The Rheopathobiology of Plasmodium vivax and Other Important Primate Malaria Parasites

Bruce M. Russell, Brian M. Cooke

Research output: Contribution to journalArticleResearchpeer-review

19 Citations (Scopus)

Abstract

Our current understanding of how malaria parasites remodel their host red blood cells (RBCs) and ultimately cause disease is largely based on studies of Plasmodium falciparum. In this review, we expand our knowledge to include what is currently known about pathophysiological changes to RBCs that are infected by non-falciparum malaria parasites. We highlight the potential folly of making generalizations about the rheology of malaria infection, and emphasize the need for more systematic studies into the erythrocytic biology of non-falciparum malaria parasites. We propose that a better understanding of the mechanisms that underlie the changes to RBCs induced by malaria parasites other than P. falciparum may be highly informative for the development of therapeutics that specifically disrupt the altered rheological profile of RBCs infected with either sexual- or asexual-stage parasites, resulting in drugs that block transmission, reduce disease severity, and help delay the onset of resistance to current and future anti-malaria drugs. Profound changes to the rheological properties of RBCs infected by Plasmodium spp. are central to the pathobiology of human malaria. However, the rheopathology of non-P. falciparum causes of human malaria remains poorly understood.The rheological properties of Plasmodium-infected RBCs are affected by parasite and host factors.The species of malaria parasite is perhaps the greatest contributor to variation in the rheology of parasite-infected RBCs. RBCs infected with mature asexual P. falciparum and Plasmodium coatnyei become knobby, adhesive and rigid. By contrast, Plasmodium vivax, Plasmodium ovale, and Plasmodium cynomolgi cause rigid human reticulocytes to become as deformable as an uninfected normocyte.Rosetting in P. vivax and other nonfalciparum species is most likely to be an adaption used to avoid destruction by the host immune system.Recent investigations of novel therapeutics that target the rheological properties of RBCs infected by Plasmodium spp. (particularly gametocytes) offer a promising new avenue not only to reduce disease severity, but also to interrupt parasite transmission.

Original languageEnglish
Pages (from-to)321-334
Number of pages14
JournalTrends in Parasitology
Volume33
Issue number4
DOIs
Publication statusPublished - Apr 2017

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