Comparison of three Plasmodium falciparum isolates in a controlled human malaria infectio

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 15

Inclusion Criteria

1. Males and females aged 18-35 years
2. In general good health based on history, physical examination and basic haematology and biochemistry
3. Negative pregnancy test for females
4. Use of adequate contraception for females
5. Signed informed consent, based on a thorough understanding of the concept and procedures of the study
6. Volunteer agrees to allow informing his/her general practitioner about participation and agrees to sign a request for medical information from the GP concerning any contra-indications for participation in the study
7. Willingness to undergo a Pf sporozoite challenge
8. Agreement to stay in a hotel close to the trial center during part of the study (day 5 until three days post-treatment)
9. Reachable (24/7) by mobile telephone during the whole study period
10. Available to attend all study visits
11. Agreement to refrain from blood donation to Sanquin or for other purposes, during the course of the study and thereafter following Sanquin guidelines.
12. Willingness to undergo an HIV, HBV and HCV screening test
13. Negative urine toxicology screening test at the screening visit and on the day before challenge
14. Willingness to take a curative regimen of Malarone®

Exclusion Criteria

1. History of malaria
2. Plans to travel outside of the Netherlands during the study period
3. Previous participation in any malaria vaccine study and/or positive serology for P. falciparum
4. Symptoms, physical signs or laboratory values suggestive of systemic disorders, including but not limited to renal, hepatic, cardiovascular, pulmonary, skin, immunodeficiency, psychiatric and other conditions, which could compromise the health of the volunteer during the study or interfere with the interpretation of the study results
5. History of diabetes mellitus or cancer (except basal cell carcinoma of the skin)
6. Clinically significant ECG abnormalities at screening, or history of arrhythmia*s or prolonged QT-interval
7. Positive family history of cardiac disease in 1st or 2nd degree relatives < 50 years old
8. An estimated ten year risk of fatal cardiovascular disease of >=5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system
9. Body Mass Index (BMI) below 18 or above 30 kg/m2
10. Any clinically significant deviation from the normal range in haematological or biochemical blood tests or urine analysis
11. Positive HIV, HBV or HCV screening tests
12. Participation in any other clinical study within 30 days prior to the onset of the study or during the study period
13. Pregnant or lactating women
14. Volunteers unable to give written informed consent
15. Volunteers unable to be closely followed during the study period for social, geographic or psychological reasons
16. Previous history of drug or alcohol abuse interfering with normal social function in the period of one year prior to study onset
17. A history of psychiatric disease or convulsions
18. Known hypersensitivity to anti-malarial drugs
19. History of severe reactions or allergy to mosquito bites
20. The use of chronic immunosuppressive drugs, antibiotics, or other immune modifying drugs within three months prior to study onset (inhaled and topical corticosteroids are allowed) or during the study period
21. Contra-indications for Malarone® use, including treatment taken by the volunteers that interferes with Malarone®
22. Any confirmed or suspected immunosuppressive or immunodeficient condition, including asplenia
23. Co-workers of the departments of Medical Microbiology of the UMC St Radboud, the department of Internal Medicine of the Havenziekenhuis or the department of Medical Microbiology & Infectious Diseases of the Erasmus MC
24. A history of sickle cell, thalasaemia trait or G6PD deficiency ;For sub-study Odour profile additionally:
25. Smokers
26. Regular medicine use

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>A significant difference in the kinetics of parasitemia between infections with<br /><br>NF54, NF135 en NF166</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>A significant difference in time to thick smear positivity between infections<br /><br>with NF54, NF135 en NF166<br /><br>A significant difference in the duration and peak height of parasitemia as<br /><br>measured by PCR between infections with NF54, NF135 en NF166<br /><br>A significant difference in the incidence of symptoms in volunteers infected<br /><br>with NF54, NF135 and NF166<br /><br>A significant difference in immunological response (serological or cellular) in<br /><br>volunteers infected with NF54, NF135 and NF166</p><br>