Clinical Trial for the Development of a Safe Malaria Challenge Model That Can be Reproduced in Humans
Condition: Plasmodium Vivax Malaria
MeSH terms: Malaria; Malaria, Vivax
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to demonstrate that volunteers can be safely and reproducibly
      infected with Plasmodium vivax (P. vivax) by the bites of experimentally infected Anopheles
      dirus (An. dirus) mosquitoes carrying P. vivax sporozoites in their salivary glands.
    

Detailed description: 
      The study is a proof-of-concept clinical investigation designed to develop a safe and
      practical sporozoite challenge model for Plasmodium vivax in humans with a goal of 100%
      infectivity rate. The development and standardization of such a model will make possible
      efficacy evaluations of candidate P. vivax vaccines in Phase 2a trials. This trial is
      conducted in collaboration with Armed Forces Research Institute of Medical Sciences (AFRIMS)
      investigators in Bangkok, Thailand, who will be recruiting adult blood donors from a pool of
      patients who present with active P. vivax infections in Thailand. Samples of P. vivax
      infected blood will be collected and fed via membrane feeding apparatus to colony-reared
      Anopheles dirus mosquitoes at the AFRIMS Entomology Lab. A portion of the same blood will
      meanwhile be screened for potential co-infections at the AFRIMS Retrovirology Laboratory.
      When screening tests have confirmed the presence of only P. vivax in the blood (no
      co-infections with other malaria species), and selected dissection on days 3-7 has revealed
      oocyst production in the blood-fed mosquitoes, the mosquitoes will be transported from the
      AFRIMS insectary in Thailand to the WRAIR insectary in the US by a standard procedure (herein
      described) including permits and assurance against accidental release of the infected
      mosquitoes. Transport will be conducted in compliance with Thai exporting and US importing
      requirements.

      Our study will involve two cohorts, each to be challenged once, in the hope of demonstrating
      reproducibility of the entire challenge procedure. Each cohort comprises up to 6 healthy
      adult volunteers. The first cohort will be challenged with 5 bites from P. vivax-infected
      mosquitoes each carrying at least a grade 2 sporozoite infection (>10 sporozoites in salivary
      gland).

      If all six volunteers in the first cohort develop P. vivax infection, the same procedure will
      be repeated in the second cohort. If the first cohort has less than 100% infectivity rate,
      the second cohort will be challenged with up to 10 grade 2 infective bites to ensure 100%
      infectivity rate. Volunteers will be closely monitored post-infection, and will be treated
      with standard chloroquine and primaquine therapies when the infection becomes patent in the
      peripheral blood.
    

Intervention name(s): Malaria Challenge
Intervention type(s): Biological
Intervention description(s): Malaria challenge
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Malaria, Plasmodium vivax