- Email: [email protected]
A Review of the Epidemiology, Pathogenesis and Management of Tetanus
3. Hinder RA, et al. Laparoscopic Nissen fundoplication is an effective treatment for gastroesophageal reflux disease. Ann Surg. 1994; 220: 472–481. 4. Cuschieri A, et al. The European experience with laparoscopic cholecystectomy. Am J Surg. 1991; 161: 385–387. 5. Peters JH, et al. Safety and efficacy of laparoscopic cholecystectomy. A prospective analysis of 100 initial patients. Ann Surg. 1991; 213: 3–12. 6. Soper NJ, Barteau JA, Clayman RV, Ashley SW and Dunnegan DL. Comparison of early postoperative results for laparoscopic versus standard open cholecystectomy. Surg Gynecol Obstet. 1992; 174: 114–118. 7. Vander Velpen GC, Shimi SM and Cuschieri A. Outcome after cholecystectomy for symptomatic gall stone disease and effect of surgical access: laparoscopic v open approach. Gut 1993; 34: 1448–1451. 8. Vitale GC, et al. Interruption of professional and home activity after laparoscopic cholecystectomy among French and American patients. Am J Surg. 1991; 161: 396–398. 9. Senagore AJ, Duepree HJ, Delaney CP, Brady KM and Fazio VW. Results of a standardized technique and postoperative care plan for laparoscopic sigmoid colectomy: a 30-month experience. Dis Colon Rectum. 2003; 46: 503–509. 10. Maartense S, Bemelman WA, Gerritsen VDH, Meijer DW and Gouma DJ. Handassisted laparoscopic surgery (HALS): a report of 150 procedures. Surg Endosc. 2004; 18: 397–401. 11. Moorthy K, Munz Y, Liddle A, Dosis A, Martin S, Rockall T and Darzi A. Objective comparison of the learning curves of laparoscopic and robotic surgery using motion analysis. Surg Endosc. 2004; 18, 282. 12. Falk V, Jacobs S, Gummert JF, Walther T and Mohr FW. Computer-enhanced endoscopic coronary artery bypass grafting: the da Vinci experience. Semin Thorac Cardiovasc Surg. 2003; 15: 104–111. 13. Davis CJ and Arregui ME. Laparoscopic repair for groin hernias. Surg Clin North Am. 2003; 83: 1141–1161. 14. Contini S and Scarpignato C. Endoscopic treatment of gastro-oesophageal reflux disease (GORD): a systematic review. Dig Liver Dis. 2003; 35: 818–838. 15. Kwoh YS, Hou J, Jonckheere EA and Hayati S. A robot with improved absolute positioning accuracy for CT guided stereotactic brain surgery. IEEE Trans Biomed Eng. 1988; 35: 153–160. 16. Davies B. A review of robotics in surgery. Proc Inst Mech Eng [H]. 2000; 214: 129–140. 17. Satava RM. Surgical robotics: the early chronicles: a personal historical perspective. Surg Laparosc Endosc Percutan Tech. 2002; 12: 6–16. 18. Geis WP, Kim HC, Brennan EJ Jr, McAfee PC and Wang Y. Robotic arm enhancement to accommodate improved efficiency and decreased resource utilization in
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complex minimally invasive surgical procedures. Stud Health Technol Inform. 1996; 29: 471–481. Arezzo A, et al. Experimental trial on solo surgery for minimally invasive therapy: comparison of different systems in a phantom model. Surg Endosc. 2000; 14: 955–959. Yavuz Y, Ystgaard B, Skogvoll E and Marvik R. A comparative experimental study evaluating the performance of surgical robots aesop and endosista. Surg Laparosc Endosc Percutan Tech. 2000; 10: 163–167. Himpens J, Leman G and Cadiere GB. Telesurgical laparoscopic cholecystectomy. Surg Endosc. 1998; 12: 1091. Cadiere GB, Himpens J, Vertruyen M and Favretti F. The world’s first obesity surgery performed by a surgeon at a distance. Obes Surg. 1999; 9: 206–209. Cadiere GB, Himpens J, Vertruyen M, Bruyns J and Fourtanier G. [Nissen fundoplication done by remotely controlled robotic technique]. Ann Chir. 1999; 53: 137–141. Degueldre M, Vandromme J, Huong PT and Cadiere GB. Robotically assisted laparoscopic microsurgical tubal reanastomosis: a feasibility study. Fertil Steril. 2000; 74: 1020–1023. Cadiere GB, et al. Feasibility of robotic laparoscopic surgery: 146 cases. World J Surg. 2001; 25: 1467–1477. Marescaux J, et al. Telerobotic laparoscopic cholecystectomy: initial clinical experience with 25 patients. Ann Surg. 2001; 234: 1–7. Shah J, Rockall T and Darzi A. Robot-assisted laparoscopic Heller’s cardiomyotomy. Surg Laparosc Endosc Percutan Tech. 2002; 12: 30–32. Undre S et al. Robot-assisted laparoscopic adrenalectomy: preliminary UK results. BJU Int. 2004; 93: 357–359. Munz Y, et al. Robotic assisted rectopexy. Am J Surg. 2004; 187: 88–92. Damiano RJ Jr, et al. Initial prospective multicenter clinical trial of robotically-assisted coronary artery bypass grafting. Ann Thorac Surg. 2001; 72: 1263–1268. Mohr FW, et al. Computer-enhanced “robotic” cardiac surgery: experience in 148 patients. J Thorac Cardiovasc Surg. 2001; 121: 842–853. Prasad SM, Ducko CT, Stephenson ER, Chambers CE and Damiano RJ Jr. Prospective clinical trial of robotically assisted endoscopic coronary grafting with 1-year follow-up. Ann Surg. 2001; 233: 725–732. Kappert U, et al. Technique of closed chest coronary artery surgery on the beating heart. Eur J Cardiothorac Surg. 2001; 20: 765–769. Chitwood WR Jr, et al. Robotic surgical training in an academic institution. Ann Surg. 2001; 234: 475–484.
International Journal of Surgery 2004; 2: 109–112
A Review of the Epidemiology, Pathogenesis and Management of Tetanus I.H. Mallick1 and M.C. Winslet2 1
Honorary Lecturer & Research Fellow, University Dept of Surgery, Royal Free & University College Medical School, London, UK Professor and Head of the University Department of Surgery, Royal Free & University College Medical School, London, UK Correspondence to: Mr Ismail Mallick, Honorary Lecturer & Research Fellow, University Dept of Surgery, Royal Free & University College Medical School, London NW3 2QG. Email: [email protected] 2
Abstract Tetanus remains an important disease worldwide. In the United Kingdom, the elderly and intravenous drug users are at particular risk of acquiring clinical tetanus. Tetanus is associated with a high morbidity and mortality. Once the diagnosis of tetanus is suspected, intensive management is necessary. In this article we review the history, epidemiology, microbiology, clinical features, mode of transmission, pathogenesis, differential diagnosis, management, complications and prevention of this life threatening disease.
Introduction Tetanus is often a fatal disease caused by the exotoxin from Clostridium tetani.1 It is essentially a disease of the central nervous system. The vast majority of patients (more than 95%) who develop tetanus have not been previously immunised or they are inadequately immunised.2 In the developed countries, high risk groups include the elderly and intravenous drug users.3 However, tetanus can be life-threatening even with full immunisation and proper treatment.4
History Tetanus has been an important disease worldwide for many generations. It is described both in the bible and in the writings of ancient
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Greek and Egyptian physicians.5 In 1884, Carle and Rattone produced tetanus in animals by injecting them with pus from a fatal human case of tetanus.6 In the same year, Nicolaeir produced tetanus in animals by injecting them with samples of soil.6 However, it was Kitasato in 1889, who isolated the organism from a human case and reported that the toxin could be neutralised by specific antibodies.6 In 1897, Nocard demonstrated the protective effects of passively transferred anti-toxin.1 Passive immunisation in humans was used during World War I.1 Tetanus Toxoid was developed by Descombey in 19241 and the effectiveness of active immunisation was demonstrated in World War II.6
Epidemiology The occurrence of tetanus is worldwide, but it is a common problem in areas that are densely populated in hot climates in which the soil is rich in organic matter.7 The incidence of tetanus in England and Wales decreased following the introduction of national immunisation in 1961.8 By law, tetanus became a notifiable disease in October 1968 in the UK.9 On average, six cases of clinical tetanus per year were reported in England and Wales between 1992 and 2002.10 Although the number of cases reported is declining, there is evidence that many cases are not being reported. Rushdy et al estimated the under-reporting to be between 54–64%.11
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Microbiology C. tetani is a gram positive, anaerobic, spore forming bacillus. It forms a terminal spore giving it a drum-stick appearance.12 C. tetani needs low oxygen tension for its survival and is very sensitive to heat. However, the spores are extremely resistant to heat and to the conventional antiseptics,13 being able to survive for many years in adverse conditions. The spores are widely distributed in nature and are killed by autoclaving at 121⬚ C for 10–15 minutes.12 Manure treated soil may contain large numbers of spores. They are found in the faeces of horses, sheep, cattle, rats, dogs, cats and chicken. In agricultural communities, a significant number of adults may harbour the organism. In intravenous drug users, the spores can also be located on the skin surfaces and in contaminated heroin.14,15
The disease usually presents with a descending pattern. The first sign is lock-jaw or trismus which is due to spasm of the masseter muscle.29 This is followed by spasm of the facial muscles leading to risus sardonicus, difficulty in swallowing, spasm of the extensors of the neck, back and legs to form a backward curvature (opisthotonus see Fig. 1), and rigidity of abdominal muscles. The patient may manifest with pyrexia of 39–41⬚C, hypertension, tachycardia and sweating. Spasms may occur frequently and last for several minutes but may continue for 3–4 weeks, with complete recovery taking several months.13,18,30 The severity of generalised tetanus is classified as mild, moderate, severe and very severe. (Table 1).16
Table 1. Classification of severity of Tetanus.
Mode of Transmission Transmission is primarily through contaminated wounds.13 The wound may be apparent or inapparent and may be minor or major.16 In fact, in about 25% of cases in the developed countries, the portal of entry is not evident at the time of diagnosis.17 Tetanus may follow surgery (elective or emergency), burns, puncture wounds, crush wounds, otitis media, animal bites, oral infections, child birth and abortion.18 In intravenous drug users, the potential sources of tetanus include contamination of drugs, adulterants (e.g. quinine), paraphernalia and skin.19–21 Tetanus is not however contagious from person to person.
Pathogenesis C. tetani usually enters the body through a wound. In the presence of low oxygen tension, spore germination occurs.12 The organism secretes two toxins namely tetanolysin and tetanospasmin. Tetanolysin can damage the viable local tissue surrounding the infection and optimises the conditions for bacterial multiplication.12,22 A powerful neurotoxin, tetanospasmin is produced and dissemination is by retrograde axonal spread to the central nervous system.2 The toxin becomes bound to gangliosides within the central nervous system, where it suppresses inhibitory influences on motor neurons.23 It inhibits the release of glycine and gamma-amino butyric acid (GABA).24–26 This can lead to unopposed muscle contractions and spasms, even seizures may develop. The autonomic nervous system may also be affected due to direct stimulation and autonomic overactivity is associated with a high mortality.27
Clinical Manifestations The incubation period varies from 3 to 21 days, with an average of 7 days.18 In general, the further the injury site is from the central nervous system, the longer the incubation period. The shorter the incubation period, the greater is the chance of death.12 Three clinical forms of tetanus have been described namely generalised tetanus, local tetanus and cephalic tetanus.17 The most common (more than 80%) form of tetanus is generalised tetanus.28
Grade
Type
Signs and symptoms
I
Mild
II
Moderate
III
Severe
IV
Very severe
mild to moderate trismus; general spasticity; no respiratory embarrassment; no spasms; little or no dysphagia moderate trismus; well-marked rigidity; mild to moderate but short spasms; moderate respiratory embarrassment with an increased respiratory rate greater than 30; mild dysphagia severe trismus; generalized spasticity; reflex prolonged spasms; increased respiratory rate greater than 40; apnoeic spells; severe dysphagia; tachycardia greater than 120 very severe: grade III plus violent autonomic disturbances involving the cardiovascular system. Severe hypertension and tachycardia alternating with relative hypotension and bradycardia, either of which may be persistent.
Local tetanus is an uncommon form of tetanus in which the patients may have persistent contraction of muscles in the same anatomical region as the injury.31 Local tetanus may be a forerunner of generalised tetanus. Cephalic tetanus is a rare form of tetanus occasionally presenting with otitis media in which C. tetani is isolated from the middle ear. There is usually involvement of the cranial nerves in the facial area. Cephalic tetanus may progress to generalised tetanus.32 The overall case fatality rate among the reported cases in England and Wales was 29% between the years 1984 and 2000.11
Investigations C. tetani is very rarely isolated from infection sites. The diagnosis is usually made on clinical grounds.11 Because of the rarity of tetanus and its similarity to other medical conditions the diagnosis can sometimes be difficult. (Box 1) The combination of a history of injury with a contaminated wound and muscular spasms (with or without risus sardonicus, trismus or opisthotonus) should raise the possibility of the diagnosis.
Box 1. Differential Diagnosis of Tetanus
Fig. 1. Sir CharlesBell’s portrait of opisthotonus in a soldier with tetanus from a wound sustained at the Battle of Corunna (1809). The painting hangs in the Royal College of Surgeons of Edinburgh (Reproduced by the kind permission of the Royal College of Surgeons of Edinburgh).
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Acute abdomen ⫾ peritonitis Dental abscesses Drug Withdrawal Dystonic reactions (e.g. due to neuroleptics) Encephalitis Head injury Hyperventilation Meningitis Rabies Sepsis Strychnine poisoning Subarachnoid haemorrhage Temporomandibular joint syndrome Tetany
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Complications (Table 2) Interference with breathing can occur due to aspiration and laryngospasm.16 Prolonged spasms, contractions or convulsions may lead to fractures of long bones or of the spine.2 Cardiovascular complications namely tachy/bradycardia, arrhythmias and hypertension may also occur due to stimulation of the autonomic nervous system.33 Nosocomial infections are common in these patients because of prolonged hospitalisation. Infections may occur from indwelling catheters, hospital acquired pneumonia, pressure sores, aspiration pneumonia, deep vein thrombosis and pulmonary embolism can also occur.34
Box 2. Management of Tetanus
Airway Breathing and Ventilation Circulation-Intravenous fluids Intravenous or (Intramuscular in multiple sites) of Tetanus Immune Globulin (TIG) Debridement of Wound Antibiotics Nutrition Immunisation with combined tetanus and diphtheria vaccine following recovery Antithrombotic measures
Table 2. Complications of Tetanus. Systems
Complications
Respiratory
apnoea, type I respiratory failure (atelectasis, aspiration pneumonia), type II respiratory failure (laryngospasm, excess sedation, truncal spasm), acute respiratory distress syndrome, complications of ventilation and tracheostomy tachy/bradycardia, hypo/hypertension, myocardial ischaemia, arrhythmias, asystole, cardiac failure infections, renal failure ileus, gastric stasis, diarrhoea, haemorrhage vertebral fracture and tendon avulsions during spasms, temporomandibular joint dislocations, nerve palsies weight loss, thromboembolic phenomenon, decubitus ulcers, multiple organ dysfunction syndrome(MODS)
Cardiovascular Renal Gastrointestinal Musculoskeletal General
Management Tetanus, when suspected, must be managed promptly and aggressively. The management of tetanus requires a multi-disciplinary team approach.35 Patients must be transferred to the intensive care unit (ITU). In a comparison study of 306 patients treated with intensive care management and 335 patients from the same hospital prior to the institution of the ITU, mortality decreased from 43.6% to 15% with ITU management.36 Early consultation with the consultant microbiologist is mandatory. Patients must be nursed in a quiet room to prevent muscular spasms from hyperexcitability. (Box 2) Airway The maintenance of the airway is a high priority. Early consultation with an anaesthetist regarding airway management in the emergency department even in cases where there is no respiratory compromise is warranted.37
Control of Spasms Benzodiazepines such as diazepam and midazolam are very useful in controlling the muscular spasms and rigidity of tetanus.13 Neuromuscular blocking agents (e.g. vecuronium) with intermittent positive pressure ventilation may be required for a prolonged period in certain cases.16 There are three uncontrolled studies that report that magnesium sulphate may reduce both the need for ventilation and the autonomic instability of severe tetanus.38–40 Tetanus Immune Globulin Tetanus immune globulin (TIG) is recommended for patients with tetanus.23 TIG can help remove unbound tetanus toxin, but cannot remove the toxin that is bound to nerve endings. The recommended dose is 500 IU administered intramuscularly.41 Due to the extreme potency of tetanospasmin, tetanus infection does not give rise to tetanus immunity. Active immunity with the combined adsorbed tetanus/low dose diphtheria vaccine should be administered intramuscularly at a site contralateral to the TIG dosing.42 Wound Debridement and Antibiotics Devitalized and necrotic tissue must be excised, foreign bodies removed and the wound thoroughly irrigated and cleansed of contaminants. Infected tissues must be debrided and abscesses if any must be drained promptly. Wounds may be left open after inspection, with delayed primary suturing performed after 7 days.43 Penicillin, erythromycin, tetracycline and metronidazole are all effective against C. tetani.6 However, the administration of intravenous metronidazole has been shown to be more effective than penicillin in preventing death when used in the treatment of tetanus.44 It has been postulated that penicillin is a centrally acting GABA antagonist, and may therefore act synergistically with tetanospasmin in producing muscular spasms.
Table 3. UK Department of Health guidelines for managing wounds to prevent tetanus.48 Tetanus Prone Wound Immunisation Status
Clean wound vaccine
Vaccine
Human Tetanus immunoglobulin #
Fully immunised i.e. has received a total of 5 doses of tetanus vaccine at appropriate intervals as single antigen or in a combined vaccine Primary immunisation complete, boosters incomplete but up to date Primary immunisation incomplete or boosters not up to date
not required
not required
only if risk especially high (e.g. contaminated with stable manure)
none required (unless next dose due soon and convenient to give now) a reinforcing dose of combined tetanus/ diphtheria vaccine and further doses as required to complete the recommended schedule (to ensure future immunity)
only if risk especially high
Not immunised or immunisation status not known or uncertain
an immediate dose of vaccine followed, if records confirm this is needed, by completion of a full 3 dose course of combined tetanus/diphtheria vaccine to ensure future immunity
none required (unless next dose due soon and convenient to give now) a reinforcing dose of combined tetanus/diphtheria vaccine and further doses as required to complete the recommended schedule (to ensure future immunity) an immediate dose of vaccine followed, if records confirm this is needed, by completion of a full 3 dose course of combined tetanus/diphtheria vaccine to ensure future immunity
yes: one dose of human tetanus immunoglobulin in a different site
yes: one dose of human tetanus immunoglobulin in a different site
# For prevention the dose of human tetanus immunoglobulin is; 250iu IM. If more than 24 hours have elapsed since injury or there is a risk of heavy contamination or following burns: 500iu IM.
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Feeding Weight loss is common in tetanus18 and there are several factors that contribute: inability to swallow due to spasm of muscles, autonomic changes in gastrointestinal function, increased basal metabolic rate from pyrexia and muscular activity and prolonged critical illness.18 Nutrition should, therefore, be established as early as possible. Enteral nutrition is associated with a lower incidence of complications and is cheaper than parenteral nutrition.45 Percutaneous endoscopic gastrostomy (PEG) may avoid the complications associated with nasogastric tube feeding.46
Prevention (Table 3) The combined adsorbed tetanus/low dose diphtheria vaccine in adults and adolescents offers effective protection against tetanus.47 A total of five doses of the vaccine at appropriate intervals confer life-long immunity. Even when a person is fully immunised tetanus can still occur, however the mechanism of immunisation failure is unclear. Theories include a burden of toxin that overwhelms the host immune defences, antigenic variability between toxin and toxoid, and selective suppression of the immune response.3 Tetanus Immunisation Following Injuries A wound that is prone to tetanus is defined as a wound or burn sustained more than six hours before surgical treatment or with any of the following characteristics: a puncture-type wound, contact with soil or manure likely to harbour tetanus and a significant degree of devitalised or dead tissue:8 Tetanus Immunisation Schedules (Table 4) 1. Adults and adolescents requiring tetanus immunisation should now receive combined adsorbed tetanus/low dose diphtheria vaccine for adults and adolescents (Td). 2. A full course of tetanus and diphtheria vaccines consists of 5 doses. 3. Visitors to areas where medical attention may not be accessible, should a tetanus prone injury occur and whose last dose of a tetanus containing vaccine was more than 10 years previously, a booster dose of Td should be given, even if the individual has received 5 doses of vaccine previously. This is a precautionary measure in case the tetanus immune globulin (TIG) is not available to the individual should a tetanus prone injury occur. Table 4. Tetanus immunisation schedule. Schedule
Children
Adults
Primary Course
3 doses of vaccine (usually as DTaP*) at 2, 3 and 4 months of age at least 3 years after the primary course, usually preschool entry (as DTaP*) aged 13–18 years before leaving school (as Td)
3 doses of vaccine (as Td) each one month apart
4th dose
5th dose
10 years after primary course (as Td) 10 years after 4th dose (as Td)
*DTaP, Diptheria-Tetanus -acellular -Pertussis
Conclusion A high index of suspicion, early recognition and aggressive management of tetanus is essential. It cannot be emphasized enough that the diagnosis is solely made on clinical grounds. While tetanus may never be eradicated, further reductions in tetanus deaths are possible. Adequate steps and measures should be taken to increase awareness of this potentially preventable disease.
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International Journal of Surgery 2004; 2: 109–112
A Review of the Epidemiology, Pathogenesis and Management of Tetanus I.H. Mallick1 and M.C. Winslet2 1
Honorary Lecturer & Research Fellow, University Dept of Surgery, Royal Free & University College Medical School, London, UK Professor and Head of the University Department of Surgery, Royal Free & University College Medical School, London, UK Correspondence to: Mr Ismail Mallick, Honorary Lecturer & Research Fellow, University Dept of Surgery, Royal Free & University College Medical School, London NW3 2QG. Email: [email protected] 2
Abstract Tetanus remains an important disease worldwide. In the United Kingdom, the elderly and intravenous drug users are at particular risk of acquiring clinical tetanus. Tetanus is associated with a high morbidity and mortality. Once the diagnosis of tetanus is suspected, intensive management is necessary. In this article we review the history, epidemiology, microbiology, clinical features, mode of transmission, pathogenesis, differential diagnosis, management, complications and prevention of this life threatening disease.
Introduction Tetanus is often a fatal disease caused by the exotoxin from Clostridium tetani.1 It is essentially a disease of the central nervous system. The vast majority of patients (more than 95%) who develop tetanus have not been previously immunised or they are inadequately immunised.2 In the developed countries, high risk groups include the elderly and intravenous drug users.3 However, tetanus can be life-threatening even with full immunisation and proper treatment.4
History Tetanus has been an important disease worldwide for many generations. It is described both in the bible and in the writings of ancient
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Greek and Egyptian physicians.5 In 1884, Carle and Rattone produced tetanus in animals by injecting them with pus from a fatal human case of tetanus.6 In the same year, Nicolaeir produced tetanus in animals by injecting them with samples of soil.6 However, it was Kitasato in 1889, who isolated the organism from a human case and reported that the toxin could be neutralised by specific antibodies.6 In 1897, Nocard demonstrated the protective effects of passively transferred anti-toxin.1 Passive immunisation in humans was used during World War I.1 Tetanus Toxoid was developed by Descombey in 19241 and the effectiveness of active immunisation was demonstrated in World War II.6
Epidemiology The occurrence of tetanus is worldwide, but it is a common problem in areas that are densely populated in hot climates in which the soil is rich in organic matter.7 The incidence of tetanus in England and Wales decreased following the introduction of national immunisation in 1961.8 By law, tetanus became a notifiable disease in October 1968 in the UK.9 On average, six cases of clinical tetanus per year were reported in England and Wales between 1992 and 2002.10 Although the number of cases reported is declining, there is evidence that many cases are not being reported. Rushdy et al estimated the under-reporting to be between 54–64%.11
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Microbiology C. tetani is a gram positive, anaerobic, spore forming bacillus. It forms a terminal spore giving it a drum-stick appearance.12 C. tetani needs low oxygen tension for its survival and is very sensitive to heat. However, the spores are extremely resistant to heat and to the conventional antiseptics,13 being able to survive for many years in adverse conditions. The spores are widely distributed in nature and are killed by autoclaving at 121⬚ C for 10–15 minutes.12 Manure treated soil may contain large numbers of spores. They are found in the faeces of horses, sheep, cattle, rats, dogs, cats and chicken. In agricultural communities, a significant number of adults may harbour the organism. In intravenous drug users, the spores can also be located on the skin surfaces and in contaminated heroin.14,15
The disease usually presents with a descending pattern. The first sign is lock-jaw or trismus which is due to spasm of the masseter muscle.29 This is followed by spasm of the facial muscles leading to risus sardonicus, difficulty in swallowing, spasm of the extensors of the neck, back and legs to form a backward curvature (opisthotonus see Fig. 1), and rigidity of abdominal muscles. The patient may manifest with pyrexia of 39–41⬚C, hypertension, tachycardia and sweating. Spasms may occur frequently and last for several minutes but may continue for 3–4 weeks, with complete recovery taking several months.13,18,30 The severity of generalised tetanus is classified as mild, moderate, severe and very severe. (Table 1).16
Table 1. Classification of severity of Tetanus.
Mode of Transmission Transmission is primarily through contaminated wounds.13 The wound may be apparent or inapparent and may be minor or major.16 In fact, in about 25% of cases in the developed countries, the portal of entry is not evident at the time of diagnosis.17 Tetanus may follow surgery (elective or emergency), burns, puncture wounds, crush wounds, otitis media, animal bites, oral infections, child birth and abortion.18 In intravenous drug users, the potential sources of tetanus include contamination of drugs, adulterants (e.g. quinine), paraphernalia and skin.19–21 Tetanus is not however contagious from person to person.
Pathogenesis C. tetani usually enters the body through a wound. In the presence of low oxygen tension, spore germination occurs.12 The organism secretes two toxins namely tetanolysin and tetanospasmin. Tetanolysin can damage the viable local tissue surrounding the infection and optimises the conditions for bacterial multiplication.12,22 A powerful neurotoxin, tetanospasmin is produced and dissemination is by retrograde axonal spread to the central nervous system.2 The toxin becomes bound to gangliosides within the central nervous system, where it suppresses inhibitory influences on motor neurons.23 It inhibits the release of glycine and gamma-amino butyric acid (GABA).24–26 This can lead to unopposed muscle contractions and spasms, even seizures may develop. The autonomic nervous system may also be affected due to direct stimulation and autonomic overactivity is associated with a high mortality.27
Clinical Manifestations The incubation period varies from 3 to 21 days, with an average of 7 days.18 In general, the further the injury site is from the central nervous system, the longer the incubation period. The shorter the incubation period, the greater is the chance of death.12 Three clinical forms of tetanus have been described namely generalised tetanus, local tetanus and cephalic tetanus.17 The most common (more than 80%) form of tetanus is generalised tetanus.28
Grade
Type
Signs and symptoms
I
Mild
II
Moderate
III
Severe
IV
Very severe
mild to moderate trismus; general spasticity; no respiratory embarrassment; no spasms; little or no dysphagia moderate trismus; well-marked rigidity; mild to moderate but short spasms; moderate respiratory embarrassment with an increased respiratory rate greater than 30; mild dysphagia severe trismus; generalized spasticity; reflex prolonged spasms; increased respiratory rate greater than 40; apnoeic spells; severe dysphagia; tachycardia greater than 120 very severe: grade III plus violent autonomic disturbances involving the cardiovascular system. Severe hypertension and tachycardia alternating with relative hypotension and bradycardia, either of which may be persistent.
Local tetanus is an uncommon form of tetanus in which the patients may have persistent contraction of muscles in the same anatomical region as the injury.31 Local tetanus may be a forerunner of generalised tetanus. Cephalic tetanus is a rare form of tetanus occasionally presenting with otitis media in which C. tetani is isolated from the middle ear. There is usually involvement of the cranial nerves in the facial area. Cephalic tetanus may progress to generalised tetanus.32 The overall case fatality rate among the reported cases in England and Wales was 29% between the years 1984 and 2000.11
Investigations C. tetani is very rarely isolated from infection sites. The diagnosis is usually made on clinical grounds.11 Because of the rarity of tetanus and its similarity to other medical conditions the diagnosis can sometimes be difficult. (Box 1) The combination of a history of injury with a contaminated wound and muscular spasms (with or without risus sardonicus, trismus or opisthotonus) should raise the possibility of the diagnosis.
Box 1. Differential Diagnosis of Tetanus
Fig. 1. Sir CharlesBell’s portrait of opisthotonus in a soldier with tetanus from a wound sustained at the Battle of Corunna (1809). The painting hangs in the Royal College of Surgeons of Edinburgh (Reproduced by the kind permission of the Royal College of Surgeons of Edinburgh).
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Acute abdomen ⫾ peritonitis Dental abscesses Drug Withdrawal Dystonic reactions (e.g. due to neuroleptics) Encephalitis Head injury Hyperventilation Meningitis Rabies Sepsis Strychnine poisoning Subarachnoid haemorrhage Temporomandibular joint syndrome Tetany
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Complications (Table 2) Interference with breathing can occur due to aspiration and laryngospasm.16 Prolonged spasms, contractions or convulsions may lead to fractures of long bones or of the spine.2 Cardiovascular complications namely tachy/bradycardia, arrhythmias and hypertension may also occur due to stimulation of the autonomic nervous system.33 Nosocomial infections are common in these patients because of prolonged hospitalisation. Infections may occur from indwelling catheters, hospital acquired pneumonia, pressure sores, aspiration pneumonia, deep vein thrombosis and pulmonary embolism can also occur.34
Box 2. Management of Tetanus
Airway Breathing and Ventilation Circulation-Intravenous fluids Intravenous or (Intramuscular in multiple sites) of Tetanus Immune Globulin (TIG) Debridement of Wound Antibiotics Nutrition Immunisation with combined tetanus and diphtheria vaccine following recovery Antithrombotic measures
Table 2. Complications of Tetanus. Systems
Complications
Respiratory
apnoea, type I respiratory failure (atelectasis, aspiration pneumonia), type II respiratory failure (laryngospasm, excess sedation, truncal spasm), acute respiratory distress syndrome, complications of ventilation and tracheostomy tachy/bradycardia, hypo/hypertension, myocardial ischaemia, arrhythmias, asystole, cardiac failure infections, renal failure ileus, gastric stasis, diarrhoea, haemorrhage vertebral fracture and tendon avulsions during spasms, temporomandibular joint dislocations, nerve palsies weight loss, thromboembolic phenomenon, decubitus ulcers, multiple organ dysfunction syndrome(MODS)
Cardiovascular Renal Gastrointestinal Musculoskeletal General
Management Tetanus, when suspected, must be managed promptly and aggressively. The management of tetanus requires a multi-disciplinary team approach.35 Patients must be transferred to the intensive care unit (ITU). In a comparison study of 306 patients treated with intensive care management and 335 patients from the same hospital prior to the institution of the ITU, mortality decreased from 43.6% to 15% with ITU management.36 Early consultation with the consultant microbiologist is mandatory. Patients must be nursed in a quiet room to prevent muscular spasms from hyperexcitability. (Box 2) Airway The maintenance of the airway is a high priority. Early consultation with an anaesthetist regarding airway management in the emergency department even in cases where there is no respiratory compromise is warranted.37
Control of Spasms Benzodiazepines such as diazepam and midazolam are very useful in controlling the muscular spasms and rigidity of tetanus.13 Neuromuscular blocking agents (e.g. vecuronium) with intermittent positive pressure ventilation may be required for a prolonged period in certain cases.16 There are three uncontrolled studies that report that magnesium sulphate may reduce both the need for ventilation and the autonomic instability of severe tetanus.38–40 Tetanus Immune Globulin Tetanus immune globulin (TIG) is recommended for patients with tetanus.23 TIG can help remove unbound tetanus toxin, but cannot remove the toxin that is bound to nerve endings. The recommended dose is 500 IU administered intramuscularly.41 Due to the extreme potency of tetanospasmin, tetanus infection does not give rise to tetanus immunity. Active immunity with the combined adsorbed tetanus/low dose diphtheria vaccine should be administered intramuscularly at a site contralateral to the TIG dosing.42 Wound Debridement and Antibiotics Devitalized and necrotic tissue must be excised, foreign bodies removed and the wound thoroughly irrigated and cleansed of contaminants. Infected tissues must be debrided and abscesses if any must be drained promptly. Wounds may be left open after inspection, with delayed primary suturing performed after 7 days.43 Penicillin, erythromycin, tetracycline and metronidazole are all effective against C. tetani.6 However, the administration of intravenous metronidazole has been shown to be more effective than penicillin in preventing death when used in the treatment of tetanus.44 It has been postulated that penicillin is a centrally acting GABA antagonist, and may therefore act synergistically with tetanospasmin in producing muscular spasms.
Table 3. UK Department of Health guidelines for managing wounds to prevent tetanus.48 Tetanus Prone Wound Immunisation Status
Clean wound vaccine
Vaccine
Human Tetanus immunoglobulin #
Fully immunised i.e. has received a total of 5 doses of tetanus vaccine at appropriate intervals as single antigen or in a combined vaccine Primary immunisation complete, boosters incomplete but up to date Primary immunisation incomplete or boosters not up to date
not required
not required
only if risk especially high (e.g. contaminated with stable manure)
none required (unless next dose due soon and convenient to give now) a reinforcing dose of combined tetanus/ diphtheria vaccine and further doses as required to complete the recommended schedule (to ensure future immunity)
only if risk especially high
Not immunised or immunisation status not known or uncertain
an immediate dose of vaccine followed, if records confirm this is needed, by completion of a full 3 dose course of combined tetanus/diphtheria vaccine to ensure future immunity
none required (unless next dose due soon and convenient to give now) a reinforcing dose of combined tetanus/diphtheria vaccine and further doses as required to complete the recommended schedule (to ensure future immunity) an immediate dose of vaccine followed, if records confirm this is needed, by completion of a full 3 dose course of combined tetanus/diphtheria vaccine to ensure future immunity
yes: one dose of human tetanus immunoglobulin in a different site
yes: one dose of human tetanus immunoglobulin in a different site
# For prevention the dose of human tetanus immunoglobulin is; 250iu IM. If more than 24 hours have elapsed since injury or there is a risk of heavy contamination or following burns: 500iu IM.
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Feeding Weight loss is common in tetanus18 and there are several factors that contribute: inability to swallow due to spasm of muscles, autonomic changes in gastrointestinal function, increased basal metabolic rate from pyrexia and muscular activity and prolonged critical illness.18 Nutrition should, therefore, be established as early as possible. Enteral nutrition is associated with a lower incidence of complications and is cheaper than parenteral nutrition.45 Percutaneous endoscopic gastrostomy (PEG) may avoid the complications associated with nasogastric tube feeding.46
Prevention (Table 3) The combined adsorbed tetanus/low dose diphtheria vaccine in adults and adolescents offers effective protection against tetanus.47 A total of five doses of the vaccine at appropriate intervals confer life-long immunity. Even when a person is fully immunised tetanus can still occur, however the mechanism of immunisation failure is unclear. Theories include a burden of toxin that overwhelms the host immune defences, antigenic variability between toxin and toxoid, and selective suppression of the immune response.3 Tetanus Immunisation Following Injuries A wound that is prone to tetanus is defined as a wound or burn sustained more than six hours before surgical treatment or with any of the following characteristics: a puncture-type wound, contact with soil or manure likely to harbour tetanus and a significant degree of devitalised or dead tissue:8 Tetanus Immunisation Schedules (Table 4) 1. Adults and adolescents requiring tetanus immunisation should now receive combined adsorbed tetanus/low dose diphtheria vaccine for adults and adolescents (Td). 2. A full course of tetanus and diphtheria vaccines consists of 5 doses. 3. Visitors to areas where medical attention may not be accessible, should a tetanus prone injury occur and whose last dose of a tetanus containing vaccine was more than 10 years previously, a booster dose of Td should be given, even if the individual has received 5 doses of vaccine previously. This is a precautionary measure in case the tetanus immune globulin (TIG) is not available to the individual should a tetanus prone injury occur. Table 4. Tetanus immunisation schedule. Schedule
Children
Adults
Primary Course
3 doses of vaccine (usually as DTaP*) at 2, 3 and 4 months of age at least 3 years after the primary course, usually preschool entry (as DTaP*) aged 13–18 years before leaving school (as Td)
3 doses of vaccine (as Td) each one month apart
4th dose
5th dose
10 years after primary course (as Td) 10 years after 4th dose (as Td)
*DTaP, Diptheria-Tetanus -acellular -Pertussis
Conclusion A high index of suspicion, early recognition and aggressive management of tetanus is essential. It cannot be emphasized enough that the diagnosis is solely made on clinical grounds. While tetanus may never be eradicated, further reductions in tetanus deaths are possible. Adequate steps and measures should be taken to increase awareness of this potentially preventable disease.
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