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Appendix B

Immunization Management Issues

Hepatitis B Vaccine Dose and Administration

  • Recommended vaccine doses vary by product, age of recipient, and needs of special populations (see Table 2). Administration of single-antigen or combination vaccine simultaneously with other childhood vaccines produces no clinically significant interference in antibody responses (1--13). Although the antigen contents of vaccines differ, vaccines made by different manufacturers are interchangeable, except for the 2-dose schedule used for adolescents aged 11--15 years, for which only Recombivax HB is approved. Combination vaccines are not approved for use as a birth dose because of potential suppression of the immune response to subsequent doses of the Haemophilus influenzae type b (Hib) component in Comvax (14) and possible decreased immunogenicity of the diphtheria component of Pediarix when administered at birth.
  • Hepatitis B vaccine should be administered by intramuscular injection. Injection into the buttock is associated with decreased immunogenicity (15--18). Intradermal administration can result in a lower seroconversion rate and final concentration of antibody to hepatitis B surface antigen compared with intramuscular administration; limited data are available to assess long-term protection from this route of administration (19,20).
  • The anterolateral thigh muscle is the recommended site of administration for neonates (aged <1 month) and infants (aged 1--12 months). For toddlers (aged 1--2 years) and older children, either the anterolateral thigh or the deltoid muscle may be used if the muscle mass is adequate. The deltoid muscle is the preferred site of administration for adolescents.
  • For intramuscular injection, the needle should be long enough to reach the muscle mass and prevent vaccine from seeping into subcutaneous tissue, but not so long as to involve underlying nerves and blood vessels or bone (21). The appropriate needle length is usually 5/8" for neonates, 7/8"--1" for infants, and 7/8"--11/ 4" for toddlers, older children, and adolescents. A 22- to 25-gauge needle should be used.
  • Hepatitis B vaccine administered by any route or site other than intramuscularly in the anterolateral thigh or deltoid muscle should not be counted as valid and should be repeated unless serologic testing indicates that an adequate response has been achieved (see Postvaccination Testing for Serologic Response).
  • Hepatitis B vaccine and other vaccines administered during the same visit should be administered in different injection sites. When more than one injection must be administered in the same limb, the anterolateral thigh is usually the preferred site, with injections separated by 1"--2" to avoid overlap in local reactions.
  • For persons at risk for hemorrhage (e.g., persons with hemophilia), the risk of bleeding after intramuscular injection can be minimized by use of a 23-gauge (or smaller) needle, application of direct pressure to the injection site for >2 minutes, and administration of vaccine immediately after infusion of coagulation factor. Subcutaneous administration of vaccine can be considered for these persons but might result in lower response and an increased local reaction.
  • Hepatitis B vaccine should be stored at 35°--46° F (2°--8° C) and should not be frozen.
  • A Vaccine Information Statement (VIS) must be provided to recipients of hepatitis B vaccine. The National Childhood Vaccine Injury Act of 1986 (42 U.S.C. § 300aa-26) requires vaccine providers to give a copy of the most current vaccine-specific VIS to all recipients (children or their guardians) of vaccines that are included on the National Vaccine Injury Compensation Program table maintained by the Health Resources and Services Administration (available at Hepatitis B vaccine is included on this table. The most current VIS for hepatitis B vaccine is available at Statements in languages other than English are available from the Immunization Action Coalition at

Hepatitis B Immune Globulin (HBIG) Dose and Administration

  • The standard dose of HBIG is 0.5 mL for postexposure prophylaxis of infants born to hepatitis B surface antigen (HBsAg)--positive women and 0.06 mL/kg for all other applications.
  • HBIG may be administered simultaneously with hepatitis B vaccine but in a different injection site.
  • HBIG is administered by intramuscular injection. For infants, HBIG should be administered intramuscularly in the anterolateral thigh using a 22--25-gauge needle that is 7/8"--1" in length. For older children and adolescents, an appropriate muscle mass (i.e., deltoid or gluteal) should be chosen in which to deliver the larger volumes of HBIG required for these age groups by using a needle length appropriate for the person's age and size (21).
  • Vaccination with certain live-virus vaccines (measles, mumps, rubella, and varicella) should be deferred for at least 3 months after administration of HBIG because HBIG can inhibit the response to these vaccines (21).
  • HBIG should be stored at 35°--46° F (2°--8° C) and should not be frozen.

Unknown or Uncertain Vaccination Status

  • A reliable vaccination history is defined as a written, dated record (personal, school, physician, or immunization registry) of each dose of a complete series.
  • In the majority of clinical practice settings and in situations when postexposure prophylaxis is indicated (see Appendix C), providers should accept only written and dated records (e.g., personal, school, physician, or immunization registry) as evidence of vaccination. Although vaccinations should not be postponed if records cannot be located, providers should try to locate missing records by contacting previous health-care providers and searching for personally held records.
  • Persons whose records cannot be located should be considered susceptible and started or continued on the age-appropriate vaccine schedule.
  • Persons who reside in the United States but were vaccinated in other countries should be considered fully vaccinated if they have written documentation of >3 doses of vaccine administered at recommended minimum intervals, including the third dose at age >24 weeks. If they were not vaccinated according to recommended minimum intervals, they should be revaccinated (see Minimum Dosing Intervals and Management of Persons Who Were Incorrectly Vaccinated). Persons without written documentation of full vaccination should complete the age-appropriate vaccine series.

Interrupted Vaccine Schedules

  • When the hepatitis B vaccine schedule is interrupted, the vaccine series does not need to be restarted.
  • If the series is interrupted after the first dose, the second dose should be given as soon as possible, and the second and third doses should be separated by an interval of at least 8 weeks.
  • If only the third dose is delayed, it should be administered as soon as possible, after age 24 weeks (164 days).
  • It is not necessary to restart the vaccine series for infants switched from one vaccine brand to another, including combination vaccines.

Minimum Dosing Intervals and Management of Persons Who Were Incorrectly Vaccinated

  • The third dose of vaccine must be administered at least 8 weeks after the second dose and should follow the first dose by at least 16 weeks; the minimum interval between the first and second doses is 4 weeks. In infants, administration of the final dose is not recommended before age 24 weeks (164 days).
  • Inadequate doses of hepatitis B vaccine (see Table 2) or doses received after a shorter-than-recommended dosing interval should be readministered.

Accelerated Vaccine Schedules

  • The Food and Drug Administration (FDA) has not approved accelerated schedules in which hepatitis B vaccine is administered more than once in a month. If clinicians choose to use an accelerated schedule (i.e., doses at days 0, 7, and 14 days), the patient should also receive a booster dose at least 6 months after the start of the series to promote long-term immunity.

Hemodialysis Patients and Other Immunocompromised Persons

  • Standard hepatitis B vaccine doses (see Table 2) are approved by FDA for vaccination of all persons aged <20 years. For hemodialysis patients and other immunocompromised persons, higher doses might be more immunogenic, but no specific recommendations have been made.
  • Serologic testing of hemodialysis patients and other immunocompromised persons is recommended 1--2 months after administration of the final dose of the primary vaccine series to determine the need for revaccination (see Postvaccination Testing for Serologic Response). In addition, booster doses of vaccine might be needed (see Booster Doses).

Prevaccination Serologic Testing for Susceptibility

  • Because of the low prevalence of HBV infection among infants, children, and adolescents born in the United States, prevaccination testing for susceptibility usually is not indicated for these age groups.
  • Prevaccination testing for susceptibility is recommended for unvaccinated household, sexual, and needle-sharing contacts of HBsAg-positive persons.
  • Anti-HBc is the test of choice for prevaccination testing.
  • Persons tested for anti-HBc and found to be anti-HBc negative are susceptible and should complete the vaccine series.
  • Persons found to be anti-HBc positive should be tested for HBsAg. HBsAg testing may be performed on the same specimen collected for anti-HBc testing. If the HBsAg test result is positive, the person should receive appropriate management (see Appendix A).
  • In most situations, the first vaccine dose should be administered immediately after collection of the blood sample for serologic testing.

Postvaccination Testing for Serologic Response

Recommendations for postvaccination testing of infants born to HBsAg-positive women are provided in this report (see Management of Infants Born to Women Who Are HBsAg Positive). This section provides recommendations for postvaccination testing of other persons.

  • Serologic testing for immunity is not necessary after routine vaccination of infants, children, or adolescents.
  • Testing after vaccination is recommended only for the following persons whose subsequent clinical management depends on knowledge of their immune status:
    --- health-care workers;
    --- chronic hemodialysis patients, HIV-infected persons, and other immunocompromised persons (e.g., hematopoietic stem-cell transplant recipients or persons receiving chemotherapy), to determine the need for revaccination and the type of follow-up testing; and
    --- sex partners of HBsAg-positive persons, to determine the need for revaccination and the need for other methods of protection against HBV infection.
  • Testing should be performed 1--2 months after administration of the last dose of the vaccine series by using a method that allows determination of a protective level of anti-HBs (>10 mIU/mL).
  • Persons found to have anti-HBs levels of >10 mIU/mL after the primary vaccine series are considered to be immune.
    --- Immunocompetent persons have long-term protection and do not need further periodic testing to assess anti-HBs levels.
    --- Immunosuppressed persons might need annual testing to assess anti-HBs levels (see Booster Doses).
  • Persons found to have anti-HBs levels of <10 mIU/mL after the primary vaccine series should be revaccinated. Administration of three doses on an appropriate schedule (Table 7), followed by anti-HBs testing 1--2 months after the third dose, is usually more practical than serologic testing after one or more doses of vaccine.
  • Persons who do not respond to revaccination should be tested for HBsAg.
    --- If the HBsAg test result is positive, the persons should receive appropriate management (see Appendix B), and any household, sexual, or needle-sharing contacts should be identified and vaccinated (see Appendix A).
    --- Persons who test negative for HBsAg should be considered susceptible to HBV infection and should be counseled about precautions to prevent HBV infection and the need to obtain HBIG postexposure prophylaxis for any known or likely parenteral exposure to HBsAg-positive blood (see Appendix C).

Booster Doses

  • Booster doses are not recommended for persons with normal immune status who were vaccinated as infants, children, or adolescents. Serologic testing is not recommended to assess antibody levels in any age group, except in specific circumstances (see Postvaccination Testing for Serologic Response).
  • For hemodialysis patients, the need for booster doses should be assessed by annual antibody to hepatitis B surface antigen (anti-HBs) testing. A booster dose should be administered when anti-HBs levels decline to <10 mIU/mL.
  • For other immunocompromised persons (e.g., HIV-infected persons, hematopoietic stem cell transplant recipients, and persons receiving chemotherapy), the need for booster doses has not been determined. Annual anti-HBs testing and booster doses when anti-HBs levels decline to <10 mIU/mL should be considered in persons with an ongoing high risk for exposure.


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  3. Yvonnet B, Coursaget P, Deubel V, Diop-Mar I, Digoutte JP, Chiron JP. Simultaneous administration of hepatitis B and yellow fever vaccines. J Med Virol 1986;19:307--11.
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  8. Aristegui J, Muniz J, Perez LA, et al. Newborn universal immunisation against hepatitis B: immunogenicity and reactogenicity of simultaneous administration of diphtheria/tetanus/pertussis (DTP) and oral polio vaccines with hepatitis B vaccine at 0, 2 and 6 months of age. Vaccine 1995;13:973--7.
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  12. Giammanco G, Moiraghi A, Zotti C, et al. Safety and immunogenicity of a combined diphtheria-tetanus-acellular pertussis-hepatitis B vaccine administered according to two different primary vaccination schedules. Vaccine 1998;16:722--6.
  13. World Health Organization. Hepatitis B vaccines: WHO position paper. Weekly Epidemiol Rec 2004;79:255--63.
  14. Ward, J. I, Bulkow, L, Wainwright, R., and Chang, S. Immune tolerance and lack of booster responses to Haemophilus influenzae (Hib) conjugate vaccination in infants immunized beginning at birth [Abstract]. Programs and Abstracts of the 32nd Interscience Conference on Antimicrobial Agents and Chemotherapy. Anaheim, California, October 11--14, 1992.
  15. CDC. Suboptimal response to hepatitis B vaccine given by injection into the buttock. MMWR 1985;34:105--8,113.
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  21. CDC. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP) and the American Academy of Family Physicians (AAFP). MMWR 2002;51(No. RR-2):1--35).

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