POTENTIAL EFFICACY OF FUMAGILLIN IN INTESTINAL MICROSPORIDIOSIS DUE TO ENTEROCYTOZOON-BIENEUSI IN PATIENTS WITH HIV-INFECTION - RESULTS OF A DRUG SCREENING STUDY

Objective: Intestinal microsporidiosis due to Enterocytozoon bieneusi is a frequent cause of chronic diarrhoea in patients with HIV infectio n for which there is no available therapy. This study was designed to search for a drug with activity against this organism. Design: Prospec tive open-labelled Phase II multicentre study. Setting: University hos pitals. Patients: Sixty HIV-infected men with intestinal E. bieneusi i nfection. Interventions: Ten drug regimens were consecutively tested o rally 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, bur each patient c ould be enrolled up to three times in the study. Outcome measure: Effi cacy was assessed primarily by the clearance of E. bieneusi from stool s and intestinal biopsies. The safety of each regimen was also assesse d. Results: Only purified fumagillin was able to clear E. bieneusi fro m stools as well as intestinal biopsies, whereas all other regimens fa iled to show antiparasitic efficacy. However, only four patients recei ved fumagillin because of drug-induced thrombocytopenia. The four pati ents who received fumagillin remained free of E. bieneusi infection af ter a mean follow-up of 10 months. Conclusion: Eradication of E. biene usi from the intestinal tract of patients with HIV infection and persi stent immunosuppression is an achievable goal. Our study allowed the i dentification of oral fumagillin as a potential treatment for intestin al microsporidiosis due to E. bieneusi.