1. Conschetta Wright, RN, MPH Dr. Richard Sterling, MD
Determinants of Hepatitis B Vaccination Among Adults in the United States: NHANES
Good morning
CSTE fellow with the CDC el paso Q station and Texas department of state health services region 9/10 in El Paso, TX
Research completed as graduate student at Virginia Commonwealth University
Background
Objectives
Methods
Results
Discussion
Conclusions
Conschetta Wright, RN, MPH
Dr. Richard Sterling, MD

2. Background
Potentially life-threatening liver infection caused by the hepatitis B virus (HBV)
Estimated 1.3 million people living with chronic HBV in the US
Liver infection caused by hep b virus
1.3 million in US chronically infected

3. Background Vaccine licensed in 1982
Recommended vaccination for adults at increased risk for HBV infection but coverage remained low
High burden of HBV-related disease resulting from infections acquired during childhood
Soon after hepatitis B vaccine was licensed in 1982, ACIP recommended vaccination for adults at increased risk for HBV infection (212). However, the recommendations were not widely implemented, and coverage among adults at risk for HBV infection remained low. By the early 1990s, the difficulty in vaccinating adults at risk for HBV infection and the substantial burden of HBV-related disease resulting from infections acquired during childhood indicated that additional hepatitis B vaccination strategies were needed (213,214). In 1991, recommendations for vaccination of unvaccinated adults at high risk for HBV infection became part of the national strategy adopted by ACIP and professional medical organizations to eliminate HBV transmission in the United States (3). However, hepatitis B vaccine still is not offered routinely in medical settings serving adults, and a substantial number of adults at risk for HBV infection remain unvaccinated.

4. Background Immunization strategy
Universal vaccination of infant beginning at birth
Routine screening of all pregnant women for hepatitis B surface antigen (HBsAg) and immmunoprophylaxis of infants born to HBsAg positive women and infants born to women with unknown HBsAg status
Advisory Committee on Immunization Practices (ACIP)

5. Background Immunization strategy (cont.)
Routine vaccination of previously unvaccinated children and adolescents
Vaccination of previously unvaccinated adults at increased risk of infection

6. Background
Adult transmission occurs principally among unvaccinated adults with risk behaviors for HBV transmission
Heterosexuals with multiple sex partners
Injection-drug users (IDUs)
Men who have sex with men (MSM)
Horizontal transmission
For adults the most common modes of transmission are among people with multiple sex partners, injection drug users, MSM, and horizontal transmission
Horizontal transmission = the spread of an infectious agent from one person or group to another, usually through contact with contaminated material, such as sputum or feces.
Other high risk groups include patients receiving hemodialysis and people with occupation risks like health care workers

7. Background Healthy People 2010 Goal 14-3: Reduce hepatitis B
Goal 14-28: Increase hepatitis B vaccine coverage among high-risk groups
14-3 to reduce hep b by targeting vaccination programs at adolescent and high risk adults; include clinic that treat STD, correctional facilities, drug treatment clinics, HIV clinics; and follow up with all household/sexual contacts for those who are hep b surface antigen positive
Health People 2010 mentions 2 goals about HBV
14-28 to increase vaccination coverage among high risk groups: These risk groups include the following: hemodialysis patients, men who have sex with men, incarcerated persons, health care and public safety workers who have exposure to blood in the workplace, persons with a history of sexually transmitted diseases or multiple sex partners, injection drug users, and household and sex contacts of HBV-infected persons. Baseline vaccination data for these groups ranged from 9 (MSM) to 70% (health care workers)
Target 60 (MSM)-98 (HCW) percent
Healthy People Goal 14-3
To reduce HBV transmission in the United States by 2010, vaccination programs must be targeted to adolescents and adults in high-risk groups. The primary means of achieving high levels of vaccination coverage in groups with behavioral risk factors for HBV infection is to identify settings where these individuals can be vaccinated. Such sites include clinics that treat sexually transmitted diseases (STDs), correctional facilities (juvenile detention facilities, prisons, jails), drug treatment clinics, and community-based HIV prevention sites. The primary means of achieving high levels of vaccine coverage among household and sex contacts of the estimated 1.25 million persons in the United States with chronic HBV infection are programs that offer follow-up for all hepatitis B surface antigen (HBsAg)-positive persons reported to State and local health departments.
Routine infant vaccination eventually will produce a highly immune population sufficient to eliminate HBV transmission in the United States. However, high rates of acute hepatitis B continue to occur, with an estimated 65,000 cases in Most cases occur in young adult risk groups, including persons with a history of multiple sex partners, men who have sex with men, injection drug users, incarcerated persons, and household and sex contacts of persons with HBV infection. Investigation of reported cases of acute hepatitis B indicates that as many as 70 percent of these individuals previously had been seen in settings, such as drug treatment clinics, correctional facilities, or clinics for the treatment of STD, where they could have received vaccine.
14-28.
Increase hepatitis B vaccine coverage among high-risk groups.
Target and baseline:
Objective
Increase in Hepatitis B Vaccine Coverage in High-Risk Groups
1995 Baseline
2010 Target
Percent
14-28a.
Long-term hemodialysis patients 35 90
14-28b.
Men who have sex with men 9 60
14-28c.
Occupationally exposed workers 71 98
Target setting method: 157 percent improvement for long-term hemodialysis patients; 567 percent improvement for men who have sex with men; 38 percent improvement for occupationally exposed workers.
Data sources: Young Men’s Survey, CDC, NCHSTP; Annual Survey of Chronic Hemodialysis Centers, CDC, NCID, and HCFA; periodic vaccine coverage surveys, CDC, NCID.
Hepatitis B vaccination has been recommended for persons with risk factors for hepatitis B virus infection since the vaccine was first licensed in These risk groups include the following: hemodialysis patients, men who have sex with men, incarcerated persons, health care and public safety workers who have exposure to blood in the workplace, persons with a history of sexually transmitted diseases or multiple sex partners, injection drug users, and household and sex contacts of HBV-infected persons. While data currently are not collected for inmates in long-term correctional facilities, it is recommended that prison officials should consider undertaking screening and vaccination programs directed at inmates with histories of high-risk behaviors.

8. Objectives
To estimate the prevalence of vaccination and HBV infection status in adults
To evaluate the trend in self-reported vaccination and seroprevalence for Hepatitis B for this population
To assess the association between vaccination rates, seroprevalence, demographic, and socioeconomic characteristics
Three objectives:
how many adults are vaccinated or have immunity
Are those who report vaccination actually immune due to the vaccination
What demographic and socioeconomic factors play a role in self reported vaccination status

9. Methods
National Health and Nutrition Examination Survey (NHANES)
Inclusion criteria
Adults aged years who completed household interview and laboratory component
Answered all questions related to sexual practices and illegal drug use
Provided specimens for HBV, HCV, HIV
National Health and Nutrition Examination Survey (NHANES)
Adults aged years who contributed data via the household interview and laboratory component
Most questions regarding sexual practices and illegal drug use were limited to this age range
Answered all questions related to sexual practices and illegal drug use
Provided specimens for HBV, HCV, HIV

10. Methods Outcome variables
“Have you ever received the 3-dose series of the hepatitis B vaccine?”
Vaccination status verified through serologic markers: HBsAg, anti-HBc, and anti-HBs
Logistic regression model weighted to consider the complex weighting scheme and adjusted to the 2000 US census population (SAS 9.2)
Two outcome variables
“Have you ever received the 3-dose series of the hepatitis B vaccine?”.
Those who answered yes to “less than three doses” and “at least three doses” were classified as vaccinated.
Vaccination status was also verified through serologic markers: HBsAg (Hepatitis B surface antigen ), anti-HBc (Antibody to hepatitis B core antigen ), and anti-HBs (Antibody to hepatitis B surface antigen ).
Serologic status was classified as vaccinated (immune due to Hepatitis B vaccination), unvaccinated (susceptible), and history of Hepatitis B infection (immune due to natural infection)
Determinants: age, gender, race/ethnicity, location of birth, education level, marital status, age at first intercourse, sexual orientation, household size, annual household income, insurance status, health care access, health status, history of alcohol abuse, current tobacco use, high risk behaviors
HIGH RISK BEHAVIORS ONLY - - sexual orientation, sexual practices, MSM, IDU, + for HBV, HCV, HIV
did not analyze data on occupational or other health risks (dialysis)
Logistic regression model weighted to consider the complex weighting scheme and adjusted to the 2000 US census population
We used logistic regression model to obtain odds ratios and their 95% confidence intervals for the association between predictor variables and vaccination status after adjusting for all potential confounding factors. SAS version 9.2 was used to produce the appropriate estimates and standard errors.

11. Interpretation of Hepatitis B Serologic
Vaccinated
Unvaccinated
History of past infection
HBsAg -
anti-HBc +
anti-HBs
Serologic status was classified as vaccinated (immune due to Hepatitis B vaccination), unvaccinated (susceptible), and history of Hepatitis B infection (immune due to natural infection)
Vaccination status was also verified through serologic markers: HBsAg (Hepatitis B surface antigen ), anti-HBc (Antibody to hepatitis B core antigen ), and anti-HBs (Antibody to hepatitis B surface antigen ).
Interpretation of Hepatitis B Serologic Test Results
CDC

12. Results Sample size 50.2% male 30.5 % of all adults vaccinated
Vaccinated n=2,220 (weighted=30,276,510)
Unvaccinated n=5,053 (weighted=68,986,610)
50.2% male
30.5 % of all adults vaccinated
Total unweighted sample size = 7273
Total weighted sample size = almost 100 million Americans
Half male/female
15 million adults at risk of HBV
But High risk adults were vaccinated at the same rate as all adults

13. Results Estimated 15 million adults at risk of HBV
32.4% of high risk adults vaccinated

14. Results Factors associated with receipt of hepatitis B vaccination
Vacc.
Unvacc.
Odds Ratios %
Crude (95% CI)
Adjusted (95% CI)
Gender
Male
25.5
74.5
0.6
(0.56, 0.69)
(0.57, 0.73)
Female
35.6
64.4
1.0
Age
20-29
46.9
53.1
3.5
(2.98, 4.21)
3.7
(2.98, 4.56)
30-39
32.4
67.6
1.9
(1.61, 2.30)
(1.53, 2.24)
40-49
1.4
(1.15, 1.63)
1.3
(1.10, 1.54)
50-59
20.0
80.0
Logistic regression (adjusted for all confounders)
age, gender, race/ethnicity, location of birth, education level, marital status, age at first
intercourse, sexual orientation, household size, annual household income, insurance status,
health care access, health status, history of alcohol abuse, and current tobacco use.
Statistically significant results highlighted in yellow
Males 40% less likely to be vaccinated
Younger people were up to 3 times more likely to be vaccinated
African Americans and people of other races were 20-40% more likely to be vaccinated

15. Results Factors associated with receipt of hepatitis B vaccination
Vacc.
Unvacc.
Odds Ratios %
Crude (95% CI)
Adjusted (95% CI)
Race/ethnicity
Non-Hispanic White
29.8
70.2
1.0
Non-Hispanic Black
35.1
64.9
1.3
(1.10, 1.48)
1.2
(1.03, 1.43)
Hispanic
29.1
70.9
(0.82, 1.14)
1.1
(0.92, 1.35)
Other
Marital status
38.2
61.8
1.5
(1.15, 1.86)
1.4
(1.06, 1.83)
Never married
41.4
58.6
1.8
(1.58, 2.11)
(1.04, 1.50)
Married
27.9
72.1
Previously married
27.4
72.6
(0.80, 1.18)
(0.87, 1.36)
Living with partner
32.2
67.8
(0.99, 1.52)
(0.79, 1.31)

16. Results Factors associated with receipt of hepatitis B vaccination
Vacc.
Unvacc.
Odds Ratios %
Crude (95% CI)
Adjusted(95% CI)
Education
Less than H.S.
22.6
77.4
0.54
(0.46, 0.65)
0.51
(0.41, 0.64)
Completed H.S.
23.8
76.3
0.58
(0.50, 0.67)
0.56
(0.47, 0.66)
Some college +
35.0
65.0
1.00
Household size
1-3 people
29.3
70.7
4-6 people
32.6
67.4
1.17
(1.02, 1.34)
1.24
(1.08, 1.44)
7 + people
30.8
69.2
1.07
(0.76, 1.51)
1.27
(0.82, 1.95)
Those were never married were 25% more likely to be vaccinated
Those with less than HS education were less likely to be vaccinated
Household size did impact vaccination likelihood but only significant for those with 4-6 people per household

17. Results Factors associated with receipt of hepatitis B vaccination
Vacc.
Unvacc.
Odds Ratios %
Crude (95% CI)
Adjusted (95% CI)
Current health insurance coverage
Yes
31.2
68.8
1.2
(1.01, 1.37)
(0.99, 1.45) No
27.8
72.3
1.0
Source of usual care
31.4
68.6
1.3
(1.11, 1.57)
1.4
(1.11, 1.64)
25.8
74.2
People who had a source of usual care were more likely to be vaccinated

18. Results Factors that had no significant impact on vaccination status
Country of birth
Income
Household size greater than 7 people
Self reported health status
History of smoking
History of alcohol abuse
Age at first intercourse
High risk behaviors
Not statistically significant factors included
Country of birth
Age at first intercourse
Household size greater than 7 people
Self reported health status
Smoking status
Risk behaviors
Income
History of alcohol abuse

19. Results Distribution of participants based on their self report vaccination status and serostatus
Self reported status
Serostatus
All 3 doses
At least 1 dose
No doses %
Vaccinated
46.9
23.1
4.5
Unvaccinated
49.0
73.4
92.0
History of Hepatitis B infection
4.2
3.5
47% of adults who reported receiving all three doses of the vaccine were seropositive for vaccination
4.5% of adults who reported never receiving the vaccine were seropositive for vaccination.
Some factors that contribute to decreased vaccination response or negative serostatus
smoking
Obesity
Genetics
Stress
immune suppression
loss of antibodies
non-response accounts for about 10-25% of cases.
Up to 50% of those vaccinated lose their antibodies within a few years.
undetectable anti-HBs levels do not necessarily indicate loss of immunity.
If exposed to HBV, the immune memory initiates an anamnestic response that
prevents acute and chronic infection.
few studies have followed the immunologic memory in adults who had lost protective antibodies after vaccination. One study found that participants
who lost their anti-HBs still had immunologic memory that was able to trigger anti-HBs
production when revaccinated.37 Other studies suggest that immunologic memory in healthy
individuals last 5-12 years This is also shown in studies that followed high-risk vaccinees.36

20. Hepatitis B Vaccination Rates for Adults based on Risk
Results
Hepatitis B Vaccination Rates for Adults based on Risk
Vaccination rate increased by almost 15 percentage points between and
Increase change of 43% for high risk adults
Increase change of 40% for all adults

21. Discussion All Adults 47% of 20-29 year olds reported vaccination
Higher vaccination rates among young adults commonly attributed to childhood and adolescent vaccination programs

22. Discussion All Adults
Non-Hispanics are more likely to be vaccinated than Hispanics
There are higher vaccination rates among those with more than a high school education
(NHIS, 2004)

23. Discussion High Risk Adults
No national vaccination program for adults like for children
Methods may increase adult vaccination coverage
Reminders to health care providers
Patient reminder systems
Comprehensive health centers for high risk adults
95% of acute HBV cases occur in adults;
High risk adults remain under-immunized because there is not national vaccination program for adults like the programs for children
Methods used that have shown increased in adult vaccination coverage include reminders
to health care providers, comprehensive health centers for high risk adults, and patient reminder
systems.7 Insufficient evidence is available regarding the effectiveness of in-clinic patient
education, providing family or patient incentives, or the implementation of state and federal
laws.31 In 2005, the ACIP recommended strategies to improve vaccination for adults at risk for
hepatitis B, by increasing access at facilities that have a high proportion of persons more likely to
be at risk.9 These sites include STD/HIV testing and treatment facilities, correctional facilities,
and drug-abuse treatment facilities.

24. Discussion Vaccination Serostatus
Social desirability
Recall bias
Factors that contribute to decreased vaccination response or negative serostatus
Smoking
Obesity
Genetics
Stress
Immune suppression
Loss of antibodies
Factors contributing to decreased vaccination response or negative serostatus
Smoking
Obesity
Genetics
Stress
Immune suppression
Loss of antibodies
The 3-dose hepatitis B vaccine series produces a protective antibody response in
approximately 30%-55% of healthy adults less than 40 years old after the first dose, 75% after
the second dose, and greater than 90% after the third dose.9 For adults over the age of 40
protective antibody response declines below 90% and is only 75% for adults over 60 years old.9
Our study found that less than 50% of adults who reported receiving all three doses were
seropositive for vaccination. Of those who reported receiving at least one dose, 27% already
showed full protection from HBV. Among adults who received no doses of the vaccine, 4.5%
had a seropositive vaccination status. About 3.5% of adults showed immunity due to history of
HBV infection.
Many factors contribute to decreased vaccination response or negative serostatus
including smoking, obesity, genetics, stress, immune suppression, and loss of antibodies.9,35-39
Other behavioral and psychological factors also influence immune functions. Studies have shown
that non-response accounts for about 10-25% of cases.9 Up to 50% of those vaccinated lose their
antibodies within a few years. However, undetectable anti-HBs levels do not necessarily indicate
loss of immunity. If exposed to HBV, the immune memory initiates an anamestic response that
prevents acute and chronic infection.37 While most studies regarding long term immune response 22
have examined children and adolescents, a few studies have followed the immunologic memory
in adults who had lost protective antibodies after vaccination. One study found that participants
who lost their anti-HBs still had immunologic memory that was able to trigger anti-HBs
production when revaccinated.37 Other studies suggest that immunologic memory in healthy
individuals last 5-12 years This is also shown in studies that followed high-risk vaccinees.36
Another factor that affects seropositivity rate is knowledge of vaccination status. In the
United States, research on the validity of self-reported vaccination status is primarily limited to
elderly adults or the pneumococcal and influenza vaccines. A study conducted among high risk
adults in Australia found that 52.2% of those who believed they were protected were not
immune.32 Previous studies on self-reports of HBV exposure and vaccination among high risk
adults have found that results were specific, but not sensitive.33 One study in Switzerland found
that knowledge of HBV vaccination status was associated with gender, language and dietary
attitudes.34 Researchers and health care providers should be cautious in using such self-reports.
However, it is also important to properly document when patients receive an immunization and
to test serostatus after the series completion so they do not receive unnecessary boosters.35-37,39
The analysis of self-report and serostatus for this data are unpublished at this time.

25. Discussion Limitations Limited to adults age 20-59
Representative of non-institutionalized population
Did not include estimates on other high risk groups
Underreporting , non-response, and recall bias
limited to adults aged who provided responses to sensitive questions regarding sexual practices, illegal drug use, also
provided laboratory examination data for HBV, HCV, and HIV
did not include estimates on other high risk participants such as people receiving hemodialysis and health care workers
Representative of non-institutionalize population. Does not include incarcerated persons, homeless, military service members, and residents in long-term care facilities.
(hemodialysis, health care workers, incarcerated)
Underreporting , non-response, and recall bias related to sensitive questions
possibility that high-risk populations were underestimated due to the lower response rates to sensitive questions. The potential of
underestimating high risk adults supports the conclusion that a substantial proportion of the US
population is at risk of HBV.
Although the question regarding hepatitis B vaccination status provided a description of
the vaccine and its recommendations, it is possible that respondents confused their vaccination
status with others collected in the survey including Hepatitis A, pneumococcal, and influenza.
However, since these vaccinations are administered to different risk groups, it is unlikely to
occur.

26. Conclusions
Being high risk was not associated with higher odds of vaccination
Rise in vaccination rates among adults is attributed to childhood immunization strategies (cohort effect)

27. Conclusions Groups less likely to be vaccinated Older adults Males
High school education or less
No source of usual care

28. Conclusions
Create a means for identifying those at risk of HBV and those already vaccinated
Educate and vaccinate adults with programs similar to children’s immunizations
Improve adult awareness about vaccinations that may have already received
and to

29. Acknowledgements Dr. Richard Sterling Dr. Miguel Escobedo
Staff at El Paso Quarantine Station
Staff at Texas Department of State Health Services Region 9/10

30. Thank You
Questions

31. Selected References
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Centers for Disease Control and Prevention. Hepatitis B FAQs for Health Professionals. Hepatitis B Available at:
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Williams IT, Boaz K, Openo Kp, et al. Missed opportunities for hepatitis B vaccination in correctional settings, sexually transmitted disease (STD) clinics, and drug treatment programs [Abstract 1031]. Presented at the 43rd Annual Meeting of the Infectious Diseases Society of America, San Francisco, CA; October 5--9, 2005.
Jose B, Friedman SR, Flom, PL. Self-report validity of hepatitis B infection and vaccination among youth. Paper presented at American Public Health Association Annual Meeting. November 11-16, Boston, MA.
Lee C, Naguel C, Gyurech D, et al. Awareness of vaccination status and its predictors among working people in Switzerland. BMC Public Health. 2003; 3:18.
Bauer T, Jilg W. Hepatitis B surface antigen-specific T and B cell memory in individuals who had lost protective antibodies after hepatitis B vaccination. Vaccine. 2006;24:
Vellinga A, Bruckers L, Weyler JJ, et al. Modelling long-term persistence of hepatitis B antibodies after vaccination. J Med Virol. 1999;57(2):100-3.