Tetanus

Tetanus (lockjaw) is an acute disease caused by neurotoxins from the bacterium Clostridium tetani. C. tetani is ubiquitous in spore form and enters the body through broken skin (e.g., deep puncture wounds). Its toxins then cause uncontrolled activation of alpha motor neurons, leading to muscular rigidity and spasms. Patients classically present with a triad of trismus, risus sardonicus, and opisthotonus. Tetanus is a clinical diagnosis, but diagnostic testing may help confirm the diagnosis. Treatment includes airway management, wound debridement, immunoglobulin therapy (e.g., human tetanus immune globulin), antibiotics (e.g., metronidazole), and pharmacological management of severe muscle spasms. Prevention of tetanus involves routine immunization with tetanus vaccines and administering postexposure prophylaxis for wounds.

• Pathogen
  • Clostridium tetani: a gram-positive, obligate anaerobic, spore-forming rod
  • Produces neurotoxins tetanospasmin and tetanolysin
  • Ubiquitous (especially animal feces and soil)
• Route of infection
  • Clostridial spores contaminate a wound (e.g., through dirt, saliva, feces).
  • Localized ischemia, necrosis, foreign bodies and/or coinfection with other bacteria predispose to infection.
  • Wounds with compromised blood supply create anaerobic conditions that are required for the germination and multiplication of C. tetani.
    • Deep, penetrating wounds (e.g., knife, gunshot, animal bites)
    • Open fractures
    • Surgical procedures (e.g., bowel, biliary tract, or dental surgery)
    • Burns
    • Umbilical stump infections
    • Septic abortion
• Groups with a higher risk: : non-immunized individuals, those with diabetes, neonates, people who inject drugs (PWID), certain patient groups (i.e., postsurgical, obstetric, dental)

Ubiquitous C. tetani spores contaminate a wound → bacterial reproduction under anaerobic conditions → production of the neurotoxins tetanospasmin and tetanolysin

• Tetanospasmin: reaches the CNS through retrograde axonal transport
  • Toxin binds to receptors of peripheral nerves and is then transported to interneurons (Renshaw cells) in the CNS via vesicles. ^[1][2]
  • Acts as protease that cleaves synaptobrevin, a SNARE protein → prevention of inhibitory neurotransmitters (i.e., GABA and glycine) release from Renshaw cells in the spinal cord → uninhibited activation of alpha motor neurons → muscle spasms, rigidity, and autonomic instability
• Tetanolysin: causes hemolysis and has cardiotoxic effects

Neurotoxins (not the pathogen itself) cause tetanic contractions.

Tetanospasmin causes tetanic spasms.

• Incubation period: 3–21 days (average: ∼ 10 days)
• Generalized tetanus: painful muscle spasms and rigidity
  • Trismus: lockjaw due to spasms of jaw musculature (commonly the first tetanus-specific symptom)
  • Risus sardonicus: sustained facial muscle spasm that causes a characteristic, apparently sardonic grin and raised eyebrows
  • Opisthotonus: backward arching of spine, neck, and head caused by spasms of the back muscles
  • Neck stiffness
  • Abdominal rigidity
• Life-threatening complications
  • Laryngospasm and/or respiratory muscles spasms → respiratory failure ^[3]
  • Autonomic dysfunction → circulatory arrest and shock ^[1][3]

Neonatal tetanus

• Occurs in infants of inadequately immunized mothers after unsterile management of the umbilical stump
• Typically occurs 5–8 days after birth, but the incubation period can take up to several weeks
• Typically a rapid onset of symptoms as axonal length in infants is shorter than in adults ^[4]
• Symptoms
  • Difficulty opening the mouth and feeding due to trismus and risus sardonicus
  • Muscle stiffness and opisthotonus
  • Clenched hands

Other types ^[5]

• Localized tetanus: Patients present with painful muscle contractions in areas surrounding the injury site only.
• Cephalic tetanus
  • In patients with open head or neck injuries.
  • Initially only affects cranial nerves (especially flaccid paralysis of CN VII), which can be mistaken for stroke

• Tetanus is a clinical diagnosis based on muscle spasms and rigidity associated with an entry point for bacteria and inadequate immunization. ^[6]
• Wound culture and serology may confirm the diagnosis but have low sensitivity and specificity.

The following relates to the treatment of clinically apparent tetanus. See "Tetanus prophylaxis after injury" for preventing tetanus in individuals with acute wounds.

Approach ^{[7][8][9][10]}

• Immediately manage life-threatening and severe symptoms (see “Acute stabilization”).
• Administer passive immunization, e.g., human tetanus immunoglobulin, as soon as possible.
• Manage acute wounds, e.g., wound irrigation and debridement
• Initiate antibiotics, preferably PO metronidazole.
• Admit all patients with suspected tetanus infection.
  • ICU admission is often required. ^[11][12][13]
  • Follow standard precautions. ^[14]
• Begin active immunization; with the tetanus vaccine once the patient is improving.

Wound care and antibiotics decrease bacterial load and toxin production. Immunoglobulin therapy neutralizes free toxins. ^[9][13]

Acute stabilization ^{[7][8][9][10]}

• Laryngospasm or respiratory muscle spasms: airway management with rapid sequence intubation (RSI) ^[13]
• Cardiac instability: immediate hemodynamic support
• Severe muscle spasms: benzodiazepines and/or paralytics; , potentially in combination with mechanical ventilation ^[8][13]

Prepare for difficult airway management and consider early RSI, as trismus and laryngospasm can limit successful intubation.

Prolonged mechanical ventilation is often required; consider early tracheostomy. ^[13]

Antibiotics ^{[7][8][9][10]}

• Preferred: PO metronidazole (off-label) ^[7][10][13]
• Alternative: penicillin G ^[7][9]

Immunization ^{[7][8][9][10]}

• Passive immunization: immunoglobulin therapy ^[7][8]
  • First-line: IM human tetanus immunoglobulin (HTIG) ^[7][8]
  • Consider infiltrating part of the HTIG dose into the affected wound. ^[7][8]
  • HTIG unavailable: Consider intravenous immunoglobulin (off-label) . ^[7][11][15]
  • HTIG and IVIG unavailable (e.g., resource-limited settings): Equine tetanus immunoglobulin may be considered. ^[7][16]
• Active immunization: tetanus vaccine administered at a separate site from HTIG ^[7][8][9]

Following immunoglobulin therapy, live vaccines (e.g., MMR vaccine, varicella vaccine) should not be given for 3–8 months (see “Contraindications to live vaccines”). ^[7]

Tetanus vaccine ^[17][18]

Routine immunization is recommended for all individuals.

• Active component: denatured tetanus toxin
• Available vaccines
  • Children < 7 years of age
    • DTaP (diphtheria, tetanus, and acellular pertussis) vaccines
    • DT (diphtheria, tetanus) if acellular pertussis vaccines are contraindicated ^[19]
  • Children ≥ 7 years of age and adults
    • Tdap (tetanus, diphtheria, pertussis): routinely, at age 11 years ^[8]
    • Td (tetanus, diphtheria) OR Tdap boosters every 10 years
• Schedule: See “ACIP immunization schedule” for details.

Boosters with Td or Tdap are recommended every 10 years for all adolescents and adults who have completed the primary Tdap and DTaP series. See “ACIP immunization schedule” for details. ^[18][20][21]

Acellular pertussis-containing vaccines are contraindicated in patients who previously developed unexplained encephalopathy within a week after receiving an acellular pertussis vaccine (i.e., DTaP or Tdap). ^[19]

Tetanus prophylaxis after injury ^{[7][8][9][22]}

• Management is based on:
  • Tetanus vaccine history
  • Wound assessment
  • Immune status (e.g., immunocompromised state, HIV infection) ^[9]
• Tetanus-prone wounds include:
  • Dirty wounds
  • Deep injuries
  • Thermal injuries

Administer HTIG to patients with severe immunodeficiency or HIV infection and a tetanus-prone wound regardless of tetanus vaccine history. ^[9]