Fumagillin treatment of intestinal microsporidiosis

Background: Intestinal microsporidiosis due to Enterocytozoon bieneusi is a cause of chronic diarrhea, malabsorption, and wasting in immunocompromised patients. Currently, there is no effective treatment. Methods: We conducted a randomized, double-blind, placebo-controlled trial of fumagillin (60 mg per day orally for two weeks) in patients with chronic E. bieneusi infection. Efficacy was assessed primarily by the clearance of microsporidia, as evidenced by analysis of stool specimens. Patients in whom microsporidia were not cleared received treatment for two weeks with open-label fumagillin. After clearance of the parasite, follow-up stool examinations were performed monthly to detect relapses. Results: Twelve patients were enrolled in this study, 10 with the acquired immunodeficiency syndrome and 2 who had received organ transplants. Clearance of microsporidia occurred in all six of the patients in the fumagillin group, as compared with none of the six in the placebo group (P=0.002). Treatment with fumagillin was also associated with increases in absorption of d-xylose (P=0.003) and in Karnofsky performance scores (P<0.001) and with decreases in loperamide use (P=0.01) and total stool weight (P=0.04). There were serious adverse events (neutropenia and thrombocytopenia) in three patients in the fumagillin group; one patient in the placebo group had severe diarrhea. All six controls subsequently had clearance of microsporidia after open-label treatment with fumagillin. Relapses of the infection were identified in two patients during follow-up (median follow-up, 10 months). Conclusions: Fumagillin is an effective treatment for chronic E. bieneusi infection in immunocompromised patients.