What is tetanus?

Causes and Symptoms

Tetanus is a disease of the nervous system caused by the bacterium Clostridium tetani (C. tetani). Humans and most species of warm-blooded animals are susceptible to tetanus. This disease is not contagious, meaning it cannot be transmitted from one individual to another. It results from the contamination of a natural or surgical wound by spores (endospores) of C. tetani. The
bacteria grow in the wound and produce a toxin that spreads throughout the body and causes the symptoms of the disease. Neonatal tetanus is the appearance of tetanus in a child less than one month old; it is usually contracted by the infant directly following birth.

C. tetani is an anaerobic, endospore-forming bacterium. Anaerobic bacteria can grow only in an oxygen-free environment. In harsh environments or at times when oxygen is present, all species of Clostridia have the unique ability to form dormant (nongrowing) structures called endospores. These structures develop inside the bacterial cell and serve to protect the genetic material of the cell from harsh environmental stresses that would destroy an actively growing cell. Endospores are very resistant to disinfectants and temperature changes; thus, the bacteria can remain dormant until the surrounding environment becomes better suited for growth. C. tetani spores are found throughout the world in soil, human and animal intestines, and especially in soil fertilized with human or animal feces.

A person can get tetanus only if spores from the soil or elsewhere in the environment enter that person under the proper conditions to become living, growing bacteria. The bacteria will grow only if they enter a wound that is free from oxygen, such as a deep puncture wound or a wound that has considerable dead or crushed tissue. There are always a few cases of tetanus, however, that follow no apparent injury. Typical causes of
wounds that could be susceptible to tetanus are compound fractures; gunshots; dog bites; punctures caused by glass, thorns, needles, splinters, or rusty nails; “skin popping” by drug addicts; bedsores; outer ear infections; and dental extractions. The most feared form of tetanus, neonatal tetanus, is usually caused by the cutting of the
umbilical cord with an unsterile instrument or by improper care of the umbilical stump. In the United States, most cases of neonatal tetanus are found in home deliveries not attended by a health professional.

Spores of C. tetani enter the body through a wound or abrasion. In the absence of oxygen, they will germinate (revert from the dormant endospore state to become living, growing cells). The bacteria will grow and multiply but not spread from the initial site of infection. In many cases, the wound hardly appears to be infected at all. As it grows, C. tetani produces a toxin called tetanospasmin that can filter through the body. Once the toxin reaches the central nervous system, it binds to nerve cells, causing the beginning stages of symptoms to be seen. Symptoms can appear from one day to several months after infection, with the average incubation period (the time during which symptoms appear after infection) being three to twenty-one days. The wide range of incubation time depends on the amount of time needed for anaerobic conditions to develop and the time required for the toxin to reach the central nervous system.

The tetanus toxin, tetanospasmin, is a simple protein. No one knows why C. tetani makes this protein. It has no apparent role in the life of the bacterium, and it is unknown whether this toxin gives the bacterium any selective advantage for survival in the environment. It is unlikely that the bacterium makes this toxin merely to kill people and animals, yet the fact that it does kill them is all that is known about the toxin. Animals vary in their susceptibility to the effects of tetanospasmin; humans and horses are the most susceptible, while birds and cold-blooded animals are resistant. Tetanospasmin is the second most dangerous known toxin, and it is so powerful that an amount of toxin the size of one period on this page could kill thirty people. One milligram of toxin could kill 200 million laboratory mice.

To understand how tetanospasmin works to cause the symptoms of tetanus, one must first understand how muscles function. Most muscles in the body occur in pairs; one muscle in the pair, when contracted, causes that part of the body to move in one direction, and the opposing muscle in the pair, when contracted, causes that part of the body to move in the opposite direction. Normally, the nerves that control the muscle pairs stimulate one muscle in a pair to contract and signal the opposing muscle to relax. In this way, that part of the body is able to move. For example, in using an arm to lift an object, the nerves send a signal to the muscle in the front of the arm to contract and at the same time send a signal to the back of the arm to relax, so that the arm can bend upward at the elbow and lift the object. If the nerves did not signal the opposing muscle to relax, the contraction of the first muscle would cause the opposing muscle to stretch and trigger the “stretch reflex” in that muscle, causing that muscle to contract and counteract the stretch. Tetanus toxin works by binding to the nerve cells at nerve-muscle junctions and somehow
blocking the signal of relaxation to the opposing muscle; therefore, when one muscle in a pair of muscles contracts, both muscles contract. The final effect is called spastic paralysis, in which the muscles are in a state of continuous contraction, pulling against each other, causing rigidity in a normally movable part of the body.

The initial symptoms of tetanus include restlessness, irritability, a stiff neck, and difficulty swallowing. In about half of all cases, the initial symptoms include stiffness or spasms of the jaw muscles, known as lockjaw. Gradually, the skeletal muscles (muscles of the arms, legs, back, and stomach) become involved. Muscles move through stages of contractions, from merely twitching to rigid spasms that are brief but may be frequent, painful, and exhausting. Severe stages of the disease are characterized by tetanic spasms (sustained contractions) of some or all of the muscle groups. The slightest disturbance of the victim may cause spasms, generalized
seizures, or both. A typical tetanic seizure is characterized by a sudden burst of tetanic spasm of all muscle groups, causing clenching of the jaw to produce a grimace, arching of the back with the neck back, flexion of arms, clenching of fists on the chest, and extension of the lower extremities. The patient is completely conscious during such episodes and experiences intense pain. Some spasms may be severe enough to cause bones to break. Eventually, the muscles of the cardiac and respiratory systems can be affected. Spasms of the throat muscles and respiratory muscles may lead to suffocation or respiratory arrest. The toxin may affect the circulatory system and heart in such a way as to increase the heart rate, increase blood pressure, and cause constriction of blood vessels. Death caused by tetanus is usually a result of circulatory collapse or respiratory failure.

Treatment and Therapy

Tetanus is diagnosed mainly on the basis of the symptoms present and the case history of the patient—the vaccination record and the type of injury sustained. A patient with no recent history of tetanus vaccination who receives a puncture or trauma wound is often treated for tetanus with an injection of antitoxin even before any symptoms appear. Antitoxin is quite effective when given to prevent the symptoms from appearing, but less so when given after the symptoms have already appeared. While other diseases are diagnosed after the organism that causes the disease is isolated from the site of the infection, it is very difficult to diagnose tetanus based on the ability to isolate the C. tetani bacteria from the wound, for several reasons. First, Clostridia are present in almost every wound, but they do not always cause disease, so finding them does not necessarily mean that the bacteria are active. Second, there are many other contaminating bacteria
in wounds, which makes it difficult to tell which may be causing disease or whether Clostridia are there at all. In addition, the number of C. tetani bacteria needed to cause disease is quite small, which makes them harder to isolate. Finally, Clostridia, because of their anaerobic nature, are difficult to grow.

Tetanus may take from a few days to several weeks to run its course. Patients who exhibit certain patterns in the course of the disease usually have a poor chance of recovery. These include patients with a short incubation period between the time of the injury and the onset of seizures, patients who exhibit a rapid development from mild muscle spasms to tetanic spasms, patients with injuries close to the head, patients with a high frequency or strong severity of seizures, and patients who are very young or very old. Patients who do recover usually return to a completely normal state after a variable period of stiffness; except for possible damage to the lungs from pulmonary complications or bone fractures, tetanus leaves no permanent damage. Unfortunately, recovery from the disease does not make the patient immune to future attacks, as with other diseases. The amount of toxin needed to kill a person is not even close to enough toxin to stimulate the patient’s immune response to make the patient immune to the disease. Only vaccination with a large dose of inactive toxin can
give a person immunity to tetanus.

Tetanus is difficult to treat because no one knows exactly what the toxin does. Doctors know only what kinds of symptoms the toxin causes, so the treatment is mainly symptomatic and is directed at preventing the production of more toxin. Antitoxin is given to block the attachment to the nerve cells of any free toxin that might be circulating in the body. Antitoxin has absolutely no effect on toxin that is already fixed to nerve tissue, but it can fully neutralize any free toxin. Originally, doctors used serum from immunized horses as a source of antitoxin, but this caused serious side effects (namely, serum sickness) in patients, so it is recommended that only pooled hyperimmune human globin (purified serum from immunized humans) be used as a source of antitoxin. Second, large doses of an antibiotic such as penicillin are given to kill any remaining bacteria, in order to prevent the bacteria from producing more toxin. If the patient is allergic to penicillin, tetracycline or clindamycin can be given instead. In addition, the wound may need to be cleansed of any dead tissue, to remove the anaerobic environment necessary for growth of the bacteria.
Third, the muscle spasms need to be controlled. Mild muscle spasms are controlled with barbiturates and diazepam (Valium); severe spasms need a curarelike agent (D tubocurarine is used to poison the paralyzed muscles so that they do not contract) that completely paralyzes the patient. These various muscle relaxants are used to ease the contractions until the toxin already present at the nerve sites wears out. The patient can be put on a positive-pressure breathing apparatus to maintain respiration. A
tracheostomy (an operation in which an opening into the trachea, or windpipe, is made) may be necessary to minimize respiratory complications. Also, patients are often kept in quiet dark rooms that reduce auditory and visual stimuli, in order to minimize the frequency and severity of the tetanic spasms. Even with all these treatment measures, three out of five persons who contract tetanus will die.

The best means of controlling tetanus is prevention. In fact, tetanus is nearly 100 percent preventable with active or passive immunization. Active immunization involves stimulating a person’s immune system to produce its own antibody to fight off the disease. An injection of tetanus toxoid is given to immunize actively against tetanus. Tetanus toxoid is purified tetanus toxin that has been treated with formaldehyde to be rendered nontoxic (meaning that it will not cause any symptoms of tetanus) but is still capable of stimulating the immune system to produce antitoxin antibody. Active immunization usually lasts a long time, because the cells that make the antibody can keep making more antibody when the first batch runs out or whenever the person comes in contact with tetanus toxin in the future. The tetanus toxoid is usually administered as part of the DPT vaccine. This vaccine protects
against diphtheria (D), pertussis (P), and tetanus (T). In the United States, it is recommended that persons be immunized against tetanus at two, four, six, and eighteen months of age, with a booster at four to six years of age and one every ten years after that. Surveys indicate, however, that more than 50 percent of adults over sixty years of age are not protected against tetanus. It is as dangerous to receive too many booster shots for tetanus as it is to receive too few. With too few shots, a person runs the risk of succumbing to the disease and dying. With too many shots, a person runs the risk of developing a potentially fatal allergic reaction to the vaccine. It is best to keep careful records of all vaccinations and to be certain that one receives a tetanus booster every ten years.

Passive immunization involves giving a person antibodies (made in an outside source) that will protect that person from a disease, instead of stimulating the individual to make antibodies. Patients thought to be at risk for tetanus can be given an injection of antitoxin for protection. This type of protection works only for a short period of time, because once the antibody in the injection is used up, the patient cannot make more. The way to immunize infants passively against neonatal tetanus is to immunize their mothers actively. A pregnant patient immunized with tetanus toxoid will produce antitoxin that is passed on to the baby’s blood through the placenta. The baby is then born carrying some antitoxin antibodies in its blood that can protect it from neonatal tetanus.

Perspective and Prospects

As early as the fourth century BCE, Hippocrates described tetanus as a common killer of women in childbirth, wounded soldiers, and infants. It was not until 1889, however, that the cause of tetanus, C. tetani, was first isolated by Shibasaburo Kitasato. In the early twentieth century, W. T. Glenny and Gaston Ramon paved the way for the development of a tetanus vaccine by discovering tetanus toxoid. War-related cases of tetanus were virtually eliminated by vaccinating soldiers. During World War II, only 12 cases of tetanus were recorded among 2,735,000 hospital admissions for wounds and injuries in soldiers previously immunized. This result led most state legislatures in America to pass laws requiring adequate immunization for tetanus before entering school.

Despite advances in treatment, the mortality rate for tetanus is quite high. The United States has about one hundred cases per year, mostly in the very young, who are in frequent contact with the soil, or in the very old, who have weakened immune systems. Many cases in the United States arise from trivial but fairly deep injuries that are thought to be too minor to bring to a physician. Sporadic cases are most frequently seen in the South, the Southeast, and the Midwest.

Tetanus is relatively rare in developed countries, where routine immunizations are available; it is, however, a common and uncontrolled disease in the developing world. Tetanus is a health problem in developing countries because of the lack of immunization, unsanitary living conditions, and the performance of common wound-causing procedures (such as ear piercing, tattooing, circumcision, and abortion) in an unsanitary manner. Neonatal tetanus is often caused by mothers or midwives who cut the umbilical cord with an unsanitary instrument. In addition, it is a tradition in many developing nations to apply soil, clay, or cow dung to the cut umbilical cord, which can inoculate tetanus spores right into the wound. Throughout the world, nearly 3.5 million children (mostly under five years of age) die yearly of three infectious diseases for which immunization is available. Two million die of measles, eight hundred thousand die of tetanus, and six hundred thousand die of whooping cough; another four million die of various kinds of diarrhea. In parts of some developing nations, 10 percent of deaths within a month of birth are caused by neonatal tetanus. The
World Health Organization is making a concerted effort to reduce the incidence of tetanus—especially neonatal tetanus—in developing nations by providing the personnel and resources needed for vaccination. Strategies for reducing the incidence of neonatal tetanus include providing passive immunity to newborns through the immunization of the mothers. Also important are promotion of safe practices, such as clean deliveries and clean cord cutting, and ensuring that unsanitary substances are not applied to cord wounds.

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