Tetanustoxin

Tetanustoxin, more commonly known as tetanospasmin, is the principal neurotoxin produced by the bacterium Clostridium tetani. It is an AB-type metalloprotease toxin, with a heavy chain that binds to neuronal membranes and a light chain that acts as the catalytic subunit. The toxin is secreted as a complex and undergoes proteolytic processing to become active.

The toxin enters peripheral nerves at the site of infection and is transported retrogradely to the central nervous system. In inhibitory interneurons of the spinal cord and brainstem, tetanospasmin cleaves SNARE proteins involved in the release of inhibitory neurotransmitters, notably synaptobrevin (VAMP) and related components. This blocks the release of gamma-aminobutyric acid (GABA) and glycine, leading to disinhibition of motor neurons and resulting in sustained, painful muscular contractions.

Clinically, tetanospasmin exposure produces the characteristic manifestations of tetanus. After an incubation period of approximately 3 to 21 days, patients commonly develop trismus (lockjaw), risus sardonicus, neck and jaw stiffness, and generalized muscle rigidity with spasms. Autonomic disturbances may occur, and severe cases can progress to respiratory compromise or opisthotonos.

Diagnosis is typically clinical, supported by history of a wound with potential C. tetani exposure and lack of sufficient vaccination. Laboratory confirmation is rarely needed for management but may include wound culture or toxin detection in specialized settings.

Treatment centers on neutralizing unbound toxin, controlling spasms, and addressing the wound. Wound debridement, antibiotics such as metronidazole, and tetanus immune globulin are standard. Sedation or paralysis with benzodiazepines, airway support, and careful management of autonomic instability are important components. Prevention through vaccination (DTaP/Tdap) and prompt wound care is highly effective in reducing disease incidence.