Genetic Determinants of Trypanotolerance in Humans

Genetic Determinants of Trypanotolerance in Humans

Issued: Thu, 14 Aug 2014 16:35:00 BST

Trypanosoma brucei gambiense causes 97% of African sleeping sickness cases and was believed to be invariably fatal. The recent discovery of asymptomatic individuals demonstrates that this is not the case. Asymptomatic (or trypanotolerant) individuals are positive for trypanosome infection using antibody and PCR assays, although no symptoms are presented nor are parasites found within the vasculature.

This asymptomatic period can be protracted – one recent case persisted for 30 years before immunosuppressive treatment for an unrelated condition caused symptoms to emerge, highlighting the involvement of immunological components in controlling the parasite.

The trypanosomes infecting asymptomatic individuals have been characterised and do not differ from those in symptomatic patients, indicating asymptomatic individuals directly moderate infection.Understanding how these asymptomatic individuals control infection may lead to interventions alleviating clinical disease in symptomatic patients.

This project proposes to analyse the transcriptomes of peripheral blood mononuclear cells (PBMCs) from uninfected, symptomatic and asymptomatic T. b. gambiense patients. These data will be used to assess gene and pathway transcriptional differences and to identify SNP variants associated with asymptomatic patients.

Additionally, previous studies on human trypanosome infections focused on cytokine levels at various stages of disease, only examining patients with symptomatic disease and thus not assessing the protective response. This study also proposes to perform cytokine analysis on all collected serum samples to bolster the PBMC transcriptomics and be the first to look at the cytokine/chemokine profiles of asymptomatic individuals.


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