Volume 82, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Human African trypanosomiasis (HAT), caused by infection with sub-species of (), 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 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 infection. Protein levels of lipocalin 2, SLPI, and the chemokine CXCL10 were found increased in CSF from and late stage HAT compared to early stage.


Article metrics loading...

Loading full text...

Full text loading...



  1. Dumas M, Preux PM, Sagui E, , 2009. Neurology in developing countries. Med Trop 69: 56.
  2. Kristensson K, Mhlanga JD, Bentivoglio M, , 2002. Parasites and the brain: neuroinvasion, immunopathogenesis and neuronal dysfunctions. Curr Top Microbiol Immunol 265: 227257.
  3. Bouteille B, Oukem O, Bisser S, Dumas M, , 2003. Treatment perspectives for human African trypanosomiasis. Fundam Clin Pharmacol 17: 171181.[Crossref]
  4. Kennedy PG, , 2004. Human African trypanosomiasis of the CNS: current issues and challenges. J Clin Invest 113: 496504.[Crossref]
  5. World Health Organization (WHO), 1998. Control and surveillance of African trypanosomiasis. Report of a WHO Expert Committee. World Health Organ Tech Rep Ser 881: 1114.
  6. Lejon V, Büscher P, , 2001. Stage determination and follow-up in sleeping sickness. Med Trop 61: 355360.
  7. Bisser S, Lejon V, Preux PM, Bouteille B, Stanghellini A, Jauberteau MO, Büscher P, Dumas M, , 2002. Blood-cerebrospinal fluid barrier and intrathecal immunoglobulins compared to field diagnosis of central nervous system involvement in sleeping sickness. J Neurol Sci 193: 127135.[Crossref]
  8. Kennedy PG, , 2008. The continuing problem of human African trypanosomiasis (sleeping sickness). Ann Neurol 64: 116126.[Crossref]
  9. Lejon V, Roger I, Mumba Ngoyi D, Menten J, Robays J, N'siesi FX, Bisser S, Boelaert M, Büscher P, , 2008. Novel markers for treatment outcome in late-stage Trypanosoma brucei gambiense trypanosomiasis. Clin Infect Dis 47: 1522.[Crossref]
  10. Ngotho M, Kagira JM, Jensen HE, Karanja SM, Farah IO, Hau J, , 2009. Immunospecific immunoglobulins and IL-10 as markers for Trypanosoma brucei rhodesiense late stage disease in experimentally infected vervet monkeys. Trop Med Int Health 14: 736747.[Crossref]
  11. Lejon V, Robays J, N'Siesi FX, Mumba D, Hoogstoel A, Bisser S, Reiber H, Boelaert M, Büscher P, , 2007. Treatment failure related to intrathecal immunoglobulin M (IgM) synthesis, cerebrospinal fluid IgM, and interleukin-10 in patients with hemolymphatic-stage sleeping sickness. Clin Vaccine Immunol 14: 732737.[Crossref]
  12. Amin DN, Rottenberg ME, Thomsen AR, Mumba D, Fenger C, Kristensson K, Büscher P, Finsen B, Masocha W, , 2009. Expression and role of CXCL10 during the encephalitic stage of experimental and clinical African trypanosomiasis. J Infectious Dis 200: 15561565.[Crossref]
  13. Courtioux B, Pervieux L, Vatunga G, Marin B, Josenando T, Jauberteau-Marchan MO, Bouteille B, Bisser S, , 2009. Increased CXCL-13 levels in human African trypanosomiasis meningo-encephalitis. Trop Med Int Health 14: 529534.[Crossref]
  14. Hainard A, Tiberti N, Robin X, Lejon V, Ngoyi DM, Matovu E, Enyaru JC, Fouda C, Ndung'u JM, Lisacek F, Müller M, Turck N, Sanchez JC, , 2009. A combined CXCL10, CXCL8 and H-FABP panel for the staging of human African trypanosomiasis patients. PLoS Negl Trop Dis 16: e459.[Crossref]
  15. Mumba Ngoyi D, Lejon V, Pyana P, Boelaert M, Ilunga M, Mertens J, Mulunda J-P, Van Nieuwenhove S, Muyembe Tamfum J-J, Büscher P, , 2010. How to shorten patient follow-up after treatment for Trypanosoma brucei gambiense sleeping sickness. J Infectious Dis 201: 453463.[Crossref]
  16. Lindberg J, af Klint E, Ulfgren AK, Stark A, Andersson T, Nilsson P, Klareskog L, Lundeberg J, , 2006. Variability in synovial inflammation in rheumatoid arthritis investigated by microarray technology. Arthritis Res Ther 8: R47.[Crossref]
  17. 2007. KTH microarray core facility home page. Available at: http://www.ktharray.se/. Accessed October 2007.
  18. 2007. R: A language and environment for statistical computing. Available at: http://www.cran.r-project.org/. Accessed October 2007.
  19. Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, Ellis B, Gautier L, Ge Y, Gentry J, Hornik K, Hothorn T, Huber W, Iacus S, Irizarry R, Leisch F, Li C, Maechler M, Rossini AJ, Sawitzki G, Smith C, Smyth G, Tierney L, Yang JY, Zhang J, , 2004. Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 5: R80.[Crossref]
  20. Smyth GK, , 2004. Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol 3: Article 3. doi:10.2202/1544-6115.1027
  21. Smyth GK, Speed T, , 2003. Normalization of cDNA microarray data. Methods 31: 265273.[Crossref]
  22. Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, Harris MA, Hill DP, Issel-Tarver L, Kasarskis A, Lewis S, Matese JC, Richardson JE, Ringwald M, Rubin GM, Sherlock G, , 2000. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 25: 2529.[Crossref]
  23. Masocha W, Rottenberg ME, Kristensson K, , 2006. Minocycline impedes African trypanosome invasion of the brain in a murine model. Antimicrob Agents Chemother 50: 17981804.[Crossref]
  24. Livak KJ, Schmittgen TD, , 2001. Analysis of relative gene expression data using realtime quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25: 402408.[Crossref]
  25. Amin DN, Masocha W, Ngan'dwe K, Rottenberg M, Kristensson K, , 2008. Suramin and minocycline treatment of experimental African trypanososmiasis at an early stage of parasite brain invasion. Acta Trop 106: 7274.[Crossref]
  26. Masocha W, Robertson B, Rottenberg ME, Mhlanga J, Sorokin L, Kristensson K, , 2004. Cerebral vessel laminins and IFN-gamma define Trypanosoma brucei brucei penetration of the blood-brain barrier. J Clin Invest 114: 689694.[Crossref]
  27. Mulenga C, Mhlanga JD, Kristensson K, Robertson B, , 2001. Trypanosoma brucei brucei crosses the blood-brain barrier while tight junction proteins are preserved in a rat chronic disease model. Neuropathol Appl Neurobiol 27: 7785.[Crossref]
  28. Thuita JK, Kagira JM, Mwangangi D, Matovu E, Turner CM, Masiga D, , 2008. Trypanosoma brucei rhodesiense transmitted by a single Tsetse fly bite in Vervet Monkeys as a model of human African trypanosomiasis. PLOS Negl Trop Dis 2: e238.[Crossref]
  29. Agrawal S, Anderson P, Durbeej M, van Rooijen N, Ivars F, Opdenakker G, Sorokin LM, , 2006. Dystroglycan is selectively cleaved at the parenchymal basement membrane at sites of leukocyte extravasation in experimental autoimmune encephalomyelitis. J Exp Med 203: 10071019.[Crossref]
  30. Flo TH, Smith KD, Sato S, Rodriguez DJ, Holmes MA, Strong RK, Akira S, Aderem A, , 2004. Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature 432: 811813.[Crossref]
  31. Marques F, Rodrigues AJ, Sousa JC, Coppola G, Geschwind DH, Sousa N, Correia-Neves M, Palha JA, , 2008. Lipocalin 2 is a choroid plexus acute-phase protein. J Cereb Blood Flow Metab 28: 450455.[Crossref]
  32. Lee S, Lee J, Kim S, Park JY, Lee WH, Mori K, Kim SH, Kim IK, Suk K, , 2007. A dual role of lipocalin 2 in the apoptosis and deramification of activated microglia. J Immunol 179: 32313241.[Crossref]
  33. Lee S, Park JY, Lee WH, Kim H, Park HC, Mori K, Suk K, , 2009. Lipocalin-2 is an autocrine mediator of reactive astrocytosis. J Neurosci 29: 234249.[Crossref]
  34. Zhang Y, DeWitt DL, McNeely TB, Wahl SM, Wahl LM, , 1997. Secretory leukocyte protease inhibitor suppresses the production of monocyte prostaglandin H synthase-2, prostaglandin E2, and matrix metalloproteinases. J Clin Invest 99: 894900.[Crossref]
  35. Wang X, Li X, Xu L, Zhan Y, Yaish-Ohad S, Erhardt JA, Barone FC, Feuerstein GZ, , 2003. Up-regulation of secretory leukocyte protease inhibitor (SLPI) in the brain after ischemic stroke: adenoviral expression of SLPI protects brain from ischemic injury. Mol Pharmacol 64: 833840.[Crossref]

Data & Media loading...

  • Received : 18 Dec 2009
  • Accepted : 21 Feb 2010

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error