This will be a single-centre, open label trial to determine the safety and feasibility of CHMI model using Plasmodium falciparum-infected cryopreserved erythrocytes administered to healthy Tanzanian adults with varying prior exposure to P. falciparum.
This study will be a single-centre controlled human malaria infection study using adults with varying degrees of prior exposure to P. falciparum. The study will take place at Bagamoyo Clinical Trail Facility of the Ifakara Health Institute, located in Bagamoyo town (about 60 km north of Dar es Salaam). Twelve healthy male adults aged 18 to 35 years will be recruited into two cohorts of high and low previous exposure consisting of 6 volunteers each as determined by anti-schizont antibody levels. Up to 5 back-up volunteers will be also be recruited and may take the place of another volunteer should they withdraw or become ineligible prior to challenge. Participants will be infected via IV administration of Plasmodium falciparum-infected human erythrocytes of the chloroquine-susceptible 3D7 strain. Participants will then be closely monitored in a clinical trial facility for a maximum of 31 (28 days plus 3 days of treatment with anti-malarial drugs) days while undergoing frequent clinical and laboratory assessment. Volunteers who do not reach malaria treatment criteria as per protocol at day 28 (C+28) will be treated presumptively with antimalarial medications (ALU + a single low dose primaquine) under direct observation and will be discharged upon completion of treatment and on discretion of the study clinician. Identifying data will not be included on any trial documentation (other than signed consent) and participants will be referred to by the trial study ID number. The study will be funded primarily by EDCTP grant supporting the evaluation of Multi-Stage Malaria Vaccine.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
12
Chloroquine sensitive P. falciparum 3D7-infected red blood cells, thawed and prepared under strict aseptic conditions, will be used as a challenge agent.
Ifakara Health Institute
Bagamoyo, Tanzania
Occurrence of adverse events to assess the safety of controlled blood-stage P. falciparum
Frequency and severity of clinical and laboratory Adverse Events and Serious Adverse Events
Time frame: 98 days
Development of parasitaemia to assess the feasibility of controlled blood-stage P. falciparum
Proportion of participants who develop detectable parasitaemia post-CHMI as measured by qPCR
Time frame: 28 days
Development of parasitaemia to assess the feasibility of controlled blood-stage P. falciparum
Proportion of participants who develop sustained parasitaemia detectable by qPCR that is then spontaneously cleared
Time frame: 28 days
Parasite multiplication rates to assess the feasibility of controlled blood-stage P. falciparum
Determine parasite multiplication rates as calculated by fitting established models to quantitative PCR data, as routinely done in the published studies (Payne et al., JID 2016; Minassian et al., submitted)
Time frame: 28 days
Cellular and Humoral Immune responses level at C-1, C+7, C+14, C+21, C+28, C+56, C+98 and diagnosis
P. falciparum specific immunogenicity following P. falciparum blood-stage infection, as assessed by antibody, B cell and T cell responses. Determined by ELISA (concentration of antibodies)
Time frame: 98 days
Cellular and Humoral Immune responses level at C-1, C+7, C+14, C+21, C+28, C+56, C+98 and diagnosis
P. falciparum specific immunogenicity following P. falciparum blood-stage infection, as assessed by antibody, B cell and T cell responses. Determined by ELISpot (spots per 10\^x PBMCs)
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Time frame: 98 days
Cellular and Humoral Immune responses level at C-1, C+7, C+14, C+21, C+28, C+56, C+98 and diagnosis
P. falciparum specific immunogenicity following P. falciparum blood-stage infection, as assessed by antibody, B cell and T cell responses. Determined by flow cytometry (% of immune cell sub-population)
Time frame: 98 days
To determine the effect of pre-exposure to malaria on parasite multiplication rates following controlled blood-stage P. falciparum infection.
Comparison of PMRs between participants with low and high prior exposure to P. falciparum.
Time frame: 28 days
To determine if malaria infection following inoculation of P. falciparum is caused by the inoculum parasite strain and not wild-type strains
Determine whole genome sequences (via whole genome analysis) following controlled blood-stage P. falciparum infection to confirm malaria infection is with inoculum strain and not wild-type parasite
Time frame: 28 days