Pharmacokinetic predictors for recurrent malaria after dihydroartemisinin- piperaquine treatment of uncomplicated malaria in Ugandan infants

Darren John Creek, Victor Bigira, Shelley McCormack, Emmanuel Arinaitwe, Humphrey Wanzira, Abel Kakuru, Jordan W Tappero, Taylor G Sandison, Niklas Lindegardh, Francois H Nosten, Francesca T Aweeka, Sunil Parikh

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Abstract

Background. Although dihydroartemisinin-piperaquine (DP) is used primarily in children, pharmacokinetic/pharmacodynamic (PK/PD) data on DP use in young children are lacking.Methods. We conducted a prospective PK/PD study of piperaquine in 107 young children in Uganda. Samples were collected up to 28 days after 218 episodes of malaria treatment, which occurred during follow-up periods of up to 5 months. Malaria follow-up was conducted actively to day 28 and passively to day 63.Results. The median capillary piperaquine concentration on day 7 after treatment was 41.9 ng/mL. Low piperaquine concentrations were associated with an increased risk of recurrent malaria for up to 42 days, primarily in those receiving trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis. In children not receiving TMP-SMX, low piperaquine concentrations were only modestly associated with an increased risk of recurrent malaria. However, for children receiving TMP-SMX, associations were strong and evident for all sampling days, with PQ concentrations of =27.3 ng/mL on day 7 associated with a greatly increased risk of recurrent malaria. Notably, of 132 cases of recurrent malaria, 119 had detectable piperaquine concentrations at the time of presentation with recurrent malaria.Conclusions. These piperaquine PK/PD data represent the first in children
Original languageEnglish
Pages (from-to)1646 - 1654
Number of pages9
JournalJournal of Infectious Diseases
Volume207
Issue number11
DOIs
Publication statusPublished - 2013
Externally publishedYes

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