Transmissibility of a new Plasmodium falciparum 3D7 bank for use in malaria volunteer infection studies evaluating transmission blocking interventions

Transmission blocking activity is an important characteristic of antimalarial drugs, and can be evaluated in malaria volunteer infection studies (VIS). We undertook a pilot VIS to evaluate the suitability of a recently manufactured P. falciparum 3D7 bank (3D7-MBE-008) for evaluating transmission blocking interventions. Four adults were inoculated with P. falciparum 3D7-MBE-008 infected erythrocytes and administered piperaquine on days 8 and 10 to clear asexual parasitemia while allowing gametocyte development. On day 25, participants were randomised (1:1) to receive either 0.25 mg/kg primaquine (primaquine group) or no intervention (control group). Transmissibility was assessed by enriched membrane feeding assays on days 25, 29, 32, and 39, with transmission intensity (proportion of mosquitoes infected) determined by 18S qPCR. All participants were infective on day 25, with a median 94% (range, 12%-100%) of mosquitoes positive for oocysts, and 76% (range, 8%-94%) positive for sporozoites. In the primaquine group, mosquito infectivity decreased substantially between days 25 and 29. In the control group, mosquito infectivity remained high up to day 32, and persisted to day 39 in one participant. The P. falciparum 3D7-MBE-008 parasite bank induced blood-stage infections that were highly transmissible to mosquitoes and is therefore suitable for evaluating transmission blocking interventions. Trial registration anzctr.org.au (registration number: ACTRN12622001097730), registered 08/08/2022.