Drug used in the treatment of sleeping sickness (human African trypanosomiasis: HAT)

Abstract

From the first decade of this century arsenicals have been the most universal and most effective drugs for all cases of sleeping sickness. Melarsoprol, introduced in the 1940s, remains the most universal of these compounds. However, resistance of trypanosomes and toxicity that may be fatal for the patient are two major shortcomings. Pentamidine, suramin and Berenil((R)) are active only in the first stage of the disease, when the parasites are confined to blood and lymph. Nifurtimox taken orally for 1 to 2 months and alpha-difluoro-methylornithine (alpha-DFMO) with an administration scheme spread over 5 weeks including 14 days of intravenous injections. provide interesting alternatives for all cases, since they reach the central nervous system. However, DFMO is known to be less active against. T. rhodesiense. Imidazoles, new arsenical derivatives and antimitotics have been successfully tested in experimental models. Combinations of drugs with additive or pontentiating effects mainly based on inhibition of decarboxylase enzymes or exposure to axidative stress appear promising.