| Summary: | Background: Treatment for severe malaria must be prompt with effective parenteral antimalarial drugs for at least
24 h to achieve fast parasite clearance, and when the patient can tolerate oral therapy, treatment should be
completed with effective artemisinin based combination therapy (ACT) for complete parasite clearance and to
prevent recrudescence. We evaluated piperaquine concentration and malaria treatment outcomes among Ugandan
children treated for severe malaria with intravenous artesunate (AS) or quinine (QN) plus dihydroartemisininpiperaquine (DP), in Tororo District Hospital in Eastern Uganda.
Methods: Capillary blood piperaquine concentration data were obtained from a randomized clinical trial whose
objective was to evaluate parasite clearance, 42-day parasitological treatment outcomes and safety, following
treatment of severe malaria with intravenous AS or QN, plus artemether-lumefantrine or DP among children in
Tororo District Hospital, in Eastern Uganda.
Results: Piperaquine concentration data from 150 participants who received DP were analyzed. Participants with
unadjusted treatment failure had lower median day 7 capillary piperaquine concentration than those with
treatment success (34.7 (IQR) (17.9–49.1) vs 66.7 (IQR) (41.8–81.9), p < 0.001), and lower than the recommended day
7 cut off level of 57 ng/mL. There was no difference in median capillary piperaquine concentrations among
participants with re-infection and recrudescence (35.3 (IQR) (17.9–55.2) vs 34.8 (IQR) (18.1–45.1), p = 0.847). The risk
of treatment failure was two times higher among children with low (< 57 ng/mL) day 7 capillary piperaquine
concentration (relative risk: 2.1 CI 1.4–3.1), p < 0.001) compared to children with high day 7 capillary piperaquine
concentrations (> 57 ng/mL).
Conclusion: Considering the low day 7 concentrations of piperaquine reported in the patients studied here, we
suggest to adopt the recently recommended higher dose of DP in young children or a prolonged 5-day dosing in
children living in malaria endemic areas who have suffered an initial episode of severe malaria in order to achieve
adequate drug exposures for effective post-treatment prophylactic effects.
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