1. Prepared by the AETC National Coordinating Resource Center based on recommendations from the CDC, National Institutes of Health, and HIV Medicine Association/Infectious Diseases Society of America Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents Microsporidiosis Slide Set

2. 2 May 2013www.aidsetc.org These slides were developed using recommendations published in May 2013. The intended audience is clinicians involved in the care of patients with HIV. Users are cautioned that, because of the rapidly changing field of HIV care, this information could become out of date quickly. Finally, it is intended that these slides be used as prepared, without changes in either content or attribution. Users are asked to honor this intent. -AETC National Resource Center http://www.aidsetc.org About This Presentation

3. 3 May 2013www.aidsetc.org  Epidemiology  Clinical Manifestations  Diagnosis  Prevention  Treatment  Considerations in Pregnancy Microsporidiosis

4. 4 May 2013www.aidsetc.org  Protists, related to fungi  Many species, including Enterocytozoon bieneusi, Encephalitozoon cuniculi, Encephalitozoon intestinalis  Ubiquitous, may be zoonotic and/or waterborne  Risk greatest with CD4 count <100 cells/µL  Incidence dramatically lower in areas with widespread use of effective ART Microsporidiosis: Epidemiology

5. 5 May 2013www.aidsetc.org  Most common: diarrheal illness  Other manifestations: cholangitis, hepatitis, encephalitis, ocular infection, sinusitis, myositis, disseminated infection  Clinical syndromes may vary by species Microsporidiosis: Clinical Manifestations

6. 6 May 2013www.aidsetc.org  Microscopic identification of stool or tissue samples  Identification requires high magnification (1,000×), selective stains to differentiate spores from cellular debris  Electron microscopy, PCR, Ab-specific stains can determine species  Evaluate 3 stool samples  Small bowel biopsy if stool studies are negative and suspicion is high  Urine examination may be useful if cause is Encephalitozoon or Trachipleistophora spp Microsporidiosis: Diagnosis

7. 7 May 2013www.aidsetc.org  Preventing exposure  Handwashing; avoidance of undercooked meat or seafood and exposure to infected animals  Patients with CD4 counts of <200 cells/μL should avoid drinking untreated water  Primary prophylaxis  Appropriate initiation of ART before severe immunosuppression should prevent disease  No chemoprophylaxis known to be effective Microsporidiosis: Prevention

8. 8 May 2013www.aidsetc.org  ART with immune restoration (to CD4 count >100 cells/µL)  Should be offered to all as part of initial management  If severe dehydration, malnutrition, wasting: hydration, nutritional support (IV therapies may be needed)  Antimotility agents, if needed for diarrhea control Microsporidiosis: Treatment

9. 9 May 2013www.aidsetc.org  E bieneusi GI infections:  ART and fluid support as above  no specific antimicrobial;  Fumagillin 60 mg PO QD or TNP-470: some evidence of efficacy but not available in United States  Nitazoxanide: limited data; cannot be recommended with confidence  Nonocular infection caused by microsporidial other than E bieneusi and V corneae:  Albendazole 400 mg PO BID Microsporidiosis: Treatment (2)

10. 10 May 2013www.aidsetc.org  Disseminated disease caused by Trachipleistophora or Anncaliia  Itraconazole 400 mg PO QD + albendazole 400 mg PO BID  Ocular infection: fumagillin (Fumidil B) eye drops 70 mcg/mL + albendazole 400 mg PO BID Microsporidiosis: Treatment (3)

11. 11 May 2013www.aidsetc.org  ART should be offered as part of initial management of this infection Microsporidiosis: Starting ART

12. 12 May 2013www.aidsetc.org  Albendazole: adverse effects are rare; monitor hepatic enzymes  Fumagillin  Topical: no known substantial side effects  Oral: thrombocytopenia  IRIS: 1 report Microsporidiosis: Adverse Events

13. 13 May 2013www.aidsetc.org  Supportive treatment  Optimization of ART Microsporidiosis: Treatment Failure

14. 14 May 2013www.aidsetc.org  Ocular:  If CD4 >200 cells/µL on ART, consider discontinuing treatment after ocular infection resolves; restart if CD4 drops to <200 cells/µL  Other manifestations:  Safety of treatment discontinuation after immune restoration with ART is not known  Reasonable to discontinue maintenance therapy in asymptomatic patients on ART with increase in CD4 count to >200 cells/µL for ≥6 months (no data to support this approach) Microsporidiosis: Prevention of Recurrence

15. 15 May 2013www.aidsetc.org  Initiate ART to restore immune function  Albendazole:  Embryotoxic and teratogenic in animals  Not recommended in 1st trimester, use during later pregnancy only if benefits expected to outweigh risks  Systemic fumagillin: growth retardation in rats: should not be used with pregnant women  Topical fumagillin appears safe Microsporidiosis: Considerations in Pregnancy

16. 16 May 2013www.aidsetc.org  Itraconazole: avoid in 1st trimester  Loperamide: possible risk of hypospadias with 1st- trimester exposure  Avoid in 1st trimester, unless benefits expected to outweigh risks  Preferred antimotility agent during late pregnancy  Tincture of opium not recommended during late pregnancy  Opiate exposure during late pregnancy associated with neonatal respiratory depression; chronic exposure may result in neonatal withdrawal Microsporidiosis: Considerations in Pregnancy (2)

17. 17 May 2013www.aidsetc.org  http://www.aidsetc.org  http://aidsinfo.nih.gov Websites to Access the Guidelines

18. 18 May 2013www.aidsetc.org  This presentation was prepared by Susa Coffey, MD, and Oliver Bacon, MD, for the AETC National Coordinating Resource Center in May 2013  See the AETC NCRC website for the most current version of this presentation: http://www.aidsetc.org About This Slide Set