Establishment of a Sporozoite Challenge Model for Plasmodium Vivax in Human Volunteers
Condition: Malaria, Vivax
MeSH terms: Malaria; Malaria, Vivax
Study type: Interventional
Phase: Early Phase 1

Summary: 
      A clinical trial aimed to standardize a vivax sporozoite infection model in human volunteers
      was conducted at the Malaria Vaccine and Drug Development Center (MVDC) in collaboration with
      the Immunology Institute at Valle State University and the Fundación Clínica Valle del Lili
      (FCVL) in Cali, Colombia.

      The primary objective was to determine if naïve human volunteers could be safely and
      reproducibly infected by the bite of An. albimanus mosquitoes carrying P. vivax sporozoites
      in their salivary glands and a secondary objective consisted in determining the minimal
      number of infected mosquitoes required to infect all volunteers, with a reproducible
      pre-patent period.

      The trial was divided into two steps: Step A directed to obtain human blood infected with
      P.vivax parasite used to infect anopheles mosquitoes and Step B to produce P. vivax
      sporozoites in Anopheles mosquitoes to determine the dose response of naive human volunteers
      exposed to 3 +/- 1, 6 +/- 1 y 9 +/- 1 mosquitoes bites. A total of 15 samples of P. vivax
      infected donors were used to infect different batches of mosquitoes.
    

Detailed description: 
      Study design:

      The study was a randomized open label clinical trial to establish a sporozoite challenge
      model for Plasmodium vivax in humans. The development and standardization 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 were recruited passively from a group of patients
      who presented with active P. vivax infection and accepted to donate infected blood. Samples
      of P. vivax infected blood was collected and was screened for infectious diseases, according
      to standard blood bank procedures. Colonized Anopheles albimanus mosquitoes were fed with
      this blood using a Membrane Feeding Assay (MFA). Sixteen (16) days after, selected positive
      mosquito batches were used for step B.

      Step B Challenge: After informed consent signature, a total of 18 healthy volunteers were
      randomly allocated to Groups 1, 2 and 3, of 6 volunteers each and were challenged with the
      bite of 3±1, 6±1 or 9±1 P. vivax infected mosquitoes. Volunteers were closely monitored post
      infection, and were treated as soon as blood infection becomes patent as ascertained by
      microscopic examination of thick blood smears (TBS). Comparison of three bite patterns was
      used to select the optimal number of P. vivax-infected mosquito bites needed to provide
      reliable and reproducible blood infection.

      Infection was expected to occur in the first 30 days. After that time, if infection was not
      documented, antimalarial treatment was planned. Nevertheless all exposed volunteers presented
      malarial infection. Despite infection was expected before day 30, a 18 month follow-up was
      performed with to be sure no delay malaria infection presented without detection. So, the
      total duration of the study was 18 months.

      Infection was determined by the detection of P. vivax parasites on TBS from volunteers
      included.

      Eligibility criteria for Blood donors Step A were:

        -  Adult, male or female (18-60 years of age).

        -  Capacity to freely understand and sign an informed consent form of participation.

        -  TBS Positive for P.vivax but negative for all other malaria species.

        -  P.vivax gametocytemia > 0.2%.

      Exclusion criteria

        -  Unable to provide free and willing written informed consent.

        -  Have or have had any illness or condition which, in the investigator's judgment, may
           substantially increase the risk associated with the blood donation.

      Eligibility and exclusion criteria for Challenge is described below in this format.

      Close monitoring of adverse events was performed, both by medical examination as by telephone
      contact.
    

Intervention name(s): Sporozoite Challenge Model for Plasmodium vivax in Humans
Intervention type(s): Biological
Intervention description(s): Eighteen naïve volunteers were exposed to the bite of carrying P. vivax sporozoites. Volunteers were randomly allocated to 1 of 6 groups and exposed to different numbers of mosquito biting, for 10 min. After feeding, dissection of all mosquitoes exposed in the cage was performed, to confirm the presence of a blood meal in their midguts and sporozoites in their salivary glands. If a volunteer did not get the number of infective bites assigned for his/her group, he/she was allowed to be bitten for a new group of mosquitoes until a total of 3±1, 6±1, or 9±1 mosquito bites were achieved.
Other intervention name(s): Controlled malaria vivax infection challenge
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Keywords: Malaria; Sporozoite; Challenge Model; Plasmodium vivax; Human Volunteers