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

Palang Chotsiri; Issaka Zongo; Paul Milligan ORCID logo; Yves Daniel Compaore ORCID logo; Anyirékun Fabrice Somé; Daniel Chandramohan ORCID logo; Warunee Hanpithakpong; François Nosten ORCID logo; Brian Greenwood ORCID logo; Philip J Rosenthal; +3 more... Nicholas J White; Jean-Bosco Ouédraogo; Joel Tarning ORCID logo; (2019) Optimal dosing of dihydroartemisinin-piperaquine for seasonal malaria chemoprevention in young children. Nature communications, 10 (1). 480-. ISSN 2041-1723 DOI: 10.1038/s41467-019-08297-9
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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.


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