Safety and feasibility of apheresis to harvest and concentrate parasites from subjects with induced blood stage Plasmodium vivax infection

Abstract Background In the absence of a method to culture Plasmodium vivax , only way source parasites is ex vivo. This hampers many aspects P. research. study aimed assess safety apheresis, for selective removal specific components blood as means extracting and concentrating parasites. Methods An iterative approach was employed across four non-immune healthy human subjects in single subject cohorts. All were inoculated with ~ 564 stage (HMP013- Pv ) subjected apheresis 10 11 days later . Blood samples collected during (haematocrit layers 0.5% 11%) tested presence concentration by microscopy, flow cytometry, 18S rDNA qPCR total parasites, pvs2 5 qRT-PCR female gametocyte transcripts. Safety determined monitoring adverse events. Malaria transmission mosquitoes assessed membrane feeding assays. Results There no serious events significant concerns. Apheresis concentrated asexual up 4.9-fold (range: 0.9–4.9-fold) gametocytes 1.45-fold 0.38–1.45-fold) compared pre-apheresis densities. No haematocrit layer contained > 40% all recovered Ex vivo Percoll gradient centrifugation whole achieved greater than apheresis. Mosquito enhanced fivefold sample pre-apheresis. Conclusion The modest level parasite suggests that use may not be an ideal harvesting vivax. Trial Registration Australia New Zealand Clinical Trials Registry (ANZCTR) ID: ACTRN12617001502325 registered on 19th October 2017. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373812.