Thalidomide: a novel therapy for microsporidiosis.

Abstract

Microsporidiosis is a common cause of chronic diarrhea in human immunodeficiency virus (HIV)-seropositive individuals and often does not respond to treatment. Fecal tumor necrosis factor alpha (TNF-alpha) is elevated in microsporidiosis; therefore, thalidomide, an anti-TNF-alpha agent, was used as therapy. Eighteen subjects with chronic diarrhea caused by Enterocytozoon bieneusi that had not responded symptomatically to albendazole and 1 untreated subject with Encephalitozoon intestinalis received 1 month of thalidomide, 100 mg nocte. Clinical response was assessed by stool frequency and body weight, histological response by light microscopy with villus height/crypt depth ratios and electron microscopy, and immunologic response by fecal TNF-alpha level. Seven subjects with chronic diarrhea due to E. bieneusi had a complete clinical response, and 3 had a partial response to thalidomide. There was a significant decrease in stool frequency from 5.3 to 3.1 per day (P = 0.001), and weight increased significantly by 1.2 kg (P < 0.02). Thalidomide significantly increased the villus height/crypt depth ratio (1.95 to 2.07; P = 0.045) and number of abnormal forms of microsporidia (P < 0.01). Fecal TNF-alpha level nonsignificantly decreased from 17.9 to 8.9 U/mL. There was apparent disruption of all stages of the life cycle of E. intestinalis. Thalidomide may be an effective therapy for diarrhea and weight loss from E. bieneusi.