OVERVIEW: What every practitioner needs to know

Are you sure your patient has Microsporidiosis? What should you expect to find?

Symptoms and physical exam findings depend on location of infection. This infection can be present in any organ system, so, in an immunocompromised host, it is in the differential for almost all conditions. The most common infections are intestinal or ocular infection.

Key infection symptoms include:

  • Intestinal infection: diarrhea, wasting, bloating, malabsorption, occasional fever

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  • Ocular infection: blurry vision, eye pain, foreign body sensation in the eye

Key physical findings include:

  • Intestinal infection: weight loss, diarrhea, loss of subcutaneous mass, occasional fever

  • Ocular infection: red conjunctiva, corneal ulcer, punctate keratoconjunctivitis

How did the patient develop Microsporidiosis? What was the primary source from which the infection spread?

Infection can occur in both immune competent and immune compromised hosts; however, severe infection has most often been associated with hosts with impaired immune systems (i.e., AIDS, organ transplant, use of anti-TNFα, cancer chemotherapy or use of other immune suppressive drugs). In immune compromised patients microsporidiosis can present in almost any organ system; although intestinal infection is the most common finding. Other rarer manifestations have included disseminated infection with a sepsis presentation, hepatitis, sinus infection, encephalitis with focal lesions resembling toxoplasmosis, myositis, and skin infections.

Which individuals are of greater risk of developing Microsporidiosis?

In the setting of HIV infection, intestinal microsporidiosis is most often seen when the CD4+ count is less than 100 cells/mm3. In other patients, it is associated with the administration of immune suppressive drugs. Recent cases indicate that transplant patients have an increased risk of microsporidiosis and that it can present as fever of unknown aetiology in these patients.

In immune competent hosts, it has been associated with travel, recreational water exposure, and, for ocular infections, with the use of contact lenses.

Beware: there are other diseases that can mimic Microsporidiosis:

Depending on the organ system involved, microspordiosis can look like many other infections. In general, in an immune suppressed patient, this disease should be suspected when infections fail to respond to standard treatments. Diagnosis usually requires a tissue biopsy, and this should be done in immune compromised hosts who fail to respond to standard treatments. In the setting of diarrhea, if no organisms are seen on routine stool examinations, special stains should be ordered to look for microsporidiosis.

What laboratory studies should you order and what should you expect to find?

Results consistent with the diagnosis

There are no specific serum or diagnostic tests, other than finding the organism, that specifically point to the diagnosis of microspordiosis.

Results that confirm the diagnosis

Demonstration of Microsporidia by light microscopy is accomplished with staining methods that produce differential contrast between the spores of the Microsporidia and the cells and debris in clinical samples in which Microsporidia are found. Adequate magnification using a 60x to 100x objective is required for visualization, as the spores are 1-3 um in size. Chromotrope 2R, calcofluor white (fluorescent brightener 28), and Uvitex 2B are useful selective stains for Microsporidia in stool specimens and other body fluids.

In a study that examined 50 electron microscopy-proven Microsporidia-positive stool specimens, both the chromotrope 2R and chemofluorescent brightening stains identified 100% of specimens if at least 50 100x objective fields were examined. The limit of detecting Microsporidia by these techniques appears to be 50,000 organisms/ml. Overall, the sensitivity of the chemofluorescent brightener-based stains is slightly higher than chromotrope-based stains, especially when low numbers of spores are present in a sample; however, the specificity of the chemofluorescent stains is lower (90 vs. 100% in one study).

Neither the chromotrope nor the chemofluorescent stain provides information on the species of Microsporidia being identified. Although it has been reported that microsporidian spores in food can give a false-positive result, and, despite the fact that Microsporidia are common in the environment, it does not appear to be a common problem when using stool specimens for diagnosing these infections. Detection kits for microsporidia in stool and environmental samples using antibodies to Encephalitozoonidae and Enterocytozoon bieneusi are now commercially available (Waterborne, Inc., New Orleans, LA). Although several species of microsporidia can be grown in tissue culture, this is not routinely used for identification of these organisms, and the most common microsporidia in human infection, Ent bieneusi, has not been cultivated in vitro.

Microsporidia in body fluids other than stool (e.g., urine, cerebrospinal fluid, bile, duodenal aspirates, bronchoalveolar lavage fluid, sputum) have been visualized using Chromotrope 2R, chemofluorescent optical brightening agents, Giemsa, Brown-Hopps Gram stain, acid-fast staining, or Warthin-Starry silver staining. Generally, it is easier to identify microsporidian spores in body fluids other than in stool owing to the absence of bacteria and debris, which can be confused with microsporidian spores. As microsporidian infections usually involve mucosa or epithelium, cytologic preparations are especially useful for diagnosis.

Specimens that have been useful for diagnosing microsporidian infections include intestinal and biliary epithelium, epithelium of the cornea and conjunctivae, epithelium of the sinonasal and tracheobrochial regions, renal tubular epithelium, and urothelium. A diagnosis has also been accomplished by examining touch preparations of biopsy material. Microscopic examination of corneal tissue in patients with microsporidian keratitis, obtained by gently rubbing the conjunctiva and cornea with a tissue swab, usually reveals multiple, gram-positive, oval organisms in epithelial cells.

A number of molecular diagnostic tests using polymerase chain reaction (PCR) based on rRNA genes have been developed for pathogenic Microsporidia. These PCR techniques have been applied to biopsy specimens, urine, cultures, and more recently stool specimens and should greatly facilitate both diagnosis and epidemiologic studies. Currently, these molecular tests are available in reference laboratories, such as the Centers for Disease Control and Prevention (CDC; Atlanta, GA, USA).

What imaging studies will be helpful in making or excluding the diagnosis of Microsporidiosis?

There are no specific imaging tests for this infection, although, depending on the organ, involved abnormalities may be seen on various tests. For example, in microsporidian encephalitis, mass lesions can be seen on CT scanning or by MRI, and these lesions resemble those seen with various infections, such as Toxoplasmosis. In other cases, microsporidiosis has been associated with sinus changes (e.g. air fluid levels and mucosal thickening) and/or pneumonia.

What consult service or services would be helpful for making the diagnosis and assisting with treatment?

If you decide the patient has Microsporidiosis, what therapies should you initiate immediately?

In general, therapy is based on the species of microsporidia identified. For infections due to microsporidia, other than Ent. beineusi, the treatment of choice is albendazole. This includes all of the microsporidia that disseminate and cause infection in organs other than the intestine. For intestinal infections due to Ent. bieneusi, fumagillin is the best therapeutic agent. For all cases of microsporidiosis, improvement in the immune status of the host is a critical treatment goal. For patients with AIDS, optimization of cART is a key element of treatment. For patients on other immune suppressive drugs, decreasing the amount of immune suppression is important in improving these infections.

For ocular disease due to microsporidiosis, topical fumagillin is the best therapeutic agent. Systemic albendazole can be added to this topical treatment if systemic symptoms are present or if the organism is found in urine specimens of patients with ocular infection (suggesting disseminated infection has occurred).

In intestinal infection with severe diarrhea, intravenous (IV) fluids may be needed to correct electrolyte disturbances. In addition, nutritional supplementation is often needed.

If I am not sure what pathogen is causing the infection what anti-infective should I order?

In general, therapy is based on the species of microsporidia identified. For infections due to microsporidia, other than Ent. beineusi, the treatment of choice is albendazole. This includes all of the microsporidia that disseminate and cause infection in organs other than the intestine. For intestinal infections due to Ent. bieneusi, fumagillin is the best therapeutic agent. For all cases of microsporidiosis, improvement in the immune status of the host is a critical treatment goal. For patients with AIDS, optimization of cART is a key element of treatment. For patients on other immune suppressive drugs, decreasing the amount of immune suppression is important in improving these infections.

For ocular disease due to microsporidiosis, topical fumagillin is the best therapeutic agent. Systemic albendazole can be added to this topical treatment if systemic symptoms are present or if the organism is found in urine specimens of patients with ocular infection (suggesting disseminated infection has occurred).

Clinical studies have demonstrated that improved immune function can result in the clinical response of patients with gastrointestinal microsporidiosis, with elimination of the organism and normalization of the intestinal architecture. Relapse has been reported in patients who developed failure of their antiretroviral therapy associated with a decline in immune function and falling CD44 counts. Overall, these observations suggest that part of the primary treatment of microsporidiosis in the setting of AIDS is the institution of effective antiretroviral therapy (ART). There have been no reports of immune reconstitution syndromes with ART and microsporidiosis.

Among the compounds tested in vitro and in vivo for treatment of microsporidiosis, fumagillin and albendazole have demonstrated the most consistent activity and have been demonstrated to have clinical efficacy in human infections with various Microsporidia. There are few placebo-controlled comparative treatment trials of microsporidiosis due to Encephalitozoon spp., but there are numerous case reports demonstrating the efficacy of 2-4 weeks of albendazole 400 mg BID for these infections.

In a double-blind, placebo-controlled trial of eight patients with AIDS and diarrhea due to Enc. intestinalis, treatment with albendazole (400 mg BID for 3 weeks) resulted in resolution of the diarrhea and elimination of the organism in all eight patients, similar to that seen in several case reports. In case reports of chronic sinusitis, respiratory infection, and disseminated infection due to Enc. hellem, treatment with 400 mg of albendazole twice daily resulted in resolution of symptoms and clearance of the organism. Clinical improvement was demonstrated with albendazole treatment in a patient with disseminated Enc. cuniculi infection involving the central nervous system (CNS), conjunctiva, sinuses, kidneys, and lungs. It has also been reported to be effective in cases of urethritis, renal failure, and disseminated infection. In addition to its efficacy in Encephalitozoon spp., disseminated infections with other Microsporidia have also been reported to respond to albendazole treatment. In patients with disseminated infection accompanied by myositis due to T. hominis and in a patient with myositis due to a Anncaliia vesicularum, albendazole (400 mg BID) resulted in clinical improvement.

In contrast to its success in treating patients with the species of Microsporidia that disseminate, albendazole has displayed only limited efficacy against Ent. bieneusi infection. In two studies examining 66 patients with diarrhea due to Ent. bieneusi during the pre-ART era, symptoms were alleviated in about 50% of the patients treated with albendazole, but the presence of Ent. bieneusi persisted during treatment in all patients and there was no improvement in any patient’s D-xylose absorption test. The symptoms rapidly recurred on discontinuing albendazole therapy in the patients who had reported symptom alleviation with it.

Most other studies have found that albendazole had no efficacy against Ent. bieneusi infection. Fumagillin has been found to have activity in vitro and in vivo against Microsporidia pathogenic for humans, including Enc. cuniculi, Enc. hellem, Enc. intestinalis, V. corneae, in the 60 mg/day group, 8 of 11 patients did not have spores in their stools at week 6 and remained free of spores in stool specimens for a mean of 11 months. A subsequent randomized trial based evaluating 12 patients (with either AIDS or transplantation) confirmed that 60 mg/day (given as 20 mg TID) effectively treated Ent. bieneusi intestinal infection. Treatment was associated with resolution of diarrhea, clearance of spores, improvement of Karnofsky scores, and improvement in D-xylose absorption tests. The main limiting toxicity of this treatment was thrombocytopenia, which was reversible on stopping fumagillin treatment.

In ocular disease solutions of the soluble salt, Fumidil B (fumagillin bicylohexylammonium; Mid-Continent Agrimarketing, Overland Park, KS, USA) applied topically have been demonstrated to be nontoxic to the cornea. Treatment of ocular microsporidiosis can be accomplished using a 3 mg/ml solution of Fumidil B in saline (fumagillin 70 ug/ml); the treatment should be continued indefinitely, as recurrence has been reported on stopping these drops. Although clearance of Microsporidia from the eye can be demonstrated, the organism is still often present systemically and can be demonstrated in the urine or in nasal smears. In such cases, the use of albendazole as a systemic agent is reasonable and effective. Keratoplasty appears to provide temporary improvement in some cases, and debulking by corneal scraping may be useful in cases not responding to medical treatment. Steroids may be useful for decreasing the associated inflammatory response but have no direct action on Microsporidia.

Table I contains a list of antibiotics and dosages used in treating Microsporidia infections.

Table I.
Organism Antibiotic Dose Alternative
All microsporidian infections cARTwith immune restoration (an increase of CD4+ count to >100 cells/µL) is associated with resolution of symptoms of enteric microsporidiosis. All patients should be offered ART as part of the initial management of microsporidial infection.Severe dehydration, malnutrition, and wasting should be managed by fluid support and nutritional supplement.Antimotility agents can be used for diarrhea control if required.
Enterocytozoon bieneusi No effective commercial treatment. Fumagillin (oral) has been effective in a clinical trial. 20mg TID Albendazole resulted in clinical improvement in up to 50% of patients in some studies, but it was not effective in other studies. Nitazoxanide 1,000mg BID with food for 60 days has been used, but it is less effective in patients with low CD4 counts
Encephalitozoonidae infection (e.g., systemic, sinusitis, encephalitis, hepatitis) Albendazole 400 mg BID
Trachipleistophora hominis Albendazole 400 mg BID Would consider adding Itraconozole>400 mg QD
Anncaliia (Brachiola) vesicularum Albendazole 400 mg BID Would consider adding Itraconozole>400 mg QD
Encephalitozoonidae keratoconjunctivitis Fumagillin solution‡ (Fumadil B 3 mg/ml) 2 drops every 2 hours for 4 days, then 2 drops 4 times a day

Patients may also need albendazole if systemic infection is present.

What complications could arise as a consequence of Microsporidiosis?

What should you tell the family about the patient's prognosis?

In patients who are immune suppressed and the immune suppression cannot be reversed, this infection can be a poor prognostic sign. One can say that these infections do respond to treatment but that the response is variable.

How do you contract Microsporidiosis and how frequent is this disease?

Microsporidia appear to be common self-limited or asymptomatic enteric pathogens in immunocompetent hosts. There have been multiple reports of Encephalitozoon bieneusi in travelers and residents of tropical countries, as well as reports of Encephalitozoon intestinalis. Serosurveys in humans have demonstrated a high prevalence of antibodies to Enc. cuniculi and Enc. hellem, suggesting asymptomatic infection is common.

In HIV-positive Czech patients, 5.3% were seropositive to Enc. cuniculi and 1.3% to Enc. hellem. In Slovakia, 5.1% of slaughterhouse workers were seropositive to Encephalitozoon spp. Another group found positive antibody titers in 8.6% of healthy adults in England, 43% of Nigerians with tuberculosis, 19% of Malaysians with filariasis, and 36% of Ghanians with malaria. In another study, 12% of travelers returning from the tropics were seropositive and no control non-travelers were positive. Antibodies to Enc. intestinalis were found among 5% of pregnant French women and 8% of Dutch blood donors. Reported prevalence rates of microsporidiosis varied between 2% and 70% among HIV-1-infected patients with diarrhea, depending on the diagnostic techniques employed and the patient population described.

Enterocytozoon bieneusi causes the majority of infections in patients with AIDS and presents as diarrhea with wasting syndrome. Infections with Ent. bieneusi have been reported in liver and in heart-lung transplantation recipients, and Encephalitozoon spp. infections have been reported in patients with kidney, pancreas, liver, or bone marrow transplantation. The incidence of microsporidiosis has declined dramatically with the widespread use of effective cART. In the immunosuppressed host, microsporidiosis is most commonly observed when the CD4+ T lymphocyte count is less than 100 cells/µL.

Most can be spread by food or water via ingestion. There are reports that suggest that some microsporidia may be spread by respiratory routes and that some may be sexually transmitted. The mode of spread depends on the species of microsporidia.

Microsporidian spores are commonly found in surface water, and human pathogenic species have been found in municipal water supplies, tertiary sewage effluent, and groundwater. Water contact has been found to be an independent risk factor for microsporidiosis in some studies, but not in others. Encephalitozoon cuniculi spores are viable for at least 6 days in water. Most microsporidian infections are transmitted by oral ingestion of spores, with the site of initial infection being the gastrointestinal tract. Microsporidia are probably zoonotic infections, given their widespread distribution in animals and birds. In addition, infective spores of Microsporidia are present in multiple human body fluids (e.g., stool, urine, and respiratory secretions) during infection, suggesting that person-to-person transmission via multiple routes (oral, respiratory, and sexual) is possible. Although congenital transmission of Enc. cuniculi has been demonstrated in rabbits, mice, dogs, horses, foxes, and squirrel monkeys, it has not been demonstrated in humans.

What pathogens are responsible for this disease?

The microsporidia reported as pathogens in humans include Encephalitozoon cuniculi, Encephalitozoon hellem, Encephalitozoon (Septata) intestinalis,Enterocytozoon bieneusi, Trachipleistophora hominis, Trachipleistophora anthropopthera, Pleistophora spp., Pleistophora ronneafiei, Vittaforma (Nosema) corneae, Microsporidium spp., Nosema ocularum, Tubulonosema acridophagus, Endoreticulatus spp., Anncaliia (Brachiola/Nosema) connori, Anncaliia (Brachiola) vesicularum, and Anncaliia (Brachiola/Nosema) algerae.

How do these pathogens cause Microsporidiosis?

Infection with Enc. cuniculi in many mammals results in chronic infection with persistently high antibody titers and ongoing inflammation (e.g., persistent encephalitis in rabbits and chronic renal disease and congenital transmission in foxes). In immunocompetent murine models of Enc. cuniculi infection, ascites develop and then clear; however, if corticosteroids are administered, the mice redevelop ascites, consistent with latent persistence of Microsporidia in these animals.

There are scant data on the immune response to microsporidia in humans. It is clear that a strong humoral response occurs during infection and it includes antibodies that react with the spore wall and polar tube. The immunosuppressive states associated with microsporidiosis (e.g., AIDS and transplantation) are those that inhibit cell-mediated immunity. Microsporidiosis is usually seen in HIV-infected patients when there is a profound defect in cell-mediated immunity (e.g., a CD4 cell count less than 100/mm3); spontaneous cure of microsporidiosis can be induced by immune reconstitution with cART Overall, these data are consistent with observations on the immunology of the mouse model of microsporidiosis in which INFγ, IL12, and CD8+ cells have been implicated as critical in the immune response to infection. It is possible that, in humans, administration of INFγ or IL12 could be useful adjuncts for treating microsporidiosis. Both natural killer (NK) cells and γδ T-cells, which are increased at early stages of infection, are likely important sources of IFN production.

Studies with Enc. intestinalis and Enc. cuniculi have demonstrated that INFγ knockout mice cannot clear infection. The importance of IL-12 is illustrated by the fact that lethal infection with Enc. cuniculi also occurs in p40 knockout mice, which are unable to produce IL-12. INFγ production by dendritic cells has been demonstrated to be important for priming the gut intraepithelial lymphocte response following oral infection with Enc. cuniculi. Mice deficient in CD8+ cells succumb to the parasitic challenge. In contrast, there was no change in mortality for mice deficient in CD4+ cells. The protective effect of CD8+ T-cells is mediated by their ability to produce cytokines and to reduce the parasite load by killing the infected targets in the host tissue The major killing mechanism exhibited by CD8+ T-cells is via the perforin pathway, and mice lacking the perforin gene die when infected with Enc. cuniculi. These observations suggest that the cytotoxic T-cell response is a key factor in the immune response to Enc. cuniculi-infected mice.

Infection of the epithelium of the gastrointestinal tract (small intestine and biliary epithelium) is the most frequent presentation of microsporidiosis. Encephalitozoon bieneusi infection does not produce active enteritis or ulceration, but infection results in variable degrees of villus blunting and crypt hyperplasia. The organism is located on the apical surface of the enterocytes of the small intestine and epithelial cells of the biliary tract and pancreas. Spores are rarely found on the basal surface or in the lamina propria. Infection may be associated with increased intraepithelial lymphocytes and epithelial disarray. The pathogenesis of Ent. bieneusi infections in immune-competent humans and non-human hosts has not been well characterized. For example, it is unknown if Ent. bieneusi persists in otherwise healthy people and reactivates under conditions of immune-deficiency.

Encephalitozoon intestinalis and other Encephalitozoon spp. are invasive; spores are found in the apical and basal sides of infected intestinal enterocytes and in the lamina propria. Histopathology can demonstrate areas of necrosis and mucosal erosion.

Encephalitozoon spp. infect the genitourinary system in most mammals, including humans, in which infection discovered in any organ (eye, gastrointestinal tract, liver, central nervous system, etc.) is often associated with the shedding of spores in the urine. Granulomatous interstitial nephritis composed of plasma cells and lymphocytes is the most frequent pathologic finding. This is associated with tubular necrosis, with the lumen of the tubules containing amorphous granular material. Spores are located in the necrotic tubes and sloughing tubular epithelial cells. As spores and infected tubular cells are shed into the bladder, they can infect other epithelial cells of the urogenital tract, causing ureteritis, prostatitis, and cystitis and infection in macrophages, muscle, and supporting fibroblasts of the associated mucosa. Lower respiratory tract infection due to Encephalitozoonidae has demonstrated erosive tracheitis, bronchitis, and bronchiolitis. In most cases, organisms are found in intact or sloughed epithelial cells. Sinus biopsies in AIDS patients with chronic sinusitis and microsporidiosis have demonstrated spores in epithelium, as well as in supporting structures.

Infection with Enc. cuniculi, Enc. hellem, or Enc. intestinalis can result in punctate keratopathy and conjunctivitis characterized by multiple punctate corneal ulcers (e.g., a superficial epithelial keratitis). Microsporidian spores are present in corneal and conjunctival epithelium that can be obtained by scraping or biopsy of the lesions. The organisms do not invade the corneal stroma but remain limited to the epithelium. Inflammatory cells are rarely present. Infections in immunocompetent hosts with other species of Microsporidia have usually involved deeper levels of the corneal stroma with associated necrosis and acute inflammatory cells, with some giant cells in several cases. Clinically, these patients have a corneal stromal keratitis and occasionally a uveitis.

What other clinical manifestations may help me to diagnose and manage Microsporidiosis?

Infection is increased in incidence in patients with immune deficiencies. HIV patients with CD4+ less than 100 cells/mm3 and those with impaired immune systems (i.e., organ transplant, use of anti-TNFα, cancer chemotherapy or use of other immune suppressive drugs).

There are no other specific physical exam findings. Findings depend on the organ system involved.

How can Microsporidiosis be prevented?

There are limited data on effective preventive strategies for microsporidiosis. Currently, no prophylactic agents have been identified for these organisms. Patients have developed microsporidiosis while on trimethoprim-sulfamethoxazole prophylaxis, and microsporidiosis has occurred in patients receiving dapsone, pyrimethamine, itraconazole, azithromycin, and atovaquone. No studies have evaluated albendazole for prophylaxis, but, given its relative lack of efficacy for Ent. bieneusi infections, it is unlikely to be effective in preventing most cases of intestinal microsporidiosis. The most effective prophylaxis is the restoration of immune function in immunocompromised hosts. Several studies in AIDS patients have demonstrated that ART can produce remission of intestinal microsporidiosis. Moreover, the declining incidence of microsporidiosis and other opportunistic infections during the ART era suggests it also prevents symptomatic infection.

Microsporidian spores can survive and remain infective in the environment for prolonged periods. Spores can be rendered noninfectious by a 30-minute exposure to most common disinfectants, so the procedures used to clean most hospital rooms should be sufficient to limit infection. Spores are also killed by the commonly used methods employed for sterilization. It is likely that most microsporidia are food- or water-borne pathogens; and the usual sanitary measures that prevent contamination of food and water with animal urine and feces should decrease the chance for infection. Hand washing and general hygienic habits probably reduce the chance of contamination of the conjunctiva and cornea with microsporidian spores.

It is not known if person-to-person respiratory transmission occurs. Given the presence of microsporidian spores in respiratory secretions in cases of disseminated microsporidiosis, it may be useful to consider preventing contact of these patients with other immunosuppressed patients until the infection has been treated. Existing guidelines for the prevention of opportunistic infections that address food, water, and animal contact may be useful for preventing microsporidiosis. The presence of these organisms in genitourinary secretions raises the possibility of sexual transmission of these infections. It is reasonable to screen close contacts of patients with index cases of microsporidiosis for the presence of these organisms. Their importance and prevalence in our water supplies is an open question, but severely immunocompromised patients may wish to consider using bottled or filtered water in some settings.

WHAT'S THE EVIDENCE for specific management and treatment recommendations?

Beauvais, B, Sarfati, C, Molina, JM, Lesourd, A, Lariviere, M, Derouin, F. “Comparative evaluation of five diagnostic methods for demonstrating microsporidia in stool and intestinal biopsy specimens”. Ann Trop Med Parasitol. vol. 87. 1993. pp. 99-102. (Useful study looking at the yield of different diagnostic techniques in enteric microsporidiosis.)

Bicart-See, A, Massip, P, Linas, MD, Datry, A. “Successful treatment with nitazoxanide of Enterocytozoon bieneusi microsporidiosis in a patient with AIDS”. Antimicrob Agents Chemother. vol. 44. 2000. pp. 167-8. (A small case series demonstrating nitazoxanide may be useful in Ent. bieneusi infection (moderate evidence).)

Conteas, CN, Berlin, OG, Speck, CE, Pandhumas, SS, Lariviere, MJ, Fu, C. “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. vol. 58. 1998. pp. 555-8. (Data on the effectiveness of immune reconstitution due to antiretroviral therapy as treatment for microsporidiosis)

Deplazes, P, Mathis, A, Weber, R. “Epidemiology and zoonotic aspects of microsporidia of mammals and birds”. Contrib Microbiol. vol. 6. 2000. pp. 236-60. (A good summary of the environmental sources of the microsporidia seen in human infection)

Didier, PJ, Phillips, JN, Kuebler, DJ. “Antimicrosporidial activities of fumagillin, TNP-470, ovalicin, and ovalicin derivatives in vitro and in vivo”. Antimicrob Agents. vol. 50. 2006. pp. 2146-55. (In vitro screen of anti-microsporidiosis drugs.)

Diesenhouse, MC, Wilson, LA, Corrent, GF, Visvesvara, GS, Grossniklaus, HE, Bryan, RT. “Treatment of microsporidial keratoconjunctivitis with topical fumagillin”. Am J Ophthalmol. vol. 115. 1993. pp. 293-8. (Case reports demonstrating the use of fumagillin in ocular microsporidosis (moderate evidence).)

Dieterich, DT, Lew, EA, Kotler, DP, Poles, MA, Orenstein, JM. “Treatment with albendazole for intestinal disease due to Enterocytozoon bieneusi in patients with AIDS”. J Infect Dis. vol. 169. 1994. pp. 178-83. (Small case series demonstrating that albendazole has poor activity against Ent. bieneusi intestinal infection (moderate evidence).)

Franzen, C, Nassonova, ES, Schölmerich, J, Issi, IV. “Transfer of the members of the genus Brachiola (Microsporidia) to the genus Anncaliia based on ultrastructural and molecular data”. J Eukaryot Microbiol. vol. 53. 2006. pp. 26-35. (Re-classificaion of Brachiola algerae as Anncaliia algerae)

Goguel, J, Katlama, C, Sarfati, C, Maslo, C, Leport, C, Molina, J-M. “Remission of AIDS-associated intestinal microsporidiosis with highly active antiretroviral therapy”. AIDS. vol. 11. 1997. pp. 1658-9. (Describes the response of microsporidiosis in AIDS to effective cART.)

Gritz, DC, Holsclaw, DS, Neger, RE, Whitcher, JP, Margolis, TP. “Ocular and sinus microsporidial infection cured with systemic albendazole”. Am J Ophthalmol. vol. 124. 1997. pp. 241-3. (Case reports demonstrating the use of albendazole in microsporidosis (moderate evidence).)

Hocevar, SN, Paddock, CD, Spak, CW, Rosenblatt, R. “Microsporidia Transplant Transmission Investigation Team. Microsporidiosis acquired through solid organ transplantation: a public health investigation”. Ann Intern Med. 2014 Feb 18. pp. 213-20. (Describes transmission of microsporidia by organ transplantation, the diagnosis of this disease, the treatment of the patients, and the outbreak investigation.)

Katiyar, SK, Edlind, TD. “In vitro susceptibilities of the AIDS-associated microsporidian Encephalitozoon intestinalis to albendazole, its sulfoxide metabolite, and 12 additional benzimidazole derivatives”. Antibicrob Agents Chemother. vol. 41. 1997. pp. 2729-32. (In vitro screen of anti-microsporidiosis drugs.)

Kotler, DP, Orenstein, JM. “Clinical syndromes associated with microsporidiosis”. Adv Parasitol. vol. 40. 1998. pp. 321-49. ( A nice sumary of diseases caused by microsporidia)

Maggi, P, Larocca, AM, Quarto, M. “Effect of antiretroviral therapy on cryptosporidiosis and microsporidiosis in patients infected with human immunodeficiency virus type 1”. Eur J Clin Microbiol Infect Dis. vol. 19. 2000. pp. 213-7. (Data on the effectiveness of antiretroviral therapy with immune reconstitution as a therapy for microsporidiosis)

Mathis, A. “Microsporidia: emerging advances in understanding the basic biology of these unique organisms”. Int J Parasitol. vol. 30. 2000. pp. 795-804. (A nice summary of the biology of the Microsporidia)

Miao, YM, Awad-El-Kariem, FM, Franzen, C. “Eradication of cryptosporidia and microsporidia following Successful anti-retroviral therapy”. J Acquir Immune Defic Syndr. vol. 25. 2000. pp. 124-9. (Data on the effectiveness of antiretroviral therapy with immune reconstitution as a therapy for microsporidiosis)

Molina, JM, Chastang, C, Goguel, J. “Albendazole for treatment and prophylaxis of microsporidiosis due to Encephalitozoon intestinalis in patients with AIDS: a randomized double-blind controlled trial”. J Infect Dis. vol. 177. 1998. pp. 1373-7. (Small clinical trial demonstrating the use of albendazole in microsporidosis due to Enc. intestinalis (moderate evidence).)

Molina, JM, Goguel, J, Sarfati, C. “Trial of oral fumagillin for the treatment of intestinal microsporidiosis in patients with HIV infection [Letter]”. AIDS. vol. 14. 2000. pp. 1341-8. (Case series data demonstrating fumagillin is effective for the treatment of gastrointestinal infection with Enterocytozoon bieneusi)

Molina, JM, Tourneur, M, Sarfati, C. “Fumagillin treatment of intestinal microsporidiosis”. N Engl J Med. vol. 346. 2002. pp. 1963-9. (Clinical trial demonstrating the use of fumagillin in enteric microsporidiosis due to Ent. bieneusi (moderate evidence).)

Weber, R, Bryan, RT, Owen, RL, Wilcox, CM, Gorelkin, L, Visvesvara, GS. “Improved light-microscopical detection of microsporidia spores in stool and duodenal aspirates”. N Engl J Med. vol. 326. 1992. pp. 161-6. (Description of the Chromotrope A stain used for identification of these organisms.)

Weiss, LM, Vossbrinck, CR. “Microsporidiosis: molecular and diagnostic aspects”. Adv Parasitol. vol. 40. 1998. pp. 351-95. (Description of the available primers and their use in molecular diagnosis of this infection.)

Wittner, M, Weiss, LM. “The microsporidia and microsporidiosis”. 1999. (Reference book containing a detailed review the biology of these pathogenic organisms.)

Weiss, LM, Becnel, JJ. Microsporidia: Pathogens of Opportunity. 2014. (Reference book containing a detailed review of the biology of these pathogenic organisms. This book is an update of Wittner and Weiss 1999.)

DRG CODES and expected length of stay

DRG code: B60.8 (Microsporidiosis)

Length of stay depends on the location of infection.