Excerpt from Tetanus

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Background

Tetanus is an infectious disorder characterized by increased muscle tone and spasms caused by the release of the neurotoxin tetanospasmin by Clostridium tetani following inoculation into a human host. Tetanus occurs in several clinical forms, including generalized, cephalic, localized, and neonatal disease.

Pathophysiology

Most cases of tetanus are caused by direct contamination of wounds with clostridial spores. Wounds with low oxidation-reduction potential, such as those with dead or devitalized tissue, a foreign body, or active infection, are ideal for germination of the spores and release of toxin. Infection by C tetani results in a benign appearance at the portal of entry because of its inability to evoke an inflammatory reaction (unless co-infection with other organisms develops).

Tetanospasmin, a zinc metalloprotease, is released in the wound and binds to the peripheral motor neuron terminal, enters the axon, and, via retrograde intraneuronal transport, reaches the nerve cell body in the brainstem and spinal cord. The toxin migrates across the synapse to presynaptic terminals where it blocks the release of the inhibitory neurotransmitters glycine and gamma-aminobutyric acid (GABA) by cleaving proteins crucial for the proper functioning of the synaptic vesicle release apparatus. One of these important proteins is synaptobrevin. This diminished inhibition results in an increase in the resting firing rate of the motor neuron, which is responsible for the observed muscle rigidity.

The lessened activity of reflexes limits the polysynaptic spread of impulses (a glycinergic activity). Agonists and antagonists may be recruited rather than inhibited, with consequent production of spasms. Loss of inhibition may also affect preganglionic sympathetic neurons in the lateral gray matter of the spinal cord and produce sympathetic hyperactivity and high levels of circulating catecholamines. Finally, tetanospasmin can block neurotransmitter release at the neuromuscular junction, causing weakness and paralysis.

Localized tetanus develops when only the nerves supplying the affected muscle are involved. Generalized tetanus develops when the toxin released at the wound spreads through the lymphatics and blood to multiple nerve terminals. The blood-brain barrier prevents direct entry of toxin to the CNS.

Frequency

United States

Neonatal tetanus is rare. Tetanus affects nonimmunized persons, partially immunized persons, or fully immunized individuals who do not maintain adequate immunity with periodic booster doses. The risk for development of tetanus and for the most severe form of the disease is highest in the elderly population. Most cases follow an acute injury, such as a puncture wound, a laceration, or an abrasion.

Tetanus can be acquired outdoors as well as indoors. The injury is usually trivial, and, often, no initial medical treatment is sought. Tetanus can also develop as a complication of some chronic conditions, such as decubitus ulcers, abscesses, and gangrene. Finally, it may complicate burns, frostbite, middle ear infections, surgery, abortion, childbirth, and intravenous or subcutaneous drug use. Fewer than 50 cases of tetanus per year have been recorded since 1995. The infection has not been transmitted from person to person.

International

C tetani is found worldwide in soil, on inanimate objects, in animal feces, and, occasionally, in human feces. The disease is common in areas where soil is cultivated, in rural areas, in warm climates, during summer months, and among males. In countries without a comprehensive immunization program, tetanus predominantly develops in neonates and young children.¹

Mortality/Morbidity

A rating scale for the severity and the prognosis of tetanus is described below.²

• Score one point for each of the following:
• • Incubation period less than 7 days
  • Period of onset less than 48 hours
  • Acquired from burns, surgical wounds, compound fractures, septic abortion, umbilical stump, or intramuscular injection
  • Narcotic addiction
  • Generalized tetanus
  • Temperature greater than 104°F (40°C)
  • Tachycardia greater than 120 beats per minute (>150 beats per minute in neonates)
• Total score indicates the severity and the prognosis as follows:
• • Score of 0-1 indicates mild severity with less than a 10% mortality rate.
  • Score of 2-3 indicates moderate severity with a 10-20% mortality rate.
  • Score of 4 indicates severe tetanus with a 20-40% mortality rate.
  • Score of 5-6 indicates very severe tetanus with greater than a 50% mortality rate.
  • Cephalic tetanus is always severe or very severe.
  • Neonatal tetanus is always very severe.

Race

No particular racial predilection has been reported.

Sex

No sex predilection has been reported, except to the extent that males may have more soil exposure in some cultures.

Age

Neonatal tetanus is most common in countries without comprehensive vaccination programs. Otherwise, most severe disease develops in elderly people. Age predilection is mostly governed by soil exposure patterns.

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