East Coast Fever
The Scottish Government BBSRC DFID

Background to East Coast fever


The tick-borne protozoan parasite Theileria parva causes an acute, often fatal disease in cattle known as East Coast fever (ECF), which is a major constraint to livestock production in an area extending over sixteen countries in eastern and southern Africa (1). ECF is the most economically important cattle disease in eleven of these countries, where 60 % of the cattle are raised in ECF-endemic areas and the economic losses due to ECF exceed USD300 million annually (2).

Imported breeds of cattle, which are increasingly being used to satisfy demands for milk production, are highly susceptible and suffer high rates of mortality. The disease has a particularly devastating impact on poor small-holder farmers, who often do not have access to control measures. Therapeutic drugs are available but their use is limited by high cost and the need to treat animals during the early stages of disease. Control of the disease by prevention of tick infestation requires essentially continuous application of acaricides and is therefore expensive and difficult to sustain. The use of acaricides also poses a threat to the environment. Because of the shortcomings of these control measures and the fatal nature of the disease, there is a demand for effective vaccines to provide a sustainable means of controlling the disease.


Current immunisation

Cattle can be immunised by infection and simultaneous treatment with long-acting tetracycline, but the immunity is only partially effective against challenge with heterologous parasite strains (3,4). However, immunisation with a mixture of three isolates of T. parva (the Muguga cocktail) has been shown to protect against experimental challenge with a variety of isolates from different geographical locations. This method of vaccination has been used locally in several countries in east Africa, but it has not been adopted for widespread use because of logistical difficulties associated with production and distribution of a live vaccine and lack of commercial uptake. The antigenic composition of the vaccine is poorly defined and there remain questions as to whether the content of parasite strains is optimal for obtaining robust immunity in the field. In the longer term, vaccination by methods that do not rely on the use of live parasites would offer major advantages. Key to the development of such subunit vaccines is an understanding of the immunity which cattle develop to T. parva infection. Available evidence indicates that CD8 T lymphocytes specific for parasitised cells play a central role in immunity (5). Recently, a number of antigens recognised by parasite-specific CD8 T cells have been identified (6) and their potential use for developing a subunit vaccine is currently being investigated. Preliminary analyses of these antigens in different parasite strains have revealed sequence polymorphism and differential recognition by specific CD8 T cells (7).

Antigenic variability in T. parva is a key parameter that needs to be addressed both for achieving improvement of current live vaccines and for developing subunit vaccines. In the wider scientific context, T. parva is also one of the best developed natural disease models for studying the basis of strain restricted immunity to complex eukaryotic pathogens. There is evidence that parasite strain restricted T cell responses are important in immunity to a number of other protozoan parasites, most notably Plasmodium and Eimeria species (8,9). Unlike these parasites, for T. parva there are well established in vitro systems to dissect T cell responses to intact parasitised cells. Hence, studies of immunity to T. parva have the potential to provide novel concepts on strain restricted immunity that will be applicable to other important protozoan parasites.

Pathogenesis and transmission

T. parva infects cattle and African buffalo (Syncerus caffer) and undergoes successive development in lymphocytes and erythrocytes, the latter being infective for the tick vector. Parasite multiplication occurs predominantly within lymphocytes and this is the pathogenic stage. Sporozoites taken up by lymphocytes rapidly escape from the endocytic vacuole into the cytosol where development to the schizont stage results in transformation and proliferation of the host cells (10,11). Division of the parasite is synchronised with that of the host cell, so that parasite multiplication occurs by clonal expansion of the infected cells. These properties enable parasitised cells to be cultured in vitro as continuously growing cell lines. In susceptible animals, parasitised lymphocytes undergo uncontrolled proliferation and disseminate throughout the lymphoid system, eventually leading to destruction of lymphoid tissues and death within three to four weeks of infection.

Mortality may be as high as 80% in highly susceptible stock. In those animals that survive the acute infection, small numbers of parasitised cells persist for prolonged periods. Such carrier infections are often undetectable microscopically but are an important source of infection for transmission by ticks.


Buffalo-derived ECF

Although T. parva does not cause disease in buffalo, transmission of buffalo parasites to cattle results in severe disease. However, these parasites differentiate poorly to the erythrocyte stage in cattle and most attempts at cattle-to-cattle transmission with ticks have failed (12). Occasional successful transmissions have been reported, one of which gave rise to one of the isolates (Serengeti) used in the Muguga cocktail vaccine. Hence, cattle residing in areas where buffalo are present are exposed to an additional subset of T. parva that are not maintained in the cattle population but nevertheless cause disease. The proposed studies of antigenic diversity in this project will include a comparison of cattle-maintained and buffalo-derived populations.


1. Irvin A.D., Morrison W.I., 1987. In: E. J. L. Soulsby (Ed.), Immune Responses in Parasitic Infections. CRC Press, Boca Raton , Florida , pp. 223-274.

2. Spielman D.J. 2008. In: National Academies of Science, Partnerships for Sustainability: Examining the Evidence. Nat.Acad, Sci,.Washington, in press.

3. Radley D.E. et al. 1975 Vet. Parasitol. 1: 35-41.

4. Radley D.E et al. 1975. Vet. Parasitol. 1: 51-60.

5. Morrison W.I. 1996. Parasitology. 112 Suppl: S53-66.

6. Graham S.P. et al. 2006. Proc. Natl Acad. Sci. USA 103: 3286-3291.

7. MacHugh N.D. et al. Eur. J .Immunol. in press.

8. Gilbert S. C. et al. 1998. Science. 279:1173-1177.

9. Smith A.L. et al. 2002. Infect Immun. 70: 2472-2479.

10. Fawcett D. et al. 1984 Tissue Cell. 16: 873-84.

11. Dobbelaere D.A., Rottenberg S. 2003. Curr Opin Microbiol. 6:377-382.

12. Burridge MJ. 1975, J. Wildlife Dis. 11, 68-75.