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Advances in sleeping sickness therapy.

The efficacy and adverse effects of nifurtimox and DFMO in the treatment of sleeping sickness are reviewed. Both new substances constitute effective novel therapeutic agents for gambiense sleeping sickness, including melarsoprol-refractory disease. DFMO is not very active in rhodesiense sleeping sickness and experience with nifurtimox in this form of trypanosomiasis is too limited to draw valid conclusions. The toxicity of nifurtimox and DFMO is not negligible. Optimum dosage and duration of therapy, modes of administration and potential for large scale use are discussed. Some recent results obtained with the classical trypanocide melarsoprol are presented to facilitate comparison. The current availability of several effective late-stage drugs (melarsoprol, nifurtimox and DFMO), that show synergistic activity in experimental models, should allow the establishment of optimum combination treatment regimens.