Abstract
BackgroundHuman 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.MethodsCerebrospinal 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 ≤5 WBC/µL) and 79 from stage 2 (trypanosomes in CSF and/or >5 WBC/µL) patients. The concentration of H-FABP, GSTP-1 and S100β in CSF was measured by ELISA. The levels of thirteen inflammation-related proteins (IL-1ra, IL-1β, IL-6, IL-9, IL-10, G-CSF, VEGF, IFN-γ, TNF-α, CCL2, CCL4, CXCL8 and CXCL10) were determined by bead suspension arrays.ResultsCXCL10 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.ConclusionThis 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.
Highlights
Human African trypanosomiasis (HAT), called sleeping sickness, is a parasitic disease that occurs in sub-Saharan Africa
We recently explored the concept of post-mortem cerebrospinal fluid (CSF) as a model of massive and global brain insult [21], which allowed the identification of potential brain damage biomarkers by proteomics strategies
The second group (GR2) encompassed IFN-c, IL-9, CCL2 and S100b, for which concentrations in the CSF were significantly different between stage 1 and stage 2 patients (0.001,p,0.01, Mann-Whitney U test)
Summary
Human African trypanosomiasis (HAT), called sleeping sickness, is a parasitic disease that occurs in sub-Saharan Africa. Trypanosomes are transmitted to humans by the bite of a tsetse fly and are initially confined to the blood, lymph nodes and peripheral tissues This corresponds to the first stage (early stage; or haemolymphatic stage) of the disease. After an unknown period that varies from weeks to months, the parasites invade the central nervous system (CNS) This is called the second stage (late stage; or neurologic; or meningo-encephalitic stage) of HAT. Human African trypanosomiasis (HAT), 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). 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
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