tetanus

tetanus is perhaps better known through its more dramatic description ‘lockjaw’. This potentially life-threatening condition is characterized by uncontrollable muscular contractions, which can be continuous or spasmodic. The immediate cause of this presentation of a disease state is the presence of a circulating poison (toxin) produced at the site of a wound by spores of the bacterium Clostridium tetani. This bacterium resides normally in human and animal intestines without causing disease, but contact with heavily manured soil or other material containing the spores, which are extremely resistant to heat and other agents, will readily infect those not immunized against such infection. Active immunization by vaccination with tetanus toxoid (an inactivated form of the toxin) is now usual in childhood, along with diphtheria and whooping cough vaccines. Also immediate passive immunization is available for anyone with a wound which could be contaminated, by injection of human immunoglobulin prepared from the plasma of blood donors; this has taken over from the earlier use of antitetanus serum from horses, which sometimes caused adverse reactions.

Insight as to the mode of action of this toxin at the cellular level has interestingly first been gained from research on muscles of the crayfish. In contrast to the single excitatory innervation by motor axons in mammalian skeletal muscle, these invertebrate muscles have a twin innervation, one type of nerve fibre exciting, and the other inhibiting transmission at the neuromuscular junction. This inhibition does not occur through a process directly affecting the muscle fibre or indeed the ‘motor endplate’ of the neuromuscular junction. Instead, it depends on the release of a chemical transmitter ‘GABA’ which acts on the excitatory motor nerve terminals by opening a chemically-gated chloride channel; the effect of this is to reduce the amplitude of the action potential that reaches the terminal, thereby reducing the amount of excitatory transmitter (acetylcholine) released. As human and mammalian muscles lack such a mixed dual action, the muscular contractions must arise centrally in the axons or motor neuron cell bodies within the spinal cord or brain stem. Experiments show that tetanus toxin actually inhibits the release of GABA in the central nervous system. GABA normally damps downs the excitation of motor neurons; the effect of tetanus toxin is therefore to allow a now unchecked excitatory barrage to cause a sustained and uncontrollable discharge of motor neurons; this accounts in turn for the muscular contractions.

Because the muscle spasms may cause airway obstruction, such as by closing the jaw and the larynx, or may render the respiratory muscles functionally useless because contractions are sustained instead of rhythmic, tetanus is potentially fatal, but it can be treated successfully by antibiotic drugs. Meanwhile the patient may need to be sedated or, in more severe intoxication, to be paralysed by muscle relaxant drugs and artificially ventilated.

Tom Sears

See also immunization; infectious diseases.