This study will assess the efficacy of Pyramax administered for three-day, two-day or one day, in clearing a P. falciparum infection in asymptomatic carriers.

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This is a randomized, open-label, three-arm, out-patient study in asymptomatic individuals with P. falciparum monoinfection confirmed at baseline, who are >5 years of age and >20kg body weight. A total of 300 participants will be randomised into the study; 100 participants in each of three treatment arms.

Patients who fulfil the entry criteria (all inclusion and none of the exclusion criteria) will be recruited and randomized to receive Pyramax orally for three days, two days or one day in a randomization ratio of 1:1:1.

All participants will be followed until Day 63 (counted from day 0) and blood samples will be taken on Days 0, 1, 2, 3, 7, 14, 21, 28, 35, 42 and 63 for malaria diagnostics, parasite density and qPCR. In addition, blood samples reverse-transcriptase (RT)-PCR will be taken on Days 0, 1, 2, 3, 7 and 14.

Participants will be administered local SOC treatment if they meet any of the protocol-specific criteria of treatment failure: Early treatment failure, Late clinical failure, or Late parasitological failure up to and including Day 63, or if the participant withdraws at any time before Day 63, and is parasite positive.

Inclusion Criteria:

1. Evidence of asymptomatic infection with Plasmodium falciparum monoinfection on thin and thick blood smears with parasite density between 20/µL and 50,000/µL
2. Absence of any clinical symptoms of malaria at the time of enrolment and within 72 hours before enrolment
3. Age >5 years old and >20 kg body weight
4. Ability to swallow oral medication
5. Evidence of a personally signed and dated Informed Consent document indicating that the participant (or a legally acceptable representative if a participant is <18 years of age) has been informed of all pertinent aspects of the study and that all questions by the participant have been sufficiently answered. Assent will be obtained from participants <18 years of age as required by national regulations.
6. Participants who are willing to and are able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

1. Haemoglobin <7 g/dL (measured at screening)

2. History of having received any antimalarial treatment (alone or in combination) during the following periods before screening:

   1. Piperaquine, mefloquine, naphthoquine or sulfadoxine-pyrimethamine within 6 weeks prior to screening
   2. Amodiaquine, chloroquine within 4 weeks prior to screening
   3. Any artemisinin derivative (artesunate, artemether or dihydroartemisinin), quinine, lumefantrine or any other anti-malarial treatment or antibiotic with antimalarial activity (including cotrimoxazole, tetracyclines, quinolones and fluoroquinolones and azithromycin) within 14 days prior to screening

3. Any herbal products or traditional medicines during the 7 days prior to screening (if spontaneously reported by the patient)

4. Known allergy to the study drugs (pyronaridine and/or any artemisinin derivatives)

5. Positive urinary pregnancy test for women of reproductive age

6. Lactating women

7. Evidence of severe malnutrition

8. Participation in other studies within 30 days before the current study begins and/or during study participation

9. Inability to comprehend and/or unwillingness to follow the study protocol

10. Previously randomized in this study

11. Severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study. Examples would include but not limited to:

    1. Immunological disorders (including known seropositive HIV antibody),
    2. Severe psychiatric disorders (active depression, recent history of depression, generalised anxiety, psychosis, schizophrenia or other major psychiatric disorders) and major medical disorders related to cardiovascular, respiratory (including active tuberculosis), renal, gastrointestinal, endocrine, infectious, malignancy, neurological (including auditory) and history of convulsions or other abnormality (including recent head trauma),
    3. Clinical signs or symptoms of hepatic injury (such as nausea, abdominal pain associated with jaundice) or known severe liver disease (i.e. decompensated cirrhosis, Child-Pugh stage 3 or 4)

12. Participant the Investigator considers at particular risk of receiving an anti-malarial or of participating in the study