None listed
Conditions
Brief summary
A renewed focus on malaria elimination has increased the priority of research towards development of interventions to block malaria transmission, including transmission blocking vaccines (TBVs). This Phase I clinical trial is designed test if our established malaria challenge system is suitable to study transmission to mosquitoes. A Plasmodium vivax malaria infection will be established in 6 human volunteers. Vector transmission studies will be undertaken with a laboratory strain of Anopheles stephensi mosquitoes to assess the transmission of parasites to the mosquitoes, both by direct feeding on volunteers and by artificial membrane feeding. Assessment of infection of the mosquitos will be done by mid gut dissection and microscopic visualisation, to evaluate the production of oocysts following the feeding experiments. Once feeding experiments have been completed, participants will then commence curative anti malarial treatment.
Interventions
The study will be conducted in 3 cohorts, each with 2 participants. All participants will receive malaria inoculum injection of ~100 viable Plasmodium vivax-infected human erythrocytes administered intravenously. Participants will be monitored on an outpatient basis including with blood collection for quantification of parasitaemia by PCR, and for unexpected early onset of symptoms of malaria or adverse events until they are admitted to the inpatient facility for curative antimalarial chemothera
The study will be conducted in 3 cohorts, each with 2 participants. All participants will receive malaria inoculum injection of ~100 viable Plasmodium vivax-infected human erythrocytes administered intravenously. Participants will be monitored on an outpatient basis including with blood collection for quantification of parasitaemia by PCR, and for unexpected early onset of symptoms of malaria or adverse events until they are admitted to the inpatient facility for curative antimalarial chemotherapy. On the three days up to the anticipated commencement day of treatment as determined by PCR, transmission studies will be undertaken. Over those 3 days blood will be collected twice daily from each participant for membrane feeding assays with An. Stephensi, and for PCR testing and exploratory research. On the morning of those 3 days participants will then be placed in the insectary and asked to allow 30 vector mosquitoes to feed on the volar surface of their forearms or thighs for a period of 15 + 5 minutes (direct feeding assay). On the day designated for commencement of treatment, as determined by the onset of clinical manifestations of malaria infection, participants will be admitted to the study unit and confined for safety monitoring and antimalarial treatment with the antimalarial drug Riamet (artemether20mg/lumefantrine120mg). This will be administered by oral administration of 6 doses of 4 tablets (total course 24 tablets) given over a period of 60 hours following food. All doses with exception of the last will be given under direct observation of clinical staff. It is expected the last dose is taken by participants at home. Following treatment, participants will be followed up as inpatients for 36 hours to ensure tolerance of therapy and clinical response. Once clinically well, they will be followed up on an outpatient basis for continued dosing of antimalarial drug, safety and clearance of malaria parasites as assessed by sensitive quantitative PCR. Follow up visits for safety assessments will be performed on day 28 after malaria challenge and participants are required to be contactable and available up to 2 weeks following this end of study visits.
Sponsors
QIMR Berghofer Medical Research Institute
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. Adults (males and non pregnant and non lactating females), aged between 18 and 50 years who do not live alone (from Day 0 until at least the end of the antimalarial drug treatment). 2. BMI within the range 18–30 kg/m2; weight greater than 50kg, with good peripheral venous access 3. Able and willing (in the Investigator’s opinion) to comply with all study requirements. 4. Non-smokers. 5. Female participants of childbearing potential must have adequate contraception in place. 6. Blood group A Duffy antigen positive.
Exclusion criteria
1. History of clinical malaria, or traveled to or lived (greater than 2 weeks) in a malaria-endemic country during the past 12 months. 2. Known severe reaction to mosquito bites other than local itching and redness. 3. Evidence of increased cardiovascular disease risk. 4. History of a severe allergic reaction, anaphylaxis or convulsions following any vaccination or infusion. 5. Being unwilling to defer blood donations for the duration of the trial and for at least 6 months after the end of their involvement in the study. 6. A history of clinically significant ECG abnormalities and known pre-existing prolongation of the QTc interval considered clinically significant. 7. Have ever received a blood transfusion.
Outcome results
None listed