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 These events have been attributed to total withdrawal of sympathetic tone, since it is unresponsive to atropine.⁹ However they may be caused by catecholamine-induced myocardial damage^8,10 or direct brainstem damage.⁸ Whatever the mechanism, patients afflicted with the autonomic dysfunction of tetanus are at risk of sudden death.

Local tetanus is an uncommon mild form of tetanus with a mortality of 1%. The signs and symptoms are confined to a limb or muscle, and may be the result of immunisation. Cephalic tetanus is also rare. It results from head and neck injuries, eye infections and otitis media. The cranial nerves, especially the seventh, are frequently involved, and the prognosis is poor. This form may progress to a more generalised form. Tetanus in heroin addicts seems to be severe, with a high mortality, but numbers are small.^8,11

DIAGNOSIS

The diagnosis is clinical and often straightforward. There are no laboratory tests specific to tetanus. C. tetani is cultured from the wound only in a third of cases. The most common differential diagnosis is dystonic reaction to tricyclics. Other differential diagnoses include strychnine poisoning, local temporomandibular disease, local oral disease, convulsions, tetany, intracraninal infections or haemorrhage and psychiatric disorders.

MANAGEMENT

Initial objectives of treatment are to neutralise circulating toxin (i.e. passive immunisation) and prevent it from entering peripheral nerves (i.e. wound care), as well as eradicating the source of the toxin (i.e. extensive surgery, hygiene, wound care and antibiotics). Treatment then aims to minimise the effect of toxin already bound in the nervous system, and to provide general supportive care.

PASSIVE IMMUNISATION^1,12

Human antitetanus toxin has now largely replaced antitetanus serum (ATS) of horse origin, as it is less antigenic. Antitetanus toxin will at best neutralise only circulating toxin, but does not affect toxins already fixed in the CNS, i.e. it does not ameliorate symptoms already present. Although never prospectively tested, present recommendations for human antitetanus toxin in tetanus are 3000–6000 units intravenously (IV). It has been suggested that unimmunised patients or those whose immunisation status is unknown should be given human rich antiserum on presentation with contaminated wounds. No controlled study has shown this to be more effective than wound toilet and penicillin administration.

Intrathecal administration of antitetanus toxin is still controversial. A large meta-analysis reported it to be ineffective.¹³ A recent trial comparing intrathecal antitetanus immunoglobulin showed better clinical progression than those treated by the intramuscular route with no difference in mortality.¹⁴ Moreover, suitable intrathecal preparations are not widely available. Side-effects of human antitetanus toxin include fever, shivering and chest or back pains. Cardiovascular parameters need to be monitored, and the infusion may need to be stopped temporarily if significant tachycardia and hypotension present.^1,5,12 If human antiserum is not available, equine ATS can be used after testing and desensitisation.¹

ERADICATION OF THE ORGANISM

SUPPRESSION OF EFFECTS OF TETANOSPASMIN

SUPPORTIVE TREATMENT

Steps should be taken to prevent contractures, nosocomial pneumonias and deep-vein thrombosis. The patient (including the mother if a neonate is afflicted) must be actively immunised. Where possible, supportive psychotherapy should be offered to both patient and family.

COMPLICATIONS^1,4,6,10,32

Muscle spasms disappear after 1–3 weeks, but residual stiffness may persist. Although most survivors recover completely by 6 weeks, cardiovascular complications, including cardiac failure, arrhythmias, pulmonary oedema and hypertensive crises, can be fatal. No obvious cause of death can be found at autopsy in up to 20% of deaths. Other complications include those associated with factors shown in Table 48.1.

Table 48.1 Factors contributing to death in tetanus

OUTCOME

Recovery from tetanus is thought to be complete. However, in 25 non-neonatal patients followed for up to 11 years,³³ 15 were reported to have one or more abnormal neurological features, such as intellectual or emotional changes, fits and myoclonic jerks, sleep disturbance, and decreased libido. Of the 10 apparently normal survivors, 6 had electroencephalogram changes. Some of these symptoms resolved within 2 years.

Mortality figures depend on the availability of intensive care. In neonates, the mortality from African countries with no ICU facilities can be up to 80% of cases, but falls to about 10% when artificial ventilation is used. In the USA, mortality in non-neonates relates directly to age, with rates from 0% in patients under 30 years rising to 50% in those 60 years or older. An average of 10% mortality would seem to be reasonable for most ICUs. However, as this disease is easily and completely preventable, loss of life is unacceptable.