EPCR and Malaria Severity: The Center of a Perfect Storm

Trends Parasitol. 2017 Apr;33(4):295-308. doi: 10.1016/j.pt.2016.11.004. Epub 2016 Dec 6.


Severe malaria due to Plasmodium falciparum infection causes nearly half a million deaths per year. The different symptomatology and disease manifestations among patients have hampered understanding of severe malaria pathology and complicated efforts to develop targeted disease interventions. Infected erythrocyte sequestration in the microvasculature plays a critical role in the development of severe disease, and there is increasing evidence that cytoadherent parasites interact with host factors to enhance the damage caused by the parasite. The recent discovery that parasite binding to endothelial protein C receptor (EPCR) is associated with severe disease has suggested new mechanisms of pathology and provided new avenues for severe malaria adjunctive therapy research.

Keywords: EPCR; PfEMP1; Plasmodium; cytoadhesion; malaria; protein C.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antigens, CD / metabolism*
  • Cell Adhesion
  • Endothelial Protein C Receptor
  • Erythrocytes / parasitology
  • Host-Parasite Interactions / physiology*
  • Humans
  • Malaria, Falciparum / immunology
  • Malaria, Falciparum / parasitology*
  • Malaria, Falciparum / physiopathology*
  • Plasmodium falciparum / metabolism
  • Receptors, Cell Surface / metabolism*


  • Antigens, CD
  • Endothelial Protein C Receptor
  • PROCR protein, human
  • Receptors, Cell Surface