The skin as a reservoir for trypanosomes: the key to understanding transmission and disease pathology (360G-Wellcome-209511_Z_17_Z)

Human African trypanosomiasis is a fatal disease caused by trypanosome parasites, transmitted between mammalian hosts by the bite of a tsetse fly. We recently discovered that trypanosomes sequester to mammalian skin during infection, forming an undiagnosed, untreated, reservoir of disease. I hypothesise that this reservoir presents a substantial barrier to current control programmes and that the detection and elimination of skin-dwelling parasites will be crucial for the elimination of trypanosomiasis. I also hypothesise that the molecular pathways involved in extravasation to the skin are shared with those allowing extravasation into other organs, leading to the main pathological consequences of infection (an evolutionary by product of the drive for transmission). I aim to test these hypotheses using a combination of field and laboratory work. The fieldwork is aimed at determining the extent and role of skin-dwelling trypanosomes in humans and livestock (reservoir hosts) and developing a Raman spectroscopy-based non-invasive diagnostic. The laboratory-based work will use transcriptomics and genetic analysis to identify the key genes involved in extravasation. Together these approaches will allow a greater understanding of extravasation that will be key for the development of new diagnostics, transmission and pathology blocking agents as well as identifying novel areas of host/parasite interaction.