Abstract
Retinopathy provides a window into the underlying pathology of life-threatening malarial coma (“cerebral malaria”), allowing differentiation between 1) coma caused by sequestration of Plasmodium falciparum-infected erythrocytes in the brain and 2) coma with other underlying causes. Parasite sequestration in the brain is mediated by PfEMP1; a diverse parasite antigen that is inserted into the surface of infected erythrocytes and adheres to various host receptors. PfEMP1 sub-groups called “DC8” and “DC13” have been proposed to cause brain pathology through interactions with endothelial protein C receptor. To test this we profiled PfEMP1 gene expression in parasites from children with clinically defined cerebral malaria, who either had or did not have accompanying retinopathy. We found no evidence for an elevation of DC8 or DC13 PfEMP1 expression in children with retinopathy. However, the proportional expression of a broad subgroup of PfEMP1 called “group A” was elevated in retinopathy patients suggesting that these variants may play a role in the pathology of cerebral malaria. Interventions targeting group A PfEMP1 may be effective at reducing brain pathology.
Highlights
Retinopathy was positive (CM-R+) in 25/80(31.25%), and negative (CM-R–) in 55/80 (68.75%), which is similar to the original study[21], suggesting good representation of the original sample
Children with coma co-presenting with respiratory distress (RD) tended to be more common among the cerebral malaria (CM)-R- group, though this was not statistically significant (p = 0.08, Table 1)
As PfEMP1 is thought to be a major ligand expressed on the infected erythrocytes (IE) responsible for sequestration, this study aimed to identify PfEMP1 subsets associated with sequestration of IE during retinopathy by comparing the var expression profile of parasites from children with cerebral malaria with and without retinopathy (CM-R+ and CM-R–)
Summary
As PfEMP1 is thought to be a major ligand expressed on the IE responsible for sequestration, this study aimed to identify PfEMP1 subsets associated with sequestration of IE during retinopathy by comparing the var expression profile of parasites from children with cerebral malaria with and without retinopathy (CM-R+ and CM-R–)
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