The emergence and spread of drug resistance are major problems in the control of malaria. Resistance to chloroquine in P. vivax was first detected in 1989 then spread to other parts of the world. In Indonesia, resistance of P. vivax to chloroquine has emerged in many parts of the country, ranging from over 50% failure rates in Papua to 20% failure rates in Nias, North Sumatera. Artemisinin derivatives are the most potent and rapidly acting antimalarial drugs available nowadays and also seem to be effective for treatment of vivax malaria, but the number of studies evaluating this is limited. If artemisinin combination therapies (ACTs) are combined with drug that can eliminate parasites in the liver, such as primaquine, this will further optimize the treatment of P. vivax infections. The addition of a course of primaquine will provide radical cure from relapse, and importantly will reduce the transmission of infection because of its gametocyticidal effects. Since 2008, Indonesian government has deployed artesunate-amodiaquine (AS-AQ) as the first line treatment for uncomplicated vivax malaria and promotes radical cure by adding primaquine (PQ). For more than 50 years, Indonesia has used standard dose of primaquine (0.25mg/kg for 14 days) sometimes without prior test of G6PD status of the patients because the screening test is not usually available especially in remote areas. Unfortunately, there is no data to evaluate the safety and efficacy of this standard dose.

Patients with fever or history of fever in preceding 48 hours who are attending the public health centre in study area (study centre) will be examined. Thick and thin blood smear will be taken, stained and examined under light microscope. Slides will be carefully read (according the procedure) for P. vivax malaria. The patients will be assessed by the trial doctor, if they meet all of the inclusion criteria and none of the exclusion criteria, they will receive detail explanation on study \& enrolment condition by trial staff. If they agree to participate in the study, they will sign the informed consent form and will be randomized to receive either AS-AQ plus PQ or DHP plus PQ. Essential laboratory tests (hemoglobin, and methemoglobin) will be performed, and filter blood paper for G6PD genotyping will be collected. No patients will be screened for G6PD status. Oral treatment dose will be given under close observation, those who vomit within half an hour will be re-dosed; if they vomit again they will be withdrawn. Patients will be managed as outpatient and be asked to return to the clinic daily, on fourteen consecutive days, days 1-14) to receive physical examination, laboratory test and study treatment and adverse events monitoring, and then weekly on days 21, 28, 35, 42 or any day if feel unwell. Patients who missed their appointments on scheduled day after day 3 will still be included in the study if they appear on the next day (24 hours), or will be visited at home. Patients who develop any acute hemolytic attack symptoms or reduction on hemoglobin during treatment will be closely observed and transfer to hospital for blood transfusion if needed and withdrawn from the study.

After days 42, patients will be visited at home every month (± 1 week from scheduled day will still be accepted) for up to 1 year. Each patient will be given serial number and an appointment card marked with the dates of follow-up.