Tetanus (Lockjaw)

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 motoneurons, leading to muscular rigidity and spasms. Patients classically present with a triad of trismus, risus sardonicus, and opisthotonus. Despite treatment with anti-tetanus toxoid immunoglobulin and antibiotics (e.g., metronidazole), the overall prognosis is poor once symptoms begin. Therefore, vaccination as primary prevention is crucial.

• 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)
    • Septic abortion
    • Burns
    • Umbilical stump infections
• Groups with a higher risk: non-immunized individuals; , those with diabetes, neonates, IV drug abusers, certain patient groups (i.e., postsurgical, obstetric, dental) ^[1]

Ubiquitous C. tetani spores contaminate a wound → bacteria reproduce under anaerobic conditions → production of 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 ^[2][3]
  • Acts as protease that cleaves synaptobrevin, a SNARE protein → prevents the release of inhibitory neurotransmitters (i.e., GABA and glycine) from Renshaw cells → uninhibited activation of alpha motor neurons → muscle spasms, rigidity, and autonomic instability
• Tetanolysin: causes hemolysis and has cardiotoxic effects

Neurotoxins cause tetanus (not the pathogen itself)!

• Incubation period: 3–21 days (average: ∼ 10 days)
• Generalized tetanus: painful muscle spasms and rigidity
  • Trismus: lockjaw due to spasms of the jaw musculature
    • Commonly the first tetanus-specific sign
  • Risus sardonicus; : grinning caused by cramps of the facial muscles
  • Neck stiffness
  • Opisthotonus: backward arching of spine, neck, and head caused by spasms of the back muscles
  • Abdominal rigidity
  • Life-threatening complications
    • Laryngospasm and/or respiratory muscles spasms → respiratory failure ^[4]
    • Autonomic dysfunction → circulatory arrest and shock ^[4]

Neonatal tetanus

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

Other types

• Localized tetanus: Patients present with painful muscle contractions in areas surrounding 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 upon 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

In addition to initial supportive care, management should focus on controlling the infection, eliminating toxin production, and neutralizing circulating toxins.

• Wound cleaning and debridement
• Antibiotic treatment
  • Drug of choice: metronidazole
  • Alternative: penicillin G
• Active and passive immunization
  • Single IM dose of human tetanus immunoglobulin (HTIG)
  • Tetanus toxoid-containing vaccine: for example, TdaP, Td, DTaP, DT, depending on age, previous immunization, or allergies (see tetanus prophylaxis after injury in “Prevention” section below for details)
    • Inject in a separate site from HTIG
    • If patient has not received initial immunization before infection: second and third dose 1–2 months and 6–12 months later, respectively
    • The still intact receptor binding site of the tetanus toxoid induces antibody production and memory cell formation (active immunity).
• Supportive care: : transfer to ICU, ventilation, benzodiazepines and/or paralytics for control of muscle spasms

Tetanus vaccination ^[7]

• Tetanus toxoid-containing vaccines according to age groups
  • For children < 7 years of age:
    • DTaP (diphtheria, tetanus, and acellular pertussis)
    • DT (diphtheria, tetanus): for children who cannot tolerate the pertussis vaccine
  • For adolescents and adults:
    • Tdap (tetanus, diphtheria, pertussis): recommended for patients 11–64 years of age, but may be considered for children > 7 years old
    • Td (tetanus, diphtheria): for patients > 11 years old
• Initial immunization recommendations: children < 7 years of age → 5 doses of DTaP (see “Immunization schedule”):
• Booster recommendations
  • Children 11–12 years of age: single dose of Tdap ^[8]
  • Adults 19–64 years of age: single dose of Tdap ^[8]
  • Adults ≥ 19 years of age: Td (tetanus, diphtheria) every 10 years

Since recovery from infection does not confer immunity following recovery, routine immunization is generally recommended!

Tetanus prophylaxis after injury

Vaccination history	Clean, minor wounds	All other wounds
Unknown or < 3 tetanus toxoid doses	Active immunization with tetanus toxoid (Td or Tdap)	Active immunization with Td or Tdap AND passive immunization with HTIG
≥ 3 tetanus toxoid doses	Active immunization with Td or Tdap if last vaccination ≥ 10 years ago	Active immunization if last vaccination ≥ 5 years ago