eMedicine Specialties > Emergency Medicine > Infectious Diseases

Tetanus

Author: Daniel J Dire, MD, FACEP, FAAP, FAAEM, Clinical Associate Professor, Department of Emergency Medicine, University of Texas-Houston
Contributor Information and Disclosures

Updated: Mar 17, 2009

Introduction

Background

Tetanus is an illness characterized by an acute onset of hypertonia, painful muscular contractions (usually of the muscles of the jaw and neck), and generalized muscle spasms without other apparent medical causes.

Although records from antiquity (5th century BC) contain descriptions of tetanus, it was Carle and Rattone in 1884 who first produced tetanus in animals. This was accomplished by injecting them with pus from a fatal human tetanus case. During that same year, Nicolaier produced tetanus in animals by injecting them with soil. In 1889, Kitasato isolated the organism from an infected human, showed that it produced disease when injected into animals, and reported that the toxin could be neutralized by specific antibodies. In 1897, Nocard demonstrated the protective effect of passively transferred antitoxin. Passive immunization in humans was used for treatment and prophylaxis during World War I. Tetanus toxoid was developed by Descombey in 1924. It was first widely used during World War II.

Despite widespread immunization of infants and children in the United States since the 1940s, tetanus still occurs in the United States. Currently, tetanus is a severe disease primarily of older adults who are unvaccinated or inadequately vaccinated. Worldwide, most reported cases of tetanus are the neonatal type. The last reported case of neonatal tetanus in the United States was in 1998; this was only the second case since 1989, and neither of the mothers had ever received tetanus vaccinations.

For more information, see Medscape's Vaccine Resource Center.

Pathophysiology

Clostridium tetani, an obligate anaerobic gram-positive bacillus, causes tetanus. This bacterium is nonencapsulated and forms spores, which are resistant to heat, desiccation, and disinfectants. The spores are ubiquitous and are found in soil, house dust, animal intestines, and human feces.

Spores that gain entry can persist in normal tissue for months to years. Under anaerobic conditions, these spores geminate and elaborate tetanospasmin and tetanolysin. Tetanolysin is not believed to be of any significance in the clinical course of tetanus. Tetanospasmin is a neurotoxin and causes the clinical manifestations of tetanus. Tetanospasmin that is released by the maturing bacilli is distributed via the lymphatic and vascular circulations to the end plates of all nerves. Tetanospasmin then enters the nervous system peripherally at the myoneural junction and is transported centripetally into neurons of the central nervous system (CNS). Per weight, tetanospasmin is one of the most potent toxins known. The estimated minimum lethal dose is 2.5 nanograms per kilogram of body weight (a nanogram is one billionth of a gram), or 175 nanograms for a 70-kg (154-lb) human.

These neurons become incapable of neurotransmitter release. The neurons, which release gamma-aminobutyric acid (GABA) and glycine, the major inhibitory neurotransmitters, are particularly sensitive to tetanospasmin, leading to failure of inhibition of motor reflex responses to sensory stimulation. This results in generalized contractions of the agonist and antagonist musculature characteristic of a tetanic spasm. The shortest peripheral nerves are the first to deliver the toxin to the CNS, which leads to the early symptoms of facial distortion and back and neck stiffness.

Once the toxin becomes fixed to neurons, it cannot be neutralized with antitoxin. Recovery of nerve function from tetanus toxins requires sprouting of new nerve terminals and formation of new synapses.

Frequency

United States

Reported incidence of tetanus has declined substantially since the mid 1940s because of the widespread use of tetanus immunizations (see Media file 1).

Of the 130 cases of tetanus reported in the United States from 1998-2000, California and Texas had the highest reported number of cases. All 50 states require that children be vaccinated prior to admission to public schools. More than 96% of children have received 3 or more diphtheria and tetanus toxoids plus pertussis (DTP) vaccinations by the time they begin school. The annual incidence of tetanus has dropped to fewer than 50 cases per year in the United States.

Heroin users, particularly persons who inject themselves subcutaneously, appear to be at high risk for tetanus. Quinine is used to dilute heroin and may support the growth of C tetani. The incidence of tetanus in people who use injection drugs increased 7.4%, from 3.6% of all cases in 1991-1994 to 11% of cases in 1995-1997. People who use injection drugs accounted for 15% of the tetanus cases in the United States from 1998-2000 (see Media file 4). Of the 19 people who used injection drugs and contracted tetanus from 1998-2000, only 1 reported an acute injury.

International

Worldwide, tetanus is predominantly a disease of underdeveloped countries located in warm, damp climates. Tetanus affects all age groups, with the highest prevalence found in newborns and young people. In 1992, an estimated 578,000 infant deaths occurred due to neonatal tetanus. In 1998, 215,000 deaths occurred with more than 50% of these on the Africa continent. Tetanus is one of the target diseases of the World Health Organization (WHO) Expanded Program on Immunization. Overall, the annual incidence of tetanus is 0.5-1 million cases. WHO estimated there were 213,000 tetanus deaths in 2002 with 198,000 occurring in children younger than 5 years.

Developed nations have incidences of tetanus similar to those observed in the United States. For instance, only 126 cases of tetanus were reported in England and Wales in 1984-1992.

Mortality/Morbidity

Overall, the mortality rate is approximately 45%. Clinical tetanus is less severe among patients who have a history of receiving a primary series of tetanus toxoid sometime during their life as compared with patients who are inadequately vaccinated or unvaccinated. The mortality rate in the United States is 6% for individuals who had previously received 1-2 doses of tetanus toxoid compared with 15% for individuals who were unvaccinated.

• The case-fatality ratio in the United States was 18% from 1998-2000 and 11% from 1995-1997; a case-fatality ratio of 91% was reported in 1947.¹
• The mortality rate is highest for people older than 60 years (40%) compared with those aged 20-59 years (8%). From 1998-2000, 75% of the deaths in the United States were in patients older than 60 years.¹
• The mortality rate is 30% for people who require mechanical ventilation but only 4% for those who do not.

Race

From 1998, the incidence of tetanus in the United States was highest among Hispanics (0.38 cases per million population), followed by whites (0.13 cases per million population), and then African Americans (0.12 cases per million population).¹

Sex

A difference in the levels of tetanus immunity exists between the sexes.

• Overall, men are believed to be better protected than women, perhaps because of additional vaccinations administered during military service or professional activities.
• In the United States from 1998-2000, the incidence of tetanus in males aged 59 years and younger was 2.8 times higher than in females in the same age range.
• In developing countries, women have an increased immunity where tetanus toxoid is administered to women of childbearing age to prevent neonatal tetanus.

Age

The incidence of tetanus increases with advancing age. From 1980 through 2000, 70% of reported cases of tetanus in the United States were among persons aged 40 years or older. Of all these patients, 36% are older than 59 years and only 9% are younger than 20 years.

Clinical

History

• From 1995-2000, 81% of cases in the United States were generalized tetanus, 15% were localized, 3% were cephalic, and 1 case of neonatal tetanus was reported.
• Almost all reported cases of tetanus are in persons who have either never been vaccinated or who completed a primary series but have not had a booster in the preceding 10 years. From 1995-1997, 54% of the reported cases in the United States had an unknown tetanus vaccination history, 22% had no known previous tetanus vaccination, 9% had 1 previous dose, 3% had 2 previous doses, 3% had 3 previous doses, and 9% had 4 or more previous doses.
• The median incubation period is 7 days, and, for most cases (73%), incubation ranges from 4-14 days.
• The incubation period is shorter than 4 days in 15% of cases and longer than 14 days in 12% of cases.
• Patients with clinical manifestations occurring within 1 week of an injury have more severe clinical courses.
• Patients with generalized tetanus present with trismus (ie, lockjaw) in 75% of cases.
• Other presenting complaints include stiffness, neck rigidity, dysphagia, restlessness, and reflex spasms.
• Subsequently, muscle rigidity becomes the major manifestation.
• Muscle rigidity spreads in a descending pattern from the jaw and facial muscles over the next 24-48 hours to the extensor muscles of the limbs.
• Dysphagia occurs in moderately severe tetanus due to pharyngeal muscle spasms, and onset is usually insidious over several days.
• Reflex spasms develop in most patients and can be triggered by minimal external stimuli such as noise, light, or touch. The spasms last seconds to minutes; become more intense; increase in frequency with disease progression; and can cause apnea, fractures, dislocations, and rhabdomyolysis.
• Laryngeal spasms can occur at any time and can result in asphyxia.
• Other symptoms include elevated temperature, sweating, elevated blood pressure, and episodic rapid heart rate.
• Sustained contraction of facial musculature produces a sneering grin expression known as risus sardonicus.

Physical

• The lower extremity is the site of antecedent acute injury in 52% of patients, the upper extremity is the site of antecedent injury in 34% of patients, and head or trunk is the site of antecedent injury in 5% of patients.
• Autonomic dysfunction in patients with severe tetanus manifests as extremes in blood pressure, dysrhythmias, and cardiac arrest.
• Neonatal tetanus presents with an inability to suck 3-10 days after birth. Presenting symptoms include irritability, excessive crying, grimaces, intense rigidity, and opisthotonus.
• Tetanic seizures may occur and portend a poor prognosis.
  • Frequency and severity of seizures are related to severity of the disease.
  • Seizures resemble epileptic seizures with the presence of a sudden burst of tonic contractions.
  • However, the patient does not lose consciousness and usually experiences severe pain.
  • Seizures frequently occur in the muscle groups causing opisthotonos, flexion and abduction of the arms, clenching of the fists against the thorax, and extension of the lower extremities.
• Localized tetanus is characterized by painful spasms of the group of muscles in close proximity to the site of injury. This disorder may persist for several weeks but is usually self-limiting.
• Cephalic tetanus is a rare form of the disease that is usually secondary to chronic otitis media or head trauma.
  • Cephalic tetanus is characterized by variable cranial nerve (CN) palsies; CN VII is most frequently involved.
  • Ophthalmoplegic tetanus is a variant that develops after penetrating eye injuries and results in CN III palsies and ptosis.
  • Patients with cephalic tetanus who are untreated progress to generalized tetanus.
• Patients with tetanus may present with abdominal tenderness and guarding, mimicking an acute abdomen. Exploratory laparotomies have been performed before the correct diagnosis was apparent.
• Tetanospasmin has a disinhibitory effect on the autonomic nervous system (ANS).
  • ANS dysfunction becomes progressively evident as the level of toxin in the CNS increases.
  • ANS disturbances, such as sweating, fluctuating blood pressure, episodic tachydysrhythmia, and increased release of catecholamines, are observed.
  • Drugs with beta-blocker effects have been used to control the cardiovascular manifestations of ANS instability, but they also have been associated with increased risk of sudden death.

Causes

• Only 12-14% of patients with tetanus in the United States have received a primary series of tetanus toxoid. During 1998-2000, only 6% of all patients with tetanus were known to be current with tetanus immunization, with no fatal cases reported among this group.¹
• In 73% of patients with tetanus in the United States, tetanus occurred after an acute injury, including puncture wounds (50%), lacerations (33%), and abrasions (9%).
• Of those who obtained medical treatment of their injury in the United States from 1998-2000, 96% were administered tetanus immune globulin as part of their treatment; 55% of patients required the use of assisted ventilation and 31% of these patients died.
• Stepping on a nail accounted for 32% of the puncture wounds.
• Tetanus can occur in burn victims; in patients receiving intramuscular injections; in persons obtaining a tattoo; and in persons with frostbite, dental infections (eg, periodontal abscesses), penetrating eye injuries, and umbilical stump infections.
• Other reported risk factors include diabetes, chronic wounds (eg, skin ulcers, abscesses, gangrene), parenteral drug abuse, and recent surgery (4% of US cases).
• Twelve percent of patients with tetanus in the United States from 1998-2000 had diabetes (with a mortality rate of 31%) compared with 2% during 1995-1997. Of these patients, 69% had acute injuries, while 25% had gangrene or a diabetic ulcer.
• The median time interval between surgery and onset of tetanus is 7 days.
• Tetanus has been reported after tooth extractions, root canal therapy, and intraoral soft tissue trauma.
• Worldwide risk factors for neonatal tetanus are as follows:
• 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 (eg, animal dung, mud, clarified butter) are risk factors for neonates.
• Immunity from tetanus decreases with advancing age.
• Serologic testing for immunity has revealed a low level among elderly individuals in the United States.
• Approximately 50% of adults older than 50 years are nonimmune because they never were vaccinated or do not receive appropriate booster doses.
• Prevalence of immunity to tetanus in the United States is greater than 80% for those aged 6-39 years but only 28% for persons older than 70 years.

• Search for CME/CE on This Topic »

• Tetanus (Infectious Diseases)
• Tetanus (Pediatrics: General Medicine)
• Stiff Person Syndrome (Neurology)
• Delayed-type Hypersensitivity (Pediatrics: General Medicine)

• Tetanus Overview
• Tetanus Causes
• Tetanus Treatment
• Infections Center
• Tetanus Symptoms

• Minimum Interval DTaP Schedule May Increase Receipt of Other Vaccines
• Jury out on Added Benefit of Combined DTP-HBV-HIB Vaccine
• Recommended Childhood Vaccines Safe for Children With Inborn Errors of Metabolism

• Licensure of a Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus, and Haemophilus b Conjugate Vaccine and Guidance for Use in Infants and Children
• It's Always Time to Immunize
• British HIV Association Guidelines for Immunization of HIV-Infected Adults 2008