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

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

Author information

1
Faculty of Tropical Medicine, Department of Clinical Pharmacology, Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, 10400, Thailand.
2
Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso.
3
Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, United Kingdom.
4
Department of Disease Control, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, United Kingdom.
5
Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, London, OX3 7LJ, United Kingdom.
6
Faculty of Tropical Medicine, Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Mae Sot, 63110, Thailand.
7
Department of Medicine, University of California, Box 0811, San Francisco, CA 94143, CA, USA.
8
Faculty of Tropical Medicine, Department of Clinical Pharmacology, Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, 10400, Thailand. joel@tropmedres.ac.
9
Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, London, OX3 7LJ, United Kingdom. joel@tropmedres.ac.

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.

PMID:
30696903
PMCID:
PMC6351525
DOI:
10.1038/s41467-019-08297-9
[Indexed for MEDLINE]
Free PMC Article

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