Patient flowchart.

<p>Patient flowchart.</p

Studies included in the meta-analysis.

<p>Full details of the references and study design are available in <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001564#pmed.1001564.s001" target="_blank">Text S1</a>.</p

Total piperaquine and dihydroartemisinin dose by age and weight categories.

<p><a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001564#pmed.1001564-WHO1" target="_blank">[5]</a>. No patient was exposed to a DHA dose >30 mg/kg.^a The WHO therapeutic guidelines recommend a target dose for PIP of 54 mg/kg over 3 days with a range from 48 to 78 mg/kg; and a target dose for DHA of 12 mg/kg over 3 days with a range from 6 to 30 mg/kg </p

Univariate and multivariate risk factors for PCR confirmed recrudescent failures at day 42.

<p><i>n</i>) for each variable/levels of factor with number of recrudescence [<i>n</i>] by day 42.^a Number of patients (</p><p><i>p</i> = 0.32 for global test for proportional hazards assumption. Variance of random effect  = 1.17. Non-significant likelihood ratio test for weight (<i>p</i> = 0.27) and hemoglobin (<i>p</i> = 0.26) and thus dropped from the multivariable analysis. Baseline gametocytemia (<i>p</i> = 0.02) improved the model but 22.3% (1,576/7,070) of patient had missing observation for this variable and hence not kept for multivariable analysis. Inclusion (or exclusion) of gametocytemia didn't alter the significance of the other variable and its effect on model coefficient for age and dose was small.^b</p>c<p>Overall PAR for model: 65.1%.</p>d<p>HR (95% CI) = 1.48 [0.99–2.19] <i>p</i> = 0.054 and AHR (95% CI) = 1.39 [0.94–2.06], <i>p</i> = 0.10 for mg/kg PIP dose <48 mg/kg in univariable and multivariable analysis, respectively.</p

Available patient data within each age category for (A) dihydroartemisinin and (B) piperaquine.

<p>The patients receiving a total mg/kg dose below the WHO therapeutic range (6 mg/kg and 48 mg/kg, respectively) are shown in dark columns and as a percentage of all patients on top of the bar.</p

Baseline characteristics of patients included in the analysis.

<p>^a Data from one study conducted in Peru.</p><p>+ 320 mg PIP or 20 mg DHA + 160 mg PIP in paediatric formulation (full details are given in <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001564#pmed.1001564.s001" target="_blank">Text S1</a>).^b DHA-PIP tablets strength was 40 mg DHA </p

Percentiles of predicted risk [5th-median-95th] of recrudescent failure at day 42 in children aged from 1 up to 5 years computed from multivariate model.

<p>Risk was calculated for each individual using their own values. The error bars show the 5th and 95th percentiles of predicted risk of recrudescence failure.</p

Parasite positivity rates on days 1, 2, and 3.

<p>^a Parasite positivity rates were calculated from those with in who a blood film was taken on that day; cases without a smear were removed from the denominator.</p