Microsporidiosis

Overview
Microspridiosis is an opportunistic intestinal infection that causes diarrhea and wasting in immunocompromised individuals (HIV, for example). It results from different species of microsporidia, a group of protozoal parasites.

In HIV infected individuals, microsporidiosis generally occurs when CD4+ T cell counts fall below 100.

Causative agents
At least 14 microsporidian species have been recognized as human pathogens, spread across eight genera:
 * Brachiola
 * B. algerae, B. connori, B. vesicularum
 * Encephalitozoon
 * E. cuniculi, E. hellem, E. intestinalis
 * Enterocytozoon
 * E. bieneusi
 * Microsporidium
 * M. ceylonensis, M. africanum
 * Nosema
 * N. ocularum
 * Pleistophora sp.
 * Trachipleistophora
 * T. hominis, T. anthropophthera
 * Vittaforma
 * V. corneae.

Life cycle


(Coded to image at right).
 * 1) The infective form of microsporidia is the resistant spore and it can survive for an exteneded period of time in the environment.
 * 2) The spore extrudes its polar tubule and infects the host cell.
 * 3) The spore injects the infective sporoplasm into the eukaryotic host cell through the polar tubule.
 * 4) Inside the cell, the sporoplasm undergoes extensive multiplication either by merogony (binary fission) or schizogony (multiple fission).
 * 5) This development can occur either in direct contact with the host cell cytoplasm (E. bieneusi) or inside a vacuole called a parasitophorous vacuole (E. intestinalis). Either free in the cytoplasm or inside a parasitophorous vacuole, microsporidia develop by sporogony to mature spores.
 * 6) During sporogony, a thick wall is formed around the spore, which provides resistance to adverse environmental conditions. When the spores increase in number and completely fill the host cell cytoplasm, the cell membrane is disrupted and releases the spores to the surroundings.
 * 7) These free mature spores can infect new cells thus continuing the cycle.

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).

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).

Source
Treating Opportunistic Infections Among HIV-Infected Adults and Adolescents. Recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association/Infectious Diseases Society of America

Related Chapters

 * Opportunistic infections
 * HIV opportunistic infections
 * HIV opportunistic infection toxoplasma gondii encephalitis: prevention and treatment guidelines
 * HIV opportunistic infection pneumocystis pneumonia: prevention and treatment guidelines