African trypanosomiasis occurs in 36 African countries following the geographic distribution of the tsetse fly. About 55 million people are at risk of acquiring infection and over 300,000 are already infected (WHO news, August 1996). Domestic animals excluded from about 70% of the land encompassing the tsetse habitat. However, many wild animals co-exist with the tsetse fly and are resistant to trypanosomiasis. Our Lab chooses Cape buffalo as a wild animal model to study the trypanoresistant mechanism. Cape buffaloes survive with low parasitemia and no sip of disease in the tsetse habitat. The superior ability of Cape buffaloes to limit the density of the trypanosome population in their bloodstream is related to the presence in their plasma or serum of material that kills all species of African trypanosome (123). The previous results from our lab had shown that the trypanocidal component in Cape buffalo serum was correlated with the presence of a 146 kDa polypeptide revealed by reducing SDS-PAGE. The amino acid sequence of the 146 polypeptide was 84-100% homologous with the sequence of human, mouse and rat xanthine:oxygen oxidoreductase (XO/XDH) suggesting that the trypanocidal protein might be XO (123).
The main objective of this thesis was to explore the mechanism of Cape buffalo to control African trypanosomiasis. My work has shown that Cape buffalo serum XO generates trypanocidal H 2 O 2 during catabolism of hypoxanthine and xanthine to uric acid. Furthermore, Cape buffalo serum contains adenosine deaminase, purine nucleoside phosphorylase, and guaninedeammase, which together with xanthine oxidase catabolize adenosine, inosine, guanosine, guanine, hypoxanthine, and xanthine to uric acid yielding H 2 O 2 . Paradoxically, Cape buffalo serum also contains catalase that catabolizes H 2 O 2 to H 2 O and prevents expression of trypanocidal activity under physiological condition. However, I have shown that an infection-induced decline of blood catalase activity results in the accumulation of H 2 O 2 in Cape buffalo blood and allows the Cape buffalo serum to express trypanocidal activity. A high xanthine oxidase activity is also found in sera from Eland, Giraffe and Greater Kudu, which might be responsible for their resistance for trypanosomiasis. Trypanosusceptible animals, which support high parasitemia and die after the infection, are unable to accumulate a trypanocidal concentration of H 2 O 2 in their bloodstream because of their low serum xanthine oxidase activity, sustained catalase activity and/or the presence of additional serum component(s) that protect trypanosomes from H 2 O 2 . The studies contribute to the data base of host anti-trypanosomiasis mechanisms, which may ultimately provide information to develop new measures to control African trypanosomiasis.
