EXPERIMENTAL-MODELS OF HUMAN AFRICAN TRYP ANOSOMIASIS

Melarsoprol has remained the chosen drug for the late-stage treatment of human African trypanosomiasis (HAT) due both to Trypanosoma brucei (T. b.) gambiense and T. b. rhodesiense : however, arsenical encephalo pathies, which are often fatal, occur in 5-10% of the treated cases. T o bate, two major problems have not been solved The first one is the p recise diagnosis of early involvement of the central nervous system (C NS) which determines the therapeutics to be administered. The second o ne is linked to the lack of data on in vivo efficacy of products which are effective in vitro agaiiist trypanosomes. Answers have to be prov ided by experimental animal models of HAT. Such models would allow for better studies of the pathology and pathogenesis of the disease, as w ell as therapeutic trials of potentially effective new drugs or combin ations. We have developed acute and chronic murine and sheep experimen tal animal models of HAT infected by T. b. brucei. Meningoencephalitis and neurological signs are relatively difficult to obtain in murine m odels and require artificial means, such as suramin treatment on day 2 1 after-infection. The chronic murine model has demonstrated CNS invol vement with meningitis, followed by meningoencephalitis with progressi ve astrocytosis. The sheep model develops a disease with CNS complicat ions and cerebrospinal fluid can be collected in the sheep model, we h ave described anti-galactocerebrosides antibodies, which represent maj or components of myelin, which may indicate an autoimmune process in t he CNS. We then described these antibodies in the cerebrospinal fluids and sera from patients at a late-stage of the disease. From a therape utic point of view, we have cured mice or sheep with low doses of mela rsoprol, or with the nitroimidazole derivatives Ro 15-0216 and megazol , alone or combined with suramin. Further studies of these nitroimidaz ole compounds, which could be proposed for human use, have to be carri ed out on a primate model infected by T. b. gambiense. To our knowledg e this primate model is not available. This is why we have recently de veloped a T. b. gambiense primate model of HAT on Cercopithecus aethio ps.