Identification of Stage Biomarkers for Human African Trypanosomiasis

Daniel Ndem Amin Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden; Institut National De Recherche Biomédicale, Kinshasa, Democratic Republic of Congo; Centre For Ticks and Tick-Borne Diseases, Lilongwe, Malawi, Section of Anatomy and Histology, Faculty of Medicine, University of Verona, Verona, Italy; Institute of Tropical Medicine, Department of Parasitology, Antwerp, Belgium; Department of Applied Therapeutics, Faculty of Pharmacy, Kuwait University, Kuwait

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Dieudonné Mumba Ngoyi Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden; Institut National De Recherche Biomédicale, Kinshasa, Democratic Republic of Congo; Centre For Ticks and Tick-Borne Diseases, Lilongwe, Malawi, Section of Anatomy and Histology, Faculty of Medicine, University of Verona, Verona, Italy; Institute of Tropical Medicine, Department of Parasitology, Antwerp, Belgium; Department of Applied Therapeutics, Faculty of Pharmacy, Kuwait University, Kuwait

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Gondwe-Mphepo Nhkwachi Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden; Institut National De Recherche Biomédicale, Kinshasa, Democratic Republic of Congo; Centre For Ticks and Tick-Borne Diseases, Lilongwe, Malawi, Section of Anatomy and Histology, Faculty of Medicine, University of Verona, Verona, Italy; Institute of Tropical Medicine, Department of Parasitology, Antwerp, Belgium; Department of Applied Therapeutics, Faculty of Pharmacy, Kuwait University, Kuwait

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Maria Palomba Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden; Institut National De Recherche Biomédicale, Kinshasa, Democratic Republic of Congo; Centre For Ticks and Tick-Borne Diseases, Lilongwe, Malawi, Section of Anatomy and Histology, Faculty of Medicine, University of Verona, Verona, Italy; Institute of Tropical Medicine, Department of Parasitology, Antwerp, Belgium; Department of Applied Therapeutics, Faculty of Pharmacy, Kuwait University, Kuwait

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Martin Rottenberg Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden; Institut National De Recherche Biomédicale, Kinshasa, Democratic Republic of Congo; Centre For Ticks and Tick-Borne Diseases, Lilongwe, Malawi, Section of Anatomy and Histology, Faculty of Medicine, University of Verona, Verona, Italy; Institute of Tropical Medicine, Department of Parasitology, Antwerp, Belgium; Department of Applied Therapeutics, Faculty of Pharmacy, Kuwait University, Kuwait

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Philippe Büscher Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden; Institut National De Recherche Biomédicale, Kinshasa, Democratic Republic of Congo; Centre For Ticks and Tick-Borne Diseases, Lilongwe, Malawi, Section of Anatomy and Histology, Faculty of Medicine, University of Verona, Verona, Italy; Institute of Tropical Medicine, Department of Parasitology, Antwerp, Belgium; Department of Applied Therapeutics, Faculty of Pharmacy, Kuwait University, Kuwait

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Krister Kristensson Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden; Institut National De Recherche Biomédicale, Kinshasa, Democratic Republic of Congo; Centre For Ticks and Tick-Borne Diseases, Lilongwe, Malawi, Section of Anatomy and Histology, Faculty of Medicine, University of Verona, Verona, Italy; Institute of Tropical Medicine, Department of Parasitology, Antwerp, Belgium; Department of Applied Therapeutics, Faculty of Pharmacy, Kuwait University, Kuwait

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Willias Masocha Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden; Institut National De Recherche Biomédicale, Kinshasa, Democratic Republic of Congo; Centre For Ticks and Tick-Borne Diseases, Lilongwe, Malawi, Section of Anatomy and Histology, Faculty of Medicine, University of Verona, Verona, Italy; Institute of Tropical Medicine, Department of Parasitology, Antwerp, Belgium; Department of Applied Therapeutics, Faculty of Pharmacy, Kuwait University, Kuwait

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Human African trypanosomiasis (HAT), caused by infection with sub-species of Trypanosoma brucei (T. b.), manifests as a hemolymphatic stage followed by an encephalitic stage. The distinction of the two stages needs improvement as drugs used for the late stage are highly toxic. Transcripts encoding 16 secreted proteins differentially expressed in the brains of mice at late stage T. b. brucei infection when the early stage drug suramin is no longer effective and different to immunoglobulins, chemokines, and cytokines, were selected by microarray analysis. Lipocalin 2 and secretory leukocyte peptidase inhibitor (SLPI) mRNA showed the highest differential expression in mice. These transcripts were also upregulated in brains from infected rats. Lipocalin 2 was increased in cerebrospinal fluid (CSF) from rats during late stage T. b. brucei infection. Protein levels of lipocalin 2, SLPI, and the chemokine CXCL10 were found increased in CSF from Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense late stage HAT compared to early stage.

Author Notes

*Address correspondence to Daniel Ndem Amin, Department of Neuroscience, Karolinska Institutet, Stockholm, SE-171 77 Sweden. E-mail: ndemamin@yahoo.co.uk

Financial support: This work was supported by a grant from the European Union (FP6-2004-INCO-DEV-3 032324; NEUROTRYP). DNA received a post-doctoral research fellowship from the International Brain Research Organization. DMN received a PhD grant from the Belgian Directorate General for Development Cooperation.

Authors' addresses: Daniel Ndem Amin, Martin Rottenberg, and Krister Kristensson, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden, E-mails: ndemamin@yahoo.co.uk, martinrottenberg@ki.se, and krister.kristensson@ki.se. Dieudonné Mumba Ngoyi, Institut National de Recherche Biomédicale, Kinshasa, DR Congo, E-mail: mumbadieudonne@yahoo.fr. Gondwe-Mphepo Nhkwachi, Centre for Ticks and Tick-Borne Diseases, Lilongwe, Malawi, E-mail: ncgondwe@yahoo.com. Maria Palomba, Section of Anatomy and Histology, Faculty of Medicine, University of Verona, Verona, Italy, E-mail: mariella@anatomy.univr.it. Philippe Büscher, Institute of Tropical Medicine, Department of Parasitology, Antwerp, Belgium, E-mail: PBuscher@itg.be. Willias Masocha, Department of Applied Therapeutics, Faculty of Pharmacy, Kuwait University, Safat, Kuwait, E-mail: masocha@hsc.edu.kw.

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