Tetanus

The Pathogen — Clostridium tetani

The Toxin — Tetanospasmin

• Plasmid-encoded protein neurotoxin (~150 kDa), cleaved by a bacterial protease into two peptides: a heavy chain (100 kDa) and a light chain (50 kDa), linked by a disulfide bond.
• Heat-labile, readily neutralized by antitoxin, destroyed by intestinal proteases.
• One of the most potent known microbial toxins — lethal in humans at ~2.5 ng/kg.
• Formaldehyde treatment converts it to a non-toxic toxoid that retains antigenicity (basis of vaccination).

Pathogenesis

Step 1 — Entry of Spores

Step 2 — Germination

1. Necrotic tissue
2. Calcium salts
3. Associated pyogenic (facultative or anaerobic) co-infections
4. Foreign bodies (splinters, soil)

Step 3 — Toxin Production and Transport

• Tetanospasmin is produced at the local wound site.
• The heavy chain binds to receptors on presynaptic membranes of lower motor neurons at the wound periphery.
• Toxin is taken up and transported retrogradely via axonal transport (at ~75–250 mm/day) in membrane-bound vesicles → travels up the motor neuron to its cell body in the anterior horn of the spinal cord and brainstem.

Step 4 — Mechanism of Action

• The light chain acts as a metalloproteinase that cleaves synaptobrevin (VAMP2) — a protein essential for docking of neurotransmitter vesicles on the presynaptic membrane.
• This blocks release of the inhibitory neurotransmitters glycine and GABA.
• Without inhibition → motor neurons fire unopposed → sustained, simultaneous contraction of agonist and antagonist muscles → spastic/spasmodic paralysis.

This is the opposite of botulism: tetanus causes spastic (rigid) paralysis by blocking inhibitory neurons; botulism causes flaccid paralysis by blocking excitatory (acetylcholine) release.

Step 5 — Autonomic Involvement

Clinical Features (Brief)

• Incubation: 4 days–3 weeks (mean 8 days); shorter incubation = more severe disease
• Trismus (lockjaw) — masseter spasm, the earliest sign in ~75% of cases
• Opisthotonos — arching spasm of paraspinal muscles

Opisthotonic posturing in generalized tetanus (Sherris & Ryan's Medical Microbiology, 8e)

• Generalized convulsions triggered by minor stimuli (sound, touch, light)
• Patient remains fully conscious throughout
• Death from respiratory failure — untreated mortality 15–60%

Short Notes on Botulism

Pathogen — Clostridium botulinum

The Toxin — Botulinum Toxin

• A heat-labile neurotoxin; the most potent biological toxin known.
• Like tetanospasmin, it is a metalloproteinase that cleaves synaptobrevin (VAMP2), blocking neurotransmitter vesicle docking.
• However, its target is peripheral cholinergic synapses (neuromuscular junctions) → blocks acetylcholine release → flaccid (descending) paralysis.
• Alkaline foods (green beans, mushrooms, fish) particularly support toxin production in improperly canned/heated foods.

Forms of Botulism

Pathogenesis

1. Preformed toxin is absorbed in the GI tract → enters bloodstream.
2. Toxin binds irreversibly to presynaptic terminals of peripheral motor neurons.
3. Blocks acetylcholine (ACh) release at the neuromuscular junction → flaccid paralysis.
4. Autonomic involvement → cardiac arrhythmias, blood pressure instability, dry mouth, constipation.
5. Recovery requires growth of new presynaptic axons and formation of new synapses (weeks–months).

Clinical Features

• Onset: 12–36 hours after ingestion
• Early: nausea, dry mouth, diarrhea
• Cranial nerve signs: blurred vision, diplopia, pupillary dilation, dysarthria, dysphagia
• Symmetric descending flaccid paralysis → respiratory muscles → complete respiratory paralysis
• Infant botulism: constipation, poor tone ("floppy baby"), lethargy, poor feeding — may mimic SIDS
• Patient remains afebrile and conscious

Diagnosis

• Toxin detection in serum, stool, or food by immunoassay (EIA) or nucleic acid amplification (NAA) — available only at reference laboratories.
• Culture of C. botulinum from stool or implicated food.

Treatment & Prevention

• Supportive care (mechanical ventilation) is the most critical intervention — with proper support, mortality <10%
• Equine botulinum antitoxin to neutralize free toxin (not for infants — hypersensitivity risk; use human-derived BabyBIG for infant botulism)
• Antibiotics only for wound botulism
• Prevention: adequate pressure cooking/autoclaving kills spores; heating food at 100°C for 10 min destroys preformed toxin; avoid damaged or bulging cans
• No vaccine available

Therapeutic use: Botulinum toxin (Botox) — injected locally for spasmodic neuromuscular conditions and cosmetic applications (wrinkle reduction).