Clostridium tetani

Clostridium tetani
CLASSIFICATION
Kingdom: Bacteria
Division: Firmicutes
Class: Clostridia
Order: Clostridiales
Family: Clostridiaceae
Genus: Clostridium
Species: C. tetani


INTRODUCTION

C.tetani with tennis racket appearance
Clostridium tetani is rod-shaped, anaerobic bacterium of the genus Clostridium. Like other Clostridium species, it is Gram-positive, and its appearance on a gram stain resembles tennis rackets or drumsticks. C. tetani is found as spores in soil or as parasites in the gastrointestinal tract of animals. C. tetani produces a potent biological toxin, tetanospasmin, and is the causative agent of tetanus.C. tetani is the causative agent of tetanus. The organism is found in soil, Clostridium especially heavily-manured soils, and in the intestinal tracts and feces of various animals.. The organism produces terminal spores within a swollen sporangium giving it a distinctive drumstick appearance.. In




1884, Arthur Nicolaier isolated the strychnine-like toxin of tetanus from free-living, anaerobic soil bacteria. The etiology of the disease was further elucidated in 1884 by Antonio Carle and Giorgio Rattone, who demonstrated the transmissibility of tetanus for the first time. They produced tetanus in rabbits by injecting their sciatic nerve with pus from a fatal human tetanus case in that same year. In 1889, C. tetani was isolated from a human victim, by Kitasato Shibasaburo who later showed that the organism could produce disease when injected into animals, and that the toxin could be neutralized by specific antibodies. In 1897, Edmond Nocard showed that tetanus antitoxin induced passive immunity in humans, and could be used for prophylaxis and treatment. Tetanustoxoid vaccine was developed by P. Descombey in 1924, and was widely used to prevent tetanus induced by battle wounds during World War II
REFERENCES www.wikipedia.com

EPIDEMIOLOGY


Tetanus cases reported worldwide (1990-2004). Ranging from strongly prevalent (in dark red) to very few cases (in light yellow) (grey, no data).
Tetanus is a global health problem. The disease occurs almost exclusively in persons who are unvaccinated or inadequately immunized. It is more common in hot, damp climates with soil rich in organic matter. This is particularly true with manure-treated soils, as the spores are widely distributed in the intestines and faeces of many non-human animals such as horses, sheep, cattle, dogs, cats, rats, guinea pigs, and chickens. In agricultural areas, a significant number of human adults may harbour the organism. The spores can also be found on skin surfaces .



Tetanus – particularly the neonatal form – remains a significant public health problem in non-industrialized countries. There are about one million cases of tetanus reported worldwide annually, causing an estimated 300,000 to 500,000 deaths each year.
In the United States, approximately 100 people become infected with tetanus each year, and there are about five deaths from tetanus each year. Nearly all of the cases in the United States occur in unimmunized individuals or individuals who have allowed their inoculations to lapse, whereas most cases in developing countries are due to the neonatal form of tetanus
REFERENCE www.wikipedia.com

DIAGNOSIS
It can be done by microscopy, culture or by animal inoculation. Microscopy is unreliable,because several bacilli present in wounds can not cause tetanus.So diagnosis by culture is dependable.Isolation is from excised bits of tissues from necrotic depths of wounds than from wound swabs.The material is inoculated on one half of blood agar plate .Production of swarming growth shows the presence of racket shaped clostridia
REFERENCE Ananthanarayan and Paniker’s text book of microbiology

TRANSMISSION
Tetanus is not directly transmitted from person to person. Instead, tetanus spores may be introduced into the body through a puncture wound contaminated with soil, street dust, animal feces; injected contaminated street drugs; lacerations; burns; or even trivial or unnoticed wounds.

REFERENCE www.pubmed.com





TETANUS
Tetanus is a highly fatal disease. The disease occurs when neurotoxin tetanospasmin is produced when spores germinate and vegetative cells grow after gaining access to wounds.Because of the widespread use of the tetanus toxoid for prophylactic immunization, fewer than 150 cases occur annually in the U.S., but the disease is a significant problem world-wide where there are >300,000 cases annually. Most cases in the U.S occur in individuals over age 60.Mortality rates are reported from 40 to 78 %.
Tetanus is an important endemic infection in India.It can be cured if all wounds are cleaned thoroughly soon after injury.


PATHOGENESIS

Most cases of tetanus result from small puncture wounds which become contaminated with C. tetani spores that germinate and produce toxin. The infection remains localized, often with only minimal inflammatory damage. The toxin is produced during cell growth, sporulation and lysis. It migrates from a local wound to sites of action in the central nervous system. The clinical pattern of generalized tetanus consists of severe painful spasms and rigidity of the voluntary muscles. The characteristic symptom of "lockjaw" involves spasms of the masseter muscle. It is an early symptom which is followed by progressive rigidity and violent spasms of the trunk and limb muscles. Spasms of the pharyngeal muscles cause difficulty in swallowing. Death usually results from interference with the mechanics of respiration.



















Sir Charles Bell's portrait of a soldier dying of tetanus. The characteristic rigidity of the body is referred to as opisthotonos and risus sardonicus
Neonatal tetanus accounts for about half of the tetanus deaths in developing countries. In a study of neonatal mortality in Bangladesh, 112 of 330 infant deaths were due to tetanus. Neonatal tetanus follows infection of the umbilical stump in infants born to nonimmune mothers (therefore, the infant has not acquired passive immunity). It usually results from a failure of aseptic technique during birthing procedures, but certain cultural practices may contribute to infection.
TETANUS TOXIN

There have been 11 strains of C. tetani distinguished primarily on the basis of flagellar antigens. They differ in their ability to produce tetanus toxin ,tetanospasmin.Tetanus toxin is one of the three most poisonous substances known to humans,toxin is produced by growing cells and released only on cell lysis. Cells lyse naturally during germination the outgrowth of spores, as well as during vegetative growth. After the inoculation of a wound with C. tetani spores, only a minimal amount of spore germination and vegetative cell growth are required until the toxin is produced.










The bacterium synthesizes the tetanus toxin as a single 150kDa polypeptide chain (called the progenitor toxin), that is cleaved extracellularly by a bacterial protease into a 100 kDa heavy chain (fragment B) and a 50kDa light chain (fragment A), which remain connected by a disulfide bridge. The specific protease that cleaves the progenitor toxin can be found in culture filtrates of C. tetani. Cleavage of the progenitor toxin into A and B fragments can also be induced artificially with trypsin.
Tetanus toxin is produced in vitro in amounts up to 5 to 10% of the bacterial weight. Because the toxin has a specific affinity for nervous tissue, it is referred to as a neurotoxin. The toxin has no known useful function to C. tetani. Why the toxin has a specific action on nervous tissue, to which the organism naturally has no access, may be an anomaly of nature. The toxin is heat labile, being destroyed at 56oC in 5 minutes, and is O2 labile. The purified toxin rapidly converts to toxoid at 0oC in the presence of formalin.


TOXIN ACTION

Tetanospasmin 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 inhibit nervous impulse. If nervous impulses cannot be checked by normal inhibitory mechanisms, it produces the generalized muscular spasms characteristic of tetanus. Tetanospasmin 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.The receptor to which tetanospasmin binds has been reported as ganglioside GT and/or GD1b, but its exact identity is still in question. Binding appears to depend on the number and position of sialic acid residues on the ganglioside. Isolated B fragments, but not A fragments, will bind to the ganglioside. The A fragment has toxic (enzymatic) activity after the B fragment secures its entry. Binding appears to be an irreversible event so that recovery depends on sprouting a new axon terminal
REFERENCES www.google.com



SYMPTOMS
The incubation period of tetanus ranges from 3 to 21 days, with an average onset of clinical presentation of symptoms in 8 days. In general, the further the injury site is from the central nervous system, the longer the incubation period. The shorter the incubation period, the higher the chance of death. In neonatal tetanus, symptoms usually appear from 4 to 14 days after birth, averaging about 7 days. On the basis of clinical findings, four different forms of tetanus have been described.
Local tetanus is an uncommon form of the disease, in which patients have persistent contraction of muscles in the same anatomic area as the injury. The contractions may persist for many weeks before gradually subsiding. Local tetanus is generally milder; only about 1% of cases are fatal, but it may precede the onset of generalized tetanus.
Cephalic tetanus is a rare form of the disease, 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 generalized form usually presents with a descending pattern. 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.
Neonatal tetanus is a form of generalized tetanus that occurs in newborn infants. It occurs in infants who have not acquired passive immunity because the mother has never been immunized. It usually occurs through infection of the unhealed umbilical stump, particularly when the stump is cut with a non-sterile instrument. Neonatal tetanus is common in many developing countries and is responsible for about 14% (215,000) of all neonatal deaths, but is very rare in developed countries.
REFERENCE . www wikipedia.com





TREATMENT

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 is no longer the treatment of choice, 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 antitetanospasmin 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.

MILD TETANUS
Mild cases of tetanus can be treated with:
• Tetanus immune globulin IV or IM
• metronidazole IV for 10 days
• diazepam
• tetanus vaccination













SEVERE TETANUS
Severe cases will require admission to intensive care. In addition to the measures listed above for mild tetanus:


Lock-jaw in a patient suffering from tetanus.
• human tetanus immunoglobulin injected intrathecally (increases clinical improvement from 4% to 35%)
• tracheostomy and mechanical ventilation for 3 to 4 weeks,
• magnesium, as an intravenous (IV) infusion, to prevent muscle spasm,
• diazepam (known under the common name Valium) as a continuous IV infusion,









autonomic effects of tetanus can be difficult to manage (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.

PREVENTION
Tetanus can be prevented by vaccination. The CDC recommends that adults receive a booster vaccine every ten years, and standard care practice in many places is to give the booster to any patient with a puncture wound who is uncertain of when he or she was last vaccinated, or if he or she has had fewer than 3 lifetime doses of the vaccine. The booster cannot prevent a potentially fatal case of tetanus from the current wound, however, as it can take up to two weeks for tetanus antibodies to form. In children under the age of seven, the tetanus vaccine is often administered as a combined vaccine, DPT vaccine, which also includes vaccines against diphtheria and pertussis. For adults and children over seven, the Td vaccine (tetanus and diphtheria) or Tdap (tetanus, diphtheria, and acellular pertussis) is commonly used.

REFERENCE www.wikipedia.com







RESULTS AND CONCLUSION

Tetanus is positively environmental hazard.Its occurrence depends upon man’s physical and ecological surroundings –soil ,agriculture,animal husbandry not on presence or absence of infection in the population . Environmental factors are compounded by social factors such as unhygienic customs and habits such as application of dust on wound,unhygienic delivery practices such as using unsterilised instruments for cutting umbilical cord,ignorance of infection and lack of primary health care services .In developed countries , urbanization ,industrialization and mechanization of agriculture have interfered with normal process of distribution of microorganism and reduced morbidity rate ,as has occurred ,ex. In UK,USA and Germany during last 40 years.

REFERENCE Text Book Of Preventive And Social Medicine By K.Park
Banarsidas Bhanot Publisher