Hepatitis B vaccination recommendations have been evolving ever since the plasmaderived vaccine was first licensed in the United States more than 2 decades ago. In this article, current recommendations for infant immunization against hepatitis B are reviewed, including indications, contraindications, scheduling, co-administration with other vaccines, storage and handling, and injection technique. Use of the vaccine in older children, adolescents, and adults is not covered in detail. In addition, answers to questions parents and healthcare providers commonly ask about hepatitis B and the vaccine are provided.
DEVELOPMENT OF HEPATITIS B VACCINE
Our understanding of hepatitis B flowered in the 1960s when Krugman confirmed the existence of two distinct forms of viral hepatitis: infectious hepatitis, transmitted by the fecal-oral route (now called hepatitis A); and serum hepatitis, transmitted by direct contact with blood or hodily fluids (now called hepatitis B).4
Around the same time, Blumberg discovered an antigen in serum - dubbed die "Australia antigen" because of its high prevalence in Australian aborigines - that was associated with hepatitis B virus (HBV) infection.5 This antigen, now called hepatitis B surface antigen (HBsAg), circulates in the blood as a result of chronic infection of the liver. The development of a vaccine was stimulated by observations that antibodies to HBsAg provided lifelong protection against re-infection wim the virus, and that injections of HBsAg-containing serum could induce antibodies to HBsAg.6 Remarkably, at this time, more than 1 billion doses of hepatitis B vaccine have been administered to people worldwide to prevent HBV infection.7
The first hepatitis B vaccines were derived in the 1970s from plasma of chronically infected people. HBsAg particles circulating in die blood were concentrated, inactivated, and formulated into a safe, immunogenic, and highly effective vaccine that was licensed in 198 1.8
However, the manufacture of plasmaderived vaccines depended on a supply of human donors, making it costly to produce. In addition, popular concern began to accumulate about the potential for spread of blood-borne pathogens through the vaccine, even though there was no evidence to support this. Consequently, plasma-derived vaccines fell from favor and were removed from the US market in 1992, although they continue to be used in other countries.
The licensure of recombinant hepatitis B vaccine (Hep-B) in 1986 set a precedent. Never before had recombinant DNA technology been employed to create a vaccine for generalized use. A plasmid carrying die gene encoding HBsAg was inserted into the DNA of common baker's yeast Sacchawmyces cerevisiae), which then produced me protein in large quantities for harvest and purification. The final preparation is adsorbed to alum and is free of most yeast-derived protein and all detectable yeast DNA.
Because no complete viral particles are used to produce these vaccines, HepB cannot cause HBV infection. Two licensed recombinant vaccines are available in the United States (Table, see page 518): Recombivax HB (licensed in 1986) and Engerix-B (licensed in 1989). Each is available in pediatric and adult formulations, and there are special formulations for immunosuppressed patients and those on dialysis.
Three combination vaccines licensed in the United States contain Hep-B (Table, see page 518): Comvax, which is combined with Haemophilus influenzae type b (Hib) conjugate (licensed in 1996); Pediarix, which is combined with diphtheria, tetanus, acellular pertussis, and inactivated poliovirus vaccines (licensed in 2002); and Twinrix, which is combined with hepatitis A vaccine and approved only for use in people 18 or older (licensed in 2001 ).
EVOLUTION OF HEPATITIS B VACCINATION RECOMMENDATIONS
Just as development of Hep-B spanned several decades, the current recommendations for this vaccine have developed with time.9
In 1982, the Advisory Committee on Immunization Practices (ACIP) of die Centers for Disease Control and Prevention (CDC) published its first official recommendations for me use of Hep-B in people known to be at high risk for HBV infection.8 Since then, the number of people considered to be at high risk for exposure has expanded, leading to the current list of indications shown in the Sidebar. Unfortunately, many high-risk people do not seek routine preventive healthcare. It is, therefore, understandable that the initial public healm strategy based on vaccinating such people failed, leading to recommendations for universal coverage.10
In 1984, the ACIP recommended that women in high-risk groups be tested for HBsAg during me prenatal period, and that those infants born to HBsAg-positive mothers receive both Hep-B and hepatitis B immune globulin (HBIG)." In 1988, recognizing that screening criteria failed to identify many infected women, me ACIP expanded the recommendation to include screening of all pregnant women for HBsAg.12 Universal vaccination of all infants was recommended in 1991, and me vaccination schedule at that time called for me first dose to be given between birth and age 2 monms.10
However, during the 1990s, it became apparent mat some infants were being exposed to HBV perinatally even though their mothers had screened negative for HBsAg. Consequently, in 2002 the ACIP established a strong preference for giving the first dose of Hep-B to all newborns at birth, regardless of maternal HBsAg status; despite dûs preference, the "official" 2004 schedule still reads birth to 2 months for me first dose.13·14
Infants and Children
In 1991, ACIP recommended that all infants receive the Hep-B series,10 which is discussed later in me article. In 1995.15 the recommendation was expanded to include all children ages 11 to 12 who had not been vaccinated previously. It was again expanded in 1999 to all unvaccinated children from birth to age 1 8. 16 At this time, many states require Hep-B immunization for school attendance.17
Deferral of Birth Dose to Reduce Thimerosal Exposure
On July 8, 1999, the American Academy of Pediatrics (AAP) and the US Public Health Service published a joint statement recommending physicians take advantage of flexibility in the infant Hep-B schedule to reduce early exposure to thimerosal, an ethylmercurycontaining preservative that was in the vaccine at that time.18 The recommendation was made to postpone me first dose of Hep-B vaccine until ages 2 to 6 months for infants born to mothers who had tested negative for HBsAg. No change in recommendation was made for infants with mothers whose statuses were HBsAg-positive or -unknown.
Unfortunately, this recommendation frequently was misinterpreted, leading many hospitals to dismantle the systems they had put in place to deliver birth doses to all infants. In the process, some infants born to HBsAg-positive mothers were not vaccinated. Although adequate supplies of preservative-free Hep-B were available by mid-September of that year, many hospitals did not reinstate newborn Hep-B vaccination policies.19"21 The recommendation for use of the birth dose was reinstated by the end of October.
Vaccines Containing Hepatitis B Available in the United States
Although the current immunization schedule recommends that the first HepB vaccine dose be administered between birth and 2 months, the ACIP has stated its preference for rountine administration of this first dose at birth for all infants, even those born to HBsAg-negative mothers.14 A birth dose of single antigen Hep-B is also preferred for infants who will receive a combination vaccine containing Hep-B as part of the primary series.
Current recommendations for the use of Hep-B can be found in the following resources: Epidemiology and Prevention of Vaccine-Preventable Diseases (the Pink Book), ' 2003 Red Book: Report of the Committee on Infectious Diseases,2 and the general recommendations on immunization.22
All women should be tested for the presence of HBsAg in serum early in pregnancy, at the same time as other routine prenatal tests are done.12 Women who are at particularly high risk should be tested again in the third trimester. Women who have not been tested, and those whose test results cannot be confirmed, should have me test done as soon as possible after admission for delivery. Prenatal testing is indicated during each pregnancy. Maternal screening is critical for infants because it determines the need for emergency perinatal prophylaxis with both Hep-B and HBIG.
An anaphylactic reaction to a prior dose of the vaccine or to any vaccine component (eg, baker's yeast) is the only absolute contraindication to HepB. As with all vaccines, the presence of a moderate to severe acute illness should prompt postponement of vaccination because a reaction to the vaccine could be confused with the concurrent illness. Pregnancy, lactation, and immunodeficiency are not contraindications.
Timing and Scheduling
There is much confusion about the complex timing and scheduling of HepB. The Table shows the recommended schedules for infant immunization with Hep-B using single antigen or combination vaccines. Schedules for older children and adolescents may be found elsewhere.17·18 Maternal HBsAg status, birth weight, birth dose preference, intervals between doses, and minimum age for the final dose all influence me infant Hep-B schedule.1·2·22
Maternal HBsAg status. For an infant whose mother's HBsAg test is positive or unknown, Hep-B administration in the infant's first 12 hours of life is a medical emergency because of the high risk of transmission and resultant chronic infection, which can lead to liver failure and cancer. HBIG also should be given to these newborns in the first 12 hours, except when the momer's HBsAg status is unknown and me birth weight is 2,000 g or more. In these cases, testing of the mother should be done immediately, and, if positive, the newborn should receive HBIG by day 7 of life. Some healthcare providers ignore these recommendations because me mother does not "look positive" or me physician believes the test result must be a false positive; such practices put infants' health at risk.
Birth weight. The immune response to Hep-B is not ideal in newborns weighing less than 2,000 g. For this reason, the first dose of Hep-B for these infants should be given at age 1 month, as long as the mother's HBsAg status is negative. If the mother's HBsAg status is positive or unknown, the first dose should be given within 12 hours of birth, but this dose should not be counted toward completion of the three-dose series. It is recognized mat in this situation, four total doses will be given, but this is not considered to be harmful.
Birth dose preference. As discussed previously, it is preferred mat the first dose of Hep-B be given at birth. The rationale is discussed later in this article. Only single antigen Hep-B should be used between birth and 6 weeks of age; neither Comvax (Hep-B plus Haemophilus influenzae type b polysaccharide conjugate) nor Pediarix (diphtheria-tetanus-acellular pertussis, Hep-B, and inactivated poliovirus vaccine) are licensed for use before age 6 weeks. These combination vaccines may be used to complete a Hep-B series initiated with single antigen vaccine. See me article by Dr. Gary Marshall on page 501 for a more detailed discussion of diese combination vaccines.
Minimum intervals between doses. Although prolonged intervals between doses in the series are not a problem, immunogenicity is threatened by intervals that are too short. There should be a minimum of 4 weeks between doses one and two, a minimum of 8 weeks between doses two and three, and a minimum of 16 weeks between doses one and three.
Minimum age for the final dose. The final dose of Hep-B should not be given before 24 weeks of age. This is also true when the final dose of Hep-B is given as part of the Pediarix series. However, when Comvax is used, me final dose should not be given before me first birthday.
Co-administration with other vaccines. Hep-B may be given at the same time as any other vaccine, and there is no minimum interval between Hep-B and any other vaccine (except for a subsequent dose of Hep-B).
Post-vaccination testing. Testing for antibodies to HBsAg is not necessary after routine immunization, but infants born to HBsAg-positive mothers should be tested for both HBsAg and antibodies to HBsAg after they complete the full series. Additionally, me 2003 Red Book18 does recommend post- vaccination testing for the following groups: immunocompromised patients at risk of exposure to hepatitis B, hemodialysis patients, people with HIV infection, people who have regular sexual contact with people with chronic hepatitis B, and people at occupational risk of sharps injuries.
Some experts also suggest post-vaccination testing for people who were vaccinated in the buttocks and may not have responded optimally. Opinions differ as to when such testing should be performed - anywhere from 1 to 9 months after the last dose. The presence of at least 10 mlU/mL of antibody indicates protection; the presence of HBsAg in the absence of HBsAg antibodies indicates chronic infection.
Administration. Hep-B should be given intramuscularly. Because it contains alum, subcutaneous administration may lead to irritation, inflammation, granuloma formation, and tissue necrosis. It should be noted diat because of the risks of intramuscular injection in patients with bleeding diatheses, these patients may receive me vaccine subcutaneously. As with all intramuscular vaccines, the needle should be long enough to reach the muscle mass - 5/8 inch for newborns, 7/8 to I inch for infants age 2 to 12 months, 7/8 to 1-1/4 inches for toddlers and older children. It should be inserted perpendicular to the muscle layer below the fat. The anterolateral thigh is the preferred site for administration in children younger than 1 . The gluteal area is not acceptable because of the risk of hitting the sciatic nerve and because Hep-B given in mis area often is ineffective. For these reasons, doses of Hep-B given in the gluteal area should not be counted as valid.
Storage. Hep-B should be stored in a refrigerator at 35° to 46° F (2° to 8° C) and should never be frozen because this can cause the vaccine to lose potency.
COMMON QUESTIONS ABOUT HEP-B
Primary care providers are being asked many questions about Hep-B, both by parents and by staff who administer me vaccine. Two factors may be at play - me first dose is given at birth when a child seems inexpressibly vulnerable, and later doses are given as part of the routine schedule when children seem to be overwhelmed wim injections. Answers to some questions may help the clinician explain me rationale for current Hep-B recommendations.
Hepatitis B is worth preventing. The global burden is staggering, wim 200 to 300 million chronic carriers and 600,000 annual HBV-related deaths.1·23 These deaths are due in small part to fulminant hepatitis, which occurs in only 1 % to 2% of infected persons but carries a high mortality rate. In the pre- vaccine era, 200 to 300 Americans died of acute hepatitis B each year. In contrast, the vast majority of HBV-related deams are caused by me sequelae of chronic infection - liver cirrhosis and hepatocellular carcinoma.23 In fact, HBV is second only to tobacco as a known human carcinogen, and, like tobacco use, hepatitis B is preventable.
Hep-B is effective against infection, carriage, and complications. Three doses are 90% to 95% efficacious in preventing HBV infection and its chronic sequelae.7 In Gambia, the prevalence of chronic infection among children has plummeted from 10% prevaccine to 0.6% in the vaccine era.24 Similar success has been achieved in other countries and among Alaskan natives.25"27
Universal infant vaccination has helped Taiwan reduce its incidence of hepatocellular carcinoma among children by almost half.28 This is the first demonstration that cancer can be prevented by a vaccine, and even greater reductions are expected in the next 30 to 50 years, the time frame for development of chronic sequelae. In the United States, acute HBV infection has decreased 67% between 1990 and 2002, with the greatest decline among children and adolescents, indicating the effectiveness of routine childhood vaccination.29
Why Vaccinate Children Who Will Never Be at High Risk?
Recent estimates show approximately 90% of US children ages 19 to 35 months have received three doses of Hep-B.30 This is expected to greatly reduce the prevalence of chronic infection and its sequelae. Early on, vaccination was targeted solely for individuals in high-risk groups, and there was no significant decline in me incidence of HBV infection.31 Why did the targeted strategy fail? A person may be at risk without being in a high-risk group. Engaging in a high-risk behavior just once, such as an unprotected sexual encounter, may result in infection.
Likewise, exposures may occur through chance encounters and misadventures (eg, rendering assistance at the scene of an accident). Chronic infection often is completely unapparent, so a person may catch HBV from someone who appears to be perfectly healthy. People who are at risk, such as healthcare workers or people with multiple sex partners, often don't recognize or acknowledge the risk. In fact, one in four Americans who contract hepatitis B do not have, or do not admit to, known risk factors.1 Any program that is not universal may miss these people.
In the United States, an estimated 18,000 children younger than 10 acquired hepatitis B each year before the implementation of me universal infant vaccination program. Approximately half were infected after the newborn period through contact with infected people other than me mother.20 Presumably, the primary care physicians of these children did not detect any risk factors.
Why Vaccinate the Infant of an HBsAg-negative Mother at Birth?
Some resistance to me birth dose has come from parents who fear side effects and feel the vaccine is an unnecessary imposition on the neonate's immune system. Resistance among healthcare providers stems from a variety of concerns, including the belief mat a birth dose is unnecessary. Providers may believe, for example, that they are in a low-prevalence area and service a lowprevalence clientele. They also may feel assured that their screening procedures will invariably pick up the HBsAg-positive mother whose infant needs Hep-B and HBIG. Some providers worry that the vaccine may be unsafe, especially when a child may receive four doses because of the use of combination vaccines. Other concerns include difficulty tracking vaccines administered in the hospital, increased cost, and the lack of reimbursement from insurance companies for a birth dose. This issue is being addressed in some states by universal purchase of Hep-B for use in birthing hospitals.32
It is important to remember, however, that a Hep-B series that begins soon after birth effectively produces long-term immunity.33 A birth dose is safe and does not increase the reactogenicity of subsequent doses of Hep-B.34 35 Omissions and errors in any maternal HBsAg screening program are inevitable - mothers may not be screened, positive tests may not be reported or accessible, results may be erroneously interpreted, and, rarely, a woman may become infected after me initial screening test is negative. The universal birth dose serves as a safety net to guard against these errors.
In addition, the stakes for perinatal infection are high; 90% of infected infants become chronic carriers, and up to 25% of these develop serious sequelae of chronic infection. There also is a strong association between administration of Hep-B in the first 7 days of life and completion of the entire Hep-B series. When compared wim infants who received a birth dose, children who received their first dose at ages 42 to 91 days were almost 8 times more likely to have an incomplete series at ages 19 to 35 months.36
Vaccination is a hot topic for parents today. The birth dose of Hep-B provides an opportunity to initiate a discussion with the parents about the importance of vaccination, an issue that will be revisited many times in the first few years of life.
What are the Effects of Subsequent Doses?
In a 2001 survey of pediatricians, 38% of respondents who were giving a birth dose of Hep-B stated that if a combination vaccine containing Hep-B became available, they would prefer to wait until age 2 months to initiate Hep-B immunization.32 These results led to concern among public health officials that the many offices using combination vaccines containing Hep-B would not offer a birth dose (single antigen), despite the birth-dose recommendation.
It is important for physicians to know that there is evidence that a birth dose of Hep-B does not increase the reactogenicity of subsequent doses of the vaccine and mat immunogenicity is not impaired. Indeed, mere is evidence mat antibody titers are higher after a four-dose series (eg, a birth dose followed by Pediarix at ages 2, 4, and 6 months) than after a three-dose series.35 The Vaccines for Children Program has supported me use of four doses of Hep-B in mis circumstance,37 but private insurance coverage varies regionally.
At What Age Should a Child Vaccinated in Infancy Get a Booster?
Routine booster doses for immunocompetent children and adults are not recommended. Because HBV has a long incubation period, an exposed person has the time to develop a vigorous anamnestic antibody response after exposure. In fact, the persistence of immune memory has been demonstrated directly. One study involved 42 children whose series were initiated with a birth dose and who demonstrated protective levels of antibody at age 9 months.38 At age 6, 81 % of these children had antibody levels below the protective level. However, after a booster dose, which serves as a surrogate for exposure to natural virus, 86% developed protective levels within 1 week.
Routine booster doses also are not recommended for healthcare workers. Post-vaccination testing for antibody to HBsAg to verify vaccine "take" is recommended for healthcare workers who are at ongoing risk for sharps injuries. Those who are seronegative after three doses should receive another three-dose series, and those who are still seronegative after this should be tested for HBsAg because chronic carriage is a reason for failure to exhibit antibodies to HBsAg. There is no recommendation to give more than one repeat three-dose series. Healthcare workers who change places of employment often are retested for antibody to HBsAg, and if the level is less than 10 mlU/tnL, revaccination is initiated. This practice is of questionable value because of the immune memory discussed previously.
The only people who should receive routine booster doses are hemodialysis patients and possibly other immunocompromised patients. These patients should be tested annually and boosted (using the high-dose dialysis formulations of vaccine) if they fall below the protective level.
In the past 2 decades, mere have been many changes in vaccine recommendations to prevent hepatitis B. It is important for healthcare providers to understand the importance of universal Hep-B administration to infants, as well as tire particulars of delivering the vaccine in practice. Questions will inevitably arise, and practitioners should be equipped to answer those questions with factual information, laying out the very large and tangible potential benefits as well as the theoretical risks.
1. Atkinson W, Hamborsky J, Wolfe C, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases (the Pink Book). 8th ed. Atlanta, GA: Education, Information and Partnership Branch, National Immunization Program, Centers for Disease Control and Prevention; 2004.
2. American Academy of Pediatrics. Hepatitis B. In: Pickering LK, ed. Red Book: 2003 Report of the Committee on Infectious Diseases. 26th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2003:318-336.
3. International travel and health: hepatitis B, 2003. Available at: http://www.who.int/ith/chapteiO5_m04_hepatitisb.html. Accessed July 7, 2004.
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5. Blumberg BS, Alter HJ, Visnich S. A "new" antigen in leukemia sera. JAMA. 1967;191:541-546.
6. Greenberg DP. Pediatric experience with recombinant hepatitis B vaccines and relevant safety and immunogenicity studies. Pediatr Infect Dis J. 1993:12(5):438-445.
7. Children's Vaccine Program. Hepatitis B Quick Facts. Available at: http://childrensvaccine.org/html/v_hepb_qf.htm. Accessed June 8.2004.
8. Recommendation of me Immunization Practices Advisory Committee (ACIP). Inactivated hepatitis B virus vaccine. MMWR Morb Mortal WkIy Rep. 1 982:3 1(24):3 17-322, 327-328.
9. Hepatitis B vaccination - United States, 1982-2002. MMWR Morb Mortal WkIy Rep. 2002:5 K 25 ):549-552.563.
10. Hepatitis B virus: a comprehensive strategy for eliminating transmission in the United States through universal childhood vaccination. Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR Recomm Rep. 1 99 1 ;40(RR- 1 3): 1 -25.
11. Postexposure prophylaxis of hepatitis B. MMWR Morb Mortal WkIy Rep. 1984;33(21 ):285-290.
12. Prevention of perinatal transmission of hepatitis B virus: prenatal screening of all pregnant women for hepatitis B surface antigen. MMWR Morb Mortal WkIy Rep. 1988;37(22):341-346,351.
13. Recommended childhood immunization schedule - United States, 2002. MMWR Morb Mortal WkIy Rep. 2O02;51(2):3l-33.
14. Centers for Disease Control and Prevention. Recommended childhood and adolescent immunization schedule-United States, January-June 2004. MMWR Morb Mortal WkIy Rep. 2004;53(l):Ql-4.
15. Update: recommendations to prevent hepatitis B virus transmission - United States. MMWR Morb Mortal WkIy Rep. 1995:44(30):574-575.
16. Update: recommendations to prevent hepatitis B virus transmission - United States. MMWR Morb Mortal WkIy Rep. 1999:48(2):33-34.
17. Immunization Action Coalition. Hepatitis B prevention mandates. Available at: http://www.immunize.org/laws/hepb.htm. Accessed July 7, 2004.
18. Thimerosal in vaccines: a joint statement of the American Academy of Pediatrics and the Public Health Service. MMWR Morb Mortal WkIy Rep. 1999;48(26):563-565.
19. Oram RJ, Daum RS, Seal JB, Lauderdale DS. Impact of recommendations to suspend die birth dose of hepatitis B vims vaccine. JAMA. 200 1:285(1 4): 1874- 1879.
20. Impact of the 1999 AAP/USPHS joint statement on thimerosal in vaccines on infant hepatitis B vaccination practices. MMWR Morb Mortal WkIy Rep. 2001;50(6):94-97.
21. Recommendations regarding the use of vaccines that contain thimerosal as a preservative. MMWR Morb Mortal WkIy Rep. 1999;48(43):996-998.
22. Atkinson WL, Pickering LK, Schwartz B, et al. General recommendations on immunization. Recommendations of die Advisory Committee on Immunization Practices (ACIP) and the American Academy of Family Physicians (AAFP). MMWR Recomm Rep. 2002:5 1(RR2): 1-35.
23. Centers for Disease Control and Prevention (CDC). Global progress toward universal childhood hepatitis B vaccination, 2003. MMWR Morb Mortal WkIy Rep. 2O03;52(36):868-87O.
24. Viviani S, Jack A. Hall AJ. et al. Hepatitis B vaccination in infancy in The Gambia: protection against carriage at 9 years of age. Vaccine. 1999:17(23-24):2946-2950.
25. Harpaz R. McMahon BJ. Margolis HS, et al. Elimination of new chronic hepatitis B virus infections: results of die Alaska immunization program. J Infect Dis. 2000;181(2):413-418.
26. Chan CY, Lee SD, Lo KJ. Legend of hepatitis B vaccination: the Taiwan experience. J Gastroenterol Hepatol. 2004; 1 9(2): 1 2 1 - 1 26.
27. McMahon BJ, Rhoades ER, Heyward WL, et al. A comprehensive programme to reduce the incidence of hepatitis B virus infection and its sequelae in Alaskan natives. Lancet. 1 987;2(8568): 1 134-1 136.
28. Chang MH, Chen CJ, Lai MS, et al. Universal hepatitis B vaccination in Taiwan and die incidence of hepatocellular carcinoma in children. Taiwan Childhood Hepatoma Study Group. N Engl J Med. 1997:336(26): 1855- 1859.
29. Centers for Disease Control and Prevention (CDC). Incidence of acute hepatitis B - United States, 1990-2002. MMWR Morb Mortal WkIy Rep. 2004;52(5 1 -52): 1 252- 1 254.
30. Centers for Disease Control and Prevention (CDC). National, state, and urban area vaccination levels among children aged 19-35 months - United States, 2002. MMWR Morb Mortal WkIy Rep. 2O03;52(31):728-732.
31. Coleman PJ, McQuillan GM, Moyer LA, Lambert SB, Margolis HS. Incidence of hepatitis B virus infection in the United States, 1976-1994: estimates from the National Health and Nutrition Examination Surveys. J Infect Dis. 1998;178(4):954-959.
32. New York State Department of Health. Free hepatitis B vaccine to New York birthing hospitals. Letter to hospital administrators. Available at: http://www.heaIth.state.ny.us/nysdoh/hepatitis/entoirthhospital.htm. Accessed July 20, 2004.
33. Williams IT, Goldstein ST, Tufa J, et al. Long term antibody response to hepatitis B vaccination beginning at birth and to subsequent booster vaccination. Pediatr Infect Dis J. 2003;22(2): 157-163.
34. Lewis E, Shinefield HR, Woodruff BA, et al. Safety of neonatal hepatitis B vaccine administration. Pediatr Infect Dis J. 200 1 ;20( 1 1 ): 1 0491054.
35. Pichichero ME, Blatter MM, Reisinger KS, et al. Impact of a birth dose of hepatitis B vaccine on the reactogenicity and immunogenicity of diphtiieria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b combination vaccination. Pediatr Infect Dis J. 20O2;2 1 (9):854-859.
36. Yusuf HR, Daniels D, Smith P, Coronado V, Rodewald L. Association between administration of hepatitis B vaccine at birth and completion of the hepatitis B and 4:3: 1 :3 vaccine series. JAMA. 20O0;284(8):978-983.
37. Advisory Committee on Immunization Practices Vaccines for Children Program. Hepatitis B: Vaccines to Prevent Hepatitis B. Available at http://www.cdc.gov/nip/vfc/acip_resolutions/1003hepb.pdf. Accessed July 19, 2004.
38. Seto D, West DJ. Ioli VA. Persistence of antibody and immunologic memory in children immunized with hepatitis B vaccine at birth. Pediatr Infect Dis J. 2002:2 1 (8):793-795.
Vaccines Containing Hepatitis B Available in the United States