Microsporidiosis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Ahmed Younes M.B.B.CH [2]

Overview

The mainstay of therapy for microsporidiosis in immunocompromised patients is highly active antiretroviral therapy (HAART). Albendazole and fumagillin have demonstrated consistent activity against other microsporidia in vitro and in vivo.

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.
• 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.
• 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).
• 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.
• 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.
• 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). 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).

Rating	Strength of recommendation
A	Both strong evidence for efficacy and substantial clinical benefit support recommendation for use. Should always be offered
B	Moderate evidence for efficacy—or strong evidence for efficacy but only limited clinical benefit—supports the recommendation for use. Should generally be offered.
C	Evidence for efficacy is insufficient to support a recommendation for or against use. Or evidence for efficacy might not outweigh adverse conse- quences (e.g. drug toxicity, drug interactions) or the cost of the treatment or alternative approaches. Optional.
D	Moderate evidence for lack of efficacy or for adverse outcome supports a recommendation against use. Should generally not be offered.
E	Good evidence for lack of efficacy or for adverse outcome supports a recommendation against use. Should never be offered.
Rating	Quality of the evidence supporting the recommendation
I	Evidence from at least one properly-designed randomized, controlled trial.
II	Evidence from at least one well-designed clinical trial without randomization, from cohort or case- controlled analytic studies (preferably from more than one center), or from multiple time-series studies, or dramatic results from uncontrolled experiments.
III	Evidence from opinions of respected authorities based on clinical experience, descriptive studies, or reports of expert committees.

Monitoring and Adverse Events

Albendazole side effects are rare but the following adverse effects should be watched for:

• Hypersensitivity (rash, pruritus, fever)
• neutropenia (reversible)
• CNS effects (dizziness, headache)
• Gastrointestinal disturbances (abdominal pain, diarrhea, nausea, vomiting)
• Hair loss (reversible)
• Elevated liver enzymes (reversible) have been reported.

Fumagillin side effects:

• 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).

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).

Antimicrobial Regimen

• Microsporidiosis

• 1. Ocular

• Preferred regimen: Albendazole 400 mg PO bid for 3 weeks AND Fumagillin eye drops.

• 2. Intestinal (diarrhea)

• Preferred regimen:

• Adult: Albendazole 400 mg PO bid for 3 weeks for E. intestinalis.
• Pediatric: Albendazole 15 mg/kg per day divided into 2 daily doses for 7 days for E. intestinalis.

• Note: Fumagillin 20 mg PO tid is the only reported effective treatment for E. bieneusi.

• 3. Disseminated

• Preferred regimen: Albendazole 400 mg po bid for 3 weeks.