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

Nat Commun. 2019 Jan 29;10(1):480. doi: 10.1038/s41467-019-08297-9.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimalarials / administration & dosage*
  • Antimalarials / pharmacokinetics
  • Artemisinins / administration & dosage*
  • Artemisinins / pharmacokinetics
  • Chemoprevention
  • Child, Preschool
  • Drug Therapy, Combination
  • Female
  • Humans
  • Malaria, Falciparum / prevention & control*
  • Male
  • Quinolines / administration & dosage*
  • Quinolines / pharmacokinetics
  • Seasons

Substances

  • Antimalarials
  • Artemisinins
  • Quinolines
  • dihydroartemisinin
  • piperaquine