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BMC Infectious Diseases
Published in: BMC Infectious Diseases 1/2014

Open Access 01-12-2014 | Research article

Plasmodium falciparumantigenic variation: relationships between widespread endothelial activation, parasite PfEMP1 expression and severe malaria

Authors: Abdirahman I Abdi, Gregory Fegan, Michelle Muthui, Esther Kiragu, Jennifer N Musyoki, Michael Opiyo, Kevin Marsh, George M Warimwe, Peter C Bull

Published in: BMC Infectious Diseases | Issue 1/2014

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Abstract

Background

Plasmodium falciparum erythrocyte membrane protein 1(PfEMP1) is a family of variant surface antigens (VSA) that mediate the adhesion of parasite infected erythrocytes to capillary endothelial cells within host tissues. Opinion is divided over the role of PfEMP1 in the widespread endothelial activation associated with severe malaria. In a previous study we found evidence for differential associations between defined VSA subsets and specific syndromes of severe malaria: group A-like PfEMP1 expression and the “rosetting” phenotype were associated with impaired consciousness and respiratory distress, respectively. This study explores the involvement of widespread endothelial activation in these associations.

Methods

We used plasma angiopoietin-2 as a marker of widespread endothelial activation. Using logistic regression analysis, we explored the relationships between plasma angiopoietin-2 levels, parasite VSA expression and the two syndromes of severe malaria, impaired consciousness and respiratory distress.

Results

Plasma angiopoietin-2 was associated with both syndromes. The rosetting phenotype did not show an independent association with respiratory distress when adjusted for angiopoietin-2, consistent with a single pathogenic mechanism involving widespread endothelial activation. In contrast, group A-like PfEMP1 expression and angiopoietin-2 maintained independent associations with impaired consciousness when adjusted for each other.

Conclusion

The results are consistent with multiple pathogenic mechanisms leading to severe malaria and heterogeneity in the pathophysiology of impaired consciousness. The observed association between group A-like PfEMP1 and impaired consciousness does not appear to involve widespread endothelial activation.
Appendix
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Metadata
Title
Plasmodium falciparumantigenic variation: relationships between widespread endothelial activation, parasite PfEMP1 expression and severe malaria
Authors
Abdirahman I Abdi
Gregory Fegan
Michelle Muthui
Esther Kiragu
Jennifer N Musyoki
Michael Opiyo
Kevin Marsh
George M Warimwe
Peter C Bull
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2014
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/1471-2334-14-170

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