About
The Evidence to Recommendations (EtR) frameworks describe information considered in moving from evidence to ACIP vaccine recommendations.
Background
Despite successful implementation of the United States’ routine hepatitis A vaccination recommendation for children aged 12–23 months, there remains a small gap to close among adolescents who have not received hepatitis A vaccine and are thus missing long-term and potential lifetime protection from hepatitis A.
Decreased hepatitis A incidence in the United States and reduced exposure to hepatitis A virus (HAV) have resulted in decreased anti-HAV seroprevalence among adults, and an increased proportion of susceptible adults, including younger adults (i.e., aged 20–29 years). Vaccinating adolescents will lead to increased protection among adults—particularly young adults—more quickly than waiting for the routinely vaccinated cohort of children to reach adulthood. It also will protect those with undisclosed risk factors (e.g., drug use, men who have sex with men [MSM]) more consistently and earlier in life.
In 2006, the Advisory Committee on Immunization Practices (ACIP) recommended routine hepatitis A vaccination for all children aged 12–23 months. Children who are not vaccinated by age 2 years can be vaccinated at subsequent health care visits, and catch-up vaccination of unvaccinated children aged 2–18 years can be considered based on shared clinical decision-making. Catch-up vaccination ensures that the percentage of children/adolescents who miss vaccination as scheduled or who were born outside of the routinely vaccinated cohort (i.e., born prior to 2006) are protected and is a way to increase herd immunity.
In 2017, national hepatitis A vaccination coverage among adolescents aged 13–17 years was 77.2% for 1 dose and 68.4% for ≥2 doses, compared to 36.2% and 25.3% for 1 and ≥2 doses, respectively, in 2008. This indicates substantial catch-up implementation and acceptance despite a recommendation based on clinical decision-making.12
The vaccines containing HAV antigen that are currently licensed in the United States for children are the inactivated, single-antigen vaccines HAVRIX® (manufactured by GlaxoSmithKline, Rixensart, Belgium) and VAQTA® (manufactured by Merck & Co., Inc., Whitehouse Station, New Jersey).
Additional background information supporting the ACIP recommendations on the use of hepatitis A vaccines can be found in the relevant publication of the recommendations referenced on the ACIP website.
Problem
Criteria | Work Group Judgments | Evidence | Additional Information |
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Is the problem of public health importance? | Yes | Incidence: The rate of reported acute hepatitis A cases in 2017 was 1.0 cases/100,000 population (3).
HAV outbreaks: Since widespread person-to-person outbreaks of hepatitis A across the United States were first identified in 2016, 23 states have publicly reported the following as of June 14, 2019 (5):
Hepatitis A vaccination coverage: In 2017, national hepatitis A vaccination coverage was 77.2% for 1 dose among adolescents aged 13–17 years and 68.4% for ≥2 doses (1). Among adolescents aged 13–17 years living in states where routine vaccination at 12–23 months was first recommended in 2006, coverage is only slightly lower than the total cohort, at 71% for 1 dose and 61% for ≥2 doses. |
Vaccinating teens protects those who may be at risk for HAV infection (e.g., persons who use drugs, persons experiencing homelessness, travelers) at present and in the future. |
Benefits and Harms
References in this table:1678910111213141516171819
Criteria | Work Group Judgments | Research Evidence | Additional Information |
---|---|---|---|
How substantial are the desirable anticipated effects? | Large | HAVRIX and VAQTA are highly immunogenic when administered to children and adolescents according to multiple schedules.
Due to demonstrated long-term protection from the vaccines, there is little concern that childhood vaccination will result in risk later in life due to waning immunity.
Vaccine-induced cellular immunity has been shown to promote HAV-specific cellular immunity similar to that induced by natural infection (18). |
Catch-up vaccination ensures children and adolescents who miss vaccination as scheduled or who were born outside of the routinely vaccinated cohort are protected and increases herd immunity.
In addition, since implementation of risk-based vaccination in adults has been poor, catch-up vaccination will more rapidly increase the proportion of adults with risk factors who are protected. |
How substantial are the undesirable anticipated effects? | Minimal | More than 20 years of safety monitoring have shown no safety concerns.
No unusual or unexpected safety patterns were observed in the Vaccine Adverse Event Reporting System for any hepatitis A vaccines (1). Rates of adverse events following TWINRIX® vaccination were similar to those seen with separately administered hepatitis A and hepatitis B vaccines (19). (TWINRIX® is approved for use in persons 18 years of age or older.) |
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Do the desirable effects outweigh the undesirable effects? | Favors intervention | Hepatitis A vaccination affords long-term protection against HAV infection.
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What is the overall certainty of this evidence for the critical outcomes? | Effectiveness of the intervention is Level 3 (No included studies) Safety of the intervention is Level 2 (No included studies) |
GRADE was not used to evaluate the evidence.
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Values
Criteria | Work Group Judgments | Research Evidence | Additional Information |
---|---|---|---|
Does the target population feel that the desirable effects are large relative to undesirable effects? | Probably yes | In 2017, national hepatitis A vaccination coverage among adolescents aged 13–17 years was 77.2% for 1 dose and 68.4% for ≥2 doses compared to 36.2% and 25.3% for 1 and ≥2 doses, respectively, in 2008 (1, 2).
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Compared to other vaccines with a routine catch-up schedule, hepatitis A adolescent 2-dose coverage is comparable (e.g., quadrivalent meningococcal conjugate vaccine) or greater (e.g., human papillomavirus vaccine), providing evidence of acceptability by the target population (1). |
Is there important uncertainty about or variability in how much people value the main outcomes? | Probably no important uncertainty or variability | The high coverage rate, despite this recommendation being based on clinical decision-making, provides strong and consistent evidence that most parents believe that it is important. |
Acceptability
References in this section:20
Criteria | Work Group Judgments | Research Evidence | Additional Information |
---|---|---|---|
Is the intervention acceptable to key stakeholders? | Probably yes | CDC currently does not have a routine catch-up recommendation for children aged 2–18 years, yet 21 states have introduced mandates for daycare, daycare plus school, or school alone. This represents an increase in states with mandates from 28% in 2011 to 40% in 2018 (20).
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Children who were 1 year of age when the routine recommendation was first published in 2006 were ~12–13 years old in 2017 when these data were collected; nearly all of the cohort of children 13–17 assessed in 2017 were not subject to the routine recommendation for children 12–23 months of age. High overall coverage in this age group demonstrates that catch-up vaccination is occurring.
As noted above, the hepatitis A adolescent 2-dose coverage is comparable or greater than other vaccines with a routine catch-up schedule, which provides evidence of acceptability by key stakeholder populations. |
Resource Use
References in this section:12122
Criteria | Work Group Judgments | Research Evidence | Additional Information |
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Is the intervention a reasonable and efficient allocation of resources? | Probably yes | Cost analysis: After universal childhood recommendation implementation, a cost-effectiveness model used to assess nationwide routine hepatitis A vaccination was adapted to assess the cost-effectiveness of catch-up hepatitis A vaccination among unvaccinated and partially vaccinated children compared with unvaccinated children (21).
Incremental costs of catch up now, given current rates of coverage among 13–17-year-olds, would be more favorable, because hepatitis A vaccination coverage rates are higher among vaccinated children who are aging into the adolescent cohort:
Achieving 80%–90% coverage among teens would require a much smaller number of additional vaccines given. In addition, HAV incidence overall is higher due to the ongoing multistate outbreaks (0.5 cases/100,000 population in 2012 versus 1.0 case/100,000 population in 2017) (1, 22). |
Other studies: To assess the population-level impact and cost-effectiveness of US hepatitis vaccination programs, an age-structured population model of hepatitis A transmission dynamics was developed to evaluate two policies of administering a 2-dose hepatitis A vaccine to children aged 12 to 18 months (22).
Additional Considerations: Cost of outbreak response and hospitalization is substantial and would offset some of additional costs of catch-up vaccination. Based on 2017 hepatitis A vaccination coverage rates:
Assumptions: 1) 2017 coverage rates apply to all children; however, in actuality, younger adolescents have higher coverage. 2) 100% of 1-dose recipients complete series when calculating cost of 80% completion. 3) Private sector covers 50% of these adolescents and CDC covers 50%. |
Feasibility
References in this section:2324
Criteria | Work Group Judgments | Research Evidence | Additional Information |
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Is the intervention feasible to implement? | Yes | Of the 30 registries American Immunization Registry Association (AIRA) were able to query to test forecasting algorithms, 27 already routinely forecast hepatitis A vaccine for an 18-year-old who has never been vaccinated. All 30 algorithms forecast the second dose in any 18-year-old who has had one dose. Essentially, these algorithms are implemented as routine catch-up. Therefore, 27 of 30 registries would not have to change to implement routine catch-up.
Findings from a 2014 survey (23) indicate:
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Routine hepatitis A catch-up already exists in states that have school mandates (21 states have introduced mandates for daycare, daycare plus school, or school alone.). In New York City, all children and adolescents not previously vaccinated should receive the two-dose hepatitis A vaccine series by their 19th birthday for long-term protection (24).
There are opportunities to administer hepatitis A vaccine to adolescents concurrently with vaccines protecting against other infections, such as human papillomavirus and meningococcal disease. |
Balance of Consequences
Desirable consequences probably outweigh undesirable consequences in most settings
Is there sufficient information to move forward with a recommendation? Yes
Recommendation (text)
Recommended for all unvaccinated children and adolescents aged 2–18 years. Children and adolescents who have not previously received hepatitis A vaccine should be vaccinated routinely at any age (i.e., children and adolescents are recommended for catch-up vaccination).
Final deliberation and decision by the ACIP
Final ACIP recommendation
ACIP recommends the intervention
i This Evidence to Recommendation table is based on the GRADE Evidence to Decision framework developed through the DECIDE project. See further information.
View the complete list of EtR Frameworks
- Unpublished data, Centers for Disease Control and Prevention.
- Nelson NP, Yankey D, Singleton JA, Elam-Evans LD. Hepatitis A vaccination coverage among adolescents (13–17 years) in the United States, 2008–2016. Vaccine. 2018 Mar 14;36(12):1650–9. doi: 10.1016/j.vaccine.2018.01.090. Epub 2018 Feb 12.
- Centers for Disease Control and Prevention. CDC Surveillance for Viral Hepatitis – United States, 2017. www.cdc.gov/hepatitis/statistics/2017surveillance/index.htm. Released November 14, 2019. Accessed January 16, 2020.
- Centers for Disease Control and Prevention. National Notifiable Diseases Surveillance System (NNDSS). Updated March 13, 2019. Accessed January 16, 2020.
- Centers for Disease Control and Prevention. Widespread outbreaks of hepatitis A across the United States. www.cdc.gov/hepatitis/outbreaks/2017March-HepatitisA.htm. Accessed January 16, 2020.
- Clemens R, Safary A, Hepburn A, Roche C, Stanbury WJ, André FE. Clinical experience with an inactivated hepatitis A vaccine. J Infect Dis. 1995;171(Suppl 1):S44–9.
- Nalin DR. VAQTA™: hepatitis A vaccine, purified inactivated. Drugs Future. 1995;20:24–9.
- McMahon BJ, Williams J, Bulkow L, et al. Immunogenicity of an inactivated hepatitis A vaccine in Alaska Native children and Native and non-Native adults. J Infect Dis. 1995;171:676–9.
- Ashur Y, Adler R, Rowe M, Shouval D. Comparison of immunogenicity of two hepatitis A vaccines—VAQTA® and HAVRIX®—in young adults. Vaccine. 1999;17:2290–6.
- Balcarek KB, Bagley MR, Pass RF, Schiff ER, Krause DS. Safety and immunogenicity of an inactivated hepatitis A vaccine in preschool children. J Infect Dis. 1995;171(Suppl 1):S70–2.
- Horng YC, Chang MH, Lee CY, Safary A, Andre FE, Chen DS. Safety and immunogenicity of hepatitis A vaccine in healthy children. Pediatr Infect Dis J. 1993;12:359–62.
- Findor JA, Cañero Velasco MC, Mutti J, Safary A. Response to hepatitis A vaccine in children after a single dose with a booster administration 6 months later. J Travel Med. 1996;3(3):156–159. doi:10.1111/j.1708-8305.1996.tb00730.x
- Sharapov UM, Bulkow LR, Negus SE, et al. Persistence of hepatitis A vaccine induced seropositivity in infants and young children by maternal antibody status: 10-year follow-up. Hepatology. 2012 Aug;56(2):516–22. doi: 10.1002/hep.25687. Epub 2012 Jun 11.
- Van Herck K, Van Damme. Prevention of hepatitis A by Havrix™: a review. Expert Rev Vaccines. 2005;4(4):459–71. doi: 10.1586/14760584.4.4.459.
- Plumb ID, Bulkow LR, Bruce MG, et al. Persistence of antibody to hepatitis A virus 20 years after receipt of hepatitis A vaccine in Alaska. J Viral Hepat. 2017 Jul;24(7):608–12. doi: 10.1111/jvh.12676. Epub 2017 Feb 2.
- Mosites E, Gounder P, Snowball M, et al. Hepatitis A vaccine immune response 22 years after vaccination. J Med Virol. 2018 Aug;90(8):1418–22. doi: 10.1002/jmv.25197. Epub 2018 May 1.
- Theeten H, Van Herck K, Van Der Meeren O, Crasta P, Van Damme P, Hens N. Long-term antibody persistence after vaccination with a 2-dose Havrix (inactivated hepatitis A vaccine): 20 years of observed data, and long-term model-based predictions. Vaccine. 2015 Oct 13;33(42):5723-5727. doi: 10.1016/j.vaccine.2015.07.008. Epub 2015 Jul 16.
- Melgaço JG, Morgado LN, Santiago MA, et al. A single dose of inactivated hepatitis A vaccine promotes HAV-specific memory cellular response similar to that induced by a natural infection. Vaccine. 2015 Jul 31;33(32):3813–20. doi: 10.1016/j.vaccine.2015.06.099. Epub 2015 Jul 2.
- TWINRIX [Hepatitis A & Hepatitis B (Recombinant) Vaccine]. [Package Insert]. Research Triangle Park, North Carolina: GlaxoSmithKline; 2018.
- Immunization Action Coalition. Hepatitis A vaccine mandates for children in daycare facilities, elementary, and secondary schools. https://www.immunize.org/laws/hepa.asp. Updated November 30, 2019. Accessed January 16, 2020.
- Hankin-Wei A, Rein DB, Hernandez-Romieu A, et al. Cost-effectiveness analysis of catch-up hepatitis A vaccination among unvaccinated/partially-vaccinated children. Vaccine. 2016;34(35):4243–9. doi:10.1016/j.vaccine.2016.06.040
- Dhankhar P, Nwankwo C, Pillsbury M, et al. Public health impact and cost-effectiveness of hepatitis A vaccination in the United States: a disease transmission dynamic modeling approach. Value Health. 2015 Jun;18(4):358–67. doi: 10.1016/j.jval.2015.02.004. Epub 2015 Apr 4.
- Nelson NP, Allison MA, Lindley MC, et al. Physician knowledge and attitudes about hepatitis A and current practices regarding hepatitis A vaccination delivery. Acad Pediatr. 2017 Jul;17(5):562–70. doi:10.1016/j.acap.2017.01.001
- NYC Health. Hepatitis A. https://www1.nyc.gov/site/doh/health/health-topics/hepatitis-a.page. Accessed January 16, 2020.