title: Potential efficacy of fumagillin in intestinal microsporidiosis due to Enterocytozoon bieneusi in patients with HIV infection: results of a drug screening study. The French Microsporidiosis Study Group.
abstract: OBJECTIVE
  Intestinal microsporidiosis due to Enterocytozoon bieneusi is a frequent cause of chronic diarrhoea in patients with HIV infection for which there is no available therapy. This study was designed to search for a drug with activity against this organism.
  
  
  METHODS
  Prospective open-labelled Phase II multicentre study.
  
  
  METHODS
  University hospitals.
  
  
  METHODS
  Sixty HIV-infected men with intestinal E. bieneusi infection.
  
  
  METHODS
  Ten drug regimens were consecutively tested orally for 3 weeks: albendazole plus metronidazole, sulphadiazine plus pyrimethamine, atovaquone, doxycycline plus nifuroxazide, itraconazole, flubendazole, chloroquine, paromomycin, sparfloxacin and fumagillin. Nine evaluable patients per regimen were required, but each patient could be enrolled up to three times in the study.
  
  
  METHODS
  Efficacy was assessed primarily by the clearance of E. bieneusi from stools and intestinal biopsies. The safety of each regimen was also assessed.
  
  
  RESULTS
  Only purified fumagillin was able to clear E. bieneusi from stools as well as intestinal biopsies, whereas all other regimens failed to show antiparasitic efficacy. However, only four patients received fumagillin because of drug-induced thrombocytopenia. The four patients who received fumagillin remained free of E. bieneusi infection after a mean follow-up of 10 months.
  
  
  CONCLUSIONS
  Eradication of E. bieneusi from the intestinal tract of patients with HIV infection and persistent immunosuppression is an achievable goal. Our study allowed the identification of oral fumagillin as a potential treatment for intestinal microsporidiosis due to E. bieneusi.
authors.affiliation: Hôpitaux de Paris, France.
authors.forename: J M
authors.initials: JM
authors.lastname: Molina
authors.forename: J
authors.initials: J
authors.lastname: Goguel
authors.forename: C
authors.initials: C
authors.lastname: Sarfati
authors.forename: C
authors.initials: C
authors.lastname: Chastang
authors.forename: I
authors.initials: I
authors.lastname: Desportes-Livage
authors.forename: J F
authors.initials: JF
authors.lastname: Michiels
authors.forename: C
authors.initials: C
authors.lastname: Maslo
authors.forename: C
authors.initials: C
authors.lastname: Katlama
authors.forename: L
authors.initials: L
authors.lastname: Cotte
authors.forename: C
authors.initials: C
authors.lastname: Leport
authors.forename: F
authors.initials: F
authors.lastname: Raffi
authors.forename: F
authors.initials: F
authors.lastname: Derouin
authors.forename: J
authors.initials: J
authors.lastname: Modaï
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000469:parasitology; D000293:Adolescent; D000328:Adult; D000818:Animals; D000981:Antiprotozoal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003510:Cyclohexanes; D003967:Diarrhea / Q000150:complications / Q000188:drug therapy; D004353:Drug Evaluation, Preclinical; D005231:Fatty Acids, Unsaturated / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007411:Intestinal Diseases, Parasitic / Q000150:complications / Q000188:drug therapy*; D008297:Male; D016816:Microsporida / Q000187:drug effects; D016881:Microsporidiosis / Q000150:complications / Q000188:drug therapy*; D015337:Multicenter Studies as Topic; D011446:Prospective Studies; D012717:Sesquiterpenes; D016896:Treatment Outcome
chemical_list: D000981:Antiprotozoal Agents; D003510:Cyclohexanes; D005231:Fatty Acids, Unsaturated; D012717:Sesquiterpenes; C026211:fumagillin