A combined CXCL10, CXCL8 and H-FABP panel for the staging of human African trypanosomiasis patients.
<h4>Background</h4>Human African trypanosomiasis (HAT), also known as sleeping sickness, is a parasitic tropical disease. It progresses from the first, haemolymphatic stage to a neurological second stage due to invasion of parasites into the central nervous system (CNS). As treatment dep...
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2009
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oai:doaj.org-article:5d21ba43dd0e4b4995dfbd239a5c42722021-11-25T06:33:19ZA combined CXCL10, CXCL8 and H-FABP panel for the staging of human African trypanosomiasis patients.1935-27271935-273510.1371/journal.pntd.0000459https://doaj.org/article/5d21ba43dd0e4b4995dfbd239a5c42722009-06-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19554086/?tool=EBIhttps://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735<h4>Background</h4>Human African trypanosomiasis (HAT), also known as sleeping sickness, is a parasitic tropical disease. It progresses from the first, haemolymphatic stage to a neurological second stage due to invasion of parasites into the central nervous system (CNS). As treatment depends on the stage of disease, there is a critical need for tools that efficiently discriminate the two stages of HAT. We hypothesized that markers of brain damage discovered by proteomic strategies and inflammation-related proteins could individually or in combination indicate the CNS invasion by the parasite.<h4>Methods</h4>Cerebrospinal fluid (CSF) originated from parasitologically confirmed Trypanosoma brucei gambiense patients. Patients were staged on the basis of CSF white blood cell (WBC) count and presence of parasites in CSF. One hundred samples were analysed: 21 from stage 1 (no trypanosomes in CSF and <or=5 WBC/microL) and 79 from stage 2 (trypanosomes in CSF and/or >5 WBC/microL) patients. The concentration of H-FABP, GSTP-1 and S100beta in CSF was measured by ELISA. The levels of thirteen inflammation-related proteins (IL-1ra, IL-1beta, IL-6, IL-9, IL-10, G-CSF, VEGF, IFN-gamma, TNF-alpha, CCL2, CCL4, CXCL8 and CXCL10) were determined by bead suspension arrays.<h4>Results</h4>CXCL10 most accurately distinguished stage 1 and stage 2 patients, with a sensitivity of 84% and specificity of 100%. Rule Induction Like (RIL) analysis defined a panel characterized by CXCL10, CXCL8 and H-FABP that improved the detection of stage 2 patients to 97% sensitivity and 100% specificity.<h4>Conclusion</h4>This study highlights the value of CXCL10 as a single biomarker for staging T. b. gambiense-infected HAT patients. Further combination of CXCL10 with H-FABP and CXCL8 results in a panel that efficiently rules in stage 2 HAT patients. As these molecules could potentially be markers of other CNS infections and disorders, these results should be validated in a larger multi-centric cohort including other inflammatory diseases such as cerebral malaria and active tuberculosis.Alexandre HainardNatalia TibertiXavier RobinVeerle LejonDieudonné Mumba NgoyiEnock MatovuJohn Charles EnyaruCatherine FoudaJoseph Mathu Ndung'uFrédérique LisacekMarkus MüllerNatacha TurckJean-Charles SanchezPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 3, Iss 6, p e459 (2009) |
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EN |
| topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
| spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Alexandre Hainard Natalia Tiberti Xavier Robin Veerle Lejon Dieudonné Mumba Ngoyi Enock Matovu John Charles Enyaru Catherine Fouda Joseph Mathu Ndung'u Frédérique Lisacek Markus Müller Natacha Turck Jean-Charles Sanchez A combined CXCL10, CXCL8 and H-FABP panel for the staging of human African trypanosomiasis patients. |
| description |
<h4>Background</h4>Human African trypanosomiasis (HAT), also known as sleeping sickness, is a parasitic tropical disease. It progresses from the first, haemolymphatic stage to a neurological second stage due to invasion of parasites into the central nervous system (CNS). As treatment depends on the stage of disease, there is a critical need for tools that efficiently discriminate the two stages of HAT. We hypothesized that markers of brain damage discovered by proteomic strategies and inflammation-related proteins could individually or in combination indicate the CNS invasion by the parasite.<h4>Methods</h4>Cerebrospinal fluid (CSF) originated from parasitologically confirmed Trypanosoma brucei gambiense patients. Patients were staged on the basis of CSF white blood cell (WBC) count and presence of parasites in CSF. One hundred samples were analysed: 21 from stage 1 (no trypanosomes in CSF and <or=5 WBC/microL) and 79 from stage 2 (trypanosomes in CSF and/or >5 WBC/microL) patients. The concentration of H-FABP, GSTP-1 and S100beta in CSF was measured by ELISA. The levels of thirteen inflammation-related proteins (IL-1ra, IL-1beta, IL-6, IL-9, IL-10, G-CSF, VEGF, IFN-gamma, TNF-alpha, CCL2, CCL4, CXCL8 and CXCL10) were determined by bead suspension arrays.<h4>Results</h4>CXCL10 most accurately distinguished stage 1 and stage 2 patients, with a sensitivity of 84% and specificity of 100%. Rule Induction Like (RIL) analysis defined a panel characterized by CXCL10, CXCL8 and H-FABP that improved the detection of stage 2 patients to 97% sensitivity and 100% specificity.<h4>Conclusion</h4>This study highlights the value of CXCL10 as a single biomarker for staging T. b. gambiense-infected HAT patients. Further combination of CXCL10 with H-FABP and CXCL8 results in a panel that efficiently rules in stage 2 HAT patients. As these molecules could potentially be markers of other CNS infections and disorders, these results should be validated in a larger multi-centric cohort including other inflammatory diseases such as cerebral malaria and active tuberculosis. |
| format |
article |
| author |
Alexandre Hainard Natalia Tiberti Xavier Robin Veerle Lejon Dieudonné Mumba Ngoyi Enock Matovu John Charles Enyaru Catherine Fouda Joseph Mathu Ndung'u Frédérique Lisacek Markus Müller Natacha Turck Jean-Charles Sanchez |
| author_facet |
Alexandre Hainard Natalia Tiberti Xavier Robin Veerle Lejon Dieudonné Mumba Ngoyi Enock Matovu John Charles Enyaru Catherine Fouda Joseph Mathu Ndung'u Frédérique Lisacek Markus Müller Natacha Turck Jean-Charles Sanchez |
| author_sort |
Alexandre Hainard |
| title |
A combined CXCL10, CXCL8 and H-FABP panel for the staging of human African trypanosomiasis patients. |
| title_short |
A combined CXCL10, CXCL8 and H-FABP panel for the staging of human African trypanosomiasis patients. |
| title_full |
A combined CXCL10, CXCL8 and H-FABP panel for the staging of human African trypanosomiasis patients. |
| title_fullStr |
A combined CXCL10, CXCL8 and H-FABP panel for the staging of human African trypanosomiasis patients. |
| title_full_unstemmed |
A combined CXCL10, CXCL8 and H-FABP panel for the staging of human African trypanosomiasis patients. |
| title_sort |
combined cxcl10, cxcl8 and h-fabp panel for the staging of human african trypanosomiasis patients. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2009 |
| url |
https://doaj.org/article/5d21ba43dd0e4b4995dfbd239a5c4272 |
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