Canadian Immunization Guide: Part 4 - Active Vaccines
Updated: July 2014
- Key Information
- Preparations Authorized for Use in Canada
- Efficacy, Effectiveness and Immunogenicity
- Recommendations for Use
- Vaccine Administration
- Serologic Testing
- Storage Requirements
- Simultaneous Administration with Other Vaccines
- Vaccine Safety and Adverse Events
- Other Considerations
- Selected References
Key Information (Refer to text for details)
- Typhoid fever is caused by Salmonella enterica subspecies enterica serovar Typhi (S. typhi).
- S. typhi is generally transmitted through ingestion of food and water contaminated with the feces of people with the disease or who are chronic S. typhi carriers.
- Clinical course ranges from mild illness with low-grade fever to severe systemic disease with abdominal perforation and extra-intestinal infection that, if untreated, may be fatal.
- There are 3 types of typhoid vaccines: parenteral (Typh-I), parenteral combined with hepatitis A (HA-Typh-I), and oral (Typh-O). These vaccines provide approximately 50% protection against clinical disease.
- Protection following Typh-I vaccine lasts for 3 years; protection following Typh-O vaccine lasts for about 7 years.
- The most commonly reported adverse events following immunization with Typh-I vaccine are injection site reactions (pain, swelling); following receipt of Typh-O vaccine are abdominal pain, nausea, diarrhea, vomiting, fever, headache and rash.
- Typhoid immunization is recommended for most persons (2 years of age and older) travelling to South Asia (which includes Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan and Sri Lanka).
- Typhoid immunization is not routinely recommended for travel outside of South Asia; however, it might be considered for travellers to areas outside of South Asia (e.g., Africa) based on individual-specific risk factors (such as travelling children; travellers visiting friends and relatives; longer duration of travel; functional or anatomic asplenia, the presence of achlorhydria or the use of acid suppression therapy) and personal preference.
- Typhoid immunization is also indicated for laboratory personnel at risk of exposure and for people in close contact with carriers.
- Give a single 0.5 mL dose of Typh-I vaccine for people 2 years of age and older.
- Give a single 1.0 mL dose of HA-Typh-I vaccine for people 16 years of age and older.
- Give one capsule on alternate days to a total of four capsules of Typh-O vaccine for people 5 years of age and older. Typh-O vaccine should be taken approximately one hour before, or two hours after a meal.
- Typh-O vaccine is contraindicated in pregnancy, individuals with an acute gastrointestinal condition or inflammatory bowel disease and in immunocompromised persons, including those with known HIV infection.
- Administration of oral cholera vaccine and Typh-O vaccine should be separated by at least 8 hours.
- Typh-O vaccine may be given concomitantly with or at any time before or after any parenteral vaccine.
- Typh-I vaccine and other travel vaccines may be given concomitantly.
- The World Health Organization (WHO) has estimated that there are 21 million cases of typhoid a year. About 2% to 5% of untreated typhoid cases become chronic carriers.
- The case fatality rate is approximately 10% for untreated cases in low income settings and <1% for patients receiving care in high income countries.
Since the publication of the 2006 Canadian Immunization Guide:
- Recommendations for the use of typhoid vaccine in travellers have been revised.
- Recommendations for concomitant administration of oral typhoid vaccine and antimalarial drugs have been revised.
- Oral typhoid vaccine is no longer available in sachet format.
This chapter was developed with the Committee to Advise on Tropical Medicine and Travel (CATMAT) and is consistent with the CATMAT Statement on International Travellers and Typhoid. For additional information, refer to the CATMAT statement.
Typhoid fever is caused by a bacterium, Salmonella enterica subspecies enterica serovar Typhi (S. typhi).
S. typhi is generally transmitted through ingestion of food and water contaminated with the feces of people with the disease or those who are chronic S. typhi carriers. The incubation period is usually 8 to 14 days (range, 3 days to more than 60 days). Individuals infected with S. typhi areinfectious as long as they are excreting the bacilli, usually from the first week of infection until symptoms have resolved. However, 10% of untreated individuals excrete the bacilli for 3 months or more after initially contracting the disease and 2% to 5% of untreated individuals become asymptomatic chronic carriers.
The overall risk of developing typhoid during travel to typhoid endemic countries is very low (less than 1 case/100,000 travellers). The strongest and most consistent predictor of typhoid risk in travellers is destination of travel. The estimated risk of developing travel-associated typhoid is about: 1/3,500 travellers for travel to South Asia (high risk), 1/50,000-100,000 for travel to Sub-Saharan Africa and South America (intermediate risk), and less than 1/300,000 for travel to the Caribbean and Central America (low risk).
It is known that people with anatomic or functional asplenia (i.e. from sickle cell disease) are at increased risk of severe disease from encapsulated bacteria. Several studies have identified travelling children, longer duration of travel, the presence of achlorhydria or use of acid suppression therapy, and travellers visiting friends or relatives as factors that increase the risk of travel-associated typhoid. It is plausible that each of these factors may increase risk of typhoid. The incremental magnitude of risk that these factors contribute in addition to travel destination is unclear.
Although immunocompromised conditions, such as HIV infection, are recognized to predispose to more severe and complicated infections, in general they do not appear to be associated with an increased risk of S. typhi infection.
In Canada, chronic carriers pose the greatest public health risk, particularly when working in the food industry.
Spectrum of clinical illness
Typhoid fever is a systemic illness of varying severity. The clinical course ranges from mild illness with low-grade fever to severe systemic disease with abdominal perforation and extra-intestinal infection that, if untreated, may be fatal. Symptoms may include fever, headache, abdominal pain, nausea, vomiting, malaise, anorexia, bradycardia, splenomegaly, cough, rose spots on trunk, and constipation. The case fatality rate is approximately 10% for untreated cases in low income settings and <1% for patients receiving care in high income countries. Between 2% and 5% of typhoid cases become chronic carriers, sometimes shedding bacteria in stool for years.
S. typhi infection continues to be a chief cause of enteric disease and remains a significant public health issue in developing countries, principally among children. The WHO estimates the global incidence of typhoid fever to be 21 million cases per year with an associated 210,000 to 840,000 deaths annually. The highest incidence of typhoid fever is among children 17 years of age and younger who live in low and middle income countries. Globally, it is estimated that more than 90% of typhoid cases and deaths occur in Asian countries, predominantly in South Asia (e.g., India).
The incidence of typhoid fever is very low in high income countries. The majority of cases of typhoid fever in these countries occur among travellers returning from endemic areas in low and middle income countries. The estimated incidence of typhoid fever in returned travellers to high income countries ranges from 3 to 30 cases per 100,000.
In Canada, where most cases occur in travellers, there were a mean of 117 (range, 78 to 175) cases of typhoid reported annually (1999 to 2008); with a mean incidence rate of 0.36 per 100,000 population (range, 0.3 to 0.5/100,000). In a recent study in Quebec, the majority of typhoid cases reported by international travellers (34 of 36, 94%) were people who were travelling for the purpose of visiting family members or friends living abroad.
Preparations Authorized for Use in Canada
- TYPHERIX® (Salmonella typhi Vi capsular polysaccharide vaccine for injection), GlaxoSmithKline Inc. (Typh-I)
- TYPHIM Vi® (Salmonella typhi Vi capsular polysaccharide vaccine for injection), Sanofi Pasteur SA (manufacturer), sanofi pasteur Ltd. (distributor) (Typh-I)
- ViVAXIM® (combined purified Vi polysaccharide typhoid and inactivated hepatitis A vaccine for injection), Sanofi Pasteur SA (manufacturer), sanofi pasteur Ltd. (distributor) (HA-Typh-I)
- Vivotif® (live, oral, attenuated TY21A typhoid vaccine), Crucell Switzerland Ltd. (manufacturer), Crucell Vaccines Inc. (distributor) (Typh-O)
For complete prescribing information, consult the product leaflet or information contained within the product monograph available through Health Canada's Drug Product Database. Refer to Contents of Immunizing Agents Available for Use in Canada in Part 1 for a list of vaccines available for use in Canada and their contents.
Efficacy, Effectiveness and Immunogenicity
Efficacy and effectiveness
All vaccine efficacy studies were performed in populations living in endemic areas; these data have been extrapolated to travellers. Efficacy of typhoid vaccine (oral and intramuscular formulations) in preventing typhoid is approximately 50%. There are no authorized vaccines to protect against S. paratyphi infection (paratyphoid). Evidence suggests that oral typhoid vaccine provides some protection against paratyphoid; however, the evidence is insufficient to recommend the off-label use of typhoid vaccine for this indication.
Immunity following Typh-I vaccine is thought to last for 3 years.
Live, attenuated oral typhoid vaccine stimulates a cell-mediated immune response, as well as inducing both secretory and humoral antibody. Protective antibodies are detectable for about 7 years following receipt of Typh-O vaccine.
Recommendations for Use
Children (2 to 17 years of age) and adults (18 years of age and older)
Most Canadian travellers visiting South Asia (including Afghanistan, India, Nepal Bangladesh, Maldives, Sri Lanka and Bhutan) should be offered typhoid vaccine.
Most Canadians travellers visiting destinations other than South Asia (e.g., Africa) should not routinely be offered typhoid vaccine. However, the decision of whether or not to offer typhoid vaccination for destinations other than South Asia should be carefully balanced against the presence of other factors that may increase the risk of travel-associated typhoid (such as travelling children; travellers visiting friends and relatives; longer duration of travel and prolonged exposure to potentially contaminated food and water; anatomic or functional asplenia (including sickle cell anemia), the presence of achlorhydria or the use of acid suppression therapy) and personal preference.
Typhoid immunization is recommended for individuals with ongoing or intimate exposure (e.g., family member) to a chronic carrier of S. typhi.
Typhoid immunization is recommended for laboratory personnel regularly working with S. typhi in clinical or research laboratories. Technicians working in routine microbiology laboratories do not need to be vaccinated.
Typh-I vaccine is indicated for persons 2 years of age and older and Typh-O vaccine may be used in people 5 years of age and older. HA-Typh-I vaccine is indicated for people 16 years of age and older.
Refer to Schedule.
Pregnancy and breastfeeding
No information is available on the safety of Typh-I vaccine in pregnancy; however, there is no theoretical reason to suspect an increased risk from inactivated vaccines. Typhoid vaccine should be considered in pregnant women like anyone else, when indicated due to place of travel, the presence of risk factors and personal preference. The appropriate vaccine for pregnant or breastfeeding women is inactivated Typh-I vaccine; pregnant women should not receive live vaccines, including Typh-O vaccine. Refer to Immunization in Pregnancy and Breastfeeding in Part 3 for additional general information.
Typh-I vaccine may be administered to immunocompromised persons if indicated; however, an adequate response may not be achieved. Typh-O vaccine should not be given to immunocompromised persons, including those with known HIV infection. For complex cases, referral to a physician with expertise in immunization and/or immunodeficiency is advised.
Healthy persons vaccinated with Typh-O vaccine do not shed vaccine-strain organisms in their stool and secondary transmission to contacts does not occur.
Travellers are generally at low risk of typhoid fever. The strongest and most consistent predictor of typhoid risk in travellers is destination of travel. The estimated risk of developing travel associated typhoid is about: 1/3,500 travellers to South Asia (high risk), 1/50,000-100,000 for travel to Sub-Saharan African and South America (intermediate risk), and less than 1/300,000 for travel to the Caribbean and Central America (low risk).
Most Canadian travellers visiting South Asia (including Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan and Sri Lanka and) should be offered typhoid vaccine. The risk of typhoid is highest for persons travelling to India, Pakistan, and Bangladesh. Data suggest that most cases of typhoid occur when travellers stay more than two weeks.
Most Canadians travellers visiting destinations other than South Asia (e.g., Africa) should not routinely be offered typhoid vaccine. However, the decision of whether or not to offer typhoid vaccination for destinations other than South Asia should be carefully balanced against the presence of other factors that may increase the risk of travel-associated typhoid (such as travelling children; travellers visiting friends and relatives; longer duration of travel; anatomic or functional asplenia (including sickle cell anemia), the presence of achlorhydria or the use of acid suppression therapy) and personal preference.
Immunization is only modestly effective against typhoid and provides no protection against other fecal-oral diseases; therefore, all travellers should be advised to adhere to basic sanitation and food and water precautions irrespective of whether they are immunized against typhoid. Refer to Immunization of Travellers in Part 3 for additional general information.
Typhoid vaccine is recommended for laboratory personnel regularly working with S. typhi in clinical or research laboratories. Technicians working in routine microbiology laboratories do not need to be vaccinated. Refer to Immunization of Workers in Part 3 for additional general information.
Typhoid immunization is not routinely recommended for the control or containment of typhoid outbreaks in Canada.
Dose, route of administration, and schedule (refer to Table 1)
- Typh-I vaccine
Persons 2 years of age and older should receive a single 0.5 mL dose intramuscularly at least 14 days prior to potential exposure.
- Typh-O vaccine
Persons 5 years of age and older should take one capsule on alternate days to a total of four capsules. All four capsules must be taken for optimal protection. Minor variations in dosing schedule are not expected to affect efficacy. However, if it is necessary to repeat the series because of a longer interval between doses (more than a week), the administration of an additional full course of vaccine is not harmful. Administer the capsules in accordance with the instructions in the manufacturer's product leaflet. Immunization (ingestion of all 4 capsules) should be completed at least 7 days prior to potential exposure.
- HA-Typh-I vaccine
Persons 16 years of age and older should receive a single 1.0 mL dose for primary immunization against typhoid at least 14 days prior to potential exposure. To provide long-term protection against hepatitis A, a booster dose of hepatitis A vaccine should be given 6 to 36 months later. Alternatively, HA-Typh-I vaccine can be given as a booster vaccine after 3 years in people who also require ongoing protection against typhoid fever. Refer to Hepatitis A Vaccine in Part 4 for additional information.
|Parenteral inactivated vaccines (Typh-I)||Oral, live attenuated vaccine (Typh-O)||Combined, parenteral inactivated vaccine (HA-Typh-I)|
|Authorized for use in persons||
2 years of age and older
5 years of age and older
16 years of age and older
14 days following vaccination
7 days following vaccination
14 days following vaccination
|Dose and schedule||
One dose: 0.5 mL
4 capsules taken on alternate days
One dose: 1.0 mL
|Route of administration||
Individuals with hypersensitivity or anaphylaxis to any component of the vaccine or its container.
Individuals with hypersensitivity or anaphylaxis to any component of the vaccine or its container.
|Re-immunizationTable 1 - Footnote 2||
Every 3 years
Every 7 yearsTable 1 - Footnote 3
Refer to Vaccine Administration Practices in Part 1 for additional information.
Booster doses and re-immunization
Periodic booster doses in persons at continued risk of typhoid may be expected to increase antibody titres and maintain protection. Booster doses should be offered when a person remains at risk in conditions of repeated or continuous exposure. For Typh-I vaccine, administer a booster dose every 3 years. For Typh-O vaccine, administer a booster of 4 doses every 7 years. For the combined HA-Typh-I vaccine, boost with a single dose of inactivated hepatitis A vaccine 6 months to 36 months later; a single dose of Typh-I vaccine may be given at or after 3 years; HA-Typh-I vaccine can be used after 3 years if boosters are needed for both hepatitis A and typhoid.
Serologic testing is not recommended before or after receiving typhoid vaccine.
Store typhoid vaccines in a refrigerator at +2°C to +8°C. Do not freeze. Protect TYPHERIX® and Typh-O vaccines from light. Protect Typh-O vaccine from moisture and high humidity. Refer to Storage and Handling of Immunizing Agents in Part 1 for additional general information.
Simultaneous Administration with Other Vaccines
The administration of oral cholera vaccine and Typh-O vaccine capsules should be separated by at least 8 hours; Typh-O vaccine can be given concomitantly with or at any time before or after any parenteral vaccine. There is no known interaction between Typh-I vaccine and other travel vaccines, such as hepatitis A vaccine, yellow fever vaccine and hepatitis B vaccine. Refer to Timing of Vaccine Administration in Part 1 for additional general information.
Vaccine Safety and Adverse Events
Refer to Vaccine Safety Part 2 for additional general information.
Common and local adverse events
Common adverse events (1% to 10% of vaccinees) include: injection site tenderness, induration, redness or pain, fever, headache, general malaise or myalgia.
Common adverse events include: abdominal pain, nausea, diarrhea, vomiting, fever, headache and rash.
Very common (more than 10% of vaccinees) adverse events include: injection site pain, induration, swelling and erythema; headache; myalgia and weakness. Common adverse events include: fever, malaise, nausea, diarrhea and dizziness. Uncommon adverse events (0.1% to less than 1% of vaccinees) include: pruritus and rash.
Less common and serious or severe adverse events
Serious adverse events are rare following immunization and, in most cases, data are insufficient to determine a causal association. Anaphylaxis following vaccination with typhoid vaccine may occur but is very rare.
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 and Vaccine Safety in Part 2 for additional information about AEFI reporting.
Contraindications and precautions
Typhoid vaccine is contraindicated in persons with history of anaphylaxis after previous administration of the vaccine and in persons with suspected or proven hypersensitivity to any component of the vaccine or its container. Refer to Contents of Immunizing Agents Available for Use in Canada in Part 1 for a list of vaccines available for use in Canada and their contents. For typhoid vaccines, potential allergens include:
- TYPHERIX® (rubber stopper in pre-filled syringe).
- TYPHIM Vi®(no known potential allergens).
- VIVAXIM® (neomycin).
- Vivotif® (gelatin).
Typh-O vaccine is contraindicated in pregnancy, individuals with an acute gastrointestinal condition or inflammatory bowel disease and in immunocompromised persons.
Administration of typhoid vaccine should be postponed in persons with severe acute illness. Persons with minor acute illness (with or without fever) may be vaccinated.
Refer to Contraindications, Precautions and Concerns in Part 2 for additional general information.
Drug-drug and drug-food interactions
The Typh-O vaccine series should be finished 3 days before commencing, or initiated 48- to 72 hours after completing, treatment with sulphonamides or other antibiotics active against S. typhi, or antimalarials. Exceptions include chloroquine, mefloquine and malarone, as these antimalarials do not affect the immune response to Typh-O vaccine and can be administered at the same time as, or at any interval before or after Typh-O vaccine.
Typh-O vaccine should be taken approximately one hour before, or two hours after a meal. Alcoholic beverages should not be consumed one hour before or two hours after taking Typh-O vaccine.
Typh-I, HA-Typh-I or Typh-O vaccines can be given before, concurrently with, or after immune globulin products.
Interchangeability of vaccines
Although there are no data regarding the interchangeability of typhoid vaccines, it is presumed that boosting can be performed with any of the available formulations regardless of the vaccine used initially. The boosting interval should correspond to the interval established for the preceding vaccine (i.e., 3 years after Typh-I vaccine; 7 years after Typh-O vaccine) Refer to Principles of Vaccine Interchangeability in Part 1 for additional general information.
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