Evaluation of Reproducibility of a Sporozoite Challenge Model for Plasmodium Vivax in Human Volunteers
Condition: MALARIA; FEVER; Sweating Fever; Chills; ANEMIA
MeSH terms: Malaria; Fever
Intervention: 413ABM; 414WRR; 418JAL
Intervention description: +/- 3 bites of Anopheles albimanus mosquitoes infected through membrane feeding with blood of the P. vivax infected volunteers 413ABM; +/- 3 bites of Anopheles albimanus mosquitoes infected through membrane feeding with blood of the P. vivax infected volunteers 414WRR; +/- 3 bites of Anopheles albimanus mosquitoes infected through membrane feeding with blood of the P. vivax infected volunteers 418JAL
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Malaria; Sporozoite; Challenge Model; Plasmodium vivax; Human Volunteers

Summary:

      The study is a randomized open label clinical trial to verify the reproducibility of a
      sporozoite challenge model for Plasmodium vivax in humans. The verification of the
      reproducibility of such a model will make it possible to evaluate the efficacy of candidate
      P. vivax vaccines in Phase 2a trials. The study is divided into two successive steps:

      Step A Parasite Blood Donation: Volunteers will be recruited passively from a group of
      patients who present with active P. vivax infection and accept to donate infected blood.
      Samples of P. vivax infected blood will be collected and will be screened for infectious
      diseases, according to standard blood bank procedures. Colonized Anopheles albimanus
      mosquitoes will be fed with this blood using a Membrane Feeding Assay (MFA). Sixteen (16)
      days after, selected positive mosquito batches will be used for step B.

      Step B Challenge: After informed consent signature, a total of 18 healthy volunteers will be
      randomly allocated to Groups 1, 2 and 3, of 6 volunteers each and will be challenged with the
      bite of 3±1, P. vivax infected mosquitoes. Each group will be exposed to a different isolated
      parasite. Volunteers will be closely monitored post infection, and will be treated as soon as
      blood infection becomes patent as ascertained by microscopic examination of thick blood
      smears (TBS). Comparison of data obtained in the three different groups will be used to
      determine reproducibility of challenge model.

      Primary objective: To demonstrate that naïve human volunteers can be safely and reproducibly
      infected by the bite of An. albimanus mosquitoes carrying P. vivax sporozoites in their
      salivary glands.

      Secondary objective: To determine the influence of the type of parasite isolated on
      reproducibility and safety of the challenge model with P. vivax in human volunteers

      Hypothesis:It is possible to safely develop a reproducible P. vivax infection in human
      volunteers using P. vivax experimentally infected An. albimanus mosquitoes.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy, adult male or non-pregnant females (18-45 years of age).

          -  Capacity to sign a free informed consent form of participation along with two
             witnesses.

          -  Use of adequate contraceptive method from the initiation of the study until three
             months after sporozoite challenge.

          -  No plans to travel to malaria endemic areas during the course of the study (a year).

          -  No plans to travel outside the study area from the 7th day until 31st day after the
             challenge.

          -  Reachable by phone during the whole study period.

          -  Able to participate during the whole study period.

        Exclusion Criteria:

          -  Are less than 18 and over 45 years of age.

          -  Are female who is pregnant at serum positive B-HCG screening, planning to become
             pregnant or who is nursing.

          -  Have a Duffy negative phenotype.

          -  Have a G-6-PD deficiency or any other hemoglobinopathy.

          -  Current or past infection with any species of malaria as demonstrated by a positive
             TBS on screening or history of a documented positive blood smear. P. vivax IFAT of 1

          -  Have a known history of allergy to antimalarial drugs or immediate type
             hypersensitivity reactions to mosquito bites.

          -  Clinical or laboratory evidence of significant systemic disease, including hepatic,
             renal, cardiac, immunologic or hematological disease, HIV positive or have any other
             known immunodeficiency (including receiving immunosuppressive therapy or a history of
             splenectomy); infected with hepatitis B or C virus; have a history of autoimmune
             disease (including inflammatory bowel disease, hemolytic anemia, autoimmune hepatitis,
             rheumatoid arthritis, lupus, etc.) or connective tissue disease or have any other
             serious underlying medical condition.

          -  Clinically significant laboratory abnormalities as determined by the Investigator(s).

          -  Plan to have surgery between enrollment and the end of the challenge follow-up.

          -  Previous history of alcoholism or drugs use which interfere with social activities of
             the volunteer

          -  Have any other conditions that are determined by at least two concurring investigators
             that may interfere with the capacity to provide free and willing informed consent.