Tetanus

Definition, Etiology, PathogenesisTop

Tetanus is an acute disease of the nervous system caused by a bacterial neurotoxin, which typically manifests as an increased tone and severe spasms of skeletal muscles. This disease is now very rare in developed countries (<1 case per 1 million people per year), primarily thanks to the use of tetanus vaccine.

1. Etiologic agent: Clostridium tetani, a gram-positive, rod-shaped, obligate anaerobe producing spores and releasing a neurotoxin (an exotoxin referred to as tetanospasmin). Tetanus toxin enters the subsynaptic zone of central inhibitory neurons (spinal cord, brainstem) and irreversibly blocks the secretion of neurotransmitters (glycine, gamma-aminobutyric acid [GABA]). This abolishes their inhibitory effects on the skeletal muscles and results in the increased muscle tone. C tetani spores are resistant to environmental factors, disinfectants, and high temperatures; they may survive in soil for many years.

2. Reservoir and transmission: Gastrointestinal tracts of various animals are reservoirs for C tetani (the bacteria are excreted with feces into the environment). Infection usually develops as a result of contamination of a wound (the site of entry) with soil fertilized with manure or other material containing spores of C tetani (eg, while tending to horses or cattle). The anaerobic conditions in the wound lead to local growth of the bacteria (no systemic dissemination) and production of tetanospasmin.

3. Risk factors: Sustaining wounds while working with soil (particularly soil fertilized with manure), plants, horses, or other livestock, as well as while using tools contaminated with soil; IV substance abuse; incompletely vaccinated or unvaccinated individuals (adults are recommended to receive booster immunization every 10 years). Wounds at exceptionally high risk for tetanus include crush wounds, deep penetrating wounds, gunshot wounds, and wounds with a retained foreign body; wounds highly contaminated with soil, excrements, saliva, or by-products of meat production; wounds infected with aerobic bacteria (which use up oxygen in the wound) that are not cleaned/debrided within 24 hours; and wounds in patients with shock (ischemia), burns, or frostbites. Wounds at low risk for tetanus are superficial wounds with good perfusion and without necrosis that have been sustained indoors.

4. Incubation and contagious period: This may last from 2 to 21 days (usually ~7 days, in rare cases up to several months), depending on type of wound and degree of contamination. Tetanus cannot be spread from person to person.

Clinical FeaturesTop

1. Prodromal phase (preceding symptomatic tetanus): Anxiety, malaise, increased muscle tone, sweating, headache, insomnia, pain and paresthesia in the areas adjacent to the wound.

2. Generalized tetanus (the most frequent form):

1) Increased muscle tone and muscle spasms (most severe during the first 2 weeks) without altered mental status. Initially dysphagia and difficulty chewing, followed by trismus (lockjaw, or increased tone of the masseter muscle) and risus sardonicus (increased tone of the orbicularis oris muscle—“sardonic smile”). Increased tone of the abdominal muscles and opisthotonus (trunk arching backward with upper extremities flexed and lower extremities hyperextended). Severe paroxysmal spasms involving various muscle groups of the trunk and extremities, which are triggered by external stimuli (noise, light, touch) and cause severe pain. Some patients develop respiratory obstruction or respiratory arrest (diaphragm spasm).

2) Autonomic instability (predominantly sympathetic) that appears within a few days, peaks during week 2, and is the most frequent cause of death. It manifests as hypertension and tachycardia alternating with hypotension and bradycardia, arrhythmias, cardiac arrest, mydriasis, hyperthermia, laryngospasm, and urinary retention.

3. Localized tetanus: Stiffness of the muscles adjacent to the entry wound. It may resolve spontaneously (as a result of partial immunity to the toxin) or, most frequently, is a prodromal symptom of generalized tetanus. Cephalic tetanus is a rare form of the disease that develops following a head injury and affects the muscles innervated by cranial nerves (most frequently nerve VII). Patients often have facial muscle weakness (due to lower motor neuron damage).

4. Neonatal tetanus: A severe generalized form that develops in newborns of tetanus-susceptible mothers (having no protection by maternal antibody transfer), usually between 4 to 14 days of life. Typically it occurs as a result of umbilical stump infection. Neonatal tetanus is observed predominantly in developing countries.

DiagnosisTop

In medical practice the diagnosis of tetanus is based exclusively on the patient’s medical history and clinical presentation. Microbiologic and serologic tests are not useful. Tetanus is generally considered reportable to public health units.

Classification of disease severity:

1) Mild tetanus: Trismus and risus sardonicus; relatively mild, isolated muscle spasms.

2) Moderate tetanus: Trismus and risus sardonicus, dysphagia, stiffness, periodic muscle spasms.

3) Severe tetanus: Generalized muscle spasms, respiratory failure, tachycardia, blood pressure fluctuations.

Differential Diagnosis

1. Strychnine poisoning: The only condition with an almost identical clinical presentation as that of tetanus (due to the inhibition of glycine-dependent signaling pathways). Medical history and toxicology test results are conclusive for diagnosis.

2. Meningitis or encephalitis: Nuchal rigidity, usually accompanied by fever and altered mental status.

3. Tetany: This is usually due to abnormalities in electrolytes such as calcium (the most common cause of tetany), phosphate, or magnesium. It can be quickly be identified through measurement of electrolytes and parathyroid hormone (PTH) levels.

4. Dystonic reactions caused by antipsychotic agents (eg, haloperidol) or phenothiazines (eg, promethazine), which may be associated with nuchal stiffness and torticollis (this is rare in patients with tetanus).

5. Inflammation or an abscess of oropharyngeal cavity (eg, a peritonsillar abscess) or the temporomandibular joint: This may be associated with trismus; other features typical for tetanus are absent.

6. Stiff person syndrome: An immune-mediated movement disorder that is associated with muscle stiffness with superimposed muscle spasms. It can be considered as part of the differential diagnosis for tetanus, although it generally has a less acute presentation and does not present with trismus.

TreatmentTop

Patients with moderate or severe tetanus should be treated in an intensive care unit (ICU). ICU supportive measures, including control of pain, agitation, delirium, and sleep as well as support of bowel and/or bladder function and nutrition should be maintained throughout.

1. Diagnosis and patient stabilization (the first hour):

1) Maintain the airway and ventilation.

2) Place the patient in a dark and quiet room (preferably in an ICU).

3) Perform biochemical and toxicologic testing (calcium level, strychnine, antipsychotic agents, phenothiazines).

4) Take the patient’s medical history. Establish the site of entry and immunization history.

5) Administer IV benzodiazepines, for instance, diazepam 10 to 40 mg every 1 to 8 hours or midazolam as needed, to sedate the patient, decrease muscle stiffness, and prevent spasms. The dosage should be subsequently tapered down to prevent withdrawal symptoms.

2. Early antitoxin administration and symptomatic treatment (the first 24 hours):

1) IM human tetanus immunoglobulin (HTIG) 3000 to 6000 IU in a single dose (no test dose is administered; dosage according to the manufacturer’s label); it has been suggested (in one small observational study) that a dose of 500 IU may be as effective. When HTIG is not available, another potential option is intravenous immunoglobulin (IVIG) at a dose of 200 to 400 mg/kg.

2) IV metronidazole 500 mg every 6 hours or 1000 mg every 12 hours for 7 to 10 days eradicates tetanus bacilli from the wound. Penicillin is a second-line option.

3) Surgical wound debridement and cleaning.

4) In case of persistent airway obstruction, intubate the patient and start mechanical ventilation.

5) Enteral feeding via a nasogastric tube.

6) In patients with muscle spasms that are severe or interfere with mechanical ventilation, supportive care and pharmacotherapy (eg, muscle relaxants or paralytic agents) could be used to help control tetanic spasms.

7) Schedule and start tetanus vaccination once the patient is stable, if possible along with the administration of HTIG. In unvaccinated patients administer a complete vaccination series.

3. Intermediate treatment phase (symptomatic treatment; weeks 2-3):

1) In patients with sympathetic hyperactivity, you may administer IV magnesium sulfate 40 mg/kg over 30 minutes followed by a continuous infusion and IV labetalol 0.25 to 1 mg/min or IV morphine 0.5 to 1 mg/kg/h in a continuous infusion. You may also consider an epidural block (case reports only).

2) In case of hypotension, administer IV crystalloids.

3) In patients with bradycardia, start cardiac pacing (see Disorders of Automaticity and Conduction).

4) Prophylaxis of venous thromboembolism (see Primary Prevention of Venous Thromboembolism).

5) Prophylaxis of pressure ulcers.

4. Convalescence (subsequent 2-6 weeks):

1) Once muscle spasms have resolved, start rehabilitation (physiotherapy and psychotherapy).

2) All patients should undergo active immunization with a full series of tetanus toxoid–containing vaccine during convalescence. Having acute tetanus does not confer immunity against subsequent episodes because of the extremely small quantities of toxin in disease pathogenesis.

ComplicationsTop

Bone fractures, aspiration pneumonia, pulmonary embolism, dehydration, respiratory failure, cardiac arrest, bacterial superinfections (including pneumonia and sepsis), rhabdomyolysis and myoglobinuria resulting in kidney failure, severe tetanus-related psychiatric sequelae (requiring psychotherapy).

PrognosisTop

In patients with mild and localized tetanus, the prognosis is good. Severe generalized tetanus and neonatal tetanus are associated with a poor prognosis.

Historically, mortality rates ranged from ~6% (mild and moderate tetanus) to 60% (severe tetanus) and may be as high as 90% in neonatal tetanus. Currently, the most frequent direct causes of death include autonomic instability and bacterial superinfections (pneumonia, sepsis).

Additional factors worsening the prognosis are incubation period <9 days, time from the onset of symptoms to the first generalized muscle spasm <48 hours, multiple bone fractures, and substance abuse.

The signs and symptoms persist for 4 to 6 weeks, whereas the increased muscle tone and periodic mild muscle spasms may occur for months.

PreventionTop

Specific Prevention

1. Vaccination is the key prevention method.

2. Postexposure prophylaxis: Vaccination, passive immunization (HTIG), or both (see Table 1 in Vaccines: Diphtheria and Tetanus; see Vaccines: Diphtheria and Tetanus).

Nonspecific Prevention

Cleaning wounds with soap and water, surgical debridement (removal of necrotic tissues, foreign bodies, purulent exudates).