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Title: Pharmacokinetic predictors for recurrent malaria after dihydroartemisinin- piperaquine treatment of uncomplicated malaria in ugandan infants
Authors: Darren J. Creek
Victor Bigira
Shelley McCormack
Emmanuel Arinaitwe
Humphrey Wanzira
Abel Kakuru
Jordan W. Tappero
Taylor G. Sandison
Niklas Lindegardh
Francois Nosten
Francesca T. Aweeka
Sunil Parikh
University of Melbourne
University of California, San Francisco
Centers for Disease Control and Prevention
University of Washington School of Medicine
Yale University
Makerere University Medical School
Mahidol University
Shoklo Malaria Research Unit
Nuffield Department of Clinical Medicine
Keywords: Medicine
Issue Date: 1-Jun-2013
Citation: Journal of Infectious Diseases. Vol.207, No.11 (2013), 1646-1654
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 <2 years of age. Piperaquine exposure on day 7 correlated with an increased risk of recurrent malaria after DP treatment in children receiving TMP-SMX prophylaxis. Interestingly, despite strong associations, infants remained at risk for malaria, even if they had residual levels of piperaquine. © 2013 The Author.
ISSN: 00221899
Appears in Collections:Scopus 2011-2015

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