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New biomarkers for stage determination in Trypanosoma brucei rhodesiense sleeping sickness patients

Natalia Tiberti1, Enock Matovu2, Alexandre Hainard1, John Charles Enyaru3, Veerle Lejon4, Xavier Robin1, Natacha Turck1, Dieudonné Mumba Ngoyi5, Sanjeev Krishna6, Sylvie Bisser78, Bertrand Courtioux78, Philippe Büscher4, Krister Kristensson9, Joseph Mathu Ndung'u10 and Jean-Charles Sanchez1*

Author Affiliations

1 Department of Human Protein Sciences, University of Geneva, Geneva, Switzerland

2 Department of Biotechnical and Diagnostics Sciences, College of Veterinary Medicine, Animal Resources and Biosecurity, Makerere University, Kampala, Uganda

3 Department of Biochemistry, College of Natural Sciences, Makerere University, Kampala, Uganda

4 Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium

5 Department of Parasitology, Institut National de Recherche Biomédicale, Kinshasa, D. R. Congo

6 Division of Cellular and Molecular Medicine, St. George’s, University of London, London, Great Britain, UK

7 INSERM UMR1094, Tropical Neuroepidemiology, Limoges, France

8 Institute of Neuroepidemiology and Tropical Neurology, University of Limoges, School of Medicine, CNRS FR 3503 GEIST, Limoges, France

9 Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden

10 Foundation for Innovative New Diagnostics (FIND), Geneva, Switzerland

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Clinical and Translational Medicine 2013, 2:1  doi:10.1186/2001-1326-2-1

Published: 7 January 2013


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.

Sleeping sickness; Biomarkers; Trypanosoma brucei rhodesiense; Cerebrospinal fluid; Stage determination