• 1.

    Price RN, Tjitra E, Guerra CA, Yeung S, White NJ, Anstey NM, 2007. Vivax malaria: neglected and not benign. Am J Trop Med Hyg 77 (Suppl): 7987.

  • 2.

    Guerra CA, Howes RE, Patil AP, Gething PW, Van Boeckel TP, Temperley WH, Kabaria CW, Tatem AJ, Manh BH, Elyazar IR, Baird JK, Snow RW, Hay SI, 2010. The international limits and population at risk of Plasmodium vivax transmission in 2009. PLoS Negl Trop Dis 4: e774.

    • Search Google Scholar
    • Export Citation
  • 3.

    Baird JK, 2009. Resistance to therapies for infection by Plasmodium vivax. Clin Microbiol Rev 22: 508534.

  • 4.

    Baird JK, Leksana B, Masbar S, Fryauff DJ, Sutanihardja MA, Suradi, Wignall FS, Hoffman SL, 1997. Diagnosis of resistance to chloroquine by Plasmodium vivax: timing of recurrence and whole blood chloroquine levels. Am J Trop Med Hyg 56: 621626.

    • Search Google Scholar
    • Export Citation
  • 5.

    Baird JK, 2011. Resistance to chloroquine unhinges vivax malaria therapeutics. Antimicrob Agents Chemother 55: 18271830.

  • 6.

    Gama BE, Lacerda MV, Daniel-Ribeiro CT, Ferreira-da-Cruz M de F, 2011. Chemoresistance of Plasmodium falciparum and Plasmodium vivax parasites in Brazil: consequences on disease morbidity and control. Mem Inst Oswaldo Cruz 106 (Suppl 1): 159166.

    • Search Google Scholar
    • Export Citation
  • 7.

    de Santana Filho FS, Arcanjo AR, Chehuan YM, Costa MR, Martinez-Espinosa FE, Vieira JL, Barbosa MG, Alecrim WD, Alecrim MG, 2007. Chloroquine-resistant Plasmodium vivax, Brazilian Amazon. Emerg Infect Dis 13: 11251126.

    • Search Google Scholar
    • Export Citation
  • 8.

    Suwanarusk R, Russell B, Chavchich M, Chalfein F, Kenangalem E, Kosaisavee V, Prasetyorini B, Piera KA, Barends M, Brockman A, Lek-Uthai U, Anstey NM, Tjitra E, Nosten F, Cheng Q, Price RN, 2007. Chloroquine resistant Plasmodium vivax: in vitro characterisation and association with molecular polymorphisms. PLoS ONE 2: e1089.

    • Search Google Scholar
    • Export Citation
  • 9.

    Marfurt J, de Monbrison F, Brega S, Barbollat L, Mueller 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.

    • Search Google Scholar
    • Export Citation
  • 10.

    JM, Nomura T, Neves J, Baird JK, Wellems TE, del Portillo HA, 2005. Plasmodium vivax: allele variants of the mdr1 gene do not associate with chloroquine resistance among isolates from Brazil, Papua, and monkey-adapted strains. Exp Parasitol 109: 256259.

    • Search Google Scholar
    • Export Citation
  • 11.

    Barnadas C, Ratsimbasoa A, Tichit M, Bouchier C, Jahevitra M, Picot S, Menard D, 2008. Plasmodium vivax resistance to chloroquine in Madagascar: clinical efficacy and polymorphisms in pvmdr-1 and pvcrt-o genes. Antimicrob Agents Chemother 52: 42334240.

    • Search Google Scholar
    • Export Citation
  • 12.

    Orjuela-Sánchez P, de Santana Filho FS, Machado-Lima A, Chehuan YF, Costa MR, Alecrim MG, del Portillo HA, 2009. Analysis of single-nucleotide polymorphisms in the crt-o and mdr1 genes of Plasmodium vivax among chloroquine-resistant isolates from the Brazilian Amazon region. Antimicrob Agents Chemother 53: 35613564.

    • Search Google Scholar
    • Export Citation
  • 13.

    Brega S, Meslin B, de Monbrison F, Severini C, Gradoni L, Udomsangpetch R, Sutanto I, Peyron F, Picot S, 2005. Identification of the Plasmodium vivax mdr-like gene (pvmdr1) and analysis of single-nucleotide polymorphisms among isolates from different areas of endemicity. J Infect Dis 191: 272277.

    • Search Google Scholar
    • Export Citation
  • 14.

    Orjuela-Sánchez P, Karunaweera ND, da Silva-Nunes M, da Silva NS, Scopel KK, Gonçalves RM, Amaratunga C, JM, Socheat D, Fairhurst RM, Gunawardena S, Thavakodirasah T, Galapaththy GL, Abeysinghe R, Kawamoto F, Wirth DF, Ferreira MU, 2010. Single-nucleotide polymorphism, linkage disequilibrium and geographic structure in the malaria parasite Plasmodium vivax: prospects for genome-wide association studies. BMC Genet 11: 65.

    • Search Google Scholar
    • Export Citation
  • 15.

    Price RN, Uhlemann AC, Brockman A, McGready R, Ashley E, Phaipun L, Patel R, Laing K, Looareesuwan S, White NJ, Nosten F, Krishna S, 2004. Mefloquine resistance in Plasmodium falciparum and increased pfmdr1 gene copy number. Lancet 364: 438447.

    • Search Google Scholar
    • Export Citation
  • 16.

    Suwanarusk R, Chavchich M, Russell B, Jaidee A, Chalfein F, Barends M, Prasetyorini B, Kenangalem E, Piera KA, Lek-Uthai U, Anstey NM, Tjitra E, Nosten F, Cheng Q, Price RN, 2008. Amplification of pvmdr1 associated with multidrug-resistant Plasmodium vivax. J Infect Dis 198: 15581564.

    • Search Google Scholar
    • Export Citation
  • 17.

    da Silva-Nunes M, Codeço CT, Malafronte RS, da Silva NS, Juncansen C, Muniz PT, Ferreira MU, 2008. Malaria on the Amazonian frontier: transmission dynamics, risk factors, spatial distribution, and prospects for control. Am J Trop Med Hyg 79: 624635.

    • Search Google Scholar
    • Export Citation
  • 18.

    da Silva NS, da Silva-Nunes M, Malafronte RS, Menezes MJ, D'Arcadia RR, Komatsu NT, Scopel KK, Braga EM, Cavasini CE, Cordeiro JA, Ferreira MU, 2010. Epidemiology and control of frontier malaria in Brazil: lessons from community-based studies in rural Amazonia. Trans R Soc Trop Med Hyg 104: 343350.

    • Search Google Scholar
    • Export Citation
  • 19.

    Orjuela-Sánchez P, da Silva NS, da Silva-Nunes M, Ferreira MU, 2009. Parasitemia recurrences and population dynamics of Plasmodium vivax polymorphisms in rural Amazonia. Am J Trop Med Hyg 81: 961968.

    • Search Google Scholar
    • Export Citation
  • 20.

    Orjuela-Sánchez P, da Silva-Nunes M, da Silva NS, Scopel KK, Gonçalves RM, Malafronte RS, Ferreira MU, 2009. Population dynamics of genetically diverse Plasmodium falciparum lineages: community-based prospective study in rural Amazonia. Parasitology 136: 10971105.

    • Search Google Scholar
    • Export Citation
  • 21.

    da Silva-Nunes M, Moreno M, Conn JE, Gamboa D, Abeles S, Vinetz JM, Ferreira MU, 2012. Amazonian malaria: asymptomatic human reservoirs, diagnostic challenges, environmentally driven changes in mosquito vector populations, and the mandate for sustainable control strategies. Acta Trop 121: 281291.

    • Search Google Scholar
    • Export Citation
  • 22.

    Kimura M, Kaneko O, Liu Q, Zhou M, Kawamoto F, Wataya Y, Otani S, Yamaguchi Y, Tanabe K, 1997. Identification of the four species of human malaria parasites by nested PCR that targets variant sequences in the small subunit rRNA gene. Parasitol Int 46: 9199.

    • Search Google Scholar
    • Export Citation
  • 23.

    Nazarenko IA, Bhatnagar SK, Hohman RJ, 1997. A closed tube format for amplification and detection of DNA based on energy transfer. Nucleic Acids Res 25: 25162521.

    • Search Google Scholar
    • Export Citation
  • 24.

    Jovel IT, Mejia RE, Banegas E, Piedade R, Alger J, Fontecha G, Ferrreira PE, Veiga MI, Enamorado IG, Bjorkman A, Ursing J, 2011. Drug resistance associated genetic polymorphisms in Plasmodium falciparum and Plasmodium vivax collected in Honduras, Central America. Malar J 10: 376.

    • Search Google Scholar
    • Export Citation
  • 25.

    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.

    • Search Google Scholar
    • Export Citation
  • 26.

    Gama BE, Oliveira NK, Souza JM, Daniel-Ribeiro CT, Ferreira-da-Cruz M de F, 2009. Characterisation of pvmdr1 and pvdhfr genes associated with chemoresistance in Brazilian Plasmodium vivax isolates. Mem Inst Oswaldo Cruz 104: 10091011.

    • Search Google Scholar
    • Export Citation
  • 27.

    Lu F, Lim CS, Nam DH, Kim K, Lin K, Kim TS, Lee HW, Chen JH, Wang Y, Sattabongkot J, Han ET, 2011. Genetic polymorphism in pvmdr1 and pvcrt-o genes in relation to in vitro drug susceptibility of Plasmodium vivax isolates from malaria-endemic countries. Acta Trop 117: 6975.

    • Search Google Scholar
    • Export Citation
  • 28.

    Mint Lekweiry K, Ould Mohamed Salem Boukhary A, Gaillard T, Wurtz N, Bogreau H, Hafid JE, Trape JF, Bouchiba H, Ould Ahmedou Salem MS, Pradines B, Rogier C, Basco LK, Briolant S, 2012. Molecular surveillance of drug-resistant Plasmodium vivax using pvdhfr, pvdhps and pvmdr1 markers in Nouakchott, Mauritania. J Antimicrob Chemother 67: 367374.

    • Search Google Scholar
    • Export Citation
  • 29.

    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.

    • Search Google Scholar
    • Export Citation
  • 30.

    Sharrock WW, Suwanarusk R, Lek-Uthai U, Edstein MD, Kosaisavee V, Travers T, Jaidee A, Sriprawat K, Price RN, Nosten F, Russell B, 2008. Plasmodium vivax trophozoites insensitive to chloroquine. Malar J 7: 94.

    • Search Google Scholar
    • Export Citation
  • 31.

    Russell B, Chalfein F, Prasetyorini B, Kenangalem E, Piera K, Suwanarusk R, Brockman A, Prayoga P, Sugiarto P, Cheng Q, Tjitra E, Anstey NM, Price RN, 2008. Determinants of in vitro drug susceptibility testing of Plasmodium vivax. Antimicrob Agents Chemother 52: 10401045.

    • Search Google Scholar
    • Export Citation
  • 32.

    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.

    • Search Google Scholar
    • Export Citation
  • 33.

    Plowe CV, Roper C, Barnwell JW, Happi CT, Joshi HH, Mbacham W, Meshnick SR, Mugittu K, Naidoo I, Price RN, Shafer RW, Sibley CH, Sutherland CJ, Zimmerman PA, Rosenthal PJ, 2007. World Antimalarial Resistance Network (WARN) III: molecular markers for drug resistant malaria. Malar J 6: 121.

    • Search Google Scholar
    • Export Citation
Past two years Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 307 133 30
PDF Downloads 96 49 2
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 

 

 

Single-Nucleotide Polymorphism and Copy Number Variation of the Multidrug Resistance-1 Locus of Plasmodium vivax: Local and Global Patterns

Rosa del Carmen Miluska Vargas-RodríguezDepartment of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; La Jolla Bioengineering Institute, San Diego, California

Search for other papers by Rosa del Carmen Miluska Vargas-Rodríguez in
Current site
Google Scholar
PubMed
Close
,
Melissa da Silva BastosDepartment of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; La Jolla Bioengineering Institute, San Diego, California

Search for other papers by Melissa da Silva Bastos in
Current site
Google Scholar
PubMed
Close
,
Maria José MenezesDepartment of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; La Jolla Bioengineering Institute, San Diego, California

Search for other papers by Maria José Menezes in
Current site
Google Scholar
PubMed
Close
,
Pamela Orjuela-SánchezDepartment of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; La Jolla Bioengineering Institute, San Diego, California

Search for other papers by Pamela Orjuela-Sánchez in
Current site
Google Scholar
PubMed
Close
, and
Marcelo U. FerreiraDepartment of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; La Jolla Bioengineering Institute, San Diego, California

Search for other papers by Marcelo U. Ferreira in
Current site
Google Scholar
PubMed
Close
Restricted access

Emerging resistance to chloroquine (CQ) poses a major challenge for Plasmodium vivax malaria control, and nucleotide substitutions and copy number variation in the P. vivax multidrug resistance 1 (pvmdr-1) locus, which encodes a digestive vacuole membrane transporter, may modulate this phenotype. We describe patterns of genetic variation in pvmdr-1 alleles from Acre and Amazonas in northwestern Brazil, and compare then with those reported in other malaria-endemic regions. The pvmdr-1 mutation Y976F, which is associated with CQ resistance in Southeast Asia and Oceania, remains rare in northwestern Brazil (1.8%) and its prevalence mirrors that of CQ resistance worldwide. Gene amplification of pvmdr-1, which is associated with mefloquine resistance but increased susceptibility to CQ, remains relatively rare in northwestern Brazil (0.9%) and globally (< 4%), but became common (> 10%) in Tak Province, Thailand, possibly because of drug-mediated selection. The global database we have assembled provides a baseline for further studies of genetic variation in pvmdr-1 and drug resistance in P. vivax malaria.

Author Notes

* Address correspondence to Marcelo U. Ferreira, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1374, 05508-900 São Paulo, Brazil. E-mail: muferrei@usp.br
† These authors contributed equally to this article.

Financial support: This study was supported by research grants from the National Institutes of Health (RO1 AI 075416 to Marcelo U. Ferreira and U19 AI089681 to Joseph M. Vinetz) and the Fundação de Amparo à Pesquisa do Estado de São Paulo (2010/51835-7). Rosa del Carmen Miluska Vargas-Rodriguez, Pamela Orjuela-Sánchez, and Marcelo Urbano Ferreira currently receive or have received scholarships from the Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil.

Authors' addresses: Rosa del Carmen Miluska Vargas-Rodríguez, Maria José Menezes, Melissa da Silva Bastos, and Marcelo U. Ferreira, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil, E-mails: miluz_vr@hotmail.com, mjmeneze@usp.br, melissabastos@yahoo.com.br, and muferrei@usp.br. Pamela Orjuela-Sánchez, La Jolla Bioengineering Institute, San Diego, CA, E-mail: pamelaorjuela@gmail.com.

Save