This study is a prospective, single arm, open-labelled clinical trial. The total number subjects will be 145 patients to receive Pyronaridine-artesunate once daily for 3 days. Dosing will be according to the body weight.

All patients will have a blood smear examined daily during the first week by microscopy until parasite clearance (2 consecutive negative slides on two consecutive days; both asexual and sexual stages). A negative blood slide will be defined as parasite count negative per 1000 WBC in two consecutive days. The sample on day 3 will be taken as close as possible to 72h after the initial blood smear.

Participant will follow up for 42 days to assess the drug efficacy and safety (Day 7, 14, 21, 28, 35 and 42).

Inclusion Criteria:

• Adults and children ≥ 20 kg
• Symptomatic of malaria infection, i.e. history of fever within 24 hours and/or presence of fever >37.5°c.
• Microscopic confirmation of asexual stages of P. falciparum (P. falciparum and mixed infection in Pailin only)
• Capability of taking an oral medication
• Written informed consent given to participate in the trial
• Willingness and ability to adhere to follow-up visit schedule

Exclusion Criteria:

• Pregnancy or lactation (urine test for β HCG to be performed on any woman of child bearing age, that is 18 to 45 y/o)

• Female aged 12-18y

• Parasitemia > 150 000/µL).

• Signs or symptoms indicative of severe malaria:

  • Impaired consciousness (Blantyre Coma Score <5)
  • Severe anaemia (Hct<15%)
  • Bleeding disorder -evidenced by epistaxis, bleeding gums, frank haematuria, bleeding from venepuncture sites
  • Respiratory distress
  • Severe jaundice

• Known hypersensitivity to artemisinins - defined as history of erythroderma/other severe cutaneous reaction, angioedema or to pyronaridine

• History of splenectomy

• Known history or evidence of clinically significant disorders, such as:

  • Known active Hepatitis A, e.g. by detection of anti HAV-IgM.
  • Known hepatitis B surface antigen (HBsAg) carrier.
  • Known hepatitis C antibody (HCV Ab).
  • Liver function tests (AST/ALT levels) more than 2.5 times the upper limit of normal range.