Clostridium tetani is the causative agent of tetanus. The organism is found in soil, especially heavily-manured soils, and in the intestinal tracts and feces of various animals. Carrier rates in humans vary from 0 to 25%, and the organism is thought to be a transient member of the flora whose presence depends upon ingestion. The organism produces terminal spores within a swollen sporangium giving it a distinctive drumstick appearance. Although the bacterium has a typical Gram-positive cell wall, it may stain Gram-negative or Gram-variable, especially in older cells.

Clostridium tetani Gram stain. Characteristic terminal endospores in a swollen sporangium exhibiting "tennis racket" shape. CDC

Tetanus is a highly fatal disease of humans. Mortality rates reported vary from 40% to 78%. The disease stems not from invasive infection but from a potent neurotoxin (tetanus toxin or tetanospasmin) produced when spores germinate and vegetative cells grow after gaining access to wounds. The organism multiplies locally and symptoms appear remote from the infection site.

Because of the widespread use of the tetanus toxoid for prophylactic immunization, fewer than 150 cases occur annually in the U.S., but the disease is a significant problem world-wide where there are >300,000 cases annually. Most cases in the U.S occur in individuals over age 60, which is taken to mean that waning immunity is a significant risk factor.

Sir Charles Bell's portrait of a soldier dying of tetanus. The characteristic rigidity of the body is referred to as opisthotonos and risus sardonicus. Original in the Royal College of Surgeons of Edinburgh, Scotland.

Neonatal tetanus accounts for about half of the tetanus deaths in developing countries. In a study of neonatal mortality in Bangladesh, 112 of 330 infant deaths were due to tetanus. Neonatal tetanus follows infection of the umbilical stump in infants born to nonimmune mothers (therefore, the infant has not acquired passive immunity). It usually results from a failure of aseptic technique during birthing procedures, but certain cultural practices may contribute to infection.

Tetanus toxin is one of the three most poisonous substances known to humans, the other two being the toxins of botulism and diphtheria. The toxin is produced by growing cells and released only on cell lysis. Cells lyse naturally during germination the outgrowth of spores, as well as during vegetative growth. After inoculation of a wound with C. tetani spores, only a minimal amount of spore germination and vegetative cell growth are required until the toxin is produced.

The bacterium synthesizes the tetanus toxin as a single 150kDa polypeptide chain (called the progenitor toxin), that is cleaved extracellularly by a bacterial protease into a 100 kDa heavy chain (fragment B) and a 50kDa light chain (fragment A), which remain connected by a disulfide bridge. The specific protease that cleaves the progenitor toxin can be found in culture filtrates of C. tetani. Cleavage of the progenitor toxin into A and B fragments can also be induced artificially with trypsin.

Tetanus toxin is produced in vitro in amounts up to 5 to 10% of the bacterial weight. Because the toxin has a specific affinity for nervous tissue, it is referred to as a neurotoxin. The toxin has no known useful function to C. tetani. Why the toxin has a specific action on nervous tissue, to which the organism naturally has no access, may be an anomaly of nature. The toxin is heat labile, being destroyed at 56^oC in 5 minutes, and is O₂ labile. The purified toxin rapidly converts to toxoid at 0^oC in the presence of formalin.

The receptor to which tetanospasmin binds has been reported as ganglioside GT and/or GD1b, but its exact identity is still in question. Binding appears to depend on the number and position of sialic acid residues on the ganglioside. Isolated B fragments, but not A fragments, will bind to the ganglioside. The A fragment has toxic (enzymatic) activity after the B fragment secures its entry. Binding appears to be an irreversible event so that recovery depends on sprouting a new axon terminal.

Prophylactic immunization is accomplished with tetanus toxoid, as part of the DPT (DTaP) vaccine or the DT (TD) vaccine. Three injections are given in the first year of life, and a booster is given about a year later, and again on the entrance into elementary school.

Whenever a previously-immunized individual sustains a potentially dangerous wound, a booster of toxoid should be injected. Wherever employed, intensive programs of immunization with toxoid have led to a striking reduction in the incidence of the disease.