Immune response in a human malaria challenge system.

This is a single-centre, controlled study using a Blood Stage Plasmodium Falciparum Challenge (BSPC) inoculum challenge to characterize molecular signatures during early Plasmodium falciparum blood stage infection The study will be conducted in 2 or more cohorts (n equal to 8 and n equal 8). Cohort 2 will not commence until at least after day 13 of the previous cohort and review by Safety Review Team following day 10 exit of the previous cohort. Each participant in the cohort will be inoculated on Day 0 with approximately 450 Plasmodium falciparum-infected human erythrocytes administered intravenously. On an outpatient basis, participants will be monitored daily (AM) or morning (AM) and evening (PM) (once PCR positive for presence of malaria parasites) from day 1 to day 9 for adverse events and the unexpected early onset of symptoms, signs or parasitological evidence of malaria. On the day designated for commencement of treatment, as determined by qPCR results, participants will be admitted to the study unit and confined for safety monitoring and antimalarial treatment. The threshold for commencement of treatment will be when PCR quantification is confirmed to be greater than or equal to 1,000 parasites/mL when the participants will be administered antimalarial treatment. If clinical or parasitological evidence of malaria (either the identification of two or more malaria parasites on a malaria thick film, platelet count less than 100 x109/L, or the onset of clinical features of malaria) occurs or PCR quantification of greater than or equal to 1,000 parasites/mL is detected before day 9 morning, allocated treatment will begin at this time. Following treatment, participants will be followed up as inpatients for at least 36 hours, to ensure tolerance of the therapy and clinical response, then if clinically well on an outpatient basis for safety and continued presence of malaria parasites via PCR and thick blood film review. Adverse events will be monitored via telephone monitoring, within the clinical research unit and on outpatient review after malaria challenge inoculation and antimalarial study drug administration. Blood samples for safety evaluation, malaria monitoring and red blood cell antibodies will be drawn at baseline and at nominated times after malaria challenge.