Tetanus 

The word tetanus comes from the Greek tetanos, which is derived from the term teinein, meaning to stretch. Tetanus was first described by the ancient Egyptians in the Edwin Smith Papyrus around 3000 BC. Tetanus has also appeared in military medical documents throughout the ages. Slapping 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. In 1884, Arthur Nicolaier discovered the anaerobic bacillus Clostridium tetani. In 1889, Shibasaburo Kitasato obtained the bacillus of tetanus in pure culture and linked the disease toanimals. The tetanus toxoid vaccine was discovered by P. Descombey in 1924 during World War II.

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 of tetanus is rare in the United States. Infection results from umbilical cord contamination during unsanitary delivery, 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. Neonatal tetanus has a very poor prognosis.^{[1, 2]}

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 ("lockjaw"), which is the inability to open the mouth secondary to masseter muscle spasm. Nuchal rigidity and dysphagia are also early complaints that cause risus sardonicus, the scornful smile of tetanus, resulting from facial muscle involvement.^[3] As the disease progresses, patients have generalized muscle rigidity with intermittent reflex spasms in response to stimuli (e.g. 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.

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.^[4]

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 the clinical manifestations of tetanus^[20] . Tetanospasmin is synthesized as a 150-kDa protein that consists of a 100 kDa heavy chain and a 50 kDa light chain joined by a disulfide bond^[29] . The heavy chain mediates binding of tetanospasmin to the presynaptic motor neuron and also creates a pore for the entry of the light chain into the cytosol. The light chain is a zinc-dependent protease that cleaves synaptobrevin.^[5]

After the light chain enters the motor neuron, it travels by retrograde axonal transport from the contaminated site to the spinal cord in 2-14 days. When the toxin reaches the spinal cord, it enters central inhibitory neurons. The light chain cleaves the protein synaptobrevin, which is integral to the binding of neurotransmitter containing vesicles to the cell membrane. GABA-containing and glycine-containing vesicles are therefore not released and there is a loss of inhibitory action on motor and autonomic neurons.^[5] With the loss of central inhibition, uncontrolled muscle contractions (spasms) occur in response to normal stimuli such as noises or lights and autonomic hyperactivity.

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; 47 cases occurred in California in 1997; and during 1998-2000, an average of 43 cases of tetanus occurred annually.^[6] 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 (eg, extremes in blood pressure, dysrhythmias, or cardiac arrest).

Race

Tetanus affects all races.

Sex

Tetanus affects both sexes.

Age

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