DON in Pediatric Cerebral Malaria

Inclusion Criteria: For Healthy Adults (Part 1): * 18 years and older * Informed consent obtained and ICF signed * Temperature ≤ 37.5 °C * BMI 18.5-25 kg/m2 * Creatinine ≤ 110 mmol/L (≤ 1.2 mg/dL; males) or ≤ 90 mmol/L (≤ 1.0 mg/dL; females) * Hemoglobin ≥ 7 g/dL or hematocrit/ packed-cell volume (PCV) ≥ 20% * Thick or thin blood smear negative for asexual forms of P. falciparum * Negative pregnancy test for persons of child-bearing potential For Adults with Uncomplicated Malaria (Part 1): * 18 years and older * Informed consent obtained and ICF signed * Temperature ≥ 38 °C or history of fever in the past 24 hours * Thick or thin blood smear positive for asexual forms of P. falciparum (parasite count and speciation documented) * Hemoglobin ≥ 7 g/dL or hematocrit/ PCV ≥ 20% * BMI 18.5-25 kg/m2 * Creatinine ≤ 110 mmol/L (≤ 1.2 mg/dL; males) or ≤ 90 mmol/L (≤ 1.0 mg/dL; females) * Glasgow coma score of 15 * Respiratory rate ≤ 20 breaths/ minute * Oxygen saturation ≥ 90% on room air * Negative pregnancy test for person of child-bearing potential For Children with Cerebral Malaria (Part 2): * Age 12 months-14 years old * Informed consent obtained and ICF signed by parent or guardian * Temperature ≥ 38 °C or history of fever in the last 24 hours * Thick or thin blood smear positive for asexual forms of P. falciparum * Blantyre coma score ≤ 2 * No other explanation for coma by history or physical exam * Hematocrit or PCV ≥ 18% * Negative pregnancy test for persons of child-bearing potential * Creatinine ≤ 1.5 mg/dL * Aspartate aminotransferase (AST) \< 280 IU/L * Alanine aminotransferase (ALT) \< 195 IU/L Exclusion Criteria (All Participants): * Pregnancy or lactation (participants of child-bearing potential ages 9-59 years will undergo pregnancy testing prior to administration of the intervention) * Participants attempting to become pregnant * Currently taking highly active antiretroviral therapy (HAART) * Currently taking anti-tuberculosis medications * Allergy to ondansetron or ceftriaxone Additional Exclusion Criteria for Children with Cerebral Malaria (Part 2): * Cloudy cerebrospinal fluid (indicative of a probable bacterial central nervous system infection) * Severe malnutrition (\>3 standard deviations below the mean weight for height and/ or mid-upper arm circumference (MUAC) ≤11.5 cm * Allergy to ondansetron or ceftriaxone * Coma for \> 72 hours * Have taken a CYP3A4 inhibitor within 7 days of enrollment