Experimental Human Malaria Infection After Immunization With Plasmodium Falciparum Sporozoites Under Chloroquine Prophylaxis

Inclusion Criteria: 1. Age \> 18 and \< 35 years healthy volunteers (males or females) 2. Good health based on history and clinical examination 3. Negative pregnancy test 4. Use of adequate contraception for females 5. All volunteers must sign the informed consent form demonstrating their understanding of the meaning and procedures of the study 6. Volunteer agrees to inform the general practitioner and agrees to sign a request to release medical information concerning contra-indications for participation in the study 7. Willingness to undergo a Pf mosquito or blood stage challenge 8. For volunteers not living in Nijmegen: agreement to stay in a hotel room close to the trial center during a part of the study (for groups 1 and 3 from challenge day till 3 days after treatment, for groups 2 and 4 from 5 days after challenge till 3 days after treatment) 9. Reachable (24/7) by mobile phone during the whole study period 10. Living with a third party that could contact the clinicians in case of alteration of consciousness or agreement to stay in a hotel room close to the trial center during a part of the study (for groups 1 and 3 from challenge day till 3 days after treatment, for groups 2 and 4 from 5 days after challenge till 3 days after treatment) 11. Available to attend all study visits 12. Agreement to refrain from blood donation to Sanquin or for other purposes, during the study period until 393 13. Willingness to undergo HIV, hepatitis B and hepatitis C tests 14. Negative urine toxicology screening test at screening visit and day before challenge 15. Willingness to take a prophylactic regime of chloroquine and curative regimen of Malarone® Exclusion Criteria: 1. History of malaria 2. Plans to travel to malaria endemic areas during the study period 3. Plans to travel outside of the Netherlands during the challenge period 4. Previous participation in any malaria vaccine study and/or positive serology for Pf 5. Symptoms, physical signs and laboratory values suggestive of systemic disorders including renal, hepatic, cardiovascular, pulmonary, skin, immunodeficiency, psychiatric, and other conditions which could interfere with the interpretation of the study results or compromise the health of the volunteers 6. History of diabetes mellitus or cancer (except basal cell carcinoma of the skin) 7. History of arrhythmias or prolonged QT-interval 8. Positive family history in 1st and 2nd degree relatives for cardiac disease \< 50 years old 9. An estimated, ten year risk of fatal cardiovascular disease of ≥5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system 10. Clinically significant abnormalities in electrocardiogram (ECG) at screening 11. Body Mass Index (BMI) below 18 or above 30 kg/m2 12. Any clinically significant deviation from the normal range in biochemistry or hematology blood tests or in urine analysis 13. Positive HIV, HBV or HCV tests 14. Participation in any other clinical study within 30 days prior to the onset of the study 15. Enrollment in any other clinical study during the study period 16. Pregnant or lactating women 17. Volunteers unable to give written informed consent 18. Volunteers unable to be closely followed for social, geographic or psychological reasons 19. Previous history of drug or alcohol abuse interfering with normal social function during a period of one year prior to enrolment in the study 20. A history of psychiatric disease 21. Known hypersensitivity to anti-malaria drugs 22. The use of chronic immunosuppressive drugs, antibiotics, or other immune modifying drugs within three months of study onset (inhaled and topical corticosteroids are allowed) and during the study period 23. Contra-indications to Malarone® or chloroquine including treatment taken by the volunteer that interferes with Malarone® or chloroquine 24. Any confirmed or suspected immunosuppressive or immunodeficient condition, including asplenia 25. Co-workers of the departments of Medical Microbiology or Internal Medicine of the RUNMC 26. A history of sickle cell anemia, sickle cell trait, thalassemia, thalassemia trait or G6PD deficiency