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Burden of disease
•Morbidity trends
-What has the universal birth dose accomplished compared to more targeted measures?
•Vertical (perinatal mother- to-child) transmission
-Targeted vaccination of at -risk infants vs. the universal birth dose?
•Horizontal transmission in childhood
- What evidence exists and has the risk to most American children been overstated?
Surveillance data: Acute hepatitis B cases are the longest and
most consistently reported metric of morbidity
MMWR 1991,
“… selective vaccinationof persons with identified risk factors … has notlowered the incidencehepatitis B.”
Data from the National Notifiable Diseases Surveillance System
•Increased blood screening for HBsAg
•Sharp declines in post transfusion hepatitis (PTH)
•Cleaner practices in dialysis
•Widespread adoption of safer sexual practices
•Needle exchange
•Screening and case management for HBsAg+ mothers
Universal birth dose contribution to acute case decline is likely very small.Sources of decline in acute hepatitis B cases
Chronic case data raise new questions
NNDSS began collecting new chronic case data in 2003
NNDSS = National Notifiable
Diseases Surveillance System
Increasing new chronic cases of hepatitis B
in older adults after 2020
Upticks after 2020
also seen in adults30-39, 40- 49, and
50-59 years old.
Data from National Notifiable
Diseases Surveillance System
Infant morbidity
Data from the National Notifiable Diseases Surveillance SystemCDC model of
perinatal infections:
Year # of Cases
2015 : 952 (Ko et al. 2016)
2023: 601 (CDC staff)36 7
•Acute cases have declined sharply from peak in 1985 for multiple reasons.
•New chronic cases have been increasing among older adults after 2020.
•Perinatal cases are down to 36 and 7 in 2015 and 2023, respectively, but
CDC model predicts many more cases.Summary of hepatitis B morbidity trends
Modeling perinatal infections
Estimate begins by tabulating how many mothers are HBsAg+,
i.e., chronic carriers of hepatitis B virus
Majority of HBsAg+ mothers in US are foreign -born
Koneru et al., 2019, Table 2 excerpts; estimated for 2015
Maternal country
of birthTotal Births HBsAg+ prevalence
(%)Estimated births to
HBsAg+ women
Total 3,978,500 20,678 (15,625 -30,640)
US-born total 3,070,700 0.17 (0.07 -0.39) 8,296 (4,031 -17,100)
Non-US-born
Total 857,105 11,981 (11,395 -12,762)
Africa 64,228 3.42 (3.27 -3.96) 2,197 (2,100 -2,543)
Asia
East Asia 66,384 8.73 (8.52 -8.93) 5,795 (5656 -5928)
Southeast Asia 62,044 3.92 (3.76 -4.08) 2,432 (2,333 -2531)
Modeling perinatal cases
based on Ko et al., 2016 model
Births to HBsAg+
women
~ 18,000
Suscep tib le
I nfantsMothe r
HBe Ag +M other HBe Ag -F = 70% 1-F = 30%
T ransmission rate K+ = 90%T ransmission rate K- = 5-20%Perinatal
I nfections
Chronic rate L = 90%Chronically
infected infantsChang et al., 2007;
Ko et al., 2016Mothe r
HBe Ag -
PEPUpdated input from C DC
in response to A C I P query .
PEP (post exposure prophylaxis)
PEP includes hepatitis B vaccine and HBIG at birth
HBsAg+ mothers
screened 88%
I nfants with
timely PEP at
birth 98.5%I nfants with no
PEP at birth
1.5%I nfants with no
PEP at birth
20.5%
M other HBe Ag -
Suscep tib le
infants 9%HB sA g+ mothers
unscreened 12%
8% failed
PEPI nfants with
timely PEP at
birth 79.5%
8% failed PEP
601 chronically infected infants in 2023 but NNDSS reports only 7 !
Updated inputs from
C DC in response to ACIP q u e r y.
Suscep tib le
infants 27%
Perinatal (mother -to-child) transmission summary
•Risk is isolated to ~0.5% of pregnancies, mainly immigrants from high endemicity
countries.
- Add hep B to immigrant medical examination.
•Improve screening measures in prenatal care and delivery. PEP is effective in
preventing transmission!
•CDC’s Ko et al. model may overestimate perinatal cases.
-U.S. infants are not all equally at risk - many mothers intentionally decline birth dose.
- Other inputs (screening rate, PEP failure rate) may be too pessimistic.
•Little published evidence documenting horizontal transmission.
•A single modeling study, Armstrong et al. [2001], raised
concerns that all young children in the U.S. are at significant
risk for horizontal transmission of hepatitis B .
•The model estimated ~ 16,000 cases/yr in children age 0- 9
years old in the pre -vaccine era due to horizontal transmission,
half in Asian immigrants, half in the general U.S. population.Modeling horizontal transmission in childhood
Armstrong G, Mast E, Wojczynski M, Margolis H. 2001. Childhood Hepatitis B Virus Infections in the
United States Before Hepatitis B Immunization, Pediatrics 108(5), 1123 -1128.
Armstrong 2001 modeled HepB horizontal transmission based on
seropositivity v. age in NHANES and among Asian immigrants
Independent calculation of Armstrong linear fits
Without the assumed
perinatal infection (Po),
seropositivity is significantly correlated
with age only for the
Southeast Asian model.
NHANES seropositivity
v. age correlation is
statistically
insignificant with a
natural intercept of
0.22% (perinatal).
Comparison of 2 SE Asian Groups
Characteristic Louisiana (Vietnamese) Wisconsin (Hmong)
All, families, US -born children N =1403, 227, 679 N=1183, 161 ,429
HBV markers used, past or present
infectionAnti -HBc Anti -HBc or HBsAg+
HBV markers used, chronic HBsAg+, anti -HBsIgM - HBsAg+
US born, % any HBV (% chronic) 16%, (4%) 14% (6%)
Asian -born, % any HBV (% chronic) 59% (11%)* (inferred) 72% (19%)**
% of children with HBsAg+ moms 9% (60/656) 16% (69/429)
Reference Mahoney et al., 1995 Hurie et al., 1992
* Nguyen and Trevison . 2020. Vietnam a country in transition: BMJ doi:10.1.1136/bmjnph -2020- 000069
does not list hepatitis B among the leading causes of death in Vietnam .
** In the Asian -born Hmong, 86% -97% of those aged 15 to >40 years had HBV blood markers.
Horizontal transmission in childhood?
•Horizontal transmission is rare among most U.S. children …
•Although it can occur in some high- risk immigrant families
•Armstrong et al.’s 16,000 cases/year are not supported by NNDSS data
~ 400 acute cases/year
pre -UBD
NNDSS = National NotifiableDiseases Surveillance System
The Informed Consent Action Network (ICAN) asked the CDC
for “documentation sufficient to reflect any case(s) of
transmission of Hepatitis B in an elementary, middle, or
high school setting. ”
The CDC responded, “A search of our records failed to
reveal any documents pertaining to your request. ”Horizontal transmission in childhood – final note
https://icandecide.org/article/cdc -concedes -it-lacks -any-proof- of-hepatitis -b-being -transmitted -in-a-
school -setting/
Summary of burden of disease
Mixed trends in hepatitis B morbidity 34 years after the Universal
Birth Dose
- Acute cases have declined sharply for multiple reasons.
- New chronic cases are increasing since 2020 in adults over 30.
- Reported perinatal cases are in the single to low double digits thanks to
P E P.
Models yield larger estimates than surveillance data - cross
checks useful
- Ko et al. model may overstate perinatal chronic cases.
- Horizontal transmission among young children is rare and was strongly
overstated by the Armstrong et al. model.
Efficacy and Waning Immunity
Many studies show reduced antibody levels over time following hepatitis B
vaccination, especially when vaccination begins in infancy or early childhood.
Age (years) at the time
of:Anti-HBs ( mIU/ml )
Before booster doseAnti-HBs ( mIU/ml)
After booster dose*
Booster Primary series GMC % with ≥ 10 (N >10/Ntotal)GMC % with ≥ 10 (N >10/Ntotal)
< 40 < 5 6.8 32% (19/59) 98.2 83% (25/30)
35 to 39 5 to 9 24.9 61% (30/49) 134.2 94% (16/17)
40 to 49 10 to 19 22.8 64% (58/90) 275.7 89% (17/19)
≥ 50 ≥ 20 8.5 40% (18/45) 179.4 89% (17/19)Native Alaskans vaccinated for hepatitis B between
ages 5 -19 years had highest titers 30 years later
Bruce et al. 2016. Protection and antib od y levels after Hep atitis B vaccine: Results of a 30 -year follow -up study and response t o a
booster dose, JID 214: 16- 22. (Tables 1,3)* B ooster dose was given to 85 people with titers < 10 m IU/ml as well as an
additional N=36 people who were not boosted in the 22 -year follow -up.
By age 16 -19 years, most US children vaccinated as infants had low
antibodies, but most responded well to a booster dose
Middleman et al. 2014. Duration of protection after infant Hep atitis B vaccination series, Ped iatrics 133(6) .Gr o u p 1 : Fir s t
vaccine ≤ 7 days Gr o u p 2 : Fir s t vaccine ≥ 4 weeks Group 1, % Group 2, % Total, % P value
1st dose
≤7 d ays1st dose
≥ 4 weeks
Baseline
seroprotection16.7 % 33.9 % 24.1 % < 0.0001
Postchallenge
dose seroprotection90.4 % 93.9 % 91.9 % 0.2T able 2 L evels of Seroprotection (anti -HBs Tite r ≥ 10 IU/m L) b y Group
Waning immunity also seen among teenagers vaccinated as
infants in NHANES data
Cohorts most likely
vaccinated as infants
Data compiled by CDCHepatitis Division
•Anti -HBs titers wane the most rapidly in children who begin
their primary series as infants, especially as newborns.
•While most vaccinees respond well to a booster dose, some
of those vaccinated as infants may lack protection when they
enter their years of highest risk for acquiring hepatitis B.Waning immunity summary and concluding thoughts
References
Armstrong G, Mast E, Wojczynski M, Margolis H. 2001. Childhood Hepatitis B Virus Infections in the United States
Before Hepatitis B Immunization, Pediatrics 108(5), 1123 -1128
Bruce et al. 2016. Protection and antibody levels after Hepatitis B vaccine: Results of a 30 -year follow -up study and
response to a booster dose, The Journal of Infections Diseases, 214(1 July) 16 -22
Chang, M -H. 2007. Hepatitis B virus infection. Seminars in Fetal & Neonatal Medicine (2007) 12, 160e167.
Hurie MB, Mast EE, Davis JP. Horizontal transmission of hepatitis B virus infection to United States -born children of
Hmong refugees. Pediatrics . 1992;89:269– 273
Klevens RM, Liu S, Roberts H, Jiles RB, Holmberg SD. 2014. Estimating acute viral hepatitis infections from nationally
reported cases. Am J Public Health, 104(3): 482 -487
Koneru, A. 2019. Estimating Annual Births to Hepatitis B Surface Antigen –Positive Women in the United States by
Using Data on Maternal Country of Birth Public Health Reports 134(3)
Ko SC et al. Estimated Annual Perinatal Hepatitis B Virus Infections in the United States, 2000 -2009. J Pediatric Infect
Dis Soc. 2016 Jun;5(2):114- 21
Mahoney FJ, Lawrence M, Scott C, et al. Continuing risk for hepatitis B virus transmission among Southeast Asian
infants in Louisiana. Pediatrics . 1995;96:1113– 1116
McQuillan GM, Townsend TR, Fields HA, et al. Seroepidemiology of hepatitis B virus infection in the United States.
1976 to 1980. Am J Med. 1989:87:5S –10S
McQuillan GM, Coleman PJ, Kruszon -Moran D, et al. Prevalence of hepatitis B virus infection in the United States: the
National Health and Nutrition Examination Surveys, 1976 through 1994. Am J Public Health. 1999; 89:14– 18
Middleman et al. 2014. Duration of protection after infant Hepatitis B vaccination series, Pediatrics 133(6)
MMWR 1991. CDC/ACIP, Hepatitis B Virus: A Comprehensive Strategy for Eliminating Transmission in the United
States Through Universal Childhood Vaccination: Recommendations of the Immunization Practices Advisory Committee (ACIP), MMWR, November 22, 1991 / 40(RR -13);1- 19,
https://www.cdc.gov/mmwr/preview/mmwrhtml/00033405.htm
Ott et al. The risk of perinatal hepatitis B virus transmission: hepatitis B e antigen ( HBeAg ) prevalence estimates for all
world regions BMC Infectious Diseases 2012, 12:131 http:// www.biomedcentral.com /1471 -2334/12/131
Smith E.A. et al., 2012. The national Perinatal Hepatitis B Prevention Program 1994 -2008. Pediatrics 129(4).
doi:10.1542/peds.2011- 2866
For more information, contact CDC
1-800- CDC- INFO (232 -4636)
TTY: 1 -888- 232- 6348 www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
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