Endothelium-based biomarkers are associated with cerebral malaria in Malawian children: a retrospective case-control study.

<h4>Background</h4>Differentiating cerebral malaria (CM) from other causes of serious illness in African children is problematic, owing to the non-specific nature of the clinical presentation and the high prevalence of incidental parasitaemia. CM is associated with endothelial activation...

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Autores principales:	Andrea L Conroy, Happy Phiri, Michael Hawkes, Simon Glover, Mac Mallewa, Karl B Seydel, Terrie E Taylor, Malcolm E Molyneux, Kevin C Kain
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a11de768a20b44279cff94443202a178
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spelling	oai:doaj.org-article:a11de768a20b44279cff94443202a1782021-11-18T07:01:03ZEndothelium-based biomarkers are associated with cerebral malaria in Malawian children: a retrospective case-control study.1932-620310.1371/journal.pone.0015291https://doaj.org/article/a11de768a20b44279cff94443202a1782010-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21209923/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Differentiating cerebral malaria (CM) from other causes of serious illness in African children is problematic, owing to the non-specific nature of the clinical presentation and the high prevalence of incidental parasitaemia. CM is associated with endothelial activation. In this study we tested the hypothesis that endothelium-derived biomarkers are associated with the pathophysiology of severe malaria and may help identify children with CM.<h4>Methods and findings</h4>Plasma samples were tested from children recruited with uncomplicated malaria (UM; n = 32), cerebral malaria with retinopathy (CM-R; n = 38), clinically defined CM without retinopathy (CM-N; n = 29), or non-malaria febrile illness with decreased consciousness (CNS; n = 24). Admission levels of angiopoietin-2 (Ang-2), Ang-1, soluble Tie-2 (sTie-2), von Willebrand factor (VWF), its propeptide (VWFpp), vascular endothelial growth factor (VEGF), soluble ICAM-1 (sICAM-1) and interferon-inducible protein 10 (IP-10) were measured by ELISA. Children with CM-R had significantly higher median levels of Ang-2, Ang-2:Ang-1, sTie-2, VWFpp and sICAM-1 compared to children with CM-N. Children with CM-R had significantly lower median levels of Ang-1 and higher median concentrations of Ang-2:Ang-1, sTie-2, VWF, VWFpp, VEGF and sICAM-1 compared to UM, and significantly lower median levels of Ang-1 and higher median levels of Ang-2, Ang-2:Ang-1, VWF and VWFpp compared to children with fever and altered consciousness due to other causes. Ang-1 was the best discriminator between UM and CM-R and between CNS and CM-R (areas under the ROC curve of 0.96 and 0.93, respectively). A comparison of biomarker levels in CM-R between admission and recovery showed uniform increases in Ang-1 levels, suggesting this biomarker may have utility in monitoring clinical response.<h4>Conclusions</h4>These results suggest that endothelial proteins are informative biomarkers of malarial disease severity. These results require validation in prospective studies to confirm that this group of biomarkers improves the diagnostic accuracy of CM from similar conditions causing fever and altered consciousness.Andrea L ConroyHappy PhiriMichael HawkesSimon GloverMac MallewaKarl B SeydelTerrie E TaylorMalcolm E MolyneuxKevin C KainPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 12, p e15291 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Andrea L Conroy Happy Phiri Michael Hawkes Simon Glover Mac Mallewa Karl B Seydel Terrie E Taylor Malcolm E Molyneux Kevin C Kain Endothelium-based biomarkers are associated with cerebral malaria in Malawian children: a retrospective case-control study.
description	<h4>Background</h4>Differentiating cerebral malaria (CM) from other causes of serious illness in African children is problematic, owing to the non-specific nature of the clinical presentation and the high prevalence of incidental parasitaemia. CM is associated with endothelial activation. In this study we tested the hypothesis that endothelium-derived biomarkers are associated with the pathophysiology of severe malaria and may help identify children with CM.<h4>Methods and findings</h4>Plasma samples were tested from children recruited with uncomplicated malaria (UM; n = 32), cerebral malaria with retinopathy (CM-R; n = 38), clinically defined CM without retinopathy (CM-N; n = 29), or non-malaria febrile illness with decreased consciousness (CNS; n = 24). Admission levels of angiopoietin-2 (Ang-2), Ang-1, soluble Tie-2 (sTie-2), von Willebrand factor (VWF), its propeptide (VWFpp), vascular endothelial growth factor (VEGF), soluble ICAM-1 (sICAM-1) and interferon-inducible protein 10 (IP-10) were measured by ELISA. Children with CM-R had significantly higher median levels of Ang-2, Ang-2:Ang-1, sTie-2, VWFpp and sICAM-1 compared to children with CM-N. Children with CM-R had significantly lower median levels of Ang-1 and higher median concentrations of Ang-2:Ang-1, sTie-2, VWF, VWFpp, VEGF and sICAM-1 compared to UM, and significantly lower median levels of Ang-1 and higher median levels of Ang-2, Ang-2:Ang-1, VWF and VWFpp compared to children with fever and altered consciousness due to other causes. Ang-1 was the best discriminator between UM and CM-R and between CNS and CM-R (areas under the ROC curve of 0.96 and 0.93, respectively). A comparison of biomarker levels in CM-R between admission and recovery showed uniform increases in Ang-1 levels, suggesting this biomarker may have utility in monitoring clinical response.<h4>Conclusions</h4>These results suggest that endothelial proteins are informative biomarkers of malarial disease severity. These results require validation in prospective studies to confirm that this group of biomarkers improves the diagnostic accuracy of CM from similar conditions causing fever and altered consciousness.
format	article
author	Andrea L Conroy Happy Phiri Michael Hawkes Simon Glover Mac Mallewa Karl B Seydel Terrie E Taylor Malcolm E Molyneux Kevin C Kain
author_facet	Andrea L Conroy Happy Phiri Michael Hawkes Simon Glover Mac Mallewa Karl B Seydel Terrie E Taylor Malcolm E Molyneux Kevin C Kain
author_sort	Andrea L Conroy
title	Endothelium-based biomarkers are associated with cerebral malaria in Malawian children: a retrospective case-control study.
title_short	Endothelium-based biomarkers are associated with cerebral malaria in Malawian children: a retrospective case-control study.
title_full	Endothelium-based biomarkers are associated with cerebral malaria in Malawian children: a retrospective case-control study.
title_fullStr	Endothelium-based biomarkers are associated with cerebral malaria in Malawian children: a retrospective case-control study.
title_full_unstemmed	Endothelium-based biomarkers are associated with cerebral malaria in Malawian children: a retrospective case-control study.
title_sort	endothelium-based biomarkers are associated with cerebral malaria in malawian children: a retrospective case-control study.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/a11de768a20b44279cff94443202a178
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Endothelium-based biomarkers are associated with cerebral malaria in Malawian children: a retrospective case-control study.

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