Canadian Immunization Guide: Part 4 - Active Vaccines
Hepatitis B Vaccine
Updated: February 2015
- Key Information
- Preparations Authorized for Use in Canada
- Efficacy, Effectiveness and Immunogenicity
- Recommendations for Use
- Table 1: Recommended recipients of hepatitis B vaccine for pre-exposure prevention
- Table 2: Hepatitis B immunization recommendations for preterm infants weighing less than 2,000 grams, by maternal hepatitis B surface antigen (HBsAg) status
- Figure 2: Management of individuals with percutaneous or mucosal exposure to an infected or high risk source
- Figure 3: Management of individuals with percutaneous or mucosal exposure to an uninfected or low risk source
- Vaccine Administration
- Serologic Testing
- Storage Requirements
- Simultaneous Administration with Other Vaccines
- Vaccine and Immune Globulin Safety and Adverse Events
- Other Considerations
- Selected References
Key Information (Refer to text for details)
- In Canada, most acute cases of hepatitis B (HB) occur in unimmunized people 25 years of age and older who acquire infection through unprotected sexual activity, sharing injection drug equipment, household contact with a HB carrier or procedures with percutaneous exposure. A high proportion of HB carriers in Canada are immigrants from HB endemic areas.
- Initial infection with HB may be asymptomatic in up to 50% of adults and 90% of children.
- Infants, young children and immunocompromised persons are at highest risk of becoming chronic HB carriers.
- HB vaccine is 95% to 100% effective pre-exposure.
- Reactions to HB vaccine are generally mild and transient and include: irritability, headache, fatigue, as well as pain and redness at the injection site.
- Routine HB immunization is recommended for all children.
- Pre-exposure HB immunization is recommended for high risk groups.
- Post-exposure prophylaxis should be offered to:
- infants born to HB-infected mothers
- persons potentially exposed to blood or bodily fluids containing HB virus
- household and sexual contacts of an acute HB case or chronic carrier
- There are many different HB-containing vaccine schedules and dosages.
- For monovalent HB vaccine, the preferred schedule (particularly for infants) is months 0, 1 and 6. The date of the first dose for infants is at birth, which is considered as month 0.
- With few exceptions, persons with indications for both hepatitis A (HA) and HB vaccine should be immunised with combined HAHB vaccine.
- Hepatitis B-containing vaccines may be administered concomitantly with other vaccines at different injection sites using separate needles and syringes.
- A person with acute HB can become a chronic carrier and remain infectious. Chronic infection may lead to serious liver disease.
- Infants born to infected mothers are at highest risk of becoming chronic HB carriers.
Significant revisions since the last chapter update are highlighted in the Canadian Immunization Guide (CIG) Table of Updates, which is available on the Public Health Agency of Canada (PHAC) website.
For additional information, refer to previously published National Advisory Committee on Immunization (NACI) Statements and Statement Updates.
Hepatitis B (HB) virus is a deoxyribonucleic acid (DNA) virus of the Hepadnavirdiae family. Several genotypes have been described. The following two antigens are important in evaluating people with HB infection and are markers of HB carriage: hepatitis B surface antigen (HBsAg), which is present in either acute or chronic infection with HB virus and hepatitis B e antigen (HBeAg), which typically is associated with higher viral loads, increased infectiousness and more actively replicating virus. Increasingly, viral loads are followed as indicators of infectiousness and response to treatment.
HB is transmitted through percutaneous or mucosal contact with infectious biological fluids. Transmission of HB occurs through close contact with infectious bodily fluids, including sharing of injection drug equipment (such as needles), sexual contact, and from mothers who are acute cases or carriers to their newborns. The risk of transfusion-related HB is extremely low because all blood and blood products are tested. Saliva is considered infectious in bite wounds with broken skin involving the inoculation of saliva, or when it is visibly tainted with blood. Almost one-third of people with HB infection have no identified risk factors.
The incubation period is 45 to 160 days (average 120 days). HBsAg can be detected in serum 30 to 60 days after exposure and persists until the infection resolves. Persons in the acute stage of HB are considered infectious. In most cases, antibody to HBsAg (anti-HBs) appears after HBsAg has disappeared and the infection has resolved. In severe acute HB infections, anti-HBs may be present simultaneously with HBsAg. Anti-HBs confers long-term immunity. In addition, antibody to HB core antigen (anti-HBc) will appear in persons who have been exposed to the virus. This group includes those who are currently infected and those who were infected in the past but have cleared the virus. Persons with anti-HBs and anti-HBc are not infectious. However, some individuals with acute HB infection will become chronic carriers. Chronic carriers will generally express HBsAg and may have HBeAg and measurable HB DNA in the blood. These individuals are infectious.
The highest risk of transmission and of subsequent chronic carriage is in infants exposed during child birth to their mothers who are carriers of HB. Other groups at higher risk of HB include injection drug users, households with HB carriers and people at risk of sexually transmitted diseases. In Canada, most cases of acute HB occur in unimmunized people 25 years of age and older who acquire infection through unprotected sexual activity, sharing injection drug equipment, household contact with an HB carrier, or treatments or procedures with percutaneous exposure. People on dialysis are considered to be at higher risk. A high proportion of HB carriers in Canada are immigrants from HB endemic areas.
Spectrum of clinical illness
Initial infection with HB may be asymptomatic in up to 50% of adults and 90% of children. When symptoms occur, they include insidious onset of anorexia, abdominal pain, nausea, vomiting and jaundice. Acute illness may last up to 3 months and has a case fatality rate of 1% to 2%, which increases with age. Although 90% of adults infected with HB recover completely, fulminant hepatitis occurs in 1% to 2% and chronic infection in approximately 10%, eventually leading to a chronic carrier state that may result in cirrhosis and hepatocellular carcinoma. The risk of becoming a chronic carrier varies inversely with the age at which infection occurs (infants - 90% to 95%; children less than 5 years of age - 25% to 50%; adults - 3% to 10%). The risk of becoming a chronic carrier is also greater in immunocompromised patients. The risk of fulminant hepatitis and death is increased in pregnant women, with consequences to the fetus including premature delivery, asphyxia and death.
Incidence and prevalence
It is estimated that there are more than 300 million HB carriers worldwide, of whom approximately 500,000 to 1.2 million die annually from HB related liver disease. Despite the availability of HB vaccines, the rates of HB related hospitalizations, cancers and deaths have more than doubled during the past decade. HB remains highly or moderately endemic in the Far East, the Middle East, Africa, South America, Eastern Europe and Central Asia, with carrier rates of 2% to 20% in the general population. View a WHO map of countries and areas of risk for HB.
Canada is considered an area of low HB endemicity. It is estimated that less than 5% of residents have markers of past infection, and less than 1% are carriers. The epidemiology of HB infection has been modified by the introduction of routine childhood HB immunization programs and the increased use of vaccine in targeted groups. The incidence of HB has decreased in all age groups in recent years, coinciding with the increasing use of vaccine, and has virtually disappeared in the cohorts that have benefited from routine immunization programs (refer to Figure 1).
Preparations Authorized for use in Canada
Hepatitis B-containing vaccines
- ENGERIX®-B (hepatitis B vaccine, recombinant), GlaxoSmithKline Inc. (HB)
- INFANRIX hexa™(adsorbed vaccine containing diphtheria and tetanus toxoids, acellular pertussis, hepatitis B [recombinant], inactivated poliomyelitis and conjugated Haemophilus influenzae type b vaccine), GlaxoSmithKline Inc. (DTaP-HB-IPV-Hib)
- RECOMBIVAX HB® (hepatitis B vaccine, recombinant), Merck Canada Inc. (HB)
- TWINRIX® and TWINRIX®Junior (combined hepatitis A and hepatitis B vaccine), GlaxoSmithKline Inc. (HAHB)
Hepatitis B immune globulin (HBIg)
- HepaGam B™ (hepatitis B immune globulin (human), Cangene Corp.
- HyperHEP B™ S/D: (hepatitis B immune globulin (human), Grifols Therapeutics Inc.
For complete prescribing information, consult the product leaflet or information contained within Health Canada's authorized product monographs available through the Drug Product Database. Refer to Contents of Immunizing Agents Available for Use in Canada in Part 1 for lists of all vaccines and passive immunizing agents available for use in Canada and their contents.
Efficacy, Effectiveness and Immunogenicity
Efficacy and effectiveness
HB vaccine is 95% to 100% effective in preventing HB in people who receive a complete vaccine series.
HB vaccination and one dose of hepatitis B immune globulin (HBIg) administered within 24 hours after birth are 85% to 95% effective in preventing HB infection in exposed neonates. Studies have demonstrated the efficacy of HBIg and HB vaccine in percutaneous or mucosal exposure to HB-positive blood, or sexual exposure to HB-positive persons. A single dose of HBIg is 75% effective if administered within 2 weeks of last sexual exposure.
People with an anti-HBs titre of at least 10 IU/L after immunization are considered protected for life, with the exception of those who are immunocompromised (refer to Immunocompromised persons). Anti-HBs titres may eventually disappear; this may occur more quickly if the initial titre was low. High titres of anti-HBs result in longer persistence of antibodies and may be predictive of a longer duration of protection. However, immune memory persists despite the disappearance of anti-HBs. In endemic regions, the duration of protection induced by vaccination has been shown to be at least 15 years in most vaccinees.
The major determinant of seroprotection rates achieved is the age at vaccination, but outcome also varies with the schedule used, the dosage, and the health of the vaccinee. While children less than 2 years of age have a 95% response rate, the best response is observed in children between the ages of 5 and 15 years with 99% seroprotection rates. Generally, the response rate for adults decreases with age. The antibody response is lower in patients with diabetes mellitus (70% to 80%), renal failure (60% to 70%), and chronic liver disease (60% to 70%). Immunization of obese people, smokers and those with alcoholism may also produce lower antibody titres. Immunocompromised patients, such as those infected with HIV, will have a diminished response in proportion to the level of immune deficiency. Most people undergoing dialysis do not respond well to HB vaccine and do not develop an immune memory.
Studies have demonstrated the immunogenicity of DTaP-HB-IPV-Hib for all six antigens in the vaccine. There is no reduction, and possibly even an increase, in seroprotection rates achieved by HAHB vaccine, compared with monovalent HA and HB vaccines.
Recommendations for Use
Infants and children
HB-containing vaccine should be given for routine immunization of infants or children and for immunization of children and adolescents who have missed HB immunization on the routine schedule. The age at which HB-containing vaccine is offered varies from jurisdiction to jurisdiction. In jurisdictions where children do not receive HB vaccine in infancy, children at increased risk should be given HB-containing vaccine as soon as the risk is identified (refer to Table 1).
If infant immunization for hepatitis B is undertaken, DTaP-HB-IPV-Hib vaccine may be used as an alternative to separately administered HB and DTaP-IPV-Hib vaccines. DTaP-HB-IPV-Hib vaccine is authorized for children 6 weeks to 23 months of age and may be given to children aged 24 months to less than 7 years, if necessary.
Persons who are at increased risk of exposure to HB should receive HB-containing vaccine (refer to Table 1). All persons who do not have immunity from past infection or previous vaccination and all persons who wish to decrease their risk of acquiring HB should be encouraged to be vaccinated. With few exceptions, combined hepatitis A and hepatitis B vaccine (HAHB) is the preferred vaccine for people with indications for immunization against both hepatitis A and hepatitis B. Refer to Hepatitis A Vaccine in Part 4 for additional information.
- All adults and children who have immigrated to Canada from areas where there is a high prevalence of HB
- Children born in Canada whose families have immigrated from areas where there is a high prevalence of HB and who may be exposed to HB carriers through their extended families or when visiting their family's country of origin.
- Children and workers in child care settings in which there is a child or worker who has acute HB or is an HB carrier. Vaccination should also be considered for all child care workers.
- Household and sexual contacts of acute HB cases and HB carriers
- Household or close contacts of children adopted from HB-endemic countries if the adopted child is HBsAg positive
- Populations or communities in which HB is highly endemic
- Residents and staff of institutions for the developmentally challenged
- Staff and inmates of correctional facilities
- Persons with lifestyle risks for infection, including:
- persons who have unprotected sex with new partners
- persons who have had more than one sexual partner in the previous 6 months
- persons with a history of sexually transmitted infections
- persons seeking evaluation or treatment for a sexually transmitted infection
- persons who engage in high risk sexual practices
- persons who use injection drugs
- men who have sex with men (MSM)
- Persons with chronic liver disease from any cause, including persons infected with hepatitis C. While these persons may not be at an increased risk of hepatitis B infection, they may be at risk of more severe disease if infection occurs.
- Hemophiliacs and other people receiving repeated infusions of blood or blood products.
- Persons with chronic renal disease or who are undergoing chronic dialysis (hemodialysis or peritoneal dialysis)
- Persons with congenital immunodeficiencies
- Persons who have undergone hematopoietic stem celltransplantation (HSCT) or are awaiting solid organ transplant
- HIV-infected persons
- Travellers to HB endemic areas
- Health care workers, emergency service workers, and others with potential occupational exposure to blood, blood products and bodily fluids that may contain HB virus
- Any person who wishes to decrease his or her risk of HB
Persons with inadequate immunization records
Children and adults lacking adequate documentation of immunization should be considered unimmunized and started on an immunization schedule appropriate for their age and risk factors (unless known to be immune based on laboratory testing). Refer to Persons with Inadequate Immunization Records in Part 3 for additional general information.
Pregnancy and breastfeeding
All pregnant women should be routinely tested for HBsAg. A pregnant woman who has no markers of HB infection but who is at high risk of HB should be offered HB vaccine at the first opportunity during the pregnancy and should be tested for antibody response (refer to Serologic Testing). HB vaccine can be used safely in pregnancy and during breastfeeding and should be administered when indicated, because acute HB in a pregnant woman may result in severe disease for the mother and chronic infection of the infant. The safety of HAHB vaccine given during pregnancy has not been studied in clinical trials. However, because the vaccine is prepared from inactivated viruses, no risk to the developing fetus is anticipated. Refer to Hepatitis A Vaccine in Part 4 for additional information. Refer to Immunization in Pregnancy and Breastfeeding in Part 3 for additional general information.
Infants born prematurely
The response to HB vaccine may be diminished in pre-term infants with a birth weight of less than 2,000 grams. Routine HB immunization of infants of mothers known to be negative for HBsAg should be delayed until the infant reaches 2,000 grams or until discharge from hospital, whichever comes first.
Premature infants who are born to women who are HBsAg positive should receive the first dose of monovalent HB vaccine and HBIg within 12 hours of birth. Premature infants weighing less than 2,000 grams at birth require four doses of HB vaccine (at birth, 1, 2 and 6 months of age). Premature infants weighing 2,000 grams or more at birth require three doses of HB vaccine (at birth, 1 and 6 months). All infants of HBsAg positive mothers should have an assessment of the anti-HBs titre 4 weeks after their series of HB vaccine has been completed to assess the success of immunoprophylaxis. Refer to Table 2 and Post-exposure immunization.
Infants born prematurely (especially those weighing less than 1,500 grams at birth) are at higher risk of apnea and bradycardia following vaccination. Hospitalized premature infants should have continuous cardiac and respiratory monitoring for 48 hours after their first immunization. Refer to Immunization of Infants Born Prematurely in Part 3 for additional general information.
|Maternal HBSAg status||Recommendation|
|NOTE: This table is adapted from the Centers for Disease Control and Prevention (CDC) table: Hepatitis B Immunization Management of Preterm Infants Weighing <2,000 g, by Maternal Hepatitis B Surface Antigen (HBsAg) Status published in Morbidity and Mortality Weekly Report (MMWR) December 7, 2007;56(48):1267. http://www.cdc.gov/hepatitis/hbv/pdfs/correctedtable4.pdf|
HB vaccine may be administered to immunocompromised persons. When considering immunization of an immunocompromised person, consultation with the individual's attending physician may be of assistance in addition to the guidance provided below. For complex cases, referral to a physician with expertise in immunization or immunodeficiency is advised.
Immunocompromised people (e.g., hematopoietic stem cell transplant recipients, solid organ transplant recipients, HIV-infected persons) often respond sub-optimally to HB vaccine and may require higher doses of antigen to respond initially (refer to Higher vaccine dosing) as well as boosters with higher dosages. Post-immunization serologic testing within 1 to 6 months of completion of the vaccine series is recommended in these immunocompromised individuals to monitor the success of immunoprophylaxis. In addition, people undergoing chemotherapy, those on other immunosuppressive therapy, and those with congenital immunodeficiency may have a lower immune response, and so require serologic testing 1 to 6 months after completing the series. Vaccinees who do not develop an anti-HBs titre of at least 10 IU/L after the first series of immunizations should receive a second series and serology should be rechecked within 1 to 6 months after completion of the second series. If a protective antibody concentration is still not present, the individual should be counselled on alternative risk reduction measures. Should protective antibody concentrations be achieved and then wane, subsequent HB exposure in these individuals can result in acute disease or carrier state. Therefore, periodic monitoring of anti-HBs titres should be considered, taking into account the severity of the immunocompromised state and whether the risk of HB is still present. Should antibody testing show subsequent suboptimal protection, a booster dose and retesting one month later should be undertaken.
Higher vaccine dosing
For some immune compromising or chronic conditions, a higher dose of monovalent HB vaccine is recommended (refer to Table 3 for schedule). This higher dose is defined as follows:
- for children 0 to less than 16 years of age, double the routine dose of monovalent HB vaccine for their age
- for adolescents 16 to less than 20 years of age:
- 40 microgram dose of ENGERIX®-B vaccine OR
- double the routine dose of RECOMBIVAX HB® vaccine for their age
- for adults 20 years of age and older:
- 40 microgram dose of monovalent HB vaccine
Congenital (primary) immunodeficiency
Individuals with congenital immunodeficiencies involving any part of the immune system should receive HB vaccine. Immunization with a higher dosage as defined in Higher vaccine dosing is recommended.
Acquired (secondary) immunodeficiency
Hematopoietic stem cell transplantation (HSCT)
HB vaccine is recommended for all persons after transplantation. Three doses are required, starting at 6 to 12 months post-transplantation following the standard intervals. Immunization with a higher dosage as defined in Higher vaccine dosing is recommended.
Solid organ transplantation
Children and adults who are transplant candidates should receive HB vaccine according to routine vaccination schedules. Immunity should be documented by measuring the anti-HBs titre. For susceptible transplant recipients, vaccination should not be initiated or re-initiated until at least 3 to 6 months after transplantation to attain optimal immunogenicity. Immunization with a higher dosage as defined in Higher vaccine dosing is recommended.
Vaccination status for hepatitis B should be reviewed for immunocompetent persons who might be anticipating initiation of immunosuppressive treatments or who have diseases that might lead to immunodeficiency. Although HB vaccine can safely be given at any time before, during, or after immunosuppression, all attempts should be made to time vaccination so that optimal immunogenicity is achieved. An exception is made for post-exposure prophylaxis, in which case HB vaccine should be given as soon as possible after the exposure.
If indicated, HB vaccine should be administered at least 14 days before the initiation of immunosuppressive therapy (e.g., high-dose systemic corticosteroids [2 mg/kg per day or 20 mg/day or more of prednisone or its equivalent] for 14 days or more; chemotherapy; radiation therapy; azathioprine; cyclosporine; cyclophosphamide; infliximab). If this time frame cannot be accomodated, a period of at least 3 months should elapse after immunosuppressive drugs (except high-dose systemic corticosteroids) have been stopped before administration of HB vaccine, in an effort to optimize immunogenicity. A period of at least 4 weeks should elapse between discontinuation of high-dose systemic steroids and administration of HB vaccine. The interval between discontinuation of immunosuppressive drugs and HB vaccine may vary with the intensity of the immunosuppressive therapy, underlying disease and other factors.
If immunosuppressive therapy cannot be stopped, HB vaccine should be given when the person is least immunosuppressed if possible.
HB vaccine is recommended for all susceptible HIV-infected individuals. Immunization should be completed as early in the course of disease as possible. Immunization with a higher dose of vaccine as defined in Higher vaccine dosing is recommended.
Susceptible household or close contacts of immunocompromised people should be given HB vaccine, for their own protection, but also to reduce the risk of infection to the immunocompromised person.
Persons with chronic diseases
Chronic renal disease or on dialysis
Individuals on dialysis are at increased risk for HB infection because of the frequent potential exposures to the blood of others on dialysis, and these individuals, as well as those with chronic renal disease, may respond sub-optimally to HB vaccinations. As well, anti-HBs concentrations decline rapidly. For dialyzed adults and children and those with chronic renal disease, immunization with higher dosing as defined in Higher vaccine dosing is recommended. Anti-HBs titres should be evaluated yearly and booster doses using a higher dose should be given when they fall below protective levels.
People with conditions such as autism spectrum disorders or demyelinating disorders (including multiple sclerosis) should receive all routinely recommended immunizations, including HB-containing vaccine.
Chronic liver disease
HB immunization is recommended for susceptible persons with chronic liver disease, including those infected with hepatitis C, because they are at risk of more severe disease if infection occurs. Vaccination should be completed early in the course of the disease, as the immune response to vaccine is suboptimal in advanced liver disease. Anti-HBs testing may be used to document vaccine response.
For people with advanced liver disease, including disease caused by hepatitis C, seroconversion should be assessed after vaccination and consideration given to offering higher doses as defined in Higher vaccine dosing to those who do not respond (i.e., who do not achieve an anti-HBs titre of at least 10 IU/L) to the first series of vaccine.
Non-malignant hematologic disorders
Persons with bleeding disorders and other people receiving repeated infusions of blood or blood products are considered to be at higher risk of contracting hepatitis B and should be offered HB vaccine. In an unvaccinated individual with a bleeding disorder in whom passive immunization with hepatitis B immune globulin (HBIg) may be indicated due to an exposure, it is recommended to give clotting factor concentrates prior to giving HBIg.
Endocrine and metabolic diseases
HB immunization for previously unvaccinated adults with type 1 or type 2 diabetes is currently under review by NACI.
The risk of HB for susceptible travellers to developing countries has been estimated to be 0.2 to 0.6/1,000 per month, and may be much higher for those engaging in high risk activities and those working in health care settings. HB vaccination should be recommended to travellers who will be residing in areas with high levels of endemic HB or working in health care facilities, and those likely to have contact with blood or to have sexual contact with residents of endemic areas. Complete HB immunization is recommended for children who will live in an HB endemic area. A map of countries and areas of risk for HB can be viewed through the WHO.
It is not necessary to request anti-HBs titres in previously immunized travellers, unless the person is a health care worker who has never had their anti-HBs titre verified. Refer to Workers.
Concomitant immunization with HA and HB vaccines is recommended, as HA vaccination is also indicated for travellers to developing countries. For those who are susceptible to both HA and HB virus, a combined HAHB vaccine can be used. For travellers presenting less than 21 days before departure, monovalent HA and HB vaccines should be administered separately, with the completion of both vaccine series after travel. Refer to Hepatitis A Vaccine in Part 4 for additional information. Refer to Immunization of Travellers in Part 3 for additional general information.
Persons new to Canada
Health care providers who see persons newly arrived in Canada should review the immunization status and update immunization for these individuals. In many countries outside of Canada, HB vaccine is in limited use. Information on vaccination schedules in other countries can be viewed through WHO.
All persons from a country that is endemic for HB should be assessed for immunity and vaccinated against HB if not immune. Individuals born in developing countries are more likely to be carriers of HB, necessitating vaccination of their sexual and household contacts. HB vaccine is recommended for all susceptible household contacts whose families have immigrated to Canada from areas where there is a high prevalence of HB, and who thus may be exposed to HB carriers through their extended families or when visiting their country of origin.
Persons new to Canada should be tested for:
- HBsAg, anti-HBs, and anti-HBc. If any member of a family is found to be positive for HBsAg, the entire family should be tested for HB markers and vaccinated if they are susceptible.
- Hepatitis C antibody. Persons chronically infected with hepatitis C should be vaccinated against HB if they are susceptible.
Children adopted from countries in which there is a high prevalence of HB infection should be screened for HBsAg and, if positive, the household and other close contacts in the adopting family should be immunized before adoption or as soon as possible thereafter. Adults going to pick-up children from these countries should be vaccinated before departure. Refer to Immunization of Persons New to Canada in Part 3 for additional general information.
Immunization with HB vaccine and post-immunization serologic testing within 1 to 6 months of completion of the vaccine series are recommended for people who are at increased risk of infection through occupational exposure to blood, blood products and bodily fluids that may contain HB virus. This group includes all health care workers and others (e.g. research or industrial laboratory workers, staff of correctional facilities or institutions for the developmentally challenged) who may be exposed to blood or blood products, or are at risk of injury by instruments contaminated by blood, or are at risk of bites or penetrating injuries from objects that may be contaminated with blood. Students in these occupations should complete their vaccine series before occupational exposure. Emergency service workers, such as police and firefighters, may also be at higher risk of exposure, although there are no data to quantify their risk. As children with HB are usually asymptomatic and the HB status of children in child care settings is generally unknown, vaccination should also be considered for all child care workers. Workers who have no contact with blood or blood products are at no greater risk than the general population.
If a worker has documentation of receiving a complete HB vaccine series but does not have documentation of anti-HBs serology following immunization, or, if a worker reports HB immunization but has no or incomplete documentation of HB immunization, serologic testing for anti-HBs should be done and then:
- If an anti-HBs titre of at least 10 IU/L is confirmed, testing need not be repeated nor should further immunization be undertaken, with the exception of immunocompromised persons who should be tested periodically for waning immunity, and persons with chronic renal disease or on dialysis, who should be tested yearly.
- If testing for anti-HBs is done 1 to 6 months after vaccination and the anti-HBs titre is less than 10 IU/L, a primary vaccine failure has occurred and the worker should be given a second vaccine series. The worker should be retested 1 to 6 months after completion of the second series.
- If the worker is tested more than 6 months after the initial series and the anti-HBs titre is less than 10 IU/L, the cause may be either a primary vaccine failure or waning antibody. Evidence shows that, in immunocompetent people, immunity is long lasting although antibody may be non-detectable. The worker should receive one booster dose and be retested one month later to document an anamnestic response; if the anti-HBs titre is still less than 10 IU/L then a second vaccine series is indicated, followed by anti-HBs serology 1 to 6 months after completing the second series.
- Workers who have documented evidence of failure to respond to two series of HB vaccine (i.e., anti-HBs titre of less than10 IU/L) are unlikely to benefit from further immunization and will need passive immunization after potential exposure to HB.
If an HB exposure occurs, and a worker has had a documented anti-HBs titre of at least 10 IU/L, no further testing is needed, unless the worker is immunocompromised or has chronic renal disease or is on dialysis. These workers should be tested for anti-HBs after a potential HB exposure and given additional vaccine and HBIg if their anti-HBs titre is less than 10 IU/L. Refer to Figure 2 and Figure 3.
Post-exposure prophylaxis should be offered to susceptible individuals in the following circumstances:
- Infants born to mothers with acute or chronic HB infection
- Percutaneous or mucosal exposure to blood or bodily fluids potentially containing HB virus
- Sexual or household contacts of an acute case or chronic carrier of HB
Infants born to a mother with acute or chronic hepatitis B infection
All pregnant women should be routinely tested for HBsAg. If maternal testing has not been conducted during pregnancy, it should be done at the time of delivery and urgent testing requested. If maternal HB status is not available within 12 hours of delivery, consideration should be given to administering HB vaccine with or without HBIg to the infant while the results are pending, taking into account the mother's risk factors and erring on the side of providing vaccine and considering HBIg if there is any suspicion that the mother could be an acute case or a carrier.
All infants born to infected mothers should be given a dose of HB vaccine within 12 hours of birth. The second and third doses should be given 1 and 6 months after the first. For these infants, the 6 month dose can be given as DTaP-HB-IPV-Hib vaccine. Premature infants weighing less than 2,000 grams at birth who are born to infected mothers should receive four doses of HB vaccine at 0, 1, 2 and 6 months of age. DTaP-HB-IPV-Hib vaccine can be used for the 2 and 6 month doses (refer to Infants born prematurely).
Vaccine is the most important intervention, providing 90% of the protection from HB; HBIg may provide some additional protection. An intramuscular (IM) dose of 0.5 mL HBIg should also be given as soon as possible and preferably within 12 hours after birth to infants born to mothers with acute or chronic hepatitis B. Vaccine and HBIg may be given at the same time but at different injection sites, using separate needles and syringes. The efficacy of HBIg decreases significantly after 48 hours, but may be given up to 7 days after birth if it has been delayed for any reason. The benefit of HBIg given more than 7 days after exposure is unknown. The timing and use of HBIg is currently under review by NACI.
Infants born to infected mothers should be tested for HBsAg and anti-HBs 4 weeks after completion of the vaccine series to assess success of immunoprophylaxis. If HBsAg is present, the child will likely become a chronic carrier. If the infant is negative for both HBsAg and anti-HBs (i.e., a vaccine non-responder), additional doses of vaccine (up to a second full course) should be given with repeated serologic testing for antibody response. Refer to Serologic Testing.
Percutaneous (needlestick, bite) or mucosal exposure
The management of potential percutaneous or mucosal exposure to HB should be based on the immunization and antibody status of the injured person and the infectious status, if known, of the source (refer to Figure 2 and Figure 3). Testing of the source should be conducted according to Health Canada/Public Health Agency of Canada guidelines An Integrated Protocol to Manage Health Care Workers Exposed to Bloodborne Pathogens. If the assessment results of the exposed person and the source are not available within 48 hours, management of the exposed person should assume possible exposure. If indicated, HBIg should be administered to susceptible individuals within 48 hours after exposure. The efficacy of HBIg decreases significantly after 48 hours, but may be given up to 7 days after exposure if it has been delayed for any reason. The benefit of HBIg given more than 7 days after exposure is unknown. The dose of HBIg for older children and adults is 0.06 mL/kg given intramuscularly (IM). All those susceptible and exposed should be counselled on the use of measures to reduce the risk of transmission to others, until the vaccine series has been completed and protective concentrations of anti-HBs demonstrated.
Sexual and household contacts of hepatitis B
All susceptible and uninfected sexual and household contacts of acute cases and chronic carriers of HB should be immunized with HB vaccine and tested for antibody response 1 to 6 months after completion of the vaccine series. HBIg is not indicated for household contacts of an acute HB case, with the exception of newborns when the mother is acutely (or chronically) infected. For sexual contacts, a single IM dose of HBIg (0.06 mL/kg) should be given within 48 hours after exposure. The efficacy of HBIg decreases significantly after 48 hours, but may be given up to 14 days after exposure from the last sexual contact, due to a lower level of exposure. Refer to Figure 2. People with identifiable exposure to the infected person's blood (e.g., sharing toothbrushes or razors) should be managed as a percutaneous or mucosal exposure (refer to Percutaneous or mucosal exposure).
Refer to Passive Immunizing Agents Part 5 for additional general information.
Dose, route of administration, and schedule
Dose and schedule
There are several authorized schedules for HB vaccines. The preferred schedule (particularly for children under 12 months of age) is 0, month 1 and month 6, with at least 4 weeks between the first and second dose, 2 months between the second and third dose and 4 months between the first and the third dose. For infants immunized at birth, this dose is considered as month 0. People with chronic renal failure or on dialysis, and others with immunocompromising conditions as outlined in Immunocompromised persons, may not respond well to HB vaccine and may require a higher dose. Refer to Table 3.
DTaP-HB-IPV-Hib vaccine may be given at 2, 4, 6 and 12 to 23 months of age but the fourth dose is unlikely to provide significant additional hepatitis B protection and will increase cost. Alternative schedules may be used -
- DTaP-HB-IPV-Hib vaccine (2, 4 and 6 months of age) with DTaP-IPV-Hib vaccine at 12 to 23 months of age
- DTaP-HB-IPV-Hib vaccine (2, 4 and 12 to 23 months of age) with DTaP-IPV-Hib vaccine at 6 months of age.
There are several authorized schedules for HAHB vaccines (refer to Table 3). In addition, studies have shown that other schedules and dosages provide good seroprotection rates. Refer to Hepatitis A Vaccine in Part 4 for additional information.
|Monovalent hepatitis B||DTaP-HB-IPV-Hib||HAHB|
|RECOMBIVAX HB®||ENGERIX®-B||INFANRIX hexa™||TWINRIX®||TWINRIX® Junior|
(Months: 1st dose = month 0)
(Months: 1st dose = month 0)
(Months: 1st dose = month 0)
(Months: 1st dose = month 0)
|Infants and children|
|Infants of HB-negative mothers||2.5||0.25||0, 1, 6Table 3 - Footnote **||10||0.5||
||10||0.5||Months of age:
||Not indicated||Not indicated|
|Infants of HB-positive mothersTable 3 - Footnote †||5||0.5||0, 1, 6Table 3 - Footnote **||10||0.5||
||Not indicated before 6 weeks of age||Not indicated||Not indicated|
|12 months to 23 months of age||2.5||0.25||0, 1, 6Table 3 - Footnote **||10||0.5||
||10||0.5||Months: 1st dose = month 0)
||20||1.0||0, 6-12||10||0.5||0, 1, 6|
|24 months to less than 11 years of age||2.5||0.25||0, 1, 6Table 3 - Footnote **||10||0.5||
||May be given to children aged 24 months to 7 years, if necessary||20||1.0||0, 6-12||10||0.5||0, 1, 6|
|11 to 15 years of age (inclusive)||
||Not indicated||20||1.0||0, 6-12||10||0.5||0, 1, 6|
|16 to 18 years of age (inclusive)||5||0.5||0, 1, 6Table 3 - Footnote **||10Table 3 - Footnote ¥||0.5||
||Not indicated||Not indicated||10||0.5||0, 1, 6|
|Dialysis, chronic renal failure and some immunocompromisedTable 3 - Footnote ^ children, under 16 years of age||double the µg dose for healthy child of same age||3 or 4 dose schedule||double the µg dose for healthy child of same age||3 or 4 dose schedule||Not indicated||Not indicated||Not indicated|
|Dialysis, chronic renal failure and some immunocompromisedTable 3 - Footnote ^ 16 to 19 years of age||double the µg dose for healthy child of same age||3 or 4 dose schedule||40||2.0||0, 1, 2, 6||Not indicated||Not indicated||Not indicated|
|19 years of age||5||0.5||0, 1, 6Table 3 - Footnote **||10Table 3 - Footnote ¥||0.5||
|20 years of age and older||10||1.0||0, 1, 6Table 3 - Footnote **||20||1.0||
|Dialysis, chronic renal failure and some immunocompromisedTable 3 - Footnote ^, 20 years of age and older||40 (adult dialysis formulation)||1.0||0, 1, 6||40||2.0||0, 1, 2, 6||Not indicated||Not indicated||Not indicated|
Route of administration
HB-containing vaccine should be administered IM. Refer to Vaccine Administration Practices in Part 1 for additional information.
Booster doses and re-immunization
Routine boosters are not recommended for immunocompetent persons. Absence of a protective antibody titre in a healthy person who has previously demonstrated an adequate anti-HBs titre does not mean lack of protection because immune memory persists. Evidence shows that immunity is long lasting even though antibody may be undetectable. People immunized as an infant, child or adolescent who are at risk of exposure to HB virus (e.g., health care workers, those with other occupational risks, men who have sex with men, injection drug users, contacts of carriers etc.) should have serology testing for anti-HBs to ensure response to vaccination (refer to Serologic Testing - post-immunization).
Immunocompromised persons, persons with chronic renal disease or on dialysis and persons undergoing chemotherapy who have responded initially to HB vaccine, may require booster doses periodically if anti-HBs titres fall below 10 IU/L (refer to Immunocompromised persons and Persons with chronic diseases). If a higher dose was indicated for the initial series, then a higher dose should also be used for the booster dose.
Additional doses of vaccine (up to three doses) will produce a protective antibody response in 50% to 70% of healthy adults and children who fail to respond after the first series of vaccine. Individuals who fail to respond to three additional doses of vaccine are unlikely to benefit from further immunization. Refer to Serologic Testing.
If HBsAg testing has not been done during pregnancy, it should be done at the time of delivery. An unimmunized pregnant woman who has no markers of acute or chronic HB infection but who is at high risk of acquiring HB should be offered a complete HB vaccination series at the first opportunity and tested for antibody response. Repeat testing before delivery should be considered in uninfected and unimmunized women with continuing high risk behaviour.
High risk groups
Routine pre-immunization serologic testing for HB is recommended for people at high risk of infection to identify those already infected or immune for whom vaccine will provide no benefit.
Children adopted from countries or family situations in which there is a high prevalence of HB should be screened for HBsAg and, if positive, household or close contacts in the adopting family should be immunized before adoption or as soon as possible thereafter.
Serologic testing of infants and children is not recommended after receiving HB-containing vaccine in routine infant and childhood programs.
Post-immunization serologic testing within 1 to 6 months of completion of the vaccine series is recommended for the following groups because it is important to ensure that they are protected against HB:
- Immunocompromised persons. Periodic monitoring of the anti-HBs titre should also be considered, taking into account the severity of the immunocompromised state and whether the risk of HB is still present. Refer to Booster doses and re-immunization and Immunocompromised persons.
- Persons with chronic renal disease or on dialysis. Anti-HBs titres should also be evaluated yearly. Refer to Booster doses and re-immunization and Immunocompromised persons.
- High risk pregnant women who are immunized before or during pregnancy. Refer to Pregnancy and breastfeeding.
- Infants born to infected mothers should be tested for HBsAg and anti-HBs one month after completion of the vaccine series. Refer to Post-exposure immunization.
- Persons with potential percutaneous or mucosal exposure, such as men who have sex with men and injection drug users. Refer to Post-exposure immunization.
- Sexual partners and household contacts of acute cases and chronic carriers of HB. Refer to Post-exposure immunization.
- Workers who have been immunized because of risk of occupational exposure. Refer to Workers.
Refer to Booster doses and re-immunization.
HB-containing vaccine should be stored at +2°C to +8°C and not fozen. Refer to Storage and Handling of Immunizing Agents in Part 1 for additional general information. Refer to Passive Immunizing Agents Part 5 for information regarding HBIg storage.
Simultaneous Administration with Other Vaccines
Hepatitis B-containing vaccines may be administered concomitantly with other vaccines at different injection sites using separate needles and syringes. Refer to Timing of Vaccine Administration in Part 1 for additional general information.
Vaccine and Immune Globulin Safety and Adverse Events
Refer to Vaccine Safety in Part 2 for additional general information.
Common and local adverse events
HB vaccine is well tolerated. Reactions are usually mild and transient, and include irritability, headache, fatigue and injection site reactions (e.g., pain and redness) in 10% or more of recipients.
There is no increase in adverse events when HAHB vaccine is compared with HA vaccine given alone or concomitantly with HB vaccine at a different injection site. When adult dose HAHB vaccine is given to children in the two dose schedule, there is no increase in adverse events compared with those occurring after administration of the pediatric dose.
Reactions are usually mild and transient, and include fever, irritability, restlessness and injection site reactions (e.g., redness, swelling and pain).
Headache, diarrhea, fever, urticaria, angioedema and injection site reactions (e.g., pain and tenderness) may occur.
Less common and serious or severe adverse events
Serious adverse events are rare following HB immunization and, in most cases, data are insufficient to determine a causal association. Anaphylaxis following vaccination with HB-containing vaccine may occur but is very rare.
Other reported adverse events and conditions
While serious events and chronic illnesses have been alleged or reported following HB vaccination, no evidence of a causal association has been demonstrated in a number of studies. These chronic illnesses or serious events include chronic fatigue syndrome, multiple sclerosis, Guillain-Barré syndrome, rheumatoid arthritis and sudden infant death syndrome.
Guidance on reporting Adverse Events Following Immunization (AEFI)
Vaccine providers are asked to report, through local public health officials, any serious or unexpected adverse event felt to be temporally related to vaccination. An unexpected AEFI is an event that is not listed in available product information but may be due to the immunization, or a change in the frequency of a known AEFI. Refer to Reporting Adverse Events Following Immunization (AEFI) in Canada in Vaccine Safety Part 2 for additional information about AEFI reporting.
Contraindications and precautions
HB-containing vaccines and HBIg are contraindicated in persons with a history of anaphylaxis after previous administration of the product and in persons with proven immediate or anaphylactic hypersensitivity to any component of the product or its container. Refer to Contents of Immunizing Agents Available for Use in Canada in Part 1 for lists of all vaccines and passive immunizing agents available for use in Canada and their contents.
For HB-containing vaccines, potential allergens include:
- ENGERIX®-B: yeast
- INFANRIX™-hexa: latex in plunger stopper of pre-filled syringe, neomycin, polymyxin B, yeast
- RECOMBIVAX HB®: latex in vial stopper, yeast
- TWINRIX® and TWINRIX® Junior: latex in plunger stopper of pre-filled syringe, neomycin, yeast
Yeast protein is used in the development of HB and HAHB vaccines. Hypersensitivity to yeast is very rare and a personal history of yeast allergy is not generally reliable. In situations of suspected hypersensitivity or non-anaphylactic allergy to vaccine components, investigation is indicated which may involve immunization in a controlled setting. Consultation with an allergist is advised.
The safety of HAHB vaccine given during pregnancy has not been studied in clinical trials. However, because the vaccine is prepared from inactivated viruses, no risk to the developing fetus is anticipated.
Routine administration of HB-containing vaccine should be postponed in persons with moderate or severe acute illness, but this is subject to a risk and benefit assessment if immunization is recommended for post-exposure management. Consultation may be advised. Persons with minor acute illness, with or without fever, may be vaccinated.
Refer to General Contraindications and Precautions in Part 2 for additional general information.
Interchangeability of vaccines
Monovalent HB vaccines may be used interchangeably, using the dosage and schedules recommended by the manufacturer for the age group. Refer to Principles of Vaccine Interchangeability in Part 1 for additional general information.
- American Academy of Pediatrics. In: Pickering LK, Baker CJ, Kimberlin DW, et al. (editors). Red Book: 2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009.
- Ascherio A, Zhang S, Hernan M et al. Hepatitis B vaccination and the risk of multiple sclerosis. N Engl J Med. 2001;344:327-32.
- Banatvala J, VanDamme P, Oehen S et al. Lifelong protection against hepatitis B: the role of vaccine immunogenicity in immune memory. Vaccine. 2001;19:877-85.
- Cangene Corp. Product Monograph - HepaGam B™. April 2009.
- Centers for Disease Control and Prevention. The Pink Book: Epidemiology and Prevention of Vaccine Preventable Diseases. Updated 11th ed.; May 2009.
- Committee to Advise on Tropical Medicine and Travel. Statement on hepatitis vaccines for travellers. Can Comm Dis Rep. 2008;34(ACS-2):1-24.
- Committee to Advise on Tropical Medicine and Travel. Statement on international adoption. Can Comm Dis Rep. 2010;36(ACS-15):1-17.
- Confavreau C, Suissa S, Saddier P et al. Vaccinations and the risk of relapse of multiple sclerosis. N Engl J Med. 2001;344:319-26.
- Duval B, Boulianne G, De Serres G. Should children with isolated anti-HBs or anti-HBc be immunized against hepatitis B virus? JAMA. 1997;287:1064.
- Duval B, Gîlca V, Boulianne N et al. Comparative long-term immunogenicity of two recombinant hepatitis B vaccines and the effect of a booster dose given after 5 years in a low endemicity country. Pediatr Infect Dis J. 2005;24:213-8.
- Duval B, Gîlca V, Boulianne N et al. Immunogenicity of two paediatric doses of monovalent hepatitis B or combined hepatitis A and B vaccine in 8-10-year-old children. Vaccine 2005;23(31):4082-87.
- FitzSimons D, François G, Hall A et al. Long-term efficacy of hepatitis B vaccine, booster policy, and impact of hepatitis B virus mutant. Vaccine 2005;23:4158-66.
- Flynn P, Cunningham C, Rudy B et al. Hepatitis B Vaccination in HIV-Infected Youth: A Randomized Trial of Three Regimens. J Acquir Immune Defic Syndr 2011;56(4):325-32.
- Gilca V, De Serres G, Boulianne N, et al. Antibody kinetics among 8-10 years old respondents to hepatitis B vaccination in a low endemic country and the effect of a booster dose given five or ten years later. Vaccine 2009;27(43):6048-53.
- GlaxoSmithKline Inc. Product Monograph - ENGERIX®-B. September 2008.
- GlaxoSmithKline Inc. Product Monograph - INFANRIX hexa™. July 2008.
- GlaxoSmithKline Inc. Product Monograph - TWINRIX®. September 2008.
- Jarroson L, Kolopp-Sarda M, Aguilar P et al. Most humoral non-responders to hepatitis B vaccines develop HBV-specific cellular immune responses. Vaccine 2004;22:3789-96.
- Losonsky GA, Wasserman SS, Stephens I et al. Hepatitis B vaccination of premature infants. Pediatrics 1999;103(2): E14.
- McMahon B, Bruden DL, Petersen K et al. Antibody levels and protection after hepatitis B vaccination: results of a 15-year follow-up. Ann Intern Med. 2005;142:333-41.
- Merck Frosst Canada Ltd. Product Monograph - RECOMBIVAX HB®. March 2009.
- National Advisory Committee on Immunization. Statement on the recommended use of pentavalent and hexavalent vaccines. Can Comm Dis Rep. 2007;33(ACS-1):1-15.
- Navas E, Salleras L, Gisbert R et al. Efficiency of the incorporation of the hepatitis A vaccine as a combined A+B vaccine to the hepatitis B vaccination programme of preadolescents in schools. Vaccine 2005;23(17-18): 2185-9.
- Public Health Agency of Canada. An integrated protocol to manage health care workers exposed to bloodborne pathogens. Can Comm Dis Rep. 1997;23S2.
- Roberton D, Marshall H, Nolan T et al. Reactogenicity and immunogenicity profile of a two-dose combined hepatitis A and B vaccine in 1-11-year-old children. Vaccine 2005(43);23:5099-105.
- Shefer A, Atkinson W, Friedman C et al. Immunization of Health-Care Personnel Recommendations of the Advisory Committee on Immunization Practices. MMWR 2011;60:1-46
- Talecris Biotherapeutics Inc. Product Monograph - HyperHEP B™ S/D. September 2006.
- Watson B, West DJ, Chilkatowsky A et al. Persistence of immunologic memory for 13 years in recipients of a recombinant hepatitis B vaccine. Vaccine 2001;19:3164-8.
- Zhongjie S, Yang Y, Wang H et al. Breastfeeding of Newborns by Mothers Carrying Hepatitis B Virus A Meta-analysis and Systematic Review. Arch Pediatri Adolesc Med 2011;165(9): 837-46.
- Date modified: