Tetanus toxoid was first produced in 1924, and tetanus toxoid immunizations were used extensively in the armed services during World War II. Tetanus cases among this population declined from 70 in World War I (13.4/100,000 wounds and injuries) to 12 in World War II (0.44/100,000). Of the 12 case-patients, half had received no prior toxoid.
Tetanus toxoid consists of a formaldehyde-treated toxin. The toxoid is standardized for potency in animal tests according to Food and Drug Administration (FDA) regulations. Occasionally, potency is mistakenly equated with Lf units, which are a measure of the quantity of toxoid, not its potency in inducing protection.
There are two types of toxoid available—adsorbed (aluminum salt precipitated) toxoid and fluid toxoid. Although the rates of seroconversion are about equal, the adsorbed toxoid is preferred because the antitoxin response reaches higher titers and is longer lasting than that following the fluid toxoid.
Tetanus toxoid is available combined with diphtheria toxoid as pediatric diphtheria-tetanus toxoid (DT) or adult tetanus-diphtheria (Td), and with both diphtheria toxoid and acellular pertussis vaccine as DTaP or Tdap. Tetanus toxoid is also available as combined DTaP-HepB-IPV (Pediarix) and DTaP-IPV/Hib (Pentacel)
Pediatric formulations (DT and DTaP) contain a similar amount of tetanus toxoid as adult Td, but contain 3 to 4 times as much diphtheria toxoid. Children younger than 7 years of age should receive either DTaP or pediatric DT. Persons 7 years of age or older should receive the adult formulation (adult Td), even if they have not completed a series of DTaP or pediatric DT. Tetanus toxoid is given in combination with diphtheria toxoid, since periodic boosting is needed for both antigens. Two brands of Tdap are available: Boostrix (approved for persons 10 and older) and Adacel (approved for persons 10 through 64 years of age). DTaP and Tdap vaccines do not contain thimerosal as a preservative.
Immunogenicity and Vaccine Efficacy
After a primary series (three properly spaced doses of tetanus toxoid in persons 7 years of age and older, or four doses in children younger than 7 years of age) essentially all recipients achieve antitoxin levels considerably greater than the protective level of 0.1 IU/mL.
Efficacy of the toxoid has never been studied in a vaccine trial. It can be inferred from protective antitoxin levels that a complete tetanus toxoid series has a clinical efficacy of virtually 100%; cases of tetanus occurring in fully immunized persons whose last dose was within the last 10 years are extremely rare.
Antitoxin levels decrease with time. While some persons may be protected for life, by 10 years after the last dose, most persons have antitoxin levels that only approach the minimal protective level. As a result, routine boosters are recommended every 10 years.
In a small percentage of individuals, antitoxin levels fall below the minimal protective level before 10 years have elapsed. To ensure adequate protective antitoxin levels, persons who sustain a wound that is other than clean and minor should receive a tetanus booster if more than 5 years have elapsed since their last dose
Vaccination Schedule and Use
DTaP (diphtheria and tetanus toxoids and acellular pertussis vaccine) is the vaccine of choice for children 6 weeks through 6 years of age. The usual schedule is a primary series of four doses at 2, 4, 6, and 15–18 months of age. The first, second, and third doses of DTaP should be separated by a minimum of 4 weeks. The fourth dose should follow the third dose by no less than 6 months and should not be administered before 12 months of age.
If a child has a valid contraindication to pertussis vaccine, pediatric DT should be used to complete the vaccination series. If the child was younger than 12 months old when the first dose of DT was administered (as DTaP or DT), the child should receive a total of four primary DT doses. If the child was 12 months of age or older at the time that the first dose of DT was administered, three doses (third dose 6–12 months after the second) completes the primary DT series.
If the fourth dose of DTaP, DTP, or DT is administered before the fourth birthday, a booster dose is recommended at 4–6 years of age. The fifth dose is not required if the fourth dose was given on or after the fourth birthday.Because of waning antitoxin titers, most persons have antitoxin levels below the optimal level 10 years after the last dose of DTaP, DTP, DT, or Td. Additional booster doses of tetanus and diphtheria toxoids are required every 10 years to maintain protective antitoxin titers. The first booster dose of Td may be given at 11 or 12 years of age if at least 5 years have elapsed since the last dose of DTaP, DTP, or DT. The Advisory Committee on Immunization Practices (ACIP) recommends that this dose be administered as Tdap. If a dose is given sooner as part of wound management, the next booster is not needed for 10 years thereafter. More frequent boosters are not indicated and have been reported to result in an increased incidence and severity of local adverse reactions.
Td is the vaccine of choice for children 7 years and older and for adults. A primary series is three or four doses, depending on whether the person has received prior doses of diphtheria-containing vaccine and the age these doses were administered. The number of doses recommended for children who received one or more doses of DTP, DTaP, or DT before age 7 years is discussed above.
For unvaccinated persons 7 years and older (including persons who cannot document prior vaccination), the primary series is three doses. The first two doses should be separated by at least 4 weeks, and the third dose given 6 to 12 months after the second. ACIP recommends that one of these doses (preferably the first) be administered as Tdap. A booster dose of Td should be given every 10 years. Tdap is approved for a single dose at this time (i.e., it should not be used for all the doses of Td in a previously unvaccinated person 7 years or older). Refer to the Pertussis chapter for more information about Tdap.
Interruption of the recommended schedule or delay of subsequent doses does not reduce the response to the vaccine when the series is finally completed. There is no need to restart a series regardless of the time elapsed between doses.
Tetanus disease does not confer immunity because of the very small amount of toxin required to produce illness. Persons recovering from tetanus should begin or complete active immunization with a tetanus toxoid-containing vaccine during convalescence.
Contraindications and Precautions to Vaccination
A severe allergic reaction (anaphylaxis) to a vaccine component or following a prior dose of tetanus toxoid is a contraindication to receipt of tetanus toxoid. If a generalized reaction is suspected to represent allergy, it may be useful to refer an individual for appropriate skin testing before discontinuing tetanus toxoid immunization.
A moderate or severe acute illness is a precaution to routine vaccination, but a minor illness is not. If moderate to severe acute illness accompanies a wound that is neither clean nor minor, the risk of withholding tetanus-toxoid vaccine outweighs the risk of administering tetanus-toxoid vaccine, so the vaccine should be given as part of wound management.
If a contraindication to using tetanus toxoid-containing preparations exists, passive immunization with tetanus immune globulin (TIG) should be considered whenever an injury other than a clean minor wound is sustained.
Adverse Events Following Vaccination
Severe systemic reactions such as generalized urticaria (hives), anaphylaxis, or neurologic complications have been reported after receipt of tetanus toxoid. A few cases of peripheral neuropathy and Guillain-Barré syndrome (GBS) have been reported following tetanus toxoid vaccine administration. A 2011 Institute of Medicine review found evidence to be inadequate to accept or reject a causal relationship between tetanus toxoid vaccine and peripheral neuropathy and GBS, and favored rejection of a causal relationship between tetanus toxoid and type 1 diabetes, and supported a causal relationship between tetanus toxoid and anaphylaxis.
Adverse Reactions Following Vaccination
Local reactions (e.g., erythema, induration, pain at the injection site) are common but are usually self-limited and require no therapy. A nodule may be palpable at the injection site of adsorbed products for several weeks. Abscess at the site of injection has been reported. Fever and other systemic symptoms are not common.
Exaggerated local (Arthus-like) reactions are not common following receipt of a diphtheria- or tetanus- containing vaccine. These reactions present as extensive painful swelling, often from shoulder to elbow. They generally begin from 2 to 8 hours after injections and are reported most often in adults, particularly those who have received frequent doses of diphtheria or tetanus toxoid.
Persons experiencing these severe reactions usually have very high serum antitoxin levels; they should not be given further routine or emergency booster doses of Td more frequently than every 10 years. Less severe local reactions may occur in persons who have multiple prior boosters.
In 1994 the Institute of Medicine concluded that the available evidence favors a causal relationship between tetanus toxoid and brachial neuritis in the 1 month after immunization at a rate of 0.5 to 1 case per 100,000 toxoid recipients.
Vaccine Storage and Handling
All tetanus-toxoid containing vaccines should be maintained at refrigerator temperature between 35°F and 46°F (2°C and 8°C). Manufacturer package inserts contain additional information and can be found at http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm093830.htm. For complete information on best practices and recommendations please refer to CDC’s Vaccine Storage and Handling Toolkit, http://www.cdc.gov/vaccines/recs/storage/toolkit/storage-handling-toolkit.pdf.