Re-exposure of EHMI-8 Human Volunteers to Live Malaria Sporozoites

Study Overview
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Brief Summary
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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.

Official Title
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Re-exposure of EHMI-8 Human Volunteers to Live Malaria Sporozoites

Conditions
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P. Falciparum Malaria

Intervention / Treatment
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* Biological: Exposure to 5 P. falciparum infected mosquitoes


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Age > 18 and < 35 years healthy volunteers (males or females). General good health based on history and clinical examination. Negative pregnancy test. Use of adequate contraception for females All volunteers have to sign the informed consent form following proper understanding of the meaning and procedures of the study Volunteer agrees to inform the general practitioner and agrees to sign a request for medical information concerning contra-indications for participation in the study Willingness to undergo a P. falciparum sporozoite challenge 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) Reachable by mobile phone during the whole study period Availability to attend all study visits Agreement to refrain from blood donation to Sanquin or for other purposes, during the course of the study Willingness to undergo an HIV, hepatitis B and C test Negative urine toxicology screening test at screening visit and day before challenge Exclusion criteria History of malaria other than participation in EHMI-8, or residence in malaria endemic areas within the past six months Plans to travel to endemic malaria areas during the study period. Only for newly recruited control volunteers: previous participation in any malaria vaccine study and/or positive serology for P. falciparum 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. History of diabetes mellitus or cancer (except basal cell carcinoma of the skin) History of arrhythmia's or prolonged QT-interval Positive family history in 1st and 2nd degree relatives of cardiac disease < 50 years old An estimated, ten year risk of fatal cardiovascular disease of ≥5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system. Any clinically significant deviation from the normal range in biochemistry or haematology blood tests or in urine analysis Positive HIV, HBV or HCV tests Participation in any other clinical study within 30 days prior to the onset of the study Volunteers enrolled in any other clinical study during the study period Pregnant or lactating women Volunteers unable to give written informed consent Volunteers unable to be closely followed for social, geographic or psychological reasons Previous history of drug or alcohol abuse interfering with normal social function during a period of one year prior to enrolment in the study A history of psychiatric disease Known hypersensitivity for anti-malaria drugs History of severe reactions or allergy to mosquito bites 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 Contra-indications to Malarone® including treatment taken by the volunteers that interfere with Malarone® Any confirmed or suspected immunosuppressive or immunodeficiency condition, including asplenia Co-workers of the departments of Medical Microbiology or Internal Medicine of the Radboud University Nijmegen Medical Centre

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EHMI8<br>Previously protected volunteers, N=10 | Biological: Exposure to 5 P. falciparum infected mosquitoes<br>* Five Anopheles Stephensi mosquitoes are infected with NF54 P.falciparum. volunteers are exposed to bites for 10 minutes.<br>|
| Active Comparator: control<br>5 malaria-naive volunteers | Biological: Exposure to 5 P. falciparum infected mosquitoes<br>* Five Anopheles Stephensi mosquitoes are infected with NF54 P.falciparum. volunteers are exposed to bites for 10 minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in immunological parameters between EHMI-8 and control volunteers. |  | 140 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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malaria, plasmodium, falciparum, human, experimental infection