Plasmodium knowlesi – Clinical Isolate Genome Sequencing to Inform Translational Same-Species Model System for Severe Malaria

Abstract

Malaria is responsible for unacceptably high morbidity and mortality, especially in Sub-Saharan African Nations. Malaria is caused by member species’ of the genusPlasmodiumand despite concerted and at times valiant efforts, the underlying pathophysiological processes leading to severe disease are poorly understood. Here we describe zoonotic malaria caused byPlasmodium knowlesiand the utility of this parasite as a model system for severe malaria. We present a method to generate long-read third-generationPlasmodiumgenome sequence data from archived clinical samples using the MinION platform. The method and technology are accessible, affordable and data is generated in real-time. We propose that by widely adopting this methodology important information on clinically relevant parasite diversity, including multiple gene family members, from geographically distinct study sites will emerge. Our goal, over time, is to exploit the duality ofP. knowlesias a well-used laboratory model and human pathogen to develop a representative translational model system for severe malaria that is informed by clinically relevant parasite diversity.