David Green, MD, PhD

Recent findings suggest a possible treatment for this usually fatal disease.

Cerebral malaria is usually caused by Plasmodium falciparum infection and is often fatal. Autopsy studies show that infected erythrocytes adhere to and occlude cerebral vessels and that fibrin deposition occurs. To clarify the pathogenesis of cerebral malaria, investigators analyzed recent studies and noted the following:

The vascular bed of every organ (brain, lung, bone marrow, placenta, etc.) has a distinctive endothelial lining, and the endothelial cells of that organ expose a unique constellation of surface receptors.

Erythrocytes infected by malarial parasites expose specific membrane proteins that mediate binding to the endothelial receptors in the various vascular beds.

Infected erythrocytes bind to the endothelial protein C receptor (EPCR) of cerebral vessels.

EPCR bound by infected erythrocytes is unable to activate protein C; activated protein C (APC) normally limits thrombin generation and fibrin deposition.

APC also has cytoprotective effects, including anti-inflammatory, anti-apoptotic, and maintenance of endothelial barrier function that are impaired in cerebral malaria.

Citation(s):

Aird WC et al. Plasmodium falciparum picks (on) EPCR. Blood 2014 Jan 9; 123:163.