Epidemiology and Immunology of Schistosomiasis and other Human Parasitic Diseases
University of Cambridge
Tennis Court Road
Schistosomiasis is a debilitating, sometimes fatal, parasitic worm infection that chronically afflicts some 200 million people in many of the world’s poorest countries. It is designated by WHO as one of the world’s ‘great neglected diseases’ and a ‘disease of poverty’. Free-living parasite larvae, released into freshwater by intermediate host snails, can rapidly penetrate intact human skin. Adult worms then develop and live in the human blood stream for many years, releasing thousands of tissue-damaging eggs daily. Effective drug treatment is available, but in schistosomiasis endemic areas, reinfection occurs rapidly after treatment, especially in children. For some 25-years, our group has carried out field-based research on human schistosomiasis in disease endemic rural areas of Africa, in long-term partnership with colleagues in Uganda, Kenya and Mali, and more recently collaborations also in Ghana, Gabon, and Tanzania with Programme funding from the EC and Wellcome Trust. We integrate this field-based work with molecular and genomic techniques in a wide-ranging multi-disciplinary approach to the understanding of schistosomiasis and other human parasitic diseases.
Our on-going projects include: characterization of the role of immunological and inflammatory responses in the intestinal and liver diseases caused by Schistosoma mansoni in Kenya and Uganda, and urogenital tract diseases caused by S. haematobium in Mali. A focus on ecological and anthropological aspects of parasite transmission, together with geo-referencing of specific immune responses, other co-infecting pathogens, clinical disease markers, and known transmission sites, allows us to analyse and model the spatial relationships between multiple-infections, environmental factors, immune responses and clinical disease. Such multidisciplinary studies have revealed, for example, that chronic co-exposure to schistosomiasis and malaria is a major risk factor for widespread childhood hepatic morbidity that is associated anti-parasite inflammatory responses.
A second major long-term interest of our group is role of IgE-mediated anti-parasite immune effector mechanisms and their regulation. We find that human populations that are constantly exposed to schistosome infection slowly develop IgE responses against specific worm antigens. These responses are associated with a unique age-dependent concomitant immunity to reinfection that leaves adults much less vulnerable to reinfection than their children. The induction and regulation of this IgE-immunity against schistosomiasis is remarkably similar to the IgE-mechanisms associated with the allergy diseases that are now epidemic in the developed world. Our current studies concurrently focus on the induction, regulation and outcomes of IgE responses on schistosomiasis, hookworm infections and allergic disease in schistosomiasis endemic countries, as an understanding of IgE mediated anti-parasite responses will provide information that is essential to combating these major health challenges in both the developed and developing world.
David Dunne is also the Director of the Wellcome Trust-Cambridge Centre for Global Health Research & Cambridge-Africa.
- Senior Research Associates:
- Research Associates:
Angela Pinot de Moira and Ed Farnell
- Research Assitant:
- Chief Research Laboratory Technicians:
Frances Jones, Maureen Laidlaw
- Graduate Students:
Sam Hall (joint with Prof Anne Cooke), Goylette Chami (joint with Andreas Kontoleon, Dept Land Economy), Florian Sessier (joint with Matt Berriman, Wellcome Trust Sanger Genome Institute).
- Visiting scientists:
Robert Tweyongyere (Uganda), Harriet Mpairwe (Uganda), Humphrey Mazigo (Tanzania)
- Wellcome Trust-Cambridge Centre for Global Health Research coordinator:
- Cambridge-Africa Partnership for Research Excellence (CAPREx) Carnegie Coordinator:
- Pinot de Moira A, Jones FM, Wilson S, Tukahebwa E, Fitzsimmons CM, Mwatha JK, Bethony JM, Kabatereine NB, Dunne DW. (2013). Childhood schistosome and hookworm co-infections: effects of treatment on IgE responses against parasite allergen-like proteins and immunity to reinfection. Infect Immun. 81:23-32.
- Wilson S, Jones FM, Fofana HKM, Loundré A, Kimani G, Mwatha JK, Sacko M, Vennervald BJ, Dunne DW. (2013) Rapidly boosted plasma IL-5 induced by treatment of human schistosomiasis haematobium is dependent on antigen dose, IgE and eosinophils. PLoS Neglected Tropical Diseases. PNTD-D-12-01323R2
- Fitzsimmons CM, Jones FM, Pinot de Moira A, Protasio AV, Khalife J, Dickinson HA, Tukahebwa EM, Dunne DW. (2012). Progressive cross-reactivity in IgE responses: an explanation for the slow development of immunity to human schistosomiasis Infect Immun. 80:4264-70
- Fitzsimmons CM, Jones FM, Stearn A, Chalmers IW, Hoffmann KF, Wawrzyniak J, Wilson S, Kabatereine NB, Dunne DW. (2012) The Schistosoma mansoni Tegumental-Allergen-Like (TAL) Protein Family: Influence of Developmental Expression on Human IgE Responses. PLoS Negl Trop Dis 6(4):e1593.
- Dunne, DW., Vennervald, BJ., Booth, M., Joseph, S., Fitzsimmons, CM., Cahen, P., Sturrock, RF., Ouma, JH., Mwatha, JK., Kimani, G., Kariuki, HC., Kazibwe, F., Tukahebwa, E., Kabatereine, NB. (2006) Applied and basic research on the epidemiology, morbidity, and immunology of schistosomiasis in fishing communities on Lake Albert, Uganda. Transactions of the Royal Society for Tropical Medicine & Hygiene 100:216-23