Microsporidiosis medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Medical Therapy
CDC Guidelines for Prevention and Treatment of Microsporidiosis Infections in HIV-Infected Adults and Adolescents
Treatment Recommendations
ART with immune restoration (an increase of CD4+ T lymphocyte count to >100 cells/µL) is associated with resolution of symptoms of enteric microsporidiosis, including that caused by E. bieneusi.[1][2][3] All patients should be offered ART as part of the initial management of their infection (AII). Nevertheless, data indicate that microsporidia are suppressed but not eliminated.[2]
No specific therapeutic agent is active against E. bieneusi infection. A controlled clinical trial suggests that E. bieneusi might respond to oral fumagillin (60 mg/day), a water insoluble antibiotic made by Aspergillus fumigatus (BII).[4][5] However, fumagillin is not available for systemic use in the United States. One report indicates that 60 days of nitazoxanide might resolve chronic diarrhea caused by E. bieneusi in the absence of ART.[6] However, the effect might be minimal among patients with low CD4+ T cell counts. Nitazoxanide is approved for use among children and is expected to be approved by the FDA for use among adults.
Albendazole and fumagillin have demonstrated consistent activity against other microsporidia in vitro and in vivo.[7][8][9][10][11] Albendazole, a benzimidazole that binds to b-tubulin, has activity against many species of microsporidia, but it is not effective for Enterocytozoon infections, although fumagillin has activity in vitro and in vivo.
Albendazole is recommended for initial therapy of intestinal and disseminated (not ocular) microsporidiosis caused by microsporidia other than E. bieneusi (AII). Itraconazole also might be useful in disseminated disease when combined with albendazole especially in infections caused by Trachipleistophora or Brachiola (CIII).
Ocular infections caused by microsporidia should be treated with topical Fumidil B (fumagillin bicylohexylammonium) in saline (to achieve a concentration of 70 mg/mL of fumagillin)(BII).[11] Topical fumagillin is the only formulation available for treatment in the United States and is investigational. Although clearance of microsporidia from the eye can be demonstrated, the organism often is still present systemically and can be detected in the urine or in nasal smears. In such cases, the use of albendazole as a companion systemic agent is recommended (BIII).
Metronidazole and atovaquone are not active in vitro or in animal models and should not be used to treat microsporidiosis (DII). Fluid support should be offered if diarrhea has resulted in dehydration (AIII). Malnutrition and wasting should be treated with nutritional supplementation (AIII).
Monitoring and Adverse Events
Albendazole side effects are rare but hypersensitivity (rash, pruritis, fever), neutropenia (reversible), CNS effects (dizziness, headache), gastrointestinal disturbances (abdominal pain, diarrhea, nausea, vomiting), hair loss (reversible), and elevated hepatic enzymes (reversible) have been reported. Albendazole is not carcinogenic or mutagenic. Topical fumagillin has not been associated with substantial side effects. Oral fumagillin has been associated with thrombocytopenia, which is reversible on stopping the drug.
Management of Treatment Failure
Supportive treatment and optimizing ART to attempt to achieve full virologic suppression are the only feasible approaches to the management of treatment failure (CIII).
Prevention of Recurrence
Treatment for ocular microsporidiosis should be continued indefinitely because recurrence or relapse might follow treatment discontinuation (BIII). Whether treatment can be safely discontinued after immune restoration with ART is unknown, although it is reasonable, on the basis of the experience with discontinuation of secondary prophylaxis (chronic maintenance therapy) for other opportunistic infections during advanced HIV-1 disease, to discontinue chronic maintenance therapy if patients remain asymptomatic with regard to signs and symptoms of microsporidiosis and have a sustained (e.g. >6 months) increase in their CD4+ T lymphocyte counts to levels >200 cells/µL after ART (CIII).
Special Considerations During Pregnancy
Among animals (i.e., rats and rabbits), albendazole is embryotoxic and teratogenic at dosages of 30 mg/kg body weight. Therefore, albendazole is not recommended for use among pregnant women (DIII). However, well-controlled studies in human pregnancy have not been performed. Systemic fumagillin has been associated with increased resorption and growth retardation in rats. No data on use in human pregnancy are available. However, because of the antiangiogenic effect of fumagillin, this drug should not be used among pregnant women (EIII). Topical fumagillin has not been associated with embryotoxic or teratogenic effects among pregnant women and might be considered when therapy with this agent is appropriate (CIII).
References
- ↑ Maggi P, Larocca AM, Quarto M, Serio G, Brandonisio O, Angarano G, Pastore G (2000). "Effect of antiretroviral therapy on cryptosporidiosis and microsporidiosis in patients infected with human immunodeficiency virus type 1". Eur. J. Clin. Microbiol. Infect. Dis. 19 (3): 213–7. PMID 10795595. Retrieved 2012-04-19. Unknown parameter
|month=ignored (help) - ↑ 2.0 2.1 Goguel J, Katlama C, Sarfati C, Maslo C, Leport C, Molina JM (1997). "Remission of AIDS-associated intestinal microsporidiosis with highly active antiretroviral therapy". AIDS. 11 (13): 1658–9. PMID 9365777. Retrieved 2012-04-19. Unknown parameter
|month=ignored (help) - ↑ Conteas CN, Berlin OG, Speck CE, Pandhumas SS, Lariviere MJ, Fu C (1998). "Modification of the clinical course of intestinal microsporidiosis in acquired immunodeficiency syndrome patients by immune status and anti-human immunodeficiency virus therapy". Am. J. Trop. Med. Hyg. 58 (5): 555–8. PMID 9598440. Retrieved 2012-04-19. Unknown parameter
|month=ignored (help) - ↑ Molina JM, Goguel J, Sarfati C, Michiels JF, Desportes-Livage I, Balkan S, Chastang C, Cotte L, Maslo C, Struxiano A, Derouin F, Decazes JM (2000). "Trial of oral fumagillin for the treatment of intestinal microsporidiosis in patients with HIV infection. ANRS 054 Study Group. Agence Nationale de Recherche sur le SIDA". AIDS. 14 (10): 1341–8. PMID 10930148. Retrieved 2012-04-19. Unknown parameter
|month=ignored (help) - ↑ Molina JM, Tourneur M, Sarfati C, Chevret S, de Gouvello A, Gobert JG, Balkan S, Derouin F (2002). "Fumagillin treatment of intestinal microsporidiosis". N. Engl. J. Med. 346 (25): 1963–9. doi:10.1056/NEJMoa012924. PMID 12075057. Retrieved 2012-04-19. Unknown parameter
|month=ignored (help) - ↑ Bicart-Sée A, Massip P, Linas MD, Datry A (2000). "Successful treatment with nitazoxanide of Enterocytozoon bieneusi microsporidiosis in a patient with AIDS". Antimicrob. Agents Chemother. 44 (1): 167–8. PMC 89645. PMID 10602740. Unknown parameter
|month=ignored (help);|access-date=requires|url=(help) - ↑ Didier ES (1997). "Effects of albendazole, fumagillin, and TNP-470 on microsporidial replication in vitro". Antimicrob. Agents Chemother. 41 (7): 1541–6. PMC 163955. PMID 9210681. Retrieved 2012-04-19. Unknown parameter
|month=ignored (help) - ↑ Katiyar SK, Edlind TD (1997). "In vitro susceptibilities of the AIDS-associated microsporidian Encephalitozoon intestinalis to albendazole, its sulfoxide metabolite, and 12 additional benzimidazole derivatives". Antimicrob. Agents Chemother. 41 (12): 2729–32. PMC 164197. PMID 9420047. Retrieved 2012-04-19. Unknown parameter
|month=ignored (help) - ↑ Molina JM, Chastang C, Goguel J, Michiels JF, Sarfati C, Desportes-Livage I, Horton J, Derouin F, Modaï J (1998). "Albendazole for treatment and prophylaxis of microsporidiosis due to Encephalitozoon intestinalis in patients with AIDS: a randomized double-blind controlled trial". J. Infect. Dis. 177 (5): 1373–7. PMID 9593027. Retrieved 2012-04-19. Unknown parameter
|month=ignored (help) - ↑ Gritz DC, Holsclaw DS, Neger RE, Whitcher JP, Margolis TP (1997). "Ocular and sinus microsporidial infection cured with systemic albendazole". Am. J. Ophthalmol. 124 (2): 241–3. PMID 9262551. Unknown parameter
|month=ignored (help);|access-date=requires|url=(help) - ↑ 11.0 11.1 Diesenhouse MC, Wilson LA, Corrent GF, Visvesvara GS, Grossniklaus HE, Bryan RT (1993). "Treatment of microsporidial keratoconjunctivitis with topical fumagillin". Am. J. Ophthalmol. 115 (3): 293–8. PMID 8117342. Unknown parameter
|month=ignored (help);|access-date=requires|url=(help)