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Wallender, Erika; Ali, Ali Mohamed; Hughes, Emma; Kakuru, Abel; Jagannathan, Prasanna; Muhindo, Mary Kakuru; Opira, Bishop; Whalen, Meghan; Huang, Liusheng; Duvalsaint, Marvin; Legac, Jenny; Kamya, Moses R.; Dorsey, Grant; Aweeka, Francesca; Rosenthal, Philip J.; Savic, Rada M.

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

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  • Media type: E-Article
  • Title: Identifying an optimal dihydroartemisinin-piperaquine dosing regimen for malaria prevention in young Ugandan children
  • Contributor: Wallender, Erika; Ali, Ali Mohamed; Hughes, Emma; Kakuru, Abel; Jagannathan, Prasanna; Muhindo, Mary Kakuru; Opira, Bishop; Whalen, Meghan; Huang, Liusheng; Duvalsaint, Marvin; Legac, Jenny; Kamya, Moses R.; Dorsey, Grant; Aweeka, Francesca; Rosenthal, Philip J.; Savic, Rada M.
  • imprint: Springer Science and Business Media LLC, 2021
  • Published in: Nature Communications
  • Language: English
  • DOI: 10.1038/s41467-021-27051-8
  • ISSN: 2041-1723
  • Keywords: General Physics and Astronomy ; General Biochemistry, Genetics and Molecular Biology ; General Chemistry ; Multidisciplinary
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:p>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 (<jats:italic>n</jats:italic> = 4573), malaria incidence data (<jats:italic>n</jats:italic> = 326), and <jats:italic>P. falciparum</jats:italic> drug resistance markers from a trial of children randomized to IPT with DP every 12 weeks (<jats:italic>n</jats:italic> = 184) or every 4 weeks (<jats:italic>n</jats:italic> = 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.</jats:p>
  • Access State: Open Access