Screening for HBsAg and Anti-HBc in North American Blood Donors

John Saldanha, Roche Molecular Systems

SoGAT XXI, 28-29 May, 2009, Brussels, Belgium

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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

HBsAg and Anti-HBc Testing

• HBsAg tests

– GS HBsAg EIA 3.0 23 January, 2003

– Ortho HBsAg ELISA Test System 3 23 April, 2003

– Abbott PRISM HBsAg ChLIA 18 July, 2006

• Anti-HBc test

– Abbott PRISM HBc ChLIA 13 October, 2005

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)

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

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

Residual Risk of HBV Infection: USA

ARC data

1997 – 1999 1:86,000 – 1:110,000

2006 – 2008 1:280,000 – 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

Residual Risk of HBV Infection: Canada

Incident rate model (repeat donors) used

2001 – 2005 1:153,000

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

HBV NAT Testing of Blood Donors

• Blood Products Advisory Committee (BPAC) meeting, 1st 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

HBV PrevalenceLinauts 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 negativeanti-HBc negative (PRISM)

• Follow up samples for 3 donors– Window case, vaccine ‘breakthrough’, chronic carrier

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

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)