Tetanus and tetanus vaccination

What is tetanus?

Tetanus is the result of infection with Clostridium tetani, a spore-forming Gram-positive obligate anaerobe. Early clinical descriptions of tetanus have been found in medical texts from ancient Egypt, India, and China, and in the writings of Hippocrates in ancient Greece.

Pathogenesis

Tetanus bacteria spores are found in virtually all soil, particularly soil rich in manure, but also in house dust and animal and human faeces. Spores can enter even the smallest wound; in the presence of anaerobic conditions found in necrotic tissue, active infection, or a foreign body, the bacteria produce a powerful exotoxin called tetanospasmin (also known as tetanus toxin (TeNT) or tetanus neurotoxin). This spreads via lymph and blood to the neuromuscular junction, where it binds to the presynaptic membrane and is transported up motor neurones to the spinal cord and/or brainstem. Here, the toxin blocks inhibitory neurotransmission that would normally suppress the activity of these motor neurones.¹ This disinhibition of lower motor neurones results in muscle hyperactivity, such as the characteristic muscle spasms (severe enough to tear muscles, cause long-bone fractures or spinal compression fractures) and rigidity seen clinically.

How common is tetanus? (Epidemiology)

Incidence and mortality

Tetanus is rare in the UK, largely due to the success of immunisation programmes. Eleven cases of tetanus were identified in England between January and December 2021;7 cases in 2020 and 4 cases in 2019.²

The disease remains problematic in resource-poor settings where immunisation coverage is low. South Asia and sub-Saharan Africa account for 82% of all tetanus cases globally.³

Despite regional disparities, the World Health Organization (WHO) estimates that in 2015 about 34,000 newborns died from neonatal tetanus (tetanus within the first 28 days of life). This is a 96% reduction from the situation in the late 1980s and is, once again, largely attributable to concerted public health efforts to eliminate the disease.⁴ In 2019, 12 countries had yet to eliminate maternal and neonatal tetanus.^{3 3}

Risk factors

• Age >60 years, lack of immunisation, poverty, injecting drug use.

• Wounds contaminated with garden soil or manure and those caused by rusty metals are particularly dangerous.

• It can also complicate burns, ulcers, gangrene, snakebite, frostbite, otitis media, septic abortion, and childbirth.

• It can also occur following intramuscular (IM) injections in surgery.

• Neonatal tetanus, which is mostly fatal, usually happens due to bacteria entering via the umbilical stump. It is particularly common in rural areas where deliveries are at home without adequate sterile procedures or cord care. For example, contaminated material such as cow dung may be used to cover the cut surface of the umbilical cord following birth.

Tetanus symptoms and presentation

The incubation period is between 4 and 21 days (on average 10 days). Most cases will occur within 14 days of infection.^{4 5} A shorter incubation period is associated with more severe disease. The incubation period of neonatal tetanus is 3-14 days, with the disease usually occurring between 6 and 8 days.⁶

15-25% of cases show no obvious evidence of recent wounds. Clinically, four forms are recognised:

• Generalised tetanus is the most common and, after a prodromal fever, malaise and headache, is usually a descending pattern of: :
  

  • Trismus (lockjaw, an associated later feature: risus sardonicus, a grin-like expression from fixed facial muscle spasm).

  • Neck stiffness (which may develop into opisthotonus: arched body with hyperextended neck).

  • Swallowing difficulties.

  • Abdominal muscle rigidity.

  • Muscular spasms (initially reflexive, then spontaneous).

• Localised tetanus is uncommon, may precede generalised tetanus but, generally, is a self-limiting illness with painful muscle spasms localised to the site of injury.

• Cephalic tetanus is also uncommon, as it is usually secondary to otitis media or a head wound, exhibiting cranial (especially facial) nerve palsies and progressing to the generalised form if untreated.

• Neonatal tetanus is a form of generalised tetanus in a newborn lacking passive immunity from a non-immune mother, infected usually via the umbilical stump through lack of antiseptic practice (see Risk factors, above). It presents with inability to suck or breastfeed, irritability, grimaces, or rigidity with spasms.

Diagnosis

The diagnosis of tetanus is made clinically. A probable case can be defined as the following:⁷

"In the absence of a more likely diagnosis, an acute illness with muscle spasms or hypertonia, and diagnosis of tetanus by a health care provider."

Generalised tetanus should include at least two of:

• Trismus.

• Painful contractions of trunk muscles.

• Generalised spasms.

Severity can be graded into mild, moderate, severe and very severe.

The spatula test is useful: touching the back of the pharynx with a spatula elicits a bite reflex in tetanus, instead of a gag reflex.

Investigations

Laboratory investigations are available to support the diagnosis, but treatment should never be delayed in order to wait for results. The main investigations are:

• Detection of C. tetani in wound samples or isolates using PCR or culture methods.

• Detection of toxin in serum.

• Detection of IgG against tetanus toxin in serum.

Negative results do not exclude tetanus.

Complications

Complications in severe generalised tetanus:

• Aspiration pneumonia.

• Laryngospasm, which may lead to asphyxia.

• Fractures from sustained contractions and convulsions.

• Respiratory embarrassment with tachypnoea, and intermittent apnoea.

• Autonomic nervous involvement leading to hypertension, dysrhythmias and cardiac arrest.

• Tetanic seizures mimicking epilepsy - frequency and severity related to the severity of illness, and indicate poor prognosis.

• Pulmonary embolus particularly in drug abusers and the elderly.

Tetanus treatment and management⁷

Early diagnosis and intervention can be life-saving. Patients will usually need access to mechanical ventilation, otherwise mortality remains high.

The clinical management of suspected tetanus includes:⁷

• Administering intravenous immunoglobulin (IVIG) or tetanus antitoxin (depending on availability) before any other action.

• Wound debridement.

• Antimicrobials (discuss with local microbiology team).

• Supportive care such as prophylactic sedation and intubation, benzodiazepines to prevent or control spasms, treatment of autonomic disturbance. Some patients will require a tracheostomy.

• Vaccination with tetanus toxoid after recovery.

Prognosis

Since the majority of tetanus cases occur in resource-poor settings, it is difficult to find good- quality or long-term prognostic studies. Most of the data come from survivors of neonatal tetanus and show evidence of neurodevelopmental delay and growth impairment.⁸

The muscle stiffness and ankle clonus can last for months after recovery and significant weight loss is always seen. Factors associated with increased mortality are:

• Older age (especially >60 years).

• Shorter duration of symptoms - trismus, rigidity and dysphagia.

• Severe disease at presentation.

• Shorter period of onset.

• Scarcity of resources (particularly mechanical ventilation).

Prevention of tetanus

Tetanus infection does not confer immunity; immediate vaccination (inactivated tetanus toxoid) is too slow to address a current infection. Antibiotic prophylaxis against tetanus in wound management is not indicated. Active infection should be treated appropriately.

Prevention of neonatal tetanus is possible by the vaccination of pregnant or non-pregnant women, or both, with tetanus toxoid and by the provision of clean delivery services.⁹

Because of concern at the low levels of immunity to diphtheria in older people in the UK, and the switch to inactivated polio vaccine (IPV), tetanus vaccine is now only given as part of combined products:

• 'Standard' tetanus/diphtheria/inactivated polio vaccine (Td/IPV) - used for adults and school leavers.

• Primary course for those aged under 10 years: diphtheria/tetanus/acellular pertussis/inactivated polio vaccine/Haemophilus influenzae type b/hepatitis B (DTaP/IPV/Hib/HepB).

• 'Pre-school booster': diphtheria/tetanus/acellular pertussis/inactivated polio vaccine(DTaP/IPV or dTaP/IPV).

The above vaccines do not contain live organisms and cannot cause tetanus. They are normally given IM into the upper arm or anterolateral thigh, except if patients have a bleeding disorder (eg, haemophilia) when deep subcutaneous injection is appropriate.

Vaccination schedule

The objective of the immunisation programme is to provide a minimum of five doses of tetanus-containing vaccine at appropriate intervals for all individuals.

For the majority of cases, a total of five doses of vaccine at the appropriate intervals is considered to give satisfactory long-term protection.

The UK schedule for primary immunisation is as follows:⁵

• Children aged under 10 years: at 2, 3 and 4 months of age. Those who miss a dose need to resume the schedule but do not need to have repeat doses. There should be a minimum for one month in between doses of the vaccine.

• Children aged over 10 years and adults: the primary course is three doses with an interval of at least one month in between doses. Those who miss a dose need to resume the schedule but do not need to have repeat doses.

The UK schedule for reinforcing immunisation is as follows:

• Children aged under 10 years: should receive the first booster (combined with diphtheria, pertussis and polio vaccines as the pre-school booster) three years after completion of the primary course.

• Children aged over 10 years and adults: should receive the first tetanus booster combined with diphtheria and polio vaccines (Td/IPV) at least five years after their primary course.

• The second booster dose of Td/IPV should be given to all people ten years after their first booster vaccine.

• NB: booster doses should be given to IV drug users who are uncertain about their immunisation status, as they are at a greater risk of getting tetanus.

Vaccination of individuals with unknown or incomplete immunisation status

• A child who has not completed the primary course should have the outstanding doses at monthly intervals and may receive their first booster dose as early as one year after the third primary dose, to re-establish them on the routine schedule.The second booster should be given at the time of leaving school to ensure long-term protection by this time, provided a minimum of five years is left between the first and second boosters.

• Where there is no reliable history of previous immunisation, it should be assumed that a person is unimmunised, and a full course of immunisations should be planned following the UK schedule.¹⁰

• Children coming to the UK may have had a fourth dose of a tetanus-containing vaccine that is given at around 18 months in some countries. This dose should be discounted, as it may not provide satisfactory protection until the time of the teenage booster. The routine pre-school and subsequent boosters should be given according to the UK schedule.

Travellers to remote areas

All travellers should ensure that they are fully vaccinated according to the UK schedule. For travellers to areas where medical attention may not be accessible and whose last dose of a tetanus-containing vaccine was more than ten years ago, a booster dose should be given prior to travelling, even if the individual has received five doses of vaccine previously. This is in case immunoglobulin is not available to the individual should a tetanus-prone injury occur. In some instances, a combined Td/IPV vaccine may be appropriate.

Contra-indications to tetanus vaccination

Absolute contra-indications

• Confirmed anaphylactic reaction to a previous tetanus-containing vaccine.

• Confirmed anaphylactic reaction to neomycin, streptomycin or polymyxin B.

Stable neurological conditions, febrile convulsions and personal or family history of seizures are not contra-indications.

Immunisation should be deferred if the child is acutely unwell with fever (vaccinate as soon as possible once the child has recovered). This is to avoid wrongly attributing their symptoms to the vaccine.

Fever, hypotonic-hyporesponsive episodes (HHEs), persistent crying or severe local reaction within 72 hours of previous vaccination are not reasons for not giving subsequent tetanus vaccinations.

Tetanus vaccines can be safely given to pregnant or breastfeeding women.

Side-effects of vaccine

Report adverse reactions to the Commission on Human Medicines (CHM) via the Yellow Card Scheme.

• Pain, redness and swelling are common.

• Fever, convulsions, high-pitched screaming and episodes of cyanosis, pallor and limpness occur with equal frequency after DTaP and DT vaccines.

• Transient nodule at injection site.

• Anaphylaxis is extremely rare.

Management of patients with tetanus-prone wounds

Clean wounds (wounds less than six hours old, non-penetrating with negligible tissue damage) are very unlikely to lead to tetanus; therefore immediate post-exposure treatment is not needed in these cases. However, people who have not received a complete primary course of the vaccine should receive an immediate reinforcing dose of the vaccine.

Tetanus-prone injuries⁷

Tetanus-prone wounds include:

• Any wound or burn with:

  • Puncture wounds, especially where there has been contact with soil or manure (eg, gardening injuries).

  • Foreign bodies (eg, splinter)

  • Compound fractures.

  • Clinical evidence of sepsis.

• Certain animal bites and scratches.

High-risk tetanus-prone wounds include any of the above with either:

• Heavy contamination with materials likely to contain tetanus spores.

• Extensive devitalised tissue.

• A delay in receiving surgical treatment, of >6 hours (even if the initial contamination was not heavy).

Management

• Thorough cleaning +/- surgical debridement of wounds is essential.

• Consider treating tetanus-prone wounds with antibiotics, depending on clinical severity, with a view to preventing tetanus.

• Based on a risk assessment of the wound category (clean, tetanus-prone or high- risk tetanus-prone) and the immunisation status of the individual, a reinforcing dose of tetanus containing vaccine +/- intramuscular tetanus immunoglobulin (IM-TIG) may be recommended. Details can be found in The Green Book on immunisation and in guidance from Public Health England.^{7 5}

• If the risk of tetanus is high, human tetanus immunoglobulin should be given, regardless of the patient's immunisation history.

• The rationale for using IM-TIG is to sufficiently and rapidly raise antibody levels in exposed individuals who have antibody levels below the protective threshold and who are not expected to make a sufficiently rapid memory response to vaccination.

• Both IM-TIG and boosting vaccines should be given promptly after exposure.

• Patients who are immunosuppressed may not be adequately protected against tetanus, despite having been fully immunised. They should be managed as if they were incompletely immunised.