Darren J. CreekVictor BigiraShelley McCormackEmmanuel ArinaitweHumphrey WanziraAbel KakuruJordan W. TapperoTaylor G. SandisonNiklas LindegardhFrancois NostenFrancesca T. AweekaSunil ParikhUniversity of MelbourneUniversity of California, San FranciscoCenters for Disease Control and PreventionUniversity of Washington School of MedicineYale UniversityMakerere University Medical SchoolMahidol UniversityShoklo Malaria Research UnitNuffield Department of Clinical Medicine2018-10-192018-10-192013-06-01Journal of Infectious Diseases. Vol.207, No.11 (2013), 1646-1654002218992-s2.0-84877277245https://repository.li.mahidol.ac.th/handle/20.500.14594/32327Background. 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.Mahidol UniversityMedicineArticleSCOPUS10.1093/infdis/jit078