What is the pathology behind tetanus?

Pathophysiology of Tetanus

Tetanus is caused by tetanospasmin, a powerful neurotoxin produced by Clostridium tetani that irreversibly binds to neural tissue and blocks the release of inhibitory neurotransmitters (GABA), resulting in unopposed muscle rigidity and tonic spasms. 1

The Causative Organism and Entry

Clostridium tetani is a ubiquitous, spore-forming, motile Gram-positive anaerobic bacillus found in high concentrations in soil and animal excrement. 2 The spores enter the body through breaches in the skin or mucous membranes, typically from contaminated wounds, puncture injuries, burns, or blunt trauma. 2, 1

Critical point: Direct person-to-person transmission does not occur—tetanus is purely a toxin-mediated disease following environmental exposure. 2

Spore Germination and Toxin Production

• Germination of C. tetani spores occurs only under anaerobic conditions, such as in necrotic tissue resulting from deep puncture wounds or blunt trauma. 1, 3
• Once germinated, the bacilli vegetate locally in the wound and produce tetanospasmin, the exotoxin responsible for all clinical manifestations. 2, 1
• The bacteria themselves do not invade tissues or disseminate systemically—the pathology is entirely toxin-mediated. 4

Mechanism of Tetanospasmin

The key pathophysiologic mechanism is that tetanospasmin prevents the release of inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the spinal cord, brainstem motor nuclei, and the brain. 1 This results in:

• Unopposed excitatory signals to skeletal muscles, producing muscle rigidity and tonic spasms 1, 5
• Loss of normal inhibitory control over motor neurons 1
• Characteristic clinical features including trismus (lockjaw), generalized muscle rigidity, and reflex spasms 5, 3

Irreversible Binding: The Critical Therapeutic Implication

Tetanospasmin binds irreversibly to neural tissue, which is the fundamental pathophysiologic feature that dictates treatment strategy. 2, 1 This means:

• Treatment focuses on neutralizing circulating toxin before it binds to neurons, not reversing already-bound toxin 1
• Once bound, the toxin cannot be removed—recovery requires regeneration of new nerve terminals 4
• This explains why tetanus immune globulin (TIG) must be given early to neutralize free toxin in circulation 4

Temporal Progression and Severity Determinants

• Incubation period varies from 3 to 21 days (median: 7 days), with extremes of 1 day to several months. 2, 1
• Shorter incubation periods are associated with more severe disease and poorer prognosis, as they indicate wounds closer to the central nervous system with more rapid toxin transport. 2, 6
• Longer incubation periods are associated with injuries furthest from the central nervous system. 2, 6

Clinical Progression and Complications

The disease course is typically intense for ≥4 weeks before subsiding, with a protracted convalescent period. 2, 6 Major complications arise from:

• Laryngeal spasm leading to airway obstruction and respiratory arrest 3
• Dysautonomia from sympathetic nervous system overactivity, requiring alpha and beta blockade 5
• Respiratory failure from chest wall rigidity and spasms 5, 3
• Long-term neurologic sequelae and intellectual/behavioral abnormalities may follow recovery 2, 6

Mortality and Prognosis

• The case-fatality ratio can be as high as 100% without high-quality medical care 2, 1
• Even in modern healthcare facilities, mortality remains approximately 10-20% 2, 1
• Mortality is highest in infants and the elderly 2, 6
• In the United States, the case-fatality ratio declined from 18% (1998-2000) to 8.0% (2001-2016) 6

Common Pitfall

Tetanus does not confer natural immunity—patients who survive must still complete a full primary immunization series after recovery, as the amount of toxin causing disease is insufficient to generate protective antibody levels. 6