• 1.

    World Health Organization, 2015. World Malaria Report 1. Available at: http://www.who.int/malaria/publications/world-malaria-report-2015/report/en/. Accessed January 20, 2016.

    • Search Google Scholar
    • Export Citation
  • 2.

    Ministério da Saúde Brazil, 2015. Boletim Epidemiologico. Available at: http://www.sivep_malaria/relatorio/rel_resumo_nacional_mensal.asp?tx_opcao_agravo=MALARIA&opcao_agravo=B54%20&dt_inicial=01/01/2014&dt_final=31/12/2014&niv_relatorio=NACIONAL. Accessed January 20, 2016.

    • Search Google Scholar
    • Export Citation
  • 3.

    World Health Organization, 2015. Global Technical Strategy for Malaria 2016–2030. Geneva, Switzerland: World Health Organization. Available at: http://www.who.int/malaria/publications/atoz/9789241564991/en/. Accessed January 20, 2016.

    • Search Google Scholar
    • Export Citation
  • 4.

    World Health Organization, 2009. Methods for Surveillance of Antimalarial Drug Efficacy. Geneva, Switzerland: World Health Organization. Available at: http://www.who.int/malaria/publications/atoz/9789241597531/en/.

    • Search Google Scholar
    • Export Citation
  • 5.

    Pan American Health Organization, 2015. RAVREDA-AMI: Amazon Network for the Surveillance of Antimalarial Drug Resistance (RAVREDA)/Amazon Malaria Initiative (AMI). Available at: http://www.paho.org/english/ad/dpc/cd/ravreda-ami.htm. Accessed August 22, 2015.

    • Search Google Scholar
    • Export Citation
  • 6.

    Departamento de Vigilância Epidemiológica, Brasil Ministério da Saúde, 2010. Guia Prático de Tratamento da Malária no Brazil. Brasilia, Brazil: Ministério da Saúde, 36.

    • Search Google Scholar
    • Export Citation
  • 7.

    Rieckmann KH, Davis DR, Hutton DC, 1989. Plasmodium vivax resistance to chloroquine? Lancet 2: 11831184.

  • 8.

    Price RN, von Seidlein L, Valecha N, Nosten F, Baird JK, White NJ, 2014. Global extent of chloroquine-resistant Plasmodium vivax: a systematic review and meta-analysis. Lancet Infect Dis 14: 982991.

    • Search Google Scholar
    • Export Citation
  • 9.

    Alecrim M das G, Alecrim W, Macedo V, 1999. Plasmodium vivax resistance to chloroquine (R2) and mefloquine (R3) in Brazilian Amazon region. Rev Soc Bras Med Trop 32: 6768.

    • Search Google Scholar
    • Export Citation
  • 10.

    Soto J, Toledo J, Gutierrez P, Luzz M, Llinas N, Cedeno N, Dunne M, Berman J, 2001. Plasmodium vivax clinically resistant to chloroquine in Colombia. Am J Trop Med Hyg 65: 9093.

    • Search Google Scholar
    • Export Citation
  • 11.

    Ruebush TK 2nd, Zegarra J, Cairo J, Andersen EM, Green M, Pillai DR, Marquino W, Huilca M, Arevalo E, Garcia C, Solary L, Kain KC, 2003. Chloroquine-resistant Plasmodium vivax malaria in Peru. Am J Trop Med Hyg 69: 548552.

    • Search Google Scholar
    • Export Citation
  • 12.

    Pan American Health Organization, 2015. Generic Protocols and Flow Diagram for In Vivo Antimalarial Drug-Efficacy Studies in the Americas. Available at: http://www.paho.org/english/ad/dpc/cd/mal-antimalarials.htm. Accessed June, 2015.

    • Search Google Scholar
    • Export Citation
  • 13.

    Imwong M, Sudimack D, Pukrittayakamee S, Osorio L, Carlton JM, Day NP, White NJ, Anderson TJ, 2006. Microsatellite variation, repeat array length, and population history of Plasmodium vivax. Mol Biol Evol 23: 10161018.

    • Search Google Scholar
    • Export Citation
  • 14.

    Imwong M, Boel ME, Pagornrat W, Pimanpanarak M, McGready R, Day NP, Nosten F, White NJ, 2012. The first Plasmodium vivax relapses of life are usually genetically homologous. J Infect Dis 205: 680683.

    • Search Google Scholar
    • Export Citation
  • 15.

    Thanapongpichat S, McGready R, Luxemburger C, Day NP, White NJ, Nosten F, Snounou G, Imwong M, 2013. Microsatellite genotyping of Plasmodium vivax infections and their relapses in pregnant and non-pregnant patients on the Thai-Myanmar border. Malar J 12: 275.

    • Search Google Scholar
    • Export Citation
  • 16.

    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: 564567.

    • Search Google Scholar
    • Export Citation
  • 17.

    McCollum AM, Soberon V, Salas CJ, Santolalla ML, Udhayakumar V, Escalante AA, Graf PC, Durand S, Cabezas C, Bacon DJ, 2014. Genetic variation and recurrent parasitaemia in Peruvian Plasmodium vivax populations. Malar J 13: 67.

    • Search Google Scholar
    • Export Citation
  • 18.

    Llanos-Cuentas A, Lacerda MV, Rueangweerayut R, Krudsood S, Gupta SK, Kochar SK, Arthur P, Chuenchom N, Mohrle JJ, Duparc S, Ugwuegbulam C, Kleim JP, Carter N, Green JA, Kellam L, 2014. Tafenoquine plus chloroquine for the treatment and relapse prevention of Plasmodium vivax malaria (DETECTIVE): a multicentre, double-blind, randomised, phase 2b dose-selection study. Lancet 383: 10491058.

    • Search Google Scholar
    • Export Citation
  • 19.

    Durand S, Cabezas C, Lescano AG, Galvez M, Gutierrez S, Arrospide N, Alvarez C, Santolalla ML, Bacon DJ, Graf PC, 2014. Efficacy of three different regimens of primaquine for the prevention of relapses of Plasmodium vivax malaria in the Amazon Basin of Peru. Am J Trop Med Hyg 91: 1826.

    • Search Google Scholar
    • Export Citation
  • 20.

    Ruebush TK, Levin A, Gonzaga V, Neyra D, Marquino W, 2003. Evaluation of a simple operational approach for monitoring resistance to antimalarial drugs in Peru. Trop Med Int Health 8: 910916.

    • Search Google Scholar
    • Export Citation
  • 21.

    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
  • 22.

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

    • Search Google Scholar
    • Export Citation
  • 23.

    Marques MM, Costa MR, Santana Filho FS, Vieira JL, Nascimento MT, Brasil LW, Nogueira F, Silveira H, Reyes-Lecca RC, Monteiro WM, Lacerda MV, Alecrim MG, 2014. Plasmodium vivax chloroquine resistance and anemia in the western Brazilian Amazon. Antimicrob Agents Chemother 58: 342347.

    • Search Google Scholar
    • Export Citation
  • 24.

    Imwong M, Snounou G, Pukrittayakamee S, Tanomsing N, Kim JR, Nandy A, Guthmann JP, Nosten F, Carlton J, Looareesuwan S, Nair S, Sudimack D, Day NP, Anderson TJ, White NJ, 2007. Relapses of Plasmodium vivax infection usually result from activation of heterologous hypnozoites. J Infect Dis 195: 927933.

    • Search Google Scholar
    • Export Citation
  • 25.

    Chen N, Auliff A, Rieckmann K, Gatton M, Cheng Q, 2007. Relapses of Plasmodium vivax infection result from clonal hypnozoites activated at predetermined intervals. J Infect Dis 195: 934941.

    • Search Google Scholar
    • Export Citation
  • 26.

    Collins WE, 2007. Further understanding the nature of relapse of Plasmodium vivax infection. J Infect Dis 195: 919920.

  • 27.

    Anez A, Moscoso M, Laguna A, Garnica C, Melgar V, Cuba M, Gutierrez S, Ascaso C, 2015. Resistance of infection by Plasmodium vivax to chloroquine in Bolivia. Malar J 14: 261.

    • Search Google Scholar
    • Export Citation
  • 28.

    Baird JK, Wiady I, Fryauff DJ, Sutanihardja MA, Leksana B, Widjaya H, Kysdarmanto Subianto B, 1997. In vivo resistance to chloroquine by Plasmodium vivax and Plasmodium falciparum at Nabire, Irian Jaya, Indonesia. Am J Trop Med Hyg 56: 627631.

    • Search Google Scholar
    • Export Citation
  • 29.

    Bennett JW, Pybus BS, Yadava A, Tosh D, Sousa JC, McCarthy WF, Deye G, Melendez V, Ockenhouse CF, 2013. Primaquine failure and cytochrome P-450 2D6 in Plasmodium vivax malaria. N Engl J Med 369: 13811382.

    • Search Google Scholar
    • Export Citation
  • 30.

    Hill DR, Baird JK, Parise ME, Lewis LS, Ryan ET, Magill AJ, 2006. Primaquine: report from CDC expert meeting on malaria chemoprophylaxis I. Am J Trop Med Hyg 75: 402415.

    • Search Google Scholar
    • Export Citation
  • 31.

    World Health Organization, 2015. Guidelines for the Treatment of Malaria. Geneva, Switzerland: World Health Organization. Available at: http://www.who.int/malaria/publications/atoz/9789241549127/en/. Accessed January 20, 2016.

    • Search Google Scholar
    • Export Citation
  • 32.

    Collins WE, Jeffery GM, 1996. Primaquine resistance in Plasmodium vivax. Am J Trop Med Hyg 55: 243249.

  • 33.

    Baird JK, Hoffman SL, 2004. Primaquine therapy for malaria. Clin Infect Dis 39: 13361345.

  • 34.

    Centers for Disease Control and Prevention, 2015. Malaria Treatment (United States). Atlanta, GA: Centers for Disease Control and Prevention. Available at: http://www.cdc.gov/malaria/diagnosis_treatment/treatment.html. Accessed January 20, 2016.

    • Search Google Scholar
    • Export Citation
  • 35.

    Lin JT, Hathaway NJ, Saunders DL, Lon C, Balasubramanian S, Kharabora O, Gosi P, Sriwichai S, Kartchner L, Chuor CM, Satharath P, Lanteri C, Bailey JA, Juliano JJ, 2015. Using amplicon deep sequencing to detect genetic signatures of Plasmodium vivax relapse. J Infect Dis 212: 9991008.

    • Search Google Scholar
    • Export Citation
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Efficacy of Chloroquine and Primaquine for the Treatment of Uncomplicated Plasmodium vivax Malaria in Cruzeiro do Sul, Brazil

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  • 1 Acre State Health Secretariat, Acre State, Brazil.
  • | 2 Instituto Evandro Chagas, Brazilian Ministry of Health, Ananindeua, Brazil.
  • | 3 Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia.
  • | 4 Atlanta Research and Education Foundation, Decatur, Georgia.
  • | 5 National Malaria Control Program, Brazilian Ministry of Health, Brasilia, Brazil.
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We evaluated the efficacy of chloroquine and primaquine on uncomplicated Plasmodium vivax malaria in Cruzeiro do Sul, Brazil, in 2014. Patients ≥ 5 years of age with either fever or history of fever, and laboratory-confirmed P. vivax monoinfection received chloroquine (total dose = 25 mg/kg) and primaquine (total dose = 3.5 mg/kg), and were followed up for 168 days (24 weeks). We used microsatellite genotyping to differentiate recurrent infections caused by heterologous parasites from those caused by homologous ones. No new P. vivax episode occurred by Day 28 among 119 enrolled patients, leading to Day 28, with adequate clinical and parasitological response (ACPR) of 100% (95% confidence interval [CI] = 96.7–100%). Twenty-eight P. vivax episodes occurred by Day 168, with uncorrected ACPR of 69.9% (95% CI = 59.5–79.0%). Fifteen of these episodes were caused by either homologous haplotypes or haplotypes that could not be determined. Excluding the 13 recurrent episodes caused by heterologous parasites, Day 168 microsatellite-corrected ACPR was estimated at 81.2% (95% CI = 71.0–89.1%). Chloroquine and primaquine remain efficacious to treat acute uncomplicated P. vivax infection, but moderate recurrence rates were observed within 24 weeks of follow-up.

Author Notes

* Address correspondence to Alexandre Macedo de Oliveira, Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, 1600 Clifton Rd., MS A-06, Atlanta, GA 30329. E-mail: acq7@cdc.gov

Financial support: Funding for this evaluation was partially provided by the U.S. Agency for International Development (USAID) through the Amazon Malaria Initiative (AMI). Stella M. Chenet was supported by the American Society of Microbiology/CDC Postdoctoral Fellowship.

Authors' addresses: Suiane Negreiros, Samela Farias, and Thayna Maria Holanda de Souza, Acre State Health Secretariat, Cruzeiro do Sul, Acre, Brazil, E-mails: omsvalle@hotmail.com, samela_86@hotmail.com, and thayna.souza21@gmail.com. Giselle Maria Rachid Viana and Marinete Marins Povoa, Instituto Evandro Chagas, Brazilian Ministry of Health, Ananindeua, Brazil, E-mails: giselleviana@iec.pa.gov.br and povoamm@gmail.com. Sheila Akinyi Okoth, Stella M. Chenet, and Alexandre Macedo de Oliveira, Malaria Branch, Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, GA, E-mails: jyo3@cdc.gov, ynw0@cdc.gov, and acq7@cdc.gov. Paola Marchesini and Ana Carolina Faria e Silva Santelli, National Malaria Control Program, Brazilian Ministry of Health, Brasilia, Brazil, E-mails: paola.marchesini@saude.gov.br and anacarolina.santelli@gmail.com. Venkatachalam Udhayakumar, Malaria Branch, Centers for Disease Control and Prevention, Chamblee, GA, E-mail: vxu0@cdc.gov.

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