2. Tetanus
• Tetanus - from the Greek tetanos, derived
from teinein, meaning to stretch
• Tetanus is a neurologic disorder, characterized
by increased muscle tone and spasms, that is
caused by tetanospasmin, a toxin elaborated
by Clostridium tetani.
3. Tetanus
• 1st described in Egypt over 3000 yrs ago
• Rituals and tetanus (in Africa & West Indies)
• “Eight days sickness" from umbilical sepsis
• C. tetani discovered in 1885 by Nicolaier
• 1st passive immunization-1893
4. Epidemiology
• WHO’s goal eradication by the year 1995
• Remains endemic in the developing world
• 1000000 deaths worldwide in 1992
– 580 000 from neonatal tetanus
– 210 000 in SE Asia and 152 000 in Africa
• Only 3 cases reported in the US during 1990–
2004
• LTH: 68 patients aged > 10 between 2001 &
‘06
6. Epidemiology
• Occurs sporadically
• Almost always affects the non-immunized
• Common in
– areas where soil is cultivated
– rural areas
– warm climate
– during summer months
– among males
7. Epidemiology
• Mortality
• Highest in elderly
– > 50% over 60 years
– Possibly related to a
decline in protective
levels of antibodies
• Low in US adults < 30
years
• Greatly reduced by
supportive ventilation
• Causes of death
– Respiratory failure
– Autonomic dysfunction
– Prolonged critical illness
8. Risk Factors
• Acute injury (puncture wound, laceration,
abrasion, etc
– may be major or trivial
– No identifiable injury or portal in some cases
• Chronic conditions: skin ulcers, abscesses, and
gangrene
• Burns, frostbite, middle-ear infection, surgery,
abortion, childbirth, body piercing, "skin
popping"
10. Microbiology
Clostridium tetani
• Mobile, spore-forming, anaerobic (obligate),
gram-positive bacillus
• Distribution in environment: Wide - soil,
human and animal feces, house dust, clothing,
air, slums, marine and freshwater sediments.
• Spores may remain dormant for years
• Spores become vegetative form in wounds
under anaerobic conditions
13. Tetanus Toxins
• Tetanospasmin
– A 150 kDa polypeptide heteromer, 1315 AA in length
– 2 chains - 100kDa & 50kDa chains joined by a
disulphide bond
– Estimated human lethal dose – 2.5ng/kg
• Tetanolysin
– increases tissue necrosis
– optimises condition for multiplication of bacteria
H
Tetanospasmin
14. Exercise – Flash Cards
• Which of the following is true about
Tetanospasmin?
A. It is a 100 kDA peptide
B. Has 2 subunits joined by a disulphide
bond
A. Has a 30 kDA light chain
B. Causes tissue necrosis
Green
Pink
Yellow
Blue
15. Exercise – Flash Cards
• Which of the following is true about
Tetanospasmin
A. It is a 100 kDA peptide
B. Has 2 subunits joined by a disulphide
bond
A. Has a 30 kDA light chain
B. Causes tissue necrosis
Pink
16. H
Ganglioside (GD1b and GT1b
)
Peripheral axon
Tetanospasmin
Binding, Entry, Light chain
liberation & Retrograde
intraneuronal transport
25. • Loss of reflex
inhibition of
antagonist muscle
groups
– Co-contraction of
agonist and
antagonist muscles
– intensely painful
spasms, may lead
to fractures &
tendon rupture
26. Autonomic Dysfunction in Tetanus
• Pre-ganglionic sympathetic neurons in the
lateral horns and the parasympathetic centers
are lateraffected
– Disinhibited autonomic discharge -> sympathetic
overactivity and excessive plasma catecholamine
levels
• Neuronal binding of toxin is irreversible
– Recovery requires the growth of new nerve
terminals
27. Exercise
• Which of the following is/are true?
A. Tetanus is a disorder of synaptic
transmisssion
B. Tetanospasmin binds to peripheral motor
neuron terminals through its carboxyl end
C. Tetanospasmin blocks the release of GABA
and glycine from synaptic vessicles
D. All of the above
28. Clinical Features
• 4 clinical Types:
– Generalized, Localized, Cephalic & Neonatal
Generalized tetanus
• Characterized by generalized rigidity & spasms
• Musclesof the jaw, face, and head often
involved first - shorter axonal pathways
29. Clinical Features
• Trismus (lockjaw)
– usually the 1st
– Due to masseter rigidity
• Risus sardonicus
– a grimace or sneer
– from sustained contraction of the facial muscles
31. Clinical Features
• Stiffness and spasms of bulbar, neck, trunk
and limb muscles
• Opisthotonos
– arched back
• Board-like abdominal rigidity
• Consciousness is preserved
• Spasms of laryngeal muscles may cause fatal
asphyxia
34. Clinical Features
Local Tetanus
• Uncommon
• Rigidity & spasms restricted to muscles
around the wound.
• Prognosis is excellent
• Occasionally becomes generalized
• Mortality: 1% to 16%; Due to generalization
35. Clinical Features
Cephalic tetanus
• Frequency: 6%
• Infection portals: Otitis media; Head injuries; Tongue
piercing
• Incubation period is usually short
• Affected muscles are weak or paralysed
• Localization: Cranial nerves
– Facial weakness - most common
– Other: EOM (6, 3, 4), Hypoglossal
– Trismus -follows other cranial nerve involvement
• May progress to generalized tetanus
• Prognosis
– Often poor: Mortality 15% to 30%
– Milder disease reported
37. Clinical Features
Neonatal Tetanus
• Causes > 50% of deaths from tetanus
worldwide
• Presentation: within a week of birth
• A short history of failure to feed, vomiting, and
‘convulsions’.
• Spasms are generalized
• Mortality is high
• Poor umbilical hygiene is the major cause
• Entirely preventableby maternal vaccination
42. Natural History
• Incubation period
– Time from injury to first symptom
– Averages 7–10 days, with a range of 1–60 days
• Period of onset (onset time)
• Time from first symptom to first spasm
• 1–7 days
• 1st week - muscle rigidity and spasms, which
increase in severity.
43. Natural History
• Autonomic disturbance usually starts several
days after the spasms and persists for 1–2
weeks
• Spasms reduce after 2–3 week
• Rigidity may persist considerably longer
• Recovery from the illness occurs because of
re-growth of axon terminals and by toxin
destruction
44. Severity Grading: Rushdy
• 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 occur.
• Grade 3a (severe):
– Severe trismus and general spasticity, severe dysphagia
and respiratory difficulties, and severe and prolonged
spasms (both spontaneous and on stimulation).
• Grade 3b (very severe):
– The same as for severe tetanus plus autonomic
dysfunction, particularly sympathetic overdrive.
Rushdy AA, White JM, Ramsay ME, Crowcroft NS. 2003
45. Severity Grading: Ablett
• I Mild:
– mild to moderate trismus; general spasticity; no respiratory
embarrassment; no spasms; little or no dysphagia.
• II Moderate:
– moderate trismus; well-marked rigidity; mild to moderate but
short spasms; moderate respiratory embarrassment with an
increased respiratory rate greater than 30; mild dysphagia.
• III Severe:
– severe trismus; generalized spasticity; reflex prolonged spasms;
increased respiratory rate greater than 40; apnoeic spells;
severe dysphagia; tachycardia greater than 120.
• IV Very severe:
– grade III and violent autonomic disturbances involving the
cardiovascular system. Severe hypertension and tachycardia
alternating with relative hypotension and bradycardia, either of
which may be persistent.
Ablett JJL, 1967
46. Prognostic scoring systems: Phillips
Factor Score
Incubation time:
<48 hours 5
2-5 days 4
5-10 days 3
10-14 days 2
>14 days 1
Site of infection:
Internal and umbilical 5
Head, neck, and body wall 4
Peripheral proximal 3
Peripheral distal 2
Unknown 1
47. Prognostic scoring systems: Phillips
State of protection:
None 10
Possibly some or maternal immunisation in
neonatal patients
8
Protected >10 years ago 4
Protected <10 years ago 2
Complete protection 0
Complicating factors:
Injury or life threatening illness 10
Severe injury or illness not immediately life
threatening
8
Injury or non-life threatening illness 4
Minor injury or illness 2
ASA Grade 1 0
Total score
48. Prognostic scoring systems: Dakar
Prognostic factor Score 1 Score 0
Incubation period <7 days 7 days or unknown
Period of onset <2 days 2 days
Entry site Umbilicus, burn, uterine,
open fracture, surgical
wound, intramuscular
injection
All others plus
unknown
Spasms Present Absent
Fever >38.4°C <38.4°C
Tachycardia Adult>120 beats/min Adult<120 beats/min
Neonate>150 beats/min Neonate<150
beats/min
Total score
52. Management
Principles of management
• Eliminate the source of toxin
• Neutralize unbound toxin
• Prevent/Control muscle spasms
• Monitor and provide support until recovery
• Active immunization
53. Management
Antitoxin
• Tetanus immune globulin 5 000 units i.v/i.m
• Antiserum, 10 000 units i.v., after test dose
Antibiotics
• Metronidazole 500 mg i.v. 6 hrly
• Penicillin should be avoided
– Acts like competitive GABA antagonist
• Erythromycin, vancomycin, and clindamycin are
alternative
54. Management
• Sedatives and muscle relaxants
– Diazepam, up to 240 mg/day i.v. in divided doses
– Magnesium sulfate if respiratory support is not
available
– Baclofen-im,iv, it
– Propofol
– Dantrolene
• Surgical debridement
• Tracheostomy
• Artificial ventilation and neuromuscular
blockade
55. Management
Autonomic and circulatory changes
• Intravenous beta blockers, propanolol, or
labetalol
• Intravenous magnesium sulphate
• A presynaptic neuromuscular blocker blocks
cathecolamine release from nerves and
adrenal medulla
• Inotropic support with dobutamine or
dopamine
• Atropine for bradycardia
56. Management
• Verapamil to treat sinus tachycardia
• ACE inhibitors to decrease angiotensin II,
which increases norepinephrine synthesis and
release from nerve terminals
• Adenosine, which reduces presynaptic
norepinephrine release
57. Management
• Nursing care
– Dark quiet environment
– Maintain airways, and adequate oxygenation
• Physiotherapy
65. Prognostic Indices
• Age
– Extremes of age
• Proximity to the CNS
• Comobidities
• Autonomic dysfunction
• Incubation period
• Period of onset
• Duration of each spasm
• Frequency of spasm
• Spontaneity of spasm
• Provacative <
Spontaneous <
combined
• Gender
– Male gender
• Muscle mass
