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Cerebrospinal fluid and serum biomarkers of cerebral malaria mortality in Ghanaian children
BACKGROUND: Plasmodium falciparum can cause a diffuse encephalopathy known as cerebral malaria (CM), a major contributor to malaria associated mortality. Despite treatment, mortality due to CM can be as high as 30% while 10% of survivors of the disease may experience short- and long-term neurologica...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2186349/ https://www.ncbi.nlm.nih.gov/pubmed/17997848 http://dx.doi.org/10.1186/1475-2875-6-147 |
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author | Armah, Henry B Wilson, Nana O Sarfo, Bismark Y Powell, Michael D Bond, Vincent C Anderson, Winston Adjei, Andrew A Gyasi, Richard K Tettey, Yao Wiredu, Edwin K Tongren, Jon Eric Udhayakumar, Venkatachalam Stiles, Jonathan K |
author_facet | Armah, Henry B Wilson, Nana O Sarfo, Bismark Y Powell, Michael D Bond, Vincent C Anderson, Winston Adjei, Andrew A Gyasi, Richard K Tettey, Yao Wiredu, Edwin K Tongren, Jon Eric Udhayakumar, Venkatachalam Stiles, Jonathan K |
author_sort | Armah, Henry B |
collection | PubMed |
description | BACKGROUND: Plasmodium falciparum can cause a diffuse encephalopathy known as cerebral malaria (CM), a major contributor to malaria associated mortality. Despite treatment, mortality due to CM can be as high as 30% while 10% of survivors of the disease may experience short- and long-term neurological complications. The pathogenesis of CM and other forms of severe malaria is multi-factorial and appear to involve cytokine and chemokine homeostasis, inflammation and vascular injury/repair. Identification of prognostic markers that can predict CM severity will enable development of better intervention. METHODS: Postmortem serum and cerebrospinal fluid (CSF) samples were obtained within 2–4 hours of death in Ghanaian children dying of CM, severe malarial anemia (SMA), and non-malarial (NM) causes. Serum and CSF levels of 36 different biomarkers (IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17, Eotaxin, FGF basic protein, CRP, G-CSF, GM-CSF, IFN-γ, TNF-α, IP-10, MCP-1 (MCAF), MIP-1α, MIP-1β, RANTES, SDF-1α, CXCL11 (I-TAC), Fas-ligand [Fas-L], soluble Fas [sFas], sTNF-R1 (p55), sTNF-R2 (p75), MMP-9, TGF-β1, PDGF bb and VEGF) were measured and the results compared between the 3 groups. RESULTS: After Bonferroni adjustment for other biomarkers, IP-10 was the only serum biomarker independently associated with CM mortality when compared to SMA and NM deaths. Eight CSF biomarkers (IL-1ra, IL-8, IP-10, PDGFbb, MIP-1β, Fas-L, sTNF-R1, and sTNF-R2) were significantly elevated in CM mortality group when compared to SMA and NM deaths. Additionally, CSF IP-10/PDGFbb median ratio was statistically significantly higher in the CM group compared to SMA and NM groups. CONCLUSION: The parasite-induced local cerebral dysregulation in the production of IP-10, 1L-8, MIP-1β, PDGFbb, IL-1ra, Fas-L, sTNF-R1, and sTNF-R2 may be involved in CM neuropathology, and their immunoassay may have potential utility in predicting mortality in CM. |
format | Text |
id | pubmed-2186349 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-21863492008-01-10 Cerebrospinal fluid and serum biomarkers of cerebral malaria mortality in Ghanaian children Armah, Henry B Wilson, Nana O Sarfo, Bismark Y Powell, Michael D Bond, Vincent C Anderson, Winston Adjei, Andrew A Gyasi, Richard K Tettey, Yao Wiredu, Edwin K Tongren, Jon Eric Udhayakumar, Venkatachalam Stiles, Jonathan K Malar J Research BACKGROUND: Plasmodium falciparum can cause a diffuse encephalopathy known as cerebral malaria (CM), a major contributor to malaria associated mortality. Despite treatment, mortality due to CM can be as high as 30% while 10% of survivors of the disease may experience short- and long-term neurological complications. The pathogenesis of CM and other forms of severe malaria is multi-factorial and appear to involve cytokine and chemokine homeostasis, inflammation and vascular injury/repair. Identification of prognostic markers that can predict CM severity will enable development of better intervention. METHODS: Postmortem serum and cerebrospinal fluid (CSF) samples were obtained within 2–4 hours of death in Ghanaian children dying of CM, severe malarial anemia (SMA), and non-malarial (NM) causes. Serum and CSF levels of 36 different biomarkers (IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17, Eotaxin, FGF basic protein, CRP, G-CSF, GM-CSF, IFN-γ, TNF-α, IP-10, MCP-1 (MCAF), MIP-1α, MIP-1β, RANTES, SDF-1α, CXCL11 (I-TAC), Fas-ligand [Fas-L], soluble Fas [sFas], sTNF-R1 (p55), sTNF-R2 (p75), MMP-9, TGF-β1, PDGF bb and VEGF) were measured and the results compared between the 3 groups. RESULTS: After Bonferroni adjustment for other biomarkers, IP-10 was the only serum biomarker independently associated with CM mortality when compared to SMA and NM deaths. Eight CSF biomarkers (IL-1ra, IL-8, IP-10, PDGFbb, MIP-1β, Fas-L, sTNF-R1, and sTNF-R2) were significantly elevated in CM mortality group when compared to SMA and NM deaths. Additionally, CSF IP-10/PDGFbb median ratio was statistically significantly higher in the CM group compared to SMA and NM groups. CONCLUSION: The parasite-induced local cerebral dysregulation in the production of IP-10, 1L-8, MIP-1β, PDGFbb, IL-1ra, Fas-L, sTNF-R1, and sTNF-R2 may be involved in CM neuropathology, and their immunoassay may have potential utility in predicting mortality in CM. BioMed Central 2007-11-12 /pmc/articles/PMC2186349/ /pubmed/17997848 http://dx.doi.org/10.1186/1475-2875-6-147 Text en Copyright © 2007 Armah et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Armah, Henry B Wilson, Nana O Sarfo, Bismark Y Powell, Michael D Bond, Vincent C Anderson, Winston Adjei, Andrew A Gyasi, Richard K Tettey, Yao Wiredu, Edwin K Tongren, Jon Eric Udhayakumar, Venkatachalam Stiles, Jonathan K Cerebrospinal fluid and serum biomarkers of cerebral malaria mortality in Ghanaian children |
title | Cerebrospinal fluid and serum biomarkers of cerebral malaria mortality in Ghanaian children |
title_full | Cerebrospinal fluid and serum biomarkers of cerebral malaria mortality in Ghanaian children |
title_fullStr | Cerebrospinal fluid and serum biomarkers of cerebral malaria mortality in Ghanaian children |
title_full_unstemmed | Cerebrospinal fluid and serum biomarkers of cerebral malaria mortality in Ghanaian children |
title_short | Cerebrospinal fluid and serum biomarkers of cerebral malaria mortality in Ghanaian children |
title_sort | cerebrospinal fluid and serum biomarkers of cerebral malaria mortality in ghanaian children |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2186349/ https://www.ncbi.nlm.nih.gov/pubmed/17997848 http://dx.doi.org/10.1186/1475-2875-6-147 |
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