Clostridium Tetani - Infection with C Tetani - Essay Example

 Clostridium tetani Clostrodium tetani is Gram positive capsulated bacillus from the genus Clostridium that is the causative agent of tetanus.It measures 4-8 micrometers long and has strait, parallel walls. In younger cultures it stains Gram positive, but in older cultures some of them may stain Gram negative. Clostridium tetani is mobile bacteria and has flagella. On one end of the bacteria there is a large, round spore that gives the bacteria a drumstick or tennis racket shape. Clostridium tetani is obligate anaerobe and doesn’t grow in the presence of oxygen. Optimal conditions for growing this bacterium are temperature of 37 degrees Celsius, with PH of 7.4. It grows on different nutrient media including agar enriched with blood. When cultivated on agar enriched with blood it manifests alpha hemolisis, but with prolonged cultivation it produces beta hemolisis. Because C. tetani is mobile bacteria and has flagella when cultivated produces the effect of swarming and tends to spread over the complete area of the culture. When cultivated produces very thin and see-through layer of bacteria that is very hard to notice with a naked eye, except on the edges of the colonies. It is difficult to obtain a pure culture of C. tetani, this is why method called Fildes technique is often used, when the bacteria is inoculated on a small area on agar plate and after incubation of 10 hours another subculteres are made from the edge of the swarming area that is constituted mostly of C Tetani (Barrow and Feltham 2004). In suboptimal conditions C tetani forms spores that are relatively resistant. Spores are killed in boiling water in 10-15 minutes, and in moist heat of 121 degrees Celsius after 20 minutes (Ryan and Ray 2004). Based on the agglutination process C. Tetani is classified in 10 serological types (only type IV doesn’t have flagella and is not mobile). All subtypes of this bacterium produce three toxins which are tetanolysin, tetanospasmin and nonspasmogenic toxine (neurotoxin). Tetanospasmin is the toxin that is produced by the vegetative form of the bacteria in absence of oxygen and is the most important toxin in the pathogenesis of tetanus. It spreads through the lymphatic system from the initial place of infection, causing systemic effects. It is protein based molecule with molecular weight of 150 kDa (Kilo Daltons) and is constitutes of two parts, heavier or B chain with weight of approximately 100 kDa and lighter A chain with molecular weight of 50 kDa. Heavier B chain of this toxin bonds to the cell membrane and helps chain A to enter the cytosol of the cell (Farrar et al. 2000). The A chain than migrates through the axons to the central nervous system. Lighter A chain of the tetanospazmin toxin in the CNS impairs the release of inhibitory neurotransmitters in the brain (GABA-gamma aminobuteric acid and glycine) by degrading protein called synaptobrevin (small membrane based protein). Consequence of this effect is hyperactivity of the skeletal muscles in the body and development of muscle contractions and muscle spasm (Schiavo et al. 1992). Infection with C Tetani may cause development of condition called tetanus. It is disease that is characterized by presence of generalized spasms of the skeletal muscles in the body that is produced by the tetanospasmin toxin. It is caused when a wound is contaminated with spores of Clostridium Tetani. C Tetani are widespread bacteria that are present in the soil, dust, manure of domestic animals, our clothing and in about 20 percents of human gastrointestinal tract (Bleck 1995). If the wound is deep enough spores of C. tetani in anaerobic conditions can develop in viable bacteria that start to release toxins. Toxins are released when the bacteria are destroyed and bacterial cytosol along with toxins is released into the human tissues. Incubation period between the infection and occurrence of first symptoms ranges between 3 and 21 days, but that depends mostly on the site of primary infection. As early sign patients may report dysphagia and sore throat and some local manifestations like muscle rigidity. This is localized tetanus where the manifestations are localized at the site of infection, but this for is very rare (about 1 % of cases) and it often progresses to generalized tetanus, progressively affecting all skeletal muscles. Common first signs of generalized tetanus are headache and muscular stiffness of the jaw (lockjaw or risus sardonicus). This is followed by stiffness and rigidity of the neck, impaired swallowing, stiffness of the muscles of the abdomen, general spasm and sweating. Later the condition can progress to severe tetanus with appearance of opistotonus (flexion of the muscles of the back that is so strong that the patient can be lifted out of the bed standing on it head and its foots, often breaking vertebral bodies in the process), titanic flexion of the arms, extension of legs etc. Tetanus is usually fatal when respiratory muscles are affected (intercostal muscles, diaphragm and other muscles) and the patient is unable to breathe (Farrar et al. 2000). Other form of generalized tetanus is neonatal tetanus which is a form of generalized tetanus that affects neonates that don’t have immunity against C Tetani toxins (if theis mothers were not properly immunized). It is acquired during delivery when the umbilical stump is cut with some unsterile instrument and is still a very common form of tetanus in many undeveloped countries (WHO 2000). Another more rare form of tetanus is cephalic tetanus that is characterized by affection of cranial nerve palsies with very fast incubation period and often fast and high mortality (Farrar et al. 2000). First and most important procedure in treating tetanus is to clean and widely open the wound in order to expose the C Tetany bacteria to oxygen. Dead tissue should be by removed by debridement and a regiment of antibiotic treatment should be started. Usually first drug of choice is metronidazole or doxyciclyne, but penicillin is effective also. C Tetani is resistant to aminoglicosides so they should be avoided. Patient must also receive human tetanus immunoglobulin intravenously of intramuscular in order to neutralize the free toxin that is still not bounded to the synaptic nerves. Immunoglobulin has no effect on already bounded toxine. Only way to remove the toxin from the affected synapses is through repair and regeneration of the synapses 4 to 6 weeks after the onset of symptoms (Lowbury et al. 1978). In order to survive in this long period patient must take medications for muscle relaxation. In milder cases large doses of diazepam can be used, but in severe cases curare (and curare like drugs) must be used in order to completely relax all skeletal muscles and the patients must be put on mechanical ventilation and artificial nutrition (nasogastric tube or complete parenteral nutrition). The best treatment for tetanus is still prevention with tetanus toxoid immunization. Because the lethal dose of C tetani toxin (tetanospasmin) is extremely small and quantities as much as 2.5 nanogramis per kilogram can be lethal human body doesn’t produce natural immunity against C tetani (Schiavo et al. 1992). This means that surviving the infection doesn’t produce immunity that will protect the patient from another infection. Development of local and generalized tetanus can be prevented with appropriate immunization (Hopkins et al. 1991). Tetanus toxoid immunization is now part of the regular immunization of the children in a form of combined vaccine with diphtheria, tetanus and pertusis (DTP) which is given in 5 doses until age 7 in young children (on 2, 4, 6 and 15-18 month and 4-6 year), and additional buster doses with DT vaccine (diphtheria tetanus) in age between age 11 and 18 years (preferably at age 11-12 years old) and another buster dose after age 18-19. This immunization protects the patient from developing tetanus 10 years after the last booster dose of tetanus. If there is a risky wound 5 or more years after the last booster dose patients should receive another booster dose of tetanus toxoid (Hopkins et al. 1991). This rigorous process of immunization has lead to very low incidence of tetanus in the modern world. For example in United states there were 560 reported cases in 1947, 101 cases in 1974 and only 43 cases on average after year 1998. Most of these 43 cases were patients who were not properly immunized. The incidence of developed tetanus in immunized population is extremely rare (4 cases on 100 millions) (Pascual et al. 2003). References: G. I. Barrow, R. K. A. Feltham (2004), Cowan and Steel's Manual for the Identification of Medical Bacteria, mbridge University Press, 2004, page 84. Farrar JJ; Yen LM; Cook T; Fairweather N; Binh N; Parry J; Parry CM (September 2000). "Tetanus". Journal of Neurology, Neurosurgery, and Psychiatry 69 (3): 292–301. PMC 1737078. PMID 10945801. Schiavo G; Benfenati F; Poulain B; Rossetto O; Polverino de Laureto P; DasGupta BR; Montecucco C (1992). "Tetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of synaptobrevin". Nature 359 (6398): 832–5. doi:10.1038/359832a0. PMID 1331807. Ryan KJ; Ray CG (editors) (2004). Sherris Medical Microbiology (4th ed. ed.). McGraw Hill. ISBN 0838585299. Bleck TP (1995), Clostridium tetani. In: Mandell GL, Bennett JE, Dolin R, eds. Bennett's Principles and Practice of Infectious Diseases. Philadelphia, Pa: Churchill Livingstone; 1995:2373-8. World Health Organization (WHO) (2000). "Maternal and Neonatal Tetanus Elimination by 2005". Retrieved 2007-01-26. Farrar JJ; Yen LM; Cook T; Fairweather N; Binh N; Parry J; Parry CM (2000). "Tetanus". Journal of Neurology, Neurosurgery, and Psychiatry 69 (3): 292–301. PMC 1737078. PMID 10945801. Schiavo G; Benfenati F; Poulain B; Rossetto O; Polverino de Laureto P; DasGupta BR; Montecucco C (1992). "Tetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of synaptobrevin". Nature 359 (6398): 832–5. doi:10.1038/359832a0. PMID 1331807. Hopkins, A.; Lahiri, T.; Salerno, R.; Heath, B. (1991). 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