In a previous study (NL33904.091.10) the investigators challenged 24 volunteers after Chloroquine Prophylaxis Sporozoites (CPS) immunization with 45, 30 or 15 infected mosquito-bites respectively. The availability of this immunized cohort opens the unique opportunity to determine protection to a heterologous challenge for both of the protected and unprotected volunteers as the previous challenge infection might have served as immunological boost to the unprotected volunteers.

In the current observational, proof of principle study, the investigators aim to investigate the protection on an individual basis of these previously immunized and challenged volunteers against a heterologous P. falciparum challenge.

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. Signing of the informed consent form, thereby demonstrating understanding of the meaning and procedures of the study
6. Agreement to inform the general practitioner and to sign a request to release medical information concerning contra-indications for participation in the study
7. Willingness to undergo a Pf controlled challenge through mosquito bites
8. Agreement to stay in a hotel room close to the trial centre during a part of the study (Day 5 after challenge till treatment is finished)
9. Reachable (24/7) by mobile phone during the whole study period
10. Available to attend all study visit
11. Agreement to refrain from blood donation to Sanquin or for other purposes, during the whole study period
12. Willingness to undergo HIV, hepatitis B and hepatitis C tests
13. Negative urine toxicology screening test at screening visit and the day before challenge
14. Willingness to take a curative regimen of Malarone®

Exclusion Criteria:

1. History of malaria (other than participation in ZonMw1 study) or residence in malaria endemic areas within the past six months
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 (except ZonMw1 volunteers)
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 events < 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. For women: being pregnant or lactating
17. Volunteers unable to give written informed consent
18. Volunteers unable to be closely followed for social, geographic or psychological reasons
19. History of drug or alcohol abuse interfering with normal social function
20. A history of treatment for psychiatric disease
21. A history of convulsions
22. Contra-indications to Malarone®, including hypersensitivity or treatment taken by the volunteer that interferes with Malarone®
23. The use of chronic immunosuppressive drugs, antibiotics, or other immune modifying drugs within three months of study onset (inhaled and topical corticosteroids and oral anti-histaminic are allowed) and during the study period
24. Any confirmed or suspected immunosuppressive or immunodeficient condition, including (functional) asplenia
25. Co-workers or trainees of the departments Infectious Diseases, Medical Microbiology or Parasitology of the Leiden University Medical Centre (LUMC) or Medical Microbiology, Parasitology, Radboud University Nijmegen (RUNMC)
26. A history of sickle cell anaemia, sickle cell trait, thalassaemia (or trait), G6PD deficiency