Artesunate: 4mg/kg once a day for 3 days, 50 mg tablet

Azithromycin 30 mg/kg once a day for 3 days, 200 mg/5cc suspension

Chloroquine: 10 mg/kg on days 0 and 1, 5 mg/kg/day on day 2, 100 mg tablet.

Adequate clinical and parasitologic response (ACPR) was defined as the absence of parasitemia at Day 28 and without previously meeting any of the criteria of early treatment or late clinical failure.

Adequate clinical and parasitologic response (ACPR) was defined as the absence of parasitemia at Day 28 and without previously meeting any of the criteria of early treatment or late clinical failure.

Adequate clinical and parasitologic response (ACPR) was defined as the absence of parasitemia at Day 28 and without previously meeting any of the criteria of early treatment or late clinical failure.

Adequate clinical and parasitologic response (ACPR) was defined as the absence of parasitemia at Day 28 and without previously meeting any of the criteria of early treatment or late clinical failure.

A case of severe malaria included one or more of the following: Hemoglobin ≤5 g/dL; prostration; respiratory distress; bleeding; recent seizures, coma or obtundation (Blantyre coma score < 5); inability to drink, or persistent vomiting. All cases were then adjudicated by a panel of investigators prior to analysis.

Hemoglobin values were assessed from blood collected at the last study visit at one year after enrollment. Group means are stratified by participants 3 years of age and under, and over 3 to 5 years of age.

Hemoglobin values were assessed from blood collected at the last study visit at one year after enrollment. Group means are stratified by participants 3 years of age and under, and over 3 to 5 years of age.

Creatine values were assessed from blood draws at Day 0 and Day 14 of each malaria episode. Samples that were below the limit of detection were reported as 44.2 micromoles/liter, equivalent to the lower limit of detection.

Creatine values were assessed from blood draws at Day 0 and Day 14 of each malaria episode. Samples that were below the limit of detection were reported as 44.2 micromoles/liter, equivalent to the lower limit of detection.

Creatine values were assessed from blood draws at Day 0 and Day 14 of each malaria episode. Samples that were below the limit of detection were reported as 44.2 micromoles/liter, equivalent to the lower limit of detection.

Creatine values were assessed from blood draws at Day 0 and Day 14 of each malaria episode. Samples that were below the limit of detection were reported as 44.2 micromoles/liter, equivalent to the lower limit of detection.

Creatine values were assessed from blood draws at Day 0 and Day 14 of each malaria episode. Samples that were below the limit of detection were reported as 44.2 micromoles/liter, equivalent to the lower limit of detection.

Creatine values were assessed from blood draws at Day 0 and Day 14 of each malaria episode. Samples that were below the limit of detection were reported as 44.2 micromoles/liter, equivalent to the lower limit of detection.

Creatine values were assessed from blood draws at Day 0 and Day 14 of each malaria episode. Samples that were below the limit of detection were reported as 44.2 micromoles/liter, equivalent to the lower limit of detection.

Creatine values were assessed from blood draws at Day 0 and Day 14 of each malaria episode. Samples that were below the limit of detection were reported as 44.2 micromoles/liter, equivalent to the lower limit of detection.

Creatine values were assessed from blood draws at Day 0 and Day 14 of each malaria episode. Samples that were below the limit of detection were reported as 44.2 micromoles/liter, equivalent to the lower limit of detection.

Creatine values were assessed from blood draws at Day 0 and Day 14 of each malaria episode. Samples that were below the limit of detection were reported as 44.2 micromoles/liter, equivalent to the lower limit of detection.

ALT values were assessed from blood draws at Day 0 and Day 14 of each malaria episode.

ALT values were assessed from blood draws at Day 0 and Day 14 of each malaria episode.

ALT values were assessed from blood draws at Day 0 and Day 14 of each malaria episode.

ALT values were assessed from blood draws at Day 0 and Day 14 of each malaria episode.

ALT values were assessed from blood draws at Day 0 and Day 14 of each malaria episode.

ALT values were assessed from blood draws at Day 0 and Day 14 of each malaria episode.

ALT values were assessed from blood draws at Day 0 and Day 14 of each malaria episode.

ALT values were assessed from blood draws at Day 0 and Day 14 of each malaria episode.

ALT values were assessed from blood draws at Day 0 and Day 14 of each malaria episode.

ALT values were assessed from blood draws at Day 0 and Day 14 of each malaria episode.

A basic age-appropriate neurological examination was conducted on Day 28 of each malaria illness episode and also at Days 112 and 224, and at 1 year. Subjects were were counted as a "change from 'normal' to 'abnormal' " if they had the 'normal' (or not-applicable) response for the initial day 28 exam and an 'abnormal' response at their last exam. If a subject did not have an exam at 1 year then the last available exam that was not associated with an illness episode (either Day 112 or 224) was used.

The presence of parasites with the mutation pfCRT 76T was measured with filter paper specimens collected at the time of enrollment and with successful parasite DNA amplification using pyrosequencing.

Participants were enrolled in the study at the time of the initial episode of malaria. If the participant presented with a subsequent episode of malaria at any time during the one year of follow-up, the presence of parasites with the mutation pfCRT 76T was measured with filter paper specimens collected at the time of enrollment and with successful parasite DNA amplification using pyrosequencing.

Participants were enrolled at the time of initial malaria episode and treated. Subsequent to treatment, subjects were monitored for the occurrence of new and recrudescent malaria infections, which were distinguished by analysis of the infecting parasites using merozoite surface protein-2 polymorphic gene length variation.

Participants were enrolled at the time of initial malaria episode and treated. Subsequent to treatment, participants who subsequently suffered new malaria episodes were monitored for the additional occurrence of new and recrudescent malaria infections, which were distinguished by analysis of the infecting parasites using merozoite surface protein-2 polymorphic gene length variation.

The cumulative hazard of having a malaria attack within one year for those participants who travelled and slept in rural areas (outside the city) versus those who did not was calculated and is presented as a life table to display the number of subjects at risk, the number with first clinical episode and the number censored at each time point. Participants are right-censored at the time of first malaria episode. Participants who did not develop malaria during follow-up or were lost to follow-up were censored at the time of their last visit.

The Global Positioning System (GPS) was used to establish the coordinates of participants' homes. The distribution of these coordinates was analyzed for evidence of clustering, or occurring closer together than would be expected on the basis of chance. Nearest Neighbor Index is a ratio of the observed mean distance over the expected mean distance. If the index is less than 1, the pattern exhibits clustering. If the index is greater than 1, the trend is toward dispersion.

1727 non-zero concentration measurements from 479 participants were pooled and used for population pharmacokinetic modeling in Monolix413s. Compartmental population pharmacokinetic modeling was used due to highly sparse data. The model was parameterized in terms of absorption rate constant for chloroquine (Ka), apparent clearance for chloroquine (CL/F, with F as the unknown oral bioavailability), apparent volume of distribution of the central and peripheral compartments for chloroquine (Vd/F), and the inter-compartmental clearance for chloroquine (Q/F). Only these primary population pharmacokinetic parameters could be estimated using the type of data collected. The best-fit population PK model was then used to estimate individual parameter estimates to derive Tmax and half-life.

1727 non-zero concentration measurements from 479 participants were pooled and used for population pharmacokinetic modeling in Monolix413s. Compartmental population pharmacokinetic modeling was used due to highly sparse data. The model was parameterized in terms of absorption rate constant for chloroquine (Ka), apparent clearance for chloroquine (CL/F, with F as the unknown oral bioavailability), apparent volume of distribution of the central and peripheral compartments for chloroquine (Vd/F), and the inter-compartmental clearance for chloroquine (Q/F). Only these primary population pharmacokinetic parameters could be estimated using the type of data collected. The best-fit population PK model was then used to estimate individual parameter estimates to derive Cmax in nanograms per milliliter (ng/mL).

Participants receive CQ at 10 mg/kg on days 0 and 1, and 5 mg/kg/day on day 2; plus Azithromycin 30 mg/kg once a day for 3 days.

Participants receive CQ at 10 mg/kg on days 0 and 1, and 5 mg/kg/day on day 2.

Total of all reporting groups

Participants receive CQ at 10 mg/kg on days 0 and 1, and 5 mg/kg/day on day 2; plus Azithromycin 30 mg/kg once a day for 3 days.

Participants receive CQ at 10 mg/kg on days 0 and 1, and 5 mg/kg/day on day 2.

Adequate clinical and parasitologic response (ACPR) was defined as the absence of parasitemia at Day 28 and without previously meeting any of the criteria of early treatment or late clinical failure.

This analysis was per protocol, which excludes participants who did not have p. falciparum or who did not receive all 3 doses of treatment.

Adequate clinical and parasitologic response (ACPR) was defined as the absence of parasitemia at Day 28 and without previously meeting any of the criteria of early treatment or late clinical failure.

This analysis was per protocol, which includes participants who had at least 1 subsequent malaria episode, but excludes participants who did if that episode was not caused by p. falciparum or if the participant did not receive all 3 doses of treatment for the first subsequent episode.

Adequate clinical and parasitologic response (ACPR) was defined as the absence of parasitemia at Day 28 and without previously meeting any of the criteria of early treatment or late clinical failure.

This analysis was per protocol, which which includes participants who had at least 2 subsequent malaria episodes, but excludes participants if the second episode was not caused by p. falciparum or if the participant did not receive all 3 doses of treatment for the second episode.

Adequate clinical and parasitologic response (ACPR) was defined as the absence of parasitemia at Day 28 and without previously meeting any of the criteria of early treatment or late clinical failure.

This analysis was per protocol, which includes participants who had at least 3 subsequent malaria episodes, but excludes participants if the third episode was not caused by p. falciparum or if the participant did not receive all 3 doses of treatment for the third episode.

Adequate clinical and parasitologic response (ACPR) was defined as the absence of parasitemia at Day 28 and without previously meeting any of the criteria of early treatment or late clinical failure.

This analysis was per protocol, which includes participants who had 4 subsequent malaria episodes, but excludes participants if the fourth episode was not caused by p. falciparum or if the participant did not receive all 3 doses of treatment for the fourth episode.

A case of severe malaria included one or more of the following: Hemoglobin ≤5 g/dL; prostration; respiratory distress; bleeding; recent seizures, coma or obtundation (Blantyre coma score < 5); inability to drink, or persistent vomiting. All cases were then adjudicated by a panel of investigators prior to analysis.

The safety cohort includes all participants.

Hemoglobin values were assessed from blood collected at the last study visit at one year after enrollment. Group means are stratified by participants 3 years of age and under, and over 3 to 5 years of age.

The safety population includes all participants. The number of participants is limited to those who attended the final 1-year visit.

Hemoglobin values were assessed from blood collected at the last study visit at one year after enrollment. Group means are stratified by participants 3 years of age and under, and over 3 to 5 years of age.

The safety population includes all participants. The number of participants is limited to those who attended the final 1-year visit.

Creatine values were assessed from blood draws at Day 0 and Day 14 of each malaria episode. Samples that were below the limit of detection were reported as 44.2 micromoles/liter, equivalent to the lower limit of detection.

The safety population includes all participants who have laboratory results reported at the time point for the episode.

Creatine values were assessed from blood draws at Day 0 and Day 14 of each malaria episode. Samples that were below the limit of detection were reported as 44.2 micromoles/liter, equivalent to the lower limit of detection.

The safety population includes all participants who have laboratory results reported at the time point for the episode.

Creatine values were assessed from blood draws at Day 0 and Day 14 of each malaria episode. Samples that were below the limit of detection were reported as 44.2 micromoles/liter, equivalent to the lower limit of detection.

The safety population includes all participants who have laboratory results reported at the time point for the episode.

Creatine values were assessed from blood draws at Day 0 and Day 14 of each malaria episode. Samples that were below the limit of detection were reported as 44.2 micromoles/liter, equivalent to the lower limit of detection.

The safety population includes all participants who have laboratory results reported at the time point for the episode.

Creatine values were assessed from blood draws at Day 0 and Day 14 of each malaria episode. Samples that were below the limit of detection were reported as 44.2 micromoles/liter, equivalent to the lower limit of detection.

The safety population includes all participants who have laboratory results reported at the time point for the episode.

Creatine values were assessed from blood draws at Day 0 and Day 14 of each malaria episode. Samples that were below the limit of detection were reported as 44.2 micromoles/liter, equivalent to the lower limit of detection.

The safety population includes all participants who have laboratory results reported at the time point for the episode.

Creatine values were assessed from blood draws at Day 0 and Day 14 of each malaria episode. Samples that were below the limit of detection were reported as 44.2 micromoles/liter, equivalent to the lower limit of detection.

The safety population includes all participants who have laboratory results reported at the time point for the episode.

Creatine values were assessed from blood draws at Day 0 and Day 14 of each malaria episode. Samples that were below the limit of detection were reported as 44.2 micromoles/liter, equivalent to the lower limit of detection.

The safety population includes all participants who have laboratory results reported at the time point for the episode.

Creatine values were assessed from blood draws at Day 0 and Day 14 of each malaria episode. Samples that were below the limit of detection were reported as 44.2 micromoles/liter, equivalent to the lower limit of detection.

The safety population includes all participants who have laboratory results reported at the time point for the episode.

Creatine values were assessed from blood draws at Day 0 and Day 14 of each malaria episode. Samples that were below the limit of detection were reported as 44.2 micromoles/liter, equivalent to the lower limit of detection.

The safety population includes all participants who have laboratory results reported at the time point for the episode.

ALT values were assessed from blood draws at Day 0 and Day 14 of each malaria episode.

The safety population includes all participants who have laboratory results reported at the time point for the episode.

ALT values were assessed from blood draws at Day 0 and Day 14 of each malaria episode.

The safety population includes all participants who have laboratory results reported at the time point for the episode.

ALT values were assessed from blood draws at Day 0 and Day 14 of each malaria episode.

The safety population includes all participants who have laboratory results reported at the time point for the episode.

ALT values were assessed from blood draws at Day 0 and Day 14 of each malaria episode.

The safety population includes all participants who have laboratory results reported at the time point for the episode.

ALT values were assessed from blood draws at Day 0 and Day 14 of each malaria episode.

The safety population includes all participants who have laboratory results reported at the time point for the episode.

ALT values were assessed from blood draws at Day 0 and Day 14 of each malaria episode.

The safety population includes all participants who have laboratory results reported at the time point for the episode.

ALT values were assessed from blood draws at Day 0 and Day 14 of each malaria episode.

The safety population includes all participants who have laboratory results reported at the time point for the episode.

ALT values were assessed from blood draws at Day 0 and Day 14 of each malaria episode.

The safety population includes all participants who have laboratory results reported at the time point for the episode.

ALT values were assessed from blood draws at Day 0 and Day 14 of each malaria episode.

The safety population includes all participants who have laboratory results reported at the time point for the episode.

ALT values were assessed from blood draws at Day 0 and Day 14 of each malaria episode.

The safety population includes all participants who have laboratory results reported at the time point for the episode.

A basic age-appropriate neurological examination was conducted on Day 28 of each malaria illness episode and also at Days 112 and 224, and at 1 year. Subjects were were counted as a "change from 'normal' to 'abnormal' " if they had the 'normal' (or not-applicable) response for the initial day 28 exam and an 'abnormal' response at their last exam. If a subject did not have an exam at 1 year then the last available exam that was not associated with an illness episode (either Day 112 or 224) was used.

Subjects who did not have an initial exam, or who did not have a subsequent exam at a routine visit are excluded.

The presence of parasites with the mutation pfCRT 76T was measured with filter paper specimens collected at the time of enrollment and with successful parasite DNA amplification using pyrosequencing.

All participants from whom samples were successfully collected and DNA successfully amplified were included.

Participants were enrolled in the study at the time of the initial episode of malaria. If the participant presented with a subsequent episode of malaria at any time during the one year of follow-up, the presence of parasites with the mutation pfCRT 76T was measured with filter paper specimens collected at the time of enrollment and with successful parasite DNA amplification using pyrosequencing.

The analysis population is limited to participants who presented with subsequent episodes of malaria from whom samples were successfully collected and DNA successfully amplified.

Participants were enrolled at the time of initial malaria episode and treated. Subsequent to treatment, subjects were monitored for the occurrence of new and recrudescent malaria infections, which were distinguished by analysis of the infecting parasites using merozoite surface protein-2 polymorphic gene length variation.

All subjects completing the initial treatment were included in the analysis population.

Participants were enrolled at the time of initial malaria episode and treated. Subsequent to treatment, participants who subsequently suffered new malaria episodes were monitored for the additional occurrence of new and recrudescent malaria infections, which were distinguished by analysis of the infecting parasites using merozoite surface protein-2 polymorphic gene length variation.

The analysis population is limited to participants who had new episodes of malaria during the follow-up period after treatment.

The cumulative hazard of having a malaria attack within one year for those participants who travelled and slept in rural areas (outside the city) versus those who did not was calculated and is presented as a life table to display the number of subjects at risk, the number with first clinical episode and the number censored at each time point. Participants are right-censored at the time of first malaria episode. Participants who did not develop malaria during follow-up or were lost to follow-up were censored at the time of their last visit.

The Global Positioning System (GPS) was used to establish the coordinates of participants' homes. The distribution of these coordinates was analyzed for evidence of clustering, or occurring closer together than would be expected on the basis of chance. Nearest Neighbor Index is a ratio of the observed mean distance over the expected mean distance. If the index is less than 1, the pattern exhibits clustering. If the index is greater than 1, the trend is toward dispersion.

The analysis included all participants for whom the GPS coordinates of the home were established.

1727 non-zero concentration measurements from 479 participants were pooled and used for population pharmacokinetic modeling in Monolix413s. Compartmental population pharmacokinetic modeling was used due to highly sparse data. The model was parameterized in terms of absorption rate constant for chloroquine (Ka), apparent clearance for chloroquine (CL/F, with F as the unknown oral bioavailability), apparent volume of distribution of the central and peripheral compartments for chloroquine (Vd/F), and the inter-compartmental clearance for chloroquine (Q/F). Only these primary population pharmacokinetic parameters could be estimated using the type of data collected. The best-fit population PK model was then used to estimate individual parameter estimates to derive Tmax and half-life.

All participants with non-zero concentration measures suitable for pharmacokinetic analysis were included.

1727 non-zero concentration measurements from 479 participants were pooled and used for population pharmacokinetic modeling in Monolix413s. Compartmental population pharmacokinetic modeling was used due to highly sparse data. The model was parameterized in terms of absorption rate constant for chloroquine (Ka), apparent clearance for chloroquine (CL/F, with F as the unknown oral bioavailability), apparent volume of distribution of the central and peripheral compartments for chloroquine (Vd/F), and the inter-compartmental clearance for chloroquine (Q/F). Only these primary population pharmacokinetic parameters could be estimated using the type of data collected. The best-fit population PK model was then used to estimate individual parameter estimates to derive Cmax in nanograms per milliliter (ng/mL).

All participants with non-zero concentration measures suitable for pharmacokinetic analysis were included.

Participants receive CQ at 10 mg/kg on days 0 and 1, and 5 mg/kg/day on day 2; plus Atovaquone-Proguanil (AP) once a day for 3 days dosed as follows: 5-8 kg, 2 pediatric tablet (PT, 62.5 mg/25mg); 9-10 kg, 3 PT; 11-20 kg, 1 full strength tablet (FST, 250mg/100 mg); 21-30 kg 2 FST; >30 kg, 3 FST.

Participants receive CQ at 10 mg/kg on days 0 and 1, and 5 mg/kg/day on day 2; plus Azithromycin 30 mg/kg once a day for 3 days.

Participants receive CQ at 10 mg/kg on days 0 and 1, and 5 mg/kg/day on day 2.