翻译完毕乙肝免疫策略资料，感谢大家

IC

Prophylaxis Against HBV Infection

Hepatitis B Vaccine

HBsAg is the antigen used for hepatitis B vaccination (79,80). Vaccine antigen can be purified from the plasma of persons with chronic HBV infection or produced by recombinant DNA technology. Vaccines available in the United States use recombinant DNA technology to express HBsAg in yeast, which is then purified from the cells by biochemical and biophysical separation techniques (81,82). Hepatitis B vaccines licensed in the United States are formulated to contain 10--40 µg of HBsAg protein/mL. Since March 2000, hepatitis B vaccines produced for distribution in the United States do not contain thimerosal as a preservative or contain only a trace amount (<1.0 mcg mercury/mL) from the manufacturing process (83,84).

Hepatitis B vaccine is available as a single-antigen formulation and also in fixed combination with other vaccines. Two single-antigen vaccines are available in the United States: Recombivax HB^® (Merck & Co., Inc., Whitehouse Station, New Jersey) and Engerix-B^® (GlaxoSmithKline Biologicals, Rixensart, Belgium). Of the three licensed combination vaccines, one (Twinrix^® [GlaxoSmithKline Biologicals, Rixensart, Belgium]) is used for vaccination of adults, and two (Comvax^® [Merck & Co., Inc., Whitehouse Station, New Jersey] and Pediarix^® [GlaxoSmithKline Biologicals, Rixensart, Belgium]) are used for vaccination of infants and young children. Twinrix contains recombinant HBsAg and inactivated hepatitis A virus. Comvax contains recombinant HBsAg and Haemophilus influenzae type b (Hib) polyribosylribitol phosphate conjugated to Neisseria meningitidis outer membrane protein complex. Pediarix contains recombinant HBsAg, diphtheria and tetanus toxoids and acellular pertussis adsorbed (DTaP), and inactivated poliovirus (IPV).

HBIG

HBIG provides passively acquired anti-HBs and temporary protection (i.e., 3--6 months) when administered in standard doses. HBIG is typically used as an adjunct to hepatitis B vaccine for postexposure immunoprophylaxis to prevent HBV infection. HBIG administered alone is the primary means of protection after an HBV exposure for nonresponders to hepatitis B vaccination.

HBIG is prepared from the plasma of donors with high concentrations of anti-HBs. The plasma is screened to eliminate donors who are positive for HBsAg, antibodies to HIV and hepatitis C virus (HCV), and HCV RNA. In addition, proper manufacturing techniques for HBIG inactivate viruses (e.g., HBV, HCV, and HIV) from the final product (85,86). No evidence exists that HBV, HCV, or HIV ever has been transmitted by HBIG commercially available in the United States. HBIG that is commercially available in the United States does not contain thimerosal.

Vaccination Schedules and Results of Vaccination

Preexposure Vaccination

Infants and Children

Primary vaccination consists of >3 intramuscular doses of hepatitis B vaccine (Table 2). Vaccine schedules for infants and children (Tables 3--5) are determined on the basis of immunogenicity data and the need to integrate hepatitis B vaccine into a harmonized childhood vaccination schedule. Although not all possible schedules for each product have been evaluated in clinical trials, available licensed formulations for both single-antigen vaccines produce high (>95%) levels of seroprotection among infants and children when administered in multiple schedules (87--91).

The immunogenicity of the combined hepatitis B-Hib conjugate vaccine (Comvax) and the combined hepatitis B-DTaP-IPV vaccine (Pediarix) is equivalent to that of their individual antigens administered separately. However, these vaccines cannot be administered to infants aged <6 weeks; only single-antigen hepatitis B vaccine may be used for the birth dose. Use of 4-dose hepatitis B vaccine schedules, including schedules with a birth dose, has not increased vaccine reactogenicity (92,93). Anti-HBs responses after a 3-dose series of hepatitis B-containing combination vaccines among infants who were previously vaccinated at birth with single-antigen hepatitis B vaccine are comparable to those observed after a 3-dose series of combination vaccine without a birth dose (93).

Birth Dose

Hepatitis B vaccine can be administered soon after birth with only minimal decrease in immunogenicity, compared with administration at older ages, and no decrease in protective efficacy (87). Administration of a birth dose of hepatitis B vaccine is required for effective postexposure immuno-prophylaxis to prevent perinatal HBV infection. Although infants who require postexposure immunoprophylaxis should be identified by maternal HBsAg testing, administering a birth dose to infants even without HBIG serves as a "safety net" to prevent perinatal infection among infants born to HBsAg-positive mothers who are not identified because of errors in maternal HBsAg testing or failures in reporting of test results (13). The birth dose also provides early protection to infants at risk for infection after the perinatal period. Administration of a birth dose has been associated with higher rates of on-time completion of the hepatitis B vaccine series (15,94). In certain populations, the birth dose has been associated with improved completion rates for all other infant vaccines (95), although findings have not been consistent (15,94).

Adolescents

Recommended vaccination schedules for adolescents balance available immunogenicity data with the need to achieve compliance with vaccination in this age group (Tables 2 and 5). Both licensed single-antigen hepatitis B vaccines administered intramuscularly at 0, 1, and 6 months produce a >95% sero-protection rate in adolescents. Equivalent seroprotection rates are achieved among adolescents vaccinated at 0, 1--2, and 4 months and 0, 12, and 24 months. The adult (10 µg) dose of Recombivax-HB administered in a 2-dose schedule to children and adolescents aged 11--15 years at 0 and 4--6 months produces antibody levels equivalent to those obtained with the 5-µg dose administered on a 3-dose schedule (96,97). However, no data on long-term antibody persistence or protection are available for 2-dose schedules. No combination vaccines containing hepatitis B vaccine antigen are approved for use in adolescents aged 11--17 years.

Nonstandard Vaccine Schedules

No apparent effect on immunogenicity has been documented when minimum spacing of doses is not achieved precisely. Increasing the interval between the first 2 doses has little effect on immunogenicity or final antibody concentration (98--100). The third dose confers the maximum level of seroprotection but acts primarily as a booster and appears to provide optimal long-term protection (101). Longer intervals between the last 2 doses result in higher final antibody levels but might increase the risk for acquisition of HBV infection among persons who have a delayed response to vaccination. No differences in immunogenicity have been observed when 1 or 2 doses of hepatitis B vaccine produced by one manufacturer are followed by doses from a different manufacturer (102).

Response to Revaccination

A study of infants born to HBsAg-positive mothers who did not respond to a primary vaccine series indicated that all those not infected with HBV responded satisfactorily to a repeat 3-dose revaccination series (103). No data suggest that children who have no detectable antibody after 6 doses of vaccine would benefit from additional doses.

Groups Requiring Different Vaccination Doses or Schedules

Preterm infants. Preterm infants weighing <2,000 g at birth have a decreased response to hepatitis B vaccine administered before age 1 month (104--106). By age 1 month, medically stable preterm infants, regardless of initial birth weight or gestational age, have a response to vaccination that is comparable to that of full-term infants (107--110).

Hemodialysis patients and other immunocompromised persons. Although data concerning the response of pediatric hemodialysis patients to vaccination with standard pediatric doses are lacking, protective levels of antibody occur in 75%--97% of those who receive higher dosages (20-µg) on either the 3- or the 4-dose schedule (111--114). Humoral response to hepatitis B vaccination is also reduced in other children and adolescents who are immunocompromised (e.g., hematopoietic stem cell transplant recipients, patients undergoing chemotherapy, and HIV-infected persons) (115--119). Modified dosing regimens, including a doubling of the standard antigen dose or administration of additional doses, might increase response rates (120). However, data on response to these alternative vaccination schedules are limited (121).

Immune Memory

Anti-HBs is the only easily measurable correlate of vaccine-induced protection. Immunocompetent persons who achieve anti-HBs concentrations >10 mIU/mL after preexposure vaccination have virtually complete protection against both acute disease and chronic infection even if anti-HBs concentrations subsequently decline to <10 mIU/mL (122--125). Although immunogenicity is lower among immunocompromised persons, those who achieve and maintain a protective antibody response before exposure to HBV have a high level of protection from infection.

After primary immunization with hepatitis B vaccine, anti-HBs concentrations decline rapidly within the first year and more slowly thereafter. Among children who respond to a primary vaccine series with antibody levels >10 mIU/mL, 15%--50% have low or undetectable concentrations of anti-HBs (anti-HBs loss) 5--15 years after vaccination (126--130). The persistence of detectable anti-HBs after vaccination, in the absence of exposure to HBV, depends on the level of postvaccination antibody concentration.

Despite declines in anti-HBs to <10 mIU/mL, nearly all vaccinated persons are still protected against HBV infection. The mechanism for continued vaccine-induced protection is thought to be the preservation of immune memory through selective expansion and differentiation of clones of antigen-specific B and T lymphocytes (131). Persistence of vaccine-induced immune memory among persons who responded to a primary childhood vaccine series 13--23 years earlier but then had levels of anti-HBs below 10 mIU/mL has been demonstrated by an anamnestic increase in anti-HBs levels in 67%--76% of these persons 2--4 weeks after administration of an additional vaccine dose (132,133). Although direct measurement of immune memory is not yet possible, these data indicate that a high proportion of vaccine recipients retain immune memory and would develop an anti-HBs response upon exposure to HBV.

Studies of cohorts of immunocompetent persons vaccinated as children or infants also indicate that, despite anti-HBs loss years after immunization, nearly all vaccinated persons who respond to a primary series remain protected from HBV infection. No clinical cases of hepatitis B have been observed in follow-up studies conducted 15--20 years after vaccination among immunocompetent vaccinated persons with antibody levels >10 mIU/mL. Certain studies have documented breakthrough infections (detected by the presence of anti-HBc or HBV DNA) in a limited percentage of vaccinated persons (130,131), but these infections are usually transient and asymptomatic; chronic infections have been documented only rarely (134). Breakthrough infections resulting in chronic infection have been observed only among vaccinated infants born to HBsAg-positive women.

Limited data are available on the duration of immune memory after hepatitis B vaccination in immunocompromised persons (e.g., HIV-infected patients, dialysis patients, patients undergoing chemotherapy, or hematopoietic stem cell transplant patients). No clinically important HBV infections have been documented among immunocompromised persons who maintain protective levels of anti-HBs. In studies of long-term protection among HIV-infected persons, breakthrough infections occurring after a decline in anti-HBs concentrations to <10 mIU/mL have been transient and asymptomatic (135). However, among hemodialysis patients who respond to the vaccine, clinically significant HBV infection has been documented in persons who have not maintained anti-HBs concentrations of >10 mIU/mL (136).

Postexposure Prophylaxis

Both passive-active postexposure prophylaxis (PEP) with HBIG and hepatitis B vaccine and active PEP with hepatitis B vaccine alone have been demonstrated to be highly effective in preventing transmission after exposure to HBV (137--140). HBIG alone has also been demonstrated to be effective in preventing HBV transmission (141--144), but with the availability of hepatitis B vaccine, HBIG typically is used as an adjunct to vaccination.

The major determinant of the effectiveness of PEP is early administration of the initial dose of vaccine. The effectiveness of PEP diminishes the longer it is initiated after exposure (17,145,146). Studies are limited on the maximum interval after exposure during which PEP is effective, but the interval is unlikely to exceed 7 days for perinatal (147) and needlestick (140--142) exposures and 14 days for sexual exposures (122, 138,139,143,144).

No data are available on the efficacy of HBsAg-containing combination vaccines when used to complete the vaccine series for PEP, but the efficacy of combination vaccines is expected to be similar to that of single-antigen vaccines because the HBsAg component induces a comparable anti-HBs response.

IC

Perinatal HBV Exposure

Passive-active PEP. PEP with hepatitis B vaccine and HBIG administered 12--24 hours after birth, followed by completion of a 3-dose vaccine series, has been demonstrated to be 85%--95% effective in preventing acute and chronic HBV infection in infants born to women who are positive for both HBsAg and HBeAg (137). Although clinical trials have evaluated the efficacy of passive-active PEP with hepatitis B vaccine and HBIG administered only within 24 hours of birth, studies of passive immunoprophylaxis have demonstrated that HBIG provided protection when administered as late as 72 hours after exposure. The majority of clinical trials have evaluated the efficacy of passive-active PEP when the second vaccine dose was administered at age 1 month (137). Administration of HBIG plus vaccine at birth, 1 month, and 6 months and at birth, 2 months, and 6 months has demonstrated comparable efficacy in prevention of acute and chronic infection among infants born to women who were both HBsAg and HBeAg positive (Cladd E. Stevens, MD, New York Blood Center, personal communication, 1994).

Infants born to HBsAg-positive/HBeAg-negative mothers who receive passive-active PEP with HBIG and hepatitis B vaccine should have the same high degree of protection as infants born to women who are HBsAg positive/HBeAg positive. However, the efficacy of this regimen has not been examined in controlled clinical trials because the low infection rate would require an unattainable sample size.

Active PEP. Active PEP with hepatitis B vaccine alone (i.e., without HBIG) is frequently used in certain remote areas (e.g., Alaska and the Pacific Islands) where implementation of maternal HBsAg testing is difficult because no access exists to a laboratory. In randomized, placebo-controlled clinical trials, administration of hepatitis B vaccine in a 3- or 4-dose schedule without HBIG beginning <12 hours after birth has been demonstrated to prevent 70%--95% of perinatal HBV infections among infants born to women who are positive for both HBsAg and HBeAg (58,148--152). Population-based studies in areas with a high endemicity of HBV infection have demonstrated that active postexposure vaccination is highly effective in preventing infection when the first dose is administered soon after birth, the second at age 1--2 months, and the third at age 6--8 months (153--155).

IC

Vaccine Safety

Hepatitis B vaccines have been demonstrated to be safe when administered to infants, children, adolescents, and adults. Since 1982, an estimated >60 million adolescents and adults and >40 million infants and children have been vaccinated in the United States.

Vaccine Reactogenicity

The most frequently reported side effects among persons receiving hepatitis B vaccine are pain at the injection site (3%--29%) and fever >99.9° F (>37.7° C) (1%--6%) (156,157). However, in placebo-controlled studies, these side effects were reported no more frequently among persons receiving hepatitis B vaccine than among persons receiving placebo (87). Administration of hepatitis B vaccine soon after birth has not been associated with an increased rate of elevated temperatures or microbiologic evaluations for possible sepsis in the first 21 days of life (158).

Adverse Events

A causal association has been established between receipt of hepatitis B vaccine and anaphylaxis (159). On the basis of data from the Vaccine Safety Datalink (VSD) project, the estimated incidence of anaphylaxis among children and adolescents who received hepatitis B vaccine is one case per 1.1 million vaccine doses distributed (95% confidence interval = 0.1--3.9) (160).

Early postlicensure surveillance of adverse events suggested a possible association between Guillain-Barré syndrome and receipt of the first dose of plasma-derived hepatitis B vaccine among U.S. adults (161). However, in a subsequent analysis of Guillain-Barré syndrome cases reported to CDC, FDA, and vaccine manufacturers, among an estimated 2.5 million adults who received >1 dose of recombinant hepatitis B vaccine during 1986--1990, the rate of Guillain-Barré syndrome occurring after hepatitis B vaccination did not exceed the background rate among unvaccinated persons (CDC, unpublished data, 1992). A review by persons with clinical expertise concluded that evidence was insufficient to reject or accept a causal association between Guillain-Barré syndrome and hepatitis B vaccination (159,162).

Multiple sclerosis (MS) has not been reported after hepatitis B vaccination among children. However, one retrospective case-control study (163,164) reported an association between hepatitis B vaccine and MS among adults. Multiple other studies (165--168) have demonstrated no association between hepatitis B vaccine and MS. Reviews of these data by panels of persons with clinical expertise have favored rejection of a causal association between hepatitis B vaccination and MS (169,170).

Chronic illnesses that have been reported in rare instances after hepatitis B vaccination include chronic fatigue syndrome (171), neurologic disorders (e.g., leukoencephalitis, optic neuritis, and transverse myelitis) (172--174), rheumatoid arthritis (175,176), type 1 diabetes (177), and autoimmune disease (178). No evidence of a causal association between these conditions or other chronic illnesses and hepatitis B vaccine has been demonstrated (159,169,170,179--182).

Reported episodes of alopecia (hair loss) after rechallenge with hepatitis B vaccine suggest that vaccination might, in rare cases, trigger episodes of alopecia (183). However, a population-based study determined no statistically significant association between alopecia and hepatitis B vaccine (184).

No evidence exists of a causal association between hepatitis B vaccination, including administration of the birth dose, and sudden infant death syndrome (SIDS) or other causes of death during the first year of life (185--187). Infant death rates, including rates of SIDS, declined substantially in the United States during the 1990s, coincident with an increase in infant hepatitis B vaccination coverage from <1% to >90% and implementation of efforts to reduce SIDS through infant sleep positioning and separation from other persons in bed (188).

The safety of hepatitis B vaccine and other vaccines is assessed continuously through ongoing monitoring of data from VSD, the Vaccine Adverse Events Reporting System (VAERS), and other surveillance systems. Any adverse events after vaccination should be reported to VAERS; report forms and assistance are available from CDC at telephone 1-800-822-7967 or at http://www.vaers.hhs.gov.

Contraindications and Precautions

Hepatitis B vaccination is contraindicated for persons with a history of hypersensitivity to yeast or to any vaccine component (92,189--191). Despite a theoretic risk for allergic reaction to vaccination in persons with allergy to Saccharomyces cerevisiae (baker's yeast), no evidence exists that documents adverse reactions after vaccination of persons with a history of yeast allergy.

Persons with a history of serious adverse events (e.g., anaphylaxis) after receipt of hepatitis B vaccine should not receive additional doses. As with other vaccines, vaccination of persons with moderate or severe acute illness, with or without fever, should be deferred until the acute phase of the illness resolves (192). Vaccination is not contraindicated in persons with a history of MS, Guillain-Barré syndrome, autoimmune disease (e.g., systemic lupus erythematosis or rheumatoid arthritis), or other chronic diseases.

Pregnancy is not a contraindication to vaccination. Limited data indicate no apparent risk for adverse events to developing fetuses when hepatitis B vaccine is administered to pregnant women (193). Current vaccines contain noninfectious HBsAg and should cause no risk to the fetus.

IC

Future Considerations

Implementation of the recommendations and strategies in this document should ultimately lead to the elimination of HBV transmission in the United States. New information will have implications for this effort, and adjustments and changes are expected to occur.

Long-Term Protection and Booster Doses

Studies are needed to assess long-term protection after vaccination and the possible need for booster doses of vaccine. The longest follow-up studies of vaccine protection have been conducted in populations with an initially high endemicity of HBV infection (i.e., >8% prevalence of chronic infection) (130). Implementation of hepatitis B vaccination programs in populations with a high endemicity of HBV infection has resulted in virtual elimination of new HBV infections by providing vaccine-induced immunity to susceptible persons. In these populations, ongoing exposure of vaccinated persons to persons with chronic HBV infection might complicate future efforts to assess long-term hepatitis B vaccine efficacy. Assessment of efficacy provided by hepatitis B immunization after 15--20 years will require studies among populations that continue to have exposures to HBsAg-positive persons (e.g., communities of immigrants from highly endemic countries, populations of injection-drug users, or health-care workers) and studies among populations with a low prevalence of infection.

Immunization Escape Mutants

Mutations in the S gene of HBV can lead to conformational changes in the a determinant of the HBsAg protein, which is the major target for neutralizing anti-HBs. These variants have been detected in humans infected with HBV, and concern has been expressed that these variants might replicate in the presence of vaccine-induced anti-HBs or anti-HBs contained in HBIG (194,195). Although no evidence suggests that S gene immunization escape mutants pose a threat to existing programs using hepatitis B vaccines (196), further studies and enhanced surveillance to detect the emergence of these variants are high priorities for monitoring the effectiveness of current vaccination strategies.

danwp1977

发不到论坛公共邮箱，只好贴上来了，请查收：

间断性接触过HBV病毒源的人群的预防策略

This appendix provides recommendations for management

of persons who are exposed to HBV through a discrete, identifiable

exposure to blood or body fluids that contain blood.

Recommendations for management of infants born to mothers

who test positive for hepatitis B surface antigen (HBsAg)-

positive mothers are provided in this report (see Prevention of

Perinatal HBV Transmission and Management of Pregnant

本附录为那些确认曾间断性接触过感染了HBV病毒的血液或者体液的人群提供预防建议，对于母亲为hbv表面抗原阳性的新生婴儿的预防建议在（this）报告中指出（参看文献：对婴儿出生前后HBV的阻断及对怀孕妇女HBV阻断处理的建议）

 

HBsAg-Positive Source

• Unvaccinated persons (Table C-1) or persons known not

to have responded to a complete hepatitis B vaccine series

should receive both hepatitis B immune globulin (HBIG)

and hepatitis B vaccine as soon as possible after exposure

(preferably <24 hours). For sexual exposures, HBIG

should not be administered more than 14 days after exposure.

Hepatitis B vaccine may be administered simultaneously

with HBIG in a separate injection site. The

hepatitis B vaccine series should be completed using the

age-appropriate vaccine dose and schedule (see Tables 2

 

接触到HbsAg阳性病毒源

·未接种（表C－1）或者经过一个疗程的免疫接种后没有产生免疫应答的人群，应当在接触病毒源后尽快（最好少于24小时）注射乙肝免疫球蛋白和乙肝免疫疫苗。如果是性方式与病毒源接触，应当在之后的连续14天内使用免疫球蛋白HBIG，乙肝疫苗可以和免疫球蛋白在不同的注射点（in a separate injection site）同时使用。应该遵循不同年龄段的注射剂量和程序要求（见表2和3）来完成整个疫苗接种过程。

• Persons who are in the process of being vaccinated but

who have not completed the vaccine series should receive

the appropriate dose of HBIG and should complete the

vaccine series.

• Children and adolescents who have written documentation

of a complete hepatitis B vaccine series and who were

did not receive postvaccination testing should receive a

single vaccine booster dose.

 

·正在接受免疫接种但一个疗程尚未结束的人群应当完成余下的疫苗注射，同时使用适量的乙肝免疫球蛋白。

·对于小孩或者成年人，如果已经完成一个疗程的疫苗注射但没有接受抗体测试的，应当再注射一针乙肝疫苗加强针。

IC

Recommendations for Hepatitis B Vaccination of Infants, Children, and Adolescents

This section outlines updated ACIP recommendations and associated implementation strategies for hepatitis B vaccination of infants, children, and adolescents. These recommendations have been summarized (Box 3).

Prevention of Perinatal HBV Infection and Management of Pregnant Women

Recommendations

Prenatal HBsAg Testing

• All pregnant women should be tested routinely for HBsAg during an early prenatal visit (e.g., first trimester) in each pregnancy, even if they have been previously vaccinated or tested.
• Women who were not screened prenatally, those who engage in behaviors that put them at high risk for infection (e.g., injection-drug use, having had more than one sex partner in the previous 6 months or an HBsAg-positive sex partner, evaluation or treatment for a sexually transmitted disease [STD], or recent or current injection-drug use) and those with clinical hepatitis should be tested at the time of admission to the hospital for delivery.
• All laboratories that provide HBsAg testing of pregnant women should use an FDA-licensed or -approved HBsAg test and should perform testing according to the manufacturer's labeling, including testing of initially reactive specimens with a licensed neutralizing confirmatory test. When pregnant women are tested for HBsAg at the time of admission for delivery, shortened testing protocols may be used and initially reactive results reported to expedite administration of immunoprophylaxis to infants.
• Women who are HBsAg positive should be referred to an appropriate case-management program to ensure that their infants receive timely postexposure prophylaxis and follow-up (see Case-Management Programs to Prevent Perinatal HBV Infection). In addition, a copy of the original laboratory report indicating the pregnant woman's HBsAg status should be provided to the hospital where delivery is planned and to the health-care provider who will care for the newborn.
• Women who are HBsAg positive should be provided with or referred for appropriate counseling and medical management (Appendix A). HBsAg-positive pregnant women should receive information concerning hepatitis B that discusses
  --- modes of transmission;
  --- perinatal concerns (e.g., infants born to HBsAg-positive mothers may be breast fed);
  --- prevention of HBV transmission to contacts, including the importance of postexposure prophylaxis for the newborn infant and hepatitis B vaccination for household, sexual, and needle-sharing contacts;
  --- substance abuse treatment, if appropriate; and
  --- medical evaluation and possible treatment of chronic hepatitis B.
• When HBsAg testing of pregnant women is not feasible (i.e., in remote areas without access to a laboratory), all infants should receive hepatitis B vaccine <12 hours of birth and should complete the hepatitis B vaccine series according to a recommended schedule for infants born to HBsAg-positive mothers (Tables 2 and 3).

Management of Infants Born to Women Who Are HBsAg Positive

• All infants born to HBsAg-positive women should receive single-antigen hepatitis B vaccine (Table 2) and HBIG (0.5 mL) <12 hours of birth, administered at different injection sites. The vaccine series should be completed according to a recommended schedule for infants born to HBsAg-positive mothers (Table 3). The final dose in the vaccine series should not be administered before age 24 weeks (164 days).
• For preterm infants weighing <2,000 g, the initial vaccine dose (birth dose) should not be counted as part of the vaccine series because of the potentially reduced immunogenicity of hepatitis B vaccine in these infants; 3 additional doses of vaccine (for a total of 4 doses) should be administered beginning when the infant reaches age 1 month (Tables 3 and 4).
• Postvaccination testing for anti-HBs and HBsAg should be performed after completion of the vaccine series, at age 9--18 months (generally at the next well-child visit). Testing should not be performed before age 9 months to avoid detection of anti-HBs from HBIG administered during infancy and to maximize the likelihood of detecting late HBV infection. Anti-HBc testing of infants is not recommended because passively acquired maternal anti-HBc might be detected in infants born to HBV-infected mothers to age 24 months.
  --- HBsAg-negative infants with anti-HBs levels >10 mIU/mL are protected and need no further medical management.
  --- HBsAg-negative infants with anti-HBs levels <10 mIU/mL should be revaccinated with a second 3-dose series and retested 1--2 months after the final dose of vaccine.
  --- Infants who are HBsAg positive should receive appropriate follow-up (Appendix A).
• Infants of HBsAg-positive mothers may be breast fed beginning immediately after birth.
• Although not indicated in the manufacturer's package labeling, HBsAg-containing combination vaccines may be used for infants aged >6 weeks born to HBsAg-positive mothers to complete the vaccine series after receipt of a birth dose of single-antigen hepatitis B vaccine and HBIG.

danwp1977

Source with Unknown HBsAg Status

• Unvaccinated persons (Table C-1) should receive the hepatitis

B vaccine series with the first dose initiated as soon as

possible after exposure, preferably <24 hours. The vaccine

series should be completed using the age-appropriate

dose and schedule (see Tables 2, 3, and 5).

• Persons who are not fully vaccinated should complete the

vaccine series.

• Children and adolescents with written documentation of

a complete hepatitis B vaccine series require no further

treatment.

接触到未知HBSAG状态的疑似病毒源

·未接种人群（表C－1）在接触疑似源后应当完成一个疗程的免疫疫苗注射，第一针最好在接触疑似源的24小时之内注射，要根据年龄段来选择注射剂量和注射程序（参看表2，3，5）。

·已经完成一个疗程的疫苗注射的大人或者小孩，无需进一步治疗。

IC

Management of Infants Born to Women with Unknown HBsAg Status

• Women admitted for delivery without documentation of HBsAg test results should have blood drawn and tested as soon as possible after admission.
• While test results are pending, all infants born to women without documentation of HBsAg test results should receive the first dose of single-antigen hepatitis B vaccine (without HBIG) <12 hours of birth (Tables 2 and 3).
  --- If the mother is determined to be HBsAg positive, her infant should receive HBIG as soon as possible but no later than age 7 days, and the vaccine series should be completed according to a recommended schedule for infants born to HBsAg-positive mothers (Table 3).
  --- If the mother is determined to be HBsAg negative, the vaccine series should be completed according to a recommended schedule for infants born to HBsAg-negative mothers (Table 3).
  --- If the mother has never been tested to determine her HBsAg status, the vaccine series should be completed according to a recommended schedule for infants born to HBsAg-positive mothers (Table 3). Administration of HBIG is not necessary for these infants.
• Because of the potentially decreased immunogenicity of vaccine in preterm infants weighing <2,000 g, these infants should receive both single-antigen hepatitis B vaccine and HBIG (0.5 mL) if the mother's HBsAg status cannot be determined <12 hours of birth. The birth dose of vaccine should not be counted as part of the 3 doses required to complete the vaccine series; 3 additional doses of vaccine (for a total of 4 doses) should be administered according to a recommended schedule on the basis of the mother's HBsAg test result (Table 3).

Vaccination of Pregnant Women

• Pregnant women who are identified as being at risk for HBV infection during pregnancy (e.g., having more than one sex partner during the previous 6 months, been evaluated or treated for an STD, recent or current injection-drug use, or having had an HBsAg-positive sex partner) should be vaccinated.
• Pregnant women at risk for HBV infection during pregnancy should be counseled concerning other methods to prevent HBV infection.

Implementation

Delivery Hospital Policies and Procedures

• All delivery hospitals should implement policies and procedures (Box 4) to ensure 1) identification of infants born to HBsAg-positive mothers and infants born to mothers with unknown HBsAg status (see Prenatal HBsAg Testing), and 2) initiation of immunization for these infants. Such policies and procedures should include the following standing orders:
  --- for all pregnant women, review of HBsAg test results at the time of admission for delivery;
  --- for women who do not have a documented HBsAg test result, HBsAg testing as soon as possible after admission for delivery;
  --- identification and management of all infants born to HBsAg-positive mothers;
  --- identification and management of all infants born to mothers with unknown HBsAg status; and
  --- for all infants, documentation on the infant's medical record of maternal HBsAg test results, infant hepatitis B vaccine administration, and administration of HBIG (if appropriate).
• Delivery hospitals should enroll in the federally funded Vaccines for Children (VFC) program to obtain free hepatitis B vaccine for administration of the birth dose to newborns who are eligible (i.e., Medicaid eligible, American Indian or Alaska Native, underinsured, or uninsured).

Case-Management Programs to Prevent Perinatal HBV Infection

• States and localities should establish case-management programs (Box 5), including appropriate policies, procedures, laws, and regulations, to ensure that
  --- all pregnant women are tested for HBsAg during each pregnancy, and
  --- infants born to HBsAg-positive women and infants born to women with unknown HBsAg status receive recommended case management.
• The location of these programs and the methods by which they operate will depend on multiple factors (e.g., population density and annual caseload of HBsAg-positive women). Programs may be located in state or local health departments, private health-care systems (e.g., health maintenance organizations), or institutions (e.g., correctional facility systems). Program administrators will need to work with prenatal care providers, delivery hospital staff, pediatric care providers, private health-care systems, and health departments.

Universal Vaccination of Infants

Recommendations

• All infants should receive the hepatitis B vaccine series as part of the recommended childhood immunization schedule (Table 5 and Appendix B). (For recommendations on management of infants born to HBsAg-positive mothers and infants born to mothers with unknown HBsAg status, see Prevention of Perinatal HBV Infection and Management of Pregnant Women.)
• For all medically stable infants weighing >2,000 g at birth and born to HBsAg-negative mothers, the first dose of vaccine should be administered before hospital discharge. Only single-antigen hepatitis B vaccine should be used for the birth dose.
• On a case-by-case basis and only in rare circumstances, the first dose may be delayed until after hospital discharge for an infant who weighs >2,000 g and whose mother is HBsAg negative.
  --- When such a decision is made, a physician's order to withhold the birth dose and a copy of the original laboratory report indicating that the mother was HBsAg negative during this pregnancy should be placed in the infant's medical record.
  --- For infants who do not receive a first dose before hospital discharge, the first dose should be administered no later than age 2 months.
  --- Situations in which the birth dose should not be delayed include any high-risk sexual or drug-using practices of the infant's mother during pregnancy (e.g., having had more than one sex partner during the previous 6 months or an HBsAg-positive sex partner, evaluation or treatment for an STD, or recent or current injection-drug use) and expected poor compliance with follow-up to initiate the vaccine series.
• Preterm infants weighing <2,000 g and born to HBsAg-negative mothers should have their first vaccine dose delayed until 1 month after birth or hospital discharge (Table 4). For these infants, a copy of the original laboratory report indicating that the mother was HBsAg negative during this pregnancy should be placed in the infant's medical record.
• The vaccine series should be completed according to a recommended schedule with either single-antigen vaccine or a combination vaccine that contains the hepatitis B vaccine antigen (e.g., Hib-hepatitis B or DTaP-IPV-hepatitis B) (Table 2). The final dose in the vaccine series should not be administered before age 24 weeks (164 days).
• Administration of 4 doses of hepatitis B vaccine to infants is permissible in certain situations (e.g., when combination vaccines are administered after the birth dose).
• In populations with currently or previously high rates of childhood HBV infection (i.e., Alaska Natives; Pacific Islanders; and immigrant families from Asia, Africa, and other regions with intermediate or high endemic rates of infection [Figure 1 and Box 2]), the first dose of hepatitis B vaccine should be administered at birth and the final dose at age 6--12 months.

Implementation

• All delivery hospitals should implement standing orders for administration of hepatitis B vaccination as part of routine medical care of all medically stable infants weighing >2,000 g at birth (Box 4).
• All delivery hospitals should implement policies and procedures for management of infants weighing <2,000 g at birth, including the following:
  --- ensuring initiation of postexposure immunization of infants born to HBsAg-positive mothers and infants born to mothers not screened for HBsAg prenatally (see Prevention of Perinatal HBV Infection and Management of Pregnant Women), and
  --- documentation of maternal HBsAg test results on the infant's medical record.
• Prenatal care education should include information regarding the rationale for and importance of newborn hepatitis B vaccination.
• States are encouraged to adopt regulations or laws that require hepatitis B vaccination for entry into child care and also for entry into kindergarten and/or elementary school to ensure high vaccine coverage among infants and children.

IC

Vaccination of Children and Adolescents Who Were Not Previously Vaccinated

Recommendations

• Hepatitis B vaccination is recommended for all children and adolescents aged <19 years.
• Children and adolescents who have not previously received hepatitis B vaccine should be vaccinated routinely at any age with an appropriate dose and schedule (Tables 2 and 5). Selection of a vaccine schedule should consider the need to achieve completion of the vaccine series. In all settings, vaccination should be initiated even though completion of the vaccine series might not be ensured.

Implementation

• To ensure high vaccination coverage among children and adolescents, the following measures are recommended:
  --- All children aged 11--12 years should have a review of their immunization records and should complete the vaccine series if they were not previously vaccinated or were incompletely vaccinated.
  --- All children and adolescents aged <19 years (including internationally adopted children) who were born in Asia, the Pacific Islands, Africa, or other intermediate- or high-endemic countries (Figure 1 and Box 2) or who have at least one parent who was born in one of these areas should have a review of their immunization records and should complete the vaccine series if they were not previously vaccinated or were incompletely vaccinated.
  --- States are encouraged to adopt regulations or laws that require hepatitis B vaccination before entry into middle school or its equivalent.
  --- Vaccination requirements should be considered for older high school students and for students before college entry, when feasible.
  --- States are encouraged to expand or implement immunization registries to include adolescents.
  --- Hepatitis B vaccine should be offered to all unvaccinated adolescents in settings that provide health-care services to this age group (Box 6), particularly those who engage in behaviors that place them at high risk for HBV infection.

Acknowledgments

Review of this report was provided by the following persons: R. Palmer Beasley, MD, School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas; F. Blaine Hollinger, MD, Baylor College of Medicine, Houston, Texas; Neal A. Halsey, MD, Johns Hopkins Bloomberg School of Public Health and Johns Hopkins School of Medicine, Baltimore, Maryland; and Craig N. Shapiro, MD, Office of Global Health Affairs, U.S. Department of Health and Human Services, Washington, DC. Allison Greenspan, MPH, Division of Viral Hepatitis, National Center for Infectious Diseases, CDC, provided vital assistance in the preparation of this report.

danwp1977

TABLE C-1. Guidelines for postexposure immunoprophylaxis of unvaccinated persons who are exposed to blodo or body fluids

that contain blood

表C－1 未接种疫苗人群在接触了含HBV血液或者体液后的治疗指南

Cause

 

 Action

Discrete exposure to an HBsAg*-positive source

Percutaneous (e.g., bite, needlestick) or mucosal exposure to HBsAg-positive

blood or body fluids that contain blood

Sexual or needle-sharing contact of an HBsAg-positive person

Victim of sexual assault/abuse by a perpetrator who is HBsAg-positive

Discrete exposure to a source with unknown HBsAg status

Victim of sexual assault/abuse by a perpetrator with unknown HBsAg status

Percutaneous (e.g., bite or needclestick) or mucosal exposure to blood or

body fluids that contain blood from a source with unknown HBsAg status

* Hepatitis B surface antigen.

†Immunoprophylaxis should be administered as soon as possible, preferably <24 hours. Studies are limited on the maximum interval after exposure during

which postexposure prophylaxis is effective, but the interval is unlikely to exceed 7 days for percutaneous exposures and 14 days for sexual exposures. The

hepatitis B vaccine series should be completed.

Administer hepatitis B vaccine and hepatitis B immune globulin

(HBIG)†

Administer hepatitis B vaccine and HBIG†

Administer hepatitis B vaccine and HBIG†

Administer hepatitis B vaccine†

Administer hepatitis B vaccine†