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Tetanus



Muscular spasms in a patient suffering from tetanus. Painting by Sir Charles Bell, 1809.

Tetanus is a medical condition that is characterized by a prolonged contraction of skeletal muscle fibers. The primary symptoms are caused by tetanospasmin, a neurotoxin produced by the Gram-positive, obligate anaerobic bacterium Clostridium tetani. Infection generally occurs through wound contamination, and often involves a cut or deep puncture wound. As the infection progresses, muscle spasms in the jaw develop hence the common name, lockjaw. This is followed by difficulty in swallowing and general muscle stiffness and spasms in other parts of the body.

The clinical manifestations of tetanus are caused when tetanus toxin blocks inhibitory nerve impulses, by interfering with the release of neurotransmitters. This leads to unopposed muscle contraction and spasm. Seizures may occur, and the autonomic nervous system may also be affected.

Tetanus can be either mild or severe. The severe type requires admission to an intensive care.

Tetanus is a global health problem since C. tetani spores are ubiquitous. The disease occurs almost exclusively in persons who are unvaccinated or inadequately immunized. Tetanus occurs worldwide but is more common in hot, damp climates with soil rich in organic matter. This is particularly true with manure-treated soils, the spores are widely distributed in the intestines and feces of many non-human animals such as horses, sheep, cattle, dogs, cats, rats, guinea pigs, and chickens. In agricultural areas, a significant number of human adults may harbor the organism. The spores can also be found on skin surfaces and in contaminated heroin.

Tetanus is not contagious from person to person and is the only vaccine-preventable disease that is infectious but is not contagious.

Contents

Signs and Symptoms
Causative Agent
Mode of Transmission
Cause
Diagnosis
Incubation Period
Pathogenesis/Pathophysiology
Prevention
Treatment
Complications
Videos
References

Signs and Symptoms

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Tetanus often begins with mild spasms in the jaw muscles (lockjaw). The spasms can also affect the chest, neck, back, and abdominal muscles. Back muscle spasms often cause arching, called opisthotonos.

Sometimes the spasms affect muscles that help with breathing, which can lead to breathing problems.

Prolonged muscular action causes sudden, powerful, and painful contractions of muscle groups. This is called tetany. These episodes can cause fractures and muscle tears.

Other symptoms include:

  • Drooling
  • Excessive sweating
  • Irritability
  • Fever
  • Hand or foot spasms
  • Uncontrolled urination or defecation
  • Swallowing difficulty

Local tetanus is an uncommon form of the disease, in which patients have persistent contraction of muscles in the same anatomic area as the injury. The contractions may persist for many weeks before gradually subsiding. Local tetanus is generally milder; only about 1% of cases are fatal, but it may precede the onset of generalized tetanus.

Lock-jaw in a patient suffering from tetanus.

Cephalic tetanus is a rare form of the disease, occasionally occurring with otitis media (ear infections) in which C. tetani is present in the flora of the middle ear, or following injuries to the head. There is involvement of the cranial nerves, especially in the facial area.

Generalized tetanus is the most common type of tetanus, representing about 80% of cases. The generalized form usually presents with a descending pattern. The first sign is trismus or lockjaw, followed by stiffness of the neck, difficulty in swallowing, and rigidity of pectoral and calf muscles. Other symptoms include elevated temperature, sweating, elevated blood pressure, and episodic rapid heart rate. Spasms may occur frequently and last for several minutes. Spasms continue for 3–4 weeks and complete recovery may take months.

An infant suffering from neonatal tetanus.

Neonatal tetanus is a form of generalized tetanus that occurs in newborn infants. It occurs in infants who have not acquired passive immunity because the mother has never been immunized. It usually occurs through infection of the unhealed umbilical stump, particularly when the stump is cut with a non-sterile instrument. It has the characteristics similar to a Generalized tetanus.

Causative Agent

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Clostridium tetani

Mode of Transmission

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Tetanus is not directly transmitted from person to person.

Spores may be introduced through contaminated puncture wounds, lacerations, burns or contaminated injected ‘street drugs’. Tetanus can result from minor wounds considered too trivial for medical consultation.

The presence of necrotic tissue or foreign bodies encourages the growth of anaerobic organism such as C. tetani. Tetanus rarely follows surgical procedures today.

Cause

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Tetanus is often associated with rust, especially rusty nails, but this concept is somewhat misleading. Objects that accumulate rust are often found outdoors, or in places that harbor anaerobic bacteria, but the rust itself does not cause tetanus nor does it contain more C. tetani bacteria. The rough surface of rusty metal merely provides a prime habitat for a C. tetani endospore to reside, and the nail affords a means to puncture skin and deliver endospore into the wound. An endospore is a non-metabolizing survival structure that begins to metabolize and cause infection once in an adequate environment. Because C. tetani is an anaerobic bacterium, it and its endospores survive well in an environment that lacks oxygen. Hence, stepping on a nail (rusty or not) may result in a tetanus infection, as the low-oxygen (anaerobic) environment is provided by the same object which causes a puncture wound, delivering endospores to a suitable environment for growth.

Diagnosis

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There are no blood tests that can be used to diagnose tetanus. The diagnosis is based on the presentation of tetanus symptoms and does not depend upon isolation of the bacteria, which is recovered from the wound in only 30% of cases and can be isolated from patients who do not have tetanus. Laboratory identification of C. tetani can only be demonstrated by production of tetanospasmin in mice.

The “spatula test” is a clinical test for tetanus that involves touching the posterior pharyngeal wall with a sterile, soft-tipped instrument, and observing the effect. A positive test result is the involuntary contraction of the jaw (biting down on the “spatula”), and a negative test result would normally be a gag reflex attempting to expel the foreign object. A short report in The American Journal of Tropical Medicine and Hygiene states that in a patient research study, the spatula test had a high specificity (zero false-positive test results) and a high sensitivity (94% of infected patients produced a positive test result).

Incubation Period

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The time between infection and the first sign of symptoms is 5 days to 15 weeks, with 7 days as the average. Most cases of tetanus in the United States occur in those who have not been properly vaccinated against the disease.

Cases with shorter incubation periods tend to have more severe disease and thereby a greater risk of death.

Pathogenesis/Pathophysiology

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The organism is found in soil, animal feces and, occasionally, human feces.

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.

Prevention

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Tetanus can be prevented by vaccination. The CDC recommends that adults receive a booster vaccine every ten years, and standard care in many places is to give the booster to any patient with a puncture wound who is uncertain of when he or she was last vaccinated, or if the patient has had fewer than 3 lifetime doses of the vaccine. The booster cannot prevent a potentially fatal case of tetanus from the current wound, as it can take up to two weeks for tetanus antibodies to form. In children under the age of seven, the tetanus vaccine is often administered as a combined vaccine, DPT vaccine or DTaP, which also includes vaccines against diphtheria and pertussis. For adults and children over seven, the Td vaccine (tetanus and diphtheria) or Tdap (tetanus, diphtheria, and acellular pertussis) is commonly used.

Treatment

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The wound must be cleaned. Dead and infected tissue should be removed by surgical debridement. Metronidazole treatment decreases the number of bacteria but has no effect on the bacterial toxin. Penicillin was once used to treat tetanus, but is no longer the treatment of choice because of a theoretical risk of increased spasms. It should still be used if metronidazole is not available. Passive immunization with human anti-tetanospasmin immunoglobulin or tetanus immune globulin is crucial. If specific anti-tetanospasmin immunoglobulin is not available, then normal human immunoglobulin may be given instead. All tetanus victims should be vaccinated against the disease or offered a booster shot.

Mild tetanus

Mild cases of tetanus can be treated with:

  • Tetanus immune globulin IV or IM
  • Metronidazole IV for 10 days
  • Diazepam
  • Tetanus vaccination

Severe tetanus

Severe cases will require admission to intensive care. In addition to the measures listed above for mild tetanus:

  • Human tetanus immunoglobulin injected intrathecally (increases clinical improvement from 4% to 35%)
  • Tracheostomy and mechanical ventilation for 3 to 4 weeks.
  • Magnesium, as an intravenous (IV) infusion, to prevent muscle spasm.
  • Diazepam (known under the common name Valium) as a continuous IV infusion.
  • The autonomic effects of tetanus can be difficult to manage (alternating hyper- and hypotension, hyperpyrexia/hypothermia) and may require IV labetalol, magnesium, clonidine, or nifedipine.

Drugs such as chlorpromazine or diazepam, or other muscle relaxants can be given to control the muscle spasms. In extreme cases it may be necessary to chemically paralyze the patient with curare-like drugs and use a mechanical ventilator.

In order to survive a tetanus infection, the maintenance of an airway and proper nutrition are required. An intake of 3500-4000 Calories, and at least 150g of protein, is often given in liquid form through a tube directly into the stomach, or through a drip into a vein. This high-caloric diet maintenance is required due to the increased metabolic strain brought on by the increased muscle activity.

Complications

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  • Airway obstruction is common.
  • Urinary retention and constipation may develop because of sphincter spasm.
  • Respiratory failure and cardiac failure are late life-threatening events.
  • Fractures may result from sustained spasms.
  • Seizures can occur.
  • Pulmonary emboli may develop.
  • Bacterial superinfections are possible complications.
  • Dehydration can develop.

Videos

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A 70 yr. old woman suffering from generalized tetanus


References

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1. Wells CL, Wilkins TD (1996). “Clostridia: Sporeforming Anaerobic Bacilli”. in Baron S, et alublisher = Univ of Texas Medical Branch. Baron’s Medical Microbiology. ISBN 0-9631172-1-1.

2. “Tetanus” (PDF). CDC Pink Book. Retrieved 2007-01-26.

3. Nitin M. Apte and Dilip R. Karnad (1995-10). “Short Report: The Spatula Test: A Simple Bedside Test to Diagnose Tetanus”. Am. J. Trop. Med. Hyg.. pp. 386–387. Retrieved 2007-10-11.

4. “MedlinePlus, Tetanus”

5. “Wikipedia, Tetanus”

6. “Victorian Government Health Information, Tetanus”

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