EPIDEMIOLOGY

Recently, tetanus has become a disease of the elderly and debilitated in developed countries, as younger people are likely to have been immunised.¹ In the USA, its incidence decreased from 0.23 per 100 000 in 1955 to 0.04 per 100 000 in 1975, and remained stable thereafter.¹ The annual world mortality from tetanus is estimated to be 400 000–2 000 000. Tetanus claimed the lives of over 433 000 infants in 1991, and accounts for 5 deaths for every 1000 live births in Africa. It is geographically prevalent in rural areas with poor hygiene and medical services. Thus, tetanus remains a significant public health problem in the developing world, primarily because of poor access to immunisation programmes. In addition, modern management requires intensive care unit (ICU) facilities, which are rarely available in the most severely afflicted populations.² Therefore, tetanus will continue to afflict developing populations in the foreseeable future.

PATHOGENESIS

C. tetani is an obligate anaerobic, spore-bearing, Gram-positive bacillus. Spores exist ubiquitously in soil and in animal and human faeces. After gaining access to devitalised tissue, spores proliferate in the vegetative form, producing toxins, tetanospasmin and tetanolysin. Tetanospasmin is extremely potent; an estimated 240 g could kill the entire world population,³ with 0.01 mg being lethal for an average man. Tetanolysin is of little clinical importance.

C. tetani is non-invasive. Hence, tetanus occurs only when the spores gain access to tissues to produce vegetative forms. The usual mode of entry is through a puncture wound or laceration, although tetanus may follow surgery, burns, gangrene, chronic ulcers, dog bites, injections such as with drug users, dental infection, abortion and childbirth. Tetanus neonatorum usually follows infection of the umbilical stump. The injury itself may be trivial, and in 20% of cases there is no history or evidence of a wound.¹ Germination of spores occurs in oxygen-poor media (e.g. in necrotic tissue), with foreign bodies, and with infections. C. tetani infection remains localised, but the exotoxin tetanospasmin is widely distributed via the blood stream, taken up into motor nerve endings and transported into the nervous system. Here it affects motor neurone end-plates in skeletal muscle (to decrease release of acetylcholine), the spinal cord (with dysfunction of polysynaptic reflexes) and the brain (with seizures, inhibition of cortical activity and autonomic dysfunction). Tetanus is not communicable from person to person.

The symptoms of tetanus appear only after tetanospasmin has diffused from the cell body through the extracellular space, and gained access to the presynaptic terminals of adjacent neurons.¹ Tetanospasmin spreads to all local neurons, but is preferentially bound by inhibitory interneurons, i.e. glycinergic terminals in the spinal cord, and γ-aminobutyric acid (GABA) terminals in the brain.² Its principal effect is to block these inhibitory pathways. Hence stimuli to and from the central nervous system (CNS) are not ‘damped down’.

ACTIVE IMMUNOPROPHYLAXIS^1,3

Natural immunity to tetanus does not occur. Tetanus may both relapse and recur. Victims of tetanus must be actively immunised. Tetanus toxoid is a cheap and effective vaccine which is thermally stable.³ It is a non-toxic derivative of the toxin which, nevertheless, elicits and reacts with antitoxic antibody. By consensus, an antibody titre of 0.01 u/ml serum is protective.⁴ None the less, tetanus has been reported in a few victims with much higher serum antibody titres.¹

In adults, a full immunisation course consists of three toxoid doses, given at an optimal interval of 6–12 weeks between the first and second doses, and 6–12 months between the second and third doses. A single dose will offer no immediate protection in the unimmunised, but a full course should never be repeated. Neonates have immunity from maternal antibodies. Children over 3 months should be actively immunised, and need four doses in total. Two or more doses to child-bearing females over 14 years will protect any child produced within the next 5 years. Pregnant females who are not immunised should thus be given two spaced-out doses 2 weeks to 2 months before delivery. Booster doses should be given routinely every 10 years.

Side-effects of tetanus toxoid are uncommon and not life-threatening. They are associated with excessive levels of antibody due to indiscriminate use.⁵ Common reactions include urticaria, angioedema and diffuse, indurated swelling at the site of injection.

CLINICAL PRESENTATION^1,4,6

The incubation period (i.e. time from injury to onset of symptoms) varies from 2 to 60 days. The period of onset (i.e. from first symptom to first spasm) similarly varies. Nearly all cases (90%), however, present within 15 days of infection.⁶ The incubation period and the period of onset are of prognostic importance, with shorter times signifying more severe disease.

Presenting symptoms are pain and stiffness. Stiffness gives way to rigidity, and there is difficulty in mouth-opening – trismus or lockjaw. Most cases (75%) of non-neonatal generalised tetanus present with trismus.⁶ Rigidity becomes generalised, and facial muscles produce a characteristic clenched-teeth expression called risus sardonicus. The disease progresses in a descending fashion. Typical spasms, with flexion and adduction of the arms, extension of the legs and opisthotonos, are very painful, and may be so intense that fractures and tendon separations occur.¹ Spasms are caused by external stimuli, e.g. noise and pressure. As the disease worsens, even minimal stimuli produce more intense and longer-lasting spasms. Spasms are life-threatening when they involve the larynx and/or diaphragm.

Neonatal tetanus presents most often on day 7 of life,⁴ with a short (1-day) history of failure of the infant to feed. The neonate displays typical spasms that can easily be misdiagnosed as convulsions of another aetiology. In addition, because these infants vomit (as a result of the increased intra-abdominal pressure) and are dehydrated (because of their inability to swallow), meningitis and sepsis are often considered first.

Autonomic dysfunction occurs in severe cases,^6–8 and begins a few days after the muscle spasms. (The toxin has further to diffuse to reach the lateral horns of the spinal cord.) There is increased basal sympathetic tone, manifesting as tachycardia and bladder and bowel dysfunction. Also, episodes of marked sympathetic overactivity involving both α- and β-receptors occur. Vascular resistance, central venous pressure and, usually, cardiac output are increased, manifesting clinically as labile hypertension, pyrexia, sweating, and pallor and cyanosis of the digits.⁷ These episodes are usually of short duration and may occur without any provocation. They are caused by reduced inhibition of postsynaptic sympathetic fibres in the intermediolateral cell column, as evidenced by very high circulating noradrenaline (norepinephrine) concentrations.^1,8 Other postulated causes of this variable sympathetic overactivity include loss of inhibition of the adrenal medulla with increased adrenaline (epinephrine) secretion, direct inhibition by tetanospasmin of the release of endogenous opiates and increased release of thyroid hormone.^1,2

The role of the parasympathetic nervous system is debatable. Episodes of bradycardia, low peripheral vascular resistance, low central venous pressure and profound hypotension are seen, and are frequently preterminal.⁷ Sudden and repeated cardiac arrests occur, particularly in intravenous drug abusers.⁸