The purpose of this study is to compare four regimens using US FDA GMP intravenous artesunate for the treatment of uncomplicated Plasmodium falciparum malaria to identify the most effective treatment regimen as determined by rapidity of parasite clearance by microscopy.

To compare the efficacy and tolerability of intravenous artesunate for the initial treatment of uncomplicated Plasmodium falciparum malaria at doses that bracket anticipated clinical doses (2.4 mg/kg once daily for 3 days; or 2.4 mg/kg initially, at 12 hours on Day 0, and then daily on Day 1 and 2) and thereby establish the safest, highly efficacious dosing regimen for use in future clinical trials.

Inclusion Criteria:

1. Acute symptomatic Plasmodium falciparum malaria infection as determined by malaria smear with a parasite density of ≥ 5000 asexual parasites/mL
2. Age: 5-65 year old males and females.
3. Written informed consent must be obtained from adults age > 18 years. Parental consent will be obtained from children and adolescents, and subject assent will also be obtained from adolescents (age 12-17 years).
4. Willing to stay hospitalized for 4 days for treatment and for 3 scheduled follow-up outpatient visits at Day 7, 14 and 28.

Exclusion Criteria:

1. Pregnant women (clinically or by positive urine β-HCG) and nursing mothers
2. Clinical evidence of severe malaria (see Appendix B)
3. Mixed malaria infection on admission by malaria smear
4. A previous history of intolerance or hypersensitivity to the study drug artesunate or other artemisinin derivatives or Malarone.
5. Efficacious malaria drug therapy administered in the past 30 days by history (i.e. quinine, mefloquine, lumefantrine and artemisinin derivatives)
6. Previous participation in this trial or participation in any other studies involving investigational or marketed products, concomitantly or within 30 days prior to entry in the study.
7. Laboratory evidence or a history of significant liver or renal functional abnormality.
8. Anyone who has received a transfusion or any blood product within 30 days
9. Unable and/or unlikely to comprehend and/or follow the protocol.
10. Likelihood of requiring treatment during the study period with drugs not permitted by the study protocol.