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

Journal article

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.

Authors: Creek, D; Bigira, V; McCormack, S; Arinaitwe, E; Wanzira, H

• Publication status: Published
• Journal: Journal of infectious diseases
• Volume: 207
• Issue: 11
• Pages: 1646-1654
• Publication date: 2013-06-01
• DOI: 10.1093/infdis/jit078
• EISSN: 1537-6613
• ISSN: 0022-1899
• Language: English
• Keywords: Plasma; Time Factors; Humans; Antimalarials; Treatment Outcome; Malaria; Female; Uganda; Chemoprevention; Infant; Follow-Up Studies; Artemisinins; Quinolines; Trimethoprim-Sulfamethoxazole Combination; Male; Secondary Prevention; Prospective Studies