Therapeutic strategies for human microsporidia infections

Abstract

Over the past 20 years, microsporidia have emerged as a cause of infectious diseases in AIDS patients, organ transplant recipients, children, travelers, contact lens wearers and the elderly. Enterocytozoon bieneusi and the Encephalitozoon spp., Encephalitozoon cuniculi, Encephalitozoon hellem and Encephalitozoon intestinalis, are the most frequently identified microsporidia in humans, and are associated with diarrhea and systemic disease. The microsporidia are small, single-celled, obligately intracellular parasites that have been identified in water sources, as well as in wild, domestic and food-producing farm animals, thereby raising concerns for waterborne, foodborne and zoonotic transmission. Current therapies for microsporidiosis include albendazole, a benzimidazole that inhibits microtubule assembly and is effective against several microsporidia, including the Encephalitozoon spp., although it is less effective against Encephalitozoon bieneusi. Fumagillin, an antibiotic and antiangiogenic compound produced by Aspergillus fumigatus, is more broadly effective against Encephalitozoon spp. and E. bieneusi; however, is toxic when administered systemically to mammals. Recent studies are also focusing on compounds that target the microsporidia polyamines (e.g., polyamine analogs), methionine aminopeptidase 2 (e.g., fumagillin-related compounds), chitin inhibitors (e.g., nikkomycins), topoisomerases (e.g., fluoroquinolones) and tubulin (e.g., benzimidazole-related compounds).

Multiplex Bead Assay for Serum Samples from Children in Haiti Enrolled in a Drug Study for the Treatment of Lymphatic Filariasis

“…Multiple doses of ALB are needed to eliminate symptoms of microsporidiosis and E. cuniculi load, and the single-dose ALB used in this study showed no effect on IgG responses to PTP3. [40][41][42] Also, in contrast to the decreases in antibodies to filarial antigens, there were no significant changes in IgG responses to MSP-1 19 from P. falciparum . The MSP-1 19 includes the portion of the antigen found in the P. falciparum merozoite surface protein that is involved in the invasion of erythrocytes, and it predominantly elicits IgG1.…”

The Evolution of Sex: a Perspective from the Fungal Kingdom

“…Interestingly, another insect microsporidian, Antonospora locustae, is used as an insecticide to control harmful locusts and grasshoppers (175). A dozen microsporidian species are known to infect humans, mainly immunocompromised hosts, causing severe and long-lasting diarrhea; in some cases, infections of immunocompetent individuals have been observed (48). Microsporidian infections of humans were recently recognized as an emerging infectious disease, and both the NIH and the Environmental Protection Agency (EPA) have issued a caution on these pathogens (reviewed in reference 49).…”

Microsporidial Keratitis

“…Albendazole-a benzimidazole prevents microtubule formation and acts effectively against Encephalitozoon species but not against E. bieneusi [39]. Fumagillin-a derivative of Aspergillus fumigatus is widely used as an effective antimicrosporidial drug [40][41][42][43].…”