OVERVIEW: What every clinician needs to know

Pathogen name and classification

Microsporidia organisms are protists related to fungi, defined by the presence of a unique invasive organelle consisting of a single polar tube that coils around the interior of the spore. They are ubiquitous organisms and are likely zoonotic and/or waterborne in origin. 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.

What is the best treatment?

Combination Antiretroviral Therapy (cART) 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 Ent. bieneusi. All patients with AIDS should be offered cART as part of the initial management of their infection. Data provide molecular evidence that suggest that, following successful cART, immune reconstitution occurs and enables the patient’s own defences to eradicate microsporidia.

No specific therapeutic agent is active against Ent. bieneusi infection. A controlled clinical trial suggested that Ent. bieneusi might respond to oral fumagillin (60 mg/day). However, fumagillin is not available for systemic use in the United States. One report indicates that 60 days of nitazoxanide (an FDA-approved drug) might resolve chronic diarrhea caused by Ent. bieneusi in the absence of cART; however, the effect might be minimal among patients with low CD4+ T-cell counts.

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Albendazole, a benzimidazole that binds to β-tubulin, has activity against many species of microsporidia, but it is not effective for Enterocytozoon bieneusi infections. Albendazole and fumagillin have demonstrated consistent activity against other microsporidia in vitro and in vivo.

Albendazole is recommended for initial therapy of intestinal and disseminated (not ocular) microsporidiosis caused by microsporidia other than Ent. bieneusi. Itraconazole might also be useful in disseminated disease when combined with albendazole, especially in infections caused by Trachipleistophora or Anncaliia.

Ocular infections caused by microsporidia should be treated additionally with topical Fumidil B (fumagillin bicylohexylammonium) in saline (to achieve a concentration of 70 mg/mL of fumagillin). 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 is often 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.

Metronidazole and atovaquone are not active in vitro or in animal models and should not be used to treat microsporidiosis. Fluid support should be offered if diarrhea has resulted in dehydration. Malnutrition and wasting should be treated with nutritional supplementation.

Monitoring and Adverse Events

Albendazole side effects are rare, but hypersensitivity (rash, pruritus, 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 cART to attempt to achieve full virologic suppression are the only feasible approaches to the management of treatment failure.

Prevention of Recurrence

Treatment for ocular microsporidiosis should be continued indefinitely, because recurrence or relapse might follow treatment discontinuation. Whether treatment of other manifestations can be safely discontinued after immune restoration with cART is unknown. However, 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., more than 6 months) increase in their CD4+ T lymphocyte counts to levels greater than 200 cells/µL after cART.

Treatment 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. 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. 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.

How do patients contract this infection, and how do I prevent spread to other patients?

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 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.

Members of the genus, Encephalitozoon, are the most common microsporidia infecting mammals and birds. The type species of this genus, Enc. cuniculi. was first identified in rabbits with motor paralysis in 1922 and was also the first microsporidian genome to be sequenced. There are now several sequenced microsporidian genomes. Enc. cuniculi has an extraordinary wide host range among mammals, such as rodents, lagomorphs, canines, equines, nonhuman primates, and humans. Enc. hellem and Enc. (syn. Septata) intestinalis were later isolated and identified from AIDS patients.

Enc. intestinalis is still considered more common in humans, whereas Enc. hellem is more common in birds with humans believed to be zoonotic hosts. Encephalitozoon species may infect enteric sites and contribute to diarrhea, but more typically cause systemic infections to persist over the life of the host unless treated with effective drugs. Disease occurs predominantly in immune-deficient hosts (e.g., AIDS patients, organ transplant recipients undergoing immunosuppressive therapy) and occurs sporadically in immune-competent hosts.

The most prevalent microsporidian in humans, Enterocytozoon bieneusi was first identified in an AIDS patient and is associated with persistent diarrhea. The host range of Ent. bieneusi appears far wider than first believed and now includes wild, farm, and pet mammals, as well as avian hosts, such as chickens, pigeons, falcons, and exotic birds. Currently, the genus Enterocytozoon contains only a single species, Ent. bieneusi. It is possible, however, that this organism is a species complex, and, as additional information is obtained, it may be split into separate species as was done with Cryptosporidium parvum. It should also be appreciated that the family Enterocytozoonidae contains fish pathogens of the genus Nucleospora that has several species, including Nucleospora salmonis that was previously named Enterocytozoon salmonis. Additional species of microsporidia less frequently identified in mammals and birds include Vittaforma corneae, Trachipleistophora spp., Anncaliia algerae, Pleistophora ronneaifiei, Nosema ocularum, Tubulonosema acridophagus, Endoreticulatus spp., and Microsporidium spp.

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 host factors protect against this infection?

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 develops and then clears; 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 that 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 lymphocyte 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.

What are the clinical manifestations of infection with this organism?

The most common manifestation of microsporidiosis is gastrointestinal tract infection with diarrhea; however, encephalitis, ocular infection, sinusitis, myositis, and disseminated infection are also described.

Clinical syndromes can vary by infecting species. Enterocytozoon bieneusi is associated with malabsorption, diarrhea, and cholangitis. Encephalitozoon cuniculi is associated with hepatitis, encephalitis, and disseminated disease. Encephalitozoon intestinalis is associated with diarrhea, disseminated infection, and superficial keratoconjunctivitis. Encephalitozoon hellem is associated with superficial keratoconjunctivitis, sinusitis, respiratory disease, prostatic abscesses, and disseminated infection. Nosema, Vittaforma, and Microsporidium are associated with stromal keratitis following trauma in immunocompetent hosts. Pleistophora, Anncaliia algerae, Tubulonosema, Endoreticulatus, and Trachipleistophora are associated with myositis. Trachipleistophora, Tubulonosema,and Anncaliia are also associated with encephalitis and disseminated disease.

What common complications are associated with infection with this pathogen?

The complications of infection with microsporidiosis vary with the organ infected. Disseminated infection can cause death if untreated. Keratitis can result in blindness. Renal infection has been associated with renal failure and hepatic infection with severe hepatitis. The most common manifestation of microsporidiosis is intestinal infection with associated diarrhea and malnutrition. This has been associated with electrolyte disturbances, as well as with chronic malnutrition. In children, this may lead to a “failure to thrive” syndrome and, in adults, a wasting syndrome with progressive weight loss. Intestinal perforation with an acute abdomen syndrome has been seen with microsporidiosis.

How should I identify the organism?

Although microsporidia belonging to the genera Encephalitozoon, Anncaliia (A. algerae), Vittaforma (V. corneae), and Trachipleistophora have been cultivated in vitro, Ent. bieneusi has not been successfully cultivated in vitro. Effective morphologic demonstration of microsporidia by light microscopy can be accomplished by staining methods that produce differential contrast between the spores of the microsporidia and the cells and debris in clinical samples (e.g., stool). In addition, because of the small size of the spores (1-5 um), adequate magnification (e.g., 1,000X) is required for visualization. Chromotrope 2R, calcofluor white, and Uvitex 2B (fluorescent brighteners) are useful as selective stains for microsporidia in stool and other body fluids.

In biopsy specimens, microsporidia can be visualized with Giemsa, tissue Gram stains (Brown-Hopps Gram stain), calcofluor white or Uvitex 2B (fluorescent brighteners) staining, acid-fast staining, Warthin-Starry silver staining, hematoxylin and eosin, or Chromotrope 2A (see Figure 2). In gastrointestinal disease, examination of three stools with chromotrope and chemofluorescent stains is often sufficient for diagnosis. If stool examination is negative and microsporidiosis is suspected, a small bowel biopsy should be performed. If the etiologic agent is an Encephalitozoon or Trachipleistophora spp., examination of urine often reveals the organism. Determination of the species of microsporidia causing disease can be made by the morphology of the organism demonstrated by transmission electron microscopy, by staining with species-specific antibodies or by polymerase chain reaction (PCR) using species or genus specific primers. Assistance of specialists familiar with the species differentiation of microsporidia should be sought.

(See Figure 1. Structure of a microsporidian spore)

Figure 1.

Structure of a microsporidian spore. Depending on the species, the size of the spore can vary from 1 to 10 um and the number of polar tubule coils can vary from a few to 30 or more. Extrusion apparatus consists of the polar tube (PT), vesiculotubular polaroplast (Vpl), lamellar polaroplast (Pl), anchoring disk (AD) and manubrium (M). This organelle is characteristic of the Microsporidia. A cross section of the coiled polar tube is illustrated. The nucleus (Nu) may be single (such as in Encephalitozoon spp.) or a pair of abutted nuclei termed a diplokaryon (such as in Nosema spp.). The endospore (En) is an inner thicker electron-lucent region. The exospore (Ex) is an outer electron-dense region. The plasma membrane (Pm) separates the spore coat from the sporoplasm (Sp), which contains ribosomes in a coiled helical array. The posterior vacuole (PV) is a membrane-bound structure. (Reproduced with permission from Wittner M, Weiss LM, eds. The Microsporidia and Microsporidiosis. Washington, DC: ASM Press; 1999.)

Figure 2.

Microsporidia in stool specimen demonstrated with chromotrope 2A (modified trichrome) stain. This organism was identified as Enterocytozoon bieneusi.

Microsporidian spores can vary 1-20 um in length. Spores of most species of microsporidia are oval in shape but may also exhibit pyriform, spherical, or rod shapes. Encephalitozoon spores measure approximately 1-2 um x 2-4 um and exhibit a typical microsporidian spore configuration of a glycoproteinaceous electron-dense exospore, electron-lucent endospore composed of chitin, and a plasma membrane containing the cytoplasmic organelles. The polar filament typically coils 5-7 times in single row arrangement and the nucleus is unikaryotic.

Spores of Ent. bieneusi are among the smallest of the microsporidia, measuring 1 um x 1.5 um, and the chitinous endospore in Ent. bieneusi is somewhat thinner than found in Encephalitozoon spores. The polar filament coils 5-7 times and commonly is observed to align in two rows. The spore wall provides resistance to environmental influences and allows for the increase in hydrostatic pressure that causes spore discharge. The spore wall is surrounded by a glycoproteinaceous electron-dense exospore and electron-lucent endospore composed primarily of chitin. Under light microscopy, viable spores are refractive, and, after histochemical staining (e.g. chromotrope, Gram), a posterior vacuole may be observed.

The unique structure that characterizes all microsporidia is the polar filament or tube that coils within the spore and is part of the germinations and infection apparatus. The arrangement and number of coils of the polar filament within the spore vary among the microsporidia species. Long considered amitochondriate, the microsporidia have been found to possess reduced mitochondria named mitosomes, as well as atypical golgi and an anchoring disk with a membranous lamellar polaroplast at the anterior end of the spore that functions to anchor and fuel the extruding polar filament during germination.

How does this organism cause disease?

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’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).)

Choudhary, MM, Metcalfe, MG, Arrambide, K, Bern, C. “Tubulinosema sp. microsporidian myositis in an immunosuppressed patient”. Emerg Infect Dis. vol. 17. 2011 Sep. pp. 1727-30.

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 antiretroviral therapy for improving microsporidiosis and the associated gastrointestinal symptoms)

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 useful summary of what is known about the animal and environmental sources of the microsporidia seen in human infections)

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 microsporidiosis (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. (This paper summarizes data on the genus Anncaliia and transfers Brachiola algerae to 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 microsporidiosis (moderate evidence).)

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 summary of the diseases caused by microsporidia in humans)

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 for improving microsporidiosis and the associated gastrointestinal symptoms)

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 diseases caused by microsporidia in humans and the biology of these pathogens)

Meissner, EG, Bennett, JE, Qvarnstrom, Y, da Silva, A. “Disseminated microsporidiosis in an immunosuppressed patient”. Emerg Infect Dis. vol. 18. 2012 Jul. pp. 1155-8.

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 for improving microsporidiosis and the associated gastrointestinal symptoms)

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 microsporidiosis 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. 1341-48. (Data on the effectiveness of fumagilin for the treatment of Enterocytozoon bieneusi infection)

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).)

Suankratay, C, Thiansukhon, E, Nilaratanakul, V, Putaporntip, C, Jongwutiwes, S. “Disseminated infection caused by novel species of Microsporidium, Thailand”. Emerg Infect Dis. vol. 18. 2012 Feb. pp. 302-4.

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 of the biology of these pathogenic organisms.)

Weiss, LM, Becnel, JJ. 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.)