In South Africa, trypanosomosis also known as Nagana, transmitted by Glossina brevipalpis and G. austeni, is the major cause of anaemia and chronic debilitating condition in cattle. There is a wealth of entomological information on the ecology of the two tsetse species generated following the devastating outbreak in cattle due to Nagana in 1990. However, it is unfortunate that these entomological data has not been supported by parallel studies on the epidemiology of the disease. Therefore, the present study presents the first intensive epidemiological investigations since 1990 to address the problem of animal trypanosomosis in South Africa. The relationship between trypanosomes herd average prevalence (HAP), herd average anaemia (HAA) and herd average packed cell volume (HA-PVC) were investigated in cattle in three communal diptanks located by the Hluhluwe-uMfolozi Game Reserve by regular monthly sampling for 15 months. The tsetse challenge with G. brevipalpis in two of the diptanks, Mvutshini and Ekuphindisweni, was high but low in the third (Ocilwane). In addition, G. brevipaplis and G. austeni coexist in Mvutshini diptank. This high and low tsetse challenge presented different disease scenarios. Cattle at Mvutshini and Ekuphindisweni diptanks had the highest HAP of 12.3% and 8.9%, respectively, which is significantly different (p = 0.001) from the HAP obtained from cattle at Ocilane (2.9%). Both cattle herds at Mvutshini and Ekuphindisweni diptanks also had the highest HAA, 27.7 and 33.4%, respectively, while cattle at Ocilwane had the lowest, 11.1% (statistically different; p = 0.001). Conversely, cattle at Ocilwane diptank had the highest HA-PCV, ranging between 29-32% while cattle at Mvutshini and Ekuphindisweni diptanks had the lowest HA-PCV (24-29%). The interaction between HAP and HAA is significant (p = 0.021). The overall effect of HAP on the animal health condition is clearly demonstrated when comparing the anaemia in trypanosomes infected and uninfected cattle at the 3 diptanks. Fifty percent, 63% and 100% of trypanosomes infected cattle were anaemic at Mvutshini, Ekuphindisweni and Ocilwane diptanks, respectively. In comparison, the prevalence of anaemia in uninfected cattle in the 3 diptanks was 20, 30 and 10% at Mvutshini, Ekuphindisweni and Ocilwane diptanks, respectively. By combining the data from the 3 diptanks (1,800 observations), the overall HAA in infected and uninfected cattle was 62 and 20%, respectively The results of trypanosomes seasonal surveys conducted at 7 communal diptanks in tsetse infested areas, showed that all cattle at the diptanks were infected with trypanosomes with mean HAP and HAA of 10.3 and 35.3%, respectively. The highest HAP (range 15-31%, n=4) was recorded in Ngwenyambili diptank. This high infection in the cattle herds produced high values of HAA (50%; range 40-60). The infection rate with trypanosomes in G. brevipalpis caught from the field showed immature infections in the midgut of 3.5% (16/458) while only one fly was found with mature infection in the proboscis (1/458, 0.22%). Very few G. austeni were collected (total of 9) during the same period and dissected. The infection rate with trypanosomes immature and mature infections was found to be very high; 5/9 (55.5%). Blood samples were collected from a total of 132 buffaloes randomly immobilized for tuberculosis testing by the Hluhluwe-uMfolozi Game Reserve Authority. Two buffaloes were found to have T. congolense infection by the buffy coat technique. The presence of trypanosomes infected buffaloes in this study confirms the occurrence of sylvatic cycle at the tsetse/livestock/Hluhluwe-uMfolozi Game Reserve, thus, presenting a high risk of serious disease to cattle. The objective of the study on the strategic treatment of trypanosomosis conducted on one farm in endemic area was to treat adult cows and calves at an arbitrary HAP threshold before the disease produces any clinical symptoms or production losses. The strategic use of ethidium bromide and novidium chloride produced attractive results whereby cattle were protected for an extended period of 3 to 6 months with no development of anaemia during this period. Therefore, two to four treatments per year may be sufficient to keep cattle productivity on the farm under the tsetse challenge Copyright / Dissertation (MSc)--University of Pretoria, 2012. / Veterinary Tropical Diseases / unrestricted