Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/147807
Title: Early endothelial activation precedes glycocalyx degradation and microvascular dysfunction in experimentally induced Plasmodium falciparum and Plasmodium vivax infection
Authors: Woodford, John
Yeo, Tsin Wen
Piera, Kim A.
Butler, Kristy
Weinberg, J. Brice
McCarthy, James S.
Anstey, Nicholas M.
Barber, Bridget E.
Keywords: Science::Medicine
Issue Date: 2020
Source: Woodford, J., Yeo, T. W., Piera, K. A., Butler, K., Weinberg, J. B., McCarthy, J. S., Anstey, N. M. & Barber, B. E. (2020). Early endothelial activation precedes glycocalyx degradation and microvascular dysfunction in experimentally induced Plasmodium falciparum and Plasmodium vivax infection. Infection and Immunity, 88(5). https://dx.doi.org/10.1128/IAI.00895-19
Journal: Infection and Immunity 
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. Forty-five healthy, malaria-naive participants were recruited from 5 studies. Osteoprotegerin and vWF levels increased in participants following inoculation with P. vivax (n = 16) or P. falciparum (n = 15), with the angiopoietin-2 level also increasing in participants following inoculation with P. falciparum For both species, the most pronounced increase was seen in osteoprotegerin. This was particularly marked in participants inoculated with P. vivax, where the osteoprotegerin level correlated with the levels of parasitemia and the malaria clinical score. There were no changes in measures of endothelial glycocalyx or microvascular function. Plasma biomarkers of endothelial activation increased in early P. falciparum and P. vivax infection and preceded changes in the endothelial glycocalyx or microvascular function. The more pronounced increase in osteoprotegerin suggests that this biomarker may play a role in disease pathogenesis.
URI: https://hdl.handle.net/10356/147807
ISSN: 0019-9567
DOI: 10.1128/IAI.00895-19
Schools: Lee Kong Chian School of Medicine (LKCMedicine) 
Rights: © 2020 American Society for Microbiology. All Rights Reserved. This paper was published in Infection and Immunity and is made available with permission of American Society for Microbiology.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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