title: Spatially and genetically distinct African Trypanosome virulence variants defined by host interferon-gamma response.
abstract: We describe 2 spatially distinct foci of human African trypanosomiasis in eastern Uganda. The Tororo and Soroti foci of Trypanosoma brucei rhodesiense infection were genetically distinct as characterized by 6 microsatellite and 1 minisatellite polymorphic markers and were characterized by differences in disease progression and host-immune response. In particular, infections with the Tororo genotype exhibited an increased frequency of progression to and severity of the meningoencephalitic stage and higher plasma interferon (IFN)- gamma concentration, compared with those with the Soroti genotype. We propose that the magnitude of the systemic IFN- gamma response determines the time at which infected individuals develop central nervous system infection and that this is consistent with the recently described role of IFN- gamma in facilitating blood-brain barrier transmigration of trypanosomes in an experimental model of infection. The identification of trypanosome isolates with differing disease progression phenotypes provides the first field-based genetic evidence for virulence variants in T. brucei rhodesiense.
authors.affiliation: School of Biological Sciences, University of Aberdeen, Aberdeen, AB24 2TZ, Scotland.
authors.forename: Lorna
authors.initials: L
authors.lastname: Maclean
authors.forename: Martin
authors.initials: M
authors.lastname: Odiit
authors.forename: Annette
authors.initials: A
authors.lastname: Macleod
authors.forename: Liam
authors.initials: L
authors.lastname: Morrison
authors.forename: Lindsay
authors.initials: L
authors.lastname: Sweeney
authors.forename: Anneli
authors.initials: A
authors.lastname: Cooper
authors.forename: Peter G E
authors.initials: PG
authors.lastname: Kennedy
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Sternberg
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000097:blood*; D001812:Blood-Brain Barrier / Q000276:immunology / Q000469:parasitology; D003128:Coma / Q000276:immunology / Q000469:parasitology; D018450:Disease Progression; D005838:Genotype; D015600:Glasgow Coma Scale; D006790:Host-Parasite Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000097:blood* / Q000134:cerebrospinal fluid; D007378:Interleukins / Q000097:blood; D016779:Malaria, Cerebral / Q000276:immunology* / Q000469:parasitology*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012720:Severity of Illness Index; D016833:Trypanosoma brucei rhodesiense / Q000235:genetics* / Q000472:pathogenicity*; D014353:Trypanosomiasis, African / Q000276:immunology*; D014454:Uganda; D014774:Virulence / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D007378:Interleukins; D007371:Interferon-gamma