This is a study of the efficacy and effectiveness of combination therapy for malaria due to P. falciparum in the Loreto Department, Iquitos, Peru. The investigators will enroll subjects ≥ 1 year-old who have a diagnosis of uncomplicated malaria due to P. falciparum. Patients will receive a treatment regimen consisting of mefloquine (25 mg/kg per day for two days) and artesunate (12 mg/kg per day for three days). Patients will be divided into two groups: one will receive drugs under direct supervision and the other will be instructed on how to take the drugs by themselves. Clinical and parasitologic response will be monitored for a follow-up period of 28 days. The findings of this study will be used to guide the Ministry of Health in evaluating its national policy for P. falciparum malaria treatment.

Inclusion Criteria:

• Age > 1 year
• Axillary temperature ≥ 37.5ºC and/or history of fever in the previous 48 hours without any other evident cause
• Unmixed infection with P. falciparum of between 250 and 100,000 asexual parasites/mm3 as determined by microscopic exam of the thick or thin smear
• An informed consent obtained from the patient or his/her guardian (in case of patients ≤ 18 years old) and assent for children (8-18 years old)
• Willingness to come to the health facility for the following 28 days

Exclusion Criteria:

• Signs or symptoms of severe malaria
• Other severe chronic diseases (e.g., cardiologic, renal, or hepatic diseases; HIV/AIDS; severe malnutrition)
• History of allergy to any of the proposed treatment or its alternatives, i.e. mefloquine, artesunate, quinine, tetracycline, or clindamycin
• Pregnancy (based on urine test), since this group of patients receives other drugs for malaria treatment in accordance with Peruvian national guidelines.