Chemotherapy of microsporidiosis: Benzimidazoles, fumagillin and polyamine analogues

Microsporidia infection in humans is becoming increasingly recognized as a problem in immunocompromised as well as immune competent hosts. Human micropsoridian infections have been caused by several different microsporidian genera encompassing at least 12 species. Currently there are few controlled trials of the treatment of microsporidiosis in humans. Albendazole has been widely used for the treatment of microsporidiosis, however, it is clear from case reports that not all microsporidia are sensitive to this agent. Fumagillin has emerged as an alternative to albendazole treatment. This chapter discusses the recently identified enzyme target of fumagillin as well as the use of fumagilin in the treatment of microsporidiosis. Studies on polyamine metabolism of Encephalitozoon cuniculi indicate this organism relies primarily on uptake and interconversion of spermine to satisfy its polyamine requirements. Polyamine analogues having a bis aryl-3-7-3 configuration as well as pentamine and oligoamine analogues interfere with polyamine metabolism and cure model infections. These data suggest that the polyamine pathway should be a useful therapeutic target for the treatment of microsporidiosis. Polyamine metabolism in Enc. cuniculi is presented and discussed along with studies on the use of polyamine analogues in experimental models of infection.