Tetanus

Definition and Causative Organism

• Goldman-Cecil Medicine, p. 3059

Epidemiology

• C. tetani spores are found in up to 25% of soil samples, especially where animal manure has been applied; also found in the intestines of various animals and up to ~10% of humans
• Most common in warm, humid climates and highly cultivated rural areas of developing countries
• The WHO reported ~15,000 cases in 2018, with an estimated ~34,000 neonatal deaths annually from unreported cases
• In the United States, cases have fallen from 4/million (1940s) to <0.01/million (2010) due to vaccination
• Highest US risk: adults >65 years old and injection drug users (50% of US cases)
• Case fatality rate: ~18% overall, approaching 50% in patients over 70
• No deaths have been reported in fully vaccinated patients
• Rosen's Emergency Medicine, p. 2589

Pathophysiology

1. Binds peripheral nerve terminals at the neuromuscular junction
2. Is transported retrograde intra-axonally (~75-250 mm/day) within membrane-bound vesicles to spinal interneurons
3. The light chain crosses to presynaptic inhibitory interneuron terminals and blocks release of glycine and GABA - the inhibitory neurotransmitters
4. Loss of inhibitory tone produces sustained, unopposed muscle contraction
5. Toxin binding is irreversible - recovery depends on growth of new axon terminals

• Goldman-Cecil Medicine, p. 3059

Clinical Manifestations

Forms of Tetanus

Progression of Generalized Tetanus

• Early: trismus (initial complaint in ~75% of cases), often leading patients to dentists; irritability, restlessness, dysphagia, diaphoresis
• Risus sardonicus: tonic spasm of facial muscles creating a grimacing expression
• Opisthotonus: arching of the whole body from paraspinous and extensor muscle spasm
• Laryngeal spasm: leads to apnoea and potentially fatal asphyxia
• Autonomic dysfunction: labile blood pressure, cardiac arrhythmias, hyperthermia, profuse diaphoresis, urinary retention, rhabdomyolysis
• Key feature: patients typically remain lucid and afebrile unless there is a complicating infection
• Any sensory stimulus (noise, touch) can precipitate spasms
• Goldman-Cecil Medicine, p. 3059-3060

Diagnosis

• Wound cultures are positive in only one-third of cases
• CSF analysis is completely normal
• Spatula test: touching the oropharynx with a tongue blade - in tetanus, reflex masseter spasm causes the patient to bite the spatula (positive result); sensitivity 94%, specificity 100%
• Serum calcium to exclude hypocalcemia
• Strychnine levels in blood/urine (the main mimic)
• CT head and EMG may help in localized or cephalic forms

Differential Diagnosis (Box 118.5)

• Rosen's Emergency Medicine, p. 2591-2592

Treatment

1. Supportive Care (Spasm Control)

• ICU environment - minimize sensory stimulation (dark, quiet room)
• Benzodiazepines (GABA agonists) are the mainstay:
  • Diazepam IV (in 5 mg increments); lorazepam and midazolam are equally effective
  • Taper over ≥2 weeks to prevent withdrawal
• Magnesium sulfate infusion: effective first-line therapy for mild-to-moderate disease; controls spasms and muscle rigidity
• Dantrolene: adjunctive direct muscle relaxant
• If spasms cannot be controlled: neuromuscular blockade + mechanical ventilation
  • Avoid succinylcholine (risk of severe hyperkalemia after day 4 of disease)
  • Preferred: non-depolarizing agents (vecuronium, rocuronium)
• Early tracheostomy should be considered in all intubated patients to reduce reflex spasms

2. Autonomic Instability

• Labetalol (combined alpha + beta blockade) for sympathetic hyperactivity - 0.25 to 1.0 mg/min
• Avoid beta-blockers alone (risk of unopposed alpha-activity and severe hypertension)
• Morphine, magnesium sulfate, clonidine, intrathecal baclofen as adjuncts
• Bradycardia may require temporary pacing

3. Neutralize Circulating Toxin

• Human tetanus immunoglobulin (HTIG): single dose of 500 IU IM as soon as possible
  • Only neutralizes unbound toxin (toxin already in neurons cannot be neutralized)
  • In full-blown disease: 3,000-10,000 U ATG
• Pooled IVIG is an alternative
• Avoid wound manipulation for 2-3 hours after antitoxin administration to minimize toxin release

4. Eliminate Toxin Source

• Surgical wound debridement to remove devitalized tissue and eliminate anaerobic environment
• Antibiotics: metronidazole 2 g/day IV for 7-10 days (preferred); alternatives include penicillin G 10-24 million U/day IV for 10-14 days
• Delayed primary or secondary wound closure

5. Active Immunization

• Give tetanus toxoid at a separate site from immunoglobulin
• Full 3-dose primary series required (prior infection does NOT confer immunity - toxin dose is subimmunogenic)
• Goldman-Cecil Medicine, p. 3060; Rosen's Emergency Medicine, p. 2592-2593; Bailey & Love's Surgery, p. 476-477

Prevention and Prophylaxis

• Protective serum antitoxin levels persist for ≥10 years after primary series
• Td booster every 10 years for adults
• All adults aged 19+ who have never received Tdap should receive a single dose (adds pertussis coverage)
• For children <7 years: DTaP; if pertussis contraindicated: DT
• Goldman-Cecil Medicine, p. 3060

Prognosis

• Overall mortality ~45% in full-blown disease (varies by access to intensive care)
• Shorter incubation period and shorter time from first symptom to first spasm = worse prognosis
• With modern ICU care, older patients may do as well as middle-aged patients
• Long-term physical complications in survivors are rare; psychological trauma is the most common persistent problem
• Recent evidence: a 2025 systematic review and meta-analysis (PMID 39814168) confirmed that unvaccinated status is the primary risk factor for fatal tetanus, reinforcing current vaccination guidelines.
• Bailey & Love's Surgery, p. 477; Rosen's Emergency Medicine, p. 2589