Tetanus

Etiology

• Clostridium tetani Clostridium tetani are anaerobic, Gram-positive, spore-forming rods, ubiquitous in nature, and spores can survive for years in the environment.
• The germination of spores of C. tetani produces tetanospasmin, the causative agent of tetanus.

Predisposing factors

General

• Clostridium tetani is ubiquitous and proliferates in anaerobic environments, such as necrotic tissue of penetrating wounds, the umbilicus of neonates, or the uterus during dystocia. In such anaerobic environments, the vegetative growth of the spores of C. tetani, ie spore germination, produces tetanospasmin.
• Tetanus can also be observed as a complication of foreign bodies, broken dentition, postoperatively, or after parturition.

Specific

• Wounds in parts of the body that are in contact with soil are more likely to become contaminated and be the route of entry for the spores of the organism.
• Parturition in dirty environments may facilitate infection of the umbilical cord and neonatal tetanus. However, difficult deliveries as a cause of tetanus in females are extremely unlikely in the rabbit.
• Deep wounds are more likely to create anaerobic conditions.

Pathophysiology

• Tetanus develops when spores are introduced into wounds or penetrating injuries. Such spores have vegetated or will vegetate in response to the anaerobic conditions present in the site of injury (abscess, necrosis, deep wound, etc).
• Tetanospasmin enters the body from the wound and reaches peripheral nerves via endocytosis; then (in generalized cases) travels to the spinal cord, where it blocks neurotransmission in inhibitory neurons, leading to clinical signs of muscle spasms and rigidity. From the spinal cord, it can reach the brain.
• If tetanospasmin enters the blood stream directly, it can spread hematogenously and enter the central nervous system. In fact, systemic intravenous administration usually results in intracranial signs (convulsions, respiratory arrest) before development of generalized limb rigidity. Tetanospasmin can cross the blood-CNS barrier. Blood can also carry the toxin to other peripheral neurons, from where the same pattern of ascension to spinal cord/brain is seen.
• The toxin is destroyed by gastric juices and does not enter the placenta.
• Tetanospasmin inhibits the release of GABA-neurotransmitters in inhibitory interneurons of the brain and spinal cord. The binding of tetanus toxin to presynaptic sites of these inhibitory neurons is irreversible; recovery depends on sprouting of new axon terminals.
• There are four recognized presentations of tetanus:
  • Localized tetanus, with clinical signs limited to the site of infection.
  • Generalized tetanus characterized by extreme, diffuse muscle rigidity.
  • Neonatal tetanus from umbilical cord infections.
  • Cephalic tetanus associated with otitis media.
• The site and route of administration of toxin are important in determining the type of disease that develops.
• Localized tetanus is more common in resistant species, eg dog/cat, where the toxin has more problems spreading through the body and into the CNS.

Timecourse

• Not properly reported in rabbits, but incubation period in other mammal species varies from one day to more than a month, and depends on level of immunity, size of inoculum, and location and nature of the primary wound.
• As a general rule, clinical signs usually occur a few days after receiving a wound. Incubation period is shorter when the wound is close to the CNS, has numerous organisms, and has a more anaerobic environment.

Epidemiology

• Unknown, as natural infection with tetanus in rabbits is not well studied despite the fact that rabbits have been used for more than 100 years as a laboratory model of tetanus infection.