Significant revisions since the last chapter update are highlighted in the Canadian Immunization Guide Chapter Updates Table which is available on the Public Health Agency of Canada website.
Hepatitis A (HA) virus is single serotype, ribonucleic acid (RNA) virus of the Picornaviridae family.
Humans, rarely chimpanzees and other primates
HA is transmitted via the fecal-oral route, which can occur from direct person-to-person contact, from contamination of the environment or objects, or through contaminated food or water. Transmission through infected blood or blood products has also been reported. Symptoms appear after an incubation period of 15 to 50 days (average 28 days). Cases are typically infectious two weeks before the onset of symptoms and remain infectious until a week after the onset of jaundice. The virus may remain infectious in the environment for several weeks. Viral shedding can be greatly prolonged in immunocompromised individuals.
Persons at increased risk of HA infection include:
Many reported cases of hepatitis A have no identifiable risk factors.
Spectrum of clinical illness
Older children and adults infected with HA typically have abrupt onset of anorexia, nausea, fatigue, fever and jaundice. In children less than 6 years of age, illness may be asymptomatic or mild; jaundice is uncommon. The severity of HA can range from a mild illness lasting 1 to 2 weeks to a severely disabling disease lasting several months. Approximately 25% of adult cases are hospitalized. The overall case fatality rate is 0.1% to 0.3%, but can reach 1.8% in adults over 50 years of age. Individuals with chronic liver disease have an increased risk of progressing to fulminant hepatic failure resulting in death. Chronic hepatitis and carrier states are not associated with HA; however, relapsing hepatitis lasting up to a year occurs in 15% of cases. Lifelong immunity to HA follows infection.
HA occurs worldwide. Regions with higher levels of endemicity and risk of HA transmission include: South Asia, Sub-Saharan Africa, Central Asia, Latin America, North Africa/Middle East, and Oceania. A map of countries and areas of risk for HA is available from the World Health Organization (WHO).
Since the introduction of HA vaccine in Canada in 1996, the incidence of HA has declined. The number of cases of HA reported annually has varied from 2,978 (1991) to 298 (2008), (10.6 and 0.9 per 100,000 population, respectively). Age specific-incidence is highest among those 5 to 9 years old with a rate of 2.1 per 100,000, followed by those aged 1 to 4 years (1.5 per 100,000 population). In recent years, there has been no significant difference in incidence rates for males and females (refer to Figure 1). Given the under-diagnosis and under-reporting of HA and the occurrence of subclinical infections, the actual number of HA cases is estimated to be seven times higher than reported.
In a 2003 nationwide seroprevalence study, 2.0% of unvaccinated Canadian-born children between 8 and 13 years of age had anti-HA antibodies. A similar study found 20% seropositivity in Canadian-born, unvaccinated adults. The study also found seroprevalence increased with age, from 2.6% of 18-29 year olds to 45.9% of 60-69 year olds.
Community HA outbreaks linked to infected food handlers have been reported in Canada. Although no outbreaks linked to imported food from endemic regions have been reported in Canada, large multi-state outbreaks have occurred in the United States. During the 1990s, there were several HA outbreaks among MSM across Canada. There have been no outbreaks reported in these communities in recent years, likely the result of targeted vaccination programs. Outbreaks with no identifiable source were reported among First Nations communities in the 1990s. There were no additional First Nations outbreaks reported for several years until a prolonged multi-community outbreak in British Columbia from 2010 to 2012.
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 in 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.
HA vaccines have demonstrated at least 90% to 97% effectiveness in preventing clinical illness.
Epidemiologic studies of HA outbreaks have shown that the use of vaccine in the susceptible population interrupts the outbreak. The protective efficacy of vaccine in one study when vaccine was used within one week of exposure was 79%.
In serologic studies of HA vaccines, 95% to 100% of vaccinees developed protective concentrations of antibody against HA after a single dose of HA vaccine, and nearly 100% seroconverted after receiving two doses.
There is no reduction, and possibly even an increase, in seroprotection rates achieved by HAHB vaccine compared with monovalent HA and HB vaccines. Equivalent seroconversion rates are achieved by HA-Typh-I vaccine compared with typhoid and monovalent HA vaccines.
HA vaccine is recommended for pre-exposure immunization of persons one year of age and older at increased risk of infection or severe HA (refer to Table 1). All persons who wish to decrease their risk of acquiring HA should be encouraged to be vaccinated. The off-label use of HA vaccine in 6 to 11 month olds (e.g., for travel to endemic areas) is under National Advisory Committee on Immunization (NACI) review. In some First Nations communities, HA vaccine is given to infants starting at 6 months of age. 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 B Vaccine in Part 4 for additional information.
Table 1: Recommended recipients of hepatitis A vaccine for pre-exposure prevention (for post-exposure prevention refer to Post-exposure immunization)
Travellers to or immigrants from HA endemic areas. Refer to Travellers.
Household or close contacts of children adopted from HA endemic countries
Populations or communities at risk of HA outbreaks or in which HA is highly endemic (e.g., some aboriginal communities).
Persons with lifestyle risks for infection, including those who use illicit drugs (injectable and non-injectable) and men who have sex with men (MSM).
Persons who have chronic liver disease from any cause, including persons infected with hepatitis B or C. While these persons may not be at increased risk of hepatitis A infection, they may be at risk of more severe disease if infection occurs.
People with hemophilia A or B receiving plasma-derived replacement clotting factors.
Military personnel and humanitarian relief workers likely to be posted to areas with high rates of HA.
Zoo-keepers, veterinarians and researchers who handle non-human primates.
Workers involved in research on HA virus or production of HA vaccine who may be exposed to HA virus.
Any person who wishes to decrease his or her risk of HA.
Human immune globulin
HA vaccine is the preferred agent for pre-exposure prophylaxis. Human immune globulin (Ig) will provide protection against HA when administered intramuscularly before exposure or during the incubation period and may be indicated for pre-exposure prophylaxis in the following circumstances:
The effectiveness of Ig depends upon the timing of administration and the dose given. The recommended dose of Ig varies according to the duration of required protection. In general, for protection lasting less than 3 months the dose is 0.02 mL/kg. If protection is required for 3 months or longer, 0.06 mL/kg should be administered and repeated every 6 months.
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. HA or HAHB vaccine may be given, if indicated, regardless of possible previous receipt of the vaccine or pre-existing immunity, because adverse events associated with repeated immunization have not been demonstrated. Refer to Immunization of Children and Adults with Inadequate Immunization Recordsin Part 3 for additional general information.
The safety of HA-containing vaccines given during pregnancy has not been studied in clinical trials. However, because the vaccines are prepared from inactivated viruses, no risk to the developing fetus is anticipated. HA vaccine should be considered for pregnant women in high risk situations when benefits outweigh risks. Refer to Hepatitis B Vaccine and Typhoid Vaccine in Part 4 for additional information. Refer to Immunization in Pregnancy and Breastfeeding in Part 3 for additional general information.
HA vaccine may be administered to immunocompromised persons. Vaccine efficacy may be reduced in the immunosuppressed; however, the vaccine will provide some protection and should be considered for pre-exposure and post-exposure use when indicated. Along with HA vaccine, Ig should be considered for pre-exposure and post-exposure management of immunocompromised persons, since they may not adequately respond to HA vaccine. Serological testing to determine immune status may be considered in immunocompromised people when considering the use of Ig prior to potential exposure (e.g., travel to high risk areas). If serology is positive, pre-exposure immune Ig and vaccine would not be indicated.
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.
Individuals with congenital immunodeficiencies involving any part of the immune system may receive HA vaccine if risks for infection with HA are present (refer to Table 1).
Hematopoietic stem cell transplantation (HSCT - autologous or allogeneic)
If indicated, HA vaccine may be given, ideally at least 6 months post-transplant. Susceptible household contacts of HSCT recipients should receive HA vaccine if risks for infection with HA are present (refer to Table 1).
Solid organ transplantation
HA vaccine is recommended for all transplant candidates with chronic liver diseases and can be given to all solid organ transplant candidates and recipients if risks for infection with HA are present (refer to Table 1). If possible, the HA vaccine series should be completed prior to transplant. If HA vaccine wasn't given or if the series was only partially completed prior to transplant, the vaccine series should be started or completed at 6 months post-transplant. Susceptible household contacts of solid organ transplant recipients should receive HA vaccine if risks for infection with HA are present (refer to Table 1).
If indicated, HA vaccine can safely be given at any time before, during or after immunosuppressive therapy. In particular, for post-exposure or outbreak management, HA vaccine should be given at any time before, during or after immunosuppressive therapy. However, to ensure optimal immunogenicity when being used for non-urgent indications, the following timelines should be followed whenever possible.
HA 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] lasting for 14 days or more; chemotherapy [e.g., azathioprine, cyclosporine, cyclophosphamide, infliximab]; or radiation therapy). If this time frame cannot be accommodated, a period of at least 3 months should elapse after immunosuppressive drugs (except high-dose systemic corticosteroids) have been stopped before administration of HA vaccine, to ensure immunogenicity. A period of at least 4 weeks should elapse between discontinuation of high-dose systemic steroids and administration of HA vaccine. The interval between discontinuation of immunosuppressive drugs and HA vaccine may vary with the intensity of the immunosuppressive therapy, underlying disease and other factors.
If immunosuppressive therapy cannot be stopped, HA vaccine should be given when the person is least immunosuppressed if possible.
HA vaccine is recommended for HIV-infected individuals with risk factors for HA (e.g., MSM or illicit drug use.)
Refer to Immunization of Immunocompromised Persons in Part 3 for additional general information.
Chronic renal disease or on dialysis
One study assessing the immune response to standard doses of HA vaccine in hemodialysis patients showed a good HA antibody response in all study subjects and no serious adverse effects were observed. HA vaccine is recommended for people with chronic renal disease with risk factors for HA or those on dialysis with risk factors for HA.
Chronic liver disease
Hepatitis A immunization is recommended for susceptible persons with chronic liver disease, including those infected with hepatitis C and chronic hepatitis B carriers, 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.
Non-malignant hematologic disorders
Hepatitis A immunization is recommended for people with haemophilia A or B receiving plasma-derived replacement clotting factors. The solvent-detergent method used to prepare all current plasma-derived factor VIII products and some factor IX concentrates does not reliably inactivate HA virus because the virus does not have an envelope. Historically, there has been evidence of transmission from clotting factors; however, with testing protocols in place currently this risk is very low.
Refer to Immunization of Persons with Chronic Diseasesin Part 3 for additional information.
Hepatitis A is one of the most common vaccine preventable diseases in travellers. Protection against HA is recommended for all travellers to developing countries, especially to rural areas or places with inadequate sanitary facilities. View a map of countries and areas of risk for HA through WHO.
Given the long incubation period for HA and the demonstrated efficacy of post-exposure use of HA vaccine, administration of HA vaccine up to the day of departure is considered appropriate and efficacious. Ig is only used for travel prophylaxis in people for whom HA vaccine is contraindicated or may not be effective, such as those who are immunocompromised. Refer to Pre-exposure immunization.
As hepatitis B (HB) vaccination is also indicated for most travellers, concurrent immunization with HA and HB vaccines, is recommended. For those who are susceptible to both HA and HB virus, a combined HAHB vaccine can be used. For travellers who present between 21 and 27 days before departure, a rapid dosing schedule with HAHB vaccine may be given to adults at 0, 7, and 21 days with a booster dose required at 12 months to achieve long term immunity. For travellers presenting less than 21 days before departure, monovalent HA (which has double the antigen content of HA compared to HAHB vaccine) and HB vaccines should be administered at different injection sites using separate needles and syringes, with the completion of both vaccine series required after travel.
A positive serologic test indicates that the vaccine is not needed, thereby avoiding the cost. Serologic testing can be considered in those likely to be already immune. Refer to Serologic testing. Refer to the CATMAT Statement on hepatitis vaccines for travellers for additional information. Refer to Immunization of Travellers in Part 3 for additional general information.
Health care providers who see persons newly arrived in Canada should review their immunization status and update immunization as needed. In many countries outside of Canada, HA vaccine is in limited use. Refer to the WHO website for information on vaccination schedules in other countries
Vaccination against HA should be considered for all persons from a country where HA is endemic. Individuals born in developing countries are more likely to be immune to HA, therefore, testing for immunity before administering HA vaccine to persons from HA endemic countries should be considered. If persons from HA endemic countries are not immune, they should be offered HA immunization because they are at increased risk for HA exposure through visits back to their country of origin, or when receiving friends and family from their country of origin.
In addition, persons new to Canada should be tested for hepatitis C antibody and susceptible persons chronically infected with hepatitis C should be vaccinated against HA and HB. Persons new to Canada should also be tested for hepatitis B and vaccinated against HA if found to be a hepatitis B carrier. Household or close contacts of children adopted from HA endemic countries should be immunized with HA-containing vaccine. Adults going to pick up adopted children from HA endemic countries should be vaccinated before travel. Refer to Immunization of Persons New to Canada in Part 3 for additional general information.
Pre-exposure HA vaccination is recommended for:
Refer to Immunization of Workers in Part 3 for additional general information.
Post-exposure prophylaxis should be offered to household and close contacts of proven or suspected cases of HA. It should be given when HA occurs in group child care centres and kindergartens, and should be offered to co-workers and clients of infected food handlers. Post-exposure prophylaxis is not necessary for other contacts, such as school, workplace or health care workers caring for HA cases, unless an outbreak is suspected.
Hepatitis A vaccine
HA vaccine is effective as post-exposure prophylaxis to prevent infection in contacts and is recommended in preference to Ig for people over one year of age. One dose of HA vaccine should be given to susceptible contacts as soon as possible and preferably within 14 days of last exposure. However, HA vaccine should still be considered if more than 14 days have elapsed since last exposure, as there are no data on the outer limit of efficacy.
Ig is the recommended post-exposure immunoprophylactic agent for infants less than one year of age, for those for whom vaccine is contraindicated, and if HA vaccine is unavailable. Immunocompromised people should receive Ig in addition to HA vaccine because they may not respond fully to the vaccine. For post-exposure prophylaxis, the dose of Ig is usually 0.02 mL/kg, given as soon as possible after an exposure. Efficacy of Ig is unknown if more than 14 days have elapsed since the last exposure. Refer to Passive Immunizing Agents Part 5 for additional general information.
Dose and schedule
One dose of monovalent HA vaccine is given for primary immunization with a booster dose given 6 to 36 months later, depending on the product. The booster dose can be given anytime thereafter, if not given during this recommended interval. Refer to Table 3.
There are several authorized schedules for HAHB vaccines (refer to Table 3). In addition, clinical trials have shown that other schedules and dosages provide good seroprotection rates. A dose of adult formulation HAHB vaccine (TWINRIX®) contains a standard adult dose of HB vaccine and one-half an adult dose of HA vaccine. For individuals 19 years of age and over, the regular schedule of HAHB vaccine is months 0, 1 and 6. There is also a rapid schedule of days 0, 7 and 21, followed by a fourth dose at month 12. For individuals from 1 to 18 years of age, the authorized schedule for pediatric/adolescent formulation HAHB (TWINRIX®Junior) vaccine is months 0, 1 and 6. Another authorized schedule is for children 1 to 15 years of age, consisting of two doses of adult HAHB vaccine, given at months 0 and 6-12. Clinical trials have shown that other schedules and dosages provide good seroprotection rates and geometric mean titres (GMT). For example, a two-dose schedule with pediatric/adolescent HAHB vaccine, given at months 0 and 6 in Canadian school children (8 to 10 years of age), has been tested with good results.
Monovalent HA vaccine may be used to complete a HA series begun with HAHB vaccine and vice versa; however, monovalent HB will also be required for complete hepatitis B protection. Once a HAHB vaccine series is begun, it is preferable to finish the series with HAHB vaccine. Refer to Table 2 for options on completing HA vaccination series. Refer to Table 3 for schedules according to age for each product.
|Adult presents with history of:||Options to complete HA series|
1 dose adult HAHB vaccine
2 doses adult HAHB vaccine OR
2 doses adult HAHB vaccine
1 dose adult HAHB vaccine OR
1 dose adult HA vaccine
1 dose adult HA vaccine OR
2 doses adult HAHB vaccineTable 2 - Note *1
|Child or adolescentTable 2 - Note *3 presents with history of:||Options to complete HA series|
1 dose pediatric/adolescent HAHB vaccine
2 doses pediatric/adolescent HAHB vaccineTable 2 - Note *4 OR
1 dose adult HAHB vaccine
1 dose adult HAHB vaccine unless 16 years or olderTable 2 - Note *5 OR
2 doses pediatric/adolescent HAHB vaccine
1 dose pediatric/adolescent HAHB vaccineTable 2 - Note *4 OR
2 doses adult HAHB vaccine
No additional doses needed unless 16 years of age or olderTable 2 - Note *5
1 dose pediatric/adolescent HA vaccine
1 dose pediatric/adolescent HA vaccine
One dose of HA-Typh-I vaccine is given for primary immunization in those 16 years of age and older. To provide long term protection against HA infection, a booster dose of monovalent HA vaccine should be given 6 to 36 months later. Alternatively HA-Typh-I can be given as a booster vaccine after 36 months. HA-Typh-I vaccine may be used as a booster vaccine in persons who have received HA vaccine 36 months earlier and who require protection against typhoid. Refer to Typhoid Vaccine Part 4 for additional information.
|Vaccine||Antigen(s)Table 3 - Note *||Dose||Schedule
(Months: 1st dose = month 0)
|AgeTable 3 - Note **|
|AVAXIM®||160 antigen units HA||0.5 mL||0, 6-36||12 years and older|
|AVAXIM® Pediatric||80 antigen units HA||0.5 mL||0, 6-12||1 to 15 years|
|HAVRIX® 1440||1440 ELISA units HA||1.0 mL||0, 6-12||19 years and older|
|HAVRIX® 720 Junior||720 ELISA units HA||0.5 mL||0, 6-12||1 to 18 years|
|VAQTA®||50 units HA||1.0 mL||0, 6||18 years and older|
|VAQTA® Pediatric||25 units HA||0.5 mL||0, 6-18||1 to 17 years|
|TWINRIX®||720 ELISA units HA, 20 µg HB||1.0 mL||0, 1, 6 or 0, day 7, day 21, month 12||19 years and older|
|0, 6-12||1 to 15 years|
|TWINRIX® Junior||360 ELISA units HA, 10 µg HB||0.5 mL||0, 1, 6||1 to 18 yearsTable 3 - Note ***|
|ViVAXIM®||160 antigen units HA, Salmonella typhi||1.0 mL||0, booster dose of HA vaccine at month 6-36 or HA-Typh-I vaccine at month 36||16 years and older|
For vaccine-specific recommendations, consult the product leaflet or information contained within Health Canada's authorized product monographs available through the Drug Product Database.
Refer to Hepatitis B Vaccine in Part 4 for additional information.
Route of administration
HA-containing vaccine should be administered intramuscularly. Refer to Vaccine Administration Practices in Part 1 for additional information.
Protective concentrations of antibody will likely persist for at least 20 years, possibly for life, following immunization with two doses of HA vaccine. Immune memory has been demonstrated, indicating that protection may persist even when antibodies are no longer measurable.
Pre-immunization serologic testing should be considered in populations with potentially higher levels of pre-existing immunity, such as Canadians born before 1945, people from HA endemic areas, and people with a history of hepatitis or jaundice that may have been caused by HA. Having a positive serologic test avoids the cost of immunization, however, there is no harm in administering the HA vaccine to someone who is already immune to HA.
Serologic testing is not routinely recommended after receiving HA-containing vaccine. Post-HA vaccine serology testing has poor sensitivity. If the serology test result is positive after immunization, the person can be assumed to be immune; however, if the test result is negative, the person cannot be assumed to still be susceptible.
HA-containing vaccine should be stored at +2°C to +8°C and not frozen. HA-Typh-I vaccine should be administered immediately after mixing. 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 Ig storage.
HA and HAHB vaccines may be administered concomitantly with other vaccines or with Ig at different injection sites using separate needles and syringes. Refer to Timing of Vaccine Administration in Part 1 for additional general information.
Refer to Vaccine Safety Part 2 for additional general information.
HA vaccine is well tolerated. Reactions are generally mild and transient, and are usually limited to soreness and redness at the injection site. Other less frequent reactions include headache, irritability, malaise, fever, fatigue and gastrointestinal symptoms. Injection site reactions occur less frequently in children than in adults (21% versus 56%, respectively) as do mild, systemic events (2%-9% versus 16%). No significant difference in reactions is evident between initial and subsequent doses of vaccine or in the presence of pre-existing immunity.
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.
Injection site pain and tenderness, urticaria and angioedema may occur.
Serious adverse events are rare following immunization and, in most cases, data are insufficient to determine a causal association. Anaphylaxis following vaccination with HA-containing vaccine may occur but is very rare.
While serious events and chronic illnesses have been alleged or reported following receipt of the HB vaccine component of HAHB vaccines, 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, autoimmune disease and sudden infant death syndrome.
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) for additional information about AEFI reporting.
HA-containing vaccines and Ig 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 HA-containing vaccines, potential allergens include:
Yeast protein is used in the development of HB and HAHB vaccines. TWINRIX® and TWINRIX® Junior contain a small amount of yeast protein. 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 HA or HAHB vaccine given during pregnancy has not been studied in clinical trials. However, because the vaccines are prepared from inactivated viruses, no risk to the developing fetus is expected.
Administration of HA-containing vaccine should be postponed in persons with moderate or severe acute illness. 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.
Monovalent HA vaccines may be used interchangeably. Any HA vaccine indicated for the age of the vaccinee will provide an effective booster dose after a first dose of vaccine from a different manufacturer. Refer to Principles of Vaccine Interchangeability in Part 1 for additional general information.