Assessing transmission of Plasmodium falciparum 3D7-MBE008 parasites from healthy participants to mosquitoes

This is a randomised study that will use the induced blood stage malaria (IBSM) model to evaluate the transmission of P. falciparum 3D7-MBE008 parasites from volunteers to mosquitoes. The study will be conducted in four participants. Eligible participants will be inoculated intravenously on Day 0 with approximately 2,800 viable P. falciparum 3D7-MBE008 infected red blood cells in a volume of 2 mL. Volunteers will be followed up daily via phone call or text message on Days 1 to 3 post-inoculation to solicit any adverse events. On Days 4 to 7 volunteers will attend the clinical unit once daily (or twice daily if required) for clinical evaluation and blood sampling to monitor the progression of parasitaemia. Malaria parasitaemia will be quantified using quantitative polymerase chain reaction (qPCR) targeting the gene encoding 18S rRNA. On Day 8 when parasitaemia for the majority of volunteers is expected to be above 10,000 parasites/mL, participants will be administered a dose of 480 mg piperaquine as oral tablets. Participants will return to the clinic on Days 9 and 10 to ensure adequate clinical and parasitological response to piperaquine dosing. An additional dose of piperaquine (960 mg as oral tablets) will be administered on Day 10. Between Day 11 and Day 24, regular outpatient visits will occur to monitor parasitaemia and perform safety assessments. On Day 25, transmission of gametocytes to Anopheles mosquitoes will be assessed with an enriched membrane-feeding assay using blood samples taken from the participants (blood sampling done at clinic as per other blood samples taken for this study). Volunteers will be randomised to receive either an oral tablet dose of approximately 0.25 mg/kg primaquine (Primacinactive control group) or no transmission blocking intervention (no drug control group) in a 1:1 ratio. No blinding will be performed. Additional enriched membrane-feeding assays will be performed on Days 26, 27, 29, 32, and 39 to determine if parasites remain transmissible over this period in the no drug control group, and to determine the effect of primaquine on transmission (active control group). All participants will begin antimalarial rescue treatment with a standard course of artemether-lumefantrine on Day 39 (Riamet; six doses of four tablets totaling 480 mg artemether and 2880 mg lumefantrine administered orally twice daily over three consecutive days), or earlier in the event that piperaquine treatment fails to clear asexual parasitaemia or prevent recrudescence. Each tablet contains 20 mg artemether and 120 mg lumefantrine. If gametocytes are present at or after the time of treatment with artemether-lumefantrine, 45 mg primaquine as oral tablets may be administered at the Investigator’s discretion. The end of study visit will occur on Day 42 plus or minus 2 days. Strategies to monitor adherence to the intervention include The Investigator or delegate administering the malaria challenge agent intravenously at the clinical trial unit. Piperaquine and primaquine will be administered at the clinical trial unit under direct observation by staff. The first dose of artemether-lumefantrine will be administered at the clinical trial unit under direct observation by staff. The subsequent five doses of artemether-lumefantrine may be taken at home. Participants will receive a phone call or text message from the clinical trial unit staff to ensure compliance.