Diagnosis>Opportunistic Infections>

PATHOGENS

• Group of obligate intracellular protozoan parasites consisting of >100 genera & >1000 spp.
• Five genera (Enterocytozoon, Encephalitozoon, Septata, Pleistophora, & Nosema), as well as unclassified microsporidial organisms may be associated with human disease. The first two genera listed are the most frequently encountered.
• Sources of infection & modes of transmission unclear (Cotte L, Rabodonirina M, Chapuis F, et al. ref.)
• Spores are quite resistant to environmental conditions and can remain infectious for several years, particularly if protected from desiccation.

CLINICAL

• Causes disease only in pts with advanced immunodeficiency (CD4 typically <100)
• Asymptomatic carriage occurs.
• Enterocytozoon bieneusi associated w/ intestinal &/or biliary illness; present in 7-50% of HIV-infected pts with CD4 <100 & otherwise unexplained chronic diarrhea.
• Main symptoms of E. bieneusi: chronic non-bloody diarrhea (up to 20 stools/day); weight loss (2 kg/mo), abdominal pain (50%); less commonly nausea & vomiting. 30% of pts are coinfected w/ other intestinal organisms. Dissemination rare.
• 3 spp., Encephalitozoon hellem, Encephalitozoon cuniculi, & Encephalitozoon intestinalis, may disseminate in pts w/ AIDS, particularly if CD4 <50.
• Encephalitozoon-associated diseases include conjunctivitis, keratitis, bronchiolitis, sinusitis, nephritis, cystitis, hepatitis, peritonitis. E. intestinalis also causes diarrhea, may disseminate to kidneys, lower airways, biliary tract.

DIAGNOSIS

• Dx: morphological demonstration of organisms by light or electron microscopic examination of clinical specimens (e.g., stool, duodenal aspirate, urine, sputum, nasal discharge, bronchoalveolar lavage fluid, conjunctival discharge).
• Modified trichrome stain: 25 l of concentrated specimen (stool, urine, or other fluid) are thinly spread onto the slides. Centrifuge specimen 10 min at 500 x g prior to smear preparation. IFA also available; PCR is research tool .
• Using chromotrope staining, spores of E. bieneusi measure 0.9 X1.5 m ovoid and refractile; spores of S. intestinalis & Encephalitozoon spp. measure 1.0-1.5 X 2.5 -3.0 µm; bigger than those of E. bieneusi.
• Organisms may be visible on Gram's or Giemsa stain or with chemofluorescent agents (e.g. calcofluor stain)

TREATMENT

• Most effective therapy is immune reconstitution with HAART (Miao YM, Awad-El-Kariem FM, Franzen C, et al. ref.)
• Fumagillin 60 mg PO once-daily X 2 wks; not widely available (Molina JM, Tourneur M, Sarfati C, et al. ref.)
• If fumagillin not available, albendazole 400 mg PO twice-daily.

• Albendazole 400 mg PO twice-daily for E. intestinalis is effective (Molina JM, Chastang C, Goguel J, et al. ref.).
• Other Encephalitazoon spp. may also respond to albendazole.
• Itraconazole: case reports have suggested efficacy in albendazole-refractory cases (Rossi P, Urbani C, Donelli G, et al. ref.)
• Most effective therapy is immune reconstitution with HAART (Miao YM, Awad-El-Kariem FM, Franzen C, et al. ref.)

• Based on case reports; no RCTs available.
• Vittaforma corneae, Pleistophora spp. & Septata intestinalis have been treated successfully w/ albendazole 400 mg PO twice-daily.
• Most effective therapy is immune reconstitution with HAART (Miao YM, Awad-El-Kariem FM, Franzen C, et al. ref.)

Drug Comments

FOLLOW UP

• Without immune reconstitution (HAART), pts. likely to relapse.
• Albendazole 400 mg PO twice-daily as maintenance therapy for E. intestinalis & other susceptible microsporidia may be effective until immune reconstitution is achieved
• Reports suggest that most pts can be taken off maintenance therapy once VL is undetectable & CD4 count is above 100 cell/mL (Miao YM, Awad-El-Kariem FM, Franzen C, et al. & Lafaurie M, Sarfati C, Menotti J, et al. refs.).
• No data on maintenance therapy w/ fumagillin

Basis for Recommendations

• Molina JM, Tourneur M, Sarfati C, et al.; Fumagillin treatment of intestinal microsporidiosis.; N Engl J Med; 2002; Vol. 346; pp. 1963-9;
  ISSN: 1533-4406;
  PUBMED: 12075057
  Rating: Basis for recommendation
  Comments:Randomized, double-blind, placebo-controlled trial of fumagillin (60 mg PO once-daily x 2 wks) in 12 patients with chronic E. bieneusi infection. Clearance of microsporidia occurred in all 6 pts in the fumagillin group vs. 0 in placebo group (p=0.002). Side effects included neutropenia and thrombocytopenia. All placebo pts subsequently responded to fumagillin. 2 pts relapsed after 10 mos. of F/U.
  
  
• Molina JM, Chastang C, Goguel J, 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; Vol. 177; pp. 1373-7;
  ISSN: 0022-1899;
  PUBMED: 9593027
  Rating: Basis for recommendation
  Comments:RCT of albendazole (400 mg PO twice-daily x 3 wks) for Rx of Encephalitozoon intestinalis resulted in clearance in 4 of 4 pts in albendazole group versus 0 of 4 in control group (p=.01). All 4 controls subsequently cleared microsporidia following open-label albendazole treatment. All 8 ps then randomly assigned to receive either albendazole (400 mg PO twice-daily) or no treatment for next 12 mos. Albendazole significantly delayed the occurrence of relapse.
  
  

REFERENCES

REFERENCED WITHIN THIS GUIDE

• Cholangiopathy, HIV
• Diarrhea
• Isospora belli