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. 2007 Dec 1;196(11):1620-8.
doi: 10.1086/522011. Epub 2007 Oct 25.

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

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

Lorna Maclean et al. J Infect Dis. .

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.

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Figures

Figure 1
Figure 1
A dendrogram generated by an unweighted arithmetic average as the clustering method, showing the similarities between trypanosome multi-locus genotypes. Bootstrap values based on 100 replicates are shown for the main nodes. Groups 1 and 2 comprise the Tororo and Soroti genotypes respectively.
Figure 2
Figure 2
Plasma concentrations of IFN-γ (a), IL-1β (b), IL-10 (c). IL-6 (d), and TGF-β (e) in patients (filled boxes) and control subjects (open boxes) in the Tororo and Soroti foci. Boxes show median and 25th and 75th percentiles. Whiskers show 10th and 90th percentiles. Dots represent outliers. *Significantly increased over control P<0.0001 Unpaired t-test on log transformed data.

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