Tetanus
Tetanus, also known as lockjaw, is a bacterial infection caused by Clostridium tetani and characterized by muscle spasms. In the most common type, the spasms begin in the jaw and then progress to the rest of the body. Each spasm usually lasts for a few minutes. Spasms occur frequently for three to four weeks. Some spasms may be severe enough to fracture bones. Other symptoms of tetanus may include fever, sweating, headache, trouble swallowing, high blood pressure, and a fast heart rate. The onset of symptoms is typically 3 to 21 days following infection. Recovery may take months; about 10% of cases prove to be fatal.
C. tetani is commonly found in soil, saliva, dust, and manure. The bacteria generally enter through a break in the skin, such as a cut or puncture wound caused by a contaminated object. They produce toxins that interfere with normal muscle contractions. Diagnosis is based on the presenting signs and symptoms. The disease does not spread between people.
Tetanus can be prevented by immunization with the tetanus vaccine. In those who have a significant wound and have had fewer than three doses of the vaccine, both vaccination and tetanus immune globulin are recommended. The wound should be cleaned, and any dead tissue should be removed. In those who are infected, tetanus immune globulin, or, if unavailable, intravenous immunoglobulin is used. Muscle relaxants may be used to control spasms. Mechanical ventilation may be required if a person's breathing is affected.
Tetanus occurs in all parts of the world but is most frequent in hot and wet climates where the soil has a high organic content. In 2015, there were about 209,000 infections and about 59,000 deaths globally. This is down from 356,000 deaths in 1990. In the US, there are about 30 cases per year, almost all of which were in people who had not been vaccinated. An early description of the disease was made by Hippocrates in the 5th century BC. The cause of the disease was determined in 1884 by Antonio Carle and Giorgio Rattone at the University of Turin, and a vaccine was developed in 1924.
Signs and symptoms
Tetanus often begins with mild spasms in the jaw muscles—also known as lockjaw. Similar spasms can also be a feature of trismus. The spasms can also affect the facial muscles, resulting in an appearance called risus sardonicus. Chest, neck, back, abdominal muscles, and buttocks may be affected. Back muscle spasms often cause arching, called opisthotonus. Sometimes, the spasms affect muscles utilized during inhalation and exhalation, which can lead to breathing problems.Prolonged muscular action causes sudden, powerful, and painful contractions of muscle groups, called tetany. These episodes can cause fractures and muscle tears. Other symptoms include fever, headache, restlessness, irritability, feeding difficulties, breathing problems, burning sensation during urination, urinary retention, and loss of stool control.
Even with treatment, about 10% of people who contract tetanus die. The mortality rate is higher in unvaccinated individuals, and in people over 60 years of age.
Incubation period
The incubation period of tetanus may be up to several months but is usually about ten days. In general, the farther the injury site is from the central nervous system, the longer the incubation period. Shorter incubation periods will have more severe symptoms. In trismus nascentium, 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.Generalized tetanus
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, then facial spasms,'' 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 up to four weeks, and complete recovery may take months.Neonatal tetanus
Neonatal tetanus is a form of generalized tetanus that occurs in newborns, usually those born to mothers who themselves have not been vaccinated. If the mother has been vaccinated against tetanus, the infants acquire passive immunity, and are thus protected. It usually occurs through infection of the unhealed umbilical stump, particularly when the stump is cut with a non-sterile instrument. As of 1998, neonatal tetanus was common in many developing countries, and was responsible for about 14% of all neonatal deaths. In 2010, the worldwide death toll was approximately 58,000 newborns. As the result of a public health campaign, the death toll from neonatal tetanus was reduced by 90% between 1990 and 2010, and by 2013, the disease had been largely eliminated from all but 25 countries. Neonatal tetanus is rare in developed countries.Local tetanus
Local tetanus is an uncommon form of the disease, in which people 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
Cephalic tetanus is the rarest form of the disease, and is limited to muscles and nerves in the head. It usually occurs after trauma to the head area, including: skull fracture, laceration, eye injury, dental extraction, and otitis media, but it has been observed from injuries to other parts of the body. Paralysis of the facial nerve is most frequently implicated, which may cause lockjaw, facial palsy, or ptosis, but other cranial nerves can also be affected. Cephalic tetanus may progress to a more generalized form of the disease. Due to its rarity, clinicians may be unfamiliar with the clinical presentation, and may not suspect tetanus as the illness. Treatment can be complicated, as symptoms may be concurrent with the initial injury that caused the infection. Cephalic tetanus is more likely than other forms of tetanus to be fatal, with the progression to generalized tetanus carrying a 15–30% case fatality rate.Cause
Tetanus is caused by the tetanus bacterium, Clostridium tetani. The disease is an international health problem, as C. tetani endospores are ubiquitous. Endospores can be introduced into the body through a puncture wound. Due to C. tetani being an anaerobic bacterium, it and its endospores thrive in environments that lack oxygen, such as a puncture wound. With the changes in oxygen levels, the turkey drumstick-shaped endospore can quickly spread.The disease occurs almost exclusively in people who are inadequately immunized. It is more common in hot, damp climates with soil rich in organic matter. Manure-treated soils may contain spores, as they are widely distributed in the intestines and feces of many animals, such as horses, sheep, cattle, dogs, cats, rats, guinea pigs, and chickens. In agricultural areas, a significant number of human adults may harbor the organism.
The spores can also be found on skin surfaces and in contaminated heroin. Rarely, tetanus can be contracted through surgical procedures, intramuscular injections, compound fractures, and dental infections. Animal bites can transmit tetanus.
Tetanus is often associated with rust, especially rusty nails. Although rust itself does not cause tetanus, objects that accumulate rust are often found outdoors or in places that harbor soil bacteria. Additionally, the rough surface of rusty metal provides crevices for dirt containing C. tetani, while a nail affords a means to puncture the skin and deliver endospores deep within the body at the site of the wound. An endospore is a non-metabolizing survival structure that begins to metabolize and cause infection once in an adequate environment. Hence, stepping on a nail may result in a tetanus infection, as the low-oxygen environment may exist under the skin, and the puncturing object can deliver endospores to a suitable environment for growth. It is a common misconception that rust itself is the cause; a related misconception is that a puncture from a rust-free nail is not a risk.
Pathophysiology
Tetanus neurotoxin binds to the presynaptic membrane of the neuromuscular junction, is internalized, and is transported back through the axon until it reaches the central nervous system. Here, it selectively binds to and is transported into inhibitory neurons via endocytosis. It then leaves the vesicle for the neuron cytosol, where it cleaves vesicle associated membrane protein synaptobrevin, which is necessary for membrane fusion of small synaptic vesicles. SSV's carry neurotransmitter to the membrane for release, so inhibition of this process blocks neurotransmitter release.Tetanus toxin specifically blocks the release of the neurotransmitters GABA and glycine from inhibitory neurons. These neurotransmitters keep overactive motor neurons from firing and also play a role in the relaxation of muscles after contraction. When inhibitory neurons are unable to release their neurotransmitters, motor neurons fire out of control, and muscles have difficulty relaxing. This causes the muscle spasms and spastic paralysis seen in tetanus infection.
The tetanus toxin, tetanospasmin, is made up of a heavy chain and a light chain. There are three domains, each of which contributes to the pathophysiology of the toxin. The heavy chain has two of the domains. The N-terminal side of the heavy chain helps with membrane translocation, and the C-terminal side helps the toxin locate the specific receptor site on the correct neuron. The light chain domain cleaves the VAMP protein once it arrives in the inhibitory neuron cytosol.
There are four main steps in tetanus's mechanism of action: binding to the neuron, internalization of the toxin, membrane translocation, and cleavage of the target VAMP.