Tetanus Toxoid

Earn CME/CE in your profession:

Continuing Education Activity

The tetanus toxoid is a vaccine used in the management and treatment of tetanus. It is in the vaccine class of medications. This activity reviews the indications, action, and contraindications for the tetanus toxoid as a valuable agent in the immunization against tetanus and wound prophylaxis. This activity will highlight the mechanism of action, adverse event profile, and other key factors such as the administration and adverse effects pertinent for members of the health care team in treating patients with tetanus.


  • Describe the indications for the administration of the tetanus toxoid.
  • Review the mechanism of action of the tetanus toxoid.
  • Summarize the symptoms of tetanus.
  • Explain the importance of knowing past immunizations to properly protect against tetanus.


The tetanus toxoid is an FDA-approved vaccination given alone or in conjunction with other vaccines. It is protective against effects from a gram-positive bacillus, Clostridium tetani.  This bacteria produces a neurotoxin called tetanospasmin, which blocks the release of an inhibitory neurotransmitter and leads to unopposed muscle contractions and spasms.[1]

The World Health Organization recommends receiving the primary series of tetanus vaccinations during adolescence. Due to the requirement for primary immunization, an absorbed form containing multiple antigens is usually utilized.[2] Children must complete the 5-dose DTaP (diphtheria, tetanus, acellular pertussis) vaccination series before the age of 7.[3] The CDC recommends the first dose at two months old, the second dose at three months old, the third dose at four months old, the fourth dose between months 15 and 18, and the fifth dose between the ages of 4 and 6. Following the first series of vaccinations, the recommendation is that adults receive boosters with Tdap (same components as DTaP, but reduced doses of diphtheria and pertussis) every ten years. Studies indicate that the Tdap booster given ten years after the initial series of vaccines is usually well-tolerated and effectively immunogenic.[4]

Furthermore, tetanus toxoid can be used alone if needed in particular circumstances. It is highly effective when used prophylactically in cases when dealing with wound care and management. The Tdap booster vaccination should also be considered in patients with any wound injury who have had less than three tetanus toxoid doses, received their last dose more than ten years ago, or if their immunization history is unknown.[5]

Mechanism of Action

Vaccinations exert their effect on the human body via priming our active immune system. Following the administration of the tetanus toxoid, the immune system is stimulated and responds to the antigens present in the vaccine. TH2 and B cells are activated, which then produce immunoglobins against the toxoid, allowing for adequate protection against future infections. This process requires multiple dosages to achieve a high immune response; however, it bears mentioning that there is no chance for the toxoid to exhibit its pathogenic features as it is an inactivated vaccine.[6]


Preparation of the tetanus toxoid is via inactivation of the toxigenic strains of Clostridium tetani. The toxic strains are grown in liquid media, purified, then treated with formaldehyde to take away the pathogenic properties. Following purification and sterilization, tetanus toxoid is combined with aluminum or calcium salts. This toxoid antigen is then usually used in combination with Diptheria and pertussis antigens in a vaccination form.

The DTaP vaccine is a 0.5 mL dose, and it is given intramuscularly. For patients who are infants to two years old, the anterolateral aspect of the thigh is the preferred injection site.  For children aged three and older, the deltoid muscle is the preferred injection site.[1]  This regimen is a 5-dose series starting at the age of two months and ending at six years old.

  • First dose: 2 months old, must be at least six weeks old
  • Second dose: 4 months old
  • Third dose: 6 months old
  • Fourth dose: 15 months to 18 months old, must be at least 12 months old, given at a minimum of six months after the third dose
  • Fith dose: 4 years to 6 years old, must be at least four years old, given at a minimum of six months after the fourth dose

As most DTaP vaccinations contain higher levels of diphtheria compared to tetanus and pertussis, Tdap has higher levels of tetanus than diphtheria and pertussis. The Tdap vaccine is a 0.5 mL dose, and it is also given as an intramuscular injection. This vaccine should only be used as a booster every ten years, starting at ages eleven to twelve.

Adverse Effects

Although vaccinations containing the tetanus toxoid are generally safe, some adverse effects can occur.  Any vaccine with tetanus toxoid as a component has the potential to cause brachial neuritis.[7] Also known as neuralgic amyotrophy,  brachial neuritis is an immune-mediated inflammatory process involving peripheral nerves.  Patients usually present with pain and muscle weakness, and sometimes cases can be severe; however, this is extremely rare, and symptoms typically subside on their own.[8]

A study of 740 patients with adverse effects to the tetanus toxoid showed that, when present, the most common symptoms are local edema and tenderness, fever, and anaphylactoid response.[9]

In the 1990s, whole-cell pertussis was replaced with acellular pertussis, which is a common component of vaccines containing the tetanus toxoid. Before the switch to acellular pertussis, swelling, redness, and pain at the injection site were commonly noted adverse events; however, these reactions are much less common today.[10]


The tetanus toxoid is generally safe for the human population; however, there are specific contraindications. One contraindication includes past anaphylaxis reaction to the tetanus toxoid. Further, in the case where encephalopathy occurs within seven days of administration of the tetanus toxoid and no other cause is found, this can also be a contraindication for future injections.[1]


Since the tetanus toxoid is generally safe and rarely leads to any severe issues, monitoring is not necessary. However, if a patient wanted to know their immunity status against tetanus, this could be accomplished by using multi-analyte fluorescent detection. It can detect the antibody titer level in their blood, confirming whether or not there is full immunity. A level of higher than 0.01 IU/ml rates as a protective concentration of tetanus antibodies.[11]

There is the possibility of an Arthus reaction (type III hypersensitivity) occurring after administering vaccines containing tetanus toxoids. Possible symptoms include, but are not limited to, severe pain, swelling, induration, edema, hemorrhage, and occasionally necrosis. However, it bears mention that this is extremely rare and usually self-limited.  Furthermore, a history of an Arthus reaction is not a contraindication to the tetanus toxoid.[3]


There is no antidote or treatment for the tetanus toxoid.  In the rare case of an anaphylactic reaction, it is treatable with epinephrine.[12]

Enhancing Healthcare Team Outcomes

Advancements in vaccinations are responsible for the decrease in multiple different infectious diseases. When inquiring about patients' past immunizations, we always have to consider the possibility of receiving false information. A study done in 2012 involved asking patients about their tetanus vaccination, then drawing titer levels to see if they were correct. This study enrolled 163 patients, and it showed that 12.8% of patients who stated their tetanus shot is up to date were not seropositive. Twenty-six people were seronegative, and all of these patients had been to a doctor in the past year. This data shows the untrustworthy nature of the immunization history given by patients.[11]

The usage of reminders has been a topic of study in Canada in a trial containing 8069 patients who were 20 or older and split into three groups. In one group, the physician was reminded at the office visit to assess the patient's tetanus protection; the second group was reminded via phone call, while the third group received a reminder letter. Statistics showed the most significant compliance occurred when the patients were given a letter as a reminder. With these reminder systems, researchers noted an increase in the rate of recorded tetanus vaccination, but it was well short of complete population coverage. These results show that to achieve complete population coverage, more intense intervention is necessary.[13]

Tetanus toxoid vaccine requires an interprofessional approach to optimize its protective effects. This includes clinicians, infectious disease specialists, mid-level practitioners, nurses, and pharmacists. Meticulous record-keeping is a must and understanding the patient's current vaccine status, potential contraindications, and proper scheduling are all factors that will benefit from interprofessional communication and coordination. [Levle 5]

Article Details

Article Author

Thomas Rabadi

Article Editor:

Mark F. Brady


5/8/2022 12:45:51 PM

PubMed Link:

Tetanus Toxoid



Ogden SA,Ludlow JT,Alsayouri K, Diphtheria Tetanus Pertussis (DTaP) Vaccine 2020 Jan;     [PubMed PMID: 31424757]


Acres SE, Statement on tetanus toxoid. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 1987 Oct 15;     [PubMed PMID: 3651946]


Liang JL,Tiwari T,Moro P,Messonnier NE,Reingold A,Sawyer M,Clark TA, Prevention of Pertussis, Tetanus, and Diphtheria with Vaccines in the United States: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports. 2018 Apr 27;     [PubMed PMID: 29702631]


Halperin SA,Donovan C,Marshall GS,Pool V,Decker MD,Johnson DR,Greenberg DP, Randomized Controlled Trial of the Safety and Immunogenicity of Revaccination With Tetanus-Diphtheria-Acellular Pertussis Vaccine (Tdap) in Adults 10 Years After a Previous Dose. Journal of the Pediatric Infectious Diseases Society. 2019 May 11;     [PubMed PMID: 29438562]


ROSS DE,KRAUT JJ, Tetanus: prophylaxis and treatment of the disease. California medicine. 1959 May;     [PubMed PMID: 13651954]


Grubbs H,Kahwaji CI, Physiology, Active Immunity 2020 Jan;     [PubMed PMID: 30020652]


Tetanus vaccines: WHO position paper – February 2017. Releve epidemiologique hebdomadaire. 2017 Feb 10;     [PubMed PMID: 28185446]


Al Khalili Y,Jain S,DeCastro A, Brachial Neuritis 2020 Jan;     [PubMed PMID: 29763017]


Jacobs RL,Lowe RS,Lanier BQ, Adverse reactions to tetanus toxoid. JAMA. 1982 Jan 1;     [PubMed PMID: 7053439]


Pertussis vaccines: WHO position paper - September 2015. Releve epidemiologique hebdomadaire. 2015 Aug 28;     [PubMed PMID: 26320265]


Moore MA,Barber KR,Britt T, Tetanus seropositive prevalence and perceived protection from emergency admissions. Emerging health threats journal. 2012;     [PubMed PMID: 22461848]


Cunningham AA, Anaphylaxis after Injection of Tetanus Toxoid. British medical journal. 1940 Oct 19;     [PubMed PMID: 20783349]


Rosser WW,Hutchison BG,McDowell I,Newell C, Use of reminders to increase compliance with tetanus booster vaccination. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 1992 Mar 15;     [PubMed PMID: 1544078]