Therapy for human gastrointestinal microsporidiosis.

Abstract

Abstract. Gastrointestinal microsporidiosis is a major cause of diarrhea and wasting in persons with acquired immune deficiency syndrome (AIDS). Microsporidia demonstrate properties of both true eukaryotes and prokaryotes. The biology of microsporidia makes its elimination from the gastrointestinal tract therapeutically challenging. This organism depends greatly on the host for its energy needs and reproduction; microsporidial spores are impervious to the elements. Microsporidial infection of the gastrointestinal tract, principally with Enterocytozoon bieneusi and Encephalitozoon intestinalis in patients with AIDS has been treated with different medical regimens with variable success. The less common pathogen, E. intestinalis, responds well to albendazole, making it excellent first-line therapy, but such is not the case for E. bieneusi. None of the benzimidazoles has been demonstrated to be efficacious for E. bieneusi. On the other hand, E. bieneusi has shown excellent clinical therapeutic response to either direct action with fumagillin or its analogue, TNP-470, or indirectly by immune enhancement by suppression of the HIV virus with more aggressive, highly effective antiretroviral therapy. Further work is necessary to fully establish proper therapeutic protocols and manage side effects of the treatments. Other promising forms of therapy such as polyamine inhibitors and thalidomide demonstrate certain effectiveness in treatment of microsporidian in vitro (polyamine inhibitors) and in selected cases in vivo (thalidomide). Lack of either sufficiently suggestive or definitive human studies prevents the endorsement of these modes of therapy for treatment of gastrointestinal microsporidiosis at this time.

Induction of a Rapid and Strong Antigen-Specific Intraepithelial Lymphocyte Response during Oral Encephalitozoon cuniculi Infection

“…2) Can the immune IELs generate a long-term memory response against E. cuniculi infection? 3) Can the role of IELs be extended to other microsporidian infections like Encephalitozoon intestinalis and Enterocytozoon bieneusii which are more prevalent in HIV-infected subjects and are well known to cause chronic diarrhea (41)(42)(43)(44)? Studies aimed at addressing these questions are currently under investigation in our laboratory.…”

Unusual Enterocytozoon bieneusi Genotypes and Cryptosporidium hominis Subtypes in HIV-Infected Patients on Highly Active Antiretroviral Therapy

“…12,13 Highly active antiretroviral therapy (HAART) has been reported to reduce the prevalence of microsporidiosis in HIVinfected patients in industrialized nations. 7,14 HAART promotes the reconstitution of the immune system of HIV-infected persons, thereby reducing the occurrence of opportunistic parasitic infections. [15][16][17] However, the effect of HAART on the prevalence of microsporidiosis in HIV-infected patients in developing countries remains unclear, where microsporidiosis is a major health problem because of the high prevalence of the disease in the general population and underfinanced healthcare systems.…”

Microsporidia

“…Albendazole is a benzimidazole that inhibits tubulin polymerization and also has been used as an anthelmintic and antifungal agent. This drug is effective against Encephalitozoon species of microsporidia that infect mammals including humans, but is only variably effective against E. bieneusi (Conteas et al, 2000;Gross, 2003). Although albendazole is likely less effective against E. bieneusi, there are reports of success with albendazole therapy in immunosuppressed patients (Metge et al, 2000).…”

“…Fumagillin is an antibiotic produced by the fungus Aspergillus fumigatus and is highly effective when used topically to treat keratoconjunctivitis due to Encephalitozoon species (Conteas et al, 2000;Chan et al, 2003). When administered systemically to humans for treatment of intestinal microsporidiosis at a dose of 20 mg orally three times daily, fumagillin was highly effective against E. bieneusi, but caused neutropenia and thrombocytopenia in some patients (Champion et al, 2010;Molina et al, 2002).…”

“…Additional drugs with variable results that have been reported for treating microsporidiosis in humans include atovaquone, azithromycin, furazolidone, itraconazole, metronidazole, nitazoxanide, octreotide, sinefungin, and sulfa drugs (Didier et al, 2004). In AIDS patients, the highly active antiretroviral therapy (HAART) regimen resulted in HIV reduction and concomitant improvement in CD4 + T cell levels with a subsequent reduction in the prevalence of many opportunistic infections including microsporidiosis (Conteas et al, 2000;Carr et al, 1998).…”