1. Screening for HBsAg and Anti-HBc in North American Blood Donors John Saldanha, Roche Molecular Systems SoGAT XXI, 28-29 May, 2009, Brussels, Belgium.

2. Background HBV screening of blood donations introduced in 1970s (HBsAg) In mid-1980s, anti-HBc testing introduced as surrogate marker for non- A, non-B (HCV) Risk of transfusion transmitted HBV greater than HCV or HIV-1 Pre-2006: –Risk 1:63,000 – 1:205,000 (mathematical modeling) –Average window period 59 days (range 37 – 87 days) Although NAT testing for HIV-1 and HCV introduced in 1999, no requirement yet for NAT testing for HBV

3. HBsAg and Anti-HBc Testing HBsAg tests –GS HBsAg EIA 3.023 January, 2003 –Ortho HBsAg ELISA Test System 3 23 April, 2003 –Abbott PRISM HBsAg ChLIA18 July, 2006 Anti-HBc test –Abbott PRISM HBc ChLIA13 October, 2005

4. Background: Incidence of Acute HBV in US 1990 – 2007: acute HBV incidence declined by 82% –2007: 4,519 acute, symptomatic cases ((1.5 cases per 100,000 population) –Underreporting and asymptomatic cases → 43,000 new infections Decline greatest amongst children <15 years –Introduction of vaccination of children against HBV MMWR, 2009;58 (SS-3)

5. HBV Vaccination and Blood Screening HBV vaccination rates –>50% among younger cohorts –>70% in blood donors in younger cohort Vaccination rates may confound HBV testing results and modeling ‘Breakthrough’ infections in vaccinated individuals –Asymptomatic, low viral loads –Risk of transfusion-transmitted HBV infection? R. Forshee, BPAC, April 2009

6. Current Incidence and Residual Risk of HBV Infection Two methods for modeling residual risk 1.Based on incidence from newly identified seroconverters (repeat donor data used) 2.Incidence based on HBsAg positive/anti-HBc negative donors (yield donors) x window period (‘New strategy’) Assumption: HBV infectious dose of 1-10 virions/20 mL plasma Zou et al, Transfusion, In Press

7. Residual Risk of HBV Infection: USA ARC data 1997 – 19991:86,000 – 1:110,000 2006 – 20081:280,000 – 1:357,000 Greatest reduction in 16 – 19 year old age group (HBV vaccination program target) 2008: 44% donors anti-HBsAg positive/HBsAg, anti-HBc negative Donors <29 years old highest rate of anti-HBsAg positivity (65%) Zou et al, Transfusion, In Press

8. Residual Risk of HBV Infection: Canada Incident rate model (repeat donors) used 2001 – 20051:153,000 56% of donors vaccinated (~ 80% under age 30) O’Brien et al, Transfusion, 2007, 47:316-325 O’Brien et al, Transfusion, 2008, 48:2323-2330

9. HBV NAT Testing of Blood Donors Blood Products Advisory Committee (BPAC) meeting, 1 st April, 2009 Three currently FDA-licensed HBV NAT tests –Roche COBAS AmpliScreen test (pools of 24)April, 2005 –Chiron Procleix Ultrio test (IDT and pools up to 16)August 2008 –Roche cobas MPX test (IDT and pools of 6)December, 2008 Recent advances in technology, automation, more sensitive tests → testing in smaller pools or IDT Potential to detect window cases, occult HBV and vaccine breakthrough cases

10. Reduction of Residual Risk for HBV Kleinman and Busch, J. Clin. Virol., 2006 *Residual risk (Canada) 6.55/million donations PRISM WP 38.3 days Reduction in WP by MPX (pools of 6) 8 days Reduction of residual risk (6.55x30.3/38.3) 5.18/million donations NAT yield 1.37/million donations * Based only on PRISM HBsAg testing

11. HBV Prevalence Linauts et al., Transfusion, 2008 COBAS ® AmpliScreen HBV Test, pools of 24 → 1:844,870 cobas ® TaqScreen MPX Test, pools of 6 & individual testing → 1:72,336 Combined data (COBAS ® AmpliScreen HBV Test, pools of 24; cobas ® TaqScreen MPX Test, pools of 6 & IDT) –3,451,815 donations tested from April 2002 - December 2008 –Yield: 5 samples MPX NAT reactive → 1:690,363 HBsAg negative anti-HBc negative (PRISM) Follow up samples for 3 donors –Window case, vaccine ‘breakthrough’, chronic carrier

12. HBV Prevalence: ARC Procleix Ultrio test ~3.7 million donors screened –9 NAT yield cases 8 detected in pools of 16 → 1:389,796 1 detected by IDT → 1:576,940 Overall rate: 1: 410,540 3 window cases 6 vaccine ‘breakthrough’ S. Stramer, BPAC, April, 2009

13. Summary Decrease in HBV prevalence due to vaccination program Incident rate (HBsAg) –USA: 1:280,000 – 1:357,000 –Canada: 1:153,000 HBV NAT yield –USA: 1:410,000 to 1:690,000 –Canada: 1: 730,000 (estimated)