Tetanus¶

Chapter 157 | Part 5: Infectious Diseases · Part 5 – Infectious Diseases: Bacterial · Chapter 157

Key Clinical Points¶

Diagnosis is primarily clinical; a positive culture of C. tetani from wounds does not confirm the diagnosis.
Tetanus toxin blocks inhibitory interneurons (GABAergic) by cleaving vesicle-associated membrane protein 2 (VAMP2), leading to unregulated motor and autonomic activity.
Human tetanus immunoglobulin (HTIG) is preferred over equine antitoxin due to a lower risk of anaphylactoid reactions.
Metronidazole is the preferred antibiotic; penicillin is an alternative but may potentially exacerbate spasms.
The Tetanus Severity Score (TSS) with a cutoff point ≥ 8 predicts death with 66% sensitivity and 91% specificity.
Autonomic nervous system disturbance (ANSD) typically occurs during the second week of severe tetanus and is a major cause of death.
Rapid development of symptoms (short incubation and onset periods) correlates with more severe disease and poorer prognosis.
Neonatal tetanus prevention relies on maternal vaccination and hygienic umbilical-cord care.
Laryngeal spasm is a life-threatening event that can lead to respiratory failure or apnea; it is the most common cause of death in untreated cases.

1. DEFINITION & OVERVIEW¶

• General Definition: A preventable disease characterized by skeletal muscle spasms and autonomic nervous system disturbance caused by a neurotoxin produced by the bacterium Clostridium tetani. • Probable Tetanus (CDC): In the absence of a more likely diagnosis, an acute illness with muscle spasms or hypertonia, and diagnosis of tetanus by a health care provider. • Neonatal Tetanus (WHO): An illness occurring in a child who has the normal ability to suck and cry in the first 2 days of life but who loses this ability between days 3 and 28 of life and becomes rigid and has spasms. • Maternal Tetanus (WHO): Tetanus during pregnancy or within 6 weeks after the end of pregnancy (whether with birth, miscarriage, or abortion).

2. EPIDEMIOLOGY¶

• Trends: Incidence has decreased over several decades due to increased vaccine coverage; the disease is rare in developed countries. • U.S. Data (2022): 28 cases reported. • Risk Factors: ◦ Lack of vaccination or missed booster shots every 10 years. ◦ Association with diabetes and intravenous drug use. • Demographics (U.S. 2009–2017): ◦ 64% occurred in individuals aged 20–64; only 13% occurred in those under 20. ◦ 3 cases of neonatal tetanus were reported. • Global Impact: ◦ Significant reduction in neonatal tetanus due to WHO, UNICEF, and UNFPA programs. ◦ Approximately 25,000 neonates died from tetanus in 2018. ◦ Estimated 30,000–62,000 deaths annually in older children and adults. ◦ Total annual global deaths: ~50,000.

3. ETIOLOGY & PATHOPHYSIOLOGY¶

• C. tetani Characteristics: ◦ Anaerobic, gram-positive, spore-forming rod. ◦ Spores are highly resilient, resisting boiling and many disinfectants; common in soil/environment. ◦ Fecal carriage is common in various animals. • Entry & Infection: ◦ Entry via abrasions, wounds, or the umbilical stump (neonates). ◦ 20–30% of cases have unclear entry wounds. ◦ Common sites: Superficial limb abrasions; high-risk sites: deep injuries, open fractures, drug injections. ◦ Neonatal risk factors: Unhygienic umbilical cutting, circumcision, or ear-piercing. • Toxin Mechanism: ◦ Only C. tetani producing tetanus toxin causes disease. ◦ Toxin is a 150-kDa protein → cleaved into heavy (100-kDa) and light (50-kDa) chains linked by a disulfide bond. ◦ Heavy chain binds to presynaptic α-motor nerve terminals (polysialogangliosides/membrane proteins). ◦ Toxin undergoes retrograde transport to the CNS. ◦ Light chain (zinc-dependent endopeptidase) cleaves VAMP2 (synaptobrevin) in GABAergic presynaptic inhibitory interneurons. ◦ Result: Blocked neurotransmitter release → inhibited inhibitory interneuron discharge → unregulated motor and autonomic activity. • Clinical Consequences: ◦ Muscle spasms and autonomic system disturbance. ◦ Increased circulating catecholamines in severe cases lead to cardiovascular complications.

4. CLINICAL FEATURES¶

• Classification of Forms: ◦ Localized: Isolated areas affected; may progress to generalized. ◦ Cephalic: Cranial nerve involvement; pharyngeal/laryngeal muscles spasm → risk of aspiration, respiratory failure, or airway obstruction. ◦ Generalized: Most common; characterized by muscle rigidity and generalized spasms. ◦ Neonatal: Inability to suck, poor feeding, and generalized spasms. • Progression of Symptoms: ◦ Initial: Trismus (lockjaw) → neck/body muscle rigidity → difficulty swallowing → pharyngeal/laryngeal spasms. ◦ Advanced: Generalized painful muscle spasms. ◦ Life-threatening: Laryngeal spasm can cause respiratory failure or apnea; primary cause of death without immediate support. • Autonomic Nervous System Disturbance (ANSD): ◦ Timing: Typically occurs during the second week of severe tetanus. ◦ Symptoms: Fluctuating heart rate (tachycardia/bradycardia) and blood pressure (hypertension/hypotension). ◦ Indicators: Gastrointestinal stasis, sweating, and increased tracheal secretions.

Ablett Classification of Severity¶

• Grade I (Mild): Mild trismus, general spasticity, no respiratory compromise, no spasms, no dysphagia. • Grade II (Moderate): Moderate trismus, rigidity, short spasms, mild dysphagia, moderate respiratory involvement, respiratory rate >30 breaths/min. • Grade III (Severe): Severe trismus, generalized rigidity, prolonged spasms, severe dysphagia, apneic spells, pulse >120 beats/min, respiratory rate >40 breaths/min. • Grade IV (Very severe): Grade 3 with autonomic dysfunction.

5. DIFFERENTIAL DIAGNOSIS¶

• General Mimics: ◦ Strychnine poisoning. ◦ Dystonic reactions to antidopaminergic drugs. ◦ Somatic symptom disorder. ◦ Stiff person syndrome. ◦ Neuroleptic malignant syndrome. • Specific Distinctions: ◦ Abdominal muscle rigidity: Continuous in tetanus (distinguish from peritonitis/acute abdominal emergency). ◦ Cephalic tetanus vs. Trismus: Pharyngeal involvement makes intubation difficult. • Neonatal Tetanus Differentials: ◦ Hypocalcemia. ◦ Meningoencephalitis. ◦ Oropharyngeal infection, cranial nerve diseases, intracranial hemorrhage, submaxillary lymphadenitis, or peritonsillar infections.

6. INVESTIGATIONS & DIAGNOSIS¶

Clinical Assessment: Primary method of diagnosis based on physical findings.
Laboratory Confirmation (Limited): ◦ Culture: Positive culture of C. tetani from wounds eq confirmation of tetanus. ◦ Serum IgG: Measure before antitoxin administration. → Level >0.1 IU/mL = protective; does not support diagnosis. → Level <0.1 IU/mL may suggest tetanus, but a negative result for toxin bioassay does not exclude the diagnosis.
Molecular Detection: ◦ PCR and recombinase polymerase amplification can detect the tetanus neurotoxin gene (promising but not standard).

7. MANAGEMENT & TREATMENT¶

Wound Management: ◦ Identify, clean, and debride wound of necrotic material to remove anaerobic foci. ◦ Timing: Perform several hours after anti-toxin administration.
Antibiotic Therapy: ◦ Preferred: Metronidazole (400 mg rectally or 500 mg IV every 6 h for 7 days). ◦ Alternative: Penicillin (100,000–200,000 IU/kg per day) → Note: may exacerbate spasms due to GABA receptor binding.
Antitoxin Administration: ◦ Goal: Neutralize unbound toxin and prevent uptake into the nervous system. ◦ Choice: Human tetanus immunoglobulin (HTIG) preferred over equine antitoxin (lower risk of anaphylactoid reactions). ◦ HTIG Dose: Single IM dose (500–5000 IU). ◦ Equine Antitoxin: Used in low/middle-income countries; 10,000–20,000 U IM after hypersensitivity testing. ◦ Note: Intrathecal HTIG shows no benefit.
Symptom Control (Spasms): ◦ Benzodiazepines: High doses tolerated; Midazolam preferred for continuous use due to fewer side effects. ◦ Propofol: Used for sedation/spasm control (note long duration of therapy). ◦ Caution: Reduce sedatives in elderly or liver disease patients. ◦ Neuromuscular Blockers: Use when sedatives alone fail; requires mechanical ventilation. ◦ Magnesium Sulfate: Used as muscle relaxant.
Autonomic Management: ◦ Magnesium Sulfate: For high blood pressure and tachycardia (target 2–4 mmol/L). ◦ Tachycardia (if Mg fails): Short-acting beta-blockers (labetalol, propranolol, esmolol) or calcium antagonists. ◦ Bradycardia/Low BP: Vasopressors required.
Airway Management: ◦ Establish secure airway early in severe cases. ◦ Tracheostomy preferred over intubation due to pharyngeal/laryngeal muscle hyperactivity.
Environment: ◦ Calm, quiet environment; light and noise trigger spasms.

8. PROGNOSIS & COMPLICATIONS¶

• Prognostic Factors: ◦ Speed of progression: Rapid development → more severe disease. ◦ Incubation Period (wound to first symptom): Shorter period → worse prognosis. ◦ Period of Onset (first symptom to first generalized/pharyngeal spasm): Shorter period → worse prognosis. • Tetanus Severity Score (TSS): → Superior to Dakar and Philip scores. → Sensitivity 66%, Specificity 91%. → Cutoff Point: ≥ 8 predicts death. → Score Components: ◦ Age: ≤70 (0); 71–80 (5); >80 (10). ◦ Difficulty breathing on admission: No (0); Yes (4). ◦ Entry sites: Internal or injection (7); Other/unknown (0). ◦ Heart Rate (first day): ≤100 (0); 101–110 (1); 111–120 (2); >120 (4). ◦ Temperature (first day): ≤38.5 (0); 38.6–39 (4); 39.1–40 (6); >40 (8). • Long-term Sequelae: ◦ Adults/Elderly: Reduced functional outcomes. ◦ Children/Neonates: Higher risk of learning disabilities, behavioral problems, cerebral palsy, and deafness. ◦ Hospital-acquired infections (VAP, BSI, UTI), DVT, and pressure sores from prolonged sedation.

9. SPECIAL POPULATIONS¶

• Neonatal Prevention: ◦ Maternal vaccination and hygiene of umbilical-cord care. • Vaccination Schedules: ◦ CDC: 5 doses (0, 4, 6, 15–18 months, 4–6 years) + boosters at 11–12 years and every 10 years thereafter. ◦ WHO: 3 doses (starting at 6 weeks, interval 4 weeks); first booster 12–23 months; subsequent boosters at 4–7 and 9–15 years. • Post-infection Immunity: ◦ Tetanus toxin is poorly immunogenic; post-infection immunity is inadequate.

KEY PEARLS & HIGH-YIELD POINTS¶

• Diagnosis: Clinical; culture eq confirmation. • Toxin Mechanism: Cleavage of VAMP2 → block GABA release → muscle spasms. • Antitoxin: HTIG preferred over equine. • Antibiotics: Metronidazole is first-line; Penicillin may worsen spasms. • Prognosis: Short incubation/onset periods and TSS ≥ 8 indicate poor prognosis. • Neonatal Risk: High risk of long-term neurodevelopmental issues.

Reference Tables¶

TABLE 157-1 Ablett Classification of Severity of Tetanus GRADE I II¶

Harrison's 22e, p.1231

GRADE	SEVERITY	SYMPTOMS
I	Mild	Mild trismus, general spasticity, no respiratory compromise, no spasms, no dysphagia
	Moderate
III	Severe	Severe trismus, generalized rigidity, prolonged spasms, severe dysphagia, apneic spells, pulse >120 beats/min, respiratory rate >40 breaths/min
	Very severe

TABLE 157-2 Tetanus Severity Score (TSS) (Sensitivity 66%, Specificity 91%), Cutoff Point to Predict Death ≥8 VARIABLES…¶

Harrison's 22e, p.1232

VARIABLES	SCORE
Age (year) ≤70 71–80 >80	0 5 10
Difficulty breathing on admission No Yes	0 4
Entry sites Internal or injection Other (including unknown)	7 0
Highest heart rate recorded during first day in hospital (beats/min) ≤100 101–110 111–120 >120	0 1 2 4
Highest temperature recorded during first day in hospital (oC) ≤38.5 38.6–39 39.1–40 >40	0 4 6 8