Tetanus (Clostridium tetani)

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Chapter 203 Tetanus (Clostridium tetani)


Tetanus occurs worldwide and is endemic in approximately 90 developing countries, although its incidence varies considerably. The most common form, neonatal (or umbilical) tetanus, kills approximately 500,000 infants each year, with about 80% of deaths in just 12 tropical Asian and African countries. It occurs in infants whose mothers are not immunized. In addition, an estimated 15,000-30,000 unimmunized women worldwide die each year of maternal tetanus, which results from postpartum, postabortal, or postsurgical wound infection with C. tetani. Approximately 50 cases of tetanus are reported each year in the USA, mostly in persons >60 yr of age, although cases also occur in toddlers and neonates. Approximately 20% of children in the USA 10-16 yr of age lack a protective antibody level. The majority of childhood cases of tetanus in the USA have occurred in unimmunized children whose parents objected to vaccination.

Most non-neonatal cases of tetanus are associated with a traumatic injury, often a penetrating wound inflicted by a dirty object such as a nail, splinter, fragment of glass, or unsterile injection. Tetanus occurring after illicit drug injection is becoming more common. The disease also occurs after the use of contaminated suture material and after intramuscular injection of medicines, most notably quinine for chloroquine-resistant falciparum malaria. The disease may also occur in association with animal bites, abscesses (including dental abscesses), ear and other body piercing, chronic skin ulceration, burns, compound fractures, frostbite, gangrene, intestinal surgery, ritual scarification, infected insect bites, and female circumcision. Rare cases have no history of trauma.


Tetanus occurs after introduced spores germinate, multiply, and produce tetanus toxin in the low oxidation-reduction potential (Eh) of an infected injury site. A plasmid carries the toxin gene. Toxin is released after vegetative bacterial cell death and lysis. Tetanus toxin (and the botulinum toxins) is a 150-kd simple protein consisting of a heavy chain (100 kd) and a light (50 kd) chain joined by a single disulfide bond. Tetanus toxin binds at the neuromuscular junction and enters the motor nerve by endocytosis, after which it undergoes retrograde axonal transport to the cytoplasm of the α-motoneuron. In the sciatic nerve, the transport rate was found to be 3.4 mm/hr. The toxin exits the motoneuron in the spinal cord and next enters adjacent spinal inhibitory interneurons, where it prevents release of the neurotransmitters glycine and γ-aminobutyric acid (GABA). Tetanus toxin thus blocks the normal inhibition of antagonistic muscles on which voluntary coordinated movement depends; in consequence, affected muscles sustain maximal contraction and cannot relax. The autonomic nervous system is also rendered unstable in tetanus.

The phenomenal potency of tetanus toxin is enzymatic in nature. The light chain of tetanus toxin (and of several botulinum toxins) is a zinc-containing endoprotease whose substrate is synaptobrevin, a constituent protein of the docking complex that enables the synaptic vesicle to fuse with the terminal neuronal cell membrane. The heavy chain of the toxin contains its binding and internalization domains.

Because C. tetani is not an invasive organism, its toxin-producing vegetative cells remain where introduced into the wound, which may display local inflammatory changes and a mixed bacterial flora.

Clinical Manifestations

Tetanus is most often generalized but may also be localized. The incubation period typically is 2-14 days but may be as long as months after the injury. In generalized tetanus, the presenting symptom in about half of cases is trismus (masseter muscle spasm, or lockjaw). Headache, restlessness, and irritability are early symptoms, often followed by stiffness, difficulty chewing, dysphagia, and neck muscle spasm. The so-called sardonic smile of tetanus (risus sardonicus) results from intractable spasms of facial and buccal muscles. When the paralysis extends to abdominal, lumbar, hip, and thigh muscles, the patient may assume an arched posture of extreme hyperextension of the body, or opisthotonos, with the head and the heels bent backward and the body bowed forward with only the back of the head and the heels touching the supporting surface. Opisthotonos is an equilibrium position that results from unrelenting total contraction of opposing muscles, all of which display the typical boardlike rigidity of tetanus. Laryngeal and respiratory muscle spasm can lead to airway obstruction and asphyxiation. Because tetanus toxin does not affect sensory nerves or cortical function, the patient unfortunately remains conscious, in extreme pain, and in fearful anticipation of the next tetanic seizure. The seizures are characterized by sudden, severe tonic contractions of the muscles, with fist clenching, flexion, and adduction of the arms and hyperextension of the legs. Without treatment, the seizures range from a few seconds to a few minutes in length with intervening respite periods, but as the illness progresses, the spasms become sustained and exhausting. The smallest disturbance by sight, sound, or touch may trigger a tetanic spasm. Dysuria and urinary retention result from bladder sphincter spasm; forced defecation may occur. Fever, occasionally as high as 40°C, is common because of the substantial metabolic energy consumed by spastic muscles. Notable autonomic effects include tachycardia, dysrhythmias, labile hypertension, diaphoresis, and cutaneous vasoconstriction. The tetanic paralysis usually becomes more severe in the 1st wk after onset, stabilizes in the 2nd wk, and ameliorates gradually over the ensuing 1-4 wk.

Neonatal tetanus, the infantile form of generalized tetanus, typically manifests within 3-12 days of birth as progressive difficulty in feeding (sucking and swallowing), associated hunger, and crying. Paralysis or diminished movement, stiffness and rigidity to the touch, and spasms, with or without opisthotonos, are characteristic. The umbilical stump may hold remnants of dirt, dung, clotted blood, or serum, or it may appear relatively benign.

Localized tetanus results in painful spasms of the muscles adjacent to the wound site and may precede generalized tetanus. Cephalic tetanus