Apheresis of healthy subjects with induced blood stage Plasmodium vivax

This is a Phase 1 study designed to determine the safety and feasibility of using apheresis as a method for extracting all lifecycle stages of malaria parasites from the blood of healthy subjects experimentally infected with blood stage Plasmodium vivax. This study will be conducted in up to 8 subjects (8 cohorts of 1 subject each). The apheresis procedure will involve the insertion of 2 large intravenous needles into large veins located in both antecubital fossae (elbow crease). Blood will be removed from the cannula in one arm and passed through the apheresis machine and then returned to the participant through the cannula in the other arm. The Spectra Optia Apheresis System acts by separating blood into its various components by density. At the same time as the blood is removed, an anticoagulant (citrate) will be infused into your other arm meaning the total blood volume will remain the same. The whole apheresis procedure will take approximately 2-4 hours. Subjects will be inoculated intravenously on Day 0 with approximately 1100 viable P. vivax HMPBS02-Pv parasite-infected erythrocytes. On an outpatient basis, subjects will be monitored daily via phone and then will attend the clinical unit daily from 4 days post-inoculation for blood sampling to measure parasitaemia via quantitative polymerase chain reaction (qPCR) targeting the P. vivax 18S rRNA gene (referred to as malaria 18S qPCR), to monitor symptoms and signs of malaria, and to record adverse events. The threshold for the commencement of apheresis and subsequent antimalarial rescue treatment with artemether/lumefantrine will occur when parasitaemia is greater than 20,000 parasites/mL or the Malaria Clinical Score is greater than 6 (within 24 hours of notification) or at the Investigator’s discretion. On the day that this threshold is reached (expected to occur on Day 10), the subject will be admitted to the clinical unit for initial safety assessments before undergoing apheresis whilst being supervised by the apheresis specialist nurse. The subject will then be administered the first dose of artemether/lumefantrine and will remain confined within the clinical unit for 72 hours to monitor for safety and tolerability of apheresis and rescue therapy, and to ensure adequate clinical and parasitological response to treatment. A course of artemether/lumefantrine treatment consists of 20 mg artemether/120 mg lumefantrine oral tablets with 6 doses of 4 tablets administered over a period of 60 hours. In the unlikely event that artemether/lumefantrine fails to clear parasitaemia, subjects will be treated with chloroquine phosphate. Chloroquine phosphate 250 mg oral tablets will be administered as an initial dose of 4 tablets, followed by a dose of 2 tablets each at 6, 24 and 48 hours (i.e. a total dose of 2.5 g chloroquine phosphate). If oral administration of either artemether/lumefantrine or chloroquine phosphate is not possible (e.g. the subject is vomiting), the subject will receive intravenous treatment with artesunate. This would be done at the recommended dose regime of 2.4 mg/kg at approximately 0, 12, 24, 48 hours and then daily for up to 7 days or until able to take oral drugs. After discharge from the clinical unit, subjects will be followed up on an out-patient basis for monitoring of safety and parasite clearance. Follow-up for safety assessments will be performed on Day 28 plus or minus 3, Day 56 plus or minus 7 (phone call only), and Day 90 plus or minus 7(End of Study).