Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2007
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
_version_ 1782145923863805952
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
work_keys_str_mv AT armahhenryb cerebrospinalfluidandserumbiomarkersofcerebralmalariamortalityinghanaianchildren
AT wilsonnanao cerebrospinalfluidandserumbiomarkersofcerebralmalariamortalityinghanaianchildren
AT sarfobismarky cerebrospinalfluidandserumbiomarkersofcerebralmalariamortalityinghanaianchildren
AT powellmichaeld cerebrospinalfluidandserumbiomarkersofcerebralmalariamortalityinghanaianchildren
AT bondvincentc cerebrospinalfluidandserumbiomarkersofcerebralmalariamortalityinghanaianchildren
AT andersonwinston cerebrospinalfluidandserumbiomarkersofcerebralmalariamortalityinghanaianchildren
AT adjeiandrewa cerebrospinalfluidandserumbiomarkersofcerebralmalariamortalityinghanaianchildren
AT gyasirichardk cerebrospinalfluidandserumbiomarkersofcerebralmalariamortalityinghanaianchildren
AT tetteyyao cerebrospinalfluidandserumbiomarkersofcerebralmalariamortalityinghanaianchildren
AT wireduedwink cerebrospinalfluidandserumbiomarkersofcerebralmalariamortalityinghanaianchildren
AT tongrenjoneric cerebrospinalfluidandserumbiomarkersofcerebralmalariamortalityinghanaianchildren
AT udhayakumarvenkatachalam cerebrospinalfluidandserumbiomarkersofcerebralmalariamortalityinghanaianchildren
AT stilesjonathank cerebrospinalfluidandserumbiomarkersofcerebralmalariamortalityinghanaianchildren