Palang ChotsiriIssaka ZongoPaul MilliganYves Daniel CompaoreAnyirékun Fabrice SoméDaniel ChandramohanWarunee HanpithakpongFrançois NostenBrian GreenwoodPhilip J. RosenthalNicholas J. WhiteJean Bosco OuédraogoJoel TarningLondon School of Hygiene & Tropical MedicineUniversity of California, San FranciscoMahidol UniversityNuffield Department of Clinical MedicineInstitut de Recherche en Sciences de la Santé2020-01-272020-01-272019-12-01Nature Communications. Vol.10, No.1 (2019)204117232-s2.0-85060817483https://repository.li.mahidol.ac.th/handle/20.500.14594/50019© 2019, The Author(s). 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 E MAX -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.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyChemistryArticleSCOPUS10.1038/s41467-019-08297-9