Following the rapid development of significant drug resistance to both chloroquine and sulfadoxine-pyrimethamine (the first line therapy in Tanzania from 2001 -2006), artemether- lumefantrine (Coartem or AL) was adopted as first line therapy in Tanzania in 2006. Now that this drug has been widely used for some time, the investigators propose to conduct an antimalarial efficacy trial to monitor the effectiveness of this therapy, to determine if this drug remains efficacious, or if significant resistance has emerged, in which case a new antimalarial strategy will need to be contemplated. The investigators hypothesize that the efficacy of Artemether-lumefantrine remains high, and that the other artemisinin combination therapies will be equally efficacious.

Children 6-59 months of age with symptomatic malaria will be randomly assigned to be treated with either artemether + lumefantrine (Coartem) or dihydroartemisinin-piperaquine (Duo-Cotecxin or Artekin). Clinical, parasitologic, and hematologic parameters will be monitored over a 42-day follow-up period and will be used to evaluate drug efficacy.

Inclusion Criteria:

1. Age 6-59 months
2. Axillary temperature ≥ 37.5º C or history of fever in the past 48 hours
3. Weight ≥ 5.0 kg
4. Slide-confirmed infection with P. falciparum, with parasitemia 2,000-200,000 asexual forms per μl
5. Live within the boundaries of the officially recognized catchment area of Miono Health Center.
6. Caregiver agrees to all blood draws and return visits.

Exclusion Criteria:

1. General danger signs or symptoms of severe malaria
2. Signs or symptoms of severe malnutrition, defined as weight-for-age ≤ 3 standard deviations below the mean (National Center for Health Statistics [NCHS]/World Health Organization [WHO] normalized reference values)
3. Slide confirmed infection with any other Plasmodium spp. besides falciparum or mixed plasmodium infection
4. Severe anemia, defined as Hb < 5 g/dl
5. Known hypersensitivity to any of the drugs being tested
6. Presence of febrile conditions caused by diseases other than malaria
7. Serious or chronic medical condition (heart failure, sickle cell disease).
8. Plan to travel or leave the area within the next 3 months.
9. Have been treated for malaria in the 2 weeks prior to enrollment.