Controlled Human Malaria Infection study to assess gametocytaemia and mosquito transmissibility in participants challenged with Plasmodium falciparum by sporozoite challenge to establish a model for the evaluation of transmission-blocking interventions

1. Subject is aged * 18 and * 35 years and in good health. ;2. Subject has adequate understanding of the procedures of the study and is able and willing (in the investigator*s opinion) to comply with all study requirements.;3. Subject is willing to complete an informed consent questionnaire and is able to answer all questions correctly. ;4. Subject is able to communicate well with the investigator and is available to attend all study visits, lives in proximity to the trial centre (<10 km) or (if >10km) is willing to stay in a hotel close to the trial centre during part of the study (from day 4 (bloodstage challenge) 5 (sporozoite challenge) post-infection until T1+4 provided that the subject has had 2 consecutive negative 18S qPCR tests (at least 24 hours apart) following T1 treatment; or until day T3+3). ;5. The subject will remain within the Netherlands during the challenge period, will not travel to a malaria-endemic area during the study period, and is reachable (24/7) by mobile telephone throughout the entire study period. ;6. Subject agrees to their general practitioner being informed and contacted about their participation in the study and agrees to sign a form to request the release by their General Practitioner (GP), and medical specialist when necessary, to the investigator(s), of any relevant medical information concerning possible contra-indications for participation in the study. ;7. The subject agrees to refrain from blood donation to Sanquin or for other purposes throughout the study period and for a defined period thereafter according to current Sanquin guidelines. ;8. For female subjects: subject agrees to use continuous adequate contraception** and not to breastfeed for the duration of study. ;9. Subject agrees to refrain from intensive physical exercise (disproportionate to the subjects usual daily activity or exercise routine) during the malaria challenge period.;10. Subject agrees to avoid additional triggers that may cause elevations in liver enzymes including alcohol from baseline up to 1 week post treatment. ;11. Subject has signed written informed consent to participate in the trial.

1. Any history, or evidence at screening, of clinically significant symptoms, physical signs or abnormal laboratory values suggestive of systemic conditions, such as cardiovascular, pulmonary, renal, hepatic, neurological, dermatological, endocrine, malignant, haematological, infectious, immunodeficient, psychiatric and other disorders, which could compromise the health of the volunteer during the study or interfere with the interpretation of the study results. These include, but are not limited to, any of the following. ;1.1. Body weight <50 kg or Body Mass Index (BMI) <18 or >30 kg/m2 at screening. ;1.2. A heightened risk of cardiovascular disease, as determined by: an estimated ten year risk of fatal cardiovascular disease of *5% at screening, as determined by the Systematic Coronary Risk Evaluation (SCORE); history, or evidence at screening, of clinically significant arrhythmia*s, prolonged QT-interval or other clinically relevant ECG abnormalities; or a positive family history of cardiac events in 1st or 2nd degree relatives <50 years old. ;1.3. A medical history of functional asplenia, sickle cell trait/disease, thalassaemia trait/disease or G6PD-deficiency. ;1.4. History of epilepsy in the period of five years prior to study onset, even if no longer on medication. ;1.5. Screening tests positive for Human Immunodeficiency Virus (HIV), active Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) ;1.6. Chronic use of i) immunosuppressive drugs, ii) antibiotics, iii) or other immune modifying drugs within three months prior to study onset (inhaled and topical corticosteroids and oral anti-histamines exempted) or expected use of such during the study period. ;1.7. Any recent or current systemic therapy with an antibiotic or drug with potential anti-malarial activity (chloroquine, doxycycline, tetracycline, piperaquine, benzodiazepine, flunarizine, fluoxetine, tetracycline, azithromycin, clindamycin, erythromycin, hydroxychloroquine, etc.) (allowable timeframe for use at the Investigator*s discretion).;1.8. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years. ;1.9. Any history of treatment for severe psychiatric disease by a psychiatrist in the past year. ;1.10. History of drug or alcohol abuse interfering with normal social function in the period of one year prior to study onset, positive urine toxicology test for cocaine or amphetamines at screening or at inclusion, or positive urine toxicology test for cannabis at inclusion. ;2. For female subjects: positive urine pregnancy test at screening and/or at the baseline visit. ;3. Abnormal ALT/AST values on baseline ;4. Any history of malaria, positive serology for P. falciparum, or previous participation in any malaria (vaccine) study. ;5. Known hypersensitivity to or contra-indications (including co-medication) for use of sulfadoxine-pyrimethamine, piperaquine, chloroquine, Malarone®, artemether-lumefantrine, primaquine or history of severe (allergic) reactions to mosquito bites. ;6. Participation in any other clinical study in the 30 days prior to the start of the study or during the study period. ;7. Being an employee or student of the department of Medical Microbiology of the Radboudumc or the department of Internal Medicine. ;8. Any other condition or situation that would, in the opinion of the investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.