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Canadian Immunization Guide
Seventh Edition - 2006
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Part 4
Active Immunizing Agents
Tetanus Toxoid
Tetanus is an acute and often fatal disease caused by an extremely potent neurotoxin produced by Clostridium tetani. The organism is ubiquitous in soil but has also been detected in the intestines of animals and humans. Wounds that are contaminated with soil or animal/human feces and that are associated with tissue injury and necrosis are most frequently associated with tetanus. Cases related to injection drug use, animal bites and lacerations have been reported as well as rare cases occurring after bowel surgery or bronchoaspiration of soil and feces. In North America, approximately 27% of cases occur in people who do not report any antecedent injury.
Since the publication of the 2002 Canadian Immunization Guide changes include 1) recommendation for adolescents aged 14-16 years of age to be vaccinated with tetanus toxoid, diphtheria toxoid and acellular pertussis (Tdap); 2) a new notation that there is no evidence of increased risk of severe adverse events for Canadian adolescents after receiving diphtheria and tetanus toxoid-containing vaccines at intervals of < 5 years; and 3) a new recommendation for subsequent vaccination of persons known to have developed Guillain-Barré syndrome (GBS) within 8 weeks of a previous tetanus vaccine dose.
Epidemiology
Tetanus is rare in Canada. During the 1920s and 1930s, 40 to 50 deaths from tetanus were reported annually. With the introduction of tetanus toxoid in Canada in 1940, morbidity and mortality rapidly declined (see Figure 15). Between 1980 and 2004, the number of cases reported annually ranged from 1 to 10, with an average of 4 per year. During this period, persons ≥ 60 years of age accounted for 49% of the cases, and 57% were males. No cases were reported among neonates. The immunization status of most of the reported cases was not known. Birth in a foreign country was indicated for 11% of 53 cases with known data. Only five deaths have been reported since 1980, the last in 1997.
Tetanus immunization programs are highly effective, provide long-lasting protection and are recommended for the whole population. However, serosurveys suggest that a substantial proportion of Canadians have nonprotective tetanus antitoxin levels. Factors associated with lack of immunity to tetanus include increasing age, birth outside Canada and absence of immunization records. Continued attention should be given to improving tetanus immunization in these groups.
Preparations approved for use in Canada
This chapter will deal only with products that are currently marketed in Canada.
- Adacel® (tetanus and diphtheria toxoids adsorbed combined with component pertussis vaccine, [Tdap]), Sanofi Pasteur Ltd
- DT Polio Adsorbed (diphtheria and tetanus toxoids adsorbed and poliomyelitis vaccine), Sanofi Pasteur Ltd.
- Pentacel® (Act-HIB [Haemophilus b conjugate vaccine (tetanus protein conjugate)] reconstituted with Quadracel®, [DTaP-IPV-Hib]), Sanofi Pasteur Ltd.
- Quadracel® (component pertussis vaccine and diphtheria and tetanus toxoids adsorbed combined with inactivated poliomyelitis vaccine, [DTaP-IPV]), Sanofi Pasteur Ltd.
- Td Adsorbed (tetanus and diphtheria), Sanofi Pasteur Ltd.
- Td Polio Adsorbed (tetanus and diphtheria toxoids and inactivated poliomyelitis vaccine, [Td-IPV]), Sanofi Pasteur Ltd.
- Tetanus Toxoid Adsorbed, Sanofi Pasteur Ltd.
- Tripacel® (component pertussis vaccine combined with diphtheria and tetanus toxoids adsorbed, [DTaP]), Sanofi Pasteur Ltd.
Tetanus toxoid is prepared by detoxification of tetanus toxin with formalin. It is combined with aluminum salts, generally aluminum phosphate, in an adsorbed form. Tetanus toxoid is available alone or in various combinations with diphtheria toxoid, acellular pertussis, inactivated poliomyelitis, hepatitis B and Haemophilus influenzae type b vaccines. All preparations contain comparable amounts of tetanus toxoid. Preparations that also contain inactivated polio vaccine may contain trace amounts of polymyxin B and neomycin from the cell growth medium.
For a list of all approved products in Canada, please refer to Table 1 in the General Considerations chapter.
Efficacy and immunogenicity
Tests for measuring the immune response to tetanus toxoid include the serum toxin neutralization bioassay performed in mice and serologic tests, which include enzyme immunoassays (EIA) as well as other assays. Because the bioassay is expensive and time-consuming, the EIA is more widely used. The definition of protective antibody level depends on the precise type of assay used. Correlation of serologic test results with the toxin bioassay is useful, as the latter assesses actual neutralization in vivo.
Protective antitoxin levels occur in virtually all healthy infants and children who receive primary immunization. A double-blind, randomized controlled trial in rural South America demonstrated that two or three doses of tetanus toxoid administered to previously unvaccinated women of childbearing age protected their infants. Efficacy in standard pre-exposure and post-wound booster immunization regimens in adults has not been assessed in randomized trials but was demonstrated by observational studies during World War II.
Most children who are perinatally infected with human immunodeficiency virus (HIV) develop adequate antitoxin antibody responses following immunization with vaccines containing tetanus toxoid. The antibody response to boosters given to adults with HIV or other humoral immune deficiencies is suboptimal. Tetanus immunity is lost in approximately half of patients undergoing chemotherapy for lymphoma or leukemia. Patients undergoing bone marrow or stem cell transplantation should be re-immunized. Please refer to the chapter on Immunization of Immunocompromised Persons.
Very rare cases of tetanus have been reported despite full immunization and the presence of toxin-neutralizing antibody. These cases may present with a clinical spectrum ranging from mild or localized to severe disease. Explanatory theories include the "overwhelming" of host defences by large quantities of toxin, selective suppression of the immune response or antigenic differences between toxin and toxoid.
Recommended usage
It is recommended that all Canadians receive a primary immunizing course of tetanus toxoid in childhood followed by routine booster doses every 10 years. Adults who have not previously received a primary tetanus toxoid series require three doses as part of an adult primary immunization regimen (see Schedule and Dosage).
Active immunization against tetanus should be undertaken for patients who have recovered from this disease, because infection does not confer protective immunity.
Schedule and dosage
The dose of the various forms of tetanus toxoid licensed in Canada is 0.5 mL. For children < 7 years of age, routine vaccine formulations contain tetanus toxoid in combination with diphtheria toxoid, acellular pertussis, inactivated polio and H. influenzae type b antigens. For adolescents aged 14-16 years of age, vaccination with tetanus toxoid, diphtheria toxoid and acellular pertussis (Tdap) is recommended. This preparation contains less diphtheria toxoid than the preparation given to younger children. Adults may receive tetanus vaccination using tetanus toxoid, in combination with diphtheria toxoid, or combined with diphtheria toxoid and acellular pertussis. Please refer to the chapters on Diphtheria Toxoid Vaccine and Pertussis Vaccine for more information.
For children commencing immunization in early infancy, the primary immunizing series of adsorbed tetanus toxoid consists of a dose at 2, 4 and 6 months of age, a fourth dose at 18 months and a fifth dose at 4 to 6 years of age (school entry). Among children who receive the fourth dose after the fourth birthday, the dose at 4 to 6 years of age is not required. For information on immunization schedules for children not vaccinated in early infancy, please refer to the Recommended Immunization Schedules chapter.
In adults requiring a primary immunization series, the first two doses of tetanus toxoid should be given 4 to 8 weeks apart and the third 6 to 12 months later (given as Td with one of the doses given as Tdap for pertussis protection).
Please refer to the Immunization of Immunocompromised Persons chapter for recommendations on hematopoietic stem cell and solid organ transplant recipients.
Route of administration
Tetanus toxoid is administered intramuscularly.
Booster doses and re-immunization
To maintain immunity to tetanus after completion of primary immunization, booster doses administered as Td are recommended at 10-year intervals. More frequent boosters may lead to severe local and systemic reactions. Some experts have suggested that booster doses may be given less frequently. Although tetanus cases are uncommon in people who received a primary immunization series but did not receive subsequent boosters every 10 years, cases have occurred in such circumstances. The National Advisory Committee on Immunization (NACI) continues to recommend tetanus boosters every 10 years based on concern regarding the decline of antibody levels with age and potential failure of single booster doses to produce protective levels in older individuals. Periodic health examinations of adults should be used as opportunities to review the need for recommended vaccines, including tetanus booster doses.
Serologic testing
There is no indication for pre- or post-immunization serology.
Storage requirements
Toxoid preparations should be stored in the refrigerator, at a temperature between +2° C and +8° C. They should not be frozen, and any that have been frozen should not be used.
Simultaneous administration with other vaccines
Tetanus toxoid-containing preparations may be given concurrently with other vaccines, using separate needles and syringes.
Adverse reactions
Serious adverse events are rare following immunization and, in most cases, data are insufficient to determine a causal association.
Adverse reactions to primary immunization with tetanus toxoid are rare, especially in children. Their incidence in adults increases with age. Following booster doses, local erythema and swelling are not uncommon. Severe local reactions occur rarely and may be associated with high levels of circulating antitoxin. Lymphadenopathy and fever may occasionally occur. Serum sickness, brachial plexus neuropathy, encephalomyelitis and transverse myelitis have rarely been reported in association with tetanus vaccination. Attribution of adverse reactions to tetanus toxoid may be confounded if other antigens are present in the preparation. Anaphylactic reactions to tetanus toxoid may rarely occur. However, in one study, 94 out of 95 persons who gave a history of anaphylactic symptoms following previous vaccination with tetanus toxoid were nonreactive following intradermal testing and tolerated a further tetanus toxoid challenge without reaction. In consultation with an allergy specialist, a search for IgE antibodies to tetanus toxoid (and other components of the administered vaccine) should be initiated in suspected cases of anaphylaxis.
Trismus associated with tetanus toxoid immunization has rarely been reported. The pathogenesis is unexplained. However, outcomes have been favourable.
Contraindications and precautions
Tetanus toxoid should not be given if a severe systemic reaction, including severe hypersensitivity or a neurologic event, followed a previous dose. People who experience a major local reaction or high fever following a dose of tetanus toxoid should not be given another dose for at least 10 years. In those who have experienced severe local reactions or fever after tetanus toxoid, plain toxoid may be considered for subsequent booster doses, since it is reported to cause fewer reactions than adsorbed toxoid. When a contraindication to tetanus toxoid exists and a patient sustains a major or unclean wound, tetanus immune globulin should be given.
Although a causal association has not been established between tetanus vaccine and GBS, at the present time it is prudent to withhold subsequent vaccinations in children and adults who developed GBS within 8 weeks of a previous tetanus vaccine dose. Those who develop GBS outside this interval or have an alternative cause identified (e.g., Campylobacter jejuni infection) may receive subsequent tetanus vaccinations.
Before a combined vaccine is given, it is most important to ensure that there are no contraindications to the administration of any of the components.
There is no evidence that tetanus toxoid is teratogenic. In the event of a tetanus-prone wound during pregnancy the recommendations in Table 13 should be followed. Neonatal tetanus may occur in infants born to unimmunized mothers under unhygienic conditions.
NACI has concluded that there is no evidence of increased risk of severe adverse events for Canadian adolescents after receiving diphtheria and tetanus toxoid-containing vaccines at intervals of < 5 years (please refer to the Pertussis Vaccine chapter for more information).
Other considerations
Post-exposure prevention of tetanus in the context of wound management
Table 13 summarizes the recommended use of immunizing agents in wound management. It is important to ascertain the number of doses of toxoid previously given and the interval since the last dose. When a tetanus booster dose is required, the combined preparation of tetanus and diphtheria toxoid (Td) is used for adults. For adolescents and adults who have not already received a pertussis booster vaccine dose, the combined preparation of diphtheria, tetanus and acellular pertussis (Tdap) is preferred.
Appropriate cleansing and debridement of wounds is imperative, and use of antibiotics may be considered.
Some individuals with humoral immune deficiency, including those with HIV infection, may not respond adequately to tetanus toxoid. Therefore, tetanus immune globulin (TIg) should be used in addition to tetanus toxoid in individuals with humoral immune deficiency who have wounds that are not clean, regardless of the time elapsed since the last booster.
Table 13. Guide to Tetanus Prophylaxis in Wound Management
| History of tetanus immunization | Clean, minor wounds | All other wounds | ||
|---|---|---|---|---|
| Td or Tdap* | TIg** | Td or Tdap* | TIg | |
| Uncertain or < 3 doses of an immunization series† | Yes | No | Yes | Yes |
| ≥ 3 doses received in an immunization series† | No‡ | No | No§ | No¶ |
* Adult-type combined tetanus and diphtheria toxoids or a combined preparation of diphtheria, tetanus and acellular pertussis. If the patient is < 7 years old, a tetanus toxoid-containing vaccine is given as part of the routine childhood immunization. ** Tetanus immune globulin, given at a separate site from Td (or Tdap) † The immunization series for tetanus is described in the text (see Schedule and Dosage). ‡ Yes, if > 10 years since last booster. § Yes, if > 5 years since last booster. More frequent boosters not required and can be associated with increased adverse events. The bivalent toxoid, Td, is not considered to be significantly more reactogenic than T alone and is recommended for use in this circumstance. The patient should be informed that Td (or Tdap) has been given. ¶ Yes, if individuals are known to have a significant humoral immune deficiency state (e.g., HIV, agammaglobulinemia), since immune response to tetanus toxoid may be suboptimal. |
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Selected references
David ST, Hemsley C, Pasquali PE et al. Enhanced surveillance for vaccine-associated adverse events: dTap catch-up of high school students in Yukon. Canada Communicable Disease Report 2005;31(11):117-26.
Fiorillo L, Robinson JL. Localized tetanus in a child. Annals of Emergency Medicine 1999;33(4):460-63.
Jacobs RL, Lowe RS, Lanier BQ. Adverse reactions to tetanus toxoid. Journal of the American Medical Association 1982;247(1):40-2.
Katz KC, Walmsley SL. Postoperative tetanus: a case report. Canadian Medical Association Journal 2000;163(5):571-73.
Martin-Munoz MR, Pereira MJ, Posadas S et al. Anaphylactic reaction to diphtheria-tetanus vaccine in a child: specific IgE/IgG determinations and cross-reactivity studies. Vaccine 2002;20(27-28):3409-12.
Mayaud C, Loupi E, Charara O et al. Trismus et vaccination antitétanique. Archives of Pediatrics 1999;6(7):752-54.
McQuillan GM, Kruszon-Moran D, Deforest A et al. Serologic immunity to diphtheria and tetanus in the United States. Annals of Internal Medicine 2002;136(9):660-66.
National Advisory Committee on Immunization. Interval between administration of vaccines against diphtheria, tetanus, and pertussis. Canada Communicable Disease Report 2005;31(ACS-9):17-22.
Pascual FB, McGinley EL, Zanardi LR et al. Tetanus surveillance - United States, 19982000. Morbidity and Mortality Weekly Report Surveillance Summaries 2003;52(3):1-8.
Shimoni Z, Dobrousin A, Cohen J et al. Tetanus in an immunised patient. British Medical Journal 1999;319(7216):1049.
Shin DH, Park JH, Jung PJ et al. A case of maternal tetanus in Korea. Journal of Korean Medical Science 2002;17(2):260-62.
Wassilak SGF, Roper MH, Murphy TV et al. Tetanus toxoid. In: Plotkin SA, Orenstein WA, eds. Vaccines. 4th edition. Philadelphia: W.B. Saunders 2004;745-81.
Yuan L, Lau W, Thipphawong J et al. Diphtheria and tetanus immunity among blood donors in Toronto. Canadian Medical Association Journal 1997;156(7):985-90.
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