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BioMed Central, Malaria Journal, 1(14), 2015

DOI: 10.1186/s12936-015-0908-8

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Variable piperaquine exposure significantly impacts protective efficacy of monthly dihydroartemisinin-piperaquine for the prevention of malaria in Ugandan children

Journal article published in 2015 by Kerstin Sundell, Prasanna Jagannathan ORCID, Liusheng Huang, Victor Bigira, James Kapisi, Mary M. Kakuru, Rada Savic, Moses R. Kamya, Grant Dorsey, Francesca Aweeka
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Abstract Background Anti-malarial chemoprevention with dihydroartemisinin-piperaquine (DHA/PQ) is a promising tool for malaria control, but its efficacy in children may be limited by inadequate drug exposure. Methods Children were enrolled in a non directly-observed trial of DHA/PQ chemoprevention in a high transmission setting in Uganda. Children were randomized at 6 months of age to no chemoprevention (n = 89) or monthly DHA/PQ (n = 87) and followed through 24 months of age, with pharmacokinetic sampling performed at variable times following monthly dosing of DHA/PQ. A previously published pharmacokinetic model was used to estimate piperaquine (PQ) exposure in each child, and associations between PQ exposure and the protective efficacy (PE) of DHA/PQ were explored. Results The incidence of malaria was 6.83 and 3.09 episodes per person year at risk in the no chemoprevention and DHA/PQ arms, respectively (PE 54 %, 95 % CI 39–66 %, P