Immunology and Pathogenesis in African trypanosome infections.
African trypanosomes are parasitic protozoans which cause sleeping sickness in man and ngana in domestic animals. These parasites are exquisite manipulators of the host immune-system. Current research is focussed on understanding the pathogenesis of disease at a range of levels from the laboratory to the field and the application of novel diagnostic methods. This includes studies of macrophage activation by trypanosome molecules, studies of the immunological response to infections in patients in Malawi and Uganda, and research into novel diagnostic methods using immunological markers and metabolomic analysis.
Novel Diagnostics in African trypanosomiasis
Effective treatment of African trypanosome infections requires us to know whether the parasites have entered the CNS of the patient of not; this is known as staging. Presently staging requires a sample of cerebrospinal fluid, and thus an invasive and often painful spinal tap. Our work on neuroinflammatory activation in the CNS stage of the disease suggests that it may be possible to diagnose the stage of the disease using blood samples only. This is presently being investigated in a programme funded by FIND (see FIND sleeping sickness pages). We also are closely involved with the roll out of novel lateral flow devices for field diagnosis and have provided the first validation study of the Bioline SD HAT produced by Standard Diagnostics (See http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0003373).
Virulence in African trypanosomiasis and trypanosome genetics
Immunological and pathology data from Human African trypanosomiasis outbreaks in Uganda and Malawi suggests that the considerable variation in virulence observed in the field is associated with distinct parasite genotypes. In collaboration with the Wellcome Centre for Molecular Parasitology in Glasgow we a currently characterising the precise relationship between parasite genotype, disease severity and the inflmmatory response which we suspect as being the primary driver of pathology.
Neuroinflammatory regulation and neurological disease in Human African trypanosomiasis
Our interest in the role of inflammatory pathology in trypanosomiasis led us to investigate its role in the CNS stage of the disease. In this collaboration with Prof. Peter Kennedy at the Dept. of Neurology at the University of Glasgow we demonstrated that progression of the CNS disease was regulated by the balance of inflammatory and anti-inflammatory mediators in the brain. In particular, evidence suggested that the cytokine IL-10 plays a major neuroprotective role in the disease. We are continuing this work using experimental models to test the effects of using IL-10 as a treatment in trypanosomiasis, and using conditional knock out models in which astrocytes do not respond to IL-10 to determine the significance of this cytokine. Additionally we are continuing a survey of sleeping sickness patients in Uganda which we will use to test the hypothesis that the inflammatory/antiinflammatory cytokine ratio in the CSF is a predictor of neurological dysfunction. We have demonstrated that IL-10 therapy has the potential to ameliorate CNS disease in an experimental model (see http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0004201)
Genetics of Tapeworms
Despite their enormous global medical and veterinary significance, little is known of the genetic systems of cestodes. We are using Schistocephalus solidus, which is readily obtained from sticklebacks and can be grown to the adult stage in vitro as model system. Our present goal is to describe the population genetics of this species, using RAPD techniques and newly developed microsatellite probes.
Imperial College, Dept of Surgery and Cancer: Prof Elaine Holmes: Metabonomic discovery of diagnostic markers in sleeping sickness.
University of Glasgow, Dept of Neurology: Prof. Peter Kennedy: Models of CNS pathogenesis in trypanosomiasis
University of Glasgow, Wellcome Centre for Molecular Parasitology: Dr Annette MacLeod and Prof. Andy Tait: Molecular epidemiology of protozoan parasites
Vrije Universiteit Brussel, VIB Department of Molecular and Cellular Interactions: Prof. Stefan Magez: Immune responses to tsetse fly saliva
Makerere University, Kampala, Uganda: Dr Enock Matovu. Clinical epidemiology and immunology in African trypanosomiasis
CNS diagnostic markers in human African trypanosomiasis 2007-2008 FIND
Validation of lateral flow devices 2012-3 FIND
Defining the therapeutic role of IL-10 in African Trypanosomiasis. Wellcome Trust 2008-2012
Energetics of trypanosome infection BBSRC 2011-2015
School of Biological Sciences Honours Project/4th year convener
Course leader for BI4016, ZO4816, BI29Z1 Wildlife Parasitology Field Course
Contributor on BI10008, BI1012 , BI2510, ZO3808, IM3802, IM4001
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Editorial Board, Parasite Immunology 2003-
Editorial Board, Infection and Immunity 2000-2003
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