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Identifying an optimal dihydroartemisinin-piperaquine dosing regimen for malaria prevention in young Ugandan children

Author

Listed:
  • Erika Wallender

    (University of California, San Francisco)

  • Ali Mohamed Ali

    (University of California, San Francisco)

  • Emma Hughes

    (University of California, San Francisco)

  • Abel Kakuru

    (Infectious Diseases Research Collaboration)

  • Prasanna Jagannathan

    (Stanford University)

  • Mary Kakuru Muhindo

    (Infectious Diseases Research Collaboration)

  • Bishop Opira

    (Infectious Diseases Research Collaboration)

  • Meghan Whalen

    (University of California, San Francisco)

  • Liusheng Huang

    (University of California, San Francisco)

  • Marvin Duvalsaint

    (University of California, San Francisco)

  • Jenny Legac

    (University of California, San Francisco)

  • Moses R. Kamya

    (Infectious Diseases Research Collaboration
    Makerere University)

  • Grant Dorsey

    (University of California, San Francisco)

  • Francesca Aweeka

    (University of California, San Francisco)

  • Philip J. Rosenthal

    (University of California, San Francisco)

  • Rada M. Savic

    (University of California, San Francisco)

Abstract

Intermittent preventive treatment (IPT) with dihydroartemisinin-piperaquine (DP) is highly protective against malaria in children, but is not standard in malaria-endemic countries. Optimal DP dosing regimens will maximize efficacy and reduce toxicity and resistance selection. We analyze piperaquine (PPQ) concentrations (n = 4573), malaria incidence data (n = 326), and P. falciparum drug resistance markers from a trial of children randomized to IPT with DP every 12 weeks (n = 184) or every 4 weeks (n = 96) from 2 to 24 months of age (NCT02163447). We use nonlinear mixed effects modeling to establish malaria protective PPQ levels and risk factors for suboptimal protection. Compared to DP every 12 weeks, DP every 4 weeks is associated with 95% protective efficacy (95% CI: 84–99%). A PPQ level of 15.4 ng/mL reduces the malaria hazard by 95%. Malnutrition reduces PPQ exposure. In simulations, we show that DP every 4 weeks is optimal across a range of transmission intensities, and age-based dosing improves malaria protection in young or malnourished children.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27051-8
    DOI: 10.1038/s41467-021-27051-8
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    References listed on IDEAS

    as
    1. Matthew Cairns & Arantxa Roca-Feltrer & Tini Garske & Anne L. Wilson & Diadier Diallo & Paul J. Milligan & Azra C Ghani & Brian M. Greenwood, 2012. "Estimating the potential public health impact of seasonal malaria chemoprevention in African children," Nature Communications, Nature, vol. 3(1), pages 1-9, January.
    2. 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.
    3. Norah Mwebaza & Vincent Cheah & Camilla Forsman & Richard Kajubi & Florence Marzan & Erika Wallender & Grant Dorsey & Philip J Rosenthal & Francesca Aweeka & Liusheng Huang, 2020. "Determination of piperaquine concentration in human plasma and the correlation of capillary versus venous plasma concentrations," PLOS ONE, Public Library of Science, vol. 15(5), pages 1-13, May.
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    Cited by:

    1. Prasanna Jagannathan & Abel Kakuru, 2022. "Malaria in 2022: Increasing challenges, cautious optimism," Nature Communications, Nature, vol. 13(1), pages 1-3, December.

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