Temperature was recorded approximately every 6 hours until 6 hours post-parasite clearance and at least daily until discharge along with scheduled follow-up visits. Change from baseline in temperature was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, and t1/2) and temperature. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time to first hospital discharge had models fit and were assessed for significance for temperature.

Systolic BP was recorded approximately every 6 hours until 6 hours post-parasite clearance and at least daily until discharge along with scheduled follow-up visits. Change from baseline in systolic BP was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, and t1/2) and systolic BP. Many participants did not have unique measurements collected for each of the four timepoints defined, thus these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time to first hospital discharge had models fit and were assessed for significance for systolic BP.

Systolic BP was recorded approximately every 6 hours until 6 hours post-parasite clearance and at least daily until discharge along with scheduled follow-up visits. Change from baseline in systolic BP was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, and t1/2) and systolic BP. Many participants did not have unique measurements collected for each of the four timepoints defined, thus these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time to first hospital discharge had models fit and were assessed for significance for systolic BP.

Diastolic BP was recorded approximately every 6 hours until 6 hours post-parasite clearance and at least daily until discharge along with scheduled follow-up visits. Change from baseline in diastolic BP was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and diastolic BP. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time to first hospital discharge had models fit and were assessed for significance for diastolic BP.

Diastolic BP was recorded approximately every 6 hours until 6 hours post-parasite clearance and at least daily until discharge along with scheduled follow-up visits. Change from baseline in diastolic BP was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, and t1/2) and diastolic BP. Many participants did not have unique measurements collected for each of the four timepoints defined, thus these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time to first hospital discharge had models fit and were assessed for significance for diastolic BP.

Serum lactate was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in serum lactate was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and serum lactate. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for serum lactate.

Serum lactate was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in serum lactate was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and serum lactate. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for serum lactate.

Serum bicarbonate was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in serum bicarbonate was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and serum bicarbonate. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for serum bicarbonate.

Serum bicarbonate was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in serum bicarbonate was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and serum bicarbonate. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for serum bicarbonate.

Serum glucose was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in serum glucose was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and serum glucose. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for serum glucose.

Serum glucose was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in serum glucose was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and serum glucose. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for serum glucose.

Total bilirubin was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in total bilirubin was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and total bilirubin. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for total bilirubin.

Total bilirubin was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in total bilirubin was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and total bilirubin. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for total bilirubin.

Direct bilirubin was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in direct bilirubin was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and direct bilirubin. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for direct bilirubin.

Direct bilirubin was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in direct bilirubin was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and direct bilirubin. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for direct bilirubin.

Hemoglobin was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in hemoglobin was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and hemoglobin. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for hemoglobin.

Hemoglobin was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in hemoglobin was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and hemoglobin. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for hemoglobin.

Creatinine was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in creatinine was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and creatinine. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for creatinine.

Creatinine was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in creatinine was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and creatinine. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for creatinine.

Blantyre coma scale is an ordinal scale designed to assess malarial coma in children. Eye movement, best motor response, and best verbal response were assessed and scored. The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness. BCS was recorded daily until discharge along with scheduled follow-up visits. The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted. Instead, summary statistics of DHA AUC0-12 for BCS score of 1 by timepoint are presented.

Blantyre coma scale is an ordinal scale designed to assess malarial coma in children. Eye movement, best motor response, and best verbal response were assessed and scored. The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness. BCS was recorded daily until discharge along with scheduled follow-up visits. The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted. Instead, summary statistics of DHA AUC0-12 for BCS score of 4 by timepoint are presented.

Blantyre coma scale is an ordinal scale designed to assess malarial coma in children. Eye movement, best motor response, and best verbal response were assessed and scored. The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness. BCS was recorded daily until discharge along with scheduled follow-up visits. The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted. Instead, summary statistics of DHA AUC0-12 for BCS score of 5 by timepoint are presented.

BCS is an ordinal scale designed to assess malarial coma in children. Eye movement, best motor response, and best verbal response were assessed and scored. The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness. BCS was recorded daily until discharge along with scheduled follow-up visits. The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted. Instead, summary statistics of DHA AUC0-12 for BCS score of 4 by timepoint are presented. Only participants who were assessed a BCS of 4 are shown.

Blantyre coma scale is an ordinal scale designed to assess malarial coma in children. Eye movement, best motor response, and best verbal response were assessed and scored. The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness. BCS was recorded daily until discharge along with scheduled follow-up visits. The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted. Instead, summary statistics of DHA AUC0-12 for BCS score of 5 by timepoint are presented.

Blantyre coma scale is an ordinal scale designed to assess malarial coma in children. Eye movement, best motor response, and best verbal response were assessed and scored. The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness. BCS was recorded daily until discharge along with scheduled follow-up visits. The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted. Instead, summary statistics of DHA Cmax for BCS score of 1 by timepoint are presented.

Blantyre coma scale is an ordinal scale designed to assess malarial coma in children. Eye movement, best motor response, and best verbal response were assessed and scored. The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness. BCS was recorded daily until discharge along with scheduled follow-up visits. The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted. Instead, summary statistics of DHA Cmax for BCS score of 4 by timepoint are presented.

Blantyre coma scale is an ordinal scale designed to assess malarial coma in children. Eye movement, best motor response, and best verbal response were assessed and scored. The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness. BCS was recorded daily until discharge along with scheduled follow-up visits. The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted. Instead, summary statistics of DHA Cmax for BCS score of 5 by timepoint are presented.

Blantyre coma scale is an ordinal scale designed to assess malarial coma in children. Eye movement, best motor response, and best verbal response were assessed and scored. The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness. BCS was recorded daily until discharge along with scheduled follow-up visits. The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted. Instead, summary statistics of DHA Cmax for BCS score of 4 by timepoint are presented. Only participants who were assessed a BCS of 4 are shown.

Blantyre coma scale is an ordinal scale designed to assess malarial coma in children. Eye movement, best motor response, and best verbal response were assessed and scored. The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness. BCS was recorded daily until discharge along with scheduled follow-up visits. The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted. Instead, summary statistics of DHA Cmax for BCS score of 5 by timepoint are presented.

Blantyre coma scale is an ordinal scale designed to assess malarial coma in children. Eye movement, best motor response, and best verbal response were assessed and scored. The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness. BCS was recorded daily until discharge along with scheduled follow-up visits. The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted. Instead, summary statistics of DHA t1/2 for BCS score of 1 by timepoint are presented.

Blantyre coma scale is an ordinal scale designed to assess malarial coma in children. Eye movement, best motor response, and best verbal response were assessed and scored. The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness. BCS was recorded daily until discharge along with scheduled follow-up visits. The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted. Instead, summary statistics of DHA t1/2 for BCS score of 4 by timepoint are presented.

Blantyre coma scale is an ordinal scale designed to assess malarial coma in children. Eye movement, best motor response, and best verbal response were assessed and scored. The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness. BCS was recorded daily until discharge along with scheduled follow-up visits. The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted. Instead, summary statistics of DHA t1/2 for BCS score of 5 by timepoint are presented.

Blantyre coma scale is an ordinal scale designed to assess malarial coma in children. Eye movement, best motor response, and best verbal response were assessed and scored. The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness. BCS was recorded daily until discharge along with scheduled follow-up visits. The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted. Instead, summary statistics of DHA t1/2 for BCS score of 4 by timepoint are presented. Only participants who were assessed a BCS of 4 are shown.

Blantyre coma scale is an ordinal scale designed to assess malarial coma in children. Eye movement, best motor response, and best verbal response were assessed and scored. The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness. BCS was recorded daily until discharge along with scheduled follow-up visits. The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted. Instead, summary statistics of DHA t1/2 for BCS score of 5 by timepoint are presented.

Dates and times of hospital admittance and discharge for each participant were collected for calculation of time to hospital discharge. Time to hospital discharge was defined as the time in days from initial participant admission to the time of first discharge. Time to hospital discharge was calculated using the actual dates and times of initial participant admission and first discharge and was rounded to the nearest tenths place.

Parasite clearance as calculated from parasite density over time, as measured by thick blood smear. Parasite density is defined as the number of parasites per 200 white blood cells (WBCs). Parasite clearance half-life (PCT50) and parasite clearance time to 90% reduction (PCT90) were estimated using the WorldWide Antimalarial Resistance Network (WWARN) parasite clearance estimator (PCE) algorithm.

Parasite clearance as calculated from parasite density over time, as measured by thick blood smear. Parasite density is defined as the number of parasites per 200 white blood cells (WBCs). Parasite clearance half-life (PCT50) and parasite clearance time to 90% reduction (PCT90) were estimated using the WorldWide Antimalarial Resistance Network (WWARN) parasite clearance estimator (PCE) algorithm.

Total parasite clearance was defined as the first negative thick blood smear (i.e., a thick blood smear for which there were no detectable P. falciparum parasites per 200 WBC) after a participant's last positive blood smear for P. falciparum. The date and time of total parasite clearance was defined as the collection date and time of the first thick blood smear to meet the definition of parasite clearance. Total parasite clearance by Day 2 was defined as a binary variable indicating whether total parasite clearance occurred within the first 50 hours post-first on-study dose of IV artesunate.

Total parasite clearance was defined as the first negative thick blood smear (i.e., a thick blood smear for which there were no detectable P. falciparum parasites per 200 WBC) after a participant's last positive blood smear for P. falciparum. The date and time of total parasite clearance was defined as the collection date and time of the first thick blood smear to meet the definition of parasite clearance. Total parasite clearance by Day 2 was defined as a binary variable indicating whether total parasite clearance occurred within the first 50 hours post-first on-study dose of IV artesunate.

Weight-for-age (WAZ) Z-scores are calculated for participants younger than 60 months according to the WHO Child Growth Standards (2006). Participants older than 60 months have a Z-score of N/A. A Z-score measures how far a child's growth measurement (height, weight) is from the median value of a reference population, expressed in standard deviation (SD) units. A 0 z-score indicates average or the 50th percentile. A +1 z-score indicates an above average, while a -1 z-score indicates below average. Underweight (Low Weight-for-Age - WAZ): Less than -2 SD. Overweight/Obese: Above +2 SD

Weight-for-age Z-score was calculated for participants younger than 60 months according to the WHO Child Growth Standards (2006).

Height-for-age (HAZ) Z-scores are calculated for participants younger than 60 months according to the WHO Child Growth Standards (2006). Participants older than 60 months have a Z-score of N/A. A Z-score measures how far a child's growth measurement (height, weight) is from the median value of a reference population, expressed in standard deviation (SD) units. A 0 z-score indicates average or the 50th percentile. A +1 z-score indicates an above average, while a -1 z-score indicates below average. Stunted (Low Height-for-Age - HAZ): Less than -2 SD.

Height-for-age Z-score was calculated for participants younger than 60 months according to the WHO Child Growth Standards (2006).

Population PK modeling was conducted to derive AUC0-12 from the concentration of DHA. The final model fit was a 1-compartment disposition of DHA with covariates for age and baseline bilirubin.

Day 1 (Sampling windows were defined as 0 (pre-dose), 0-1 hour, 1 - 2.5, 2.5-4, 4-6 and 6-24 hours post first on-study dose of IV artesunate)

The analysis population for the population PK modeling included all participants who received at least one on-study dose of IV artesunate and at least one DHA concentration data were available.

Population PK modeling was conducted to derive t1/2 from the concentration of DHA. The final model fit was a 1-compartment disposition of DHA with covariates for age and baseline bilirubin.

The analysis population for the population PK modeling included all participants who received at least one on-study dose of IV artesunate and at least one DHA concentration data were available.

Population Pharmacokinetic (PK) modeling was conducted to derive PK parameters from the concentration of DHA. The final model fit was a 1-compartment disposition of DHA with covariates for age and baseline bilirubin. From the simulation, the Tmax was assumed to be 0 as the simulation replicates artesunate administered as an IV bolus directly into the central compartment.

The analysis population for the population PK modeling included all participants who received at least one on-study dose of IV artesunate and at least one DHA concentration data were available.

Temperature was recorded approximately every 6 hours until 6 hours post-parasite clearance and at least daily until discharge along with scheduled follow-up visits. Change from baseline in temperature was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK Parameters (AUC0-12, Cmax, and t1/2) and temperature. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time to first hospital discharge had models fit and were assessed for significance for temperature.

The primary PD analysis population included all participants meeting the definition of severe malaria at enrollment that received < 24 hours of artemisinin therapy prior to enrollment for which exposure parameters were estimated from the final population PK model and for which post-baseline response data were available.

Temperature was recorded approximately every 6 hours until 6 hours post-parasite clearance and at least daily until discharge along with scheduled follow-up visits. Change from baseline in temperature was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, and t1/2) and temperature. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time to first hospital discharge had models fit and were assessed for significance for temperature.

Sensitivity analyses were conducted on the subset of the PD analysis population who did not receive any IV artesunate or other artemisinin-based therapy before enrollment. The PD analysis population included all participants meeting the definition of severe malaria at enrollment that received < 24 hours of artemisinin therapy prior to enrollment for which exposure parameters were estimated from the final population PK model and for which post-baseline response data were available.

Systolic BP was recorded approximately every 6 hours until 6 hours post-parasite clearance and at least daily until discharge along with scheduled follow-up visits. Change from baseline in systolic BP was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, and t1/2) and systolic BP. Many participants did not have unique measurements collected for each of the four timepoints defined, thus these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time to first hospital discharge had models fit and were assessed for significance for systolic BP.

The primary PD analysis population included all participants meeting the definition of severe malaria at enrollment that received < 24 hours of artemisinin therapy prior to enrollment for which exposure parameters were estimated from the final population PK model and for which post-baseline response data were available.

Systolic BP was recorded approximately every 6 hours until 6 hours post-parasite clearance and at least daily until discharge along with scheduled follow-up visits. Change from baseline in systolic BP was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, and t1/2) and systolic BP. Many participants did not have unique measurements collected for each of the four timepoints defined, thus these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time to first hospital discharge had models fit and were assessed for significance for systolic BP.

Sensitivity analyses were conducted on the subset of the PD analysis population who did not receive any IV artesunate or other artemisinin-based therapy before enrollment. The PD analysis population included all participants meeting the definition of severe malaria at enrollment that received < 24 hours of artemisinin therapy prior to enrollment for which exposure parameters were estimated from the final population PK model and for which post-baseline response data were available.

Diastolic BP was recorded approximately every 6 hours until 6 hours post-parasite clearance and at least daily until discharge along with scheduled follow-up visits. Change from baseline in diastolic BP was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and diastolic BP. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time to first hospital discharge had models fit and were assessed for significance for diastolic BP.

The primary PD analysis population included all participants meeting the definition of severe malaria at enrollment that received < 24 hours of artemisinin therapy prior to enrollment for which exposure parameters were estimated from the final population PK model and for which post-baseline response data were available.

Diastolic BP was recorded approximately every 6 hours until 6 hours post-parasite clearance and at least daily until discharge along with scheduled follow-up visits. Change from baseline in diastolic BP was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, and t1/2) and diastolic BP. Many participants did not have unique measurements collected for each of the four timepoints defined, thus these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time to first hospital discharge had models fit and were assessed for significance for diastolic BP.

Sensitivity analyses were conducted on the subset of the PD analysis population who did not receive any IV artesunate or other artemisinin-based therapy before enrollment. The PD analysis population included all participants meeting the definition of severe malaria at enrollment that received < 24 hours of artemisinin therapy prior to enrollment for which exposure parameters were estimated from the final population PK model and for which post-baseline response data were available.

Serum lactate was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in serum lactate was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and serum lactate. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for serum lactate.

The primary PD analysis population included all participants meeting the definition of severe malaria at enrollment that received < 24 hours of artemisinin therapy prior to enrollment for which exposure parameters were estimated from the final population PK model and for which post-baseline response data were available.

Serum lactate was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in serum lactate was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and serum lactate. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for serum lactate.

Sensitivity analyses were conducted on the subset of the PD analysis population who did not receive any IV artesunate or other artemisinin-based therapy before enrollment. The PD analysis population included all participants meeting the definition of severe malaria at enrollment that received < 24 hours of artemisinin therapy prior to enrollment for which exposure parameters were estimated from the final population PK model and for which post-baseline response data were available.

Serum bicarbonate was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in serum bicarbonate was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and serum bicarbonate. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for serum bicarbonate.

The primary PD analysis population included all participants meeting the definition of severe malaria at enrollment that received < 24 hours of artemisinin therapy prior to enrollment for which exposure parameters were estimated from the final population PK model and for which post-baseline response data were available.

Serum bicarbonate was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in serum bicarbonate was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and serum bicarbonate. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for serum bicarbonate.

Sensitivity analyses were conducted on the subset of the PD analysis population who did not receive any IV artesunate or other artemisinin-based therapy before enrollment. The PD analysis population included all participants meeting the definition of severe malaria at enrollment that received < 24 hours of artemisinin therapy prior to enrollment for which exposure parameters were estimated from the final population PK model and for which post-baseline response data were available.

Serum glucose was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in serum glucose was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and serum glucose. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for serum glucose.

The primary PD analysis population included all participants meeting the definition of severe malaria at enrollment that received < 24 hours of artemisinin therapy prior to enrollment for which exposure parameters were estimated from the final population PK model and for which post-baseline response data were available.

Serum glucose was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in serum glucose was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and serum glucose. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for serum glucose.

Sensitivity analyses were conducted on the subset of the PD analysis population who did not receive any IV artesunate or other artemisinin-based therapy before enrollment. The PD analysis population included all participants meeting the definition of severe malaria at enrollment that received < 24 hours of artemisinin therapy prior to enrollment for which exposure parameters were estimated from the final population PK model and for which post-baseline response data were available.

Total bilirubin was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in total bilirubin was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and total bilirubin. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for total bilirubin.

The primary PD analysis population included all participants meeting the definition of severe malaria at enrollment that received < 24 hours of artemisinin therapy prior to enrollment for which exposure parameters were estimated from the final population PK model and for which post-baseline response data were available.

Total bilirubin was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in total bilirubin was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and total bilirubin. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for total bilirubin.

Sensitivity analyses were conducted on the subset of the PD analysis population who did not receive any IV artesunate or other artemisinin-based therapy before enrollment. The PD analysis population included all participants meeting the definition of severe malaria at enrollment that received < 24 hours of artemisinin therapy prior to enrollment for which exposure parameters were estimated from the final population PK model and for which post-baseline response data were available.

Direct bilirubin was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in direct bilirubin was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and direct bilirubin. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for direct bilirubin.

The primary PD analysis population included all participants meeting the definition of severe malaria at enrollment that received < 24 hours of artemisinin therapy prior to enrollment for which exposure parameters were estimated from the final population PK model and for which post-baseline response data were available.

Direct bilirubin was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in direct bilirubin was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and direct bilirubin. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for direct bilirubin.

Sensitivity analyses were conducted on the subset of the PD analysis population who did not receive any IV artesunate or other artemisinin-based therapy before enrollment. The PD analysis population included all participants meeting the definition of severe malaria at enrollment that received < 24 hours of artemisinin therapy prior to enrollment for which exposure parameters were estimated from the final population PK model and for which post-baseline response data were available.

Hemoglobin was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in hemoglobin was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and hemoglobin. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for hemoglobin.

The primary PD analysis population included all participants meeting the definition of severe malaria at enrollment that received < 24 hours of artemisinin therapy prior to enrollment for which exposure parameters were estimated from the final population PK model and for which post-baseline response data were available.

Hemoglobin was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in hemoglobin was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and hemoglobin. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for hemoglobin.

Sensitivity analyses were conducted on the subset of the PD analysis population who did not receive any IV artesunate or other artemisinin-based therapy before enrollment. The PD analysis population included all participants meeting the definition of severe malaria at enrollment that received < 24 hours of artemisinin therapy prior to enrollment for which exposure parameters were estimated from the final population PK model and for which post-baseline response data were available.

Creatinine was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in creatinine was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and creatinine. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for creatinine.

The primary PD analysis population included all participants meeting the definition of severe malaria at enrollment that received < 24 hours of artemisinin therapy prior to enrollment for which exposure parameters were estimated from the final population PK model and for which post-baseline response data were available.

Creatinine was recorded daily until discharge along with scheduled follow-up visits. Change from baseline in creatinine was reported at pre-defined timepoints: 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Primary exposure-response analyses were performed to assess the relationship between DHA PK parameters (AUC0-12, Cmax, t1/2) and creatinine. Many participants did not have unique measurements collected for each of the four timepoints defined, therefore these participants were using the same values at multiple timepoints. To meet the independence assumption of the Benjamini-Hochberg procedure, only 24-hours post-first IV artesunate and time of completion of planned IV artesunate dosing had models fit and were assessed for significance for creatinine.

Sensitivity analyses were conducted on the subset of the PD analysis population who did not receive any IV artesunate or other artemisinin-based therapy before enrollment. The PD analysis population included all participants meeting the definition of severe malaria at enrollment that received < 24 hours of artemisinin therapy prior to enrollment for which exposure parameters were estimated from the final population PK model and for which post-baseline response data were available.

Blantyre coma scale is an ordinal scale designed to assess malarial coma in children. Eye movement, best motor response, and best verbal response were assessed and scored. The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness. BCS was recorded daily until discharge along with scheduled follow-up visits. The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted. Instead, summary statistics of DHA AUC0-12 for BCS score of 1 by timepoint are presented.

The PD analysis population included all participants meeting the definition of severe malaria at enrollment that received < 24 hours of artemisinin therapy prior to enrollment for which exposure parameters were estimated from the final population PK model and for which post-baseline response data were available. Only participants who were assessed a BCS of 1 are shown.

Blantyre coma scale is an ordinal scale designed to assess malarial coma in children. Eye movement, best motor response, and best verbal response were assessed and scored. The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness. BCS was recorded daily until discharge along with scheduled follow-up visits. The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted. Instead, summary statistics of DHA AUC0-12 for BCS score of 4 by timepoint are presented.

The PD analysis population included all participants meeting the definition of severe malaria at enrollment that received < 24 hours of artemisinin therapy prior to enrollment for which exposure parameters were estimated from the final population PK model and for which post-baseline response data were available. Only participants who were assessed a BCS of 4 are shown.

Blantyre coma scale is an ordinal scale designed to assess malarial coma in children. Eye movement, best motor response, and best verbal response were assessed and scored. The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness. BCS was recorded daily until discharge along with scheduled follow-up visits. The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted. Instead, summary statistics of DHA AUC0-12 for BCS score of 5 by timepoint are presented.

The PD analysis population included all participants meeting the definition of severe malaria at enrollment that received < 24 hours of artemisinin therapy prior to enrollment for which exposure parameters were estimated from the final population PK model and for which post-baseline response data were available.

BCS is an ordinal scale designed to assess malarial coma in children. Eye movement, best motor response, and best verbal response were assessed and scored. The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness. BCS was recorded daily until discharge along with scheduled follow-up visits. The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted. Instead, summary statistics of DHA AUC0-12 for BCS score of 4 by timepoint are presented. Only participants who were assessed a BCS of 4 are shown.

Sensitivity analyses were conducted on the subset of the PD analysis population who did not receive any IV artesunate or other artemisinin-based therapy before enrollment. The PD analysis population included all participants meeting the definition of severe malaria at enrollment that received < 24 hours of artemisinin therapy prior to enrollment for which exposure parameters were estimated from the final population PK model and for which post-baseline response data were available.

Blantyre coma scale is an ordinal scale designed to assess malarial coma in children. Eye movement, best motor response, and best verbal response were assessed and scored. The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness. BCS was recorded daily until discharge along with scheduled follow-up visits. The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted. Instead, summary statistics of DHA AUC0-12 for BCS score of 5 by timepoint are presented.

Sensitivity analyses were conducted on the subset of the PD analysis population who did not receive any IV artesunate or other artemisinin-based therapy before enrollment. The PD analysis population included all participants meeting the definition of severe malaria at enrollment that received < 24 hours of artemisinin therapy prior to enrollment for which exposure parameters were estimated from the final population PK model and for which post-baseline response data were available.

Blantyre coma scale is an ordinal scale designed to assess malarial coma in children. Eye movement, best motor response, and best verbal response were assessed and scored. The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness. BCS was recorded daily until discharge along with scheduled follow-up visits. The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted. Instead, summary statistics of DHA Cmax for BCS score of 1 by timepoint are presented.

The PD analysis population included all participants meeting the definition of severe malaria at enrollment that received < 24 hours of artemisinin therapy prior to enrollment for which exposure parameters were estimated from the final population PK model and for which post-baseline response data were available. Only participants who were assessed a BCS of 1 are shown.

Blantyre coma scale is an ordinal scale designed to assess malarial coma in children. Eye movement, best motor response, and best verbal response were assessed and scored. The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness. BCS was recorded daily until discharge along with scheduled follow-up visits. The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted. Instead, summary statistics of DHA Cmax for BCS score of 4 by timepoint are presented.

The PD analysis population included all participants meeting the definition of severe malaria at enrollment that received < 24 hours of artemisinin therapy prior to enrollment for which exposure parameters were estimated from the final population PK model and for which post-baseline response data were available. Only participants who were assessed a BCS of 4 are shown.

Blantyre coma scale is an ordinal scale designed to assess malarial coma in children. Eye movement, best motor response, and best verbal response were assessed and scored. The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness. BCS was recorded daily until discharge along with scheduled follow-up visits. The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted. Instead, summary statistics of DHA Cmax for BCS score of 5 by timepoint are presented.

The PD analysis population included all participants meeting the definition of severe malaria at enrollment that received < 24 hours of artemisinin therapy prior to enrollment for which exposure parameters were estimated from the final population PK model and for which post-baseline response data were available.

Blantyre coma scale is an ordinal scale designed to assess malarial coma in children. Eye movement, best motor response, and best verbal response were assessed and scored. The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness. BCS was recorded daily until discharge along with scheduled follow-up visits. The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted. Instead, summary statistics of DHA Cmax for BCS score of 4 by timepoint are presented. Only participants who were assessed a BCS of 4 are shown.

Sensitivity analyses were conducted on the subset of the PD analysis population who did not receive any IV artesunate or other artemisinin-based therapy before enrollment. The PD analysis population included all participants meeting the definition of severe malaria at enrollment that received < 24 hours of artemisinin therapy prior to enrollment for which exposure parameters were estimated from the final population PK model and for which post-baseline response data were available.

Blantyre coma scale is an ordinal scale designed to assess malarial coma in children. Eye movement, best motor response, and best verbal response were assessed and scored. The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness. BCS was recorded daily until discharge along with scheduled follow-up visits. The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted. Instead, summary statistics of DHA Cmax for BCS score of 5 by timepoint are presented.

Sensitivity analyses were conducted on the subset of the PD analysis population who did not receive any IV artesunate or other artemisinin-based therapy before enrollment. The PD analysis population included all participants meeting the definition of severe malaria at enrollment that received < 24 hours of artemisinin therapy prior to enrollment for which exposure parameters were estimated from the final population PK model and for which post-baseline response data were available.

Blantyre coma scale is an ordinal scale designed to assess malarial coma in children. Eye movement, best motor response, and best verbal response were assessed and scored. The total BCS score was then calculated as the sum of the scores for these three assessments with possible values of 0, 1, 2, 3, 4, or 5. Lower BCS values were indicative of impaired consciousness. BCS was recorded daily until discharge along with scheduled follow-up visits. The number of participants in each BCS were reported at pre-defined timepoints: baseline, 24 and 48 hours post-first IV artesunate, time of completion of planned IV artesunate dosing, and time of first hospital discharge. Due to the lack of variability in BCS scores, proportional odds mixed effects models to assess the relationship between BCS scores and each PK exposure parameter were not conducted. Instead, summary statistics of DHA t1/2 for BCS score of 1 by timepoint are presented.

The PD analysis population included all participants meeting the definition of severe malaria at enrollment that received < 24 hours of artemisinin therapy prior to enrollment for which exposure parameters were estimated from the final population PK model and for which post-baseline response data were available. Only participants who were assessed a BCS of 1 are shown.