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 Cryptosporidiosis 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 Users are cautioned that, because of the rapidly changing field of HIV care, this information could become out of date quickly.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 Cryptosporidiosis

4. 4 May 2013www.aidsetc.org  Caused by Cryptosporidium species  Protozoan parasites  Infect small intestine mucosa; in immunosuppressed patients, also infect large intestine and other sites  Advanced immunosuppression (eg, CD4 <100 cells/µL) associated with prolonged, severe, or extraintestinal disease Cryptosporidiosis: Epidemiology

5. 5 May 2013www.aidsetc.org  Infection results from ingestion of oocysts excreted in feces of infected humans or animals  Water supplies and recreational water sources (oocysts may withstand standard chlorination)  Person-to-person transmission common, via oral-anal contact, from infected children to adults (eg, during diapering), or care of patients with diarrhea Cryptosporidiosis: Epidemiology (2)

6. 6 May 2013www.aidsetc.org  Common cause of chronic diarrhea in AIDS patients in developing countries  In developed countries with low rates of envrionmental contamination and widespread use of effective ART, <1 case per 1,000 person-years in AIDS patients Cryptosporidiosis: Epidemiology (3)

7. 7 May 2013www.aidsetc.org  Acute or subacute onset of profuse watery, nonbloody diarrhea, often with nausea, vomiting, and abdominal cramping  Fever in 1/3 of patients  Can be very severe, especially with immune suppression  Malabsorption is common; dehydration, electrolyte abnormalities, malnutrition may result  Biliary tract and pancreatic duct may be infected, causing scleroding cholangitis and pancreatitis  Pulmonary infection is possible Cryptosporidiosis: Clinical Manifestations

8. 8 May 2013www.aidsetc.org  Microscopic identification of oocysts in stool or tissue  DFA very sensitive, specific, is current gold standard for stool specimens  Acid-fast staining often used  PCR extremely sensitive  ELISA or immunochromatographic tests  Small intestine biopsy with identification of Cryptosporidium organisms Cryptosporidiosis: Diagnosis

9. 9 May 2013www.aidsetc.org  Single specimen usually sufficient in profuse diarrhea  Repeat stool sampling is recommended in mild disease Cryptosporidiosis: Diagnosis (2)

10. 10 May 2013www.aidsetc.org  Preventing exposure  Avoid exposure to infected contacts  Contact with diarrhea  Potential oral exposure to feces during sex  Direct contact with farm animals, stool from pets  Scrupulous handwashing after potential contact with feces (eg, after diapering), after handling pets or other animals, gardening, before preparing food or eating, before and after sex Cryptosporidiosis: Prevention

11. 11 May 2013www.aidsetc.org  Avoid exposure to contaminated water, food  Do not drink or swallow water from recreational sources (lakes, streams, pools)  Ice, fountain beverages, water fountains may be contaminated  Avoid raw oysters Cryptosporidiosis: Prevention (2)

12. 12 May 2013www.aidsetc.org  Boil tap water for ≥1 minute during outbreaks or when community advisory is issued  Submicron water filters or bottled water may reduce risk  For non-outbreak settings, data are inadequate to recommend that all persons with low CD4 counts avoid drinking tap water  Consider drinking only filtered water Cryptosporidiosis: Prevention (3)

13. 13 May 2013www.aidsetc.org  Preventing disease  Primary prophylaxis:  Appropriate initiation of ART before severe immunosuppression should prevent disease  Rifabutin and possibly clarithromycin are protective, but data insufficient to recommend as chemoprophylaxis Cryptosporidiosis: Prevention (4)

14. 14 May 2013www.aidsetc.org  Preferred strategies  ART with immune restoration (to CD4 count >100 cells/µL)  Usually results in complete resolution; should be offered as part of initial management of cryptosporidiosis  Symptomatic treatment: antidiarrheals  Tincture of opium may be more effective than loperamide  Octreotide usually not recommended (no more effective than other antidiarrheals)  Supportive care: aggressive hydration, electrolyte repletion, nutritional support (IV therapies may be needed) Cryptosporidiosis: Treatment

15. 15 May 2013www.aidsetc.org  Alternative strategies  No consistently effective antimicrobial therapy in absence of ART  Consider nitazoxanide or other antiparasitic drugs in conjunction with ART, not instead of ART  Nitazoxanide 500-1,000 mg PO BID for 14 days + ART and other measures above  Some studies show clinical improvement with nitazoxanide  Paromomycin 500 mg PO QID for 14-21 days + ART and other measures above  Limited data; may improve clinical response in conjunction with ART Cryptosporidiosis: Treatment (2)

16. 16 May 2013www.aidsetc.org  ART should be offered as part of initial management of this infection  PIs inhibit Cryptosporidium in animal models – some experts prefer PI-based ART Cryptosporidiosis: Starting ART

17. 17 May 2013www.aidsetc.org  Monitor closely for volume depletion, electrolyte loss, weight loss, and malnutrition  TPN may be indicated  IRIS not reported Cryptosporidiosis: Monitoring and Adverse Events

18. 18 May 2013www.aidsetc.org  Supportive treatment  Optimization of ART Cryptosporidiosis: Treatment Failure

19. 19 May 2013www.aidsetc.org  No effective prevention, other than immune restoration with ART Cryptosporidiosis: Prevention of Recurrence

20. 20 May 2013www.aidsetc.org  Rehydration and ART initiation as with nonpregnant adults  Nitazoxanide not teratogenic in animals, but no data in pregnant humans  Use after 1st trimester in severely symptomatic women  Paromomycin: limited information on teratogenicity; minimal systemic absorption with PO administration  Use after 1st trimester in severely symptomatic women Cryptosporidiosis: Considerations in Pregnancy

21. 21 May 2013www.aidsetc.org  Loperamide: possible risk of hypospadias with 1st- trimester exposure  Avoid during 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 Cryptosporidiosis: Considerations in Pregnancy (2)

22. 22 May 2013www.aidsetc.org  http://www.aidsetc.org  http://aidsinfo.nih.gov Websites to Access the Guidelines

23. 23 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