CLOSTRIDIUM TETANI

CLOSTRIDIUM TETANI
CLASSIFICATION :-
Division-Prokaryotes
Kingdom - Bacteria
Phylum - Firmicutes
Class - Clostridia
Order - Clostridiales
Family - Clostridiaceae
Genus - Clostridium
Species - Clostridium tetani

INTRODUCTION:-
Clostridium tetani was discovered in 1884 by a German physician Arthur Nicolaier. He found that C.tetani causes tetanus when he injecting test animals with garden soil which contain bacteria. Clostridium tetani is an anaerobic bacterium that is found in soil and animal intestinal tracts. C. tetani bacteria are single-celled and do not contain any membrane-bound organelles, such as a nucleus. It is a Gram-positive bacteria as it lacks an outer lipopolysaccharide membrane and possesses only a thick peptidoglycan cell wall.C.tetani is a rod-shaped bacteria and have flagella in vegetative form and drumstick in shape in its spore form. Eleven strains of C.tetani are identified and all of these strains produce an neurotoxin known as tetanospasmin. This toxin is responsible for Tetanus.[1]
As Clostridium tetani bacteria are anaerobic so they derieve nutrition by the process of fermentation. Acetic acid, butyric acid, butanol and acetone are byproducts of the bacterial fermentation. Certain strains of C. tetani produce different enzymes that are used to externally digest organic material in preparation for fermentation. In the anaerobic condition C. tetani is primarily found in soil, manure, and intestinal tracts. [2]
Clostridium tetani bacteria have two primary life stages, sporular and vegetative. The latter stage is extremely anaerobic and bacteria of this state are unable to survive oxygen exposure where as sporular form is quite hardy and can withstand oxygen and environmental extremes. Clostridium tetani reproduces by an asexual reproduction process known as binary fission. In this process a single bacteria cell after reaching maxium growth stage divides into two smaller identical clone bacteria cells. Due to this process, C. tetani growth is exponential.
Figure: Clostridium tetani in the sporular state[3].

C. tetani usually enters a host through a wound to the skin and then it replicates. On entering the host C. tetani produces two exotoxins known as tetanolysin and tetanospasmin. Eleven strains of C. tetani have been identified which only differ in flagellar antigens and their ability to produce tetanospasmin. The genes that produce toxin are encoded on a plasmid which is present in all toxigenic strains.Tetanolysin serves no known function to C. tetani. Tetanospasmin is a neurotoxin and causes tetanus. Tetanus toxin is generated in living bacteria and is released when the bacteria lyses such as during spore germination or during vegetative growth. A minimum amount of spore germination and vegetative cell growth are required for toxin production. Tetanospasmin is a zinc-dependent metalloproteinase which is similar in structure to botulinum toxin but each toxin have different effects. C. tetani [which remain connected with a disulfide bridge. Cleavage of the tetanospasmin toxin into A and B fragments can also be induced artificially with trypsin.If infections of C. tetani left untreated or ineffectively treated then they may result in the commonly fatal tetanus. Tetanus is a potentially deadly nervous system disease. Tetanus causes muscular spasms (tightening of the muscles) that can cause paralysis of the respiratory (breathing) system and lead to death. The disease is also known as lockjaw because there is a a common symptom of tetanus in which the jaw muscles become tight and rigid and a person becomes unable to open his mouth. Sometimes tetanus affects only one part of the body but usually the infection spreads throughout the body until the entire body becomes paralyzed. The incubation period for tetanus is from two to fifty days. The incubation period is the time between infection and the first appearance of symptoms. There are increased chances of death if symptoms occur early. In neonatal tetanus, symptoms usually appear from 4 to 14 days after birth, averaging about 7 days.
There are mainly three types of tetanus Local tetanus, Cephalic tetanus and generalised tetanus. Local tetanus is an uncommon form of the disease, in which patients have persistent contraction of muscles in the same anatomic area where the injury is present. The contractions may persist for many weeks before gradually subsiding. Local tetanus is generally milde only about 1% of cases are fatal, but it may lead to the generalized tetanus. Cephalic tetanus is a rare form of the disease and is 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 first sign is trismus or lockjaw and the facial spasms called risus sardonicus, 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 with the body shaped into a characteristic form called opisthotonos. Spasms continue for 3–4 weeks, and complete recovery may take months.[4]


Figure: case of untreated tetanus [4]



Figure: map of the world telling about the concentration of tetanus cases. Darker area represents high concentration of tetanus cases. [5]






METHODOLOGY:-
The infection begins when endospores of C. tetani enter an anaerobic wound. Tetanus can also occur in burn victim, in patients receiving intramuscular injections, person obtaining a tattoo, in persons with frostbite, dental infections, penetrating eye injuries and umbilical stump infections. Other risk factors include diabetes, chronic wounds(skin ulcers.gangrene) parental drug abuse and recent surgery .Unvaccinated mother, home delivery, and unhygienic cutting of the umbilical cord increase susceptibility to tetanus. History of neonatal tetanus in a previous child is a risk factor for subsequent neonatal tetanus. Potentially infectious substances applied to the umbilical stump (e.g., animal dung, mud, clarified butter) are risk factors for neonates. Immunity from tetanus decreases with advancing age. Since the bacterium is an obligate anaerobe, an anaerobic environment is needed for the endospores to germinate and the vegetative bacteria to grow. Vegetative bacteria eventually produce tetanospasmin which is responsible for symptoms of tetanus. The tetanus toxin initially binds to peripheral nerve terminals. It is transported within the axon and across synaptic junctions until it reaches the central nervous system. There it becomes rapidly fixed to gangliosides at the presynaptic inhibitory motor nerve endings and is taken up into the axon by endocytosis. The effect of the toxin is to block the release of inhibitory neurotransmitters (glycine and gamma-amino butyric acid) across the synaptic cleft which is required to check the nervous impulse. If nervous impulses cannot be checked by normal inhibitory mechanisms it produces the generalized muscular spasms characteristic of tetanus. The toxin appears to act by selective cleavage of a protein component of synaptic vesicles synaptobrevin II and this prevents the release of neurotransmitters by the cells. Major symptoms of tetanus spasms and tightening of the jaw muscle known as lockjaw, stiffness and spasms of various muscle groups like neck muscles, chest muscles, abdominal muscles, back muscles.Painful,powerful muscle contraction,irritability,fever.Additional symptoms that may be associated with this disease are excessive sweating,swallowing,hand or foot swamps, uncontrolled urination[6]

DIAGNOSIS: -
The symptoms of tetanus are quite distinctive and a doctor can diagnose the disease simply by observing the patient. Painless spasm of the muscles of the jaw, difficulty in opening the mouth, contraction of the muscles on the forehead and mouth are the characteristic symptoms. Knowing whether or not the patient has had a tetanus vaccination also helps a doctor make their diagnosis. Other signs of being generally irritable, muscle spasms, and poor ability to take in liquids (poor sucking response), Irregular heartbeat, changes in blood pressure
Tetanus can be tested by spatula test. This simple test involves touching the oropharynx with a spatula or tongue blade. This test typically elicits a gag reflex and the patient tries to expel the spatula (which indicates a negative test result). If tetanus is present patients develop a reflex spasm of the masseters and bite the spatula (which indicates a positive test result). [6]




TREATMENT:-
When a tetanus infection becomes established, treatment usually focuses on controlling muscle spasms stopping toxin production, and neutralizing the effects of the toxin. Treatment includes administration of tetanus immune globulin (TIG) which comprises antibodies which inhibit tetanus toxin (also known as tetanus antitoxins) by binding to and removing unbound tetanus toxin from the body. Binding of the toxin to the nerve endings is an irreversible event, and TIG is ineffective at removing bound toxin. Recovery of affected nerves requires the sprouting of a new axon terminal. Large doses of antibiotic drugs (such as metronidazole or intramuscular penicillin G) are also given once tetanus infection is suspected, to halt toxin production. 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 this treatment is no longer used, owing to a theoretical risk of increased spasms. However, its use is recommended 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.

An infant suffering from neonatal tetanus.

Treatment of tetanus is based on whether it is mild or sever tetanus. Mild cases of tetanus can be treated with: Tetanus immune globulin IV or IM ,metronidazole IV for 10 days ,diazepam tetanus vaccination .

Lock-jaw in a patient suffering from tetanus.
Human tetanus immunoglobulin injected intrathecally, tracheotomy and mechanical ventilation for 3 to 4 weeks, magnesium as an intravenous (IV) infusion to prevent muscle spasm, diazepam (Valium) as a continuous IV infusion, the autonomic effects of tetanus can be difficult to manage like alternating hyper- and hypotension, hyperpyrexia/ hypothermia and may require IV labetalol, magnesium, clonidine, or nifedipine. Drugs such as diazepam or other muscle relaxants can be given to control the muscle spasms. In extreme cases it may be necessary to 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 per day, 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 because of the increased metabolic strain brought on by the increased muscle activity. [7]
PREVENTION:
There are two important ways to prevent tetanus: getting vaccinated against tetanus along with other routine immunizations, or, after an injury that could cause tetanus, receiving a shot (post-exposure tetanus prophylaxis).For kids, tetanus immunization is part of the DTaP (diphtheria, tetanus, and a cellular pertussis) vaccinations. They typically receive a series of four doses of DTaP vaccine before 2 years of age, followed by a booster dose at 4 to 6 years of age. After that, a booster (Tdap) is recommended at 11 to 12 years of age, and then a tetanus and diphtheria booster every 10 years through adulthood. Post-exposure tetanus prophylaxis also involves getting tetanus shots, but after an injury occurs. Shots given will depend on the number of years since the patient's last booster, the total number of tetanus vaccinations the patient has received, and the nature of the wound. The doctor may recommend a tetanus booster Td, DTaP, or Tdap, depending on the patient's age and previous immunizations and an injection of tetanus immune globulin (TIG) to neutralize any toxin released by the bacteria. Neonatal tetanus can be prevented by making sure that all pregnant women have had their tetanus immunizations, by delivering babies in sanitary conditions, and by proper umbilical cord care. If you are pregnant, discuss your immunization record with your obstetrician well before your due date. Any skin wound — especially a deep puncture or a wound that may be contaminated with feces, soil, or saliva — should be cleaned and dressed right away. Although it's important to clean all wounds, remember that cleaning is not a substitute for immunization [8].

RESULTS AND DISCUSSION:
Tetanus remains a severe disease occurring primarily among persons who are unvaccinated or inadequately vaccinated. Adults aged greater than or equal to 60 years continue to be at highest risk for tetanus and for severe disease. However, the overall incidence of tetanus has decreased slightly since the late 1980s and early 1990s. Older adults are at highest risk for tetanus because of the low prevalence of immunity to tetanus. Tetanus remains a clinical diagnosis because confirmatory laboratory tests are not available for routine use. Isolation of the organism from wounds is neither sensitive nor specific: anaerobic cultures of tissues or aspirates usually are not positive, and the organism might be grown from wounds in the absence of clinical signs and symptoms of disease. Tetanus is preventable through both routine vaccination and appropriate wound management. Vaccination with a primary series of three doses of TT-containing vaccine and booster doses of Td every 10 years are highly effective in preventing tetanus.





CONCLUSION:-
Tetanus (commonly called lockjaw) is a disease manifested by uncontrolled muscle spasms. Tetanus is caused by the toxin (poison) produced by the bacteria, Clostridium tetani. This disease is frequently fatal, especially to the very old or very young. Tetanus is preventable by immunization or through administration of tetanus immune globulin.It occurs predominantly in developing countries among newborn infants, children, and young adults, especially in unimmunized or inadequately immunized adults over 50 years of age. The symptoms are often jaw or neck stiffness, difficulty swallowing, and irritability. There may be pain or tingling at the site of inoculation (where the tetanus bacteria entered), followed by spasticity of nearby muscles. The diagnosis is made clinically by the medical history and physical findings. Immune globulin, given intramuscularly, is the immediate treatment of unimmunized individuals exposed to material likely to contain the tetanus bacteria. Treatment includes bed rest and quiet conditions.Antimicrobial drugs, such as penicillin, are used to eradicate the bacteria. Tetanus is completely preventable by active immunization.













REFERENCES:-
1. http://en.wikipedia.org/wiki/Clostridium_tetani
2. http://bioweb.uwlax.edu/bio203/s2008/unrein_bren/nutrition.htm
3. http://bioweb.uwlax.edu/bio203/s2008/unrein_bren/adaptation.htm
4. http://www.textbookofbacteriology.net/clostridia.html
5. http://kidshealth.org/parent/infections/bacterial_viral/tetanus.html
6. http://www.umm.edu/ency/article/000615.html
7. http://www.cdc.gov/vaccines/vpd-vac/tetanus/default.htm
8. http://en.wikipedia.org/wiki/Tetanus