Biology 112: Biology of <a href="/keyword/infectious-disease/" >infectious disease</a> Tetanus I. Symptomology A. A disease characterized by muscle rigidity and spasms, derived from the Greek word, , to contract. Highly variable incubation period 1. 2. C. D. E. Usually 2 14 days Can be months B. Trismus (lockjaw) Muscle stiffness, backache Spasms stimulated by loud noises, bright lights, physical manipulation 1. 2. 3. 4. Excruciatingly painful Can break bones Risus sardonicus (sardonic smile) Opisthotonus (arched body; Fig. 6-1) F. G. Death is usually due to asphyxia or aspiration pneumonia Even upon recovery, overstimulation of the autonomic nervous system sometimes leads to permanent damage, particularly to the heart. Sunday, September 16, 2007 Page 49 10:03:33 AM BIOLOGY 112: BIOLOGY OF <a href="/keyword/infectious-disease/" >infectious disease</a> LECTURE 06: TETANUS Figure 6-1. Victim of tetanus, a soldier wounded at the battle of Corunna in 1809, is seen in a drawing made by the Scottish surgeon and anatomist Sir Charles Bell and published in 1832 in his book The Anatomy and Philosophy of Expression. The patient's muscles are working against one another, leaving him in a state of spastic paralysis; his jaw is set in the &quot;sardonic smile&quot; of tetanus, or lockjaw. VAN HEYNINGEN, W. E. Tetanus. Scientific American 218(4): 69 77, April 1968. H. Neonatal tetanus 1. 2. Infection of the umbilical stump; 90% untreated mortality Not helped by dirty instruments and local customs such as covering the umbilical stump with ashes, charcoal powder, cow dung poultices, ghee, powdered pepper, snail saliva, turmeric, leaves, or dirty rags. A study at the Dublin Lying-In Hospital in 1782 noted that of 17,650 infants born, 2,944 died within a fortnight from neonatal tetanus. Neonatal tetanus is still a problem worldwide. 3. 4. Sunday, September 16, 2007 Page 50 10:03:33 AM BIOLOGY 112: BIOLOGY OF <a href="/keyword/infectious-disease/" >infectious disease</a> LECTURE 06: TETANUS II. Pathogenesis1,2 A. Clostridium tetani, the causative agent, is ubiquitous in the environment. 1. Gram-positive, drumstick-shaped cell (0.5 1.7 m x 2.1 18.1 m), obligate anaerobe, forms terminal endospores Regularly inhabits animal guts without any effect on the animal 2. B. Spores are extremely environmentally resistant 1. 2. Can be boiled for several minutes Killed in the autoclave in 15 20 min 1 THWAITES, C. L., N. T. N. NGA, &amp; M. D. SMITH. Tetanus. Chapter 62 of COOK, GORDON C., &amp; ALIMUDDIN I. ZUMLA. Manson's Tropical Diseases. 21st ed. Saunders, 2003, pp. 1119 1124. 2 NATHAN, BARNETT R., &amp; THOMAS P. BLECK. Tetanus. Chapter 46 of GUERRANT, RICHARD L., DAVID H. WALKER, &amp; PETER F. WELLER. Tropical <a href="/keyword/infectious-diseases/" ><a href="/keyword/infectious-disease/" >infectious disease</a> s</a> : Principles, Pathogens, &amp; Practice. Philadelphia: Churchill Livingstone, 1999, pp. 517 526. Sunday, September 16, 2007 Page 51 10:03:33 AM BIOLOGY 112: BIOLOGY OF <a href="/keyword/infectious-disease/" >infectious disease</a> LECTURE 06: TETANUS 3. Resistant to desiccation, household disinfectants, and marked changes in pH C. Causes symptoms only when spores contaminate a necrotic wound 1. Intramuscular injection of quinine is strongly associated with tetanus, apparently because the quinine is toxic to the muscle tissue. Since narcotics are frequently &quot;cut&quot; with quinine, this put intravenous drug abusers at particular risk. 2. D. E. No human-to-human transmission Clostridium tetani secretes tetanospasmin, a protein exotoxin that is taken up by animal neurons. 1. 2. Tetanospasmin is encoded on a plasmid Strains of Clostridium without the plasmid are harmless. F. From peripheral neurons, tetanospasmin makes its way by retrograde transport to the spinal cord. Although tetanospasmin rather generally inhibits the action of neurons by inhibiting the release of synaptic vesicles, the most sensitive neurons appear to be the inhibitory interneurons of the spinal cord that use -aminobutyric acid as a neurotransmitter. This produces the spastic paralysis (see Fig. 6-2). G. H. Sunday, September 16, 2007 Page 52 10:03:33 AM BIOLOGY 112: BIOLOGY OF <a href="/keyword/infectious-disease/" >infectious disease</a> LECTURE 06: TETANUS Figure 6-2. Nervous control of muscles that raise and lower the forearm is diagrammed very schematically. In a normal individual (left) impulses from the brain can excite a motoneuron (1) to cause the biceps to contract, stretching the triceps. A stretch-sensitive receptor (2) in the triceps would thereupon cause a triceps motoneuron (3) to fire and oppose the stretching--except that this firing is inhibited by impulses from an inhibitory nerve (4). In tetanus (right) the inhibitory impulses to the triceps motoneuron are blocked (6); both muscles contract, causing a spasm. From VAN HEYNINGEN, W. E. Tetanus. Scientific American 218(4): 69 77, April 1968. Sunday, September 16, 2007 Page 53 10:03:33 AM BIOLOGY 112: BIOLOGY OF <a href="/keyword/infectious-disease/" >infectious disease</a> LECTURE 06: TETANUS III. Treatment is generally supportive A. To prevent further toxin release 1. 2. B. Wound debridement Antibiotics To neutralize unbound toxin 1. Antitoxin (passive immunization) a) b) Horse antitoxin Human tetanus immune globulin C. To alleviate symptoms 1. 2. 3. Quiet room Nasogastric feeding Diazepam directly opposes the effect of tetanospasmin on inhibitory interneurons Paralysis with curare and ventilation 4. D. With modern care, mortality has been reduced to about 10% IV. Prevention A. Active immunization 1. The modern aluminum phosphate adsorbed vaccine is safe (1 nonfatal anaphylactic reaction every 1.5 to 2 million doses) and effective (nearly 100%). a) b) This is the T in the DPT immunization Administered at 2 months, 4 months, 6 months, 15 18 months, and 4 6 years of age You should be actively immunized every 10 years thereafter. c) Sunday, September 16, 2007 Page 54 10:03:33 AM BIOLOGY 112: BIOLOGY OF <a href="/keyword/infectious-disease/" >infectious disease</a> LECTURE 06: TETANUS B. Active immunization of women prevents neonatal tetanus 1. WHO wanted to eradicate neonatal tetanus by the year 2000; it didn't happen... V. History3 A. Accurately described by Hippocrates (c. 460 c. 370 BC) A man who was struck from behind by a sharp dart a little below the neck had a wound which did not look serious because it did not go deep. But sometime later when the point had been extracted the patient was seized with backward-bending convulsions like those of opisthotonus. His jaws were locked, and any liquid that he attempted to swallow was returned through his nostrils. He died on the second day. 1. He recommended treatments such as black pepper, hellebore, fat bird soup, vapor baths, cold water baths, and phlebotomy. B. Also accurately described by Aretaeus the Cappodocian (c. 200 AD) 1. Perhaps with misplaced emphasis calling the disease &quot;a great misfortune of the physician&quot; because of its horror and incurability, nevertheless recommends treatments: special diets, forcing liquids, a quiet house, phlebotomy, massage with oils, fomentations, and cupping C. William Osler, in his famous 1892 textbook of medicine, estimated an 80% mortality rate once symptoms had set in. 1. He recommends the use of a nasogastric tube for feeding and hydration, morphine for sedation, chloroform as a muscle relaxant, and antiseptic treatment of the associated wound. D. The Cambridge World History of Disease sums it up very nicely: It is fair to say that from Hippocrates to Osler -- and to today -- ther...