Spatially and genetically distinct African Trypanosome virulence variants defined by host interferon-gamma response

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.