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.
Molina
Jean-Michel
JM
Department of Infectious Diseases, Hôpital Saint-Louis and University of Paris VII, Paris, France. jean-michel.molina@sls.ap-hop-paris.fr
Tourneur
Muriel
M
Sarfati
Claudine
C
Chevret
Sylvie
S
de Gouvello
Amaury
A
Gobert
Jean-Gérard
JG
Balkan
Suna
S
Derouin
Francis
F
D000328:Adult; D000981:Antiprotozoal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002908:Chronic Disease; D003510:Cyclohexanes; D004311:Double-Blind Method; D021862:Enterocytozoon / Q000302:isolation & purification; D005231:Fatty Acids, Unsaturated / Q000009:adverse effects / Q000627:therapeutic use*; D005243:Feces / Q000469:parasitology; D006801:Humans; D016867:Immunocompromised Host; D007411:Intestinal Diseases, Parasitic / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D016881:Microsporidiosis / Q000175:diagnosis / Q000188:drug therapy*; D009894:Opportunistic Infections / Q000188:drug therapy*; D012717:Sesquiterpenes
D000981:Antiprotozoal Agents; D003510:Cyclohexanes; D005231:Fatty Acids, Unsaturated; D012717:Sesquiterpenes; C026211:fumagillin