Tetanus is an acute, often fatal disease caused by an exotoxin produced in a wound by Clostridium tetani.

Clostridium tetani is a gram-positive, nonencapsulated, motile, obligatively anaerobic bacillus. It exists in vegetative and sporulated forms. Spores are highly resistant to disinfections by chemical or heat, but vegetative forms are susceptible to the bactericidal effect of heat, chemical disinfectants, and a number of antibiotics. Clostridium tetani is a noninvasive organism. It is found in soil and in the intestine and feces of horses, sheep, cattle, dogs, cats, rats, guinea pigs and chicken. Manuretreated soil may contain large numbers of spores too. Tetanus occurs after spores or vegetative bacteria gain access to tissues and produce toxin locally. The usual mode of entry is trough a puncture wound or laceration. Tetanus may also follow elective surgery, burn wounds, otitis media, dental infection, abortion and pregnancy. Neonatal tetanus usually follows infection of the umbilical stump. In the presence of anaerobic conditions, the spores germinate. Toxins,including tetanolysin (which potentiates infection) and tetanospasmin (a potent neurotoxin) are produced. Tetanospasmin, often referred to as tetanus toxin, causes clinical tetanus. The toxin produced is disseminated through the bloodstream and lymphatic system. However, it does not enter the central nervous system through this route, as it cannot cross the blood brain barrier except at the fourth ventricle. The toxin is exclusively taken up by the neuromuscular junction, where it migrates retrograde transynaptically at the rate 75-250mm/day, a process which takes 3-14 days, protected from neutralizing antitoxin, predominantly to inhibitory synapses to prevent the release of acetylcholine. The toxin acts after the incubation period (3-14) days) at several sites within the central nervous system, including peripheral motor end plates, spinal cord, brain and sympathetic nervous system. The typical clinical manifestations of tetanus are caused when tetanus toxin interferes with release of neurotrasmitters, blocking inhibitor impulses. Blockade of spinal inhibition is produced when the toxin acts at the synapse of interneurons of inhibitory pathways and motor neurons. General muscle rigidity arises from uninhibited afferent stimuli entering the central nervous system from the periphery. The effect of the toxin on the brain is controversial; direct inoculation can cause seizures. One of the many complications from tetanus is respiratory failure secondary to spasms, obstruction by secretions, exhaustion and pulmonary aspiration. Cardiovascular complications thought to be due to hyperactivity of the sympathetic nervous system include tachycardia, with heart rates over 180 beats per minute, severe vasoconstriction and hypertension. Autonomic dysfunction is seen as increased basal sympathetic activity and episodes of sympathetic over activity. (SOA). Tetanus Overview Tetanus is an infectious disease caused by contamination of wounds from the bacteria Clostridium tetani, or the spores they produce that live in the soil, and animal feces. Tetanus has been recognized for centuries; the term is derived from the ancient Greek words tetanos and teinein, meaning taut and stretched, which describe the condition of the muscles affected by the toxin, tetanospasm, produced by Clostridium tetani. The causative bacterium, Clostridium tetani, is a hardy organism capable of living many years in the soil in a form called a spore. The bacterium was first isolated in 1889 by S. Kitasato while he was working with R. Koch in Germany. Kitasato also found the toxin responsible for tetanus and developed the first protective vaccine against the disease. Tetanus occurs when a wound becomes contaminated with Clostridium tetani bacterial spores. Infection follows when spores become activated and develop into gram-positive bacteria that multiply and produce a very powerful toxin (tetanospasmin) that affects the muscles. Tetanus spores are found throughout the environment, usually in soil, dust, and animal waste. The usual locations for the bacteria to enter the body are puncture

wounds, such as those caused by rusty nails, splinters, or insect bites. Burns, any break in the skin, and IV drug access sites are also potential entryways for the bacteria. Tetanus is acquired through contact with the environment; it is not transmitted from person to person. Tetanus results in severe, uncontrollable muscle spasms. For example, the jaw is "locked" by muscle spasms, causing the disease to sometimes be called "lockjaw." In severe cases, the muscles used to breathe can spasm, causing a lack of oxygen to the brain and other organs that may possibly lead to death. The disease in humans is the result of infection of a wound with the spores of the bacteria Clostridium tetani. These bacteria produce the toxin (poison) tetanospasmin, which is responsible for causing tetanus. Tetanospasmin binds to motor nerves that control muscles, enters the axons (filaments that extend from nerve cells), and travels in the axon until it reaches the body of the motor nerve in the spinal cord or brainstem (a process termed retrograde intraneuronal transport). Then the toxin migrates into the synapse (small space between nerve cells critical for transmission of signals among nerve cells) where it binds to presynaptic nerve terminals and inhibits or stops the release of certain inhibitory neurotransmitters (glycine and gamma-aminobutyric acid). Because the motor nerve has no inhibitory signals from other nerves, the chemical signal to the motor nerve of the muscle intensifies, causing the muscle to tighten up in a huge continuous contraction or spasm. If tetanospasmin reaches the bloodstream or lymphatic vessels from the wound site, it can be deposited in many different presynaptic terminals resulting in the same effect on other muscles. In the United States, because of widespread immunization and careful wound care, the total annual number of cases has averaged about 40-50 cases per year since 1995. In developing countries of Africa, Asia, and South America, tetanus is far more common. The annual worldwide incidence is between 500,000-1 million cases. The majority of new cases worldwide are in neonates in third-world countries.

The disease can show four possible types: Generalized tetanus can affect all skeletal muscles. It is the most common as well as the most severe form of the four types. o Local tetanus manifests with muscle spasms at or near the wound that has been infected with the bacteria. o Cephalic tetanus primarily affects one or several muscles in the face rapidly (in one to two days) after a head injury or ear infection. Trismus ("lockjaw") may occur. The disease can easily progress to generalized tetanus. o Neonatal tetanus is similar to generalized tetanus except that it affects a baby that is less than 1 month old (called a neonate). This condition is rare in developed countries.
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SYMPTOMS Tetanus affects skeletal muscle, a type of striated muscle used in voluntary movement. The other type of striated muscle, cardiac or heart muscle, cannot be tetanized because of its intrinsic electrical properties. Mortality rates reported vary from 40% to 78%. In recent years, approximately 11% of reported tetanus cases have been fatal. The highest mortality rates are in unvaccinated people and people over 60 years of age. In general, the further the injury site is from the central nervous system, the longer the incubation period. The shorter the incubation period, the more severe the symptoms. 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. Complications

Airway obstruction is common. Urinary retention and constipation may develop because of sphincter spasm. Respiratory failure and cardiac failure are late life-threatening events. Fractures may result from sustained spasms. Seizures can occur. Pulmonary emboli may develop. Bacterial superinfections are possible complications. Dehydration can develop.

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 because of a theoretical risk of increased spasms. It should still be used if metronidazole is not available. Passive immunization with human antitetanospasmin 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:

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. The autonomic effects of tetanus can be difficult to manage (alternating hyperand hypotension, hyperpyrexia/hypothermia) and may require IV labetalol, magnesium, clonidine, or nifedipine.

Drugs such as chlorpromazine or diazepam, or other muscle relaxants can be given to control the muscle spasms. In extreme cases it may be necessary to chemically 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, 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 due to the increased metabolic strain brought on by the increased muscle activity.