Are Booster Doses of Hepatitis B Vaccine Necessary? Current CDC - - PowerPoint PPT Presentation

Are Booster Doses of Hepatitis B Vaccine Necessary?

Division of Viral Hepatitis Centers for Disease Control and Prevention, USA

Current CDC Recommendations And Gaps in Knowledge

Current United States Recommendations for Hepatitis B Vaccination

• Selective vaccination of children, adolescents, and

adults at increased risk of infection (1982)

• Prevention of perinatal transmission through routine

screening of pregnant women (1984)

• Routine vaccination of infants beginning at birth (1991)
• Routine vaccination of adolescents (11-12 yrs) (1995)
• Catch-up vaccination of unvaccinated children and

adolescents (through 18 yrs) (1999)

Recommendations endorsed by the U.S. Advisory Committee on Immunization Practices (ACIP), American Academy of Pediatrics (AAP), American Academy of Family Physicians (AAFP), and American Medical Association (AMA).

High-Risk Groups

• Injecting drug users
• Sexually active homosexual & bisexual men
• Heterosexual men and women with >1 sex partner
• Persons recently tx for another STD
• Sex contacts of persons with chronic hep B
• Household contacts of persons with chronic HBV infection
• Persons with occupational exposure (e.g., HCW’s)
• Recipients of certain blood products (clotting factors)
• Clients and staff of institutions for developmentally disabled
• Chronic hemodialysis patients
• International travelers
• Inmates of long-term correctional facilities
• Adoptees from high HBV endemic countries

Hepatitis B Vaccination in the United States: Coverage and Impact

Incidence of Acute Hepatitis B, United States, 1980-2001

Overall, 76% decline Since 1990, 66% decline

2 4 6 8 10 12 14 1980 1983 1986 1989 1992 1995 1998 2001

Year Cases per 100,000 population

11.7 per 100,000 2.8 per 100,000 8.1 per 100,000

Source: CDC National Notifiable Diseases Surveillance System Source: CDC National Notifiable Diseases Surveillance System

Hepatitis B Vaccination Coverage Among Children*, United States, 1990-2002

8 16 37 68 82 87 88 90 89 90 84 20 40 60 80 100 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002

Year Coverage (%)

* 19-35 months old

Source: National Immunization Survey Source: National Immunization Survey, CDC

Hepatitis B Vaccination Coverage Among Adolescents*, United States

10 20 30 40 50 60 70 80 90 100

1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005

Year % immunized

Target coverage 90% Vaccine coverage gap Adolescent vaccination recommended *13-15 years old

Source: National Health Interview Survey, CDC

Incidence of Acute Hepatitis B by Age, United States, 1990-2001

2 4 6 8 10 12 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001

Year Cases/100,000 population

65% decline 85% decline 89% decline 20+ years old

0.5 1 1.5

1990 1992 1994 1996 1998 2000

0-11 years old 12-19 years old

Source: CDC National Notifiable Diseases Surveillance System Source: National Notifiable Diseases Surveillance System, CDC

HBV Prevalence Among U.S. Born Children of Asian Immigrants, Atlanta, 1986 and 2002

Anti-HBc HBsAg

2 4 6 8 10 12

Percent infected

6.6% 0.6% 11.7% 0.6% 1986 (pre-vaccination; n=251) 2002 (vaccination coverage >3 doses=98%; n=157)

Sources: Franks. N Engl J Med. 1989; CDC and GA Department of Health, 2001-2002.

Hepatitis B Incidence Among Health Care Workers & General Population United States, 1982-1998

50 100 150 200 250 300 350 400 450 1 9 8 2 1 9 8 4 1 9 8 6 1 9 8 8 1 9 9 1 9 9 2 1 9 9 4 1 9 9 6 1 9 9 8

Year Infections per 100,000 Health care workers General population

Source: Mahoney. Arch Intern Med. 1997; CDC

Current Booster Dose Recommendations

Current Recommendations for Booster Doses of Hepatitis B Vaccine

Booster doses of hepatitis B vaccine are not currently recommended Recommendation based on:

• Long-term efficacy studies published to date
• Booster dose studies published to date
• U.S. surveillance data

– of acute hepatitis B cases among children and adolescents, none report being vaccinated – suggests no breakthrough infections occurring among vaccinated infants and adolescents

Long-Term Protection Studies Among Vaccinated Infants

Country China Alaska The Gambia Hong Kong Taiwan Senegal Taiwan Taiwan Italy Italy Thailand Yrs f/u 15 15 14 12 12 9-12 10 10 10 10 8-10 Anti-HBc positive 6% 1% 31% 1% 2.7% 27% 14% 12% 1% 9% Anti-HBs >10 mIU/m 50% 61% 64% 74% 37% 68% 85% 67% 68% 68% 62% n 52 119 175 148 951 41 805 118 53 474 76 HBsAg positive 2% 2.8%

• 2%

0.4%

Liao Vaccine 1999; McMahon In press; Whittle BMJ 2002; Yuan Hepatology 1999; Lin JID 2003; Coursaget J Hepatol 1994; Wu JID 1999; Huang Hepatol 1999; Resti Vaccine 1997; Davilla Vaccine 1996; Poovorawan Ann Trop Med Parasit 2000.

Country (Group) Alaska (20-49 yo) Italy (HCW) U.S. (MSM) Alaska2 U.S. (MSM) Years of follow-up 15 10 10 9-10 7-9 Anti-HBc Positive <2%1 4% 7% Anti-HBs >10 mIU/m 59% 85% 91% 65-84% 48% n 182 310 127 1194 232 HBsAg Positive <0.2%1 1% <1%

1 Results for all 783 persons in study, not just those vaccinated at age 20-49 years. 2 Includes vaccinated children.

Long-Term Protection Studies Among Vaccinated Adults

McMahon in press 2004. Floreani Vaccine 2004 Stevens Peds 1992;Wainwright JID 1997; Hadler VHLD 1991.

Summary of Long-Term Protection Data

10-15 years after vaccination of infants, children and adults:

• Decline in detectable levels anti-HBs

–48-91% >10 mIU/ml

• Serologic evidence of HBV infection in some

vaccinated persons –<1% to 37% (highest in Gambia & Senegal)

• No symptomatic infections
• Development of chronic infection very rare
• Suggests despite decline in anti-HBs,

protection persists

Booster Doses Response Among Persons Vaccinated as Infants

Pre-boost anti-HBs >10 mIU/m 24% 31% 67% 68% 39% 01 Post-boost anti-HBs >10 mIU/ml 76% 94% 100% 100% 93% 95% Years follow-up 12.5 12 10 10 9 8 Known Responder Yes Yes Yes (?) Yes No No Country Alaska Alaska Taiwan Italy Samoa Thailand n 17 16 118 53 41 90

1Included only those with anti-HBs<10 mIU/ml

Peterson In prep 2004; Peterson In prep 2004; Huang Hepatol 1999; Resti Vaccine 1997; Williams PIDJ2003; Chongarisawat SE Asia J Trop Med Parasitol 2000.

Country (group) U.S. (adults) Alaska (HCW) Italy (HCW) Spain (adults, kids) 2,3 Years follow-up 13 3-13 6 6 n 7 59 955 182

1 Included only those with anti-HBs<10 mIU/ml 2 Average age: 30 years 3 Used anti HBs >100 mIU/ml

Booster Doses Response Among Persons Vaccinated as Adults

Pre-boost anti-HBs >10 mIU/m 71% 01 67% (3 dose) 94% (4 dose) 64%3 Post-boost anti-HBs >10 mIU/ml 100% 97-100% 97% (3 dose) 94% (4 dose) 96%3

Watson Vaccine 2001; Williams Vaccine 2001; Trivello Vaccine 1995; Ayerbe Eur J Epidemiol 2001.

Summary of Booster Dose Studies

• Among vaccinated infants and adults who lose

detectable levels anti-HBs – majority respond to booster doses of vaccine – among documented responders, 97-100% boost

• Suggests presence of immune memory despite loss
• f anti-HBs

CDC Booster Dose Study: American Samoa

• 70 children born in 1991
• Received 3 doses recombinant hepatitis B vaccine

at birth, 1, 6 months

• Tested for anti-HBs after primary series
• Received booster dose at 5 yrs old
• Anti-HBs testing at 2 wks, 4 wks, 1 yr post-boost

dose

Anti-HBs Response to Primary Series and Booster Dose: American Samoa

Post-Boost Post-primary (13 months) Pre-boost (60 months)

63 (90%) 7 (10%) 70 26 (41%) 37 (59%) 7 (100%) 26 (100%) 4 (57%) 3 (43%) 37 (100%)

Anti-HBs >10 mIU/ml Anti-HBs <10 mIU/ml

Distribution of Anti-HBs in Response to Booster Dose of Vaccine: Samoa

10-99 <10 100-999 >1,000 Anti-HBs (mIU/ml): 20 40 60 100

Percent

Primary series Booster dose 80 0 0 1 7 13

Age in months

60 64 64 65 76

Booster Doses Response Among Persons Vaccinated in Infancy: Samoa

1 10 100 1,000 10,000 100,000 6 12 18 24 30 36 42 48 54 60 66 72 78 84

GMT anti-HBs (mIU/ml)

Age in months

Primary Series Booster Dose >1,000 mIU/ml 100-999 mIU/ml 10-99 mIU/ml Anti-HBs

Unanswered Questions and Gaps in Knowledge

• Age at vaccination
• GMC post primary series
• Receipt of HBIG
• Vaccine type: plasma-derived vs. recombinant
• Infection pressure: endemicity, maternal HBV

status, vaccination coverage

• Natural boosting

– birth – later infancy – childhood – adulthood

Unanswered Questions

Of the various determinants of duration of protection, which are the most important?

Natural Boosting and Infection Pressure

Is natural boosting important? Is infection pressure important? What is the relationship between the two?

• High vs. low endemic areas
• Areas with catch-up vaccination of older children,

adolescents, adults (i.e., Alaska)

• Implications for movement to from low to high

endemic areas and potential for exposure

Protection from Infection: Infection Pressure vs. Natural Boosting

No infection: Protected Persistent protection Persistent natural boosting Continued infection pressure No infection: No infection pressure Not protected No natural boosting No infection pressure

Example: China – Infant vaccination – No catch-up vaccination – More HBsAg/HBeAg among adults Example: Alaska – Infant vaccination – Catch-up of all susceptibles – Less HBsAg/HBeAg among adults Example: U.S. and W Europe – low endemicity

Protection from Infection: Infection Pressure vs. Natural Boosting

No infection: Protected Persistent protection Persistent natural boosting Continued infection pressure No infection: No infection pressure Not protected No natural boosting No infection pressure Exposure: sexual, HCW, move to high endemic area No infection??? Infection???

Ongoing CDC Long-Term Protection and Booster Dose Studies

Palau (high endemic)

• Adolescents (9-10 yrs) vaccinated at birth with

recombinant vaccine Alaska (Anchorage, low endemic)

• Children (5-7 yrs) and adolescents (10-13 yrs)

vaccinated at birth with recombinant vaccine Alaska (villages, high endemic) (Vax Demo)

• 22-23 year follow-up of infants (>6 months),

children, and adults vaccinated with plasma- derived vaccine