The main purpose of this study is to compare artesunate-mefloquine combination therapy given for 2 and 3 days at the same total dose for the treatment of uncomplicated falciparum malaria.

This will be a randomized, open-label comparison of two versus three days artesunate-mefloquine treatment in patients with uncomplicated falciparum malaria. Primary endpoints will be 63-day parasitological cure rates in the 2 treatment groups. Secondary endpoints will be parasitological failure rates at each of the weekly follow-up visits to Day 56, occurence of treatment-emergent adverse events on days 0, 1 and 2, mefloquine blood concentrations on days 7, 14 and 28, and in vitro drug sensitivity profiles for parasite isolates as measured by inhibitory concentrations. Genotyping of parasites for known markers of drug resistence will be performed.

Inclusion Criteria:

1. Age 5 to 70 years inclusive. If aged < 18 years the subject must have a parent or guardian in attendance.
2. Asexual stages of P. falciparum parasites in a thick or thin blood film with no other visible plasmodial species.
3. Willing to give informed consent. Parents or guardians of children and adolescents must agree to give informed consent. Assent is necessary in addition to parental informed consent.
4. Able to tolerate oral therapy.
5. Willing to attend follow-up appointments and undergo study procedures.

Exclusion Criteria:

1. History of anti-malarial drug use within the past two weeks or mefloquine (MQ) use within 4 weeks.
2. Bleeding tendency (by history or based on medical records).
3. Severe/complicated malaria as determined by the investigator (coma or seizures, pulmonary edema, shock, renal failure, jaundice, severe anemia, spontaneous bleeding, hyperparasitemia (>5% RBCs infected), or prostration).
4. History of allergy to or intolerance of study medications.
5. Mixed malaria infection by Giemsa stain.
6. Any other condition that in the opinion of the study investigator warrants parenteral antimalarial treatment.
7. Pregnant woman or nursing mother