Clinical Features:
Human microsporidiosis represents an important and rapidly emerging opportunistic disease, occurring mainly, but not exclusively, in severely immunocompromised patients with AIDS.  Additionally, cases of microsporidiosis in immunocompromised persons not infected with HIV as well as in immunocompetent persons also have been reported.  The clinical manifestations of microsporidiosis are very diverse, varying according to the causal species with diarrhea being the most common.

*Two reports of E. bieneusi in respiratory samples have also been published, one in 1992 and the other in 1997.

Laboratory Diagnosis:
There are several methods for diagnosing microsporidia:

• Light microscopic examination of the stained clinical smears, especially the fecal samples, is an inexpensive method of diagnosing microsporidial infections even though it does not allow identification of microsporidia to the species level.  The most widely used staining technique is the Chromotrope 2R method or its modifications.  This technique stains the spore and the spore wall a bright pinkish red.  Often, a belt-like stripe, which also stains pinkish red, is seen in the middle of the spore.  This technique, however, is lengthy and time consuming and requires about 90 min.  A recently developed “Quick-Hot Gram Chromotrope technique” however, cuts down the staining time to less than 10 min and provides a good differentiation from the lightly stained background fecal materials so that the spores stand out for easy visualization.  The spores stain dark violet and the belt-like stripe is enhanced. In some cases dark staining Gram positive granules are also clearly seen.  Chemofluorescent agents such as Calcofluor white are also useful in the quick identification of spores in fecal smears.  The spores measure from 0.8 to 1.4 µm in the case of Enterocytozoon bieneusi, and 1.5 to 4 µm in Anncaliia algerae, Encephalitozoon spp., Vittaforma corneae, and Nosema spp.
• Transmission electron microscopy (TEM) is still the gold standard and is necessary for the identification of the microsporidian species.  However, TEM is expensive, time consuming, and not feasible for routine diagnosis.
• Immunofluorescence assays (IFA) using monoclonal and/or polyclonal antibodies are being developed for the identification of microsporidia in clinical samples.
• Molecular methods (mainly Polymerase Chain Reaction, PCR) is an alternative method for the laboratory diagnosis of microsporidiosis.  PCR is available only in research laboratories and has been successfully used for the identification of Anncliia algerae, Enterocytozoon bieneusi, Encephalitozoon intestinalis, Encephalitozoon hellem, and Encephalitozoon cuniculi.  The principal drawback is that it does not work well on formalin-fixed samples stored for long term.

Treatment:
Initiation or optimization of antiretroviral therapy is the cornerstone of treatment of microsporidiosis in HIV-infected patients. Immune restoration to CD4 cell count >100 cells/mm3 is associated with resolution of symptoms of enteric microsporidiosis. Management of severe dehydration, malnutrition, and wasting with fluid support and nutritional supplementation should be provided. Use of antimotility agents for diarrhea control can be considered in infected adults.

For gastrointestinal infections caused by Enterocytozoon bieneusi, fumagillin 20 mg orally three times daily is the only drug with proven efficacy. However, its use is associated with severe thrombocytopenia in 30-50% of patients, which is reversible upon discontinuation of treatment, and the drug is not currently available in the United States.

For disseminated (not ocular) and intestinal infection attributed to microsporidia other than E. bieneusi and Vittaforma corneae, the drug of choice is albendazole 400 mg orally twice daily. Treatment should continue until immune reconstitution has been maintained for at least 6 months. Itraconazole 400 mg orally daily plus albendazole 400 mg orally twice daily may have activity for disseminated disease attributed to Trachipleistophora or Anncaliia.

For ocular infection, the treatment of choice is topical fumagillin bicylohexylammonium (Fumidil B) 3 mg/mL in saline (fumagillin 70 µg/mL) eye drops: two drops every 2 hours for 4 days, then two drops four times daily (investigational use only in United States) plus albendazole 400 mg orally twice daily for management of systemic infection.

For further information, see:
Prevention and Treatment of Opportunistic Infections Guidelines: Adults and Adolescents
Prevention and Treatment of Opportunistic Infections Guidelines: Children

* This drug is approved by the FDA, but considered investigational for this purpose.