Abstract
BackgroundThe lack of a continuous long-term in vitro culture system for Plasmodium vivax severely limits our knowledge of pathophysiology of the most widespread malaria parasite. To gain direct understanding of P. vivax human infections, we used Next Generation Sequencing data mining to unravel parasite in vivo expression profiles for P. vivax, and P. falciparum as comparison.ResultsWe performed cloud and local computing to extract parasite transcriptomes from publicly available raw data of human blood samples. We developed a Poisson Modelling (PM) method to confidently identify parasite derived transcripts in mixed RNAseq signals of infected host tissues. We successfully retrieved and reconstructed parasite transcriptomes from infected patient blood as early as the first blood stage cycle; and the same methodology did not recover any significant signal from controls. Surprisingly, these first generation blood parasites already show strong signature of transmission, which indicates the commitment from asexual-to-sexual stages. Further, we place the results within the context of P. vivax’s complex life cycle, by developing mathematical models for P. vivax and P. falciparum and using sensitivity analysis assess the relative epidemiological impact of possible early stage transmission.ConclusionThe study uncovers the earliest onset of P. vivax blood pathogenesis and highlights the challenges of P. vivax eradication programs.
Highlights
The lack of a continuous long-term in vitro culture system for Plasmodium vivax severely limits our knowledge of pathophysiology of the most widespread malaria parasite
Using cloud-based computational pipelines to mine parasite derived transcript To understand P. vivax in vivo pathogenesis, we first utilized a set of publicly available Next Generation Sequencing (NGS) ( Generation Sequencing) raw data from Rojas-Pina et al [13] that examined human immune responses against malaria
The post-infection RNA sequencing (RNAseq) was produced around day 9, i.e., the first blood stage cycle after the liver stage infection which usually lasts for about 6–7 days [4, 5]
Summary
The lack of a continuous long-term in vitro culture system for Plasmodium vivax severely limits our knowledge of pathophysiology of the most widespread malaria parasite. Plasmodium vivax (P. vivax) infection has the most widespread distribution across different continents of any malaria parasite, with up to 2.6 billion people estimated to be at risk [1]. It can lead to severe disease and death but, despite the high disease burden [2], there is a lack of in-depth understanding of the distinct pathogenesis of P. vivax. This has resulted in a lack of targeted control measures. Whether sexual commitment in P. vivax occurs early still needs to be determined
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