Preventing and treating tetanus

One hundred and twenty years ago, the BMJ contained the following report: “Death from tetanus induced by hypodermic injection. An inquest was held by the coroner for the city of Dublin last week on the body of a governess, aged fifty-six years, [who] used to inject morphia herself subcutaneously, for the relief of neuralgia arising from bad teeth . . . Dr Austin Meldon was of the opinion that the cause of tetanus must have been the injury of some nerve by the needle.”¹

In fact, the governess's tetanus probably resulted from chronic dental infection or using a dirty needle, not the nerve injury the doctor supposed. Six years after this report, Arthur Nicolaier showed that tetanus resulted from contamination of wounds with soil bacilli, which, he correctly deduced, produced a “strychnine-like” toxin responsible for the disease.²

More than a century later much more is known about the tetanus toxin; its deoxyribonucleic acid has been sequenced and its mechanism of action established. We are equipped with antitoxin and a vaccine to prevent the disease, yet tetanus continues to be a major public health problem throughout much of the developing world.

In 2000 only 18 833 cases of tetanus were reported to the World Health Organization worldwide.³ Seventy six countries, including many of the countries most at risk, did not supply data, and the information of those that did was often incomplete. Surveys indicated that only 3% of neonatal tetanus is reported.⁴ On the basis of the WHO data, studies by Stanfield and Galazka,⁵ and our data from Vietnam (our hospital admits about 300 patients with tetanus each year) we estimate a true global incidence of 700 000 to 1 000 000 cases per year.

Incidence has genuinely declined over the past 20 years, coinciding with an increase in primary immunisation coverage. In most countries, however, no provision exists for vaccinating people who were born before these programmes were implemented, providing the boosters required for long term protection, or protecting those who miss schedules during periods when public health infrastructures break down—for example, during wars and mass displacement of people. As a result older children and adults remain at risk. Even in countries with good primary immunisation programmes, elderly people may still be vulnerable, either because of incomplete primary vaccination or because protective antibody levels decline over time,⁶ as illustrated by a case report in the BMJ this year.⁷

The clinical features of tetanus arise from the action of tetanus toxin, which blocks inhibitory input of gamma aminobutyric acid to motor neurones,⁸ resulting in unchecked motor nerve activity. Muscle tone is increased, producing the characteristic trismus, “risus sardonicus,” and opisthotonus. Spasms typically develop one to four days after the initial symptoms. They usually affect the whole body and, if frequent or prolonged, impede respiration. In severe tetanus, the autonomic nervous system is affected, which results in marked cardiovascular instability with rapidly fluctuating blood pressure.

Wounds do not need to be obviously contaminated for tetanus to develop, and in unvaccinated individuals or people with waning immunity even minor wounds can cause fatal disease. The database of the tetanus unit at the Hospital for Tropical Diseases, Vietnam, records the following probable causes of infection: acupuncture, necrotic tumours, ear piercing, pedicures, middle ear infection, and intravenous and intramuscular injections, in addition to other more typical sources. In 25% of patients no obvious entry site is found.⁸

Prognosis of tetanus depends on the facilities available.² Without mechanical ventilation, asphyxia is the commonest cause of death,¹¹ resulting from laryngeal muscle spasm (and acute airway obstruction), respiratory muscle spasm, or extreme fatigue. In places fortunate enough to have facilities for ventilation these problems can be overcome by using sedation and non-depolarising neuromuscualr blocking agents.⁹ Unfortunately, with patients now surviving the initial acute phase of their illness, new problems have emerged—autonomic dysfunction and hospital acquired pneumonia (often with multiresistant organisms) are now the commonest causes of death. Furthermore, the prolonged intensive medical and nursing care required by many patients places extra demands on an already stretched healthcare budget.

Almost no evidence exists to support any therapeutic intervention in tetanus. A search of the literature over the last 30 years produces only nine randomised controlled trials. Diazepam, the mainstay of treatment, has never been evaluated properly. The situation is no better with new treatments. Three uncontrolled studies of magnesium sulphate in tetanus have been published and indicate that it may reduce both the need for ventilation and the autonomic instability of severe disease.^10–12 But these studies give widely differing interpretations of the effects and side effect profile of magnesium. A variety of treatments, from vitamins to alpha and beta adrenergic receptor blockers, have been suggested for tetanus. None of them has been adequately evaluated and on the basis of the available evidence none of them, including magnesium, can be recommended for routine use until such treatments are subjected to well conducted large trials.

Successful implementation of the prevention strategies already available could mean that tetanus could in theory be eradicated from the world, but realistically this is not going to happen. Clostridium tetani is a ubiquitous organism, and successful prevention depends on sustained vaccination with high quality vaccine. Breakdown in public health infrastructure resulting from underinvestment, wars, or natural disasters, combined with growing public mistrust of immunisations, means that tetanus will continue to be a major global health problem. Since the introduction of penicillin in the 1940s, no major new specific treatment for tetanus has emerged, and effective treatment requires the full array of modern intensive care facilities. Such facilities are rarely available in the countries where most cases of tetanus occur, and for most patients the outlook remains as bleak as it was for Dr Meldon's patient. Only appropriate research and preventive measures can avoid similar case reports appearing in the BMJ another 120 years from now.