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TETANUS
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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
Key Points
Summary
Questions
Tetanus
Angela Houston
Angela Houston is a specialist registrar in Infectious
disease, microbiology and virology in London and the south
coast.
This session provides an overview of tetanus - its clinical
presentation, differential diagnosis, treatment and
prevention.
Edited by Prof Tom Solomon, Dr Agam Jung and
Dr Sam Nightingale
Learning Objectives
TETANUS
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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
Key Points
Summary
Questions
By the end of this session you will be able to:
•Illustrate the impact of tetanus worldwide, its microbiology
and transmission
•Describe the actions of tetanus toxin
•Recognise the clinical presentation of tetanus and
differential diagnosis
•Explain the treatment of tetanus
Introduction
TETANUS
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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
Key Points
Summary
Questions
In this session you will learn about the neurological
presentation of tetanus, its microbiology, routes of
transmission, presentation, treatment and prevention.
TETANUS
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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
Key Points
Summary
Questions
Impact of Tetanus Worldwide,
and Transmission I
First described over 3000 years ago, tetanus still causes major
health problems in much of the developing world.
There are an estimated 800,000 to 1,000,000 deaths worldwide
every year despite a safe and effective vaccine being available.
Over half of these deaths are in neonates. Worldwide elimination of
neonatal tetanus by 1995 was one of the targets of the World Health
Organization (WHO), and the number of countries in which neonatal
tetanus occurs is progressively decreasing.
There are approximately 5-15 cases per year in the UK and these
are predominantly in adults aged over 65 (who may have missed
vaccination campaigns or have wavering immunity).
There are occasional outbreaks in injecting drug users when batches
of heroin have become contaminated
TETANUS
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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
Key Points
Summary
Questions
Impact of Tetanus Worldwide,
and Transmission II
.
Tetanus cases reported worldwide 1990-2004. Ranging
from high prevalence (dark red) to very few cases
(yellow).
Clinical Features
TETANUS
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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
Key Points
Summary
Questions
The clinical features of tetanus arise from the actions of a potent
neurotoxin produced by the obligate Gram positive anaerobic
bacteria Clostridium tetini.
The toxin blocks the inhibitory action of gamma aminobutyric acid
(GABA) to motor neurones, resulting in unopposed motor nerve
activity. This causes increased muscle tone, painful muscle spasms
and the characteristic 'risus sardonicus' (lock jaw – shown below),
and opisthotonus associated with tetanus.
Clostridial
Clostridial
sp.
live
in
the
gastrointestinal tract of many
mammals including farm animals
and horses.
The bacteria is able to form spores
which are extremely stable and
can survive in the soil and
environment for long periods of
time and are able to withstand
many household detergents.
Lock jaw in male patient
with tetanus
TETANUS
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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
Key Points
Summary
Questions
Infection and Action of
Tetanus Toxin I
Infection occurs when spores are introduced into the body usually
via a deep penetrating wound where the necrotic or anaerobic
conditions in the tissues allow the spores to germinate and bacterial
growth to occur.
The most common sites are:
•Wounds on the lower limbs
•Postpartum or post abortion infections of the uterus
•Non-sterile intramuscular injections
•Compound fractures
Even minor trauma can lead to disease and in up to 30% of patients
no portal of entry is apparent. The incubation period is usually
between 3-21 days.
Micrograph depicting clostridium
tetani bacteria that cause tetanus in
humans.
TETANUS
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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
Key Points
Summary
Questions
Infection and Actions of
Tetanus Toxin II
The bacteria contain a plasmid which encode the toxin. The toxin
is a polypeptide which undergoes post translational cleavage to
produce an active metalloprotease known as tetanospasmin
(tetanus toxin).
After death of the clostridial bacterium, the toxin is released and
then activated by bacterial or tissue proteases into its active form.
This travels through the lymphatic or vascular system until it
reaches the neuromuscular junction (NMJ) where it exerts its
action.
The tetanus toxin is composed of a heavy chain necessary for
binding and entry into neurons and a light chain responsible for its
toxic properties. At the NMJ the heavy chain of the toxin binds to
disialogangliosides (GD2 and GD1b) on the neuronal membrane
and is endocytosed into the neurone.
TETANUS
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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
Key Points
Summary
Questions
Infection and Actions of
Tetanus Toxin III
It then travels by retrograde axonal
transport along the motor neuron from
the peripheral to the central nervous
system.
The active light chain cleaves
synaptobrevin which is a protein found
in vesicle membranes and is essential
for the fusion of synaptic vesicles with
the presynaptic membrane.
This prevents release the inhibitory
neurotransmitter GABA into the
synaptic cleft. The α-motor neurons
are therefore under no inhibitory
control
and
undergo
sustained
excitatory
discharge
causing
increased
muscle
tone,
painful
spasms, and widespread autonomic
instability characteristic of tetanus.
Botulism and Tetanus
TETANUS
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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
Key Points
Summary
Questions
Tetanus toxin is highly homologous in amino acid sequence to the
family of botulinum neurotoxins, which like tetanus toxin, inhibits
neurotransmitter release by cleavage of proteins involved in vesicle
fusion.
The difference in clinical symptoms between botulism and tetanus is
due to the location of toxin action.
Botulinum toxin is not transported to the CNS and remains at the
periphery where it inhibits the release of acetylcholine This results in
an acute flaccid paralysis.
Clinical presentation I
TETANUS
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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
Key Points
Summary
Questions
The most common presentation is generalised severe
tetanus usually presenting with trismus (lockjaw), intensively
painful tonic contractors and signs of autonomic over activity
with little or no impairment of conscious level.
Spasms may be triggered by the smallest of stimuli including
noise, light or movement. The characteristic signs are:
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Opisthotonus
Risus sardonicus (sardonic smile - shown opposite)
Rigid abdomen
Dysphagia
Periods of apnoea due to spasm of thoracic muscles
Recovery requires the growth of new axonal nerve terminals
as the tetanus toxin binds irreversibly. This can take weeks
to recover.
Clinical presentations II
TETANUS
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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
Key Points
Summary
Questions
Rarely tetanus can present with localised muscle spasms but this
invariably develops into generalised tetanus over time
Neonatal tetanus presents within the first 14 days of life with:
•Seizures
•Spasms
•Trismus
•Inability to suck
This is usually caused by contamination of the umbilical stump in
mothers who are poorly immunised.
An infant with neonatal
tetanus
TETANUS
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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
Key Points
Summary
Questions
Differential diseases and
clinical features I
Drug induced dystonia
•Often produces deviation of the eyes, chorioform movements and
absence of tonic muscle contractions between spasms.
•Tetanus does not produce deviation of the eyes.
•Drug induced dystonias may improve with administration of
anticholinergic antagonists.
Malignant neurolepitc syndrome
This may present with autonomic instability and muscular spasms
but is usually accompanied with a fever and altered mental status.
Trismus due to dental infection
Deep dental root abscess may rarely trigger trismus but usually
careful clinical examination can aid diagnosis of this.
TETANUS
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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
Key Points
Summary
Questions
Differential diseases and
clinical features II
Strychnine poisoning
•Looks very similar to tetanus
•Blood assays available if suspicious
•Both require supportive care
Stiff man syndrome
Rare neurological disorder causing severe muscle rigidity and
spasms. Antibodies can be detected against glutamic acid
decarboxylase (GAD).
Treatment of Tetanus
TETANUS
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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
Key Points
Summary
Questions
Treatment should usually be carried out in the intensive care
unit and involves:
• Wound management – careful examination and
debridement of necrotic tissue to prevent infection.
• Halting toxin production
• Neutralisation of unbound toxin
• Control of muscle spasms
• Management of dysautonomia
• Generalised supportive measures
Halting Toxin Production
TETANUS
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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
Key Points
Summary
Questions
Antibiotics act only as an adjunct in the treatment of tetanus as it is
a toxin driven disease. Treatment is usually 7-10 days
Penicillin and metronidazole are
both
effective
at
killing
clostridium bacteria although
antibiotics have a limited role in
the treatment of tetanus.
Their is some evidence to
suggest that metronidazole may
be superior as it may result in the
use of fewer muscle relaxants
compared to penicillin which has
antagonistic effects on GABA
TETANUS
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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
Key Points
Summary
Questions
Neutralisation of
Circulating Toxin
Tetanus toxin binds irreversibly to
tissue and neurones so only
circulating unbound toxin is
available for neutralisation. This
has been demonstrated in 10% of
patients with clinical tetanus
Human tetanus immunoglobulin
5000-10,000IU should be given as
soon as diagnosis is considered.
This is given intramuscularly and
required up to 30mls which can
cause major discomfort.
Normal
preparations
of
immunoglobulin
contain
reasonable levels of tetanus
antibody and can be used as an
alternative
TETANUS
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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
Key Points
Summary
Questions
Active Immunisation/
Tetanus Vaccine
Tetanus is one of the few bacterial infections that confers no
immunity post infection so all patients should receive active
immunisation as soon as a diagnosis is suspected
The vaccine is made from a cell free purified toxin extracted form a
strain of C. Tetani. This is treated with formaldehyde that confer it
into a tetanus toxoid with is absorbed onto an adjunct
The vaccine is not live and therefore can be given to
immunosuppressed patients. Tetanus vaccine is part iof a combined
vaccine given in combination with diphtheria acellular pertussus,
polio or Hib B
A total of 5 doses at an interval
determined by that nation’s
immunisation programme
should be sufficient to give long
term protection.
Control of Muscle Spasms
TETANUS
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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
Key Points
Summary
Questions
Tetanus causes painful muscular spasms which can result in life
threatening respiratory compromise and exhaustion. Spasms can
be triggered by any stimuli including light/sound and movement.
Nursing in a quiet calm environment is paramount to treatment.
Benzodiazepines are the mainstay of treatment in terms of muscle
relaxants and sedations an frequently require very large doses for
long periods.
Muscle relaxants when sedation is inadequate neuromuscular
blocking agents such as baclofen can be used.
Magnesium sulphate is given as an iv infusion and can reduce
cardiovascular instability and significantly reduces the need for
sedation.
Supportive Treatment
TETANUS
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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
Key Points
Summary
Questions
Since patients with tetanus recover slowly and often require long
periods in the intensive care unit ventilated, the majority of
treatment is supportive.
Supportive care
Early tracheostomy, total parental nutrition, fluid balance,
prophalaxysis against thrombo-embolism and physiotherapy along
with protection against opportunistic infections.
Prognosis
In developing world the case fatality ranges between 8-30%
Neonatal mortality was universal but now rates are between 1060%. Those with severe disease and short incubation tend to do
worse and are often left with long term neurological problems.
Key points
TETANUS
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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
Key Points
Summary
Questions
• Tetanus is a rare but severe neurological infection caused by a
toxin produced by the anaerobic bacteria Clostridium tetani
• The toxin binds irreversibly to the neuromuscular junction travels
by retrograde axonal transport to the central nervous system
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The toxin blocks the inhibitory action of GABA to motor neurones
• This results in unopposed motor nerve activity which causes
increased muscle tone and painful muscle spasms with normal
conscious level
• Recovery takes weeks as it requires the growth of new axonal
nerve terminals
• The mainstay of treatment is debridement of wounds and
supportive measures to reduce muscle spasms using
benzodiazepines and iv magnesium and respiratory support
Summary
TETANUS
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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
Key Points
Summary
Questions
Having completed this session you will now be able to:
• Illustrate the impact of tetanus worldwide, microbiology and
transmission
• Describe the actions of tetanus toxin
• Recognise the clinical presentation of tetanus and differential
diagnosis
• Explain the treatment of tetanus
Further Reading
Cook, T., R. Protheroe, and J. Handel, Tetanus: a review of the literature.
British Journal of Anaesthesia, 2001. 87(3): p. 477-487.
Montecucco, C. and G. Schiavo, Mechanism of action of tetanus and
botulinum neurotoxins. Molecular microbiology, 1994. 13(1): p. 1-8.
Cooke, M., Are current UK tetanus prophylaxis procedures for wound
management optimal? Emergency Medicine Journal, 2009. 26(12): p. 845.
Attygalle, D. and N. Rodrigo, Magnesium as first line therapy in the
management of tetanus: a prospective study of 40 patients*. Anaesthesia,
2002. 57(8): p. 778-817.
Beeching, N. and N. Crowcroft, Tetanus in injecting drug users. British Medical
Journal, 2005. 330(7485): p. 208.
Acknowledgements
Centers for Disease Control Public Health Library
Question 1
TETANUS
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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
Key Points
Summary
Questions
Select the single best answer from the options given. Click on the
answer to see if it is correct and read an explanation.
With regards to the tetanus toxin which statement is
INCORRECT?
a. The toxin is encoded on the clostridium tetani chromosome
b. The toxin acts as a metalloprotease
c. The heavy chain is responsible for binding to the
neuromuscular junction
d. The toxin travels by retrograde axonal transport to reach the
central nervous system