Author: Jonathan Tipping / Editor: Yasmin Sultan, Chris Gray / Reviewer: Jamie Sillett / Code: IC5, NeuC13, SLO1Published: 20/04/2023

Context

Since the introduction of tetanus immunisation in the 1940s, acute tetanus has become rare in the developed world.

Total tetanus global immunisation coverage

The World Health Organization [WHO] reported over 14,000 confirmed cases of tetanus worldwide in 2019 [1], however it is estimated that the actual number is much higher. For that same year, the Global Burden of Disease project estimated over 73,000 cases, and over 34,000 deaths. [2]

With a modelling study by Causey et al. [3] predicting 30 million children missed routine tetanus vaccinations in 2020 due to the Covid-19 pandemic, these numbers could increase.

In England there were 11 cases of tetanus and 1 death recorded in 2021. All cases were partially or non-immunised. There was a total of 22 cases and five deaths in the preceding five years. [4]

Tetanus is a notifiable disease in the UK. There is a statutory duty on all medical practitioners to notify the ‘proper officer’ at their local council or health protection team of suspected cases of certain infectious diseases. A full list of these, together with further details, is available on the government website.[5]

Definition

Tetanus is an acute disease caused by production of a neurotoxin within a host infected by the bacterium Clostridium tetani.

The Clostridium genus of bacteria is probably one of the most unfortunate to get infected with – as well as tetanus, it also contains Clostridium difficile (C. diff), C. bolulinum (botulism) and C. perfringens (gas gangrene).

Aetiology

Clostridium tetani is gram positive, anaerobic, and shaped like tennis rackets. It survives well outside of the body, and is commonly found in soil and manure, making it essentially impossible to eradicate as there’s always somewhere it can hide.

The bacteria can get into your body through puncture wounds, scratches, burns, or bites. Also, body piercings and tattoos with usterile and contaminated needles, or injecting contaminated drugs. Tetanus isn’t contagious, but it does have a 10-90% mortality, highest in infants and the elderly. [6]

The incubation period of tetanus is around 10 days, so symptoms generally appear around this time after exposure. [6]

How the Toxin Works

Two toxins are released by the bacilli:

Tetanolysin, which causes local tissue damage and may help to optimise conditions for the organism but has no known role in the pathogenesis of the disease.

Tetanospasmin, which is the potent neurotoxin that causes tetanus.

The LD50 of tetanus toxin has been measured to be around 2.5-3ng/kg (albeit in mice), making it the second deadliest toxin known to man after botulinum toxin. [7]

Tetanospasmin enters nerve endings at the neuromuscular junction, by direct infiltration from infected muscle or systemically via vascular and lymphatic routes. Intraneural migration to the neurones of the spinal cord and brainstem follows, where it moves into inhibitory nerve terminals blocking release of neurotransmitters, particularly gamma-aminobutyric acid (GABA) and glycine. [8]

This leads to uncontrolled motor neuron activity, increased muscle tone, and spasms. Spasms may cause dysphagia, respiratory distress, poor suckling in infants, abdominal rigidity, long bone fractures and joint dislocations.

Tetanospasmin also affects neurones of the autonomic nervous system leading to cardiovascular instability.

If the distance from the entry point to the central nervous system is shorter, the onset of symptoms will be quicker, for example in cases with head and neck wounds.

Learning bite

Intra-neural toxin cannot be neutralised and so a patient’s condition may continue to deteriorate after the onset of treatment. Recovery requires new synapse formation which takes 2-4 months.

Presenting Features

Tetanus is a clinical diagnosis.

The most common presentation of tetanus is generalised tetanus, where the key clinical features include at least two of the following:

  • Trismus
  • Painful muscular contractions of trunk muscles
  • Generalised spasms, frequently position of opisthotonos [9]

Another classical feature is risus sardonicus or rictus grin, which is an abnormal sustained facial muscle spasm that appears to produce grinning.

Patients remain conscious during these episodes, which are extremely painful.

There are three other forms

  • Localised tetanus – rigidity and spasms confined to the area around the site of infection
  • Cephalic tetanus – localised tetanus after a head or neck injury involving primarily muscles supplied by the cranial nerves
  • Maternal and neonatal tetanus (MNT) – this has been eliminated in the UK for decades, however cases are linked to inequality in access to healthcare services. MNT still remains a threat in 12 countries across Africa and Asia. 25,000 neonates died of tetanus in 2019. [10]

Learning bite

With an average of less than ten cases per year reported in England and Wales over the last three decades, the number of emergency department clinicians that have seen or diagnosed a case will be few and far between, so it’s important to have this disease in the back of your mind.

Autonomic Nervous System Involvement

Involvement of the autonomic nervous system occurs several days after the onset of spasms, and causes:

  • Blood pressure instability
  • Tachyarrhythmias, bradyarrhythmias, and asystole
  • Sweating, hypersalivation, and hyperthermia
  • Urinary retention and high-output renal failure

Sudden cardiac death is now the most frequent cause of mortality in tetanus in ventilated patients. [8]

Abdominal pain and rigidity may mimic an acute abdomen. Constipation, diarrhoea, and ileus may also occur.

Pharyngeal and laryngeal spasm may cause airway obstruction. The combination of poor swallow, increased saliva, inadequate cough and raised intra-abdominal pressure increases risk of aspiration.

Spatula Test

The spatula test is a simple diagnostic test. Touching the oropharynx with a spatula in normal patients elicits a gag reflex and efforts to expel the spatula; a negative result.

If tetanus is present, reflex spasm of the masseters occurs, and the patient bites the spatula; a positive result.

In 400 patients, this test had a sensitivity of 94% and a specificity of 100%, with no adverse effects [11].

Learning bite

The spatula test is very specific and highly sensitive for the diagnosis of tetanus.

The differential diagnosis for tetanus includes:

  • Orofacial infection
  • Quinsy
  • Dystonic drug reactions
  • Atypical seizures
  • Hypocalcaemia
  • Strychnine poisoning
  • Temporomandibular joint disorders

Fever is not an early diagnostic feature of acute tetanus but may occur in severe tetanus due to autonomic dysfunction. Diagnosis is clinical, with two out of three of

  • Trismus
  • Painful muscular contractions of trunk muscles
  • Generalised spasms, frequently position of opisthotonus [9]

Several investigations may confirm the diagnosis of tetanus:

Serum tetanus toxin should be sent prior to administration of immunoglobulin but treatment should never be delayed waiting for the lab result.

  • A positive result confirms the diagnosis
  • A negative result does not exclude it

The most sensitive test involves detection of C. tetani by PCR and culture in samples of debrided tissue. This can also be useful as debridement has an additional therapeutic benefit.

Wound swabs can be sent however a positive result is rare. Low or undetectable serum antibody levels can support the diagnosis of tetanus. [9]

The clinician should be aware of the following facts concerning prognosis:

Cause of death

Prior to development of critical care services, most deaths were caused by respiratory failure, with a high mortality.

Now that ventilatory support is more widely available, the most common cause of death in acute tetanus is sudden cardiac death caused by autonomic instability. [9] Overall case mortality in high-income countries is between 10-20%, whilst in low-income countries it is 30-50%, with a higher mortality for those sick enough to require ventilation. [12]

The effect of age

Age affects outcomes, and mortality is higher in the older population worldwide. However, in high-income countries, recent studies [12, 13] of patients with tetanus on intensive care reported mortality rates of 16% in their populations with a median age of 80 and 76 respectively.

Predictors

Predictors of a more-severe illness

Tetanus which remains localised has a good prognosis, however cephalic and neonatal tetanus have a much worse prognosis, with neonatal mortality exceeding 70%. [9]

Tetanus grading system

Table 1: Tetanus grading system

Grading of severity

 

Grade 1 (mild)

Mild to moderate trismus and general spasticity, little or no dysphagia, no respiratory embarrassment

Grade 2 (moderate)

Moderate trismus and general spasticity, some dysphagia and respiratory embarrassment, and fleeting spasms

Grade 3a (severe)

Severe trismus and general spasticity, severe dysphagia and respiratory difficulty, and severe prolonged spasms (both spontaneous and on stimulation)

Grade 3b (very severe)

As for severe tetanus plus autonomic dysfunction, particularly sympathetic overdrive

The most used grading system for acute tetanus is that reported by Ablett and used by the UK Health Security Agency. This is reproduced in the table above. [9, 14]

Vaccination

Completion of a full vaccination course does not guarantee immunity. Partial vaccination offers some protection and results in less-severe disease. [9]

Recovery

Patients who survive tetanus usually make a full recovery after 2-4 months. Occasionally, patients are left with residual weakness and hypotonia.

Initial and Secondary Management Strategies

 

Initial management  – make the diagnosis and manage the patient

ABCDE – perform a full assessment, providing airway, respiratory or circulatory support as needed.

Environment – dark and quiet to minimise external stimulation and resultant spasms.

IV access – and take routine bloods, creatine kinase, and serum to test for tetanus toxin and serology.

Get help – this is not a patient to manage on your own, they will need early multidisciplinary input such as airway management, supportive therapy, and wound debridement.

Reassess – monitor vital signs and ECG to detect respiratory compromise or autonomic instability.

 

Secondary management – prevent further toxin release and control symptoms

Antibiotics – metronidazole is the drug of choice and stops bacterial replication and therefore production of new toxin.

Immunoglobulin – the mainstay of treatment is intravenous tetanus immunoglobulin (TIG), however this is no longer available in the UK. If TIG is not available then intravenous Intravenous Immunoglobulin (IVIG) should be used, at a dose of 5,000 units in patients under 50kg, and 10,000 units in those over.

Wounds – should be debrided to remove the reservoir of tetanus bacilli, however IVIG can cause release of toxin from the wound site so surgery should be delayed until several hours after administration.

Muscle spasms – diazepam is the most common treatment [15] though this can be combined with other therapies such as chlorpromazine and phenobarbitone. A Cochrane review [16] found there was insufficient evidence to recommend a change from local usual practice though there was a suggestion that combination therapy did not give any further benefit and may cause harm. If diazepam is not sufficient, ventilation and neuromuscular blockade may be required.

Analgesia – should be given as needed.

Autonomic dysfunction – no drug has been consistently proven effective in treating autonomic dysfunction, though beta blockade has been generally unsuccessful, with increased rates of profound hypotension and sudden death.[17]

  • History of vaccination does not exclude the diagnosis
  • Failure to recognise that trismus is characteristic of tetanus
  • Failure to perform the spatula test
  • Laryngospasm may be severe and occur without warning, or may be precipitated by stimulation
  • Severe muscular spasms may compromise respiration
  • Administration of penicillin when metronidazole is the drug of choice
  • Autonomic instability requires active management to reduce the risk of sudden cardiac death
  • Neonatal tetanus could present in at-risk groups where maternal immunity is low, for example in patients migrating from areas where there is a low uptake of vaccination
  • The very non specific presentation may mask the diagnosis
  1. World Health Organization – Global Health Observatory data repository. 2022. [Accessed Jan 23, 2023].
  2. Global Burden of Disease (GBD). IHME, 2019.
  3. Causey K, et al. Estimating global and regional disruptions to routine childhood vaccine coverage during the COVID-19 pandemic in 2020: A modelling study. The Lancet, 2021 398(10299), 522–534.
  4. UK Health Security Agency. Tetanus in England: 2021. [Accessed Jan 23, 2023].
  5. UK Health Security Agency. Notifiable diseases and causative organisms: how to report. Published May 2022. [Accessed Jan 23, 2023].
  6. Department of Health. Immunisation Green Book – Chapter 30 Tetanus. Published June 2022. [Accessed January 23, 2023].
  7. Tetanus vaccines: WHO position paper – February 2017. Wkly Epidemiol Rec. 2017;92(6):53-76.
  8. Cook TM, Protheroe RT, Handel JM. Tetanus: a review of the literature. Br J Anaesth. 2001 Sep;87(3):477-87.
  9. UK Health Security Agency. Tetanus: advice for health professionals. Published July 2019. [Accessed January 23, 2023].
  10. Eliminating Maternal and Neonatal Tetanus. Kiwanis.
  11. Apte NM, Karnad DR. Short report: the spatula test: a simple bedside test to diagnose tetanus. Am J Trop Med Hyg. 1995 Oct;53(4):386-7.
  12. Mahieu R, et al. Admission of tetanus patients to the ICU: a retrospective multicentre study. Ann. Intensive Care 7, 112, 2017.
  13. Filia A, Bella A, et al. Tetanus in Italy 2001-2010: A continuing threat in older adults. Vaccine (2014);32(6):639-644.
  14. Ablett JJL. Analysis and main experiences in 82 patients treated in the Leeds Tetanus Unit. In: Ellis M, ed. Symposium on Tetanus in Great Britain. Boston Spa, UK: National Lending Library, 1967;1-10.
  15. National Institute for Health and Care Excellence. Diazepam. NICE BNF [Accessed January 23, 2023].
  16. Okoromah CAN, Lesi AFE. Diazepam for treating tetanus. Cochrane Database of Systematic Reviews 2004, Issue 1. Art. No.: CD003954. DOI: 10.1002/14651858.CD003954.pub2
  17. Reddy VG. Pharmacotherapy of tetanus–a review. Middle East J Anaesthesiol. 2002 Feb;16(4):419-42.