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Optimal dosing of dihydroartemisinin-piperaquine for seasonal malaria chemoprevention in young children

Author

Listed:
  • Palang Chotsiri

    (Mahidol University)

  • Issaka Zongo

    (Institut de Recherche en Sciences de la Santé)

  • Paul Milligan

    (London School of Hygiene and Tropical Medicine)

  • Yves Daniel Compaore

    (Institut de Recherche en Sciences de la Santé)

  • Anyirékun Fabrice Somé

    (Institut de Recherche en Sciences de la Santé)

  • Daniel Chandramohan

    (London School of Hygiene and Tropical Medicine)

  • Warunee Hanpithakpong

    (Mahidol University)

  • François Nosten

    (University of Oxford
    Mahidol University)

  • Brian Greenwood

    (London School of Hygiene and Tropical Medicine)

  • Philip J. Rosenthal

    (University of California)

  • Nicholas J. White

    (Mahidol University
    University of Oxford)

  • Jean-Bosco Ouédraogo

    (Institut de Recherche en Sciences de la Santé)

  • Joel Tarning

    (Mahidol University
    University of Oxford)

Abstract

Young children are the population most severely affected by Plasmodium falciparum malaria. Seasonal malaria chemoprevention (SMC) with amodiaquine and sulfadoxine-pyrimethamine provides substantial benefit to this vulnerable population, but resistance to the drugs will develop. Here, we evaluate the use of dihydroartemisinin-piperaquine as an alternative regimen in 179 children (aged 2.33–58.1 months). Allometrically scaled body weight on pharmacokinetic parameters of piperaquine result in lower drug exposures in small children after a standard mg per kg dosage. A covariate-free sigmoidal EMAX-model describes the interval to malaria re-infections satisfactorily. Population-based simulations suggest that small children would benefit from a higher dosage according to the WHO 2015 guideline. Increasing the dihydroartemisinin-piperaquine dosage and extending the dose schedule to four monthly doses result in a predicted relative reduction in malaria incidence of up to 58% during the high transmission season. The higher and extended dosing schedule to cover the high transmission period for SMC could improve the preventive efficacy substantially.

Suggested Citation

  • Palang Chotsiri & Issaka Zongo & Paul Milligan & Yves Daniel Compaore & Anyirékun Fabrice Somé & Daniel Chandramohan & Warunee Hanpithakpong & François Nosten & Brian Greenwood & Philip J. Rosenthal &, 2019. "Optimal dosing of dihydroartemisinin-piperaquine for seasonal malaria chemoprevention in young children," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08297-9
    DOI: 10.1038/s41467-019-08297-9
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    Cited by:

    1. Erika Wallender & Ali Mohamed Ali & Emma Hughes & Abel Kakuru & Prasanna Jagannathan & Mary Kakuru Muhindo & Bishop Opira & Meghan Whalen & Liusheng Huang & Marvin Duvalsaint & Jenny Legac & Moses R. , 2021. "Identifying an optimal dihydroartemisinin-piperaquine dosing regimen for malaria prevention in young Ugandan children," Nature Communications, Nature, vol. 12(1), pages 1-13, December.

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