P. Falciparum Malaria
Conditions
Keywords
malaria, plasmodium, falciparum, human, experimental infection
Brief summary
In the EHMI-8 study (CMO 2006/207) the investigators induced sterile protection against P. falciparum challenge in healthy Dutch volunteers by repeated exposure to infected mosquitoes whilst under chloroquine prophylaxis. The surprisingly efficient induction of protection in this study strongly supports the development of whole parasite vaccines and is therefore an important finding to malaria vaccine development. In this study (EHMI8B) the investigators would like to explore the longevity of the protective immune response and simultaneously further characterise immune mechanisms responsible for protection by re-exposing EHMI-8 volunteers to infected mosquito bites.
Interventions
BIOLOGICALExposure to 5 P. falciparum infected mosquitoes
Five Anopheles Stephensi mosquitoes are infected with NF54 P.falciparum. volunteers are exposed to bites for 10 minutes.
Sponsors
Radboud University Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
Yes
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 challenge 8. Resident near the RUNMC, Nijmegen or agree to stay in a hotel room during the intensive period of the study (Day 5 till Day T +3) 9. Reachable by mobile phone during the whole study period 10. Availability to attend all study visits 11. Agreement to refrain from blood donation to Sanquin or for other purposes, during the course of the study 12. Willingness to undergo an HIV, hepatitis B and C test 13. Negative urine toxicology screening test at screening visit and day before challenge
Exclusion criteria
1. History of malaria other than participation in EHMI-8, or residence in malaria endemic areas within the past six months 2. Plans to travel to endemic malaria areas during the study period. 3. Only for newly recruited control volunteers: previous participation in any malaria vaccine study and/or positive serology for P. falciparum 4. 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. 5. History of diabetes mellitus or cancer (except basal cell carcinoma of the skin) 6. History of arrhythmia's or prolonged QT-interval 7. Positive family history in 1st and 2nd degree relatives of cardiac disease \< 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. Any clinically significant deviation from the normal range in biochemistry or haematology blood tests or in urine analysis 10. Positive HIV, HBV or HCV tests 11. Participation in any other clinical study within 30 days prior to the onset of the study 12. Volunteers enrolled in any other clinical study during the study period 13. Pregnant or lactating women 14. Volunteers unable to give written informed consent 15. Volunteers unable to be closely followed for social, geographic or psychological reasons 16. Previous history of drug or alcohol abuse interfering with normal social function during a period of one year prior to enrolment in the study 17. A history of psychiatric disease 18. Known hypersensitivity for anti-malaria 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 before study onset (inhaled and topical corticosteroids are allowed) and during the study period 21. Contra-indications to Malarone® including treatment taken by the volunteers that interfere with Malarone® 22. Any confirmed or suspected immunosuppressive or immunodeficiency condition, including asplenia 23. Co-workers of the departments of Medical Microbiology or Internal Medicine of the Radboud University Nijmegen Medical Centre
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| A significant difference in time of thick smear positivity between EHMI-8 and control volunteers | 21 days |
| A significant quantitative difference in parasitemia as measured by PCR between EHMI-8 and control volunteers | 21 days |
| A significant difference in kinetics of parasitemia between EHMI-8 and control volunteers as measured by PCR. | 21 days |
| A difference in occurrence of signs or symptoms between EHMI-8 and control volunteers | 21 days |
Secondary
| Measure | Time frame |
|---|---|
| Difference in immunological parameters between EHMI-8 and control volunteers. | 140 days |
Countries
Netherlands
Outcome results
None listed