Presentation to BPAC May 1, 2008 Robert Duncan, PhD

1. Current considerations for Implementation of Blood Donor Screening for Infection with Trypanosoma cruzi and the Use of Serological Tests to Reduce the Risk of Transmission of T. cruzi Infection in Whole Blood and Blood Components for Transfusion and Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) Presentation to BPAC May 1, 2008 Robert Duncan, PhD

2. Background Trypanosoma cruzi: causative agent of Chagas disease • Small protozoan parasite • Chronic, asymptomatic infection • Difficult or impossible to treat, severe symptoms late in about 30% of cases • Endemic to portions of Mexico, Central America, and South America, 16-20 million people infected • Transmission: feces of an infected triatomine insect, congenital, organ transplant, transfusion, oral (breast milk), via conjunctiva, laboratory accident • Blood transfusion transmission is a recognized problem in endemic areas. An infected unit is estimated to have a 12-20% probability of causing infection in the recipient (WHO TRS 905, 2002)

3. Background: Risk and Epidemiology in the US • 7 cases of transfusion transmission documented in US/Canada • 5 cases of solid organ transplant transmission • Rare natural transmission of T. cruzi in the US • Seroprevalence in US donor population has been estimated in the range of 0.01-0.2% with the higher rates in areas with large numbers of immigrants from Central and South America. • Increasing rates of immigration raises concern about the potential for increased transmission. Triatomine bug

4. Background (Continued) • December 2006- FDA approves the first blood donor screening assay (the Ortho® T. cruzi ELISA Test System) • No FDA licensed supplemental test for T. cruzi antibodies is currently available • April 26, 2007 – Issues related to implementation of blood donor and cell/tissue donor screening presented and discussed with BPAC: • Donor management, product management, areas needing additional research, potential for cell/tissue transmission

5. Blood donor screening for Chagas disease • Chagas screening with the Ortho ELISA initiated by ARC and BSI on January 29, 2007, other centers have followed. Through Apr. 25, 2008, over11.8 million donors had been screened, resulting in detection of 1,492 repeatedly reactive (0. 01%). • Retested on a more specific, unlicensed T. cruzi RIPA:980 non-reactive, 3 indeterminate, 452 (31%) reactive, 57 pending. • 99.99% specificity, 0.0038% prevalence

6. Continental U.S. Map: RIPA Positives (updated 04/25/08)

7. Blood donor screening for Chagas disease • Is there evidence of vector borne transmission within the USA? • Among the RIPA reactives, 15 (3.3%) had no history of immigration, travel to, nor parents immigrating from an endemic area • Is there new evidence of transfusion transmission? • Lookback: 65 recipients of blood products from 37 seropositive donors have been tested for T. cruzi. • 57 recipients are negative on all tests • 1 recipient is seropositive (born in El Salvador), • 6 recipients have a single reactive test on RIPA or PCR only, judged to be false positives. • 1 pending

8. Issues for Implementation of Blood Donor Screening : Donor Management • We are considering whetherblood establishments should: • Test donations for antibodies to T. cruzi • Universal screening • Potential for selective testing if appropriately validated • Defer (indefinitely) and notify all donors repeatedly reactive by the licensed test • Allow reentry only once a supplemental test is licensed

9. Donor Management (Continued) • Counseling: • inform all repeatedly reactive donors about likelihood and medical significance of infection; referral for additional medical diagnostic testing may be useful • Medical follow up for cross-reacting diseases • Specific counseling of repeatedly reactive donors with no apparent exposure or negative results on more specific medical diagnostic tests for further medical follow up based on risk factors

10. Issues for Implementation of Blood Donor Screening : Product Management • We are considering whetherblood establishments should: • Index donations • quarantine and label all repeatedly reactive donations • Products from prior collections • retrieve, quarantine and label • Lookback (recipient tracing) • notify consignees to enable notification of recipients of prior donations from repeatedly reactive donors who are • repeatedly reactive by a licensed test for T. cruzi antibodies, and • for whom there is additional information indicating risk of T. cruzi infection, such as a positive test result on a licensed T. cruzi supplemental test, when such test is available. Until such a licensed supplemental test is available, geographical risk for exposure in an endemic area, or medical diagnostic testing of the donor may provide additional information

11. Product Management (Continued) • We are considering whetherblood establishments should: • Autologous donations • test when allogeneic use of these units is allowed or units are shipped to centers where allogeneic use is allowed. • Repeatedly reactive units for autologous use must be labeled “Biohazard” (21 CFR 610.40)

12. Product Management (Continued) • We are considering whetherblood establishments should: • Label and Circular of Information • update to include T. cruzi antibody testing • Biological Product Deviation Report and Fatality report • report release of reactive units or any fatality related to a reactive unit

13. Product Management (Continued) • We are considering whetherblood establishments should: • Report test Implementation – Annual Report