Tetanus

Definition: It is a neurologic disorder, characterized by increased muscle tone and spasms, that is caused by tetanospasmin, a powerful protein toxin elaborated by Clostridium tetani toxin from wound contamination with spores.

C. tetani is an anaerobic, motile, gram-positive rod that forms an oval colorless terminal spore giving it the appearance of a drumstick.

Spores are resistant and survive for years in some environments, resistant to various disinfectants and to boiling water for 20 min.

Tetanospasmin is formed by vegetative cells under plasmid control. It is a zinc metalloproteinase. With autolysis, the single chain toxin is released and is cleaved to form a heterodimer consisting of a heavy chain (100 kDa), which mediates binding to and entry into nerve cells, and a light chain (50 kDa), which blocks neurotransmitter release.

Toxins released in the wound binds to peripheral motor neurons terminals, enters the axons, and is transported to the nerve-cell body in the brainstem and spinal cord by retrograde intraneuronal transport. The toxin then migrates across the synapse to presynaptic terminals, where it blocks the release of the inhibitory neurotransmitters glycine and GABA from vesicles. Tetanospasmin cleaves synaptobrevin, a protein essential to proper function of the synaptic release apparatus. With diminished inhibition, the resting firing rate of the alpha motor neuron increases, producing rigidity. With lessened activity of reflexes that limit polysynaptic spread of impulses (a glycinergic activity), agonists and antagonists are recruited than inhibited, with consequent production of spasms.

Forms: Generalized, neonatal, and localized disease.

Prevention:

Tetanus is best prevented by immunization. For high-risk wounds, human tetanus immunoglobulin, 250 units IM, is used.

Diagnosis:

Classical presentation is w/ muscle weakness and intensely painful rigidity, and spasms frequently precipitated by sensory stimuli, followed by autonomic dysfunction. Initial sx are in the face and neck muscles, such as masseter spasm (trismus). Delirium and high fever are usually absent. Diagnosis is clinical.

Tx:

Human tetanus immunoglobulin, 3000-5000 units IM.

Benzodiazepines or paralytics can be used to control spasms.

Surgical debridement is critical.

ABx, usually metronidazole 2 g/d IV or PO, are controversial. Care is otherwise supportive.