Hepatitis B virus immunization in infants, children, and adolescents
- Jan E Drutz, MD
Jan E Drutz, MD
- Section Editor — General Pediatrics
- Professor of Pediatrics
- Baylor College of Medicine
- Section Editors
- Teresa K Duryea, MD
Teresa K Duryea, MD
- Section Editor — General Pediatrics
- Associate Professor of Pediatrics
- Baylor College of Medicine
- Morven S Edwards, MD
Morven S Edwards, MD
- Section Editor — Pediatric Infectious Diseases
- Professor of Pediatrics
- Baylor College of Medicine
Hepatitis B virus (HBV) immunization before HBV exposure is the most effective means to prevent HBV transmission. Hepatitis B immunization in infants, children, and adolescents will be discussed here, focusing on immunization of infants, children, and adolescents in the United States. Our recommendations are consistent with those of the Advisory Committee on Immunization Practices, the American Academy of Pediatrics, and the American Academy of Family Physicians. Hepatitis B immunization in adults and elsewhere in the world are discussed separately. (See "Hepatitis B virus vaccination".)
HEPATITIS B INFECTION
HBV is a DNA hepadnavirus. The viral particle is composed of an outer lipoprotein envelope, which contains hepatitis B surface antigen (HBsAg), and an inner nucleocapsid which consists of hepatitis B core antigen (HBcAg) .
HBV can be transmitted vertically from mother to infant during labor or delivery, through sexual intercourse, or by exposure to contaminated blood or body fluids. In utero transmission is uncommon. Infants born to HBsAg-positive women are at increased risk of HBV infection. Adolescents also are at increased risk as a result of sexual behavior or injection drug use. (See "Epidemiology, transmission, and prevention of hepatitis B virus infection", section on 'Transmission of HBV'.)
Each year in the United States an estimated 25,000 infants are born to women who are HBV carriers . As many as 90 percent of these infants will acquire acute HBV infection if no preventive measures are taken [3,4]. Acquisition of HBV at a younger age is associated with an increased risk of developing chronic HBV infection (figure 1). Approximately 25 percent of people infected with chronic HBV during infancy infection die prematurely from cirrhosis or liver cancer [5-7]. Most people with chronic HBV infection remain asymptomatic until the onset of cirrhosis or end-stage liver disease and may be unaware of their infection, increasing the risk of transmission to household, sexual, or needle-sharing contacts. (See "Hepatitis B and pregnancy", section on 'Mother-to-child transmission' and "Clinical manifestations and natural history of hepatitis B virus infection", section on 'Sequelae and prognosis of chronic HBV infection'.)
Two single antigen (ie, monovalent) recombinant hepatitis B (HepB) vaccines, are available for use in the United States: Engerix-B and Recombivax HB [1,8]. These vaccines are supplied in different concentrations and have different doses (table 1). They can be used interchangeably , except that only Recombivax HB can be used for the two-dose series in adolescents age 11 to 15 years .
- Mast EE, Margolis HS, Fiore AE, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1: immunization of infants, children, and adolescents. MMWR Recomm Rep 2005; 54:1.
- Smith EA, Jacques-Carroll L, Walker TY, et al. The national Perinatal Hepatitis B Prevention Program, 1994-2008. Pediatrics 2012; 129:609.
- Margolis HS, Coleman PJ, Brown RE, et al. Prevention of hepatitis B virus transmission by immunization. An economic analysis of current recommendations. JAMA 1995; 274:1201.
- Beasley RP, Trepo C, Stevens CE, Szmuness W. The e antigen and vertical transmission of hepatitis B surface antigen. Am J Epidemiol 1977; 105:94.
- Beasley RP, Hwang LY, Lin CC, Chien CS. Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22 707 men in Taiwan. Lancet 1981; 2:1129.
- Hoofnagle JH, Shafritz DA, Popper H. Chronic type B hepatitis and the "healthy" HBsAg carrier state. Hepatology 1987; 7:758.
- McMahon BJ, Alberts SR, Wainwright RB, et al. Hepatitis B-related sequelae. Prospective study in 1400 hepatitis B surface antigen-positive Alaska native carriers. Arch Intern Med 1990; 150:1051.
- American Academy of Pediatrics. Hepatitis B. In: Red Book: 2015 Report of the Committee on Infectious Diseases, 30th ed, Kimberlin DW, Brady MT, Jackson MA, Long SS (Eds), American Academy of Pediatrics, Elk Grove Village, IL 2015. p.400.
- Seto D, West DJ, Gilliam RR, et al. Antibody responses of healthy neonates of two mixed regimens of hepatitis B vaccine. Pediatr Infect Dis J 1999; 18:840.
- Langley JM, Halperin SA, Rubin E, et al. Safety and immunogenicity of 2 mixed primary infant immunization schedules of pentavalent diphtheria, tetanus, acellular pertussis, inactivated poliomyelitis, and Haemophilus influenzae Type B vaccines at 2, 4, and 6 months of age: a randomized controlled trial. Pediatr Infect Dis J 2012; 31:189.
- Pertussis vaccination: use of acellular pertussis vaccines among infants and young children. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 1997; 46:1.
- Centers for Disease Control and Prevention. Pertussis. In: Epidemiology and Prevention of Vaccine-Preventable Diseases. The Pink Book: Course Textbook, 13th ed, Hamborsky J, Kroger A, Wolfe S (Eds). Public Health Foundation, Washington, DC 2015. Available at: www.cdc.gov/vaccines/pubs/pinkbook/index.html (Accessed on June 02, 2015).
- Centers for Disease Control and Prevention. Current vaccine shortages and delays. Available at: www.cdc.gov/VACCINes/vac-gen/shortages/default.htm (Accessed on January 08, 2015).
- Engerix-B. US Food & Drug Administration (FDA) approved product information. Revised November 2013. Available at: www.fda.gov/biologicsbloodvaccines/vaccines/approvedproducts/ucm093833.htm (Accessed on May 29, 2015).
- Recombivax HB. US Food & Drug Administration (FDA) approved product information. Revised May 2014. Available at: www.fda.gov/biologicsbloodvaccines/vaccines/approvedproducts/ucm093833.htm (Accessed on May 29, 2015).
- Diphtheria and tetanus toxoids and acellular pertussis adsorbed, hepatitis B (recombinant) and inactivated poliovirus vaccine combined. US Food & Drug Administration (FDA) approved product information. Revised November 2013. Available at: www.fda.gov/biologicsbloodvaccines/vaccines/approvedproducts/ucm093833.htm (Accessed on May 29, 2015).
- Twinrix. US Food & Drug Administration (FDA) approved product information. Revised November 2013. Available at: www.fda.gov/biologicsbloodvaccines/vaccines/approvedproducts/ucm093833.htm (Accessed on May 29, 2015).
- Centers for Disease Control and Prevention. Hepatitis B. In: Epidemiology and Prevention of Vaccine-Preventable Diseases. The Pink Book: Course Textbook, 13th ed, Hamborsky J, Kroger A, Wolfe S (Eds). Public Health Foundation, Washington, DC 2015. Available at: www.cdc.gov/vaccines/pubs/pinkbook/index.html#toc (Accessed on May 20, 2015).
- Centers for Disease Control and Prevention (CDC). Implementation of newborn hepatitis B vaccination--worldwide, 2006. MMWR Morb Mortal Wkly Rep 2008; 57:1249.
- Robinson CL, Advisory Committee on Immunization Practices (ACIP), ACIP Child/Adolescent Immunization Work Group. Advisory Committee on Immunization Practices Recommended Immunization Schedules for Persons Aged 0 Through 18 Years--United States, 2016. MMWR Morb Mortal Wkly Rep 2016; 65:86.
- Stevens CE, Beasley RP, Tsui J, Lee WC. Vertical transmission of hepatitis B antigen in Taiwan. N Engl J Med 1975; 292:771.
- Nelson NP, Jamieson DJ, Murphy TV. Prevention of Perinatal Hepatitis B Virus Transmission. J Pediatric Infect Dis Soc 2014; 3 Suppl 1:S7.
- Lee C, Gong Y, Brok J, et al. Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers. Cochrane Database Syst Rev 2006; :CD004790.
- Schillie S, Walker T, Veselsky S, et al. Outcomes of infants born to women infected with hepatitis B. Pediatrics 2015; 135:e1141.
- Centers for Disease Control and Prevention (CDC). Postvaccination serologic testing results for infants aged ≤24 months exposed to hepatitis B virus at birth: United States, 2008-2011. MMWR Morb Mortal Wkly Rep 2012; 61:768.
- Pichichero ME, Blatter MM, Reisinger KS, et al. Impact of a birth dose of hepatitis B vaccine on the reactogenicity and immunogenicity of diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b combination vaccination. Pediatr Infect Dis J 2002; 21:854.
- Losonsky GA, Wasserman SS, Stephens I, et al. Hepatitis B vaccination of premature infants: a reassessment of current recommendations for delayed immunization. Pediatrics 1999; 103:E14.
- Belloni C, Chirico G, Pistorio A, et al. Immunogenicity of hepatitis B vaccine in term and preterm infants. Acta Paediatr 1998; 87:336.
- Hadler SC, de Monzon MA, Lugo DR, Perez M. Effect of timing of hepatitis B vaccine doses on response to vaccine in Yucpa Indians. Vaccine 1989; 7:106.
- Halsey NA, Moulton LH, O'Donovan JC, et al. Hepatitis B vaccine administered to children and adolescents at yearly intervals. Pediatrics 1999; 103:1243.
- Jilg W, Schmidt M, Deinhardt F. Vaccination against hepatitis B: comparison of three different vaccination schedules. J Infect Dis 1989; 160:766.
- Schönberger K, Riedel C, Rückinger S, et al. Determinants of Long-term protection after hepatitis B vaccination in infancy: a meta-analysis. Pediatr Infect Dis J 2013; 32:307.
- Yusuf HR, Daniels D, Smith P, et al. Association between administration of hepatitis B vaccine at birth and completion of the hepatitis B and 4:3:1:3 vaccine series. JAMA 2000; 284:978.
- Lauderdale DS, Oram RJ, Goldstein KP, Daum RS. Hepatitis B vaccination among children in inner-city public housing, 1991-1997. JAMA 1999; 282:1725.
- Luman ET, Fiore AE, Strine TW, Barker LE. Impact of thimerosal-related changes in hepatitis B vaccine birth-dose recommendations on childhood vaccination coverage. JAMA 2004; 291:2351.
- Chawareewong S, Jirapongsa A, Lokaphadhana K. Immune response to hepatitis B vaccine in premature neonates. Southeast Asian J Trop Med Public Health 1991; 22:39.
- Lau YL, Tam AY, Ng KW, et al. Response of preterm infants to hepatitis B vaccine. J Pediatr 1992; 121:962.
- Linder N, Vishne TH, Levin E, et al. Hepatitis B vaccination: long-term follow-up of the immune response of preterm infants and comparison of two vaccination protocols. Infection 2002; 30:136.
- Patel DM, Butler J, Feldman S, et al. Immunogenicity of hepatitis B vaccine in healthy very low birth weight infants. J Pediatr 1997; 131:641.
- Blondheim O, Bader D, Abend M, et al. Immunogenicity of hepatitis B vaccine in preterm infants. Arch Dis Child Fetal Neonatal Ed 1998; 79:F206.
- Huang FY, Lee PI, Lee CY, et al. Hepatitis B vaccination in preterm infants. Arch Dis Child Fetal Neonatal Ed 1997; 77:F135.
- Kim SC, Chung EK, Hodinka RL, et al. Immunogenicity of hepatitis B vaccine in preterm infants. Pediatrics 1997; 99:534.
- Qu C, Chen T, Fan C, et al. Efficacy of neonatal HBV vaccination on liver cancer and other liver diseases over 30-year follow-up of the Qidong hepatitis B intervention study: a cluster randomized controlled trial. PLoS Med 2014; 11:e1001774.
- Chiang CJ, Yang YW, You SL, et al. Thirty-year outcomes of the national hepatitis B immunization program in Taiwan. JAMA 2013; 310:974.
- Bruce MG, Bruden D, Hurlburt D, et al. Antibody Levels and Protection After Hepatitis B Vaccine: Results of a 30-Year Follow-up Study and Response to a Booster Dose. J Infect Dis 2016; 214:16.
- McMahon BJ, Dentinger CM, Bruden D, et al. Antibody levels and protection after hepatitis B vaccine: results of a 22-year follow-up study and response to a booster dose. J Infect Dis 2009; 200:1390.
- Middleman AB, Baker CJ, Kozinetz CA, et al. Duration of protection after infant hepatitis B vaccination series. Pediatrics 2014; 133:e1500.
- Immunization Action Coalition. Ask the Experts: Diseases & Vaccines. Hepatitis B. http://www.immunize.org/askexperts/experts_hepb.asp#recommendations (Accessed on July 07, 2016).
- National Center for Immunization and Respiratory Diseases. General recommendations on immunization --- recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2011; 60:1.
- Shaw FE Jr, Guess HA, Roets JM, et al. Effect of anatomic injection site, age and smoking on the immune response to hepatitis B vaccination. Vaccine 1989; 7:425.
- Cook IF, Murtagh J. Comparative immunogenicity of hepatitis B vaccine administered into the ventrogluteal area and anterolateral thigh in infants. J Paediatr Child Health 2002; 38:393.
- Redfield RR, Innis BL, Scott RM, et al. Clinical evaluation of low-dose intradermally administered hepatitis B virus vaccine. A cost reduction strategy. JAMA 1985; 254:3203.
- Coleman PJ, Shaw FE Jr, Serovich J, et al. Intradermal hepatitis B vaccination in a large hospital employee population. Vaccine 1991; 9:723.
- Gasparini R, Tregnaghi M, Keshavan P, et al. Safety and Immunogenicity of a Quadrivalent Meningococcal Conjugate Vaccine and Commonly Administered Vaccines After Coadministration. Pediatr Infect Dis J 2016; 35:81.
- Schwarz KB, Cloonan YK, Ling SC, et al. Children with Chronic Hepatitis B in the United States and Canada. J Pediatr 2015; 167:1287.
- Kloster B, Kramer R, Eastlund T, et al. Hepatitis B surface antigenemia in blood donors following vaccination. Transfusion 1995; 35:475.
- Lunn ER, Hoggarth BJ, Cook WJ. Prolonged hepatitis B surface antigenemia after vaccination. Pediatrics 2000; 105:E81.
- Mast EE, Weinbaum CM, Fiore AE, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) Part II: immunization of adults. MMWR Recomm Rep 2006; 55:1.
- Notice to readers: Alternate two-dose hepatitis B vaccination schedule for adolescents aged 11 to 15 years. MMWR Morb Mortal Wkly Rep 2000; 49:261.
- Levy M, Koren G. Hepatitis B vaccine in pregnancy: maternal and fetal safety. Am J Perinatol 1991; 8:227.
- Lewis E, Shinefield HR, Woodruff BA, et al. Safety of neonatal hepatitis B vaccine administration. Pediatr Infect Dis J 2001; 20:1049.
- Bohlke K, Davis RL, Marcy SM, et al. Risk of anaphylaxis after vaccination of children and adolescents. Pediatrics 2003; 112:815.
- Schillie S, Murphy TV, Fenlon N, et al. Update: Shortened Interval for Postvaccination Serologic Testing of Infants Born to Hepatitis B-Infected Mothers. MMWR Morb Mortal Wkly Rep 2015; 64:1118.
- Euler GL, Copeland JR, Rangel MC, Williams WW. Antibody response to postexposure prophylaxis in infants born to hepatitis B surface antigen-positive women. Pediatr Infect Dis J 2003; 22:123.
- Ko SC, Schillie SF, Walker T, et al. Hepatitis B vaccine response among infants born to hepatitis B surface antigen-positive women. Vaccine 2014; 32:2127.
- Tan KL, Goh KT, Oon CJ, Chan SH. Immunogenicity of recombinant yeast-derived hepatitis B vaccine in nonresponders to perinatal immunization. JAMA 1994; 271:859.
- Collier AC, Corey L, Murphy VL, Handsfield HH. Antibody to human immunodeficiency virus (HIV) and suboptimal response to hepatitis B vaccination. Ann Intern Med 1988; 109:101.
- Hovi L, Valle M, Siimes MA, et al. Impaired response to hepatitis B vaccine in children receiving anticancer chemotherapy. Pediatr Infect Dis J 1995; 14:931.
- Wilson CM, Ellenberg JH, Sawyer MK, et al. Serologic response to hepatitis B vaccine in HIV infected and high-risk HIV uninfected adolescents in the REACH cohort. Reaching for Excellence in Adolescent Care and Health. J Adolesc Health 2001; 29:123.
- Polychronopoulou-Androulakaki S, Panagiotou JP, Kostaridou S, et al. Immune response of immunocompromised children with malignancies to a recombinant hepatitis B vaccine. Pediatr Hematol Oncol 1996; 13:425.
- Zuin G, Principi N, Tornaghi R, et al. Impaired response to hepatitis B vaccine in HIV infected children. Vaccine 1992; 10:857.
- HEPATITIS B INFECTION
- VACCINE FORMULATIONS
- ROUTINE INFANT IMMUNIZATION
- In the United States
- - HBsAg-positive mother
- - HBsAg-negative mother, birth weight ≥2 kg
- - HBsAg-negative mother, birth weight <2 kg
- - Mother's HBsAg status unknown, birth weight ≥2 kg
- - Mother's HBsAg status unknown, birth weight <2 kg
- In other countries
- Efficacy and effectiveness
- Duration of immunity
- VACCINE ADMINISTRATION
- CATCH-UP IMMUNIZATION
- Target groups
- Need for prevaccination serology
- SPECIAL POPULATIONS
- Hemodialysis patients
- Immune compromised patients
- Travelers to HBV endemic areas
- CONTRAINDICATIONS AND PRECAUTIONS
- ADVERSE REACTIONS
- POSTVACCINATION SEROLOGY
- POSTEXPOSURE IMMUNIZATION
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS