Abstract
Accurate stage determination is crucial in the choice of treatment for patients suffering from sleeping sickness, also known as human African trypanosomiasis (HAT). Current staging methods, based on the counting of white blood cells (WBC) and the detection of parasites in the cerebrospinal fluid (CSF) have limited accuracy. We hypothesized that immune mediators reliable for staging T. b. gambiense HAT could also be used to stratify T. b. rhodesiense patients, the less common form of HAT.A population comprising 85 T. b. rhodesiense patients, 14 stage 1 (S1) and 71 stage 2 (S2) enrolled in Malawi and Uganda, was investigated. The CSF levels of IgM, MMP-9, CXCL13, CXCL10, ICAM-1, VCAM-1, neopterin and B2MG were measured and their staging performances evaluated using receiver operating characteristic (ROC) analyses.IgM, MMP-9 and CXCL13 were the most accurate markers for stage determination (partial AUC 88%, 86% and 85%, respectively). The combination in panels of three molecules comprising CXCL13-CXCL10-MMP-9 or CXCL13-CXCL10-IgM significantly increased their staging ability to partial AUC 94% (p value < 0.01).The present study highlighted new potential markers for stage determination of T. b. rhodesiense patients. Further investigations are needed to better evaluate these molecules, alone or in panels, as alternatives to WBC to make reliable choice of treatment.
Highlights
Human African trypanosomiasis (HAT), commonly known as sleeping sickness, is a neglected tropical disease caused by the Trypanosoma brucei parasite and transmitted to humans through the bite of the tsetse fly [1]
According to World health organisation (WHO), patients having ≤ 5 white blood cells (WBC) per microliter of cerebrospinal fluid (CSF) and absence of parasites are considered to be in the first stage of the disease, while patients having more than 5 WBC/μL and/or presence of parasites in the CSF are considered as stage 2 (S2) [10]
Concentration of markers in patients’ CSF The CSF levels of IgM, B2MG, MMP-9, CXCL13, CXCL10, ICAM-1, VCAM-1 and neopterin were measured on a population of 85 patients, comprising 14 stage 1 and 71 stage 2 (Table 1)
Summary
Human African trypanosomiasis (HAT), commonly known as sleeping sickness, is a neglected tropical disease caused by the Trypanosoma brucei parasite and transmitted to humans through the bite of the tsetse fly [1]. According to WHO, patients having ≤ 5 white blood cells (WBC) per microliter of CSF and absence of parasites are considered to be in the first stage of the disease, while patients having more than 5 WBC/μL and/or presence of parasites in the CSF are considered as S2 [10]. These methods suffer from limited specificity and reproducibility of the counting of WBC and lack of sensitivity in finding of parasites in CSF [11,12] (Dieudonné Mumba Ngoyi, personal communication)
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