Skip to main content
Top
Published in: Malaria Journal 1/2010

Open Access 01-12-2010 | Research

Brazilian Plasmodium falciparum isolates: investigation of candidate polymorphisms for artemisinin resistance before introduction of artemisinin-based combination therapy

Authors: Bianca E Gama, Natália K Almeida de Oliveira, José M de Souza, Fátima Santos, Leonardo JM de Carvalho, Yonne FC Melo, Philip J Rosenthal, Cláudio T Daniel-Ribeiro, Maria de Fátima Ferreira-da-Cruz

Published in: Malaria Journal | Issue 1/2010

Login to get access

Abstract

Background

This study was performed to better understand the genetic diversity of known polymorphisms in pfatpase6 and pfmdr1 genes before the introduction of ACT in Brazil, in order to get a genotypic snapshot of Plasmodium falciparum parasites that may be used as baseline reference for future studies.

Methods

Parasites from P. falciparum samples collected in 2002, 2004 and 2006-2007 were genotyped using PCR and DNA sequencing at codons 86, 130, 184, 1034, 1042, 1109 and 1246 for pfmdr1 gene, and 243, 263, 402, 431, 623, 630, 639, 683, 716, 776, 769 and 771 for pfatpase6 gene.

Results

A pfmdr1 haplotype NEF/CDVY was found in 97% of the samples. In the case of pfatpase6, four haplotypes, wild-type (37%), 630 S (35%), 402 V (5%) and double-mutant 630 S + 402 V (23%), were detected.

Conclusion

Although some polymorphism in pfmdr1 and pfatpase6 were verified, no reported haplotypes in both genes that may mediate altered response to ACT was detected before the introduction of this therapy in Brazil. Thus, the haplotypes herein described can be very useful as a baseline reference of P. falciparum populations without ACT drug pressure.
Literature
1.
go back to reference Sinclair D, Zani B, Donegan S, Olliaro P, Garner P: Artemisinin-based combination therapy for treating uncomplicated malaria. Cochrane Database Syst Rev. 2009, 3: CD007483-PubMed Sinclair D, Zani B, Donegan S, Olliaro P, Garner P: Artemisinin-based combination therapy for treating uncomplicated malaria. Cochrane Database Syst Rev. 2009, 3: CD007483-PubMed
2.
go back to reference Jambou R, Legrand E, Niang M, Khim N, Lim P, Volney B, Ekala M, Bouchier C, Esterre P, Fandeur T, Mercereau-Puijalon O: Resistance of Plasmodium falciparum field isolates to in-vitro artemether and point mutations of the SERCA-type PfATPase6. Lancet. 2005, 366: 1960-1963. 10.1016/S0140-6736(05)67787-2.CrossRefPubMed Jambou R, Legrand E, Niang M, Khim N, Lim P, Volney B, Ekala M, Bouchier C, Esterre P, Fandeur T, Mercereau-Puijalon O: Resistance of Plasmodium falciparum field isolates to in-vitro artemether and point mutations of the SERCA-type PfATPase6. Lancet. 2005, 366: 1960-1963. 10.1016/S0140-6736(05)67787-2.CrossRefPubMed
3.
go back to reference Ferreira I, Lopes D, Martinelli A, Ferreira C, do Rosário V, Cravo P: In vitro assessment of artesunate, artemether and amodiaquine susceptibility and molecular analysis of putative resistance-associated mutations of Plasmodium falciparum from São Tomé and Príncipe. Trop Med Int Health. 2007, 12: 353-362. 10.1111/j.1365-3156.2006.01789.x.CrossRefPubMed Ferreira I, Lopes D, Martinelli A, Ferreira C, do Rosário V, Cravo P: In vitro assessment of artesunate, artemether and amodiaquine susceptibility and molecular analysis of putative resistance-associated mutations of Plasmodium falciparum from São Tomé and Príncipe. Trop Med Int Health. 2007, 12: 353-362. 10.1111/j.1365-3156.2006.01789.x.CrossRefPubMed
4.
go back to reference Ferreira I, Martinelli A, Rodrigues L, do Carmo E, do Rosário V, Póvoa M, Cravo P: Plasmodium falciparum from Pará state (Brazil) shows satisfactory in vitro response to artemisinin derivatives and absence of the S769N mutation in the SERCA-type PfATPase6. Trop Med Int Health. 2008, 13: 199-207. 10.1111/j.1365-3156.2007.01991.x.CrossRefPubMed Ferreira I, Martinelli A, Rodrigues L, do Carmo E, do Rosário V, Póvoa M, Cravo P: Plasmodium falciparum from Pará state (Brazil) shows satisfactory in vitro response to artemisinin derivatives and absence of the S769N mutation in the SERCA-type PfATPase6. Trop Med Int Health. 2008, 13: 199-207. 10.1111/j.1365-3156.2007.01991.x.CrossRefPubMed
5.
go back to reference Tahar R, Ringwald P, Basco L: Molecular epidemiology of malaria in Cameroon. XXVIII. In vitro activity of dihydroartemisinin against clinical isolates of Plasmodium falciparum and sequence analysis of the P. falciparum ATPase 6 gene. Am J Trop Med Hyg. 2009, 81: 13-18.PubMed Tahar R, Ringwald P, Basco L: Molecular epidemiology of malaria in Cameroon. XXVIII. In vitro activity of dihydroartemisinin against clinical isolates of Plasmodium falciparum and sequence analysis of the P. falciparum ATPase 6 gene. Am J Trop Med Hyg. 2009, 81: 13-18.PubMed
6.
go back to reference Noedl H, Se Y, Schaecher K, Smith B, Socheat D, Fukuda M: Evidence of artemisinin-resistant malaria in western Cambodia. N Engl J Med. 2008, 359: 2619-2620. 10.1056/NEJMc0805011.CrossRefPubMed Noedl H, Se Y, Schaecher K, Smith B, Socheat D, Fukuda M: Evidence of artemisinin-resistant malaria in western Cambodia. N Engl J Med. 2008, 359: 2619-2620. 10.1056/NEJMc0805011.CrossRefPubMed
7.
go back to reference Dondorp A, Nosten F, Yi P, Das D, Phyo A, Tarning J, Lwin K, Ariey F, Hanpithakpong W, Lee SJ, Ringwald P, Silamut K, Imwong M, Chotivanich K, Lim P, Herdman T, An SS, Yeung S, Singhasivanon P, Day NP, Lindegardh N, Socheat D, White NJ: Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2009, 361: 455-467. 10.1056/NEJMoa0808859.PubMedCentralCrossRefPubMed Dondorp A, Nosten F, Yi P, Das D, Phyo A, Tarning J, Lwin K, Ariey F, Hanpithakpong W, Lee SJ, Ringwald P, Silamut K, Imwong M, Chotivanich K, Lim P, Herdman T, An SS, Yeung S, Singhasivanon P, Day NP, Lindegardh N, Socheat D, White NJ: Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2009, 361: 455-467. 10.1056/NEJMoa0808859.PubMedCentralCrossRefPubMed
8.
go back to reference Reed M, Saliba K, Caruana S, Kirk K, Cowman A: Pgh1 modulates sensitivity and resistance to multiple antimalarials in Plasmodium falciparum. Nature. 2000, 403: 906-909. 10.1038/35002615.CrossRefPubMed Reed M, Saliba K, Caruana S, Kirk K, Cowman A: Pgh1 modulates sensitivity and resistance to multiple antimalarials in Plasmodium falciparum. Nature. 2000, 403: 906-909. 10.1038/35002615.CrossRefPubMed
9.
go back to reference Meshnick S: Artemisinin: mechanisms of action, resistance and toxicity. Int J Parasitol. 2002, 32: 1655-1660. 10.1016/S0020-7519(02)00194-7.CrossRefPubMed Meshnick S: Artemisinin: mechanisms of action, resistance and toxicity. Int J Parasitol. 2002, 32: 1655-1660. 10.1016/S0020-7519(02)00194-7.CrossRefPubMed
10.
go back to reference Duraisingh M, Jones P, Sambou I, von Seidlein L, Pinder M, Warhurst D: 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. 2000, 108: 13-23. 10.1016/S0166-6851(00)00201-2.CrossRefPubMed Duraisingh M, Jones P, Sambou I, von Seidlein L, Pinder M, Warhurst D: 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. 2000, 108: 13-23. 10.1016/S0166-6851(00)00201-2.CrossRefPubMed
11.
go back to reference Sidhu A, Uhlemann A, Valderramos S, Valderramos J, Krishna S, Fidock D: Decreasing pfmdr1 copy number in Plasmodium falciparum malaria heightens susceptibility to mefloquine, lumefantrine, halofantrine, quinine, and artemisinin. J Infect Dis. 2006, 194: 528-535. 10.1086/507115.PubMedCentralCrossRefPubMed Sidhu A, Uhlemann A, Valderramos S, Valderramos J, Krishna S, Fidock D: Decreasing pfmdr1 copy number in Plasmodium falciparum malaria heightens susceptibility to mefloquine, lumefantrine, halofantrine, quinine, and artemisinin. J Infect Dis. 2006, 194: 528-535. 10.1086/507115.PubMedCentralCrossRefPubMed
12.
go back to reference Sidhu A, Valderramos S, Fidock D: pfmdr1 mutations contribute to quinine resistance and enhance mefloquine and artemisinin sensitivity in Plasmodium falciparum. Mol Microbiol. 2005, 57: 913-926. 10.1111/j.1365-2958.2005.04729.x.CrossRefPubMed Sidhu A, Valderramos S, Fidock D: pfmdr1 mutations contribute to quinine resistance and enhance mefloquine and artemisinin sensitivity in Plasmodium falciparum. Mol Microbiol. 2005, 57: 913-926. 10.1111/j.1365-2958.2005.04729.x.CrossRefPubMed
13.
go back to reference Pickard A, Wongsrichanalai C, Purfield A, Kamwendo D, Emery K, Zalewski C, Kawamoto F, Miller R, Meshnick S: Resistance to antimalarials in Southeast Asia and genetic polymorphisms in pfmdr1. Antimicrob Agents Chemother. 2003, 47: 2418-2423. 10.1128/AAC.47.8.2418-2423.2003.PubMedCentralCrossRefPubMed Pickard A, Wongsrichanalai C, Purfield A, Kamwendo D, Emery K, Zalewski C, Kawamoto F, Miller R, Meshnick S: Resistance to antimalarials in Southeast Asia and genetic polymorphisms in pfmdr1. Antimicrob Agents Chemother. 2003, 47: 2418-2423. 10.1128/AAC.47.8.2418-2423.2003.PubMedCentralCrossRefPubMed
14.
go back to reference Sisowath C, Strömberg J, Mårtensson A, Msellem M, Obondo C, Björkman A, Gil J: In vivo selection of Plasmodium falciparum pfmdr1 86N coding alleles by artemether-lumefantrine (Coartem). J Infect Dis. 2005, 191: 1014-1017. 10.1086/427997.CrossRefPubMed Sisowath C, Strömberg J, Mårtensson A, Msellem M, Obondo C, Björkman A, Gil J: In vivo selection of Plasmodium falciparum pfmdr1 86N coding alleles by artemether-lumefantrine (Coartem). J Infect Dis. 2005, 191: 1014-1017. 10.1086/427997.CrossRefPubMed
15.
go back to reference Sisowath C, Ferreira P, Bustamante L, Dahlström S, Mårtensson A, Björkman A, Krishna S, Gil J: The role of pfmdr1 in Plasmodium falciparum tolerance to artemether-lumefantrine in Africa. Trop Med Int Health. 2007, 12: 736-742. 10.1111/j.1365-3156.2007.01843.x.CrossRefPubMed Sisowath C, Ferreira P, Bustamante L, Dahlström S, Mårtensson A, Björkman A, Krishna S, Gil J: The role of pfmdr1 in Plasmodium falciparum tolerance to artemether-lumefantrine in Africa. Trop Med Int Health. 2007, 12: 736-742. 10.1111/j.1365-3156.2007.01843.x.CrossRefPubMed
16.
go back to reference Happi C, Gbotosho G, Folarin O, Sowunmi A, Hudson T, O'Neil M, Milhous W, Wirth D, Oduola A: Selection of Plasmodium falciparum multidrug resistance gene 1 alleles in asexual stages and gametocytes by artemether-lumefantrine in Nigerian children with uncomplicated falciparum malaria. Antimicrob Agents Chemother. 2009, 53: 888-895. 10.1128/AAC.00968-08.PubMedCentralCrossRefPubMed Happi C, Gbotosho G, Folarin O, Sowunmi A, Hudson T, O'Neil M, Milhous W, Wirth D, Oduola A: Selection of Plasmodium falciparum multidrug resistance gene 1 alleles in asexual stages and gametocytes by artemether-lumefantrine in Nigerian children with uncomplicated falciparum malaria. Antimicrob Agents Chemother. 2009, 53: 888-895. 10.1128/AAC.00968-08.PubMedCentralCrossRefPubMed
17.
go back to reference Dokomajilar C, Nsobya S, Greenhouse B, Rosenthal P, Dorsey G: Selection of Plasmodium falciparum pfmdr1 alleles following therapy with artemether-lumefantrine in an area of Uganda where malaria is highly endemic. Antimicrob Agents Chemother. 2006, 50: 1893-1895. 10.1128/AAC.50.5.1893-1895.2006.PubMedCentralCrossRefPubMed Dokomajilar C, Nsobya S, Greenhouse B, Rosenthal P, Dorsey G: Selection of Plasmodium falciparum pfmdr1 alleles following therapy with artemether-lumefantrine in an area of Uganda where malaria is highly endemic. Antimicrob Agents Chemother. 2006, 50: 1893-1895. 10.1128/AAC.50.5.1893-1895.2006.PubMedCentralCrossRefPubMed
18.
go back to reference Humphreys G, Merinopoulos I, Ahmed J, Whitty C, Mutabingwa T, Sutherland C, Hallett R: Amodiaquine and artemether-lumefantrine select distinct alleles of the Plasmodium falciparum mdr1 gene in Tanzanian children treated for uncomplicated malaria. Antimicrob Agents Chemother. 2007, 51: 991-997. 10.1128/AAC.00875-06.PubMedCentralCrossRefPubMed Humphreys G, Merinopoulos I, Ahmed J, Whitty C, Mutabingwa T, Sutherland C, Hallett R: Amodiaquine and artemether-lumefantrine select distinct alleles of the Plasmodium falciparum mdr1 gene in Tanzanian children treated for uncomplicated malaria. Antimicrob Agents Chemother. 2007, 51: 991-997. 10.1128/AAC.00875-06.PubMedCentralCrossRefPubMed
19.
go back to reference Sisowath C, Petersen I, Veiga M, Mårtensson A, Premji Z, Björkman A, Fidock D, Gil J: In vivo selection of Plasmodium falciparum parasites carrying the chloroquine-susceptible pfcrt K76 allele after treatment with artemether-lumefantrine in Africa. J Infect Dis. 2009, 199: 750-757. 10.1086/596738.PubMedCentralCrossRefPubMed Sisowath C, Petersen I, Veiga M, Mårtensson A, Premji Z, Björkman A, Fidock D, Gil J: In vivo selection of Plasmodium falciparum parasites carrying the chloroquine-susceptible pfcrt K76 allele after treatment with artemether-lumefantrine in Africa. J Infect Dis. 2009, 199: 750-757. 10.1086/596738.PubMedCentralCrossRefPubMed
20.
go back to reference Dahlström S, Veiga M, Ferreira P, Mårtensson A, Kaneko A, Andersson B, Björkman A, Gil J: Diversity of the sarco/endoplasmic reticulum Ca(2+)-ATPase orthologue of Plasmodium falciparum (PfATP6). Infect Genet Evol. 2008, 8: 340-345. 10.1016/j.meegid.2008.02.002.CrossRefPubMed Dahlström S, Veiga M, Ferreira P, Mårtensson A, Kaneko A, Andersson B, Björkman A, Gil J: Diversity of the sarco/endoplasmic reticulum Ca(2+)-ATPase orthologue of Plasmodium falciparum (PfATP6). Infect Genet Evol. 2008, 8: 340-345. 10.1016/j.meegid.2008.02.002.CrossRefPubMed
21.
go back to reference Egan T: Artemisinin-resistant Plasmodium falciparum: can the genie be put back in the bottle?. Future Microbiol. 2009, 4: 637-639. 10.2217/fmb.09.42.CrossRefPubMed Egan T: Artemisinin-resistant Plasmodium falciparum: can the genie be put back in the bottle?. Future Microbiol. 2009, 4: 637-639. 10.2217/fmb.09.42.CrossRefPubMed
22.
go back to reference Zalis M, Pang L, Silveira M, Milhous W, Wirth D: Characterization of Plasmodium falciparum isolated from the Amazon region of Brazil: evidence for quinine resistance. Am J Trop Med Hyg. 1998, 58: 630-637.PubMed Zalis M, Pang L, Silveira M, Milhous W, Wirth D: Characterization of Plasmodium falciparum isolated from the Amazon region of Brazil: evidence for quinine resistance. Am J Trop Med Hyg. 1998, 58: 630-637.PubMed
23.
go back to reference Póvoa M, Adagu I, Oliveira S, Machado R, Miles M, Warhurst D: Pfmdr1 Asn1042Asp and Asp1246Tyr polymorphisms, thought to be associated with chloroquine resistance, are present in chloroquine-resistant and -sensitive Brazilian field isolates of Plasmodium falciparum. Exp Parasitol. 1998, 88: 64-68. 10.1006/expr.1998.4195.CrossRefPubMed Póvoa M, Adagu I, Oliveira S, Machado R, Miles M, Warhurst D: Pfmdr1 Asn1042Asp and Asp1246Tyr polymorphisms, thought to be associated with chloroquine resistance, are present in chloroquine-resistant and -sensitive Brazilian field isolates of Plasmodium falciparum. Exp Parasitol. 1998, 88: 64-68. 10.1006/expr.1998.4195.CrossRefPubMed
24.
go back to reference Gama B, Pereira-Carvalho G, Lutucuta Kosi F, Almeida de Oliveira N, Fortes F, Rosenthal P, Daniel-Ribeiro C, Ferreira-da-Cruz MF: Plasmodium falciparum isolates from Angola show the StctVMNT haplotype in the pfcrt gene. Malar J. 2010, 9: 174-10.1186/1475-2875-9-174.PubMedCentralCrossRefPubMed Gama B, Pereira-Carvalho G, Lutucuta Kosi F, Almeida de Oliveira N, Fortes F, Rosenthal P, Daniel-Ribeiro C, Ferreira-da-Cruz MF: Plasmodium falciparum isolates from Angola show the StctVMNT haplotype in the pfcrt gene. Malar J. 2010, 9: 174-10.1186/1475-2875-9-174.PubMedCentralCrossRefPubMed
25.
go back to reference Menegon M, Sannella A, Majori G, Severini C: Detection of novel point mutations in the Plasmodium falciparum ATPase6 candidate gene for resistance to artemisinins. Parasitol Int. 2008, 57: 233-235. 10.1016/j.parint.2007.12.004.CrossRefPubMed Menegon M, Sannella A, Majori G, Severini C: Detection of novel point mutations in the Plasmodium falciparum ATPase6 candidate gene for resistance to artemisinins. Parasitol Int. 2008, 57: 233-235. 10.1016/j.parint.2007.12.004.CrossRefPubMed
26.
go back to reference Otto T, Vasconcellos E, Gomes L, Moreira A, Degrave W, Mendonça-Lima L, Alves-Ferreira M: ChromaPipe: a pipeline for analysis, quality control and management for a DNA sequencing facility. Genet Mol Res. 2008, 7: 861-871. 10.4238/vol7-3X-Meeting04.CrossRefPubMed Otto T, Vasconcellos E, Gomes L, Moreira A, Degrave W, Mendonça-Lima L, Alves-Ferreira M: ChromaPipe: a pipeline for analysis, quality control and management for a DNA sequencing facility. Genet Mol Res. 2008, 7: 861-871. 10.4238/vol7-3X-Meeting04.CrossRefPubMed
27.
go back to reference Zalis M, Ferreira-da-Cruz M, Balthazar-Guedes H, Banic D, Alecrim W, Souza J, Druilhe P, Daniel-Ribeiro C: Malaria diagnosis: standardization of a polymerase chain reaction for the detection of Plasmodium falciparum parasites in individuals with low-grade parasitemia. Parasitol Res. 1996, 82: 612-616. 10.1007/s004360050173.CrossRefPubMed Zalis M, Ferreira-da-Cruz M, Balthazar-Guedes H, Banic D, Alecrim W, Souza J, Druilhe P, Daniel-Ribeiro C: Malaria diagnosis: standardization of a polymerase chain reaction for the detection of Plasmodium falciparum parasites in individuals with low-grade parasitemia. Parasitol Res. 1996, 82: 612-616. 10.1007/s004360050173.CrossRefPubMed
28.
go back to reference Uhlemann A, McGready R, Ashley E, Brockman A, Singhasivanon P, Krishna S, White N, Nosten F, Price R: Intrahost selection of Plasmodium falciparum pfmdr1 alleles after antimalarial treatment on the northwestern border of Thailand. J Infect Dis. 2007, 195: 134-141. 10.1086/509809.PubMedCentralCrossRefPubMed Uhlemann A, McGready R, Ashley E, Brockman A, Singhasivanon P, Krishna S, White N, Nosten F, Price R: Intrahost selection of Plasmodium falciparum pfmdr1 alleles after antimalarial treatment on the northwestern border of Thailand. J Infect Dis. 2007, 195: 134-141. 10.1086/509809.PubMedCentralCrossRefPubMed
29.
go back to reference Mugittu K, Genton B, Mshinda H, Beck H: Molecular monitoring of Plasmodium falciparum resistance to artemisinin in Tanzania. Malar J. 2006, 5: 126-10.1186/1475-2875-5-126.PubMedCentralCrossRefPubMed Mugittu K, Genton B, Mshinda H, Beck H: Molecular monitoring of Plasmodium falciparum resistance to artemisinin in Tanzania. Malar J. 2006, 5: 126-10.1186/1475-2875-5-126.PubMedCentralCrossRefPubMed
30.
go back to reference Echeverry D, Holmgren G, Murillo C, Higuita J, Björkman A, Gil J, Osorio L: Short report: polymorphisms in the pfcrt and pfmdr1 genes of Plasmodium falciparum and in vitro susceptibility to amodiaquine and desethylamodiaquine. Am J Trop Med Hyg. 2007, 77: 1034-1038.PubMed Echeverry D, Holmgren G, Murillo C, Higuita J, Björkman A, Gil J, Osorio L: Short report: polymorphisms in the pfcrt and pfmdr1 genes of Plasmodium falciparum and in vitro susceptibility to amodiaquine and desethylamodiaquine. Am J Trop Med Hyg. 2007, 77: 1034-1038.PubMed
31.
go back to reference Mehlotra R, Mattera G, Bockarie M, Maguire J, Baird J, Sharma Y, Alifrangis M, Dorsey G, Rosenthal P, Fryauff D, Kazura JW, Stoneking M, Zimmerman PA: Discordant patterns of genetic variation at two chloroquine resistance loci in worldwide populations of the malaria parasite Plasmodium falciparum. Antimicrob Agents Chemother. 2008, 52: 2212-2222. 10.1128/AAC.00089-08.PubMedCentralCrossRefPubMed Mehlotra R, Mattera G, Bockarie M, Maguire J, Baird J, Sharma Y, Alifrangis M, Dorsey G, Rosenthal P, Fryauff D, Kazura JW, Stoneking M, Zimmerman PA: Discordant patterns of genetic variation at two chloroquine resistance loci in worldwide populations of the malaria parasite Plasmodium falciparum. Antimicrob Agents Chemother. 2008, 52: 2212-2222. 10.1128/AAC.00089-08.PubMedCentralCrossRefPubMed
32.
go back to reference Ibrahim M, Khim N, Adam H, Ariey F, Duchemin J: Polymorphism of PfATPase in Niger: detection of three new point mutations. Malar J. 2009, 8: 28-10.1186/1475-2875-8-28.PubMedCentralCrossRefPubMed Ibrahim M, Khim N, Adam H, Ariey F, Duchemin J: Polymorphism of PfATPase in Niger: detection of three new point mutations. Malar J. 2009, 8: 28-10.1186/1475-2875-8-28.PubMedCentralCrossRefPubMed
33.
go back to reference Jambou R, Martinelli A, Pinto J, Gribaldo S, Legrand E, Niang M, Kim N, Pharath L, Volnay B, Ekala M, Bouchier C, Fandeur T, Berzosa P, Benito A, Ferreira ID, Ferreira C, Vieira PP, Alecrim MG, Mercereau-Puijalon O, Cravo P: Geographic structuring of the Plasmodium falciparum sarco(endo)plasmic reticulum Ca2+ ATPase (PfSERCA) gene diversity. PLoS One. 2010, 5: e9424-10.1371/journal.pone.0009424.PubMedCentralCrossRefPubMed Jambou R, Martinelli A, Pinto J, Gribaldo S, Legrand E, Niang M, Kim N, Pharath L, Volnay B, Ekala M, Bouchier C, Fandeur T, Berzosa P, Benito A, Ferreira ID, Ferreira C, Vieira PP, Alecrim MG, Mercereau-Puijalon O, Cravo P: Geographic structuring of the Plasmodium falciparum sarco(endo)plasmic reticulum Ca2+ ATPase (PfSERCA) gene diversity. PLoS One. 2010, 5: e9424-10.1371/journal.pone.0009424.PubMedCentralCrossRefPubMed
34.
go back to reference Imwong M, Dondorp A, Nosten F, Yi P, Mungthin M, Hanchana S, Das D, Phyo A, Lwin K, Pukrittayakamee S, Lee SJ, Saisung S, Koecharoen K, Nguon C, Day NP, Socheat D, White NJ: Exploring the contribution of candidate genes to artemisinin resistance in Plasmodium falciparum. Antimicrob Agents Chemother. 2010, 54: 2886-2892. 10.1128/AAC.00032-10.PubMedCentralCrossRefPubMed Imwong M, Dondorp A, Nosten F, Yi P, Mungthin M, Hanchana S, Das D, Phyo A, Lwin K, Pukrittayakamee S, Lee SJ, Saisung S, Koecharoen K, Nguon C, Day NP, Socheat D, White NJ: Exploring the contribution of candidate genes to artemisinin resistance in Plasmodium falciparum. Antimicrob Agents Chemother. 2010, 54: 2886-2892. 10.1128/AAC.00032-10.PubMedCentralCrossRefPubMed
35.
go back to reference Witkowski B, Lelièvre J, Barragán M, Laurent V, Su X, Berry A, Benoit-Vical F: Increased tolerance to artemisinin in Plasmodium falciparum is mediated by a quiescence mechanism. Antimicrob Agents Chemother. 2010, 54: 1872-1877. 10.1128/AAC.01636-09.PubMedCentralCrossRefPubMed Witkowski B, Lelièvre J, Barragán M, Laurent V, Su X, Berry A, Benoit-Vical F: Increased tolerance to artemisinin in Plasmodium falciparum is mediated by a quiescence mechanism. Antimicrob Agents Chemother. 2010, 54: 1872-1877. 10.1128/AAC.01636-09.PubMedCentralCrossRefPubMed
Metadata
Title
Brazilian Plasmodium falciparum isolates: investigation of candidate polymorphisms for artemisinin resistance before introduction of artemisinin-based combination therapy
Authors
Bianca E Gama
Natália K Almeida de Oliveira
José M de Souza
Fátima Santos
Leonardo JM de Carvalho
Yonne FC Melo
Philip J Rosenthal
Cláudio T Daniel-Ribeiro
Maria de Fátima Ferreira-da-Cruz
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2010
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-9-355

Other articles of this Issue 1/2010

Malaria Journal 1/2010 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.