Penina Haber, MPH and Sarah Schillie, MD, MPH, MBA
Hepatitis B
- Epidemic jaundice described by Hippocrates in 5th century BCE
- First recorded cases in 1883 following administration of smallpox vaccine containing human lymph
- Transmission via blood further emphasized in 1943
- HBsAg first described in 1965
- Plasma-derived HepB vaccine licensed in 1981 replaced in 1986 with recombinant HepB vaccines
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Viral hepatitis is a term commonly used for several diseases that are clinically similar but etiologically and epidemiologically distinct. Hepatitis A [formerly called “infectious hepatitis”] and hepatitis B [formerly called “serum hepatitis”] have been recognized as separate entities since the early 1940s and can be diagnosed with specific serologic tests. Hepatitis D, or Delta hepatitis, is an infection dependent on the hepatitis B virus [HBV]. It may occur as a coinfection with acute HBV infection or as superinfection of an HBV carrier.
Epidemic jaundice was described by Hippocrates in the 5th century BCE. The first recorded cases of serum hepatitis are thought to be those that followed the administration of smallpox vaccine containing human lymph to shipyard workers in Germany in 1883. In the early and middle parts of the 20th century, serum hepatitis was repeatedly observed following the use of contaminated needles and syringes. The role of blood as a vehicle for virus transmission was further emphasized in 1943, when Paul Beeson described jaundice that had occurred in seven recipients of blood transfusions. Australia antigen, later called hepatitis B surface antigen [HBsAg], was first described in 1965, and the Dane particle [complete hepatitis B virion] was identified in 1970. Identification of serologic markers for HBV infection followed and helped to clarify the natural history of the disease. Ultimately, HBsAg, the surface protein of HBV, was manufactured in quantity and now comprises the immunogen in highly effective vaccines for prevention of HBV infection.
A plasma-derived Hepatitis B [HepB] vaccine was first licensed for use in the United States in 1981. The vaccine was safe and effective but was not well accepted, possibly because of unsubstantiated fears of transmission of live HBV and other blood-borne pathogens. Recombinant HepB vaccines replaced plasma-derived HepB vaccines beginning in 1986. Plasma-derived HepB vaccines are no longer used in the United States.
Hepatitis B Virus
- Hepadnaviridae family [DNA]
- Multiple serologic markers for infection
- Classified by serologic subtype and genotype, which vary geographically
- Infectious for at least 7 days on surfaces
Hepatitis B Virus [HBV]
HBV is a small, double-stranded DNA virus in the family Hepadnaviridae. Serologic markers for HBV infection include HBsAg, antibody to HBsAg [anti-HBs], immunoglobulin class M [IgM] antibodies to hepatitis B core antigen [IgM anti-HBc], and immunoglobulin class G [IgG] anti-HBc [IgG anti-HBc]. At least one serologic marker is present during the different phases of infection. Hepatitis B e antigen [HBeAg] can be detected in persons with acute or chronic HBV infection; the presence of HBeAg correlates with viral replication, high viral levels of HBV DNA, and high infectivity; antibody to HBeAg [anti-HBe] usually correlates with the decrease of replicating virus, although reversion to HBeAg positivity can occur.
HBV has been classified by two separate systems: serologic subtype and genotype. Nine serologic subtypes based on the heterogeneity of HBsAg have been described. Ten HBV genotypes, designated A through J, have been described. HBV serotypes and genotypes vary geographically. HBV genotypes are associated with the modes of HBV transmission [vertical versus horizontal] and with the risk of certain outcomes of chronic infection, such as cirrhosis and hepatocellular carcinoma [HCC]. For example, in Alaska, HBV genotype F is associated with HCC in children as well as adults younger than age 30 years, while in Asia as well as Alaska, HBV genotype C has been associated with a significantly higher risk of HCC than other genotypes. Infection or immunization with one HBV genotype generally confers immunity to all genotypes.
HBV remains infectious for at least 7 days on environmental surfaces and is transmissible in the absence of visible blood.
Hepatitis B Pathogenesis
- Transmission by parenteral or mucosal exposure
- Replicates in hepatocytes
- Unique reverse transcription replication
Hepatitis B Clinical Features
- Incubation period 60 to 90 days
- Clinical signs and symptoms more common in adults
- Prodromal phase lasts 3 to 10 days; abrupt onset of fever, malaise, anorexia, nausea, abdominal discomfort, and dark urine before jaundice
- Icteric phase lasts 1 to 3 weeks; jaundice, light or gray stools, hepatic tenderness, hepatomegaly
- Convalescent phase lasts weeks to months; malaise and fatigue persist while jaundice, anorexia, and other symptoms disappear
- Most adults recover while most infants progress to chronic infection
Pathogenesis
HBV is transmitted by parenteral or mucosal exposure to HBsAg-positive body fluids from persons who have acute or chronic HBV infection. It replicates in hepatocytes through a unique reverse transcription process.
Clinical Features
The clinical course of acute hepatitis B is indistinguishable from that of other types of acute viral hepatitis. The incubation period typically ranges from 60 to 90 days. Clinical signs and symptoms occur more often in adults than in infants or children; infants and young children usually are asymptomatic. Approximately 50% of adults who have acute infections are asymptomatic.
The preicteric, or prodromal, phase from initial symptoms to onset of jaundice usually lasts 3 to 10 days. It is nonspecific and is characterized by abrupt onset of fever, malaise, anorexia, nausea, abdominal discomfort, and dark urine beginning 1 to 2 days before the onset of jaundice. The icteric phase is variable but usually lasts from 1 to 3 weeks and is characterized by jaundice, light or gray stools, hepatic tenderness, and hepatomegaly [splenomegaly is less common]. During convalescence, malaise and fatigue may persist for weeks or months, while jaundice, anorexia, and other symptoms disappear.
Most acute HBV infections in adults result in complete recovery with elimination of HBsAg from the blood and the production of anti-HBs, creating immunity to future infection. In contrast, as many as 90% of HBV infections in infants progress to chronic infection. Perinatal transmission from mother to infant at birth [vertical transmission] is highly efficient. Prior to the widespread availability of postexposure prophylaxis, the proportion of infants born to HBsAg-positive women that acquired HBV infection was approximately 30% for those born to HBeAg-negative mothers and 85% for those born to HBeAg-positive mothers. With postexposure prophylaxis, comprised of HepB vaccine and hepatitis B immune globulin [HBIG] at birth, followed by completion of the HepB vaccine series, 0.7% through 1.1% of infants develop infection; infants born to mothers with high viral loads are at greatest risk for infection despite receipt of HepB vaccine and HBIG.
Hepatitis B Complications
- Fulminant hepatitis in about 1% to 2% of acutely infected adults
Chronic Hepatitis B Virus Infection [HBV]
- Proportion of persons with acute HBV that progress to chronic HBV
- As many as 90% of infants
- 30% to 50% of children between age 1 and 5 years
- 5% of adults
- Often asymptomatic
- Responsible for most HBV-related morbidity and mortality
- 25% of persons infected as children and 15% of persons infected as adults will die prematurely
Complications
While most acute HBV infections in adults result in complete recovery, fulminant hepatitis occurs in about 1% to 2% of acutely infected persons. Although the consequences of acute HBV infection can be severe, most of the serious complications associated with HBV infection are due to chronic infection.
Chronic HBV Infection
The proportion of persons with acute HBV infection who progress to chronic infection varies with age and immune status. As many as 90% of infants who acquire HBV infection from their mothers at birth or in infancy become chronically infected. Of children who become infected with HBV between age 1 and 5 years, 30% to 50% become chronically infected. The risk of acquiring chronic HBV infection when infected during adulthood is approximately 5%. Acute HBV progresses to chronic HBV in approximately 40% of hemodialysis patients and up to 20% of patients with immune deficiencies.
Persons with chronic infection are often asymptomatic and may not be aware they are infected; however, they are capable of infecting others and have been referred to as carriers. Chronic infection is responsible for most HBV-related morbidity and mortality, including chronic hepatitis, cirrhosis, liver failure, and HCC. Approximately 25% of persons who become chronically infected during childhood and 15% of those who become chronically infected after childhood will die prematurely from cirrhosis or liver cancer.
An estimated 257 million persons worldwide are living with HBV infection. HBV infection is an established cause of acute and chronic hepatitis and cirrhosis. The frequency of infection and patterns of transmission vary in different parts of the world. In China, Southeast Asia, most of Africa, most Pacific Islands, parts of the Middle East, and the Amazon Basin, 8% to 15% of the population has chronic HBV infection. In these high-prevalence areas, most infections are acquired at birth or during early childhood when the risk of developing chronic infections is greatest. In these areas, because most infections are asymptomatic, very little acute disease related to HBV occurs, but rates of chronic liver disease and liver cancer among adults are very high. In the United States, Western Europe, and Australia, HBV infection is a disease of low endemicity. Infection occurs primarily during adulthood, and only 0.1% to 0.5% of the population has chronic HBV infection.
Laboratory Testing
Diagnosis is based on clinical, laboratory, and epidemiologic findings. HBV infection cannot be differentiated based on clinical symptoms alone, and definitive diagnosis depends on the results of serologic testing. Serologic markers of HBV infection vary depending on whether the infection is acute or chronic.
HBsAg is the most used test for diagnosing acute HBV infections or detecting carriers. HBsAg can be detected as early as 1 or 2 weeks and as late as 11 or 12 weeks after exposure to HBV. The presence of HBsAg indicates that a person is infectious, regardless of whether the infection is acute or chronic. Transient HBsAg positivity can occur up to 18 days following vaccination [up to 52 days among hemodialysis patients] and is clinically insignificant.
Anti-HBs is a protective, neutralizing antibody. The presence of anti-HBs following acute HBV infection generally indicates recovery and immunity against reinfection. Anti-HBs can also be acquired as an immune response to HepB vaccine or passively transferred by administration of HBIG. The level of anti-HBs considered as a protective level of immunity when following a complete vaccination series is 10 mIU/mL. Persons who recover from natural HBV infection are typically positive for both anti-HBs and anti-HBc, whereas persons who respond to HepB vaccine are positive only for anti-HBs.
Anti-HBc develops in all HBV infections, appears shortly after HBsAg in acute disease, and indicates HBV infection at some undefined time in the past. Anti-HBc generally persists for life. Persons who are HBsAg-negative and anti-HBc-positive can experience reactivation of infection during chemotherapy or immunosuppressive therapy, with reappearance of HBsAg.
IgM anti-HBc appears in persons with acute disease about the time of illness onset and indicates recent infection with HBV. IgM anti-HBc is generally detectable 4 to 6 months after onset of illness and is the best serologic marker of acute HBV infection.
HBeAg is a marker that is associated with a high number of infective HBV particles in the serum and a higher risk of infectivity. Anti-HBe correlates with a reduction of replicating virus and lower infectivity, although reversion to HBeAg positivity can occur.
HBV DNA assays are used to monitor response to treatment, assess the likelihood of perinatal HBV transmission, and detect the presence of occult HBV infection [i.e., infection in someone who tests HBsAg-negative]. In resource-limited settings, HBeAg may replace the use of HBV DNA for some purposes, e.g., assessment of perinatal HBV transmission risk.
Medical Management
There is no specific therapy for acute HBV infection. Treatment is supportive. Guidelines for management of chronic HBV infection in children and adults, including disease monitoring and antiviral therapy, are available from the American Association for the Study of Liver Diseases [AASLD, //www.AASLD.org]. Antiviral therapy, while not curative, can reduce the level of HBV DNA and quiet liver inflammation. Following the AASLD Guidelines/Guidance, antiviral therapy should generally be initiated in patients with chronic HBV infection who have high levels of virus and active liver inflammation characterized by elevated liver transaminase levels. These persons are at high risk for liver-related morbidity.
AASLD suggests antiviral therapy to reduce perinatal HBV transmission when maternal HBV DNA is greater than 200,000 IU/mL starting in the third trimester. Maternal therapy is generally discontinued at birth to 3 months postpartum.
Persons with acute or chronic HBV infections should prevent their blood and other potentially infective body fluids from contacting other persons. They should not donate blood or share toothbrushes or razors with household members. In health care settings, patients with HBV infection should be managed with standard precautions.
Hepatitis B Epidemiology
- Reservoir
- Human
- Some primates
- Transmission
- Body fluids [highest concentration in blood and serous fluids]
- Temporal Pattern
- No temporal pattern
- Communicability
- Persons with acute or chronic HBV infection are infectious any time HBsAg present in blood
- Persons with acute HBV infection can have HBsAg in blood 1-2 months before and after onset of symptoms
Epidemiology
Occurrence
HBV infection occurs worldwide. The frequency of infection varies in different parts of the world but is more common in some countries in Asia, Africa, South America, and the Caribbean.
Reservoir
HBV infection affects humans. Additionally, some primates [chimpanzee, gorilla, orangutan, gibbon] in Africa and Southeast Asia are infected with HBV.
Transmission
HBV is transmitted by parenteral or mucosal exposure to HBsAg-positive body fluids from persons who have acute or chronic HBV infection. The highest concentrations of virus are in blood and serous fluids; lower titers are found in other fluids, such as saliva, tears, urine, and semen. Semen is a vehicle for sexual transmission and saliva can be a vehicle of transmission through bites; other types of exposure [e.g., to saliva through kissing] are unlikely modes of transmission. HBsAg is also found in other body fluids [e.g., breast milk, bile, feces, nasopharyngeal washings, and sweat]. However, most body fluids are not efficient vehicles of transmission [unless they contain blood] because they contain low quantities of infectious HBV.
In the United States, the most important routes of transmission are injection-drug use, perinatal, and sexual contact with an infected person. Fecal-oral transmission does not appear to occur. However, transmission occurs among men who have sex with men [MSM], possibly via contamination from asymptomatic rectal mucosal lesions. In the 2000s and 2010s, outbreaks of hepatitis B occurred in long-term care facilities [e.g., assisted living facilities and nursing homes] as the result of inadequate infection control practices related to blood glucose monitoring. Transmission occurs in households from persons who have immigrated from endemic areas and who have chronic HBV infection.
Temporal Pattern
HBV infection is reported throughout the year. There is no known temporal pattern.
Communicability
Persons with either acute or chronic HBV infection should be considered infectious any time that HBsAg is present in the blood. When symptoms are present in persons with acute HBV infection, HBsAg can be found in blood and body fluids for 1 to 2 months before and after the onset of symptoms.
Direct, percutaneous inoculation of HBV by needles during injection-drug use is an important mode of transmission. Breaks in the skin without overt needle puncture, such as fresh, cutaneous scratches, abrasions, burns, or other lesions, may also serve as routes for entry. Exposures such as transfusion of blood or blood products, hemodialysis, use of meters and lancets for blood glucose monitoring, insulin pens, and needle-stick or other sharps injuries sustained by health care personnel [HCP] have all resulted in HBV transmission. Outbreaks have been reported among patients in dialysis centers in many countries through failure to adhere to recommended infection control practices. Past outbreaks have been traced to tattoo parlors, acupuncturists, and barbers.
Hepatitis B Secular Trends in the United States
- Acute HBV infection
- Before vaccine, about 9.6 per 100,000 cases
- Following vaccine, about 1 per 100,000 cases in 2018 [~90% decrease]
- During 2009 through 2013, KY, TN, and WV experienced 114% increase associated with injection-drug use
- Incidence greatest for persons 40 through 49 years and lowest for persons 19 years or younger
- Chronic HBV infection
- Estimated 850,000 to 2.2. million persons infected in the U.S.; most immigrated from endemic countries
Secular Trends in the United States
Hepatitis B became nationally notifiable as a distinct entity during the 1970s after serologic tests to differentiate different types of hepatitis became widely available.
In 2018, a total of 3,322 cases of acute hepatitis B were reported to CDC, for an overall incidence rate of 1.0 cases per 100,000 population. After adjusting for under-ascertainment and under-reporting, an estimated 21,600 acute hepatitis B cases occurred in 2018. The rate of reported acute HBV infections declined approximately 90% since recommendations for HepB vaccination were first issued, from 9.6 cases per 100,000 population in 1982 to 1.0 cases per 100,000 population in 2018.
During 2009 through 2013, the combined incidence of acute HBV infection in three states [Kentucky, Tennessee, and West Virginia] increased 114% and was associated with increasing injection-drug use. Incidence is greatest for persons age 40 through 49 years [2.5 per 100,000 population]; persons age 19 years or younger have the lowest incidence [0.02 cases per 100,000 population], likely a result of routine infant vaccination.
Although HBV infection is uncommon among adults in the general population [the lifetime risk of infection is less than 20%], it is highly prevalent in certain groups. Generally, the highest risk for HBV infection is associated with lifestyles, occupations, or environments in which contact with blood from infected persons is frequent. Chronic HBV infection has been identified in 3.5% to 20.0% of persons who inject drugs [PWID] in a variety of settings, and 22.6% of PWID have evidence of past infection.
An estimated 850,000 to 2.2 million persons in the United States are chronically infected with HBV. Most persons in the United States with chronic HBV infection have immigrated from endemic countries in the world. While screening persons who immigrate for HBsAg, anti-HBc and anti-HBs is recommended, it is not enforced. Therefore, clinicians and public health workers should screen all persons born in countries with high endemicity of HBV virus.
Among children born during 2015–2016, 75.0% received the HepB vaccine birth dose administered from birth through age 3 days. This was an increase from 71.8% for children born during 2013–2014. By age 24 months, 91.0% of children had received at least 3 doses of HepB vaccine. In 2017, 25.8% of adults age 19 years or older had received at least 3 doses of HepB vaccine; the coverage was 34.3% and 16.6% for adults age 19 through 49 years and age 50 years or older, respectively. Among HCP with direct patient contact, 70% had received at least 3 doses of HepB vaccine.
Hepatitis B Prevention Strategies
HepB vaccination is the mainstay of hepatitis B prevention efforts. A comprehensive strategy to eliminate HBV transmission includes universal vaccination of infants beginning at birth, routine vaccination of previously unvaccinated children less than age 19 years, and vaccination of adults at risk for HBV infection, including those requesting protection from HBV without acknowledgement of a specific risk factor. It also includes universal testing of pregnant women for HBsAg to identify newborns who require immunoprophylaxis for prevention of perinatal infection and to pregnant women who can benefit from antiviral therapy to reduce perinatal transmission.
Hepatitis B Vaccines
- DTaP-HepB-IPV [Pediarix]
- DTaP-IPV-Hib-HepB [Vaxelis]
- HepA-HepB [Twinrix]
- HepB [Engerix-B, Heplisav-B, and Recombivax HB]
Hepatitis B Vaccine
The first recombinant HepB vaccine, Recombivax HB, was licensed in the United States in 1986. A second recombinant vaccine, Engerix-B, was licensed in 1989. Recombivax HB and Engerix-B are available in both pediatric and adult formulations. A third recombinant vaccine with a novel adjuvant, Heplisav-B, was licensed in 2017 for use in adults age 18 years or older. HBV infection cannot result from use of the recombinant vaccine since no potentially infectious viral DNA or complete viral particles are produced in the recombinant system.
There are two combination vaccines that contain HepB vaccine. DTaP-HepB-IPV [Pediarix] is licensed for children age 6 weeks through 6 years. HepA-HepB [Twinrix] is licensed for persons age 18 years or older. A third combination vaccine, DTaP-IPV-Hib-HepB [Vaxelis], is licensed in the United States.
Hepatitis B Vaccine Characteristics
- Administered by intramuscular injection
- Contain yeast protein
- Contain aluminum adjuvant [Engerix-B and Recombivax HB] or synthetic adjuvant [Heplisav-B]
- Some presentations contain latex
- Ingredients in combination vaccines differ; all contain antibiotics
Characteristics
Recombinant HepB vaccine is produced by inserting a plasmid containing the gene for HBsAg into yeast [Saccharomyces cerevisiae or Hansenula polymorpha]; HepB vaccines contain yeast protein. HepB vaccines are administered by intramuscular injection. Each dose of HepB vaccine contains aluminum as an adjuvant or, for Heplisav-B, a small synthetic immunostimulatory oligodeoxynucleotide 1018 adjuvant. Each dose of DTaP-HepB-IPV contains antibiotics neomycin and polymyxin B; each dose of DTaP-IPV-Hib-HepB contains neomycin, polymyxin B, and streptomycin; each dose of HepA-HepB contains neomycin. HepB vaccines contain no preservative. Presentations of HepB vaccines contain latex rubber. Specific ingredients in combination vaccines containing HepB vaccine differ.
Recombivax HB and Engerix-B are available in both pediatric and adult formulations and are typically administered as a 3-dose series on a 0, 1, 6 month schedule. Although their antigen content differs, the two vaccines are interchangeable except for a 2-dose series for adolescents age 11 through 15 years, for which only Recombivax HB is approved. Heplisav-B is administered as a 2-dose series on a 0, 1 month schedule and is approved for persons age 18 years or older.
Hepatitis B Vaccination Schedule
- Infants: See Hepatitis B vaccine schedule for infants
- Adolescents: All children and adolescents through age 18 years not previously vaccinated
- 3-dose series at 0, 1, 6 months
- Adolescents age 11 through 15 years may use 2-dose series of Recombivax HB separated by 4 to 6 months
- Adults: All unvaccinated adults at risk for or requesting protection from HBV infection
- 2-dose series at 0 and 1 month [Heplisav-B] or 3-dose series at 0, 1 and 6 months [Engerix-B and Recombivax HB]
- 3-dose series at 0, 1 and 6 months [Twinrix]
- 3-dose series with doses at 0, 7, 21-30 days, and booster 12 months after dose 1 [Twinrix, accelerated]
Vaccination Schedule and Use
Infants and Children
HepB vaccination is recommended for all medically stable infants weighing at least 2,000 grams within 24 hours of birth. Only single-component vaccine should be used for the birth dose and doses administered before age 6 weeks. The usual schedule is 0, 1 through 2, and 6 through 18 months.
All pregnant women found to be HBsAg-positive should have their sera tested for HBV DNA. If HBV DNA levels are greater than 200,000 IU/mL, Tenofovir [preferable] or lamivudine should be administered to the pregnant woman starting at the beginning of the third trimester and continued one to three months after birth. Infants born to mothers who are HBsAg-positive should receive the HepB vaccine birth dose and HBIG within 12 hours of birth. HepB vaccine and HBIG should be administered in separate limbs. For infants weighing less than 2,000 grams, the birth dose should not be counted as part of the vaccine series because of potentially reduced immunogenicity; 3 additional doses of vaccine [for a total of 4 doses] should be administered beginning when the infant reaches age 1 month. Infants whose mothers are HBsAg-positive should receive the last dose by age 6 months but not before age 24 weeks.
Infants born to mothers whose HBsAg status is unknown should receive the HepB birth dose within 12 hours of birth. Infants weighing less than 2,000 grams should also receive HBIG within 12 hours of birth. The mother’s HBsAg status should be assessed as soon as possible. If the mother is determined to be HBsAg-positive, infants weighing at least 2,000 grams should also receive HBIG as soon as possible but no later than age 7 days. As with infants born to HBsAg-positive mothers, for infants weighing less than 2,000 grams, the birth dose should not be counted as part of the vaccine series because of potentially reduced immunogenicity; 3 additional doses of vaccine [for a total of 4 doses] should be administered beginning when the infant reaches age 1 month. Infants with mothers whose HBsAg status is unknown should receive the last dose by age 6 months but not before age 24 weeks.
Preterm infants weighing less than 2,000 grams have a decreased response to HepB vaccine administered before 1 month of age. However, by chronologic age 1-month preterm infants, regardless of initial birth weight or gestational age, are as likely to respond as adequately as full-term infants. Preterm infants of low birth weight whose mothers are HBsAg-negative can receive the first dose of HepB vaccine at chronologic age 1 month. Preterm infants discharged from the hospital before chronologic age 1 month can receive HepB vaccine at discharge if they are medically stable and have gained weight consistently, even if they are less than 2,000 grams.
The third HepB dose must be administered at least 8 weeks after the second dose, and at least 16 weeks after the first dose. The minimum interval between the first and second dose is 4 weeks.
Hepatitis B vaccine schedules for infants [≥2,000 g birthweight], by maternal HBsAg status
Hepatitis B vaccine schedules for infants| 1 | Birth [≤12 hrs] | 1 | Birth [≤12 hrs] |
| HBIG§ | Birth [≤12 hrs] | HBIG§ | Birth [≤12 hrs] |
| 2 | 1-2 mos | 2 | 2 mos |
| 3 | 6 mos¶ | 3 | 4 mos |
| N/A | N/A | 4 | 6 mos¶ |
| 1 | Birth [≤12 hrs] | 1 | Birth [≤12 hrs] |
| 2 | 1-2 mos | 2 | 2 mos |
| 3 | 6 mos¶ | 3 | 4 mos |
| N/A | N/A | 4 | 6 mos¶ |
| 1 | Birth [≤24 hrs] | 1 | Birth [≤24 hrs] |
| 2 | 1-2 mos | 2 | 2 mos |
| 3 | 6–18 mos¶ | 3 | 4 mos |
| N/A | N/A | 4 | 6 mos¶ |
* Mothers should have blood drawn and tested for HBsAg as soon as possible after admission for delivery; if the mother is found to be HBsAg positive, the infant should receive HBIG as soon as possible but no later than age 7 days.
† Pediarix and Vaxelis should not be administered before age 6 weeks.
§ HBIG should be administered at a separate anatomical site from vaccine.
¶ The final dose in the vaccine series should
not be administered before age 24 weeks [164 days].