Re-exposure of Previously Immunized and Challenged Human Volunteers to a Heterologous Strain of P. Falciparum Sporozoites
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Enrollment
- 21
- Locations
- 1
- Primary Endpoint
- Duration of prepatent period after challenge infection as measured by microscopy
Study Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 35 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Age ≥ 18 and ≤ 35 years healthy volunteers (males or females)
- •Good health based on history and clinical examination
- •Negative pregnancy test
- •Use of adequate contraception for females
- •Signing of the informed consent form, thereby demonstrating understanding of the meaning and procedures of the study
- •Agreement to inform the general practitioner and to sign a request to release medical information concerning contra-indications for participation in the study
- •Willingness to undergo a Pf controlled challenge through mosquito bites
- •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)
- •Reachable (24/7) by mobile phone during the whole study period
- •Available to attend all study visit
- •Agreement to refrain from blood donation to Sanquin or for other purposes, during the whole study period
- •Willingness to undergo HIV, hepatitis B and hepatitis C tests
- •Negative urine toxicology screening test at screening visit and the day before challenge
- •Willingness to take a curative regimen of Malarone®
Exclusion Criteria
- •History of malaria (other than participation in ZonMw1 study) or residence in malaria endemic areas within the past six months
- •Plans to travel to malaria endemic areas during the study period
- •Plans to travel outside of the Netherlands during the challenge period
- •Previous participation in any malaria vaccine study and/or positive serology for Pf (except ZonMw1 volunteers)
- •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 arrhythmias or prolonged QT-interval
- •Positive family history in 1st and 2nd degree relatives for cardiac events < 50 years old
- •An estimated, ten year risk of fatal cardiovascular disease of ≥5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system
- •Clinically significant abnormalities in electrocardiogram (ECG) at screening
- •Body Mass Index (BMI) below 18 or above 30 kg/m2
- •Any clinically significant deviation from the normal range in biochemistry or hematology 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
- •Enrollment in any other clinical study during the study period
- •For women: being pregnant or lactating
- •Volunteers unable to give written informed consent
- •Volunteers unable to be closely followed for social, geographic or psychological reasons
- •History of drug or alcohol abuse interfering with normal social function
- •A history of treatment for psychiatric disease
- •A history of convulsions
- •Contra-indications to Malarone®, including hypersensitivity or treatment taken by the volunteer that interferes with Malarone®
- •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
- •Any confirmed or suspected immunosuppressive or immunodeficient condition, including (functional) asplenia
- •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)
- •A history of sickle cell anaemia, sickle cell trait, thalassaemia (or trait), G6PD deficiency
Arms & Interventions
Heterologous challenge
Biological: Heterologous challenge with 5 infected mosquito bites (NF135) after previous CPS immunization and challenge.
Drug: Malarone treatment When thick smear positive, of at day 21 after challenge, all volunteers will be treated with malarone.
Other Name: atovaquone/proguanil
Intervention: Heterologous challenge (Biological)
Heterologous challenge
Biological: Heterologous challenge with 5 infected mosquito bites (NF135) after previous CPS immunization and challenge.
Drug: Malarone treatment When thick smear positive, of at day 21 after challenge, all volunteers will be treated with malarone.
Other Name: atovaquone/proguanil
Intervention: Malarone treatment (Drug)
Challenge control
Biological: Plasmodium falciparum mosquito challenge by the bites of 5 Plasmodium falciparum infected mosquitoes (NF135).
Drug: Malarone treatment When thick smear positive, of at day 21 after challenge, all volunteers will be treated with malarone.
Other Name: atovaquone/proguanil
Intervention: Heterologous challenge (Biological)
Challenge control
Biological: Plasmodium falciparum mosquito challenge by the bites of 5 Plasmodium falciparum infected mosquitoes (NF135).
Drug: Malarone treatment When thick smear positive, of at day 21 after challenge, all volunteers will be treated with malarone.
Other Name: atovaquone/proguanil
Intervention: Malarone treatment (Drug)
Outcomes
Primary Outcomes
Duration of prepatent period after challenge infection as measured by microscopy
Time Frame: 21 days after challenge
Secondary Outcomes
- • Parasitemia and kinetics of parasitemia as measured by PCR(21 days after challenge)
- Frequency of signs or symptoms in study groups(21 days after challenge)
- • Immune responses between study groups(21 days after challenge)