Dihydroartemisinin—Piperaquine Rescue Treatment of Multidrug-resistant Plasmodium falciparum Malaria in Pregnancy: A Preliminary Report

Marcus J. Rijken Shoklo Malaria Research Unit, Mae Sot, Tak, Thailand; Academic Medical Center, Amsterdam, The Netherlands; Mahidol-Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand; Centre for Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom

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Rose McGready Shoklo Malaria Research Unit, Mae Sot, Tak, Thailand; Academic Medical Center, Amsterdam, The Netherlands; Mahidol-Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand; Centre for Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom

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Machteld E. Boel Shoklo Malaria Research Unit, Mae Sot, Tak, Thailand; Academic Medical Center, Amsterdam, The Netherlands; Mahidol-Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand; Centre for Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom

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Marion Barends Shoklo Malaria Research Unit, Mae Sot, Tak, Thailand; Academic Medical Center, Amsterdam, The Netherlands; Mahidol-Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand; Centre for Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom

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Stephane Proux Shoklo Malaria Research Unit, Mae Sot, Tak, Thailand; Academic Medical Center, Amsterdam, The Netherlands; Mahidol-Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand; Centre for Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom

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Mupawjay Pimanpanarak Shoklo Malaria Research Unit, Mae Sot, Tak, Thailand; Academic Medical Center, Amsterdam, The Netherlands; Mahidol-Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand; Centre for Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom

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Pratap Singhasivanon Shoklo Malaria Research Unit, Mae Sot, Tak, Thailand; Academic Medical Center, Amsterdam, The Netherlands; Mahidol-Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand; Centre for Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom

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François Nosten Shoklo Malaria Research Unit, Mae Sot, Tak, Thailand; Academic Medical Center, Amsterdam, The Netherlands; Mahidol-Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand; Centre for Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United Kingdom

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Dihydroartemisinin-piperaquine (DHA-PPQ) is a promising new artemisinin combination treatment. There are no published data on the intentional use of the drug in pregnancy. Between June 2006 and January 2007, 50 Karen pregnant women with recurrent P. falciparum infections, despite 7-day treatments with quinine or artesunate (+/−clindamycin) or both, were treated with DHA-PPQ. This rescue treatment was effective and well tolerated and there was no evidence of toxicity for the mothers or the fetus. The PCR adjusted cure rate by Kaplan Meier analysis at day 63 was 92.2% (95% CI: 76.9–97.4).

Author Notes

  • 1

    Nosten F, McGready R, Mutabingwa T, 2007. Case management of malaria in pregnancy. Lancet Infect Dis 7 :118–125.

  • 2

    Brockman A, Price RN, van Vugt M, Heppner DG, Walsh D, Sookto P, Wimonwattrawatee T, Looareesuwan S, White NJ, Nosten F, 2000. Plasmodium falciparum antimalarial drug susceptibility on the north-western border of Thailand during five years of extensive use of artesunate-mefloquine. Trans R Soc Trop Med Hyg 94 :537–544.

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  • 3

    Dolan G, ter Kuile FO, Jacoutot V, White NJ, Luxemburger C, Malankirii L, Chongsuphajaisiddhi T, Nosten F, 1993. Bed nets for the prevention of malaria and anaemia in pregnancy. Trans R Soc Trop Med Hyg 87 :620–626.

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  • 4

    McGready R, Hamilton KA, Simpson JA, Cho T, Luxemburger C, Edwards R, Looareesuwan S, White NJ, Nosten F, Lindsay SW, 2001. Safety of the insect repellent N,N-diethyl-M-toluamide (DEET) in pregnancy. Am J Trop Med Hyg 65 :285–289.

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  • 5

    McGready R, Cho T, Samuel, Villegas L, Brockman A, van Vugt M, Looareesuwan S, White NJ, Nosten F, 2001. Randomized comparison of quinine-clindamycin versus artesunate in the treatment of falciparum malaria in pregnancy. Trans R Soc Trop Med Hyg 95 :651–656.

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  • 6

    McGready R, Stepniewska K, Lindegardh N, Ashley EA, La Y, Singhasivanon P, White NJ, Nosten F, 2006. The pharmacokinetics of artemether and lumefantrine in pregnant women with uncomplicated falciparum malaria. Eur J Clin Pharmacol 62 :1021–1031.

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  • 7

    Ashley EA, McGready R, Hutagalung R, Phaiphun L, Slight T, Proux S, Thwai KL, Barends M, Looareesuwan S, White NJ, Nosten F, 2005. A randomized, controlled study of a simple, once-daily regimen of dihydroartemisinin-piperaquine for the treatment of uncomplicated, multidrug-resistant falciparum malaria. Clin Infect Dis 41 :425–432.

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  • 8

    Kamya MR, Yeka A, Bukirwa H, Lugemwa M, Rwakimari JB, Staedke SG, Talisuna AO, Greenhouse B, Nosten F, Rosenthal PJ, Wabwire-Mangen F, Dorsey G, 2007. Artemether-lumefantrine versus dihydroartemisinin-piperaquine for treatment of malaria: a randomized trial. PLoS Clin Trials 18 :e20.

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  • 9

    McGready R, Keo NK, Villegas L, White NJ, Looareesuwan S, Nosten F, 2003. Artesunate-atovaquone-proguanil rescue treatment of multidrug-resistant Plasmodium falciparum malaria in pregnancy: a preliminary report. Trans R Soc Trop Med Hyg 97 :592–594.

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  • 10

    Ashley EA, Krudsood S, Phaiphun L, Srivilairit S, McGready R, Leowattana W, Hutagalung R, Wilairatana P, Brockman A, Looareesuwan S, Nosten F, White NJ, 2004. Randomized, controlled dose-optimization studies of dihydroartemisinin-piperaquine for the treatment of uncomplicated multidrug-resistant falciparum malaria in Thailand. J Infect Dis 190 :1773–1782.

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