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Identifying an optimal dihydroartemisinin-piperaquine dosing regimen for malaria prevention in young Ugandan children.
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.
Afiliación
  • Wallender E; Department of Clinical Pharmacy, University of California, San Francisco, San Francisco, CA, USA.
  • Ali AM; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
  • Hughes E; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
  • Kakuru A; Infectious Diseases Research Collaboration, Kampala, Uganda.
  • Jagannathan P; Department of Medicine, Stanford University, Palo Alto, CA, USA.
  • Muhindo MK; Infectious Diseases Research Collaboration, Kampala, Uganda.
  • Opira B; Infectious Diseases Research Collaboration, Kampala, Uganda.
  • Whalen M; Department of Clinical Pharmacy, University of California, San Francisco, San Francisco, CA, USA.
  • Huang L; Department of Clinical Pharmacy, University of California, San Francisco, San Francisco, CA, USA.
  • Duvalsaint M; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Legac J; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Kamya MR; Infectious Diseases Research Collaboration, Kampala, Uganda.
  • Dorsey G; Department of Medicine, Makerere University, Kampala, Uganda.
  • Aweeka F; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Rosenthal PJ; Department of Clinical Pharmacy, University of California, San Francisco, San Francisco, CA, USA.
  • Savic RM; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Nat Commun ; 12(1): 6714, 2021 11 18.
Article en En | MEDLINE | ID: mdl-34795281
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Plasmodium falciparum / Quinolinas / Malaria Falciparum / Complicaciones Parasitarias del Embarazo / Artemisininas Tipo de estudio: Clinical_trials / Incidence_studies / Prognostic_studies / Risk_factors_studies Límite: Child / Child, preschool / Female / Humans / Infant / Male / Pregnancy País/Región como asunto: Africa Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Plasmodium falciparum / Quinolinas / Malaria Falciparum / Complicaciones Parasitarias del Embarazo / Artemisininas Tipo de estudio: Clinical_trials / Incidence_studies / Prognostic_studies / Risk_factors_studies Límite: Child / Child, preschool / Female / Humans / Infant / Male / Pregnancy País/Región como asunto: Africa Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido