Study of Controlled Human Plasmodium Vivax Infection
Condition: Malaria, Vivax
MeSH terms: Malaria; Malaria, Vivax
Study type: Interventional

Summary: 
      This is a sporozoite-challenge clinical study with the primary aim of assessing the safety
      and feasibility of controlled human P. vivax malaria infection in two healthy volunteers. The
      investigators will also assess the growth of and the immune response to P. vivax infection,
      and assess the induction of sexual gametocytaemia post-CHMI via the natural route of malaria
      infection (mosquito bite). A secondary objective is to develop a blood inoculum of P.
      vivax-infected blood for future testing of candidate vaccines.
    

Detailed description: 
      This is a sporozoite-challenge clinical study with the primary aim of assessing the safety
      and feasibility of controlled human P. vivax malaria infection in two healthy volunteers. The
      investigators will also assess the growth of and the immune response to P. vivax infection,
      and assess the induction of sexual gametocytaemia post-CHMI via the natural route of malaria
      infection (mosquito bite). A secondary objective is to develop a blood inoculum of P.
      vivax-infected blood for future testing of candidate vaccines.

      Two healthy, malaria-naïve adults aged between 18 and 50 years will be recruited at the
      CCVTM, Oxford. CHMI by sporozoites will be delivered by mosquito bite at Imperial College,
      London, and follow-up during the post-challenge period will be at the CCVTM in Oxford.

      The two volunteers will have blood taken at regular intervals post-CHMI to assess the immune
      response to primary P. vivax infection, and also the gametocytaemia following P. vivax
      infection, and the volunteers will be monitored closely until the volunteers meet the
      criteria for treatment. Up to 250 mL (half a unit) of blood will be taken just prior to
      treatment from the two successfully infected volunteers (as determined by measurement of the
      parasitaemia) and frozen down for future use in blood-stage CHMI trials. The volunteers will
      be treated with a standard 60-hour course of oral artemether-lumefantrine (Riamet) followed
      by a 2-week course of partially-observed oral Primaquine for radical cure of P. vivax
      hypnozoites. The volunteers will be followed up for 3 months in the clinic and email
      follow-up will continue out to 5 years to monitor for clinical relapse.
    

Intervention name(s): Plasmodium vivax infection; Collection of 250mL blood from each volunteer (N=2)
Intervention type(s): Other; Procedure
Intervention description(s): Two healthy human volunteers are exposed to the bites of five infectious mosquitoes per participant (by placing their forearms over the pot containing mosquitoes) for 5-10 minutes. Fed mosquitoes (as indicated by the presence of a blood meal in the abdomen) are individually dissected and assessed for sporozoite load (graded 0 to +4; a gland rating of +2 or more, representing 10 or more observed sporozoites, qualifies as being infectious). If, by this method the volunteer is found to have been inoculated by less than five infected mosquitoes, further mosquitoes are allowed to feed on the volunteer until a total of 5 appropriately infected mosquitoes have fed. The bite-challenge procedure continues until the subject has been bitten by 5 infectious mosquitoes.; Collection of 250mL of P. vivax-infected blood from each volunteer when a threshold parasitaemia/ symptoms are met
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Other