eMedicine Specialties > Infectious Diseases > CNS Infections

Tetanus

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital

Updated: Jul 18, 2006

Introduction

Background

The word tetanus comes from the Greek tetanos, which is derived from the term teinein, meaning to stretch. Tetanus appears in military medical documents throughout the ages. Slapping infected dung on the umbilical cords of newborns (ie, as part of ritualistic ceremonies) caused rampant tetanus neonatorum or trismus nascentium in the West Indies and in Africa. Osler's textbook describes the "eight days sickness" caused by umbilical sepsis, which killed 84 of 125 children within a fortnight of birth in St. Kilda, Scotland. During World War I, tetanus occurred in 1.47 per 1000 British wounded and in 12.5 per 1000 persons involved in the Peninsular campaign. Nicolaier discovered the anaerobic bacillus Clostridium tetani in 1885. In 1889, Koch's pupil, Kitasato, obtained the bacillus of tetanus in pure culture and associated the disease to animals.

Although rare, the disease has not been eradicated, and early diagnosis and intervention are life saving. Prevention is the ultimate management strategy for tetanus. The 4 clinical types of tetanus are generalized, local, cephalic, and neonatal.

Neonatal tetanus is a major cause of infant mortality in underdeveloped countries, but this form is rare in the United States. Infection results from cord contamination during unsanitary delivery conditions, coupled with a lack of maternal immunization. At the end of the first week of life, infected infants become irritable, feed poorly, and develop rigidity with spasms. This form of tetanus has a very poor prognosis for survival.

Cephalic tetanus is uncommon and usually occurs following head trauma or otitis media. Patients with this form present with cranial nerve palsies. The infection may be localized or may become generalized.

Patients with local tetanus present with persistent rigidity in the muscle group close to the injury site. The muscular rigidity is caused by a dysfunction in the interneurons that inhibit the alpha motor neurons of the affected muscles. No further CNS involvement occurs, and this form has very low mortality rates.

Approximately 50-75% of patients with generalized tetanus present with trismus secondary to masseter muscle spasm. Nuchal rigidity and dysphagia also are early complaints that cause risus sardonicus, the ironic smile of tetanus, resulting from facial muscle involvement. As the disease progresses, patients have generalized muscle rigidity with intermittent reflex spasms in response to stimuli (ie, noise, touch). Tonic contractions cause opisthotonus (ie, flexion and adduction of the arms, clenching of the fists, extension of the lower extremities). During these episodes, patients have intact sensorium and feel severe pain. The spasms can cause fractures, tendon ruptures, and acute respiratory failure.

Pathophysiology

Tetanus results from infection with C tetani, a mobile, spore-forming, anaerobic, gram-positive bacillus. This bacillus is found in or on soil, manure, dust, clothing, skin, and 10-25% of human GI tracts. The spores need tissue with the proper anaerobic conditions to germinate; the ideal media are wounds with tissue necrosis.

Under anaerobic conditions, the spores of C tetani germinate and produce 2 toxins: tetanolysin (a hemolysin with no recognized pathologic activity) and tetanospasmin, which is responsible for tetanus. The action of the latter helps explain the clinical manifestations of the disease.

Tetanospasmin is synthesized as a single 151-kd chain and is cleaved to generate toxins with 2 chains joined by a single disulfide bond. The heavy chain (100 kd) is responsible for specific binding to neuronal cells and for protein transport. The light chain (50 kd) blocks the release of neurotransmitters.

These processes are accompanied by autonomic nervous system instability. The toxin binding may be irreversible; recovery depends on the sprouting of new axonal terminals. Once the toxin is synthesized, it moves from the contaminated site to the spinal cord in 2-14 days. When the toxin reaches the spinal cord, localized or cephalic tetanus may occur initially, followed by generalized tetanus.

Frequency

United States

Incidence has declined with the advent of active immunization. Reports indicate that 560 cases occurred in 1947; 101 cases occurred in 1974; 60-80 cases occurred each year during the 1980s; and 47 cases occurred in California in 1997. Almost all cases occur in persons who are partially immunized or nonimmunized. The incidence of patients who contract tetanus despite full immunization is extremely rare (ie, ~4 per 100 million persons who are immunocompetent and vaccinated).

International

Reports show up to 1 million cases annually, mostly in underdeveloped countries. Neonatal tetanus accounts for 50% of the tetanus-related deaths in developing countries.

Mortality/Morbidity

• Tetanus results in approximately 5 deaths per year in the United States.
• Mortality in the United States resulting from generalized tetanus is 30% overall, 52% in patients older than 60 years, and 13% in patients younger than 60 years.
• Residual neurologic sequelae are uncommon. Mortality usually results from autonomic dysfunction (ie, extremes in blood pressure, dysrhythmia, cardiac arrest).

Age

In the United States, 59% of cases and 75% of deaths occur in persons aged 60 years or older.

Clinical

History

Most cases in the United States occur in patients with a history of only partial immunization. Persons who inject drugs also constitute a high-risk group.

• Symptoms usually begin 8 days after the infection, but onset may range from 3 days to 3 weeks.
• Patients may report a sore throat with dysphagia (early sign).
• Localized tetanus causes muscle rigidity at the site of spore inoculation.
• The initial manifestation may be local tetanus, in which the rigidity affects only 1 limb or area of the body where the clostridium-containing wound is located.

Physical

Common first signs of tetanus are headache and muscular stiffness in the jaw (ie, lockjaw), followed by neck stiffness, difficulty swallowing, rigidity of abdominal muscles, spasms, and sweating.

• Patients often are afebrile.
• Severe tetanus results in opisthotonos, flexion of the arms, extension of the legs, periods of apnea resulting from spasm of the intercostal muscles and diaphragm, and rigidity of the abdominal wall.
• Late in the disease, autonomic dysfunction develops, with hypertension and tachycardia alternating with hypotension and bradycardia.

Causes

The source of infection usually is a wound (~65%), which often is minor (eg, wood or metal splinters, thorns). Chronic skin ulcers are the source in approximately 5% of cases, and in the remainder of cases, no obvious source is identified.

• The US Centers for Disease Control and Prevention (CDC) statistics from 1982-84 are as follows:
  • Infected lacerations or puncture wounds (69%)
  • Infected chronic wounds and abscesses (20%)
  • Exposure via intravenous drug abuse (3%)
  • Neonates (1%)
  • Other or no identifiable cause (7%)
• Possible causes not usually associated with tetanus
  • Otitis media
  • Burns
  • Intranasal foreign bodies
  • Corneal abrasions
  • Foreign bodies
  • Dental or surgical procedures

Differential Diagnoses

Dystonia, Tardive

Other Problems to Be Considered

Strychnine poisoning
Dental infections
Local infections
Hysteria
Neoplasms
Encephalitis

Workup

Laboratory Studies

• Laboratory findings are not diagnostically valuable, but they may help exclude strychnine poisoning.
• Blood counts and blood chemical findings are unremarkable.
• A lumbar puncture is not necessary. Cerebrospinal fluid (CSF) is normal, except for an increased opening pressure, especially during spasms.
• Blood counts and blood chemical findings are unremarkable.
• Serum antitoxin levels more than 0.01 U/mL usually are protective, making the diagnosis less likely.

Imaging Studies

• Imaging studies of the head and spine reveal no abnormalities.

Treatment

Medical Care

Passive immunization with human tetanus immune globulin (TIG) shortens the course of tetanus and may lessen its severity. A dose of 500 U appears as effective as larger doses.

• Supportive therapy may include ventilatory support and pharmacologic agents that treat reflex muscle spasms, rigidity, and tetanic seizures.
• Benzodiazepines have emerged as the mainstay of symptomatic therapy for tetanus. To prevent spasms that last longer than 5-10 seconds, administer diazepam intravenously, typically 10-40 mg every 1-8 hours. Vecuronium (by continuous infusion) or pancuronium (by intermittent injection) are adequate alternatives.
• Penicillin G, which has been used widely for years, is not the drug of choice. Metronidazole (eg, 0.5 g q6h) has comparable or better antimicrobial activity, and penicillin is a known antagonist of GABA, as is tetanus toxin.
• Physicians also use sedative hypnotics, narcotics, inhalational anesthetics, neuromuscular blocking agents, and centrally acting muscle relaxants (eg, intrathecal baclofen).
• To date, reports indicate that more than 26 adults with severe tetanus have been treated with intrathecal baclofen. A representative dose of the continuous infusion is 1750 mcg per day. Case reports and small case series outline the efficacy of intrathecal baclofen in controlling muscle rigidity. The effects of baclofen begin within 1-2 hours and persist 12-48 hours. The half-life elimination of baclofen in CSF ranges from 0.9-5 hours. After lumbar intrathecal administration, the cervical-to-lumbar concentration ratio is 1:4. The major adverse effect of baclofen is a depressed level of consciousness (LOC) and respiratory compromise.

Medication

The goals of pharmacotherapy are to prevent complications and to reduce morbidity.

Antimicrobials

Therapy must cover all likely pathogens in the context of the clinical setting.

Metronidazole (Flagyl)

A study comparing oral metronidazole to intramuscular penicillin showed better survival, shorter hospitalization, and less progression of disease in the metronidazole group (dosed at 0.5 g q6h or 1 g q12h IV for 7-10 d).

Dosing

Adult

0.5 g PO q6h for 7-10 d; alternatively, 1 g IV q12h for 7-10 d

Pediatric

15-30 mg/kg/d PO divided bid/tid for 7 d, or 40 mg/kg once; not to exceed 2 g/d
Weight-based dosing:
Body weight <2000 g
0-7 days: 7.5 mg PO/IV q24h
8-28 days: 7.5 mg PO/IV q12h
Body weight >2000 g
0-7 days: 7.5 mg PO/IV q12h
8-28 days: 15 mg PO/IV q12h

Interactions

Cimetidine may increase toxicity of metronidazole; may increase effects of anticoagulants; may increase toxicity of lithium and phenytoin; disulfiramlike reaction may occur with orally ingested ethanol

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Adjust dose in hepatic disease; monitor for seizures and development of peripheral neuropathy

Penicillin G (Pfizerpen)

Interferes with synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms.

Dosing

Adult

4 million U IV q4h

Pediatric

100,000-250,000 U/kg/d divided qid

Weight-based dosing:
Body weight <2000 g
<7 days: 50,000 U IV q12h
8-28 days: 75,000 U IV q12h
Body weight >2000 g
<7 days: 50,000 U IV q8h
> 8 days: 50,000 U IV q6h

Interactions

Probenecid can increase effects; coadministration of tetracyclines can decrease effects

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Caution in impaired renal function

Doxycycline (Vibramycin)

Inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.

Dosing

Adult

100 mg IV q12h

Pediatric

<8 years: Not recommended
>8 years: 2-4 mg/kg/d IV q12h

Interactions

Bioavailability minimally decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

D - Unsafe in pregnancy

Precautions

Photosensitivity is rare; use during tooth development (last half of pregnancy through 8 y) can cause permanent discoloration of teeth

Follow-up

Further Inpatient Care

• Administer a second dose (usually the first is upon discharge from the hospital) of tetanus-diphtheria vaccine or diphtheria-pertussis-tetanus vaccine, and administer a third dose 4 weeks after the second dose.

Deterrence/Prevention

• An effective vaccine termed tetanus toxoid has been available for many years. Administer tetanus toxoid in combination with diphtheria toxoid and pertussis vaccine (DTP) to children at ages 2 months, 4 months, 6 months, 12-15 months, and between 4-6 years. Administer tetanus and diphtheria (TD) toxoid to children aged 7 years or older. Recommend a tetanus booster shot every 10 years.
• Administer tetanus and diphtheria (TD) toxoid to children aged 7 years or older. Recommend a tetanus booster shot every 10 years.
• The tetanus vaccine and the combination TD vaccine are very safe and effective; however, infrequent adverse effects include a slight fever and soreness, redness, or swelling at the injection site.
• Patients cannot contract tetanus from the vaccine.
• Candidates for TD vaccine include all adults who have not had a booster shot in the last 10 years, adults who have recovered from tetanus (ie, lockjaw) disease, and adults who have never received immunization against tetanus.
• Physicians must thoroughly clean wounds and remove dead or devitalized tissue. If the patient has not had a tetanus toxoid booster in the previous 10 years, administer a single booster injection on the day of injury. For severe wounds, consider administering a booster if more than 5 years have elapsed since the last dose.
• Consider administering TIG, antitoxin, or antibiotics if the patient has not been previously immunized with a series of at least 3 doses of toxoid.
• Given the risk of tetanus after bites of all kinds, administer TIG and tetanus toxoid to patients who have had 2 or fewer primary immunizations. Physicians may administer tetanus toxoid alone to patients who have completed a primary immunization series but who have not received a booster in more than 5 years.
• Almost 70% of a random sample of US residents aged 6 years or older have protective levels of tetanus antibodies. By age 60-69 years, the prevalence of protective antibodies is less than 50%, and by age 70 years, the prevalence is approximately 30%.
• Tetanus toxoid is a very effective immunogen that stimulates a protective response in virtually all immunocompetent subjects. Studies of former military personnel show that up to 88% have protective antibody levels 15 years after vaccination.

Complications

• Complications include spasm of the vocal cords and/or spasms of the respiratory muscles that cause interference with breathing. Other complications include fractures of the spine or long bones, hypertension, abnormal heartbeats, coma, generalized infection, clotting in the blood vessels of the lung, pneumonia, and death.
• Patients experience severe pain during each spasm. During the spasm, the upper airway can be obstructed, or the diaphragm may participate in the general muscular contraction.
• Sympathetic overactivity is the major cause of tetanus-related death in the intensive care unit. Sympathetic hyperactivity usually is treated with labetalol at 0.25-1 mg per minute as needed for blood pressure control or with morphine at 0.5-1 mg/kg per hour by continuous infusion.
• Neonatal tetanus follows infection of the umbilical stump, most commonly resulting from a failed aseptic technique in a mother who is inadequately immunized. The mortality rate of neonatal tetanus exceeds 90%, and developmental delays are common among survivors.

Prognosis

• Current statistics indicate that the mortality rate in mild and moderate tetanus is approximately 6%; for severe tetanus, the mortality rate may be as high as 60%.
• CDC reports from 1982-90 show that the overall case-fatality rate in the United States is 21-31%.

Patient Education

• For excellent patient education resources, visit eMedicine's Infections Center. Also, see eMedicine's patient education article Tetanus.

Miscellaneous

Special Concerns

• Strychnine poisoning is the only condition that truly mimics tetanus.
• A number of conditions (eg, dental or other local infections, hysteria, neoplasms, encephalitis) may cause trismus, and physicians must differentiate these conditions from tetanus. The conditions listed do not cause manifestations of tetanus, other than trismus.

References

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Keywords

tetanus, lockjaw, nuchal rigidity, dysphagia, risus sardonicus, Clostridium tetani, C tetani, tetanus neonatorum, trismus nascentium, umbilical sepsis, generalized tetanus, local tetanus, cephalic tetanus, neonatal tetanus, tetanolysin, tetanospasmin

Contributor Information and Disclosures

Author

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Medical Editor

Gregory William Rutecki, MD, Associate Professor, Program Director, Department of Internal Medicine, Feinberg School of Medicine, Northwestern University
Gregory William Rutecki, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society of Nephrology, National Kidney Foundation, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Richard B Brown, MD, FACP, Chief, Division of Infectious Diseases, Baystate Medical Center; Professor, Department of Internal Medicine, Tufts University School of Medicine
Richard B Brown, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Chest Physicians, American College of Physicians, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America, and Massachusetts Medical Society
Disclosure: Nothing to disclose.

CME Editor

Michael E Zevitz, MD, Assistant Professor of Medicine, Finch University of the Health Sciences, The Chicago Medical School; Consulting Staff, Private Practice
Michael E Zevitz, MD is a member of the following medical societies: American College of Cardiology, American College of Physicians, American Medical Association, and Michigan State Medical Society
Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

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