eMedicine Specialties > Infectious Diseases > Parasitic Infections

Microsporidiosis

Valda M Chijide, MD, Clinical Professor, Department of Medicine, University of Saskatchewan; Consultant in Infectious Diseases, Regina, Saskatchewan, Canada

Updated: Sep 18, 2008

Introduction

Background

Microsporidiosis (also known as microsporidiasis) is caused by infection with microsporidia, which are obligately intracellular, spore-forming parasites that belong to the phylum Microspora and the order Microsporida. Microsporidia are eukaryotic organisms that contain 70S ribosomes but lack mitochondria, peroxisomes, Golgi membranes, and other typically eukaryotic organelles. The phylum Microspora contains over 1000 species. They are ubiquitous organisms with an extensive host range, including honeybees, fish, mosquitoes, ticks, grasshoppers, rodents, rabbits, and other fur-bearing mammals. Species identified as causing microsporidiosis in humans include the following:

• Enterocytozoon bieneusi
• Encephalitozoon hellem
• Encephalitozoon intestinalis (previously Septata intestinalis)
• Encephalitozoon cuniculi
• Pleistophora species
• Trachipleistophora hominis
• Trachipleistophora anthropophthera
• Nosema connori (see Image 1)
• Nosema ocularum
• Brachiola vesicularum
• Vittaforma corneae (previously Nosema corneum)
• Microsporidium ceylonensis
• Microsporidium africanum
• Brachiola algerae

Currently, most cases of human microsporidiosis are associated with HIV infection or other forms of immunosuppression, particularly in organ transplant recipients; however, cases have been reported in immunocompetent individuals.

Pathophysiology

Humans acquire microsporidiosis through ingestion or inhalation of microsporidia spores. Studies have isolated Encephalitozoon species in the urinary tract in those with disseminated infections, suggesting that sexual transmission is possible. The spore is the infective form. Spores are environmentally resistant and are surrounded by an outer electron-dense glycoprotein layer and an electron-lucent endospore layer composed primarily of chitin. The spore extrudes its polar tubule and injects the infective sporoplasm into the host cell. Once inside the cell, it multiplies by binary fission or schizogony. Development can occur directly inside the host cell cytoplasm or inside parasitophorous vacuoles. As mature spores develop and accumulate, the cell expands and eventually ruptures, releasing the spores.

Frequency

United States

Currently, most cases of microsporidiosis are reported in immunosuppressed adults, especially those with HIV-related immunosuppression. Studies have found that E bieneusi infection of small intestinal enterocytes is detected in 15-34% of patients with AIDS with chronic diarrhea and no other identified causes.

E bieneusi infection has also been found in renal transplant recipients with chronic weight loss and diarrhea. A case of fatal myositis due to B algerae infection has been documented in a woman with diabetes and rheumatoid arthritis who had been prescribed infliximab.¹

International

Microsporidia have a worldwide distribution. Cases of microsporidiosis have been reported in both developed and developing countries and among both immunosuppressed and immunocompetent individuals. Microsporidiosis has been reported in the Americas, Asia, Europe, and Africa.

Mortality/Morbidity

Clinical symptoms and manifestations of microsporidiosis depend on the infecting species and the host's immune status. Microsporidial keratoconjunctivitis has been identified in healthy immunocompetent individuals, and the use of topical steroids may have been the initial predisposing factor in one case series.² The individuals in this case series exhibited unilateral punctate epithelial involvement of the cornea. V corneae infection was identified as a cause of unilateral stromal keratitis in a case report by Font et al, and topical steroid use had also preceded the diagnosis.³

• Bilateral punctate epithelial involvement of the cornea is the typical manifestation of ocular microsporidiosis in immunocompromised individuals.
• Most cases of intestinal and disseminated microsporidiosis in patients infected with HIV are reported in those who are severely immunocompromised (CD4 <100/µL); in these patients, morbidity can be significant. E bieneusi infections often result in protracted debilitating illness with diarrhea, which may last several months. E bieneusi infections carry a mortality of up to 56%. In addition to chronic diarrhea, malabsorption and wasting can occur in persons with AIDS. E bieneusi is responsible for more than 90% of intestinal microsporidiosis cases in this population; E intestinalis accounts for the remainder.
• Reports of E bieneusi infections are increasing among travelers and residents of tropical countries who do not have HIV infection. E intestinalis infection associated with chronic diarrhea has been reported in immunocompetent travelers.
• E bieneusi is usually found only in enterocytes. E intestinalis is more invasive and produces disseminated disease involving the small and large intestines, gallbladder, urinary tract epithelium, and respiratory tract epithelium. Biliary tract involvement that progresses to cholangitis and cholecystitis is common in patients with AIDS who have E bieneusi infection.
• Myositis due to Pleistophora infection has been documented.

Race

Microsporidiosis has no known racial predilection.

Sex

Microsporidiosis has no known gender predilection.

Age

Microsporidiosis has no known age predilection.

Clinical

History

• Intestinal or biliary microsporidiosis
  • Chronic diarrhea (loose, watery, nonbloody)
  • Weight loss
  • Abdominal pain
  • Nausea
  • Vomiting
• Disseminated microsporidiosis
  • Symptoms of cholecystitis, renal failure, and respiratory tract infections occur.
  • Patients with respiratory tract involvement may present with persistent cough, dyspnea, and wheezing.
  • Headache, nasal congestion or discharge, ocular pain, and loss of taste may indicate sinus involvement.
  • Patients with urinary tract involvement are frequently asymptomatic.
• Ocular microsporidiosis
  • Foreign body sensation, eye pain, or both
  • Light sensitivity
  • Ocular redness
  • Excessive tearing
  • Blurred or decreased vision
• Musculoskeletal microsporidiosis: Myalgia, generalized muscle weakness, and fever are common in patients with myositis and severe cellular immunodeficiency.
• Dermatologic microsporidiosis: Microsporidia have been associated with a nodular cutaneous lesion in patients with HIV infection.
• CNS microsporidiosis: Patients with microsporidiosis of the brain may experience seizures and headache.

Physical

• Head, eyes, ears, nose, and throat (HEENT) examination
  • Patients with ocular involvement due to Encephalitozoon infection may develop conjunctival hyperemia. A slit-lamp examination may reveal keratoconjunctivitis, which is characterized by diffuse, superficial, punctate keratopathy. The infection is frequently bilateral in immunosuppressed individuals.
  • Corneal ulceration is rare in patients with AIDS who have microsporidiosis. Retinal involvement has not been reported.
  • Those in whom microsporidiosis involves the sinuses may have nasal crusting or purulence, polypoid tissue, or thickened and granular-appearing mucosa.
• Abdominal examination
  • Patients with intestinal or biliary microsporidiosis may have abdominal tenderness.
  • Clinical jaundice due to microsporidiosis is rare.
  • Severe wasting and signs of malnourishment are usually observed in patients with prolonged severe diarrhea.
• Musculoskeletal examination: Muscle tenderness and generalized weakness may be noted in patients with microsporidiosis-related myositis.
• Skin examination: A skin examination may reveal nodules or necrotic lesions.

Causes

• Microsporidiosis is believed to be a zoonosis. Evidence suggests that microsporidia may be water-borne pathogens and may be transmitted from human to human.
• Most cases of microsporidiosis in patients with HIV infection occur in those with severe immunodeficiency.
• Cases of microsporidiosis have been reported in individuals who are HIV negative and who are immunocompromised secondary to transplant surgery or prolonged steroid use.
• Self-limited diarrhea due to microsporidiosis has been reported in immunocompetent travelers; waterborne transmission may play a role in these cases.

Differential Diagnoses

Other Problems to Be Considered

AIDS enteropathy⁴
Cyclosporiasis

Workup

Laboratory Studies

• Body fluid specimens
  • Microscopic examination of stained stool samples allows the most rapid diagnosis of microsporidiosis, but it does not allow identification of the specific infecting species.
  • Examine stools for other parasites (ova and parasite examination) and bacteria. Fecal WBCs are usually absent.
  • The modified trichrome stain (chromotrope 2R) is commonly used to detect microsporidia in urine, stool, and mucus. The microsporidia appear as ovoid, refractile spores with bright red walls. Some spores may have an equatorial beltlike stripe.
  • The rapid Gram chromotrope method can be performed more quickly (about 11 min) and combines the chromotrope method with a Gram-staining step. The spores stain dark violet, and the equatorial stripe is enhanced. E bieneusi spores measure about 0.9 µm X 1.5 µm; Encephalitozoon species measure about 1.5 µm X 3 µm.
  • Cytologic and histologic examinations are useful for diagnosis of microsporidiosis. A conjunctival scraping or swab frequently reveals the organism after a Gram stain (organisms usually stain gram-positive) or chromotrope stain. Microsporidial spores can be identified in tissue specimens obtained by biopsy or at autopsy. Stains used to detect microsporidia include the Brown Brenn Gram stain, Warthin-Starry silver stain, Giemsa stain, and trichrome blue stain.
  • Fluorochrome stains, including calcofluor white and uvitex 2B, have a high affinity for chitin. They can be used to detect microsporidia in urine, stool, mucus, and tissue sections.
  • Microsporidia stain poorly with hematoxylin-eosin.
• Transmission electron microscopy: This is the criterion standard for diagnosis confirmation and allows species identification based on ultrastructure, but it is too costly and time consuming for routine use.
• Polymerase chain reaction: This study is available in some research laboratories and can be used to diagnose infection with E bieneusi, V corneae, or Nosema species.
• Immunofluorescence assays using monoclonal or polyclonal antibodies: These are available in some research laboratories and can be performed on most specimens, including formalin-fixed tissues. These studies allow visualization of spores and extruded polar tubules.
• Urinalysis: Routinely examine the urine for spores because disseminated infection with E intestinalis or E hellem frequently involves the kidney.
• Liver function tests
  • Levels of alkaline phosphatase, gamma-glutamyltransferase, and aspartate and alanine aminotransferases are often elevated.
  • The bilirubin level is usually normal.
• Creatine phosphokinase and aldolase: These values may be elevated in patients with myositis.
• CD4: Patients with disseminated microsporidiosis are usually severely immunocompromised, and the CD4 count is generally below 100/µL.
• D-xylose test and qualitative fecal fat: Patients with prolonged diarrhea can develop malabsorption of fats, vitamins, and other nutrients; therefore, stool studies are required to assess for malabsorption in patients with microsporidiosis of the gastrointestinal tract.

Imaging Studies

• CT scanning
  • CT scanning of the sinuses is used to search for evidence of sinusitis and middle ear involvement in patients with sinus symptoms.
  • CT scanning of the brain is used to determine if any ring-enhancing lesions are present in patients who present with headache.
  • Abdominal CT scan is used to assess for intrahepatic and extrahepatic ductal dilatation, gallbladder abnormalities, and liver parenchymal abnormalities in patients with signs of hepatic involvement.
• Conduct abdominal ultrasonography in patients with elevated liver function tests to evaluate for cholelithiasis or other abnormalities in the biliary system.
• Chest radiography is used to evaluate for pneumonia in patients with respiratory symptoms.

Other Tests

• Micronutrients
  • Diarrhea may cause micronutrient deficiency. Vitamin B-12 is the micronutrient that is most commonly deficient in persons with HIV infection; vitamin B-12 deficiency may lead to cognitive dysfunction and anemia.
  • Depending on symptoms, pay special attention to the levels of micronutrients, especially when a particular deficiency syndrome is detected.
  • Other assays to consider in patients with microsporidiosis include vitamin B-6 and other B vitamins, fat-soluble vitamins, zinc, and selenium.

Procedures

• Small-bowel endoscopy: The parasite burden is greatest in the proximal jejunum. Obtain biopsy samples from this site whenever possible. Microsporidia spores can often be found in duodenal fluid.
• Slit-lamp examination: Keratoconjunctivitis due to microsporidiosis is characterized by diffuse, superficial, punctate keratopathy.
• Punch biopsy of skin: Use Gram stain or other staining methods to identify microsporidia.

Histologic Findings

Histologic sections from the small bowel tend to reveal a mild inflammatory infiltrate (primarily lymphocytic) and a patchy distribution of infected enterocytes; therefore, a high index of suspicion is needed. Intestinal biopsy specimens from patients suspected of having microsporidiosis should undergo Gram staining. Villous atrophy and fusion, crypt elongation, and goblet cell depletion are common in affected mucosa.

E intestinalis is more invasive than E bieneusi. E intestinalis can infect enterocytes and cells in the lamina propria, fibroblasts, and macrophages.

Encephalitozoon infections may cause granulomatous lesions in the kidneys and liver.

Foamy histiocytes were observed in the lower dermis of a patient reported to have nodular skin lesions.

Treatment

Medical Care

• Pay attention to volume replacement and electrolyte repletion in patients with microsporidiosis who develop severe diarrhea.
• Evaluate the patient by assessing dentition and addressing difficulty of chewing or swallowing. Then, focus on providing adequate nutritional support with the aid of a dietitian.
• Consider enteral feeding in patients who are too ill to obtain adequate nutrition by mouth. Substitution of medium-chain for long-chain triglycerides can decrease fat malabsorption.⁵ Parenteral nutrition is reserved for situations in which the small intestine is nonfunctional.

Consultations

• Gastroenterologist for colonoscopy and small-bowel endoscopy
• Ophthalmologist for a slit-lamp examination in patients with symptomatic microsporidiosis

Diet

One study has found that individuals infected with HIV and who have microsporidiosis-related diarrhea had less diarrhea and malabsorption on a medium-chain triglyceride diet as opposed to a long-chain triglyceride diet.⁶

Medication

Albendazole is the drug of choice for ocular, intestinal, and disseminated microsporidiosis. Albendazole has been shown to abate gastrointestinal symptoms, histopathologic evidence of clearance in the intestine, and weight gain in patients with E intestinalis infection. No consistently effective therapies exist for E bieneusi infection. Albendazole is reported to reduce frequency and volume of diarrhea and stabilize the weight of patients with E bieneusi infection in some studies, but this is not associated with clearance of the organism on stool specimens or duodenal biopsy specimens. Metronidazole was associated with a good clinical response in patients with AIDS who had E bieneusi enteritis in a few reports, but the parasite was not eradicated. Most studies have not found metronidazole to be efficacious against microsporidiosis.

Topical fumagillin is used to treat microsporidial keratoconjunctivitis. This may elicit a clinical response in as little as 1 week, but long-term use is usually required to prevent recurrence. Oral fumagillin is useful in the treatment of E bieneusi infection but is associated with thrombocytopenia.

One study found that thalidomide treatment once per month decreased stool frequency and improved weight in patients with HIV infection but did not significantly decrease fecal levels of tumor necrosis factor alpha (TNF-alpha), which are typically elevated in persons with microsporidiosis.⁷ Because of the significant toxicity of thalidomide, consider it only in microsporidiosis cases that have failed other treatments. Thalidomide has no known direct antimicrobial action but has been shown to selectively inhibit TNF-alpha in a monocytic cell line.

Improved immune function due to antiretroviral therapy seems to lead to normalization of intestinal architecture, clearance of parasites in the stool, and clinical improvement.

Anthelmintics

Parasite biochemical pathways are sufficiently different from the human host to allow selective interference by chemotherapeutic agents in relatively small doses.

Albendazole (Albenza)

A benzimidazole carbamate drug that appears to cause selective degeneration of cytoplasmic microtubules in intestinal and tegmental cells of intestinal helminths and their tissue-dwelling larvae. Converted in the liver to its primary metabolite, albendazole sulfoxide. Less than 1% of the primary metabolite is excreted in the urine. Used in symptomatic patients with diarrhea or disseminated disease.

Dosing

Adult

400 mg PO bid for 2-4 wk

Pediatric

<60 kg: 15 mg/kg/d PO bid for 2-4 wk
>60 kg: Administer as in adults

Interactions

Administration with a fatty meal enhances oral bioavailability; carbamazepine decreases effect; dexamethasone and praziquantel increase effect; cimetidine increases levels of albendazole in bile

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Elevated LFTs; order LFTs and CBCs with differential at therapy initiation and q2wk during therapy; conduct a pregnancy test prior to therapy; avoid pregnancy during and 1 mo after therapy; abdominal pain, anorexia, nausea, vomiting, and pseudomembranous colitis have occurred during therapy

Antibiotics

Therapy should cover all likely organisms in the context of the clinical setting.

Fumagillin (Fumidil)

An antiangiogenesis factor consisting of an antibiotic derived from Aspergillus fumigatus that exerts its effect by binding to the metalloprotease methionine aminopeptidase type 2. Effective for ocular lesions demonstrated to be caused by microsporidia, especially Encephalitozoon species. The Food and Drug Administration (FDA) has not approved fumagillin for microsporidiosis. It is available in the United States and can be obtained by calling 1-800-547-1392.

Dosing

Adult

3 mg/mL ophthalmic drops q1h to affected eye while awake

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Monitor patients with cancer and other immunosuppression-related conditions for toxic effects on bone marrow; close monitoring of blood counts are mandatory (discontinue treatment if platelet counts fall to <75,000/µL); ocular symptoms frequently recur in patients who are HIV infected, long-term maintenance therapy usually required; evaluate patients with HIV infection and with ocular disease due to microsporidia for disseminated disease (eg, stool, urine, sputum, sinus evaluation)

Immunomodulators

These agents modulate key factors of the immune system.

Thalidomide (Thalomid)

A toxic drug with immunosuppressive effects that is used for various immune-mediated conditions. Also, used for chronic diarrhea unresponsive to albendazole or other therapies.

Dosing

Adult

100 mg PO qhs

Pediatric

Not established

Interactions

Can potentiate the sedative effects of alcohol, barbiturates, chlorpromazine, and reserpine

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Do not donate blood; male patients should not donate sperm; causes sedation, orthostatic hypotension; increase in HIV viral load; peripheral neuropathy; avoid pregnancy during and 1 mo after therapy; due to teratogenic effects, women must use 2 additional methods of contraception or abstain from intercourse

Antiprotozoals

These agents are used in symptomatic patients with diarrhea.

Metronidazole (Flagyl, Protostat)

Oral synthetic drug with antiprotozoal and antibacterial action.

Dosing

Adult

500 mg PO tid for 2 wk

Pediatric

35-50 mg/kg/d PO divided q8h for 10 d

Interactions

Alcohol induces disulfiramlike reaction during and for 3 d after therapy; phenytoin and phenobarbital decrease serum levels; increases lithium levels and toxicity

Contraindications

Documented hypersensitivity; first trimester of pregnancy

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in hepatic disease; monitor for seizures and development of peripheral neuropathy; CNS disorder

Follow-up

Further Inpatient Care

• Patients with severe fluid loss due to diarrhea should undergo volume replacement with intravenous fluids.
• Monitor electrolytes frequently and replace as necessary.

Further Outpatient Care

• Follow-up visit: In patients with microsporidiosis who have persistent diarrhea, obtain stool samples to assess response to therapy and evaluate for other etiologies. In addition, consider repeating small-bowel endoscopy.
• Nutritional assessment: Question patients regarding dietary habits at each routine clinic visit. Dietary referral may be needed to assist in obtaining a dietary history and calorie count. Immediately address complaints regarding loss of appetite and weight loss to determine if an opportunistic infection is the underlying cause. Bioimpedance analysis (BIA) is a rapid noninvasive technique that uses a portable analyzer to help assess lean body mass.⁸ When BIA is performed on subsequent visits, the information obtained can be used to determine the need for intervention, such as anabolic steroids.

Inpatient & Outpatient Medications

• Postantibiotic treatment: After patients with microsporidiosis undergo an adequate course of antibiotic treatment, those with significant weight loss or appetite loss require further assessment to determine whether to institute nutritional supplements, drugs, or both to reverse these effects (eg, anabolic steroids such as testosterone or oxandrolone, appetite stimulant such as megestrol acetate).

Deterrence/Prevention

• Counsel immunosuppressed patients on the importance of frequent handwashing, thorough cooking of meat, and limiting exposure to animals suspected of being infected with microsporidia.
• Inform patients with microsporidiosis that this disease may be transmitted sexually and to consider screening of sexual partners.

Prognosis

• Most patients who develop intestinal microsporidiosis are severely immunosuppressed; therefore, the prognosis is usually poor in these patients.
• Diarrhea generally resolves spontaneously in immunocompetent patients who develop microsporidiosis.

Patient Education

• Counsel patients regarding meticulous handwashing to help decrease the risk of opportunistic infections.

Miscellaneous

Medicolegal Pitfalls

• Ocular microsporidiosis occurs in 1-2% of persons with HIV infection who have advanced illness; therefore, an ophthalmologic examination is indicated in this group of patients.
• Microsporidiosis in persons with AIDS may relapse if the antiretroviral regimen fails.
• Suspect ocular microsporidiosis in HIV-negative individuals with unilateral eye symptoms, especially in those who have used topical steroids.

Multimedia

Media file 1: Electron micrograph (X30,000) of Nosema connori in diaphragm showing a coiled polar filament (arrow). Courtesy of the Armed Forces Institute of Pathology (AFIP 71-11521-4).

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Keywords

microsporidiosis, microsporidiasis, microsporidia, Enterocytozoon bieneusi, E bieneusi, Encephalitozoon hellem, E hellem, Encephalitozoon intestinalis, E intestinalis, Septata intestinalis, S intestinalis, Encephalitozoon cuniculi, E cuniculi, Pleistophora, Trachipleistophora hominis, T hominis, Trachipleistophora anthropophthera, T anthropophthera, Nosema connori, N connori, Nosema ocularum, N ocularum, Brachiola vesicularum, B vesicularum, Vittaforma corneae, V corneae, Nosema corneum, N corneum, Microsporidium ceylonensis, M ceylonensis, Microsporidium africanum, M africanum, microsporidial keratoconjunctivitis, ocular microsporidiosis, intestinal microsporidiosis, disseminated microsporidiosis, biliary microsporidiosis

Contributor Information and Disclosures

Author

Valda M Chijide, MD, Clinical Professor, Department of Medicine, University of Saskatchewan; Consultant in Infectious Diseases, Regina, Saskatchewan, Canada
Valda M Chijide, MD is a member of the following medical societies: American College of Physicians, HIV Medicine Association of America, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Medical Editor

Joseph Richard Masci, MD, Chief of Infectious Diseases, Associate Director, Associate Professor, Department of Internal Medicine, Division of Infectious Diseases, Elmhurst Hospital Center, Mount Sinai School of Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

John W King, MD, Professor of Medicine, Section of Infectious Diseases, Louisiana State University Health Sciences Center; Director, Viral Therapeutics Clinics for Hepatitis; Consulting Staff, Department of Infectious Diseases, Overton Brook Veterans Affairs Medical Center
John W King, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Federation for Medical Research, American Society for Microbiology, Association of Subspecialty Professors, Infectious Diseases Society of America, and Sigma Xi
Disclosure: emedicine $50.00 author of chapter

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

The author would like to thank Deidrea Parker, BS, and the Medical College of Georgia Department of Pharmacy for assistance in the literature review of the drug therapy for microsporidiosis.

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