Experimental human malaria infection after immunization with Plasmodium falciparum sporozoites under chloroquine prophylaxis.

Completed

Conditions: Malaria
Plasmodium falciparum
10037072

Registration Number: NL-OMON36473

Lead Sponsor: niversitair Medisch Centrum Sint Radboud

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 25

Inclusion Criteria

1. Age > 18 and < 35 years healthy volunteers (males or females)
2. General good health based on history and clinical examination
3. Negative pregnancy test
4. Use of adequate contraception for females
5. All volunteers have to sign the informed consent form following proper understanding of the meaning and procedures of the study
6. Volunteer agrees to inform the general practitioner and agrees to sign a request for medical information concerning contra-indications for participation in the study
7. Willingness to undergo a P. falciparum sporozoite of 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 (Day 5 after challenge till 3 days after treatment for mosquito challenge, from day of challenge till 3 days after treatment for blood-stage challenge)
9. Reachable 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. Availability to attend all study visits
12. Agreement to refrain from blood donation to Sanquin or for other purposes, during the course of the study
13. Willingness to undergo an HIV, hepatitis B and C test
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-malarial 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

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary study endpoint: Duration of prepatent period as measured by microscopy<br /><br>Other main study endpoints:<br /><br>• Parasitemia and kinetics of parasitemia as measured by PCR<br /><br>• Frequency of signs or symptoms in study groups </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>• Antibody production in groups 1, 2, 3 and 4<br /><br>• Cellular immune response in groups 1, 2, 3 and 4<br /><br>• Cytokine profile in groups 1, 2, 3 and 4</p><br>