Experimental Falciparum Transmission to Anopheles

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 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 to be desired 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, 3 standard drinks per day) or drug habituation, or any prior intravenous usage of