Tetanus

Tetanus is a bacterial infection caused by Clostridium tetani, a gram-positive obligate anaerobic bacterium commonly found in soil that enters the body through a contaminated wound. C. tetani produces a neurotoxin that blocks the release of inhibitory neurotransmitters and causes prolonged tonic muscle contractions. It presents with lockjaw, neck stiffness, opisthotonus, rigid abdomen and severe painful muscle spasms. Diagnosis is made on clinical grounds, as it is rarely possible to isolate the infectious agent from the wound. It is treated with antibiotic therapy and the human tetanus antitoxin. Untreated tetanus can lead to respiratory failure and cardiovascular complications and can be fatal. With appropriate treatment, however, most patients will recover.

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Overview

Definition

Tetanus is a nervous system disorder caused by the bacterium Clostridium tetani.

Etiology

  • Pathogen: Clostridium tetani:
    • Gram-positive bacillus
    • Spore-forming, obligate anaerobe
    • 10 serotypes have been identified.
    • All 10 of the serotypes contain 2 common toxins: tetanolysin and tetanospasmin
  • Toxins:
    • Tetanolysin causes local tissue destruction but is not relevant to the pathogenesis of tetanus.
    • Tetanospasmin is a potent neurotoxin (exotoxin) that causes clinical tetanus.
  • Habitat:
    • Soil
    • Freshwater
    • Marine sediments
    • Intestinal tract of humans and animals
    • Spores can be airborne.

The micrograph depicts a group of Clostridium tetani bacteria, responsible for causing tetanus in humans:
Note the slender bacillus with a characteristic “drumstick” appearance caused by the spherical terminally located spores.

Image: “This micrograph depicts a group of Clostridium tetani bacteria, responsible for causing tetanus in humans” by CDC. License: Public Domain

Epidemiology

  • Can occur in any age group, but neonates are the age group at highest risk. 
    • Neonatal tetanus is extremely dangerous; it has a mortality rate of nearly 100%.
    • Occurs mainly in developing countries with unclean delivery techniques and poor postnatal hygiene
  • Most cases of tetanus occur in countries where there is a lack of immunization.
  • Elderly individuals are also at risk because of reduced immunity.
  • Spores of C. tetani are present in the soil irrespective of geographical location.

Mode of infection

  • Through contaminated wounds (most common)
  • Complication of IV drug use
  • Through the middle ear (cephalic tetanus)
  • Through the umbilical stump (neonatal tetanus)
  • Risk factors for developing tetanus: 
    • Burns
    • Surgical wounds
    • IV drug use
    • Diabetes
    • Immunosuppression

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Pathophysiology

Types

  • Generalized tetanus: most common and severe form
  • Local tetanus: mild form with symptoms that develop only near the infected wound
  • Cephalic tetanus: rare but fatal infection that usually enters through the middle ear
  • Neonatal tetanus: due to infection of the umbilical stump

Pathophysiology

Inoculation:

  • C. tetani has little invasive power.
  • Spores usually enter the organism through contaminated wounds.
  • Not every inoculation will result in infection.
  • Spores germinate under anaerobic conditions: wound ischemia, tissue necrosis, devitalized tissue
  • Average incubation period is 7–10 days (can last from 1 to 60 days).
  • Neonatal tetanus usually presents with a shorter incubation period (5–7 days after birth).

Pathogenesis:

  • Exotoxins (tetanospasmin and tetanolysin) are produced by germinated bacteria.
  • Tetanolysin may play a role in local tissue destruction, but tetanospasmin is responsible for the neurologic symptoms.
  • Tetanospasmin is released into the blood and enters the presynaptic terminals of the neuromuscular end plate of motor neurons.
  • Inhibit release of GABA and glycine (inhibitory neurotransmitters)
  • Toxin then travels to the CNS via retrograde axonal transport, where it also blocks GABA and glycine release.
  • A lack of inhibitory neurotransmitters causes a continuous excitatory state of the motor neuron → spastic paralysis
  • Continuous unopposed muscle activity can lead to bone fractures and muscle tears.

Pathophysiologic mechanism caused by Clostridium tetani:
Tetanospasmin blocks the binding of neurotransmitters (GABA/glycine) to their receptors on the postsynaptic membrane, leading to inhibitory neurotransmission

Image by Lecturio.

Clinical Presentation and Diagnosis

Clinical presentation

Generalized tetanus is the most common and severe clinical form of tetanus.

  • General malaise
  • Trismus, or lockjaw (80%): 
    • Caused by spasm of the masseter muscles, which causes difficulty in opening the mouth and difficulty in mastication
    • The most important early symptom; preceded by general malaise
    • Spasms may be triggered by visual, auditory, and mechanical stimuli.
  • Stiffness of the neck
  • Risus sardonicus, or sardonic smile:
    • Due to tonic rigidity involving muscles of the face, neck, and trunk
    • Contraction of the frontalis muscles and muscles of the angle of the mouth produces a characteristic grinning expression.
  • Opisthotonus:
    • A varying degree of rigidity develops in the muscles of the neck, back, and trunk.
    • The back is usually arched, and the abdominal wall appears broad.
  • Rigid abdomen
  • Convulsions: 
    • Painful, violent, exhausting, reflex spasms that last for 3–4 minutes
    • Develop within 24–72 hours after the initial onset of symptoms
  • Laryngeal spasm: causes difficulty breathing
  • Esophageal spasm: causes dysphagia
  • Urethral spasm: causes urinary retention
  • Autonomic nervous system overactivity:
    • Sweating
    • Tachycardia
    • Fevers
    • Cardiovascular complications: labile blood pressure, arrhythmias

Neonatal tetanus: 

  • Refusal to feed and difficulty opening the mouth due to trismus in an infant previously able to feed and cry properly
  • Poor sucking
  • Irritability
  • Grimacing
  • Clenched hands and dorsiflexed feet
  • Intense rigidity and spasms can lead to opisthotonus.

Neonate displaying body rigidity seen in neonatal tetanus

Image: “Neonatal tetanus 6374” by CDC. License: Public Domain

Local tetanus

  • Tonic contractions/spasms limited to one body region/extremity
  • Will often progress to generalized tetanus

Cephalic tetanus: 

  • Rare, but frequently fatal
  • Trismus
  • Peripheral facial paralysis (facial nerve most commonly involved)
  • Ophthalmoplegia
  • Dysphagia
  • Can progress to generalized tetanus

Diagnosis

  • Diagnosis is made on clinical grounds, as it is difficult to isolate C. tetani from its original site of entry.
  • History:
    • History of a previous tetanus-prone injury
    • History of inadequate immunization for tetanus
    • History of immunosuppression or presence of risk factors
  • Physical exam: 
    • Presence of characteristic findings
    • “Spatula test”: Touching the back of the throat elicits jaw contraction instead of normal gag reflex.
  • Serum antitoxin level:
    • Not always readily available
    • Level ≥ 0.01 IU/mL makes tetanus less likely.

Management

Supportive management:

  • Toxin bound to synaptic endings cannot be neutralized.
  • The effects of toxin can, therefore, last for weeks, and supportive management is required.
    • ICU admission
    • Endotracheal intubation is frequently needed to protect airway.
    • Tracheostomy may be needed if prolonged intubation is required.
    • Maintenance of hydration
    • Enteral feeding to maintain nutrition
    • Prophylaxis against thromboembolism by the administration of anticoagulants
    • Prevention and treatment of secondary infections
    • Physical therapy after the cessation of spasms
    • Control of muscle spasms:
      • Place the patient in a quiet room and avoid unnecessary stimuli.
      • Benzodiazepines/IV diazepam
      • Baclofen is used in a few cases.
    • Management of autonomic dysfunction:
      • Magnesium sulfate
      • Labetalol

Halting production of toxin:

  • Debride wound to lower bacterial counts.
  • Antibiotic therapy: 
    • Metronidazole (best choice) for 7–10 days
    • Penicillin
    • Doxycycline
    • Cephalosporins if co-infection with another organism is suspected

Neutralization of unbound toxin:

  • IM human tetanus immunoglobulin (HTIG) is administered and infiltrated around the wound.
  • If HTIG is not available, then intravenous immunoglobulin may be administered.
  • In countries where HTIG is not readily available, IM equine tetanus immunoglobulin can be administered.
  • Because of high chances of allergic reaction with equine immunoglobulin, a test dose should be administered.

Complications

  • Fractures: Severe spasms can lead to fractures in the vertebrae and other bones.
  • Laryngospasm: 
    • A brief spasm of the larynx, usually lasting 30–60 seconds
    • Laryngospasm prevents oxygen from reaching the lungs, making breathing difficult.
    • In severe cases, laryngospasm leads to asphyxia and ultimately death.
  • Aspiration pneumonia: Tetanus causes muscle rigidity, leading to difficulty in coughing and swallowing, which can result in aspiration pneumonia.
  • Acute renal failure:
    • Severe muscle spasms associated with tetanus can cause rhabdomyolysis.
    • Rhabdomyolysis results in the excretion of myoglobin in the urine, leading to acute kidney failure.
  • Complications of prolonged immobilization:
    • Deep vein thrombosis and pulmonary embolism
    • Nosocomial infections

Prophylaxis

  • Tetanus is a vaccine-preventable disease.
  • Tetanus vaccines are based on tetanus toxoid and are available as single or combination vaccines.
  • Combined diphtheria–tetanus–pertussis vaccine is administered as a part of the normal immunization schedule, which provides protection up to adolescence.
  • Administered to pregnant women and those of childbearing age to prevent neonatal tetanus
  • Patients presenting with wounds:
    • Clean wounds: administer vaccine:
      • If < 3 previous doses
      • If last dose > 10 years ago
    • Contaminated wounds:
      • Give vaccine if last dose > 5 years ago
      • Human tetanus immune globulin if < 3 doses of toxoid vaccine
  • For patients affected with tetanus:
    • Immunity following tetanus is incomplete and does not prevent recurrent episodes.
    • A full schedule of active immunization is therefore instituted with tetanus and diphtheria toxoid–containing vaccines.

Wound management and prophylaxis of tetanus:
The time from the last dose determines the treatment given to an individual to prevent contracting the disease.
Immunity categories:
A: The patient has had a complete course of toxoid or a booster within the past 5 years.
B: The patient has had a complete course of toxoid or a booster between 5 and 10 years ago.
C: The patient has had a complete course of toxoid or a booster dose > 10 years ago.
D: The patient has not had a complete course of toxoid or immunity status is unknown.

Image by Lecturio.

Prognosis

  • The majority of those affected will recover with appropriate care.
  • Shorter incubation periods are associated with more severe disease.
  • In resource-limited countries, the case fatality ranges from 5% to 50%.
  • Neonatal tetanus has mortality rates of 3%–88%.
  • Residual neurologic deficits are common in survivors.

Differential Diagnosis

  • Strychnine poisoning: Strychnine is a toxic alkaloid used in pesticides. After ingestion, patients present with symptoms of muscle spasms, cramping, stiffness, agitation, tachycardia, hypertension, tachypnea, mydriasis, and nystagmus. Diagnosis is by a thorough history and laboratory assays of blood, urine, and tissue. There is no specific treatment; only supportive management is required.
  • Phenothiazine overdose: Phenothiazine is a drug used to treat schizophrenia. Symptoms of overdose include deviation of eyes, writhing movements of head and neck, drooling, and shallow breathing. Diagnosis is by detailed history and blood and urine analysis. Treatment is by the administration of the anticholinergic agent benztropine.
  • Tetany: carpopedal spasms, muscle cramps, tremors or spasms of the face, and calf muscles: Tetany is caused by hypocalcemia secondary to an underlying disorder or deficiency. Diagnosis is by blood analysis and the presence of 2 clinical signs: Chvostek and Trousseau. Treatment is by the administration of calcium gluconate and resolution of the underlying cause.
  • Meningitis: an inflammation of the meninges commonly caused by bacterial and viral infections: Symptoms include headache, fever, stiff neck, and lethargy, as well as refusal to feed and irritability in infants. Diagnosis is by blood analysis and spinal tap. Treatment includes antibiotics or antiviral therapy and supportive management.

References

  1. George EK, De Jesus O, Vivekanandan R. (2020). Clostridium tetani. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK482484/
  2. Boloor A, Nayak R. (2018). Exam Preparatory Manual for Undergraduates Medicine. 2nd ed. Xxxxx: Xxxxx, p. 122.
  3. Bourget D. (2020). Tetanus. StatPearls. Retrieved March 12, 2021, from https://www.statpearls.com/articlelibrary/viewarticle/29997/
  4. Ralston SH, et al. (Eds.). (2018). Davidson’s Principles and Practice of Medicine, 23rd ed. Xxxxx: Xxxxx, pp. 1125–1126.
  5. World Health Organization. (2021). Tetanus Disease and Epidemiology. Retrieved March 12, 2021, from http://www.emro.who.int/health-topics/tetanus/vaccine-vaccination.html
  6. Thwaites L. (2020). Tetanus. UpToDate. Retrieved March 12, 2021, from https://www.uptodate.com/contents/tetanus#H1917381

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