Early Endothelial Activation Precedes Glycocalyx Degradation and Microvascular Dysfunction in Experimentally Induced Plasmodium falciparum and Plasmodium vivax Infection

Author:

Woodford John12,Yeo Tsin W.34ORCID,Piera Kim A.3,Butler Kristy1,Weinberg J. Brice5ORCID,McCarthy James S.12,Anstey Nicholas M.3,Barber Bridget E.13

Affiliation:

1. Clinical Tropical Medicine Laboratory, QIMR-Berghofer Medical Research Institute, Brisbane, Queensland, Australia

2. University of Queensland, Brisbane, Queensland, Australia

3. Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia

4. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore

5. Duke University & VA Medical Centers, Durham, North Carolina, USA

Abstract

Endothelial activation and microvascular dysfunction are key pathogenic processes in severe malaria. We evaluated the early role of these processes in experimentally induced Plasmodium falciparum and P. vivax infection. Participants were enrolled in induced blood-stage malaria clinical trials. Plasma osteoprotegerin, angiopoietin-2, and von Willebrand Factor (vWF) levels were measured as biomarkers of endothelial activation. Microvascular function was assessed using peripheral arterial tonometry and near-infrared spectroscopy, and the endothelial glycocalyx was assessed by sublingual videomicroscopy and measurement of biomarkers of degradation.

Funder

HHS | National Institutes of Health

U.S. Department of Veterans Affairs

Department of Health | National Health and Medical Research Council

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Immunology,Microbiology,Parasitology

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