Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Exposed and HIV-Infected Children

Evidence Summary Table of Microsporidiosis

Last Updated: December 15, 2016; Last Reviewed: December 15, 2016

Microsporidiosis: PICO Question and Tabular Evidence Summary
Question I: In children with HIV infection, what are the best interventions (compared with no intervention) to treat microsporidiosis? 
Search terms: microsporidiosis, microsporidia; HIV  
Reference Study Design (N)
Patient Characteristics Intervention Comparison Outcome Measures Main Findings Evidence Quality: 
  • Begin with basic study design.
  • Downgrade for risk of bias, imprecise estimates, inconsistency, and indirectness. 
  • Upgrade for large effect size and dose-response gradient, or if likely biases would reduce apparent effect.
 
Miao et al 2000 Observational cohort (n = 4)
4 patients with documented E. bieneusi infection followed with stool samples and duodenal biopsy pre-ART, then 1–3 and 6 months post-ART
ART None Eradication of symptoms and organism 
If patients responded to ART, symptoms improved within 1 month and organism was eradicated at 6 months.
Observational. Downgraded for small sample size, incomplete assessment by duodenal biopsy at 6 months, and indirectness (no children).
Weber et al 19932
Case report (n = 1)
Report of a 9-year-old boy with E. bieneusi infection who did not respond to albendazole
Albendazole
None
Symptoms
No response to albendazole therapy.
Case report. Downgraded for small sample size.
Molina et al 20023
Randomized, double-blind, placebo-controlled (n = 12), open-label treatment of randomized treatment failures
10 adult patients with AIDS and 2 adults with organ transplants with E. bieneusi intestinal infection
Fumagillin, 20 mg TID for 2 weeks
Placebo for 2 weeks
Stool microscopy
All 6 patients randomized to the fumagillin group cleared parasites from the gut compared to 0 of 6 placebo patients by days 15–17. All 6 placebo treatment failures cleared following open-label fumagillin treatment.
Randomized controlled trial. Downgraded based on small sample size and indirectness (adult-only population). Upgraded based on effect size and crossover design with complete clearance.
Dore et al 19954
Adults with disseminated E. intestinalis infection (n = 9)
Observational cohort
Albendazole, 400 mg, BID
None Symptoms 7 of the 9 patients were treated with albendazole and had improvement in symptoms and reduction or resolution of diarrhea; complete clearance of the organism from all sites studied was reported in 5 and partial clearance in the remaining 2.
Observational cohort. Downgraded for small sample size, no selection criteria, and indirectness (adults).
Leder et al 19985
Adult patients who received either albendazole or metronidazole or both for treatment of microsporidial disease (n = 25)
Observational cohort
Albendazole, 400 mg, BID 
Metronidazole, 400 mg TID
Amount of diarrhea All 8 patients with E. intestinalis infection treated with albendazole had clinical response. 1 of these patients had been previously treated with metronidazole and had no response. Among patients with E. bieneusi infections, 4 received metronidazole alone, 8 received albendazole alone, and 5 received both agents. Although there was some initial reduction in symptoms, no patient had a complete clinical response.
Observational cohort. Downgraded for sample size, mixed treatment, inclusion of multiple treatments with no specified treatment criteria, and indirectness (adults).
Tremoulet et al 20046
Immunocompetent Costa Rican children with subacute diarrhea and microsporidia (n = 200)
Randomized, open-label study
Albendazole, 15 mg/kg/ day divided BID for 7 days
Supportive therapy
Clinical improvement within 48 hours of initial therapy
95% of albendazole and 30% of supportive care-only arms improved by 48 hours.
Randomized trial. Downgraded based on comparator arm, indirectness (immunocompetent children), and no speciation of microsporidia.
Diesenhouse et al 19937
Open-label study of topical fumagillin in E. hellum keratoconjunctivitis (n = 2)
Case series
Topical fumagillin
None Clinical improvement Both patients had improvement in symptoms while receiving the agent but recurrence with temporary discontinuation. Responded to reintroduction and maintenance therapy.
Case series. Downgraded based on small sample size and lack of comparator group.
Question II: In HIV-infected children who have been treated for microsporidiosis, when can treatment (secondary prophylaxis) be safely discontinued? 
Search terms: microsporidiosis, microsporidia; HIV 
Miao et al 20001 Observational cohort (n = 4)
4 patients with documented E. bieneusi infection followed with stool samples and duodenal biopsy pre-ART and 1-3 and 6 months post-ART
ART
None Eradication of symptoms and organism 
If patients responded to ART, symptoms improved within 1 month and organism was eradicated at 6 months.
Observational. Downgraded for small sample size, incomplete assessment by duodenal biopsy at 6 months, and indirectness (no children). 
Key to Acronyms: ART = antiretroviral therapy; BID = twice a day; TID = three times a day 

References

  1. Miao YM, Awad-El-Kariem FM, Franzen C, et al. Eradication of cryptosporidia and microsporidia following successful antiretroviral therapy. J Acquir Immune Defic Syndr. 2000;25(2):124-129. Available at http://www.ncbi.nlm.nih.gov/pubmed/11103042.
  2. Weber R, Sauer B, Luthy R, Nadal D. Intestinal coinfection with Enterocytozoon bieneusi and Cryptosporidium in a human immunodeficiency virus-infected child with chronic diarrhea. Clin Infect Dis. 1993;17(3):480-483. Available at http://www.ncbi.nlm.nih.gov/pubmed/8218693.
  3. Molina JM, Tourneur M, Sarfati C, et al. Fumagillin treatment of intestinal microsporidiosis. N Engl J Med. 2002;346(25):1963-1969. Available at http://www.ncbi.nlm.nih.gov/pubmed/12075057.
  4. 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(1):70-76. Available at http://www.ncbi.nlm.nih.gov/pubmed/7578763.
  5. Leder K, Ryan N, Spelman D, Crowe SM. Microsporidial disease in HIV-infected patients: a report of 42 patients and review of the literature. Scand J Infect Dis. 1998;30(4):331-338. Available at http://www.ncbi.nlm.nih.gov/pubmed/9817510.
  6. Tremoulet AH, Avila-Aguero ML, Paris MM, Canas-Coto A, Ulloa-Gutierrez R, Faingezicht I. Albendazole therapy for Microsporidium diarrhea in immunocompetent Costa Rican children. Pediatr Infect Dis J. 2004;23(10):915-918. Available at http://www.ncbi.nlm.nih.gov/pubmed/15602190.
  7. Diesenhouse MC, Wilson LA, Corrent GF, Visvesvara GS, Grossniklaus HE, Bryan RT. Treatment of microsporidial keratoconjunctivitis with topical fumagillin. Am J Ophthalmol. 1993;115(3):293-298. Available at http://www.ncbi.nlm.nih.gov/pubmed/8117342.