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Identifying an optimal dihydroartemisinin-piperaquine dosing regimen for malaria prevention in young Ugandan children. Nature communications Wallender, E., Ali, A. M., Hughes, E., Kakuru, A., Jagannathan, P., Muhindo, M. K., Opira, B., Whalen, M., Huang, L., Duvalsaint, M., Legac, J., Kamya, M. R., Dorsey, G., Aweeka, F., Rosenthal, P. J., Savic, R. M. 2021; 12 (1): 6714

Abstract

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 15.4ng/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.

View details for DOI 10.1038/s41467-021-27051-8

View details for PubMedID 34795281