Lockjaw Tetanus

Tetanus is frequently fatal; fortunately, it is rare in economically advanced countries. There is no reasonable way to avoid exposure to the causative organism because its spores are widespread in dust and dirt, frequently contaminating clothing, skin, and wounds. Even a trivial wound in a non-immunized person can result in tetanus if the wound provides conditions sufficiently anaerobic to allow germination of the spores.

Symptoms

Tetanus is characterized by sustained, painful, and uncontrollable cramplike muscle spasms, which are usually generalized but can be limited to one area of the body (figure 27.7). The spasms often begin with the jaw muscles, giving the disease the popular name

Nester-Anderson-Roberts: I IV. Infectious Diseases I 27. Wound Infections I © The McGraw-Hill

Microbiology, A Human Companies, 2003

Perspective, Fourth Edition

Animals That Have Lockjaw
Figure 27.7 Marked Muscular Spasm of the Wrist and Hand of an Individual with Tetanus In most tetanus cases, the spasms are generalized, meaning they involve all the body's muscles.

"lockjaw." The early symptoms include restlessness, irritability, difficulty swallowing, contraction of the muscles of the jaw, and sometimes convulsions, particularly in children. As more muscles tense, the pain grows more severe and is similar to that of a severe leg cramp. Breathing becomes labored, and after a period of almost unbearable pain, the infected person often dies of pneumonia or from stomach contents regurgitated into the lung.

Causative Agent

The causative agent, Clostridium tetani, an anaerobic, spore-forming Gram-positive rod-shaped bacterium (figure 27.8), shows two striking features: (1) a spherical endospore that forms at the end of the bacillus, in contrast to the oval endospore that develops near the center of the rod in other pathogenic species of Clostridium, and (2) swarming growth that quickly spreads over the surface of solid media, making it easy to obtain pure cultures. Final identification of C. tetani depends on identifying its toxin,

'imAi m

i Ti rkyi

Spores

27.3 Diseases Due to Anaerobic Bacterial Wound Infections 699

which is coded by a plasmid. ■ bacterial toxins, pp. 472,475 ■ Clostridium, p. 275 ■ plasmids, pp. 66,209 ■ C. botulinum spores, figure 26.12, p. 673

Isolation of C. tetani from wounds does not prove that a person has tetanus. The reasons are that tetanus endospores may contaminate wounds that are not sufficiently anaerobic to allow germination and toxin production, or the person may simply be immune to the toxin by prior vaccination. Only vegetative cells, not endospores, synthesize toxin. Conversely, failure to find the organism in a person's wound cultures does not eliminate the possibility of tetanus.

Pathogenesis

Clostridium tetani is not invasive, and colonization is generally localized to a wound. Its pathologic effects are entirely the result of a 150,000 molecular weight exotoxin called tetanospasmin, released from the organism during the stationary phase of growth. The toxin is composed of two chains joined by a disulfide bond. The heavier chain attaches specifically to receptors on motor neurons, which then take up the toxic, lighter chain by endocytosis. The toxin is carried by the cytoplasm of the neuron's axon to its cell body in the spinal cord. There, the motor neuron is in contact with other neurons that control its action. Some of these other neurons cause stimulation of the motor nerve cell, thereby producing a muscle contraction, and some make the motor neuron resistant to stimulation, thereby inhibiting muscle contraction. Tetanospasmin blocks the action of the inhibitory neurons, so that the muscles continuously contract (figure 27.9). The toxin generally spreads across the spinal cord to the side opposite the wound and then downward. Thus, typically, spastic muscles first appear on the side of the wound, then on the opposite

NORMAL (Flexion)

NORMAL (Extension)

Motor neuron inhibited; this muscle relaxes

Motor neuron stimulated; this muscle contracts

Motor neuron inhibited; this muscle relaxes

There is no inhibition; both muscles contract

There is no inhibition; both muscles contract

5 mm

Figure 27.8 Clostridium tetani Terminal endospores are characteristic of this species.

Figure 27.9 Tetanus The exotoxin tetanospasmin blocks the action of inhibitory neurons, allowing all muscles to contract at the same time.

700 Chapter 27 Wound Infections side, and then downward, depending on the amount of toxin. Tetanospasmin released from the infected wound often enters the bloodstream, which carries it to the central nervous system. In these cases, inhibitory neurons of the brain are first affected, and the muscles of the jaw are among the first to become spastic.

Neurons exert their effect on other nerve cells by releasing chemicals called neurotransmitters. Tetanospasmin prevents the release of neurotransmitters from inhibitory neurons. Like other neurotransmitters, glycine and its main counterpart in the brain, y-aminobutyric acid, exist in the inhibitory neurons in tiny membrane-bound sacs called vesicles. In order for the neuro-transmitters to be released to another neuron, the vesicles must first attach specifically to receptors on their cell's membrane to initiate the process of exocytosis. Tetanospasmin is a peptidase, and it acts by removing from the vesicles the ligand responsible for attachment to the cell membrane. Thus, exocytosis cannot occur, and the inhibitory effect of the neuron is blocked (figure 27.10).

Epidemiology

Clostridium tetani occurs not only in dirt and dust, but in the gastrointestinal tract ofhumans and other animals that have eaten foods contaminated with its spores. About half of the cases result from puncture wounds, including stepping on a nail, body piercing, tattooing, animal bites, splinters, injected-drug abuse, and insect stings. Cases also occur following medical procedures such as hemorrhoid inhibitory ^ neuron

Spinal cord

Stimulatory neuron

Motor neuron

Neuron membrane

Neuro-transmitte

Motor neuron

Neuron membrane

Neuro-transmitte

Heroin Puncture Wound

Vesicles cannot attach to membrane

NORMAL (contraction is inhibited)

TETANUS (contraction is not inhibited)

Vesicles cannot attach to membrane

NORMAL (contraction is inhibited)

TETANUS (contraction is not inhibited)

removal or knee surgery. Surface abrasions and burns can result in tetanus if the wound is anaerobic by virtue of dirt, dead tissue, or exclusion of air. Ordinarily, 30 to 60 cases are reported annually in the United States, with a mortality rate around 25%. Age is an important factor (figure 27.11), probably because maintaining immunity is neglected by many older people. Due to lack of immunization and proper care of wounds, tetanus occurs much more frequently on a global basis than it does in the economically advanced countries. In some parts of the world, babies commonly die of neonatal tetanus as a result of their umbilical cord being cut with unsterile instruments contaminated with C. tetani.

Prevention and Treatment

Active immunization with tetanus toxoid, which is inactivated tetanospasmin, is by far the best preventive weapon against tetanus. Immunization is usually begun during the first year of life. For infants and young children, the tetanus toxoid is given at two, four, six and 18 months of age in combination with diphtheria toxoid and pertussis vaccine. The three together are commonly known as DPT. A booster dose is given when children enter school. Once immunity has been established by this regimen, additional booster doses of tetanus toxoid are given at 10-year intervals to maintain an adequate level of protection. Any injury, burn, or contemplated surgery is an occasion to make sure immunization is up to date. Updating of booster doses of toxoid more frequently than every 10 years is not recommended because there is danger of an allergic reaction following intensive immunization. This type of reaction can occur when the toxoid is injected into an individual who already has large quantities of antitoxin, meaning antibodies against the toxoid. Individuals who have recovered from tetanus are not immune to the disease and must be immunized. ■ toxoid, p. 423

Even though tetanus is easily prevented by immunization with tetanus toxoid, about 97% of the people who developed tetanus in recent years were never immunized. To help prevent tetanus after a wound has been sustained, active immunization with toxoid, and passive immunization with immune globulin containing antitoxin, may be indicated (table 27.3).

0-4 5-19 20-29 30-39 40-49 50-59 60-69 70-79 >80 Age group (years)

Figure 27.11 Average Annual Incidence of Tetanus for Different Age Groups, United States, 1995 to 1997

Figure 27.10 Inhibitory Neuron Function In the normal situation, vesicles containing neurotransmitter attach to the inhibitory neuron membrane and discharge their contents by exocytosis. In tetanus, tetanospasmin prevents the vesicles from attaching to the membrane, and therefore exocytosis cannot occur.

0-4 5-19 20-29 30-39 40-49 50-59 60-69 70-79 >80 Age group (years)

Figure 27.11 Average Annual Incidence of Tetanus for Different Age Groups, United States, 1995 to 1997

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Responses

  • christian
    What are the causative agent of Tetanus?
    3 years ago
  • Luciano
    What is the causative agent of lock jaw?
    2 years ago
  • yohannes
    What is tetanuscausative agent?
    2 years ago
  • TYTTI TALLBERG
    What is the causative agent of Lockjaw?
    9 months ago

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