What is the pathophysiology of tetanus?

Pathophysiology of Tetanus

Tetanus pathophysiology involves environmental spore entry through wounds, germination in anaerobic conditions, production of the irreversibly-binding neurotoxin tetanospasmin, and blockade of inhibitory neurotransmitters causing characteristic muscle rigidity and spasms that can lead to respiratory failure and death. 1

Causative Organism and Environmental Entry

• Clostridium tetani is a ubiquitous, spore-forming, motile Gram-positive anaerobic bacillus found in high concentrations in soil and animal excrement 1
• The spores enter the body through breaches in the skin or mucous membranes, including puncture wounds, lacerations, abrasions, burns, surgical sites, and umbilical stumps in neonates 2, 1, 3
• Tetanus is unique among vaccine-preventable diseases because it is noncommunicable—it cannot spread person-to-person 2

Germination and Toxin Production

• Spore germination occurs only under anaerobic conditions, such as in necrotic tissue resulting from deep puncture wounds or blunt trauma with oxygen-poor environments 2, 1
• Once germinated, the vegetative bacilli multiply and elaborate tetanospasmin, a potent neurotoxin that is one of the most lethal biological toxins known 2, 1, 3
• The toxin is produced locally at the wound site and enters the general circulation 4

Neurotoxin Mechanism and Neural Binding

• Tetanospasmin binds to peripheral motor neurons and sensory neurons at neuromuscular junctions 4
• The toxin undergoes retrograde axonal transport to the spinal cord and brainstem motor nuclei 5, 4
• Once in the central nervous system, tetanospasmin enters inhibitory interneurons and irreversibly binds to neural tissue 1, 3
• The toxin acts as a metalloprotease that prevents the release of inhibitory neurotransmitters gamma-aminobutyric acid (GABA) and glycine in the spinal cord, brainstem, and brain 1, 4

Clinical Manifestations from Neurotransmitter Blockade

• Loss of inhibitory neurotransmission produces muscle rigidity and tonic spasms of skeletal muscles 2, 1
• Generalized tetanus typically presents with trismus (lockjaw) as the initial manifestation, followed by generalized rigidity caused by painful contractions of skeletal muscles 2, 6
• Progressive disease can impair respiratory function through respiratory muscle involvement 2
• Glottic spasm, respiratory failure, and autonomic instability (sympathetic nervous system overactivity) represent life-threatening complications that can result in death 2, 6

Temporal Course and Irreversibility

• The incubation period from injury to symptom onset varies from 3 to 21 days (median: 7 days), with extremes of 1 day to several months 1, 7
• Shorter incubation periods correlate with more severe disease and poorer prognosis because they indicate wounds closer to the central nervous system and higher toxin loads 1, 7
• The irreversible binding of tetanospasmin to neural tissue is the critical pathophysiologic feature explaining why treatment focuses on neutralizing circulating toxin before it binds, rather than reversing already-bound toxin 1, 3
• Recovery requires the generation of new nerve terminals and synapses, which explains the protracted disease course of ≥4 weeks and prolonged convalescent period 7

Mortality and Morbidity

• The case-fatality ratio ranges from 10-20% even in modern healthcare facilities with intensive care, and can approach 100% without high-quality medical care 1, 8
• Mortality is highest in infants and the elderly 7, 8
• Long-term neurologic sequelae and intellectual and behavioral abnormalities may follow recovery 7

Key Clinical Pitfall

• Tetanus does not confer natural immunity—patients who survive must complete a full primary immunization series after recovery because infection does not provide protective antibodies 7