Comparison of the transfusion risk for CJD vs. vCJD

1. Comparison of the transfusion risk for CJD vs. vCJD Steven Anderson, Ph.D, MPP Office of Biostatistics & Epidemiology Center for Biologics Evaluation & Research U.S. Food & Drug Administration TSE Advisory Committee Meeting February 12, 2004

2. CJD and vCJD – risk of transmission via blood • Animal experiments have suggested that both Creutzfeldt-Jakob disease (CJD) and Bovine Spongiform Encephalopathy (BSE) can be transmitted via blood transfusion • Humans • CJD - Prion protein not found in lymphoreticular system • vCJD - Prion protein found in lymphoreticular system - tonsils, appendix, lymph nodes and spleen

3. I. vCJD: Possible vCJD transmission via human blood transfusion • On Dec 17, 2003 U.K. reported a 69 year old male died of variant Creutzfeldt-Jakob disease (vCJD) 6.5 years after transfusion • Above recipient received RBCs from donor in 1996 that died 3 years later from vCJD

4. Study of vCJD donors and recipients Study in United Kingdom by National Surveillance Unit and National Blood Service • Followed donations from 15 donors later diagnosed vCJD • 48 Individuals received blood products from the 15 donors • Whole blood, RBCs, plasma, platelets, etc. • *Llewelyn, et al. Lancet, 2004.

5. Additional potential vCJD exposures via blood products in the U.K. • 18 units of plasma from vCJD infected donors included in fractionated products prior to 1998 • Thousands of potential exposures • vCJD has not been observed to date for these products

6. II. CJD and Blood epidemiology: CJD Donors and Recipients • CJD • Rare disease -incidence ~ 1 per million population • Occurs largely in individuals > 60 yrs old • Long incubation period estimated at 4 – 40 yrs • CJD transmission via transfusion considered a low risk • If risk was significant – might see increase in CJD rate annually • CJD rate stable last 10 to 20 years

7. ARC – CDC – NBDRC - CJD blood lookback study • American Red Cross – CDC - National Blood Data Resource Center (NBDRC)– CJD transfusion lookback study • Includes transfusions from 1959 to 2002 • 331 transfusion recipients who received blood from donors later diagnosed with CJD • 116 of the recipients have lived >5 years post-transfusion • 95 recipients (29%) still alive • 0 observed CJD infections to date

8. CJD and Transfusion Epidemiology Studies • No observed association between CJD and Transfusion • Study of 2,479 CJD patients - Wilson, et al. BMJ 2000 from 5 case control studies

9. CJD studies in U.S. hemophilia populations • CDC study of CNS tissues from 30 severe hemophilia patients – died with CNS symptoms after 1983 • Received clotting factor & concentrates – 15 to 23 years • No indication of CJD(Operskalski et al, Lancet 1995; 346:1224) • Continuation of the CDC study • ~12,000 hemophilia patients assessed for CJD • Neurologic tissue evaluated from additional ~ 10 decedents • No observed CJD to date

10. Studies in U.K. hemophilia populations of vCJD and CJD • U.K. retrospective postmortem study • 33 hemophilia patients • clotting factor concentrates (1962 – 1995) for 3 to 27yrs • No indication of vCJD or CJD(Lee et al, Thromb Haemost 1998:80:909)

11. Comparison between data for vCJD and CJD • U.K. study – vCJD transfusion infection • 48 recipients of product • 15 recipients survived > 5 years • 1 presumptive vCJD infection (Dec 23, 2003) • National Blood Data Resource Center (NBDRC) and CDC – CJD transfusion lookback study • 331 transfusion recipients • 116 recipients survived > 5 years • 0 observed infections to date

12. Incubation period Iatrogenic transmission of CJD • Incubation periods for iatrogenic CJD • Tissues - Cornea / EEG – 16 months • Within or close proximity to brain • Human growth hormone – 4.5 years • Injectable – intramuscularly • Assumed similar to the infusion route for blood

13. Comparison ofRecipients surviving >5yrs post transfusion of blood products from CJD/vCJD patients • Percentage of recipients surviving longer than 5 years post-transfusion in two groups was similar • vCJD = 15 out of 48 or 31.3% • CJD = 116 out of 331 or 35%

14. Comparison ofRecipients surviving >5yrs post transfusion of blood products from CJD/vCJD patients Given the relatively small size of each group it is difficult to say much about the two groups Except that additional data and research are needed

15. Challenges for comparing vCJD and CJD infection rates • Caveats and challenges for comparing vCJD and CJD data: • Size (N) of groups is small • Incubation period is long • Survival duration post-transfusion often exceeds incubation period