This clinical trial evaluates the advantage of prolonging the therapeutic life span of Artemether-lumefantrine from 3 days to 6 days, and addition of single low dose of Primaquine 0.25mg/kg. The study will have two arms, one that will receive standard treatment of uncomplicated malaria with Artemether-lumefantrine, and the other arm will receive the prolonged dose of 6 days together with single low dose primaquine. This approach is expected to provide strategies for malaria control in an era of imminent Plasmodium falciparum resistance.

Despite documented high cure rates of ACT in Tanzania, and Africa elsewhere, clinical trials conducted in Tanzania with Swedish International Development cooperation Agency (SIDA) and Swedish Research Council support, provide evidence for in vivo selection of lumefantrine tolerant/resistant parasites among recurrent infections. Similarly, molecular epidemiology studies from Bagamoyo District, Tanzania, have shown temporal selection of lumefantrine associated genetic tolerance/resistance markers in the parasite population following wide scale use of Artemether-lumefantrine, but without signs of compromised treatment efficacy.

During the last decade, and despite the documented rapid microscopy determined parasite clearance of artemether-lumefantrine in Bagamoyo District, interest has developed in understanding the observation of high residual polymerase chain reaction (PCR) determined positivity rate on day 3 after supervised artemether-lumefantrine treatment in the magnitude of almost 30% in previous assessments from 2015. Using deep sequencing approaches studies have recently detected PCR determined delayed parasite clearance curves in P. falciparum sub-populations in Bagamoyo District. The clearance times by PCR of these sub-populations were similar to artemisinin resistant parasites in Myanmar as assessed by microscopy, but the former did, importantly, not harbor any of the described mutations in Kelch13 propeller associated with artemisinin resistance. However, these Tanzanian parasite sub-populations need to be further studied and characterized since they may provide important clues to the understanding of artemisinin survival strategies among the East African P. falciparum parasite population.

Taken together, longitudinal clinical and molecular data described above from Tanzania, East Africa, extending from pre-ACT implementation, (before 2006), to a decade of wide scale artemether-lumefantrine use in Bagamoyo district, provide evidence for declining susceptibility to ACT, both to artemether and lumefantrine, among the P. falciparum population. These parasites ("last man standing") that survived 10 years of ACT exposure have indeed shown excellent survival instincts and may thus be particularly resistant prone. However, if P. falciparum resistance to ACT develops in Africa, this will have devastating effects on malaria morbidity and mortality and may swiftly ruin the improvements the global malaria community achieved during the past decade with ACT as a key component for success.

Based on the above the investigators suggest prolonged treatment with ACT and addition of transmission blocking treatment using a single low dose of primaquine administered on the last day of ACT treatment.

Inclusion Criteria:

1. Age more than 1 year and less than 65 years.
2. Weight 10 kg and above;
3. Body temperature ≥37.5°C or history of fever in the last 24 hours;
4. Microscopy determined asexual P. falciparum mono-infection regardless of parasitemia
5. Normal - corrected QT Interval in Baseline ECG of less than 440ms in male and 460ms in females

Exclusion Criteria:

1. Symptoms/signs of severe malaria or danger signs;
2. Pregnancy, Breastfeeding or unwilling to practice birth control during participation in the study.
3. Known allergy to study medications;
4. Hb <8 g/dl;
5. Reported antimalarial intake within last 2 weeks;
6. On regular medication, which may interfere with antimalarial pharmacokinetics and
7. Blood transfusion within last 90 days.

Due to the objectives of the study, the identity of test and control treatments will be known only to investigators, research staff, but NOT patients. The following study procedures will be in place to ensure single-blind administration of study treatments.

1. Access to the randomization code will be strictly controlled.
2. A taste-matching agent for the placebo.
3. Packaging and labeling of test and control treatments will be identical to maintain the blind.

During the study, the blind may be broken only in emergencies when knowledge of the patient's treatment group is necessary for further patient management. When possible, the Investigator should discuss the emergency with the Medical Monitor prior to un-blinding