Exposure of Naive and Pre-immune Subjects to P. Vivax Challenge
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This study is a randomized clinical trial designed to compare the susceptibility of naive and
      pre-immune volunteers to infectious challenge with viable Plasmodium vivax sporozoites. The
      term preimmune hereafter denoted only previous experience with infection by this parasite and
      not a definite state of immunity to malaria infection. The study hypothesis is that
      pre-immune volunteers present a delayed onset of malaria clinical and parasitological
      manifestations when compared to naive individuals. The development of this study will
      establish a protocol for evaluating the effectiveness of vaccine candidates against P. vivax
      in subsequent Phases IIa and IIb clinical trials.
    

Detailed description: 
      This study is a prospective controlled, blinded clinical trial, designed to establish the
      differences on infectivity of an infectious challenge with P. vivax sporozoites between human
      volunteers with and without history of malaria.

      Study subjects

      This study will require the involvement of two types of volunteers:

      - Parasite donors: 5-15 P. vivax-infected patients who will serve as parasites donors for
      experimental infection of mosquitoes, who will be enrolled in the endemic area.

      - Volunteers for infectious challenge Two other groups of volunteers will be exposed to
      mosquitoes infected with P. vivax sporozoites. A group of 7 people without previous exposure
      to malaria (naive) and another 12 people with a history of previous malaria infection
      (pre-immune).

      Methodology

        -  Recruitment of infected patients Parasite donors will be recruited among P. vivax
           infected patients attending a diagnostic center in the endemic area.

        -  Infection of mosquitoes Blood from donors will be used to feed three days old mosquitoes
           by artificial membrane feeding technique. At day 7 a sample of mosquitoes will be
           examined to determine the degree of infection by dissection of the mosquito gut. On day
           14, a small amount of mosquitoes with a good degree of infectivity will be used to
           infect challenged volunteers.

        -  Recruitment of pre-immune and naive volunteers Volunteers for the challenge will be
           recruited both in the city of Cali, non-endemic region, and in Buenaventura, a malaria
           endemic region, through various activities such as conferences, meetings and other means
           approved by the IRB like posters and flyers.

      Infection of volunteers

      The "feeding cage" will be placed on the forearm of a volunteer for 10 minutes, allowing that
      the feeding window, wich will be covered by a mesh surface be placed against the volunteer's
      skin.

      Follow Up

      Volunteers will be educated about the signs and symptoms of malaria and they will have a
      daily telephone contact during the first 6 days.

      Between days 7 and 23 the volunteers will be asked to go to the Clinical Trials Unit daily in
      order to establish the presence or absence of disease through thick blood smear and samples
      will be collected for retrospective real time PCR P. vivax.

      From day 23 until day 31, volunteers will receive physical and laboratory evaluation every
      other day and will have daily telephone contact.

      Once the patients present signs and symptoms of the disease curative treatment will be
      immediately provided, and 15 ml of blood will be drawn, which will be used for immune
      response assessment.

      If the volunteers do not develop the disease during the follow-up period, on day 31 they will
      be given antimalarial treatment.

      Treatment

      Volunteers will be treated with antimalarial drugs approved by the Colombian Ministry of
      Social Protection: chloroquine (three (3) doses: 600 mg initially, followed by 450mg at 24,
      and 48 hours), associated with primaquine (30mg/día) for 14 days. All the volunteers will be
      asked to return two weeks after starting treatment for a thick blood smear test to ensure
      cure of malaria.
    

Intervention name(s): P. vivax infected mosquito bites
Intervention type(s): Biological
Intervention description(s): All volunteers will receive one dose of 2-4 P. vivax infected mosquito bites. All the mosquitoes will correspond to the same mosquito batch to make sure that all volunteers receive the same P. vivax strain.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Plasmodium vivax; Malaria; Challenge; Anopheles albimanus