NCT03377296

Study of Controlled Human Plasmodium Vivax Infection

A Clinical Study to Assess the Safety of Controlled Human Plasmodium Vivax Malaria Infection Through Experimental Sporozoite Infection of Healthy Malaria-naïve UK Adults, and to Characterise Parasite Growth and Immune Responses to P.Vivax

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 2 (actual)
• Sponsor: University of Oxford · Academic / Other
• Sex: All
• Age: 18 Years – 50 Years
• Healthy volunteers: Accepted

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.

Conditions

• Malaria, Vivax

Interventions

Type	Name	Description
OTHER	Plasmodium vivax infection	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.
PROCEDURE	Collection of 250mL blood from each volunteer (N=2)	Collection of 250mL of P. vivax-infected blood from each volunteer when a threshold parasitaemia/ symptoms are met

Timeline

• Start date: 2018-03-03
• Primary completion: 2023-04-13
• Completion: 2023-04-13
• First posted: 2017-12-19
• Last updated: 2023-06-29

Locations

2 sites across 1 country: United Kingdom