• 1.

    Pukrittayakamee S, Vanijanonta S, Chantra A, Clemens R, White NJ, 1994. Blood stage antimalarial efficacy of primaquine in Plasmodium vivax malaria. J Infect Dis 169: 932935.

    • Search Google Scholar
    • Export Citation
  • 2.

    Baird JK, Lacy MD, Basri H, Barcus MJ, Maguire JD, Bangs MJ, Gramzinski R, Sismadi P, Krisin, Ling J, Wiady I, Kusumaningsih M, Jones TR, Fryauff DJ & Hoffman SL 2001. Randomized, parallel placebo-controlled trial of primaquine for malaria prophylaxis in Papua, Indonesia. Clin Infect Dis 33: 19901997.

    • Search Google Scholar
    • Export Citation
  • 3.

    Soto J, Toledo J, Rodriquez M, Sanchez J, Herrera R, Padilla J, Berman J, 1998. Primaquine prophylaxis against malaria in nonimmune Colombian soldiers: efficacy and toxicity. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 129: 241244.

    • Search Google Scholar
    • Export Citation
  • 4.

    Bunnag D, Karbwang J, Thanavibul A, Chittamas S, Ratanapongse Y, Chalermrut K, Bangchang KN, Harinasuta T, 1994. High dose of primaquine in primaquine resistant vivax malaria. Trans R Soc Trop Med Hyg 88: 218219.

    • Search Google Scholar
    • Export Citation
  • 5.

    Wilairatana P, Silachamroon U, Krudsood S, Singhasivanon P, Treeprasertsuk S, Bussaratid V, Phumratanaprapin W, Srivilirit S, Looareesuwan S, 1999. Efficacy of primaquine regimens for primaquine-resistant Plasmodium vivax malaria in Thailand. Am J Trop Med Hyg 61: 973977.

    • Search Google Scholar
    • Export Citation
  • 6.

    Luxemburger C, van Vugt M, Jonathan S, McGready R, Looareesuwan S, White NJ, Nosten F, 1999. Treatment of vivax malaria on the western border of Thailand. Trans R Soc Trop Med Hyg 93: 433438.

    • Search Google Scholar
    • Export Citation
  • 7.

    Krudsood S, Tangpukdee N, Wilairatana P, Phophak N, Baird JK, Brittenham GM, Looareesuwan S, 2008. High-dose primaquine regimens against relapse of Plasmodium vivax malaria. Am J Trop Med Hyg 78: 736740.

    • Search Google Scholar
    • Export Citation
  • 8.

    Silachamroon U, Krudsood S, Treeprasertsuk S, Wilairatana P, Chalearmrult K, Mint HY, Maneekan P, White NJ, Gourdeuk VR, Brittenham GM, Looareesuwan S, 2003. Clinical trial of oral artesunate with or without high-dose primaquine for the treatment of vivax malaria in Thailand. Am J Trop Med Hyg 69: 1418.

    • Search Google Scholar
    • Export Citation
  • 9.

    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
  • 10.

    World Health Organisation Global Malaria Programme, 2006. The Treatment of Malaria. Geneva: WHO.

  • 11.

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

  • 12.

    Alving AS, Arnold J, Hockwald RS, Clayman CB, Dern RJ, Beutler E, Flanagan CL, 1955. Potentiation of the curative action of primaquine in vivax malaria by quinine and chloroquine. J Lab Clin Med 46: 301306.

    • Search Google Scholar
    • Export Citation
  • 13.

    Pukrittayakamee S, Chantra A, Simpson JA, Vanijanonta S, Clemens RS, White NJ, 2000. Therapeutic responses to different antimalarial drugs in vivax malaria. Antimicrob Agents Chemother 44: 16801685.

    • Search Google Scholar
    • Export Citation

 

 

 

 

A Comparison of Two Short-Course Primaquine Regimens for the Treatment and Radical Cure of Plasmodium vivax Malaria in Thailand

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  • 1 Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; The Royal Institute, Grand Palace, Bangkok, Thailand; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Churchill Hospital, Oxford, United Kingdom

Thai adult males (N = 85) with acute Plasmodium vivax malaria and normal glucose-6-phosphate dehydrogenase screening were randomized to receive 30 mg or 60 mg primaquine daily for 7 days (N = 43 and 42, respectively). The regimens were well tolerated and all patients recovered fully. Median fever clearance (47 hours; range 4 to 130 hours), mean ± SD parasite clearance times (87.7 ± 25.3 hours), gametocyte clearance, and adverse effects were similar in the 2 groups. Two patients, 1 from each group, had a 30% reduction in hematocrit. The cumulative 28 day relapse rate (95% confidence interval) by Kaplan Meier survival analysis was 29% (16–49%) in the 30 mg group compared with 7% (2–24%) in the 60 mg group; P = 0.027. Comparison with previous data obtained at this same site suggests that the recurrences comprised approximately 17% recrudescences and 12% relapses in the 30 mg/day group compared with 3% recrudescences and 4% relapses in the 60 mg/day group. These data suggest that the dose-response relationships for primaquine's asexual stage and hypnozoitocidal activities in-vivo are different. A 1 week course of primaquine 60 mg daily is an effective treatment of vivax malaria in this region.

Author Notes

*Address correspondence to Nicholas J. White, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. E-mail: nickw@tropmedres.ac

Financial support: This study was part of the Wellcome Trust Mahidol University-Oxford Tropical Medicine Research Programme funded by the Wellcome Trust of Great Britain.

Authors' addresses: Sasithon Pukrittayakamee, Mallika Imwong, Kesinee Chotivanich, Pratap Singhasivanon, Nicholas P. J. Day, and Nicholas J. White, Department of Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand, E-mails: sasithon@tropmedres.ac, noi@tropmedres.ac, nok@tropmedres.ac, tmpsh@mahidol.ac.th, nickd@tropmedres.ac, and nickw@tropmedres.ac.

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