Cohort Study of Antibody Levels in a Yupik Eskimo Population 30 Years after Hepatitis B Vaccine Vax Demo 30 Michael Bruce MD MPH Arctic Investigations Program Anchorage, Alaska Centers for Disease Control and Prevention
Hepatitis B A double-stranded DNA virus Transmission: Person to person Mother to baby Child to child Sexual contact Contaminated blood or needles Causes Liver infection Sometimes for life Cirrhosis, Cancer Prevention Hepatitis B is preventable with the currently available safe and effective vaccine
Hepatitis B 2 billion people worldwide have been exposed to hepatitis B virus (HBV) 378 million are chronically infected At risk for severe disease and death 600,000 people die every year due to the acute or chronic consequences of hepatitis B
Hepatitis B in Alaska Natives 1970 s Highest rates of hepatitis B in the United States Among the highest rates in the world High rates of liver cancer and cirrhosis
Hepatitis B in Alaska Natives 1970 s Highest rates of hepatitis B in the United States Among the highest rates in the world High rates of liver cancer and cirrhosis Norton Sound Yukon Kuskokwim Delta
Alaska HBV Vaccine Demonstration Project (Vax Demo) 1530 children* and adults immunized in 1981 who responded % with anti-hbs levels > 10 miu/ml 5 years: 81% (JAMA 1989) 7 years: 74% (Arch Int Med 1991) 15 years: 66% (Ann Int Med 2005) 22 years: 60% (JID 2009) * 6 months and older
Vax Demo 30 Study Questions Are all persons who received the hepatitis B vaccine 30 years ago still protected? If not, what are the risk factors for lack of protection?
Investigation Team Liver and Hepatitis Program, Division of Community Health Services, Alaska Native Tribal Health Consortium CDC, Anchorage, Alaska CDC, Atlanta, Georgia YK Delta Health Corporation Norton Sound Health Corporation
Cohort Study Vax Demo 30 Study Design The Cohort: group that you are following over time Serologic survey & booster dose Participant questionnaire Age, sex, vaccine history, residence etc. Chart review Vaccine history, underlying medical conditions
Vax Demo 30 Methods Study Setting 13 of the original 16 villages in the YK Delta and Norton Sound Eligible Study Population All village residents of 13 villages who participated in the original study in 1981 who responded to the full series of plasma-derived Hepatitis B vaccine Excluded persons who received a booster dose of vaccine anytime over the past 30 years
How Did We Calculate Sample Size Needed for The Study? Alaska death records were used to estimate the proportions of each age group who may have died Based on extrapolations from the 22-year follow-up: We expected ~450 persons in this 30-year follow-up study We estimated that 125 persons would have hepatitis B antibodies and would be eligible for a HB vaccine dose We needed 110 participants in the booster study in order to detect that 90% will have protective antibodies 10 to 14 days after vaccination
Approval Process Approvals obtained from CDC and Alaska Area IRB for the study Approvals by the YK Delta Health Corp and Norton Sound Health Corp Approvals by the Tribal Councils of each participating village
Vax Demo 30 Methods Visit 1 - initial blood draw, assess anti HBs levels Visit 2 - booster dose to persons with anti-hbs <10 MIU/mL Visit 3 - post booster dose draw 35 separate trips to villages!
Vax Demo 30 Results 435 persons recruited 50% had protective antibodies at 30 years
435 persons recruited Vax Demo 30 Results 50% had protective antibodies at 30 years Having antibodies at 30 years was associated with a strong antibody response after initial vaccine series No association between protective antibody level and: Gender, BMI, Diabetes, or things that could result in a poor immune response* *Diagnosis of cancer, radiation therapy, organ transplant or use of immune modulating medications in the past 2 years
anti-hbs GMT (miu/ml) Antibody Decline 10000 1000 100 10 1 0 5 10 15 20 25 30 Years Since Primary HBV Series
Vax Demo 30 Visit 3 (Booster dose follow-up) A booster dose was given only to persons who had anti-hbs < 10 miu/ml
Anti-HBs levels > 10 miu/ml Proportion who Responded to booster dose at 30 years 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 88% responded to booster dose 88% Cohort
Limitations Participants in our study received the primary hepatitis B vaccination series with the plasmaderived vaccine, which is no longer used in the United States We assumed that an anti-hbs level > 10 miu/ml was protective based on the original hepatitis B vaccine studies by Szmuness, et al. (1980) and Francis, et al. (1982)
Anti-HBs levels > 10 miu/ml Vax Demo 30 Summary Antibodies have continued to decline over the past 30 years 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 81% 74% 66% 60% 50% 5 Years 7 Years 15 Years 22 Years 30 Years
Vax Demo 30 Summary 50% had anti-hbs level > 10 miu/ml at 30 years 88% boosted to > 10 miu/ml Overall, 94% had evidence of immunity: either boosted or had anti-hbs > 10 miu/ml at 30 years Higher anti-hbs after primary series was associated with protective antibody levels at 30 years
Vax Demo 30 Conclusions/Recommendations Our study findings likely apply to populations currently using the recombinant vaccine ACIP closely follows data from the Alaska cohort No recommendation for booster at this time Protection by primary immunization with plasma-derived Hep B vaccine lasts at least 30 years Booster doses not needed
Steps in This Study Apply for and get money Study protocol/data collection forms created Approval from IRBs, Health Corporations, Tribal Councils Power calculations done, sample size identified Staff identified to perform the study Recruitment letters to all potential participants Chart reviews 35 village trips blood draws and questionnaire Data collected Analysis Letters back to study participants with results Dissemination of findings
Acknowledgements Arctic Investigations Program, CDC Richard Baum Steve Bentley Dana Bruden Lisa Bulkow Tom Hennessy Debby Hurlburt Tony Kretz Debbie Parks Greg Raczniak Lisa Rea Karen Rudolph Gail Thompson Michele Toomey Lyn Zanis Alaska Native Tribal Health Consortium Brian McMahon Lisa Townsend Brenna Simons Mary Snowball Sue Negus Jim Gove Yukon Kuskokwim Health Corporation Joseph Klejka Norton Sound Health Corporation David Head Division of Viral Hepatitis, CDC Dale Hu Phil Spradling
Thank you!