 Following treatment with MMV390048, participants will be followed up as inpatients for at least 72 hours to ensure tolerance of the treatment and clinical response, then on an outpatient basis if clinically well for monitoring of safety and clearance of malaria parasites. Compulsory treatment with Riamet artemether-lumefantrine will start on day 16 3 days post study treatment unless required earlier. Early intervention can occur if either poor responses or fast responses are seen following MMV390048 treatment. This is to ensure participant safety and to avoid participant inconvenience if useful data cannot be obtained. Pre-emptive treatment with Riamet can commence whenever necessary. Participants will be treated with a single dose 45 mg of primaquine PrimacinTM at the end of their Riamet treatment if gametocytes are identified, to ensure complete clearance of any gametocytes present. 