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For Clinicians

Pathogenesis

Clostridium tetani (C. tetani) spores usually enter the body through a wound or breach in the skin. Neonatal tetanus usually occurs because of umbilical stump infections. In the presence of anaerobic conditions, the spores germinate. Toxins are produced and disseminated via the blood stream and lymphatic system. Toxins act at several sites within the central nervous system, including peripheral motor end plates, spinal cord, and brain, as well as in the sympathetic nervous system. The typical clinical manifestations of tetanus are caused when tetanus toxin interferes with release of neurotransmitters, blocking inhibitor impulses. This leads to unopposed muscle contraction and spasm. Seizures may occur, and the autonomic nervous system may also be affected.


Symptoms and Diagnosis

Tetanus is a clinical syndrome without confirmatory laboratory tests. The disease is characterized by painful muscular contractions, primarily of the masseter and neck muscles and secondarily of trunk muscles. A common first sign suggestive of tetanus in older children and adults is abdominal rigidity, although rigidity is sometimes confined to the region of injury. Generalized spasms occur, frequently induced by sensory stimuli. History of an injury or apparent portal of entry may be lacking. The organism is rarely recovered from the site of infection.


Clinical Features

The incubation period ranges from 3 to 21 days, averaging about 10 days. In general, the further the injury site is from the central nervous system, the longer the incubation period. A shorter incubation period is associated with more severe disease, complications, and a higher chance of death. In neonatal tetanus, symptoms usually appear from 4 to 14 days after birth, averaging about 7 days.

On the basis of clinical manifestations, three different forms of tetanus have been described: generalized, localized, and cephalic.

Generalized Tetanus

Generalized tetanus is the most common form, accounting for more than 80% of cases. The most common initial sign is spasm of the muscles of the jaw or "lockjaw". This may be followed by painful spasms in other muscle groups in the neck, trunk, and extremities and by generalized, seizure-like activity or convulsions in severe cases. Generalized tetanus can be accompanied by nervous system abnormalities, as well as a variety of complications related to severe spasm and prolonged hospitalization. The clinical course of generalized tetanus is variable and depends on the degree of prior immunity, the amount of toxin present, and the age and general health of the patient. Even with modern intensive care, generalized tetanus is associated with death rates of 10% to 20%.

Localized Tetanus

Localized tetanus is an unusual form of the disease consisting of muscle spasms in a confined area close to the site of the injury. Although localized tetanus often occurs in people with partial immunity and is usually mild, progression to generalized tetanus can occur.

Cephalic Tetanus

The rarest form, cephalic tetanus, is associated with lesions of the head or face and has been described in association with otitis media. The incubation period is short, usually 1 to 2 days. Unlike generalized and localized tetanus, cephalic tetanus results in flaccid cranial nerve palsies rather than spasm. Spasm of the jaw muscles may also be present. Like localized tetanus, cephalic tetanus can progress to the generalized form.


Complications of Tetanus

  • Laryngospasms
  • Fractures
  • Hypertension
  • Nosocomial infections
  • Pulmonary embolism
  • Aspiration pneumonia
  • Death

Treatment

Tetanus is a medical emergency requiring hospitalization, immediate treatment with human tetanus immune globulin (TIG), agents to control muscle spasm, aggressive wound care, antibiotics, and a tetanus toxoid booster. If tetanus immune globulin is unavailable, Immune Globulin Intravenous (IGIV) can be used.

A patent airway should be maintained and, depending on the severity of disease, endotracheal intubation or tracheostomy and mechanically assisted respiration may be lifesaving. Sedation and muscle relaxant drugs should be used as indicated to control muscle spasms. Agents to control autonomic nervous system instability may be required. Active immunization may be initiated concurrently with treatment.

Treatment of tetanus cases with TIG

A single dose of human TIG is recommended for treatment of persons with tetanus. Although the optimal therapeutic dose has not been established, experts recommend 500 international units (IU), which appears to be as effective as higher doses ranging from 3,000 to 6,000 IU and causes less discomfort.

Available preparations must be administered intramuscularly; TIG preparations available in the United States are not licensed or formulated for intrathecal or intravenous use.

Infiltration of part of the dose locally around the wound is usually recommended (see Red Book), although its efficacy approach has not been proven.

If TIG is not available, IGIV can be used at a dose of 200 to 400 milligrams per kilogram (mg/kg). However, the Food and Drug Administration has not approved IGIV for this use. In addition, anti- tetanus antibody content varies from lot to lot.


Vaccination during Recovery

Tetanus disease does not result in tetanus immunity. Active immunization with a tetanus toxoid-containing vaccine should begin or continue as soon as the person’s condition has stabilized.


Wound Management for Tetanus Prevention

Risk of tetanus disease depends on the type and condition of the wound and immune status of the patient. The following steps should be taken to prevent tetanus:

  • Assess the type of wound and provide appropriate wound care.
    Wounds may be clean or contaminated and dirty, superficial or deep and penetrating. Dirty wounds pose an increased risk for tetanus. Wounds should be considered dirty if contaminated with dirt, soil, feces, or saliva (e.g., animal or human bites). Penetrating or puncture wounds are considered contaminated and may pose a higher risk for tetanus. Wounds containing devitalized tissue (e.g., necrotic or gangrenous wounds), frostbite, crush injuries, avulsion fractures, and burns are particularly conducive for proliferation of C. tetani.

    All wounds should be cleaned, dirt or foreign material removed, and necrotic material removed or debrided.

  • Evaluate the immunization status of the patient.

    Unvaccinated persons should start and complete a primary series with an age-appropriate tetanus toxoid-containing vaccine (DTaP, TdaP, or Td) as currently recommended by CDC.

    Persons with unknown or uncertain history of receiving previous prior doses tetanus toxoid-containing vaccines should be considered to have had no previous tetanus toxoid-containing vaccine and a primary series should be completed. This is because early doses of toxoid may not induce adequate immunity, but only prime the immune system.

    Persons who have completed a 3-dose primary tetanus vaccination series:

    • If the last dose of a tetanus toxoid-containing vaccine was received less than 5 years earlier, they are considered protected against tetanus and do not require another dose of tetanus toxoid-containing vaccine as part of the current wound management.
    • If the last dose of a tetanus toxoid-containing vaccine was received 5 or more years earlier, then a booster dose of an age-appropriate tetanus toxoid-containing vaccine should be administered.
    • Rarely have cases of tetanus occurred in persons with a documented primary series of tetanus toxoid.
  • Assess need for administering TIG for prophylaxis.
    TIG provides temporary immunity by directly providing antitoxin. TIG can only help remove unbound tetanus toxin but cannot neutralize toxin that is already bound to nerve endings.

    Persons who have contaminated and dirty wounds and are either unvaccinated or have not received a primary series of tetanus toxoid-containing vaccines should receive TIG for prophylaxis. The dose of TIG for prophylaxis is 250 IU administered intramuscularly.

    People with HIV infection or severe immunodeficiency who have contaminated wounds (including minor wounds) should also receive TIG, regardless of their history of tetanus immunizations.

  • Do not use antibiotics for prophylaxis against tetanus.
    Antibiotic prophylaxis against tetanus is not recommended, but wounds should be observed for signs of infection and promptly treated if signs of infection are detected.

Summary of Tetanus Prophylaxis with TIG in Routine Wound Management

History of adsorbed tetanus toxoid-containing vaccines (doses) Clean, minor wound All other wounds*
DTaP, Tdap or Td TIG DTaP, Tdap or Td TIG
Unknown or <3 Yes No Yes Yes**
Unknown or ≥3 No§ No No No

Footnotes

Abbreviations: DTaP = Diphtheria and Tetanus toxoids and acellular pertussis vaccine; Tdap = tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis; Td = tetanus and diphtheria toxoids; TIG = Tetanus immune globulin
*Such as, but not limited to, wounds contaminated with dirt, feces, soil, and saliva; puncture wounds; avulsions; and wounds resulting from missiles, crushing, burns, and frostbite.
**The dose of TIG for prophylaxis is 250 IU administered intramuscularly.
† DTaP is recommended for children <7 years of age. Tdap is preferred to Td for persons aged 11 years or older who have not previously received Tdap. Persons aged 7 years or older who are not fully immunized against pertussis, tetanus, or diphtheria should receive one dose of Tdap for wound management and as part of the catch-up series.
‡ People with HIV infection or severe immunodeficiency who have contaminated wounds (including minor wounds) should also receive TIG, regardless of their history of tetanus immunizations.
§ Yes, if ≥10 years since the last tetanus toxoid-containing vaccine dose.
¶ Yes, if ≥5 years since the last tetanus toxoid-containing vaccine dose.


References

  1. Diphtheria, Tetanus, and Pertussis: Recommendations for Vaccine Use and Other Preventive Measures Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR. 1991;40(RR10):1–28.
  2. Preventing Tetanus, Diphtheria, and Pertussis Among Adolescents: Use of Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccines. MMWR. 2006;55(RR03):1–34.
  3. Preventing Tetanus, Diphtheria, and Pertussis Among Adults: Use of Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccines. MMWR. 2006;55(RR17):1–33.
  4. American Academy of Pediatrics. Tetanus. In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book®: 2015 Report of the Committee on Infectious Diseases. American Academy of Pediatrics; 2015; 773–8.
  5. Pink Book’s Chapter on Tetanus
    Epidemiology & Prevention of Vaccine-Preventable Diseases

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