Microsporidia are ubiquitous obligate intracellular organisms that were once thought to be parasites but are now considered to be fungi.1,2 Recent work suggests that microsporidiosis may be a zoonotic infection.3 Although recognised as a veterinary disease for many years, microsporidiosis was first described as a human disease in 1985 in a patient with acquired immune deficiency syndrome (AIDS) and unexplained diarrhoea.4 As with cryptosporidiosis, microsporidiosis is a rare manifestation of human immunodeficiency virus (HIV) disease in the era of eﬀective combination antiretroviral therapy (cART) yet continues to be problematic in areas of the world with limited access to cART.5
The small intestine is the most common site of microsporidiosis. Enterocytozoon bieneusi and Encephalitozoon intestinalis are the most common microsporidial species identiﬁed in patients with HIV infection. E. bieneusi infection is usually conﬁned to the small intestine (and occasionally involves the biliary tree). It causes 80% of microsporidial diarrhoea. E. intestinalis infects the small intestine, but can also cause more widespread disease. The capacity of the latter species to infect lamina propria macrophages is thought to explain its capacity for disseminatated disease.6
Infection occurs following ingestion or inhalation of microsporidial spores. Transmission of spores is thought to be primarily through faecal-oral or urinary-oral routes. Encephalitozoon keratoconjunctivitis may occur through contact with aerosols or surfaces contaminated with urine containing microsporidia.7
The most common clinical manifestation of microsporidiosis in patients with AIDS is diarrhoea. Like cryptosporidia, microsporidia can cause self-limiting diarrhoea in immunocompetent patients.8 Microsporidial infection accounts for up to 20% of diarrhoeal illness in patients with AIDS.9 Typically, patients have a CD4 T lymphocyte cell (CD4) count of < 50/μL.1 Immunodeﬁcient patients present with chronic (initially intermittent) non-bloody diarrhoea that may be accompanied by fever, anorexia and weight loss. E. bieneusi may cause cholangitis or cholecystitis. Uncommon non-gastrointestinal manifestations of microsporidial infection include sinusitis, keratoconjunctivitis, hepatitis, peritonitis, adrenalitis, nephritis, pituitary gland infection, osteomyelitis, encephalitis, myositis and pneumonia.10
Microsporidial disease has been reported to present as an ‘unmasking’ immune reconstitution inflammatory syndrome (IRIS) in a very immunodeficient patient (CD4 counts < 20 cells/μL) who had unrecognised microsporidial infection before commencing cART and presented with diarrhoea and diffuse abdominal pain one month after commencing cART. While diarrhoea and detection of microsporidia in stool specimens resolved after albendazole therapy, abdominal pain associated with diffuse peritoneal and small bowel granulomas continued and only resolved following immune reconstitution.11
Stool microscopy is the investigation of choice in the diagnosis of microsporidiosis. As microsporidial shedding may be intermittent, at least three stool specimens are required. Special stains, such as the modiﬁed Ziehl-Nielsen, Warthin- Starry, ﬂuorescent and trichrome stains have varying speciﬁcity and sensitivity for diﬀerent species of microsporidia. These stains, however, do not provide species-speciﬁc identiﬁcation, which requires either electron microscopic analysis of a small bowel biopsy or polymerase chain reaction (PCR) analysis.12 Electron microscopy is considered the gold standard, but is not routinely available. The use of monoclonal antibodies and oligonucleotide microarray assays to detect pathogenic species of microsporidia in human clinical specimens have been reported recently and may increase the diagnostic yield.13,14
No speciﬁc therapy is required in patients with self-limited microsporidial enteritis in whom CD4 counts are > 200 cells/μL. For patients with lower CD4 cell counts, the most important management strategy is achieving immune recovery following the initiation of cART.15 HIV protease inhibitors such as lopinavir, ritonavir and saquinavir have been shown to have antimicrosporidial eﬀects in vitro, however there are no reports of improved responses using a protease inhibitor-based antiretroviral regimen.16
Albendazole (400 mg twice a day) is successful in the treatment of E. intestinalis infection but other microsporidial species have variable responses to this drug.17,18 Although clearance of microsporidia has been reported with cART alone, treatment with albendazole is recommended to reduce the duration of symptoms. Fumagillin (20 mg taken three times a day) is active against E. bieneusi and has been demonstrated to eradicate the organism,19 but is not licensed in Australia. Uncontrolled studies have suggested that thalidomide may reduce stool frequency and lead to weight gain in patients with microsporidial diarrhoea.20 The potential mechanisms are unclear as thalidomide has no direct antimicrosporidial eﬀect.21 The following drugs have been used with variable success to treat microsporidiosis: metronidazole, atovaquone, azithromycin, itraconazole, sulfa-based drugs and nitazoxanide.
Speciﬁc dietary intervention is advantageous in patients with microsporidiosis and malabsorption. Medium-chain triglyceride-based diets, as opposed to long-chain triglyceride-based diets, reduce stool frequency and lead to weight gain.22 Octreotide may provide symptomatic reduction in stool frequency and volume.
Therapeutic strategies for primary prophylaxis have not been defined. Patients with microsporidiosis caused by species other than E. intestinalis frequently relapse following cessation of albendazole therapy in the absence of cART-induced immune recovery. These patients may require long-term suppressive therapy with albendazole or an alternative agent. The role of fumagillin in this context has not been studied.
 Didier ES, Weiss LM. Microsporidiosis: current status. Curr Opin Infect Dis 2006;19:485-92.
 Gill EE, Fast NM. Assessing the microsporidia-fungi relationship: Combined phylogenetic analysis of eight genes. Gene 2006;375:103-9.
 Mathis A, Weber R, Deplazes P. Zoonotic potential of the microsporidia. Clin Microbiol Rev 2005;18:423-45.
 Modigliani R, Bories C, Le Charpentier Y, Salmeron M, Messing B, Galian A, et al. Diarrhoea and malabsorption in acquired immune deﬁciency syndrome: a study of four cases with emphasis on opportunistic protozoan infestations. Gut 1985;26:179-87.
 Didier ES, Weiss LM. Microsporidiosis: not just in AIDS patients. Curr Opin Infect Dis 2011;24:490-5.
 Huppmann AR, Orenstein JM. Opportunistic disorders of the gastrointestinal tract in the age of highly active antiretroviral therapy. Hum Pathol 2010;41:1777-87.
 Bryan RT. Microsporidiosis as an AIDS-related opportunistic infection. Clin Infect Dis 1995;21 Suppl 1:S62-S65.
 Bryan RT, Weber R, Schwartz DA. Microsporidiosis in patients who are not infected with human immunodeﬁciency virus. Clin Infect Dis 1997;24:534-5.
 Molina JM, Sarfati C, Beauvais B, Lemann M, Lesourd A, Ferchal F, et al. Intestinal microsporidiosis in human immunodeﬁciency virus-infected patients with chronic unexplained diarrhea: prevalence and clinical and biological features. J Infect Dis 1993;167:217-21.
 Orenstein JM, Gaetz HP, Yachnis AT, Frankel SS, Mertens RB, Didier ES. Disseminated microsporidiosis in AIDS: are any organs spared? AIDS 1997;11:386-7.
 Sriaroon C, Mayer CA, Chen L, Accurso C, Greene JN, Vincent AL. Diffuse intra-abdominal granulomatous seeding as a manifestation of immune reconstitution inflammatory syndrome associated with microsporidiosis in a patient with HIV. AIDS Patient Care STDS 2008;22:611-2.
 Franzen C, Muller A. Molecular techniques for the detection, species diﬀerentiation, and phylogenetic analysis of microsporidia. Clin Microbiol Rev 1999;12:243-85.
 Sheoran AS, Feng X, Singh I, Chapman-Bonoﬁglio S, Kitaka S, Hanawalt J, et al. Monoclonal antibodies against Enterocytozoon bieneusi of human origin. Clin Diagn Lab Immunol 2005;12:1109-13.
 Wang J Clin Microbiol 2005;43:4121-28. Wang Z, Orlandi PA, Stenger DA. Simultaneous detection of four human pathogenic microsporidian species from clinical samples by oligonucleotide microarray. J Clin Microbiol 2005;43:4121-8.
 Carr A, Marriott D, Field A, Vasak E, Cooper DA. Treatment of HIV-1-associated microsporidiosis and cryptosporidiosis with combination antiretroviral therapy. Lancet 1998;351:256-61.
 Menotti J, Santillana-Hayat M, Cassinat B, Sarfati C, Derouin F, Molina JM.Inhibitory activity of human immunodeﬁciency virus aspartyl protease inhibitors against Encephalitozoon intestinalis evaluated by cell culture-quantitative PCR assay. Antimicrob Agents Chemother 2005;49:2362-6.
 Dore GJ, Marriott DJ, Hing MC, Harkness JL, Field AS. Disseminated microsporidiosis due to Septata intestinalis in nine patients infected with the human immunodeﬁciency virus: response to therapy with albendazole. Clin Infect Dis 1995;21:7076.
 Molina JM, Chastang C, Goguel J, Michiels JF, Sarfati C, Desportes-Livage I, et al. Albendazole for treatment and prophylaxis of microsporidiosis due to Encephalitozoon intestinalis in patients with AIDS: a randomized double-blind controlled trial. J Infect Dis 1998;177:1373-7.
 Molina JM, Tourneur M, Sarfati C, Chevret S, de Gouvello A, Gobert JG, et al. Fumagillin treatment of intestinal microsporidiosis. N Engl J Med 2002;346:1963-9.
 Sharpstone D, Rowbottom A, Francis N, Tovey G, Ellis D, Barrett M, et al. Thalidomide: a novel therapy for microsporidiosis. Gastroenterology 1997;112:1823-9.
 Ridoux O, Drancourt M. Lack of in vitro antimicrosporidian activity of thalidomide. Antimicrob Agents Chemother 1999;43:2305-6.
 Wanke CA, Plesko D, DeGirolami PC, Lambl BB, Merkel K, Akrabawi S. A medium chain triglyceride-based diet in patients with HIV and chronic diarrhoea reduces diarrhoea and malabsorption: a prospective, controlled trial. Nutrition 1996;12:766-71.