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Infection and Immunity, December 2004, p. 7040-7044, Vol. 72, No. 12
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.12.7040-7044.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Severity of Human African Trypanosomiasis in East Africa Is Associated with Geographic Location, Parasite Genotype, and Host Inflammatory Cytokine Response Profile

Lorna MacLean,¹ John E. Chisi,² Martin Odiit,³ Wendy C. Gibson,⁴ Vanessa Ferris,⁴ Kim Picozzi,⁵ and Jeremy M. Sternberg^1*

College of Medicine, University of Malawi, Blantyre, Malawi,² Sleeping Sickness Special Programme, LIRI, Tororo, Uganda,³ School of Biological Sciences, University of Bristol, Bristol,⁴ CTVM, University of Edinburgh, Easter Bush, Roslin,⁵ School of Biological Sciences, University of Aberdeen, Aberdeen, United Kingdom¹

Received 1 July 2004/ Returned for modification 3 August 2004/ Accepted 12 August 2004

The mechanisms underlying virulence in human African trypanosomiasis are poorly understood, although studies with experimental mice suggest that unregulated host inflammatory responses are associated with disease severity. We identified two trypanosomiasis foci with dramatically different disease virulence profiles. In Uganda, infections followed an acute profile with rapid progression to the late stage (meningoencephalitic infection) in the majority of patients (86.8%). In contrast, infections in Malawi were of a chronic nature, in which few patients progressed to the late stage (7.1%), despite infections of several months' duration. All infections were confirmed to be Trypanosoma brucei rhodesiense by testing for the presence of the serum resistance-associated (SRA) gene, but trypanosomes isolated from patients in Uganda or Malawi were distinguished by an SRA gene polymorphism. The two disease profiles were associated with markedly different levels of tumor necrosis factor alpha (TNF-) and transforming growth factor ß (TGF-ß) in plasma. In Uganda but not Malawi early-stage TNF- was elevated, while in Malawi but not Uganda early-stage TGF-ß was elevated. Thus, rapid disease progression in Uganda is associated with TNF--mediated inflammatory pathology, whereas in the milder disease observed in Malawi this may be ameliorated by counterinflammatory cytokines. These differing host responses may result either from differing virulence phenotypes of northern and southern trypanosomes or from immune response polymorphisms in the different host populations.

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* Corresponding author. Mailing address: School of Biological Sciences, University of Aberdeen, Zoology Building, Aberdeen AB24 2TZ, United Kingdom. Phone: 01224 272272. Fax: 01224 272396. E-mail: j.sternberg{at}abdn.ac.uk.

Editor: W. A. Petri, Jr.

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Infection and Immunity, December 2004, p. 7040-7044, Vol. 72, No. 12
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.12.7040-7044.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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