Tetanus


Article Author:
Crystal Bae


Article Editor:
Daniele Bourget


Editors In Chief:
Rodrigo Kuljis
Oleg Chernyshev
Aninda Acharya


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
Benjamin Eovaldi
Radia Jamil
Sobhan Daneshfar
Pritesh Sheth
Hassam Zulfiqar
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes
Kavin Sugumar


Updated:
2/20/2019 12:48:31 PM

Introduction

Tetanus is an infection that is characterized by muscle spasms, also known as lockjaw or trismus. The disease most commonly occurs in those who are not vaccinated or in the elderly with waning immunity. Currently, vaccination campaigns have decreased the incidence and prevalence of tetanus worldwide. The spasms from tetanus may last for minutes or may occur up to 4 weeks, with spasms starting in the face and then descending to the rest of the body. Symptoms are caused by toxins produced by the bacterium, Clostridium tetani. There are four main types of tetanus: generalized, neonatal, local, and cerebral tetanus, based on clinical features. Tetanus, a clinical diagnosis, has no particular laboratory test to confirm the diagnosis. Treatment includes tetanus immunoglobulin, antibiotic therapy, neuromuscular blockade, and supportive care for respiratory complications, autonomic instability, and muscle spasms. Full tetanus immunization is required after recovery from the disease. Long-term sequelae have been reported from survivors.[1][2][3][4]

Etiology

Tetanus is due to infection from the bacterium, Clostridium tetani, which is found in soil, dust or animal feces. It is a gram-positive, spore-forming, obligate anaerobic bacillus. This bacteria and its spores are found worldwide, however, more frequently found in hot and wet climate where the soil is rich with organic matter. C. tetani may enter the human body through wound puncture, laceration, skin breaks, or inoculation with an infected syringe or insect bites. High-risk populations include those that have not been vaccinated, intravenous drug users, and those who are immunosuppressed. Other causes of infection have been documented through surgical procedures, intramuscular injections, compound fractures, dental infections, and dog bites.[5][6][7]

Epidemiology

The World Health Organization (WHO) reports improvement in mortality rates from tetanus, associated with aggressive vaccination campaigns in recent years. The WHO estimates worldwide tetanus deaths in 1997 at around 275,000 with improved rates in 2011 at 14,132 cases. However, of these cases, the prevalence of tetanus is still disproportionately higher (some studies showing 135 times higher) in low-resource settings than rates in developed countries, with mortality rates of 20% to 45% with the infection. Mortality rates vary based on the availability of resources, especially mechanical ventilation, invasive blood pressure monitoring, and early treatment.

The incidence of neonatal tetanus is decreasing due to routine vaccination (DPT) worldwide which is combined with other vaccines, Pertussis and Diphtheria. The occurrence of tetanus among neonates is mostly due to incomplete vaccination of the infant. In 2013, approximately 84% of children less than 12 months of age had coverage of tetanus worldwide.

In high resource countries, such as the United States, cases of tetanus occur in the unimmunized or in the elderly who have decreased immunity over time. Intravenous drug users are also at risk with contaminated needles or drugs.

Pathophysiology

C. tetani secrete the toxins, tetanospasmin, and tetanolysin, causing the characteristic “tetanic spasm,” a generalized contraction of agonist and antagonistic muscles. Specifically, tetanospasmin affects the nerve and muscle motor end-plate interaction, causing the clinical syndrome of rigidity, muscle spasms, and autonomic instability. Tetanolysin damages tissue.

At the site of inoculation, tetanus spores enter the body, germinate in the wound, and release tetanospasmin into the bloodstream.  This toxin enters the presynaptic terminals in the neuromuscular end plate of motor neurons and inhibits neurotransmitter release of glycine and GABA. This paralyzes muscle fibers. Subsequently, this toxin, via retrograde axonal transport, travels to neurons in the central nervous system where it also inhibits neurotransmitter release; this occurs approximately 2 to 14 days after inoculation. Since glycine and GABA are major inhibitory neurotransmitters, cells fail to inhibit the motor reflex response to sensory stimulation, causing a tetanic spasm. This can cause such powerful unopposed muscle activity and contraction that bone fractures and muscle tears can occur.

The incubation period can last from one to 60 days but is, on average, around 7 to 10 days. Symptom severity depends based on the distance from the central nervous system with more severe symptoms associated with shorter incubation periods. Once the neurotoxin enters the brainstem, autonomic dysfunction occurs, typically the second week of symptom onset. With the loss of autonomic control, patients can present with labile blood pressure and heart rate, diaphoresis, bradyarrhythmias, and cardiac arrest. Symptoms can last for weeks to months with a mortality rate of 10% of those infected, higher in those without prior vaccination. There has been the frequent motor and long-term neuropsychiatric complications in survivors, however, many make full recoveries.

History and Physical

The clinical features of tetanus include lockjaw, grimace facial expression (risus sardonicus), generalized muscle spasms associated with severe pains, drooling, uncontrolled urination and defecation, and back arching spasm (opisthotonus) that may cause respiratory distress. Most commonly, trismus appears as the first symptom, with the progression of spasms throughout the rest of the body. Spasms can last a few minutes each time and frequently occur for the following weeks.

There are four forms of tetanus based on clinical findings: generalized, neonatal, local, and cephalic tetanus. Generalized tetanus is the most common form of tetanus, occurring in approximately 80% of cases. Patients present with a descending pattern of muscle spasms, first presenting with lockjaw, risus sardonicus. This can progress to a stiff neck, difficulty swallowing, and rigid pectoral and calf muscles. These spasms can occur for up to 4 weeks, with a full recovery taking months. Autonomic instability can also occur in these patients with fever, dysrhythmia, labile blood pressure and heart rate, respiratory difficulties, catecholamine excretion, and even early death.

Neonatal tetanus is a generalized form of tetanus in newborns of unimmunized mothers or from infection through a contaminated instrument when cutting the umbilical cord. Infants of immunized mothers generally do not get tetanus due to passive immunity from the mother. For those who are infected, there have been case reports of long-term consequences in survivors of neurodevelopmental impairments, behavioral problems, and deficits in gross motor and speech and language development.

Local tetanus and cephalic tetanus are the rarest forms of tetanus. Local tetanus is the persistent contraction of muscles at the site of injury that can persist for weeks. This type is uncommonly fatal, however, can progress to the generalized form of tetanus, which is more fatal. Cephalic or cerebral tetanus is limited to the muscles and nerves of the head. Cephalic tetanus occurs most commonly after head trauma such as a skull fracture, head laceration, eye injury, dental procedures, otitis media, or from another injury site. It presents with neck stiffness, dysphagia, trismus, retracted eyelids, deviated gaze, and risus sardonicus. The facial nerve is most frequently involved. However other cranial nerves can also be affected. These findings can lead to further complications such as broncho-aspiration, paralysis of respiratory and laryngeal muscles, and respiratory failure. This type can also progress to generalized tetanus.

Evaluation

The diagnosis of tetanus is clinical with no particular laboratory test. Clinicians may find a positive wound culture and the isolation of the organism, however, this occurs in only 30% of cases. Key features to note when diagnosing tetanus include acute onset, muscle contractures with generalized spasms with no other medical cause. Some patients can elicit a history of injury, but not all.

There have been reports of the “spatula test” that shows high specificity and sensitivity for the clinical diagnosis of tetanus. This involves using a soft-tipped instrument to touch the posterior pharyngeal wall. If this elicits an involuntary jaw contraction instead of the normal gag reflex, this suggests a positive test.

It is important to note that infections occur in people with no immunity or low-serum levels of anti-tetanus antibodies. However, it is not possible to exclude a tetanus infection with protective levels of antibodies. Life-threatening complications from tetanus can occur and include pneumonia secondary to aspiration and laryngospasm, rhabdomyolysis, upper gastrointestinal bleed, cardiovascular instability such as transient cardiac arrest, tachycardia or bradycardia, arrhythmias, and hypertension, acute renal failure, and secondary wound infections. Mortality from the infection occurs from respiratory failure and cardiovascular collapse, associated with autonomic dysfunction.

Treatment / Management

The treatment of tetanus is based on the severity of disease. However, all patients must have early wound debridement, antibiotic therapy, early intramuscular or intravenous administration of the human tetanus immunoglobulin (HTIG), and neuromuscular blockade. First-line therapy includes HTIG which removes released tetanospasmin toxin, however, does not affect the toxin that is already bound to the central nervous system. Debridement of the wound will control the source of toxin production. Although toxins are the main cause of disease, Metronidazole has been shown to slow progression of the disease. Penicillin, which was used in the past for treatment, is no longer recommended after discovering that it may have synergistic effects with tetanospasmin. Anti-spasmodics such as baclofen, vecuronium, pancuronium, and propofol have been used based on the clinical scenario.

For more severe tetanus, patients are likely hospitalized in the intensive care unit (ICU) and need sedation and mechanical ventilation, which can affect mortality and long-term sequelae. Tracheostomy is preferred because endotracheal tubes may be a stimulus for muscle spasms. Intravenous magnesium has been shown to prevent muscle spasm. Diazepam or midazolam, GABA-agonist benzodiazepines, are given as a continuous infusion to prevent respiratory or cardiovascular complications. HTIG is injected intrathecally, especially for cases of cerebral tetanus.

Clinicians must also provide supportive care, especially for patients with autonomic instability (labile blood pressure, hyperpyrexia, hypothermia). Providing high caloric diets from increased metabolic use from muscle contractions is also important.

Management of respiratory status, cardiovascular complications, and autonomic dysfunction are essential for survival. Moreover, all patients require full tetanus toxoid immunization at recovery; having the infection does not give the future patient immunity.[8][9]

Pearls and Other Issues

The tetanus vaccination has been considered as a routine vaccine in addition to pneumococci and influenza vaccines among older adults. Protection against tetanus by vaccines is essential because there is no natural immunity against tetanus. The tetanospasmin toxin is very lethal and will cause death before initiating an immune response. After recovery from an infection, patients must receive full immunity. In addition, post-exposure prophylaxis can also be provided through tetanus toxoid with or without tetanus immunoglobulin intravenous or intramuscular, depending on the wound.

Enhancing Healthcare Team Outcomes

Tetanus is a lethal infection and it is best managed by a multidisciplinary team that includes an emergency department physician, nurse practitioner, infectious disease expert, neurologist, pulmonologist and an intensivist. 

The treatment of tetanus is based on the severity of disease. However, all patients must have early wound debridement, antibiotic therapy, early intramuscular or intravenous administration of the human tetanus immunoglobulin (HTIG), and neuromuscular blockade. Patients with severe symptoms should be admitted to the ICU for close monitoring and mechanical ventilation. The healthcare providers must also provide supportive care, especially for patients with autonomic instability (labile blood pressure, hyperpyrexia, hypothermia). Providing high caloric diets from increased metabolic use from muscle contractions is also important. Moreover, all patients require full tetanus toxoid immunization at recovery; having the infection does not give the future patient immunity. For those who are treated with tetanus toxoid, recovery is assured but the rehabilitation may take weeks or months.[10]


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Tetanus - Questions

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What is the mechanism of action tetany secondary to Clostridium tetani?



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A patient who has sustained a dirty wound is seen in the ER. It is decided to perform a spatula test on him. This test is done to rule out which disorder?



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Which is false of Clostridium tetani?



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A patient is brought to the emergency department after she stepped on a rusty nail and sustained a puncture wound to the foot. The patient has been on a therapeutic dose of steroids for the past five years for ulcerative colitis. Her last tetanus toxoid booster was eight years ago. Which of the following should this patient now receive?



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A patient has suffered an injury from a rusty nail. He presents 12 hours later. The patient had a tetanus shot 5 years ago. Which of the following is most appropriate for the treatment of this patient?



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A patient with a stab wound presents 24 hours later with a dirty-appearing wound. The patient completed a primary series of tetanus toxoid-containing vaccine 6 years ago. Which of the following is most appropriate for this patient?



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Which statement is false about tetanus?



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Which of the following statements is false about the treatment of tetanus?



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In a symptomatic patient with tetanus, what is the drug of choice?



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A 17-year-old girl sustains a large laceration contaminated with dirt after falling. She is homeschooled and may not have received 3 doses of tetanus toxoid. What is the best treatment?



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Trismus may be seen in which condition?



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One is most likely to see trismus in a patient with which of the following?



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A young child came with a contaminated deep cut on his hand and leg sustained after playing flag football and running into a barbed wire fence. He never received tetanus vaccine before now. What vaccine should he receive now?



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Which of the following is not a routine vaccination for a 65 year old?



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Which is true regarding tetanus?



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Which is not true regarding tetanus?



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Which is a type of tetanus?



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Which of the following is the cause of tetanus?



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Release of which of the following is inhibited by tetanus toxin?



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A young male with tetanus is in the intensive care unit on a ventilator because of difficulty with breathing. While on the ventilator he continues to develop generalized spasms and trismus. He already is on a midazolam drip, but the spasms persist. What other agent may be of benefit in this patient?



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Travis is bitten by his dog "Old Yeller". The dog had recently fended off an attack by a wild wolf. Travis presents to the emergency department with grimaced facial expression, generalized muscle spasms associated with severe pain, drooling, uncontrolled urination and defecation, and back arching spasm. He has moderate respiratory distress. What is the best approach to making the diagnosis?



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Travis is bitten by his dog "Old Yeller". The dog had recently fended off an attack by a wild wolf. Travis presents to the emergency department with grimaced facial expression, generalized muscle spasms associated with severe pain, drooling, uncontrolled urination and defecation, and back arching spasm. He has moderate respiratory distress. Which of the following is true?



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Tetanus - References

References

Mertens T, [Vaccination in Germany - Recommendations of STIKO]. Deutsche medizinische Wochenschrift (1946). 2019 Feb;     [PubMed]
Randi BA,Sejas ONE,Miyaji KT,Infante V,Lara AN,Ibrahim KY,Lopes MH,Sartori AMC, A systematic review of adult tetanus-diphtheria-acellular (Tdap) coverage among healthcare workers. Vaccine. 2019 Feb 14;     [PubMed]
Vaccines for travelers. The Medical letter on drugs and therapeutics. 2018 Nov 19;     [PubMed]
Forstner C,Kwetkat A,Schleenvoigt B,Pletz MW, [Vaccinations in the elderly - who, when and which vaccine to use]. MMW Fortschritte der Medizin. 2018 Dec;     [PubMed]
Dong M,Masuyer G,Stenmark P, Botulinum and Tetanus Neurotoxins. Annual review of biochemistry. 2018 Nov 2;     [PubMed]
Fava JP,Stewart B,Dudzinski KM,Baker M,Volino L, Emerging Topics in Vaccine Therapeutics for Adolescents and Adults: An Update for Immunizing Pharmacists. Journal of pharmacy practice. 2018 Oct 23;     [PubMed]
Berkowitz AL, Tetanus, Botulism, and Diphtheria. Continuum (Minneapolis, Minn.). 2018 Oct;     [PubMed]
Fletcher M,Rankin S,Sarangarm P, The Effect of Pharmacy-Driven Education on the Amount of Appropriately Administered Tetanus Vaccines in the Emergency Department. Hospital pharmacy. 2019 Feb;     [PubMed]
Duss FR,Voide C, [Toxin-infections and toxin-related diseases due to Clostridia other than {i}Clostridium difficile{/i}]. Revue medicale suisse. 2018 Oct 10;     [PubMed]
Ma XY,Tian LX,Liang HP, Early prevention of trauma-related infection/sepsis. Military Medical Research. 2016;     [PubMed]

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