall A, Parzy D, Spiegel A, Fusai T, Hienne R, Trape JF, Doury JC, 1998. In-vitro activity of pyronaridine and amodiaquine against African isolates (Senegal) of Plasmodium falciparum in comparison with standard antimalarial agents. J Antimicrob Chemother 42: 333–339.
-
17.
Schildbach S, Wernsdorfer WH, Suebsaeng L, Rooney W, 1990. In vitro sensitivity of multiresistant Plasmodium falciparum to new candidate antimalarial drugs in western Thailand. Southeast Asian J Trop Med Public Health 21: 29–38.
-
18.
Warsame M, Wernsdorfer WH, Payne D, Bjorkman A, 1991. Positive relationship between the response of Plasmodium falciparum to chloroquine and pyronaridine. Trans R Soc Trop Med Hyg 85: 570–571.
-
19.
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.
-
20.
Djimde A et al. 2001. A molecular marker for chloroquine-resistant falciparum malaria. N Engl J Med 344: 257–263.
-
21.
Duraisingh MT, Jones P, Sambou I, von Seidlein L, Pinder M, Warhurst DC, 2000. The tyrosine-86 allele of the pfmdr1 gene of Plasmodium falciparum is associated with increased sensitivity to the anti-malarials mefloquine and artemisinin. Mol Biochem Parasitol 108: 13–23.
-
22.
Reed MB, Saliba KJ, Caruana SR, Kirk K, Cowman AF, 2000. Pgh1 modulates sensitivity and resistance to multiple antimalarials in Plasmodium falciparum. Nature 403: 906–909.
-
23.
Setthaudom C, Tan-ariya P, Sitthichot N, Khositnithikul R, Suwandittakul N, Leelayoova S, Mungthin M, 2011. 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 85: 606–611.
-
24.
Cowman AF, Galatis D, Thompson JK, 1994. Selection for mefloquine resistance in Plasmodium falciparum is linked to amplification of the pfmdr1 gene and cross-resistance to halofantrine and quinine. Proc Natl Acad Sci USA 91: 1143–1147.
-
25.
Wilson CM, Volkman SK, Thaithong S, Martin RK, Kyle DE, Milhous WK, Wirth DF, 1993. Amplification of pfmdr1 associated with mefloquine and halofantrine resistance in Plasmodium falciparum from Thailand. Mol Biochem Parasitol 57: 151–160.
-
26.
Pickard AL, Wongsrichanalai C, Purfield A, Kamwendo D, Emery K, Zalewski C, Kawamoto F, Miller RS, Meshnick SR, 2003. Resistance to antimalarials in southeast Asia and genetic polymorphisms in pfmdr1. Antimicrob Agents Chemother 47: 2418–2423.
-
27.
Sidhu AB, Valderramos SG, Fidock DA, 2005. pfmdr1 mutations contribute to quinine resistance and enhance mefloquine and artemisinin sensitivity in Plasmodium falciparum. Mol Microbiol 57: 913–926.
-
28.
Uhlemann AC, Ramharter M, Lell B, Kremsner PG, Krishna S, 2005. Amplification of Plasmodium falciparum multidrug resistance gene 1 in isolates from Gabon. J Infect Dis 192: 1830–1835.
-
29.
Pradines B, Briolant S, Henry M, Oeuvray C, Baret E, Amalvict R, Didillon E, Rogier C, 2010. Absence of association between pyronaridine in vitro responses and polymorphisms in genes involved in quinoline resistance in Plasmodium falciparum. Malar J 9: 339.
-
30.
Trager W, Jensen JB, 1976. Human malaria parasites in continuous culture. Science 193: 673–675.
-
31.
Desjardins RE, Canfield CJ, Haynes JD, Chulay JD, 1979. Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique. Antimicrob Agents Chemother 16: 710–718.
-
32.
Wooden J, Kyes S, Sibley CH, 1993. PCR and strain identification in Plasmodium falciparum. Parasitol Today 9: 303–305.
-
33.
Ariey F et al. 2014. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature 505: 50–55.
-
34.
Vijaykadga S, Rojanawatsirivej C, Cholpol S, Phoungmanee D, Nakavej A, Wongsrichanalai C, 2006. In vivo sensitivity monitoring of mefloquine monotherapy and artesunate-mefloquine combinations for the treatment of uncomplicated falciparum malaria in Thailand in 2003. Trop Med Int Health 11: 211–219.
-
35.
Looareesuwan S, Kyle DE, Viravan C, Vanijanonta S, Wilairatana P, Wernsdorfer WH, 1996. Clinical study of pyronaridine for the treatment of acute uncomplicated falciparum malaria in Thailand. Am J Trop Med Hyg 54: 205–209.
-
36.
Childs GE, Hausler B, Milhous W, Chen C, Wimonwattrawatee T, Pooyindee N, Boudreau EF, 1988. In vitro activity of pyronaridine against field isolates and reference clones of Plasmodium falciparum. Am J Trop Med Hyg 38: 24–29.
-
37.
Witkowski B et al. 2013. Novel phenotypic assays for the detection of artemisinin-resistant Plasmodium falciparum malaria in Cambodia: in-vitro and ex-vivo drug-response studies. Lancet Infect Dis 13: 1043–1049.
-
38.
Elueze EI, Croft SL, Warhurst DC, 1996. Activity of pyronaridine and mepacrine against twelve strains of Plasmodium falciparum in vitro. J Antimicrob Chemother 37: 511–518.
-
39.
Pradines B, Mabika Mamfoumbi M, Parzy D, Owono Medang M, Lebeau C, Mourou Mbina JR, Doury JC, Kombila M, 1999. In vitro susceptibility of African isolates of Plasmodium falciparum from Gabon to pyronaridine. Am J Trop Med Hyg 60: 105–108.
-
40.
Price RN, Marfurt J, Chalfein F, Kenangalem E, Piera KA, Tjitra E, Anstey NM, Russell B, 2010. In vitro activity of pyronaridine against multidrug-resistant Plasmodium falciparum and Plasmodium vivax. Antimicrob Agents Chemother 54: 5146–5150.
-
41.
Okombo J, Kiara SM, Mwai L, Pole L, Ohuma E, Ochola LI, Nzila A, 2012. Baseline in vitro activities of the antimalarials pyronaridine and methylene blue against Plasmodium falciparum isolates from Kenya. Antimicrob Agents Chemother 56: 1105–1107.
-
42.
Kurth F, Pongratz P, Belard S, Mordmuller B, Kremsner PG, Ramharter M, 2009. In vitro activity of pyronaridine against Plasmodium falciparum and comparative evaluation of anti-malarial drug susceptibility assays. Malar J 8: 79.
-
43.
Pascual A, Madamet M, Briolant S, Gaillard T, Amalvict R, Benoit N, Travers D, Pradines B; French National Reference Centre for Imported Malaria Study Group, 2015. Multinormal in vitro distribution of Plasmodium falciparum susceptibility to piperaquine and pyronaridine. Malar J 14: 49.
-
44.
White NJ, 2004. Antimalarial drug resistance. J Clin Invest 113: 1084–1092.
-
45.
Madamet M, Briolant S, Amalvict R, Benoit N, Bouchiba H, Cren J, Pradines B; French National Centre for Imported Malaria Study Group, 2016. The Plasmodium falciparum chloroquine resistance transporter is associated with the ex vivo P. falciparum African parasite response to pyronaridine. Parasit Vectors 9: 77.
-
46.
Leang R et al. 2015. Evidence of Plasmodium falciparum malaria multidrug resistance to artemisinin and piperaquine in western Cambodia: dihydroartemisinin-piperaquine open-label multicenter clinical assessment. Antimicrob Agents Chemother 59: 4719–4726.
-
47.
Amaratunga C et al. 2016. Dihydroartemisinin-piperaquine resistance in Plasmodium falciparum malaria in Cambodia: a multisite prospective cohort study. Lancet Infect Dis 16: 357–365.
-
48.
Mungthin M, Suwandittakul N, Chaijaroenkul W, Rungsrihirunrat K, Harnyuttanakorn P, Seugorn A, Na Bangchang K, 2010. The patterns of mutation and amplification of Plasmodium falciparum pfcrt and pfmdr1 genes in Thailand during the year 1988 to 2003. Parasitol Res 107: 539–545.
-
49.
Mungthin M, Intanakom S, Suwandittakul N, Suida P, Amsakul S, Sitthichot N, Thammapalo S, Leelayoova S, 2014. Distribution of pfmdr1 polymorphisms in Plasmodium falciparum isolated from southern Thailand. Malar J 13: 117.
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In Vitro Sensitivity of Pyronaridine in Thai Isolates of Plasmodium falciparum
Kittiya Mahotorn
Kittiya Mahotorn
Department of Microbiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand;
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Peerapan Tan-ariya
Peerapan Tan-ariya
Department of Microbiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand;
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Thunyapit Thita
Thunyapit Thita
Department of Microbiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand;
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Toon Ruang-areerate
Toon Ruang-areerate
Department of Parasitology, Phramongkutklao College of Medicine, Bangkok 10400, Thailand
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Naruemon Sittichot
Naruemon Sittichot
Department of Parasitology, Phramongkutklao College of Medicine, Bangkok 10400, Thailand
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Nantana Suwandittakul
Nantana Suwandittakul
Department of Parasitology, Phramongkutklao College of Medicine, Bangkok 10400, Thailand
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Mathirut Mungthin
Mathirut Mungthin
Department of Parasitology, Phramongkutklao College of Medicine, Bangkok 10400, Thailand
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Pyronaridine, a Mannich base antimalarial agent with a high activity against chloroquine-resistant Plasmodium falciparum, has been combined with artesunate as a new artemisinin based combination therapy (ACT). Pyronaridine–artesunate combination could be one of the choices for the treatment of uncomplicated falciparum malaria in multidrug-resistant areas including Thailand. The aim of this study was to determine in vitro sensitivity and cross-resistance pattern of pyronaridine in Thai isolates of P. falciparum. In addition, the influence of resistant genes concerning in vitro pyronaridine sensitivity was determined. The mean pyronaridine 50% inhibitory concentration (IC50) of 118 parasite isolates was 5.6 ± 3.1 nM (range = 0.2–15.4 nM) with a significant positive correlation with artesunate IC50 (r = 0.246, P = 0.008) and amodiaquine IC50 (r = 0.220, P = 0.042) and a significant negative correlation with quinine IC50 (r = −0.185, P = 0.047). Parasites containing the pfmdr1 86Y allele exhibited significantly reduced pyronaridine sensitivity compared with those with the pfmdr1 N86 allele (7.6 ± 3.3 nM and 5.4 ± 3.0 nM, respectively, P = 0.032, independent t test); however, the difference may not be clinically relevant. Pyronaridine–artesunate could be the candidate ACT to treat multidrug-resistant falciparum malaria in Thailand with careful monitoring.
Author Notes
Financial support: This study was financially supported by the Health System Research Institute/National Science and Technology Development Agency (P-13-50112), the Phramongkutklao Research Fund, and the Science Achievement Scholarship of Thailand.
Authors’ addresses: Kittiya Mahotorn, Peerapan Tan-ariya, and Thunyapit Thita, Department of Microbiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand, E-mails: k.mahotorn@gmail.com, peerapan.tan@mahidol.ac.th, and aomay_ao@hotmail.com. Toon Ruang-areerate, Naruemon Sitthichot, Nantana Suwandittakul, and Mathirut Mungthin, Department of Parasitology, Phramongkutklao College of Medicine, Bangkok 10400, Thailand, E-mails: youangtr@yahoo.com, mude_143@hotmail.com, suwanna_b@hotmail.com, and mathirut@hotmail.com.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
World Health Organization, 2012. World Malaria Report 2012. Geneva, Switzerland: World Health Organization.
-
2.
Takala-Harrison S et al. 2013. Genetic loci associated with delayed clearance of Plasmodium falciparum following artemisinin treatment in southeast Asia. Proc Natl Acad Sci USA 110: 240–245.
-
3.
Dondorp AM et al. 2009. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 361: 455–467.
-
4.
Ashley EA et al..; Tracking Resistance to Artemisinin Collaboration, 2014. Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 371: 411–423.
-
5.
Price RN et al. 2004. Mefloquine resistance in Plasmodium falciparum and increased pfmdr1 gene copy number. Lancet 364: 438–447.
-
6.
Chavchich M, Gerena L, Peters J, Chen N, Cheng Q, Kyle DE, 2010. Role of pfmdr1 amplification and expression in induction of resistance to artemisinin derivatives in Plasmodium falciparum. Antimicrob Agents Chemother 54: 2455–2464.
-
7.
Slater HC, Griffin JT, Ghani AC, Okell LC, 2016. Assessing the potential impact of artemisinin and partner drug resistance in sub-Saharan Africa. Malar J 15: 10.
-
8.
Croft SL, Duparc S, Arbe-Barnes SJ, Craft JC, Shin CS, Fleckenstein L, Borghini-Fuhrer I, Rim HJ, 2012. Review of pyronaridine anti-malarial properties and product characteristics. Malar J 11: 270.
-
9.
Rueangweerayut R et al. Pyronaridine-Artesunate Study Team, 2012. Pyronaridine-artesunate versus mefloquine plus artesunate for malaria. N Engl J Med 366: 1298–1309.
-
10.
Kayentao K et al. 2012. Pyronaridine-artesunate granules versus artemether-lumefantrine crushed tablets in children with Plasmodium falciparum malaria: a randomized controlled trial. Malar J 11: 364.
-
11.
Poravuth Y et al. 2011. Pyronaridine-artesunate versus chloroquine in patients with acute Plasmodium vivax malaria: a randomized, double-blind, non-inferiority trial. PLoS One 6: e14501.
-
12.
Tshefu AK et al..; Pyronaridine-artesunate Study Team, 2010. Efficacy and safety of a fixed-dose oral combination of pyronaridine-artesunate compared with artemether-lumefantrine in children and adults with uncomplicated Plasmodium falciparum malaria: a randomised non-inferiority trial. Lancet 375: 1457–1467.
-
13.
Duparc S, Borghini-Fuhrer I, Craft CJ, Arbe-Barnes S, Miller RM, Shin CS, Fleckenstein L, 2013. Safety and efficacy of pyronaridine-artesunate in uncomplicated acute malaria: an integrated analysis of individual patient data from six randomized clinical trials. Malar J 12: 70.
-
14.
Ramharter M et al. 2008. Fixed-dose pyronaridine-artesunate combination for treatment of uncomplicated falciparum malaria in pediatric patients in Gabon. J Infect Dis 198: 911–919.
-
15.
Pradines B, Tall A, Fusai T, Spiegel A, Hienne R, Rogier C, Trape JF, Le Bras J, Parzy D, 1999. In vitro activities of benflumetol against 158 Senegalese isolates of Plasmodium falciparum in comparison with those of standard antimalarial drugs. Antimicrob Agents Chemother 43: 418–420.
-
16.
Pradines B, Tall A, Parzy D, Spiegel A, Fusai T, Hienne R, Trape JF, Doury JC, 1998. In-vitro activity of pyronaridine and amodiaquine against African isolates (Senegal) of Plasmodium falciparum in comparison with standard antimalarial agents. J Antimicrob Chemother 42: 333–339.
-
17.
Schildbach S, Wernsdorfer WH, Suebsaeng L, Rooney W, 1990. In vitro sensitivity of multiresistant Plasmodium falciparum to new candidate antimalarial drugs in western Thailand. Southeast Asian J Trop Med Public Health 21: 29–38.
-
18.
Warsame M, Wernsdorfer WH, Payne D, Bjorkman A, 1991. Positive relationship between the response of Plasmodium falciparum to chloroquine and pyronaridine. Trans R Soc Trop Med Hyg 85: 570–571.
-
19.
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.
-
20.
Djimde A et al. 2001. A molecular marker for chloroquine-resistant falciparum malaria. N Engl J Med 344: 257–263.
-
21.
Duraisingh MT, Jones P, Sambou I, von Seidlein L, Pinder M, Warhurst DC, 2000. The tyrosine-86 allele of the pfmdr1 gene of Plasmodium falciparum is associated with increased sensitivity to the anti-malarials mefloquine and artemisinin. Mol Biochem Parasitol 108: 13–23.
-
22.
Reed MB, Saliba KJ, Caruana SR, Kirk K, Cowman AF, 2000. Pgh1 modulates sensitivity and resistance to multiple antimalarials in Plasmodium falciparum. Nature 403: 906–909.
-
23.
Setthaudom C, Tan-ariya P, Sitthichot N, Khositnithikul R, Suwandittakul N, Leelayoova S, Mungthin M, 2011. 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 85: 606–611.
-
24.
Cowman AF, Galatis D, Thompson JK, 1994. Selection for mefloquine resistance in Plasmodium falciparum is linked to amplification of the pfmdr1 gene and cross-resistance to halofantrine and quinine. Proc Natl Acad Sci USA 91: 1143–1147.
-
25.
Wilson CM, Volkman SK, Thaithong S, Martin RK, Kyle DE, Milhous WK, Wirth DF, 1993. Amplification of pfmdr1 associated with mefloquine and halofantrine resistance in Plasmodium falciparum from Thailand. Mol Biochem Parasitol 57: 151–160.
-
26.
Pickard AL, Wongsrichanalai C, Purfield A, Kamwendo D, Emery K, Zalewski C, Kawamoto F, Miller RS, Meshnick SR, 2003. Resistance to antimalarials in southeast Asia and genetic polymorphisms in pfmdr1. Antimicrob Agents Chemother 47: 2418–2423.
-
27.
Sidhu AB, Valderramos SG, Fidock DA, 2005. pfmdr1 mutations contribute to quinine resistance and enhance mefloquine and artemisinin sensitivity in Plasmodium falciparum. Mol Microbiol 57: 913–926.
-
28.
Uhlemann AC, Ramharter M, Lell B, Kremsner PG, Krishna S, 2005. Amplification of Plasmodium falciparum multidrug resistance gene 1 in isolates from Gabon. J Infect Dis 192: 1830–1835.
-
29.
Pradines B, Briolant S, Henry M, Oeuvray C, Baret E, Amalvict R, Didillon E, Rogier C, 2010. Absence of association between pyronaridine in vitro responses and polymorphisms in genes involved in quinoline resistance in Plasmodium falciparum. Malar J 9: 339.
-
30.
Trager W, Jensen JB, 1976. Human malaria parasites in continuous culture. Science 193: 673–675.
-
31.
Desjardins RE, Canfield CJ, Haynes JD, Chulay JD, 1979. Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique. Antimicrob Agents Chemother 16: 710–718.
-
32.
Wooden J, Kyes S, Sibley CH, 1993. PCR and strain identification in Plasmodium falciparum. Parasitol Today 9: 303–305.
-
33.
Ariey F et al. 2014. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature 505: 50–55.
-
34.
Vijaykadga S, Rojanawatsirivej C, Cholpol S, Phoungmanee D, Nakavej A, Wongsrichanalai C, 2006. In vivo sensitivity monitoring of mefloquine monotherapy and artesunate-mefloquine combinations for the treatment of uncomplicated falciparum malaria in Thailand in 2003. Trop Med Int Health 11: 211–219.
-
35.
Looareesuwan S, Kyle DE, Viravan C, Vanijanonta S, Wilairatana P, Wernsdorfer WH, 1996. Clinical study of pyronaridine for the treatment of acute uncomplicated falciparum malaria in Thailand. Am J Trop Med Hyg 54: 205–209.
-
36.
Childs GE, Hausler B, Milhous W, Chen C, Wimonwattrawatee T, Pooyindee N, Boudreau EF, 1988. In vitro activity of pyronaridine against field isolates and reference clones of Plasmodium falciparum. Am J Trop Med Hyg 38: 24–29.
-
37.
Witkowski B et al. 2013. Novel phenotypic assays for the detection of artemisinin-resistant Plasmodium falciparum malaria in Cambodia: in-vitro and ex-vivo drug-response studies. Lancet Infect Dis 13: 1043–1049.
-
38.
Elueze EI, Croft SL, Warhurst DC, 1996. Activity of pyronaridine and mepacrine against twelve strains of Plasmodium falciparum in vitro. J Antimicrob Chemother 37: 511–518.
-
39.
Pradines B, Mabika Mamfoumbi M, Parzy D, Owono Medang M, Lebeau C, Mourou Mbina JR, Doury JC, Kombila M, 1999. In vitro susceptibility of African isolates of Plasmodium falciparum from Gabon to pyronaridine. Am J Trop Med Hyg 60: 105–108.
-
40.
Price RN, Marfurt J, Chalfein F, Kenangalem E, Piera KA, Tjitra E, Anstey NM, Russell B, 2010. In vitro activity of pyronaridine against multidrug-resistant Plasmodium falciparum and Plasmodium vivax. Antimicrob Agents Chemother 54: 5146–5150.
-
41.
Okombo J, Kiara SM, Mwai L, Pole L, Ohuma E, Ochola LI, Nzila A, 2012. Baseline in vitro activities of the antimalarials pyronaridine and methylene blue against Plasmodium falciparum isolates from Kenya. Antimicrob Agents Chemother 56: 1105–1107.
-
42.
Kurth F, Pongratz P, Belard S, Mordmuller B, Kremsner PG, Ramharter M, 2009. In vitro activity of pyronaridine against Plasmodium falciparum and comparative evaluation of anti-malarial drug susceptibility assays. Malar J 8: 79.
-
43.
Pascual A, Madamet M, Briolant S, Gaillard T, Amalvict R, Benoit N, Travers D, Pradines B; French National Reference Centre for Imported Malaria Study Group, 2015. Multinormal in vitro distribution of Plasmodium falciparum susceptibility to piperaquine and pyronaridine. Malar J 14: 49.
-
44.
White NJ, 2004. Antimalarial drug resistance. J Clin Invest 113: 1084–1092.
-
45.
Madamet M, Briolant S, Amalvict R, Benoit N, Bouchiba H, Cren J, Pradines B; French National Centre for Imported Malaria Study Group, 2016. The Plasmodium falciparum chloroquine resistance transporter is associated with the ex vivo P. falciparum African parasite response to pyronaridine. Parasit Vectors 9: 77.
-
46.
Leang R et al. 2015. Evidence of Plasmodium falciparum malaria multidrug resistance to artemisinin and piperaquine in western Cambodia: dihydroartemisinin-piperaquine open-label multicenter clinical assessment. Antimicrob Agents Chemother 59: 4719–4726.
-
47.
Amaratunga C et al. 2016. Dihydroartemisinin-piperaquine resistance in Plasmodium falciparum malaria in Cambodia: a multisite prospective cohort study. Lancet Infect Dis 16: 357–365.
-
48.
Mungthin M, Suwandittakul N, Chaijaroenkul W, Rungsrihirunrat K, Harnyuttanakorn P, Seugorn A, Na Bangchang K, 2010. The patterns of mutation and amplification of Plasmodium falciparum pfcrt and pfmdr1 genes in Thailand during the year 1988 to 2003. Parasitol Res 107: 539–545.
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