tetanospasmin

Tetanospasmin, also known as tetanus toxin, is an extremely potent neurotoxin produced by the bacterium Clostridium tetani. It is a protein toxin released under anaerobic conditions, commonly from infected wounds, and is one of the most powerful toxins known.

The toxin is a two-chain protein composed of a heavy and a light chain. The heavy chain binds to neuronal membranes and facilitates retrograde transport to the central nervous system. The light chain is a zinc-dependent metalloprotease that cleaves SNARE proteins, such as synaptobrevin (VAMP), in inhibitory interneurons of the spinal cord and brainstem. This blocks the release of the inhibitory neurotransmitters gamma-aminobutyric acid (GABA) and glycine, leading to disinhibition and continuous motor neuron activation. The result is sustained muscle rigidity and painful spasms.

Clinically, tetanus has an incubation period of about 3 to 21 days. Early signs include trismus (lockjaw), jaw stiffness, and difficulty swallowing, followed by generalized muscle stiffness, spasms, and sometimes opisthotonus. Autonomic dysfunction can occur, with fluctuations in heart rate and blood pressure. Without treatment, tetanus can be life-threatening due to respiratory compromise and autonomic instability.

Diagnosis is clinical, supported by wound history. Management involves wound debridement, administration of tetanus immune globulin to neutralize circulating toxin, and antibiotics (metronidazole preferred) to eradicate the organism. Supportive care includes airway protection and control of spasms with benzodiazepines; magnesium sulfate may be used for autonomic instability. Vaccination with tetanus toxoid provides long-term protection; booster doses every 10 years are recommended, and post-exposure prophylaxis depends on vaccination status.