Effectiveness of OZ439 as a Gametocytocidal and Transmission Blocking Agent

Inclusion Criteria: Demography: * Adult (male and females) participants between 18 and 55 years of age, inclusive who do not live alone (from Day 0 until at least the end of the anti-malarial drug treatment) and be contactable and available for the duration of the trial (maximum of 6 weeks). * Body weight, minimum 50.0 kg, body mass index between 18.0 and 32.0 kg/m Health status: * Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination). * Normal vital signs after 10 minutes resting in supine position: * 90mmHg \< systolic blood pressure (SBP) \<140 mmHg, * 50 mmHg \< diastolic blood pressure (DBP) \<90 mmHg, * 40 bpm\< heart rate (HR) \<100 bpm. * Normal standard 12-lead electrocardiogram (ECG) after 5 minutes resting in supine position, QTcF=450 ms average with absence of second or third degree atrioventricular block or abnormal T wave morphology. * Laboratory parameters within the normal range, unless the Investigator considers an abnormality to be clinically irrelevant for healthy participants enrolled in this clinical investigation. More specifically for serum creatinine, hepatic transaminase enzymes (aspartate aminotransferase, alanine aminotransferase), and total bilirubin (unless the Participant has documented Gilbert syndrome) should not exceed the upper laboratory norm and haemoglobin must be equal or higher than the lower limit of the normal range, - - As there is the risk of adverse effects of OZ439, Riamet and primaquine in early pregnancy, it is important that any participants involved in this study do not get pregnant or get their female partners pregnant. Regulations: \- Having given written informed consent prior to undertaking any study-related procedure. Exclusion Criteria: Medical history and clinical status: * Any history of malaria or participation to a previous malaria challenge study * Must not have travelled to or lived (\>2 weeks) in a malaria-endemic country during the past 12 months or planned travel to a malaria-endemic country during the course of the study. * Known severe reaction to mosquito bites other than local itching and redness * Has evidence of increased cardiovascular disease risk (defined as \>10%, 5 year risk) as determined by the method of Gaziano et al. (1). Risk factors include sex, age, systolic blood pressure (mm/Hg), smoking status, body mass index (BMI, kg/m) and reported diabetes status. * History of splenectomy. * Presence or history of drug hypersensitivity, or allergic disease diagnosed and treated by a physician or history of a severe allergic reaction, anaphylaxis or convulsions following any vaccination or infusion. * Presence of current or suspected serious chronic diseases such as cardiac or autoimmune disease (HIV or other immunodeficiencies), insulin-dependent and NIDDM diabetes (excluding glucose intolerance if E04 is met ), progressive neurological disease, severe malnutrition, acute or progressive hepatic disease, acute or progressive renal disease, psoriasis, rheumatoid arthritis, asthma, epilepsy or obsessive compulsive disorder, skin carcinoma excluding non-spreadable skin cancers such as basal cell and squamous cell carcinoma * Participants with history of schizophrenia, bi-polar disease, or other severe (disabling) chronic psychiatric diagnosis including depression or receiving psychiatric drugs or who has been hospitalized within the past 5 years prior to enrollment for psychiatric illness, history of suicide attempt or confinement for danger to self or others. * Frequent headaches and/or migraine, recurrent nausea, and/or vomiting (more than twice a month). * Presence of acute infectious disease or fever (e.g., sub-lingual temperature = 38.5°C) within the five days prior to inoculation with malaria parasites. * Evidence of acute illness within the four weeks before trial prior to screening that the Investigator deems may compromise subject safety. * Significant intercurrent disease of any type, in particular liver, renal, cardiac, pulmonary, neurologic, rheumatologic, or autoimmune disease by history, physical examination, and/or laboratory studies including urinalysis. * Participant has a clinically significant disease or any condition or disease that might affect drug absorption, distribution or excretion, e.g. gastrectomy, diarrhoea. * Participation in any investigational product study within the 12 weeks preceding the study. * Blood donation, any volume, within 1 month before inclusion or participation in any research study involving blood sampling (more than 450 mL/ unit of blood), or blood donation to Red Cross (or other) blood bank during the 8 weeks preceding the reference drug dose in the study. * Participant unwilling to defer blood donations for 6 months. * Medical requirement for intravenous immunoglobulin or blood transfusions. * Participant who has ever received a blood transfusion. * Symptomatic postural hypotension at screening, irrespective of the decrease in blood pressure, or asymptomatic postural hypotension defined as a decrease in systolic blood pressure =20 mmHg within 2-3 minutes when changing from supine to standing position. * History or presence of alcohol abuse (alcohol consumption more than 40 g per day) or drug habituation, or any prior intravenous usage of an illicit substance. * Smoking more than 5 cigarettes or equivalent per day and unable to stop smoking for the duration of the study. * Ingestion of any poppy seeds within the 24 hours prior to the screening blood test (participants will be advised by phone not to consume any poppy seeds in this time period). Interfering substance: * Any medication (including St John's Wort) within 14 days before inclusion or within 5 times the elimination half-life (whichever is longer) of the medication, * Any vaccination within the last 28 days. * Any corticosteroids, anti-inflammatory drugs, immunomodulators or anticoagulants. Any participant currently receiving or having previously received immunosuppressive therapy, including systemic steroids including adrenocorticotrophic hormone (ACTH) or inhaled steroids in dosages which are associated with hypothalamic-pituitary-adrenal axis suppression such as 1 mg/kg/day of prednisone or its equivalent or chronic use of inhaled high potency corticosteroids (budesonide 800 µg per day or fluticasone 750 µg). * Any recent or current systemic therapy with an antibiotic or drug with potential anti-malarial activity (chloroquine, piperaquine, benzodiazepine, flunarizine, fluoxetine, tetracycline, azithromycin, clindamycin, hydroxychloroquine, etc.). General conditions: * Any participant who, in the judgment of the Investigator, is likely to be noncompliant during the study, or unable to cooperate because of a language problem or poor mental development. * Any participant in the exclusion period of a previous study according to applicable regulations. * Any participant who lives alone (from Day 0 until at least the end of the anti-malarial drug treatment). * Any participant who cannot be contacted in case of emergency for the duration of the trial and up to 2 weeks following end of study visit. * Any participant who is the Investigator or any sub-investigator, research assistant, pharmacist, study coordinator, or other staff thereof, directly involved in conducting the study. * Any participant without a good peripheral venous access. Biological status: * Positive result on any of the following tests: hepatitis B surface (HBs Ag) antigen, antihepatitis B core antibodies (anti-HBc Ab), anti-hepatitis C virus (anti-HCV) antibodies, anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV1 and anti HIV2 Ab), * Participant is found to be G6PD deficient. * Any drug listed in Table 2 in the urine drug screen unless there is an explanation acceptable to the medical investigator (e.g., the participant has stated in advance that they consumed a prescription or OTC product which contained the detected drug) and/or the Participant has a negative urine drug screen on retest by the pathology laboratory. * Positive alcohol - breath test. Specific to the study: * Cardiac/QT risk: * Known pre-existing prolongation of the QTc interval considered clinically significant * Family history of sudden death or of congenital prolongation of the QTc interval or known congenital prolongation of the QTc-interval or any clinical condition known to prolong the QTc interval. History of symptomatic cardiac arrhythmias or with clinically relevant bradycardia. * Known hypersensitivity to OZ439, piperaquine or any of its excipients or 4-aminoquinolines, artemether or other artemisinin derivatives, lumefantrine, or other arylaminoalcohols. * Unwillingness to abstain from quinine containing foods/beverages such as tonic water, lemon bitter, from inoculation (Day 0) to the end of the malaria treatment. * Any history or presence of lactose intolerance. On dosing day, and during the blood collection intervals: * Ingestion of any other drug, in the two weeks prior to dosing or during the blood sampling period that, in the opinion of the Medical Investigator, could compromise the study, e.g., through pharmacokinetic or metabolic interactions, or analytical interference. However the Medical Investigator may permit the use of paracetamol for the treatment of headache or other pain. If drug therapy other than paracetamol or drug specified in the protocol, is required during the study periods, a decision to continue or discontinue the participant's participation will be made by the Medical Investigator, based on the nature of the medication and the time the medication was taken. * Failure to conform to the requirements of the protocol. * Detection of any drug listed in this protocol in the urine drug screen unless there is an explanation acceptable to the medical investigator (e.g., the participant has stated in advance that they consumed a prescription or OTC product which contained the detected drug). * Vital signs outside the reference range and considered as clinically significant by the Investigator or his representative.