African Trypanosomasis is caused by protozoan parasites of the genus Trypanosoma.

The trypanosomes cause disease in both humans and animals. The trypanosomes are transmitted by the tsetse flies of the genus Glossina. In man, the disease is known as Human African Trypanosomosis (HAT) and is caused by Trypanosoma brucei subspecies; Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense. T. b. rhodesiense causes the acute form of the disease found in East and Southern Africa and is primarily zoonotic. T. b. gambiense causes the chronic form found in Central and West Africa. HAT is now reemerging with an estimate of 300,000 to 500,000 cases per annum and 60 million people being at risk of infection (WHO, 1998, Welburn and Odiit 2002). The number of cases reported is very low because there are no active screening practices in the affected areas and also due to the poor diagnostic tools used (WHO, 2006, Fevre et al., 2008b). The disease is prevalent in sub Saharan Africa and many of these cases are found in isolated rural areas where it is the major cause of human morbidity and mortality (Kennedy, 2004). African animal trypanosomosis (AAT) is a major constraint to livestock productivity that has a significant impact on the life of millions people in African developing countries, costing several billion US dollars each year. In cattle it is called Nagana or the wasting disease. Trypanosoma congolense, Trypanosoma vivax and, to a lesser extent, Trypanosoma brucei brucei, are the agents of trypanosomosis in livestock. (Hide and Tait, 2004, OGorman et al., 2006, OGorman et al., 2009). Immunosuppression appears to be a nearly universal feature of infection with African trypanosomes and thus may represent an essential element of the host-parasite relationship, possibly by reducing the host's ability to mount a protective immune response. Antibody, T cell and macrophage/monocyte responses of infected cattle are depressed in both trypanosusceptible and trypanotolerant breeds of cattle (Taylor and Martens, 1999). Anemia is the most prominent and consistent clinical sign of infection and is the main

indicator for treatment rather than parasitemia (Noyes, et al., 2011). Many untreated cases are fatal. Some African cattle, like Bos taurus breeds are highly tolerant of infection, but the potentially more productive Bos indicus zebu breeds are much more susceptible. Zebu cattle are well adapted for plowing and haulage, and increasing their tolerance of trypanosomiasis could have a major impact on crop cultivation as well as dairy and beef production. This in turn causes serious consequences for human health and welfare (Kristjanson, et al., 1999). AAT is found mainly in those regions of Africa where its biological vector, the tsetse fly, exists and this includes Uganda. This tsetse fly infested region is known as the tsetse belt which covers 37 African countries with an approximation of 10 million square kilometers (OGorman, et al., 2006). The disease is the cause of death of more than 3 million animals per annum with 50 million animals at risk of infection in the region (Chitanga, et al., 2011). In North East Uganda the prevalence of infection in domestic animals is estimated to be about 18% (Welburn et al., 2001, Magona and Walubengo 2011.) Transmission occurs through the bite of infected tsetse flies. The infection results in a chronic disease which is characterized by anaemia, leukocytopaenia, immunosuppression and cachexia (OGorman et. al., 2009, Lutje et. al., 1996). After infection the parasites enter the bloodstream and evade immunological control by continuously switching their surface glycoprotein coat. As the Variant Surface Glycoproteins (VSG) covers the African trypanosomes plasma membrane (Cross 1975), antibodies are directed against it so as to destroy the parasites. Owing to transcriptional switching of the VSG genes and subsequent expression of variant antigenic types on the plasma membrane, the trypanosomes can invade the hosts immune response. This brings about successive waves of parasitaemia which is a major disease characteristic. Thus sterile immunity is never achieved and this is why the disease becomes chronic (Borst and Cross 1982, Lutje et al 1996).

Some African Bos taurus cattle breeds, such as NDama, are tolerant of infection with T. congolense, remaining apparently healthy despite the presence of parasites. This capacity to remain productive while harboring potentially lethal trypanosome infections is known as trypanotolerance (Murray et al., 1984). These cattle breeds have evolved a mechanism of disease resistance or tolerance as a result of their long coexistence with the parasite. These cattle can control parasitaemia and severe anemia through mechanisms which are not yet well understood but thought to involve an effective immune response to trypanosome antigens and differential cytokines (Murray et al., 1982, Lutje et al., 1996, Kazuhiro et al., 2006). It has been observed that a balance between pro- and counter-inflammatory cytokines is central to the outcome of the disease in mouse models (Kennedy, 2008a). Cytokines play different roles in the control of infection, but over production of some (TNF- & IFN-) can lead to exacerbated pathological changes (Magez et al., 2004). Some studies have suggested that Interleukin 4 (IL-4) to play a protective role (Mertens et, al., 1999), Interferon Gamma (IFN-) stimulates parasite growth (Bakhiet et al., 1996) while Tumor Neucrosis Factor alpha (TNF-) has a trypanocidal effects (Lucas et al., 1994). Increased production of counter-inflammatory cytokines (IL-10, IL-8 and IL-6) is associated with decreased pathology and resistance to infection (Sternberg et al., 2005).