Proportion of patients with adverse events of any grade.

<p>Proportion of patients with adverse events of any grade.</p

Proportion of patients who cleared fever.

<p>Proportion of patients who cleared fever.</p

Treatment outcome stratified by age groups.

<p>Treatment outcome stratified by age groups.</p

Characteristics of the enrolled patients at baseline.

<p>Characteristics of the enrolled patients at baseline.</p

Box plot for the distribution of PQ concentration by treatment outcome.

<p>The dotted lines represent a previously proposed cut-off for piperaquine concentrations quantified in venous (30 ng/ml) and capillary (57 ng/ml) blood samples (Tarning et al. 2012).</p

Efficacy and Day 7 Plasma Piperaquine Concentrations in African Children Treated for Uncomplicated Malaria with Dihydroartemisinin-Piperaquine

<div><p>Background</p><p>One promising new Artemisinin-based combination therapies (ACTs) is dihydroartemisinin-piperaquine (DHA-PQ). However, the pharmacokinetics of piperaquine and the relationship between drug levels and clinical efficacy are incompletely characterized, particularly in children.</p><p>Methods</p><p>We performed a single-arm open-label trial in Bobo-Dioulasso, Burkina Faso. A total of 379 participants aged 6 months or more with uncomplicated falciparum malaria were enrolled. Each participant received daily dose of DHA-PQ for three days and followed for 42 days. Parasitological efficacy was analyzed, considering rates of recrudescence and overall recurrence. PK was an exploratory endpoint and a priori, no sample size had been determined. Day 7 capillary and venous plasma concentrations of piperaquine were measured in children aged 2–10 years.</p><p>Results</p><p>Of the 379 participants, 365 (96.3%) completed 42 days of follow-up. The median daily dose of PQ was 18.5 mg/kg [6.5–24]. Treatment with DHA-PQ was well tolerated with fever and parasitemia resolution within 48 hours in nearly all children. Recurrent malaria within 42 days of follow-up occurred in 31.3% (10/34) of children less than 2 years old, 16.0% (16/106) of those aged 2–5 years, 9.4% (15/160) of those aged 5–10 years, and none (0/68) of those over 10 years old. After genotyping, 3 of 41 recurrent episodes were recrudescence. An exploratory analysis shows that children with successful treatment outcomes had significantly higher median plasma concentrations of PQ compared to those with recurrent malaria within 42 days after therapy, considering either capillary samples (68 ng/ml [50–85] compared to 48 ng/ml [36–55], p<0.001) or venous samples (42 ng/ml [29–59] compared to 25 ng/ml [19–44], p<0.001).</p><p>Conclusion</p><p>DHA-PQ was effective for uncomplicated P. falciparum malaria treatment and offers an alternative to other ACTs. Recurrent malaria was mainly due to new infections after treatment and was correlated with low day 7 PQ concentration in the youngest patients.</p><p>Trial Registration</p><p>Controlled-Trials.com <a href="http://www.controlled-trials.com/ISRCTN59761234" target="_blank">ISRCTN59761234</a></p></div

Plasma concentrations of PQ and treatment outcomes among children 2–10 years.

<p>Success represents adequate clinical and parasitological response; failure represents recurrent parasitemia.</p

Capillary and venous concentrations of PQ by age.

<p>Median values [interquartile ranges] are shown; Wilcoxon Rank Sum Test; Wilcoxon Paired Sign Rank Test.</p

Summary of MOI and <i>F_WS</i> estimates in Burkina Faso, Mali and the combined (West Africa) population.

<p>Summary of MOI and <i>F_WS</i> estimates in Burkina Faso, Mali and the combined (West Africa) population.</p

Different methodological approaches to the assessment of efficacy of three artemisinin-based combination antimalarial treatments for the treatment of uncomplicated falciparum malaria in African children-0

Od of analysis.<p><b>Copyright information:</b></p><p>Taken from "Different methodological approaches to the assessment of efficacy of three artemisinin-based combination antimalarial treatments for the treatment of uncomplicated falciparum malaria in African children"</p><p>http://www.malariajournal.com/content/7/1/154</p><p>Malaria Journal 2008;7():154-154.</p><p>Published online 9 Aug 2008</p><p>PMCID:PMC2527011.</p><p></p