Parasite biomass-related inflammation, endothelial activation, microvascular dysfunction and disease severity in vivax malaria
Plasmodium vivax can cause severe malaria, however its pathogenesis is poorly understood. In contrast to P. falciparum, circulating vivax parasitemia is low, with minimal apparent sequestration in endothelium-lined microvasculature, and pathogenesis thought unrelated to parasite biomass. However, th...
Saved in:
Main Authors: | , , , , , , , |
---|---|
Other Authors: | |
Format: | Article |
Language: | English |
Published: |
2015
|
Subjects: | |
Online Access: | https://hdl.handle.net/10356/79442 http://hdl.handle.net/10220/25271 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Institution: | Nanyang Technological University |
Language: | English |
id |
sg-ntu-dr.10356-79442 |
---|---|
record_format |
dspace |
spelling |
sg-ntu-dr.10356-794422022-02-16T16:30:24Z Parasite biomass-related inflammation, endothelial activation, microvascular dysfunction and disease severity in vivax malaria Grigg, Matthew J. Parameswaran, Uma Piera, Kim A. Price, Ric N. Yeo, Tsin W. Anstey, Nicholas M. Barber, Bridget E. William, Timothy Stevenson, Mary M. Lee Kong Chian School of Medicine (LKCMedicine) DRNTU::Science::Biological sciences::Zoology::Invertebrates Plasmodium vivax can cause severe malaria, however its pathogenesis is poorly understood. In contrast to P. falciparum, circulating vivax parasitemia is low, with minimal apparent sequestration in endothelium-lined microvasculature, and pathogenesis thought unrelated to parasite biomass. However, the relationships between vivax disease-severity and total parasite biomass, endothelial autocrine activation and microvascular dysfunction are unknown. We measured circulating parasitemia and markers of total parasite biomass (plasma parasite lactate dehydrogenase [pLDH] and PvLDH) in adults with severe (n = 9) and non-severe (n = 53) vivax malaria, and examined relationships with disease-severity, endothelial activation, and microvascular function. Healthy controls and adults with non-severe and severe falciparum malaria were enrolled for comparison. Median peripheral parasitemia, PvLDH and pLDH were 2.4-fold, 3.7-fold and 6.9-fold higher in severe compared to non-severe vivax malaria (p = 0.02, p = 0.02 and p = 0.015, respectively), suggesting that, as in falciparum malaria, peripheral P. vivax parasitemia underestimates total parasite biomass, particularly in severe disease. P. vivax schizonts were under-represented in peripheral blood. Severe vivax malaria was associated with increased angiopoietin-2 and impaired microvascular reactivity. Peripheral vivax parasitemia correlated with endothelial activation (angiopoietin-2, von-Willebrand-Factor [VWF], E-selectin), whereas markers of total vivax biomass correlated only with systemic inflammation (IL-6, IL-10). Activity of the VWF-cleaving-protease, ADAMTS13, was deficient in proportion to endothelial activation, IL-6, thrombocytopenia and vivax disease-severity, and associated with impaired microvascular reactivity in severe disease. Impaired microvascular reactivity correlated with lactate in severe vivax malaria. Findings suggest that tissue accumulation of P. vivax may occur, with the hidden biomass greatest in severe disease and capable of mediating systemic inflammatory pathology. The lack of association between total parasite biomass and endothelial activation is consistent with accumulation in parts of the circulation devoid of endothelium. Endothelial activation, associated with circulating parasites, and systemic inflammation may contribute to pathology in vivax malaria, with microvascular dysfunction likely contributing to impaired tissue perfusion. Published version 2015-03-24T08:07:40Z 2019-12-06T13:25:22Z 2015-03-24T08:07:40Z 2019-12-06T13:25:22Z 2015 2015 Journal Article Barber, B. E., William, T., Grigg, M. J., Parameswaran, U., Piera, K. A., Price, R. N., et al. (2015). Parasite biomass-related inflammation, endothelial activation, microvascular dysfunction and disease severity in vivax malaria. PLoS pathogens, 11(1), e1004558-. 1553-7374 https://hdl.handle.net/10356/79442 http://hdl.handle.net/10220/25271 10.1371/journal.ppat.1004558 25569250 en PLoS pathogens © 2015 Barber et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 13 p. application/pdf |
institution |
Nanyang Technological University |
building |
NTU Library |
continent |
Asia |
country |
Singapore Singapore |
content_provider |
NTU Library |
collection |
DR-NTU |
language |
English |
topic |
DRNTU::Science::Biological sciences::Zoology::Invertebrates |
spellingShingle |
DRNTU::Science::Biological sciences::Zoology::Invertebrates Grigg, Matthew J. Parameswaran, Uma Piera, Kim A. Price, Ric N. Yeo, Tsin W. Anstey, Nicholas M. Barber, Bridget E. William, Timothy Parasite biomass-related inflammation, endothelial activation, microvascular dysfunction and disease severity in vivax malaria |
description |
Plasmodium vivax can cause severe malaria, however its pathogenesis is poorly understood. In contrast to P. falciparum, circulating vivax parasitemia is low, with minimal apparent sequestration in endothelium-lined microvasculature, and pathogenesis thought unrelated to parasite biomass. However, the relationships between vivax disease-severity and total parasite biomass, endothelial autocrine activation and microvascular dysfunction are unknown. We measured circulating parasitemia and markers of total parasite biomass (plasma parasite lactate dehydrogenase [pLDH] and PvLDH) in adults with severe (n = 9) and non-severe (n = 53) vivax malaria, and examined relationships with disease-severity, endothelial activation, and microvascular function. Healthy controls and adults with non-severe and severe falciparum malaria were enrolled for comparison. Median peripheral parasitemia, PvLDH and pLDH were 2.4-fold, 3.7-fold and 6.9-fold higher in severe compared to non-severe vivax malaria (p = 0.02, p = 0.02 and p = 0.015, respectively), suggesting that, as in falciparum malaria, peripheral P. vivax parasitemia underestimates total parasite biomass, particularly in severe disease. P. vivax schizonts were under-represented in peripheral blood. Severe vivax malaria was associated with increased angiopoietin-2 and impaired microvascular reactivity. Peripheral vivax parasitemia correlated with endothelial activation (angiopoietin-2, von-Willebrand-Factor [VWF], E-selectin), whereas markers of total vivax biomass correlated only with systemic inflammation (IL-6, IL-10). Activity of the VWF-cleaving-protease, ADAMTS13, was deficient in proportion to endothelial activation, IL-6, thrombocytopenia and vivax disease-severity, and associated with impaired microvascular reactivity in severe disease. Impaired microvascular reactivity correlated with lactate in severe vivax malaria. Findings suggest that tissue accumulation of P. vivax may occur, with the hidden biomass greatest in severe disease and capable of mediating systemic inflammatory pathology. The lack of association between total parasite biomass and endothelial activation is consistent with accumulation in parts of the circulation devoid of endothelium. Endothelial activation, associated with circulating parasites, and systemic inflammation may contribute to pathology in vivax malaria, with microvascular dysfunction likely contributing to impaired tissue perfusion. |
author2 |
Stevenson, Mary M. |
author_facet |
Stevenson, Mary M. Grigg, Matthew J. Parameswaran, Uma Piera, Kim A. Price, Ric N. Yeo, Tsin W. Anstey, Nicholas M. Barber, Bridget E. William, Timothy |
format |
Article |
author |
Grigg, Matthew J. Parameswaran, Uma Piera, Kim A. Price, Ric N. Yeo, Tsin W. Anstey, Nicholas M. Barber, Bridget E. William, Timothy |
author_sort |
Grigg, Matthew J. |
title |
Parasite biomass-related inflammation, endothelial activation, microvascular dysfunction and disease severity in vivax malaria |
title_short |
Parasite biomass-related inflammation, endothelial activation, microvascular dysfunction and disease severity in vivax malaria |
title_full |
Parasite biomass-related inflammation, endothelial activation, microvascular dysfunction and disease severity in vivax malaria |
title_fullStr |
Parasite biomass-related inflammation, endothelial activation, microvascular dysfunction and disease severity in vivax malaria |
title_full_unstemmed |
Parasite biomass-related inflammation, endothelial activation, microvascular dysfunction and disease severity in vivax malaria |
title_sort |
parasite biomass-related inflammation, endothelial activation, microvascular dysfunction and disease severity in vivax malaria |
publishDate |
2015 |
url |
https://hdl.handle.net/10356/79442 http://hdl.handle.net/10220/25271 |
_version_ |
1725985503560335360 |