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 Zambia HIV National Guidelines
 


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 Guide Editors
 Editor In Chief
    Joel E. Gallant, MD, MPH

Pharmacology Editor
    Paul Pham, PharmD, BCPS

Zambia Guideline Team
   Peter Mwaba MMed PhD FRCP
   Alywn Mwinga MMed
   Isaac Zulu MMed MPH
   Velepie Mtonga MMed
   Albert Mwango MBChB
   Jabbin Mulwanda MMed FCS
 

 

 

Diagnosis>Opportunistic Infections>
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Microsporidiosis

Khalil Ghanem, M.D.
02-06-2009

  • Microsporidiosis endemic in Zambia and a common cause of persistent diarrhea in HIV+ Zambians.
  • Diagnostic testing limited in Zambia;  diarrhea typically treated empirically per routine guidelines (see Diarrhea).
  • If specifically diagnosed, treatment recommendations are similar to those in developed world.
  • Nitazoxanide is a novel treatment for protozoan infections that has been studied in Zambian pts with AIDS and persistent diarrhea, but still be considered experimental for microsporidiosis.
  • Fumagillin not readily available in Zambia.

REFERENCES

Zambia Information Author: Larry William Chang, MD, MPH

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

Enterocytozoon bieneusi

  • 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.
Encephalitozoon spp.  

  • 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.)
Other microsporidia

  • 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

DrugRecommendations/Comments
Albendazole For Encephalitozoon spp.,Vittaforma corneae, Pleistophora spp.

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

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