4. Learning Objectives
• By the end of this lecture, you should be able to know the:
• Mode of transmission of tetanus
• Types of Tetanus
• Clinical features and management
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6. Introduction
• Tetanus was first derived from a Greek word tetanos which means
“stretch”
• Common in many developing countries
• Highest in unvaccinated children and children born from unvaccinated
mothers
• It is responsible for about 14% of neonatal death
• It occurs worldwide but more common in hot, damp climate with soil
reach in organic matter.
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7. Cont…
• This is particularly true with manure treated soil, as spores are widely
distributed through faeces.
DEFINITION: it is a disease of neonate which affect the nervous
system cause by “Clostridium tetani “ and is characterized by
generalized body rigidity and fever.
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8. Aetiology
• Clostridium tetani is a motile, gram-positive, spore-forming obligate
anaerobe.
• The organism's natural habitat worldwide is soil, dust, and the
alimentary tracts of various animals.
• C. tetani forms spores terminally, with a classic morphologic
appearance resembling a drumstick or tennis racket microscopically.
• Spores are extremely stable, although immersion in boiling water for
15 minutes kills most spores.
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9. TRANSMISSION
• Infection is acquired by contamination of wounds with Clostridium
tetani spores; a tiny breach in skin or mucosa (e.g.. Skin abrasion,
punctured wounds, burns, animal bites, unsterile surgery, aseptic
abortion, unsterile instruments to cut umbilical cord etc.) leads to
introduction of spores.
• The spores are widely distributed in the intestines and faeces of many
non-human animals such as horses, sheep, cattle, dogs, cats, rats,
guinea pigs, and chickens.
• Tetanus is not spread from person to person.
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10. Host Factors
• Age : It is the disease of active age (5-40 years), New born baby,
female during delivery or abortion
• Sex : Higher incidence in males than females
• Occupation : Agricultural workers are at higher risk
• Rural –Urban difference: Incidence of tetanus in urban areas is much
lower than in rural areas
• Immunity : Herd immunity does not protect the individual
• Environmental and social factors: Unhygienic custom habits,
Unhygienic delivery practices
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11. ROUTE OF ENTRY
• Apparently trivial injuries
• Animal bites
• Open fractures
• Burns
• Gangrene
• In neonates usually via infected umbilical stumps
• Abscess
• Parenteral drug abuse
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12. Pathogenesis
• Spores that gain entry can persist in normal tissue for
months to years under anaerobic conditions.
• When the oxygen levels in the surrounding tissue is
sufficiently low, the implanted C. tetani spore then
germinates into a new, active vegetative cell that grows
and multiplies and most importantly produces tetanus
toxin - tetanospasmin and tetanolysin.
4Bleck TP et al
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13. Pathogenesis
• Tetanolysin is not believed to be of any significance in the clinical
course of tetanus.
• Tetanospasmin is a neurotoxin and causes the clinical manifestations
of tetanus.
• Tetanospasmin is synthesized as a 150-kd protein consisting of a 100-
kd heavy chain and a 50-kd light chain joined by a disulfide bond.
• The heavy chain mediates binding of tetanospasmin to the presynaptic
motor neuron and also creates a pore for the entry of the light chain
into the cytosol.
5. Sanford JP. Tetanus-forgotten but not gone.
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14. Pathogenesis
• The toxin migrates across the synapse (small space between nerve cells
critical for transmission of signals among nerve cells) where it binds to
presynaptic nerve terminals and inhibits or stops the release of certain
inhibitory neurotransmitters (glycine and gamma-aminobutyric acid).
• Loss of inhibition of preganglionic neurons – sympathetic hyperactivity
• These neurons become incapable to release neurotransmitter.
• The neurons, which release gamma-aminobutyric acid (GABA) and glycine,
the major inhibitory neurotransmitters, are particularly sensitive to
tetanospasmin, leading to failure of inhibition of motor reflex responses to
sensory stimulation. 6
6Yen FL et al. 2010
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15. Pathogenesis
• This results in generalized contractions of the agonist and antagonist
musculature characteristic of a tetanic spasm.
• The shortest peripheral nerves are the first to deliver the toxin to
the CNS, which leads to the early symptoms of facial distortion
and back and neck stiffness.
• Once the toxin becomes fixed to neurons, it cannot be neutralized with
antitoxin. Recovery of nerve function from tetanus toxins requires
sprouting of new nerve terminals and formation of new synapses.
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16. 1. C. tetani enters body through wound
3. Germinates under anaerobic conditions
and begins to multiply and produce
tetanospasmin
5. Travels along the axons to the spinal
cord.
2. Stays in Sporulated form until anaerobic
conditions are presented
4. Tetanospasmin spreads using blood
and lymphatic system, and binds to
motor neurons.
6. Binds to sites responsible for inhibiting
skeletal muscle contraction.
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19. Neonatal tetanus
• The usual incubation period after birth is 3-12 days
• Tetanus neonatorum (7th day disease)
• Usually fatal if untreated
• Children born to inadequately immunized mothers, after unsterile
treatment of umbilical stump
• Poor feeding ,rigidity, facial grimacing and spasms with touch
• Mortality exceeds 70%
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22. DIAGNOSIS
Is mainly Clinical
DIRECT SMEAR
• Show Gram-positive bacilli with drum-stick appearance.
CULTURE
• Done in blood agar under anaerobic condition or in Robertson’s cooked
meat medium.
• Produces swarming growth after 1-2 days of incubation.
• In contaminated specimen heat at 80°C for 10mins before culture to destroy
non-sporing organisms.
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23. DIAGNOSIS
Spatula Test
• The spatula test is a simple diagnostic bedside test that involves
touching the oropharynx with a spatula or tongue blade.
• In normal circumstances, it elicits a gag reflex, and the patient tries to
expel the spatula (i.e. a negative test result).
• If tetanus is present, patients develop a reflex spasm of the masseters
and bite the spatula (i.e. a positive test result).
• In 400 patients, this test had a sensitivity of 94% and a specificity of
100%. No adverse sequelae (eg, laryngeal spasm) were reported.
8Apte NM et al
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25. PRINCIPLE OF TREATMENT
1. Neutralization of unbound toxin
-HTIG/ATS
2. Prevention of further toxin production
-Wound debridement & antibiotics
3. Antibiotics
4. Control of spasm
-Anticonvulsants, Sedatives, Muscle relaxants etc.
5. Management of autonomic dysfunction
-MGSO4, Betablockers etc.
6. Supportive care
-Physiotherapy, Nutrition, Thromboembolism prophylaxis ABC etc…
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26. PRINCIPLE OF TREATMENT
• Admit patients to the intensive care unit (ICU).
• Because of the risk of reflex spasms, maintain a dark and quiet environment
for the patient.
• Avoid unnecessary procedures and manipulations.
• Attempting endotracheal intubation may induce severe reflex laryngospasm;
prepare for emergency tracheostomy.
• Seriously consider prophylactic tracheostomy in all patients with
moderate-to-severe clinical manifestations.
• Intubation and ventilation are required in 67% of patients.
• Tracheostomy has also been recommended after onset of the first
generalized seizure.
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27. 1. Neutralization of unbound toxin
• Tetanus immune globulin (TIG) is recommended for treatment of
tetanus.
• It should be kept in mind that TIG can only help remove unbound
tetanus toxin; it cannot affect toxin bound to nerve endings.
• A single intramuscular (IM) dose of 3000-6000 units is generally
recommended for children and adults, with part of the dose infiltrated
around the wound if it can be identified.9
9Tetanus—Puerto Rico, 2002.
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28. 1. Neutralization of unbound toxin
• The WHO recommends TIG 500 units by IM injection or
intravenously (IV)—depending on the available preparation—as soon
as possible;
• In addition, 0.5 mL of an age-appropriate tetanus toxoid−containing
vaccine, should be administered by IM injection at a separate site.
• Tetanus disease does not induce immunity
• Patients without a history of primary tetanus toxoid vaccination should
receive a second dose 1-2 months after the first dose and a third dose
6-12 months later.
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29. 2. PREVENTION OF FURTHER TOXIN PRODUCTION
• Debridement of Wound to remove organisms and to create an aerobic
environment.
• The current recommendation is to excise at least 2 cm of normal
viable-appearing tissue around the wound margins.
• Incise and drain abscesses.
• Delay any wound manipulation until several hours after administration
of antitoxin due to risk of releasing tetanospasmin into the bloodstream.
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30. 3. ANTIBIOTICS
• Theoretically, antibiotics may prevent multiplication of C tetani, thus
halting production of toxin. Penicillin G was the drug of choice
initially but now Metronidazole is preferred drug.
• Penicillin G aqueous : 100,000U/kg/day administered at 4-6 hr
intervals, with a daily maximum 12 million U)
• A 10- to 14-d course of treatment is recommended Metronidazole:
(30 mg/kg/day, given at 6 hr intervals; maximum dose, 4 g/day)
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31. 3. ANTIBIOTICS
• A 10- to 14-d course of treatment is recommended. Some consider this
the DOC since penicillin G is also a GABA agonist, which may
enhance effects of the toxin.
• Doxycycline, Clindamycin and Erythromycin are alternative for
penicillin allergic patients who can not tolerate metronidazole.
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32. 4. Control of spasm
• Nursing in quiet environment, avoid unnecessary stimuli, Protecting
the airway.
• Drugs used to treat muscle spasm, rigidity, and tetanic seizures include
sedative-hypnotic agents, general anesthetics, centrally acting muscle
relaxants, and neuromuscular blocking agents.
Anticonvulsants
• Sedative-hypnotic agents are the mainstays of tetanus treatment.
• Benzodiazepines are the most effective primary agents for muscle
spasm prevention and work by enhancing GABA inhibition.
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33. 4. Control of spasm
Diazepam :
• Mainstay of treatment of tetanic spasms and tetanic seizures.
• Depresses all levels of CNS, including limbic and reticular formation,
possibly by increasing activity of GABA, a major inhibitory
neurotransmitter.
• Diazepam reduces anxiety, produces sedation, and relaxes muscles.
• The initial dose of 0.1- 0.2 mg/kg every 3-6 hr intravenously is
subsequently titrated to control the tetanic spasms
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34. 4. Control of spasm
• Lorazepam is an effective alternative.
• Midazolam can be given as an intravenous infusion.
• Phenobarbitone (5mg/kg IV or PO/NG 1 – 2 divided doses), and
phenothiazines may be added as an adjunctive sedative.
• Propofol, dantrolene, intrathecal baclofen, succinylcholine &
magnesium sulfate can be tried
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35. Skeletal muscle relaxants
• These agents can inhibit both monosynaptic and polysynaptic reflexes
at spinal level, possibly by hyperpolarization of afferent terminals.
• Muscle relaxation is indicated where sedation alone is inadequate.
Vecuronium (0.1 mg/kg IV as needed) or atracurium (0.5 mg/kg IV)
are appropriate.
• Pancuronium may worsen autonomic instability by inhibiting
catecholamine reuptake.
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36. BACLOFEN
• Intrathecal (IT) baclofen, a centrally acting muscle relaxant, has been
used experimentally to wean patients off the ventilator and to stop
diazepam infusion.
• IT baclofen is more potent than PO baclofen.
• May induce hyperpolarization of afferent terminals and inhibit both
monosynaptic and polysynaptic reflexes at spinal level.
• Entire dose of baclofen is administered as a bolus injection. Dose may
be repeated after 12 h or more if spontaneous paroxysms return.
• It can also be given as T. Baclofen 5mg tds, increase 5mg/day every
3 days, maximum dose 80mg
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37. 5. MANAGEMENT OF AUTONOMIC DYSFUNCTION
• Magnesium sulfate can be used alone or in combination with
benzodiazepines for this purpose.
• It should be given IV in a loading dose of 5 g (or 75 mg/kg), followed
by continuous infusion at a rate of 2-3 g/h until spasm control is
achieved
• The patellar reflex should be monitored; areflexia (absence of the
patellar reflex) occurs at the upper end of the therapeutic range (4
mmol/L). If areflexia develops, the dosage should be reduced.
10 WHO Technical note January 2010
11Thwaites CL et al.
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38. 5. MANAGEMENT OF AUTONOMIC DYSFUNCTION
• Morphine is an option. In the past, beta blockers were used, but they
can cause hypotension and sudden death; Only Esmolol is currently
recommended
• Hypotension requires fluid replacement and dopamine or
norepinephrine administration. Parasympathetic over-activity is rare,
but if bradycardia is sustained, a pacemaker may be needed..
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39. 6. SUPPORTIVE CARE
• Airway management and supportive measures
• Endotracheal intubation is justified initially, but early tracheostomy is
frequently indicated because of the likelihood of prolonged mechanical
ventilation
• Energy demands in tetanus may be extremely high, so early nutritional
support is mandatory.
• Enteral feeding is preferred if enough calories can be administered by this
route.
• Placement of Percutaneous endoscopic gastrostomy (PEG) is commonplace,
since this route may prevent gastroesophageal reflux, which may be induced
by nasogastric tubes.
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40. SUPPORTIVE CARE
• Prophylactic treatment with sucralfate or acid blockers may be used to
prevent gastroesophageal hemorrhage from stress ulceration.
• Prophylaxis of thromboembolism with heparin, low molecular weight
heparin or other anticoagulants should be administered early
• Physical therapy should be started as soon as spasms have ceased,
since tetanus patients often are left with disability from prolonged
drug-induced paralysis and immobilization
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41. PREVENTION
• Tetanus is completely preventable by active tetanus immunization.
• Immunization is thought to provide protection for 10 years.
• Begins in infancy with the DTP series of shots. The DTP vaccine is a
"3-in-1" vaccine that protects against diphtheria, pertussis, and tetanus.
• Recovered clinical tetanus does not produce immunity to further
attacks because very small amount of tetanus toxin produced can not
elicit strong protective immune response.
• Therefore, even after recovery patients must receive a full course of
tetanus toxoid.
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43. PASSIVE IMMUNIZATION
• Temporary protection – human tetanus immunoglobulin /ATS
• Human Tetanus Hyperimmunoglobulin : 250-500 IU
• Produces protective antibody level for at least 4-6 weeks.
• Does not cause serum sickness
• Longer passive protection compared to horse ATS( 30 days / 7 -10
days )
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44. PASSIVE IMMUNIZATION
• ATS ( EQUINE ) :
• 1500 IU s/c after sensitivity testing 7 – 10 days
• High risk of serum sickness
• It stimulates formation of antibodies to it , hence a person who has
once received ATS tends to rapidly eliminate subsequent doses.
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45. PREVENTION OF NEONATAL TETANUS
• Clean delivery practices
• 3 cleans : clean hands, clean delivery surface, clean cord care
• Tetanus toxoid protects both mother & child
• Unimmunized pregnant women : 2 doses tetanus toxoid (16th-36th
week)
• To newborn of unimmunized mother, 500U HTIG within 6 hours of
birth.
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46. Complications of Tetanus
• Long bone fractures
• Glenohumeral joint and temporomandibular joint dislocations
• Hypoxic injury and aspiration pneumonia
• Adverse effects of autonomic instability, including hypertension and
cardiac dysrhythmias
• Paralytic ileus, pressure sores, and urinary retention
• Malnutrition and stress ulcers
• Coma, nerve palsies, neuropathies, psychological after effects, and
flexion contractures
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47. Prognosis
A rating scale has been developed for assessing the severity of tetanus and
determining the prognosis12. On this scale, 1 point is given for each of the
following:
• Incubation period shorter than 7 days
• Period of onset shorter than 48 hours
• Tetanus acquired from burns, surgical wounds, compound fractures, septic
abortion, umbilical stump, or intramuscular injection
• Narcotic addiction
• Generalized tetanus
• Temperature higher than 104°F (40°C)
• Tachycardia exceeding 120 beats/min (150 beats/min in neonates)
12Bleck TP et al
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48. Prognosis
The total score indicates disease severity and prognosis as follows:
• 0 or 1 – Mild tetanus; mortality below 10%
• 2 or 3 – Moderate tetanus; mortality of 10-20%
• 4 – Severe tetanus; mortality of 20-40%
• 5 or 6 – Very severe tetanus; mortality above 50%
• Cephalic tetanus is always severe or very severe.
• Neonatal tetanus is always very severe.
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49. Prognosis
A high risk of mortality is associated with the following:
• Short incubation period
• Early onset of convulsions
• Delay in treatment
• Contaminated lesions of the head and the face
• Neonatal tetanus
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