DON in Pediatric Cerebral Malaria
The goal of this clinical trial is to evaluate the safety of a single intravenous dose of DON in healthy adults, adults with uncomplicated malaria, and children 12 months-14 years old with clinically defined Cerebral Malaria. The main objectives are:
* Evaluate the safety of a single intravenous dose of DON in healthy adults and adults with uncomplicated malaria ( Part 1)
* Determine the safety of a single dose of DON in children 12 months-14 years old with World Health Organization (WHO) clinically defined CM (Part 2 :Cohort 1-4)
* Determine the pharmacokinetic (PK) profile of a single dose of DON in healthy adults, adults with uncomplicated malaria and children with CM (Part 1, and Cohorts 1-4 of Part 2)
* Determine if administration of a single intravenous dose of DON as an adjunctive therapy in children with CM is associated with improved intracerebral blood flow dynamics on transcranial doppler (TCD) (Part 2 :Cohort 1-4)
* Determine if administration of a single intravenous dose of DON as an adjunctive therapy in children with CM is associated with a reduction in brain volume score on magnetic resonance imaging (MRI) (Part 2 :Cohort 1-4)
* Determine if administration of a single intravenous dose of DON as an adjunctive therapy in children with cerebral malaria is associated with changes in electroencephalogram (EEG) pattern (Part 2 :Cohort 1-4)
* Exploratory: Explore the metabolic mechanisms of action of adjunctive DON in children with CM
Healthy adult participants will receive:
* anti-emetic ondansetron
* one dose of DON
Adults with uncomplicated malaria will receive:
* anti-emetic ondansetron
* one dose of DON
* artemisinin-combination therapies per Malawi Ministry of Health guidelines
Pediatric participants will receive:
* one dose of DON
* anti-emetic ondansetron and per Malawi Ministry of Health guidelines:
* enteral lumefantrine-artemether therapy, and
* artesunate therapy
Gender: All
Ages: 12 Months - Any
