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الانزيمات
Clostridium tetani
المؤلف:
Stefan Riedel, Jeffery A. Hobden, Steve Miller, Stephen A. Morse, Timothy A. Mietzner, Barbara Detrick, Thomas G. Mitchell, Judy A. Sakanari, Peter Hotez, Rojelio Mejia
المصدر:
Jawetz, Melnick, & Adelberg’s Medical Microbiology
الجزء والصفحة:
28e , p188-189
2025-08-14
35
C. tetani, which causes tetanus, is worldwide in distribution in the soil and in the feces of horses and other animals. Several types of C. tetani can be distinguished by specific flagellar antigens. All share a common O (somatic) antigen, which may be masked, and all produce the same antigenic type of neurotoxin, tetanospasmin.
Toxin
The vegetative cells of C. tetani produce the plasmid-encoded toxin tetanospasmin (150 kDa) that is cleaved by a bacterial protease into two peptides (50 and 100 kDa) linked by a disulfide bond. The larger peptide initially binds to receptors on the presynaptic membranes of motor neurons. It then migrates by the retrograde axonal transport system to the cell bodies of these neurons to the spinal cord and brainstem. The toxin diffuses to terminals of inhibitory cells, including both glycinergic interneurons and γ-aminobutyric acid (GABA) secreting neurons from the brainstem. The smaller peptide degrades synaptobrevin (also called VAMP2), a protein required for docking of neurotransmitter vesicles on the presynaptic membrane. Release of the inhibitory glycine and GABA is blocked, and the motor neurons are not inhibited. Hyperreflexia, muscle spasms, and spastic paralysis result. Extremely small amounts of toxin can be lethal for humans.
Pathogenesis
C. tetani is not an invasive organism. The infection remains strictly localized in the area of devitalized tissue (wound, burn, injury, umbilical stump, surgical suture) into which the spores have been introduced. The volume of infected tissue is small, and the disease is almost entirely a toxemia. Germi nation of the spore and development of vegetative organisms that produce toxin are aided by (1) necrotic tissue, (2) calcium salts, and (3) associated pyogenic infections, all of which aid establishment of low oxidation–reduction potential.
The toxin released from vegetative cells reaches the central nervous system and rapidly becomes fixed to receptors in the spinal cord and brainstem and exerts the actions described.
Clinical Findings
The incubation period may range from 4 to 5 days up to 3 weeks. The disease is characterized by tonic contraction of voluntary muscles. Muscular spasms often involve first the area of injury and infection and then the muscles of the jaw (trismus, lockjaw), which contract so that the mouth cannot be opened. Gradually, other voluntary muscles become involved, resulting in tonic spasms. Any external stimulus may precipitate a tetanic generalized muscle spasm. The patient is fully conscious, and pain may be intense. Death usually results from interference with the mechanics of respiration. The mortality rate in generalized tetanus is very high.
Diagnosis
The diagnosis rests on the clinical picture and a history of injury, although only 50% of patients with tetanus have an injury for which they seek medical attention. The primary differential diagnosis of tetanus is strychnine poisoning. Anaerobic culture of tissues from contaminated wounds may yield C. tetani, but neither preventive nor therapeutic use of anti-toxin should ever be withheld pending such demonstration.
Proof of isolation of C. tetani must rest on production of toxin and its neutralization by specific antitoxin.
Prevention and Treatment
The results of treatment of tetanus are not satisfactory. Therefore, prevention is all important. Prevention of tetanus depends on (1) active immunization with toxoids, (2) aggressive wound care, (3) prophylactic use of antitoxin, and (4) administration of penicillin.
The intramuscular administration of 250–500 units of human antitoxin (tetanus immune globulin) gives adequate systemic protection (0.01 unit or more per milliliter of serum) for 2–4 weeks. It neutralizes the toxin that has not been fixed to nervous tissue. Active immunization with tetanus toxoid should accompany antitoxin prophylaxis.
Patients who develop symptoms of tetanus should receive muscle relaxants, sedation, and assisted ventilation. Sometimes, they are given very large doses of antitoxin (3000 10,000 units of tetanus immune globulin) intravenously in an effort to neutralize toxin that has not yet been bound to nervous tissue. However, the efficacy of antitoxin for treatment is doubtful except in neonatal tetanus, in which it may be lifesaving.
Surgical debridement is vitally important because it removes the necrotic tissue that is essential for proliferation of the organisms. Hyperbaric oxygen has no proven effect.
Penicillin strongly inhibits the growth of C. tetani and stops further toxin production. Antibiotics may also control associated pyogenic infection.
When a previously immunized individual sustains a potentially dangerous wound, an additional dose of toxoid should be injected to restimulate antitoxin production. This “recall” injection of toxoid may be accompanied by a dose of antitoxin if the patient has not had current immunization or boosters or if the history of immunization is unknown.
Control
Tetanus is a totally preventable disease. Universal active immunization with tetanus toxoid should be mandatory. Tetanus toxoid is produced by detoxifying the toxin with formalin and then concentrating it. Aluminum salt-adsorbed toxoids are used. Three injections comprise the initial course of immunization followed by another dose about 1 year later. Initial immunization should be carried out in all children during the first year of life. A “booster” injection of toxoid is given upon entry into school. Thereafter, “boosters” can be spaced 10 years apart to maintain serum levels of more than 0.01unit antitoxin per milliliter. In young children, tetanus toxoid is often combined with diphtheria toxoid and acellular pertussis vaccine.
Environmental control measures are not possible because of the wide dissemination of the organism in the soil and the long survival of its spores.
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