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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
http://www.hrsa.gov). Hepatitis B vaccine is included on this table. The most current VIS for
hepatitis B vaccine is available at
http://www.cdc.gov/nip/publications/vis. Statements in languages other than
English are available from the Immunization Action
Coalition at http://www.immunize.org.
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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