TETANUS Tetanus

• Learning Objectives
• Introduction
• Impact of tetanus
Angela Houston
• Clinical features
• Infection and action
• Botulism and Angela Houston is a specialist registrar in Infectious
tetanus disease, microbiology and virology in London and the south
• Clinical coast.
presentation
• Differential
Diagnosis
This session provides an overview of tetanus - its clinical
• Treatment presentation, differential diagnosis, treatment and
• Halting toxin prevention.
production
• Immunisation
• Supportive
Edited by Prof Tom Solomon, Dr Agam Jung and
treatment
Dr Sam Nightingale
• Key Points
• Summary
• Questions
 Learning Objectives
TETANUS
• Learning Objectives By the end of this session you will be able to:
• Introduction
• Impact of tetanus •Illustrate the impact of tetanus worldwide, its microbiology
• Clinical features
and transmission
• Infection and action
• Botulism and
tetanus •Describe the actions of tetanus toxin
• Clinical
presentation •Recognise the clinical presentation of tetanus and
• Differential differential diagnosis
Diagnosis
• Treatment •Explain the treatment of tetanus
• Halting toxin
production
• Immunisation
• Supportive
treatment
• Key Points
• Summary
• Questions
 Introduction
TETANUS In this session you will learn about the neurological
• Learning Objectives presentation of tetanus, its microbiology, routes of
• Introduction transmission, presentation, treatment and prevention.
• Impact of tetanus
• Clinical features
• Infection and action
• Botulism and
tetanus
• Clinical
presentation
• Differential
Diagnosis
• Treatment
• Halting toxin
production
• Immunisation
• Supportive
treatment
• Key Points
• Summary
• Questions
 Impact of Tetanus Worldwide,
TETANUS
and Transmission I
• Learning Objectives First described over 3000 years ago, tetanus still causes major
• Introduction health problems in much of the developing world.
• Impact of tetanus
• Clinical features There are an estimated 800,000 to 1,000,000 deaths worldwide
• Infection and action every year despite a safe and effective vaccine being available.
• Botulism and Over half of these deaths are in neonates. Worldwide elimination of
tetanus neonatal tetanus by 1995 was one of the targets of the World Health
• Clinical Organization (WHO), and the number of countries in which neonatal
presentation tetanus occurs is progressively decreasing.
• Differential
Diagnosis There are approximately 5-15 cases per year in the UK and these
• Treatment are predominantly in adults aged over 65 (who may have missed
• Halting toxin vaccination campaigns or have wavering immunity).
production
• Immunisation There are occasional outbreaks in injecting drug users when batches
• Supportive of heroin have become contaminated
treatment
• Key Points
• Summary
• Questions
 Impact of Tetanus Worldwide,
TETANUS
and Transmission II
• Learning Objectives
• Introduction
.
• Impact of tetanus
• Clinical features
• Infection and action
• Botulism and
tetanus
• Clinical
presentation
• Differential
Diagnosis
• Treatment
• Halting toxin
production
• Immunisation
• Supportive
treatment Tetanus cases reported worldwide 1990-2004. Ranging
• Key Points from high prevalence (dark red) to very few cases
• Summary (yellow).
• Questions
 Clinical Features
The clinical features of tetanus arise from the actions of a potent
TETANUS
neurotoxin produced by the obligate Gram positive anaerobic
• Learning Objectives bacteria Clostridium tetini.
• Introduction
• Impact of tetanus The toxin blocks the inhibitory action of gamma aminobutyric acid
• Clinical features (GABA) to motor neurones, resulting in unopposed motor nerve
• Infection and action activity. This causes increased muscle tone, painful muscle spasms
• Botulism and and the characteristic 'risus sardonicus' (lock jaw – shown below),
tetanus and opisthotonus associated with tetanus.
• Clinical
Clostridial
presentation
Clostridial sp. live in the
• Differential
gastrointestinal tract of many
Diagnosis
mammals including farm animals
• Treatment
and horses.
• Halting toxin
production
The bacteria is able to form spores
• Immunisation
which are extremely stable and
• Supportive
can survive in the soil and
treatment
environment for long periods of
• Key Points Lock jaw in male patient
time and are able to withstand
• Summary with tetanus
many household detergents.
• Questions
 Infection and Action of
TETANUS
Tetanus Toxin I
• Learning Objectives Infection occurs when spores are introduced into the body usually
• Introduction via a deep penetrating wound where the necrotic or anaerobic
• Impact of tetanus conditions in the tissues allow the spores to germinate and bacterial
• Clinical features growth to occur.
• Infection and action
• Botulism and The most common sites are:
tetanus •Wounds on the lower limbs
• Clinical •Postpartum or post abortion infections of the uterus
presentation •Non-sterile intramuscular injections
• Differential •Compound fractures
Diagnosis
• Treatment Even minor trauma can lead to disease and in up to 30% of patients
• Halting toxin no portal of entry is apparent. The incubation period is usually
production between 3-21 days.
• Immunisation
• Supportive Micrograph depicting clostridium
treatment tetani bacteria that cause tetanus in
• Key Points humans.
• Summary
• Questions
 Infection and Actions of
TETANUS Tetanus Toxin II
• Learning Objectives The bacteria contain a plasmid which encode the toxin. The toxin
• Introduction is a polypeptide which undergoes post translational cleavage to
• Impact of tetanus produce an active metalloprotease known as tetanospasmin
• Clinical features (tetanus toxin).
• Infection and action
• Botulism and After death of the clostridial bacterium, the toxin is released and
tetanus then activated by bacterial or tissue proteases into its active form.
• Clinical This travels through the lymphatic or vascular system until it
presentation reaches the neuromuscular junction (NMJ) where it exerts its
• Differential action.
Diagnosis
• Treatment The tetanus toxin is composed of a heavy chain necessary for
• Halting toxin binding and entry into neurons and a light chain responsible for its
production toxic properties. At the NMJ the heavy chain of the toxin binds to
• Immunisation disialogangliosides (GD2 and GD1b) on the neuronal membrane
• Supportive and is endocytosed into the neurone.
treatment
• Key Points
• Summary
• Questions
 Infection and Actions of
TETANUS Tetanus Toxin III
• Learning Objectives It then travels by retrograde axonal
• Introduction transport along the motor neuron from
• Impact of tetanus the peripheral to the central nervous
• Clinical features system.
• Infection and action
• Botulism and The active light chain cleaves
tetanus synaptobrevin which is a protein found
• Clinical in vesicle membranes and is essential
presentation for the fusion of synaptic vesicles with
• Differential the presynaptic membrane.
Diagnosis
• Treatment This prevents release the inhibitory
• Halting toxin neurotransmitter GABA into the
production synaptic cleft. The α-motor neurons
• Immunisation are therefore under no inhibitory
• Supportive control and undergo sustained
treatment excitatory discharge causing
• Key Points increased muscle tone, painful
• Summary spasms, and widespread autonomic
• Questions instability characteristic of tetanus.
 Botulism and Tetanus
TETANUS Tetanus toxin is highly homologous in amino acid sequence to the
family of botulinum neurotoxins, which like tetanus toxin, inhibits
• Learning Objectives neurotransmitter release by cleavage of proteins involved in vesicle
• Introduction fusion.
• Impact of tetanus
• Clinical features The difference in clinical symptoms between botulism and tetanus is
• Infection and action due to the location of toxin action.
• Botulism and
tetanus Botulinum toxin is not transported to the CNS and remains at the
• Clinical periphery where it inhibits the release of acetylcholine This results in
presentation an acute flaccid paralysis.
• Differential
Diagnosis
• Treatment
• Halting toxin
production
• Immunisation
• Supportive
treatment
• Key Points
• Summary
• Questions
 Clinical presentation I
TETANUS The most common presentation is generalised severe
tetanus usually presenting with trismus (lockjaw), intensively
• Learning Objectives painful tonic contractors and signs of autonomic over activity
• Introduction
with little or no impairment of conscious level.
• Impact of tetanus
• Clinical features
• Infection and action Spasms may be triggered by the smallest of stimuli including
• Botulism and noise, light or movement. The characteristic signs are:
tetanus
• Clinical • Opisthotonus
presentation • Risus sardonicus (sardonic smile - shown opposite)
• Differential • Rigid abdomen
Diagnosis
• Dysphagia
• Treatment
• Halting toxin • Periods of apnoea due to spasm of thoracic muscles
production
• Immunisation Recovery requires the growth of new axonal nerve terminals
• Supportive as the tetanus toxin binds irreversibly. This can take weeks
treatment to recover.
• Key Points
• Summary
• Questions
 Clinical presentations II
Rarely tetanus can present with localised muscle spasms but this
TETANUS
invariably develops into generalised tetanus over time
• Learning Objectives
• Introduction Neonatal tetanus presents within the first 14 days of life with:
• Impact of tetanus
• Clinical features •Seizures
• Infection and action •Spasms
• Botulism and •Trismus
tetanus •Inability to suck
• Clinical
presentation This is usually caused by contamination of the umbilical stump in
• Differential mothers who are poorly immunised.
Diagnosis
• Treatment
• Halting toxin
production An infant with neonatal
• Immunisation
tetanus
• Supportive
treatment
• Key Points
• Summary
• Questions
 Differential diseases and
TETANUS
clinical features I
• Learning Objectives Drug induced dystonia
• Introduction
• Impact of tetanus •Often produces deviation of the eyes, chorioform movements and
• Clinical features absence of tonic muscle contractions between spasms.
• Infection and action
• Botulism and •Tetanus does not produce deviation of the eyes.
tetanus
• Clinical •Drug induced dystonias may improve with administration of
presentation anticholinergic antagonists.
• Differential
Diagnosis Malignant neurolepitc syndrome
• Treatment
• Halting toxin This may present with autonomic instability and muscular spasms
production but is usually accompanied with a fever and altered mental status.
• Immunisation
• Supportive Trismus due to dental infection
treatment
• Key Points Deep dental root abscess may rarely trigger trismus but usually
• Summary careful clinical examination can aid diagnosis of this.
• Questions
 Differential diseases and
TETANUS clinical features II
• Learning Objectives
Strychnine poisoning
• Introduction
• Impact of tetanus
• Clinical features •Looks very similar to tetanus
• Infection and action •Blood assays available if suspicious
• Botulism and •Both require supportive care
tetanus
• Clinical Stiff man syndrome
presentation
• Differential
Rare neurological disorder causing severe muscle rigidity and
Diagnosis
• Treatment spasms. Antibodies can be detected against glutamic acid
• Halting toxin decarboxylase (GAD).
production
• Immunisation
• Supportive
treatment
• Key Points
• Summary
• Questions
 Treatment of Tetanus
TETANUS Treatment should usually be carried out in the intensive care
• Learning Objectives unit and involves:
• Introduction
• Impact of tetanus • Wound management – careful examination and
• Clinical features debridement of necrotic tissue to prevent infection.
• Infection and action • Halting toxin production
• Botulism and • Neutralisation of unbound toxin
tetanus • Control of muscle spasms
• Clinical
• Management of dysautonomia
presentation
• Differential • Generalised supportive measures
Diagnosis
• Treatment
• Halting toxin
production
• Immunisation
• Supportive
treatment
• Key Points
• Summary
• Questions
 Halting Toxin Production
TETANUS
Antibiotics act only as an adjunct in the treatment of tetanus as it is
• Learning Objectives a toxin driven disease. Treatment is usually 7-10 days
• Introduction
• Impact of tetanus Penicillin and metronidazole are
• Clinical features both effective at killing
• Infection and action clostridium bacteria although
• Botulism and antibiotics have a limited role in
tetanus the treatment of tetanus.
• Clinical
presentation Their is some evidence to
• Differential suggest that metronidazole may
Diagnosis be superior as it may result in the
• Treatment use of fewer muscle relaxants
• Halting toxin compared to penicillin which has
production antagonistic effects on GABA
• Immunisation
• Supportive
treatment
• Key Points
• Summary
• Questions
 Neutralisation of
TETANUS
Circulating Toxin
• Learning Objectives Tetanus toxin binds irreversibly to
• Introduction tissue and neurones so only
• Impact of tetanus circulating unbound toxin is
• Clinical features available for neutralisation. This
• Infection and action has been demonstrated in 10% of
• Botulism and patients with clinical tetanus
tetanus
• Clinical Human tetanus immunoglobulin
presentation 5000-10,000IU should be given as
• Differential soon as diagnosis is considered.
Diagnosis This is given intramuscularly and
• Treatment required up to 30mls which can
• Halting toxin cause major discomfort.
production
• Immunisation Normal preparations of
• Supportive immunoglobulin contain
treatment reasonable levels of tetanus
• Key Points antibody and can be used as an
• Summary alternative
• Questions
 Active Immunisation/
TETANUS
Tetanus Vaccine
• Learning Objectives Tetanus is one of the few bacterial infections that confers no
• Introduction immunity post infection so all patients should receive active
• Impact of tetanus immunisation as soon as a diagnosis is suspected
• Clinical features
• Infection and action The vaccine is made from a cell free purified toxin extracted form a
• Botulism and strain of C. Tetani. This is treated with formaldehyde that confer it
tetanus into a tetanus toxoid with is absorbed onto an adjunct
• Clinical
presentation The vaccine is not live and therefore can be given to
• Differential immunosuppressed patients. Tetanus vaccine is part iof a combined
Diagnosis vaccine given in combination with diphtheria acellular pertussus,
• Treatment polio or Hib B
• Halting toxin
production A total of 5 doses at an interval
• Immunisation determined by that nation’s
• Supportive immunisation programme
treatment should be sufficient to give long
• Key Points term protection.
• Summary
• Questions
 Control of Muscle Spasms
Tetanus causes painful muscular spasms which can result in life
TETANUS
threatening respiratory compromise and exhaustion. Spasms can
• Learning Objectives be triggered by any stimuli including light/sound and movement.
• Introduction Nursing in a quiet calm environment is paramount to treatment.
• Impact of tetanus
• Clinical features Benzodiazepines are the mainstay of treatment in terms of muscle
• Infection and action relaxants and sedations an frequently require very large doses for
• Botulism and long periods.
tetanus
• Clinical Muscle relaxants when sedation is inadequate neuromuscular
presentation blocking agents such as baclofen can be used.
• Differential
Diagnosis Magnesium sulphate is given as an iv infusion and can reduce
• Treatment cardiovascular instability and significantly reduces the need for
• Halting toxin sedation.
production
• Immunisation
• Supportive
treatment
• Key Points
• Summary
• Questions
 Supportive Treatment
Since patients with tetanus recover slowly and often require long
TETANUS
periods in the intensive care unit ventilated, the majority of
• Learning Objectives treatment is supportive.
• Introduction
• Impact of tetanus Supportive care
• Clinical features Early tracheostomy, total parental nutrition, fluid balance,
• Infection and action prophalaxysis against thrombo-embolism and physiotherapy along
• Botulism and with protection against opportunistic infections.
tetanus
• Clinical Prognosis
presentation In developing world the case fatality ranges between 8-30%
• Differential Neonatal mortality was universal but now rates are between 10-
Diagnosis 60%. Those with severe disease and short incubation tend to do
• Treatment worse and are often left with long term neurological problems.
• Halting toxin
production
• Immunisation
• Supportive
treatment
• Key Points
• Summary
• Questions
 Key points
• Tetanus is a rare but severe neurological infection caused by a
TETANUS toxin produced by the anaerobic bacteria Clostridium tetani
• Learning Objectives
• Introduction • The toxin binds irreversibly to the neuromuscular junction travels
• Impact of tetanus by retrograde axonal transport to the central nervous system
• Clinical features
• Infection and action • The toxin blocks the inhibitory action of GABA to motor neurones
• Botulism and
tetanus • This results in unopposed motor nerve activity which causes
• Clinical increased muscle tone and painful muscle spasms with normal
presentation conscious level
• Differential
Diagnosis • Recovery takes weeks as it requires the growth of new axonal
• Treatment nerve terminals
• Halting toxin
production • The mainstay of treatment is debridement of wounds and
• Immunisation supportive measures to reduce muscle spasms using
• Supportive benzodiazepines and iv magnesium and respiratory support
treatment
• Key Points
• Summary
• Questions
 Summary
Having completed this session you will now be able to:
TETANUS
• Illustrate the impact of tetanus worldwide, microbiology and
• Learning Objectives transmission
• Introduction • Describe the actions of tetanus toxin
• Impact of tetanus • Recognise the clinical presentation of tetanus and differential
• Clinical features diagnosis
• Infection and action • Explain the treatment of tetanus
• Botulism and
tetanus Further Reading
Cook, T., R. Protheroe, and J. Handel, Tetanus: a review of the literature.
• Clinical
British Journal of Anaesthesia, 2001. 87(3): p. 477-487.
presentation Montecucco, C. and G. Schiavo, Mechanism of action of tetanus and
• Differential botulinum neurotoxins. Molecular microbiology, 1994. 13(1): p. 1-8.
Diagnosis Cooke, M., Are current UK tetanus prophylaxis procedures for wound
• Treatment management optimal? Emergency Medicine Journal, 2009. 26(12): p. 845.
• Halting toxin Attygalle, D. and N. Rodrigo, Magnesium as first line therapy in the
production management of tetanus: a prospective study of 40 patients*. Anaesthesia,
2002. 57(8): p. 778-817.
• Immunisation
Beeching, N. and N. Crowcroft, Tetanus in injecting drug users. British Medical
• Supportive Journal, 2005. 330(7485): p. 208.
treatment
• Key Points Acknowledgements
• Summary Centers for Disease Control Public Health Library
• Questions
 Question 1
Select the single best answer from the options given. Click on the
TETANUS answer to see if it is correct and read an explanation.
• Learning Objectives
• Introduction
• Impact of tetanus
• Clinical features With regards to the tetanus toxin which statement is
• Infection and action INCORRECT?
• Botulism and
tetanus a. The toxin is encoded on the clostridium tetani chromosome
• Clinical
presentation b. The toxin acts as a metalloprotease
• Differential
Diagnosis c. The heavy chain is responsible for binding to the
• Treatment neuromuscular junction
• Halting toxin
production d. The toxin travels by retrograde axonal transport to reach the
• Immunisation central nervous system
• Supportive
treatment
• Key Points
• Summary
• Questions