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

Publication ,  Journal Article
Woodford, J; Yeo, TW; Piera, KA; Butler, K; Weinberg, JB; McCarthy, JS; Anstey, NM; Barber, BE
Published in: Infect Immun
April 20, 2020

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.

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Published In

Infect Immun

DOI

EISSN

1098-5522

Publication Date

April 20, 2020

Volume

88

Issue

5

Location

United States

Related Subject Headings

  • Young Adult
  • Prospective Studies
  • Plasmodium vivax
  • Plasmodium falciparum
  • Middle Aged
  • Microvessels
  • Microbiology
  • Male
  • Malaria, Vivax
  • Malaria, Falciparum
 

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Woodford, J., Yeo, T. W., Piera, K. A., Butler, K., Weinberg, J. B., McCarthy, J. S., … Barber, B. E. (2020). Early Endothelial Activation Precedes Glycocalyx Degradation and Microvascular Dysfunction in Experimentally Induced Plasmodium falciparum and Plasmodium vivax Infection. Infect Immun, 88(5). https://doi.org/10.1128/IAI.00895-19
Woodford, John, Tsin W. Yeo, Kim A. Piera, Kristy Butler, J Brice Weinberg, James S. McCarthy, Nicholas M. Anstey, and Bridget E. Barber. “Early Endothelial Activation Precedes Glycocalyx Degradation and Microvascular Dysfunction in Experimentally Induced Plasmodium falciparum and Plasmodium vivax Infection.Infect Immun 88, no. 5 (April 20, 2020). https://doi.org/10.1128/IAI.00895-19.
Woodford J, Yeo TW, Piera KA, Butler K, Weinberg JB, McCarthy JS, Anstey NM, Barber BE. Early Endothelial Activation Precedes Glycocalyx Degradation and Microvascular Dysfunction in Experimentally Induced Plasmodium falciparum and Plasmodium vivax Infection. Infect Immun. 2020 Apr 20;88(5).

Published In

Infect Immun

DOI

EISSN

1098-5522

Publication Date

April 20, 2020

Volume

88

Issue

5

Location

United States

Related Subject Headings

  • Young Adult
  • Prospective Studies
  • Plasmodium vivax
  • Plasmodium falciparum
  • Middle Aged
  • Microvessels
  • Microbiology
  • Male
  • Malaria, Vivax
  • Malaria, Falciparum