2. Definition
• Tetanus is a nervous system disorder characterized by
muscle spasms that is caused by the toxin-producing
anaerobe, Clostridium tetani
• CDC defines tetanus as "the acute onset of hypertonia or.
. .painful muscular contractions (usually of the muscles of
the jaw and neck) and generalized muscle spasms
without other apparent medical cause
3. • Neonatal tetanus is defined by the World Health
Organization (WHO) as
• "an illness occurring in a child who has the normal ability to
suck and cry in the first 2 days of life but who loses this
ability between days 3 and 28 of life and becomes rigid and
has spasms."
Definition
4. • In 20% of cases of tetanus, no puncture entry wound is
found.
• Superficial abrasions to the limbs are the commonest
infection sites in adults.
• Deeper infections (e.g., attributable to open fracture,
abortion, or drug injection) are associated with more
severe disease and worse outcomes.
5. • An anaerobic, gram-positive, spore-forming rod
• Spores are highly resilient and can survive readily in the
environment throughout the world.
• Spores resist boiling and many disinfectants. In addition, C.
tetani spores and bacilli survive in the intestinal systems of
many animals, and fecal carriage is common
• Transmission – puncture wounds, trauma, human bites
Clostridium Tetani
6. • Studies have shown that in much of the world only 2–10%
of tetanus cases are recorded
Epidemiology
7. Pathogenesis
• C. tetani produces two exotoxins: tetanolysin and
tetanospasmin.
• Tetanolysin: related to the clostridial toxins and streptolysin,
• Plays no role in the pathogenesis of the disease.
• Tetanospasmin: generally referred to as "tetanus toxin,"
• Is the neurotoxin that causes the manifestations of disease
• Very low concentrations of this highly potent toxin can
result in tetanus (minimum lethal human dose, 2.5 ng/kg).
8. • Release of tetanospasmin from vegetative C. Tetani
the toxin binds to peripheral motor neuron terminals
Retrograde intra-axonal transport of toxin to the spinal
cord and brain stem Blockade of inhibitory
neurotransmitters (glycine and GABA) release in
presynaptic terminalsresting firing rate of motor
neurons Rigidity Simultaneous recruitment of
agonist and antagonistic muscles 20 to limited glycinegic
activity Spasm
Pathogenesis
9. • After reaching the spinal cord and brainstem via
retrograde axonal transport and binding tightly and
irreversibly to receptors at these sites, tetanus toxin
blocks neurotransmission by its cleaving action on
membrane proteins involved in neuroexocytosis of
inhibitory neurotransmitters (glycine and GABA) release in
presynaptic terminals
• The net effect is disinhibition of neurons that modulate
excitatory impulses from the motor cortex.
• Disinhibition of anterior horn cells and autonomic neurons
results in increased muscle tone, painful spasms, and
widespread autonomic instability
Pathogenesis
10. Pathogenesis
• Muscular rigidity in tetanus occurs though a complex
mechanism that involves an increase in the resting firing
rate of disinhibited motor neurons and lack of inhibition of
reflex motor responses to afferent sensory stimuli
• Lack of neural control of adrenal release of
catecholamines induced by tetanus toxin produces a
hypersympathetic state that manifests as sweating,
tachycardia and hypertension
11. • Relatively little is known about the processes of recovery
from tetanus. Recovery can take several weeks
(Harrison’s: 4-6 weeks).
• Peripheral nerve sprouting is involved in recovery from
botulism, and similar central nervous system sprouting
may occur in tetanus.
• Other evidence suggests toxin degradation as a
mechanism of recovery.
Pathogenesis
12. • Forms of Tetanus:
• Generalized tetanus,
• Localized Tetanus
• Cephalic Tetanus
• Neonatal Tetanus
Clinical Features
13. • Generalized Tetanus
• Most common presentation of tetanus
• Trismus (lockjaw) 20 to masseter muscle hypertonicity
• Neck shoulder and back muscle stiffness and pain
• Rigid abdomen and stiff proximal limb muscles
• Risus sardonicus, Arched back (Opisthotonus)
• Paroxysmal generalized muscle spasm apnea /Cyanosis
/laryngospasm (spontaneous or provoked)
• Hyperpyrexia with clear mentation
Clinical Features
14. Mild tetanus Moderate
Tetanus
Severe Tetanus
- IP > 14 days
- Onset time
>7days
- Mild trismus
- Localized spasm
and rigidity
- No autonomic
dysfn
- IP= 7-14 days
- Period of onset >
3-6days
- Marked trismus
- Mild dysphagia
- Rigidity and spasm
- No autonomic
dysfn
- IP <7 days
- Period of onset <
3days
- frequent explosive
spasms
- spontaneous
spasm
- Asphyxia,
dysphagia
- Autonomic
dysfunction
Clinical Features
15. • Neonatal tetanus
• Generalized form of tetanus
• Develops in neonates born in unimmunized mothers after
unsterile treatment of the umbilical cord stump
• Occurs within 2 weeks of neonatal life
• Manifests with poor feeding, rigidity and spasm
• High rate of mortality
• Local tetanus
• Uncommon form of tetanus
• Manifests with localized muscle contraction near the wound
• good prognosis
Clinical Features
16. • Cephalic tetanus
• Rare form of local tetanus
• Follows head injury or ear infection
• Manifests with trismus and CN palsy (often VII CN)
• High mortality
• Diagnosis: Entirely on clinical findings
• Spatula test – gag stimulation causes masseter muscle
spasm
Clinical Features
19. • The patient with tetanus requires simultaneous attention
to several concerns
Treatment
20. • A. Assess airway and ventilation. If necessary, perform
endotracheal intubation
• B. Obtain samples for antitoxin level, strychnine and
dopamine antagonist assays, electrolytes, blood urea
nitrogen, creatinine, creatine kinase, and urinary
myoglobin determination
• C.Determine the portal of entry, incubation period, period
of onset, and immunization history
Treatment
21. • D. Administer benztropine (1 to 2 mg, intravenously) or
diphenhydramine (50 mg, intravenously) to rule out a
dystonic reaction to a dopamine blocking agent
• E. Administer a benzodiazepine intravenously* to control
spasm and decrease rigidity.
• Initially, employ a dose that is adequate to produce sedation
and minimize reflex spasms.
• If this dose compromises the airway or ventilation, intubate
using a short-acting neuromuscular blocking agent.
• Transfer the patient to a quiet, darkened area of the intensive
care unit
Treatment
22. • Control of spasms
• Spasms are controlled by heavy sedation using
benzodiazepines.
• Chlorpromazine or phenobarbital are commonly used
worldwide, and IV magnesium sulfate has been used as a
muscle relaxant.
• Infusions of propofol have also been used successfully to
control spasms and provide sedation
Treatment
23. Treatment
• Control of spasms
• Neuromuscular blocking agents are used when sedation
alone is inadequate.
• Pancuronium , a long acting agent, has been traditionally
used.
• However, it may worsen autonomic instability because it is an
inhibitor of catecholamine reuptake.
• Vecuronium can also be administered and is less likely to
cause autonomic problems, but since it is short acting, it
must be given as continuous infusion to provide adequate
effects.
• Monitoring of patients on these drugs is extremely important
to avoid or recognize complications, and these drugs should
be stopped at least once a day in order to assess the
24. Treatment
• Control of spasms
• Baclofen , which stimulates postsynaptic GABA beta
receptors, has been used in a few small studies*
• The preferred route is intrathecal, and it may be given either in a
bolus of 1000 mcg or by continuous intrathecal infusion
• Phenothiazines and barbiturates were used in the past to
control spasms but have largely been displaced by
neuromuscular blocking agents
25. • Antitoxins: should be given early in an attempt to
deactivate any circulating tetanus toxin and prevent its
uptake into the nervous system.
• Two preparations are available: human tetanus immune
globulin (TIG) and equine antitoxin (TAT)
• TIG is the preparation of choice as it is less likely to be
associated with anaphylactoid reactions.
• Standard therapy is 3000–6000 IU of TIG or 10,000–20,000
U of equine antitoxin as a single IM dose*
Treatment
26. • Wound management & Antibiotics
• If possible, the entry wound should be identified, cleaned,
and debrided of necrotic material in order to remove
anaerobic foci of infection and prevent further toxin
production.
• Metronidazole (400 mg rectally or 500 mg IV every 6 h for 7
days) is the preferred antibiotic.
• An alternative is penicillin (100,000–200,000 IU/kg per day),
although this drug theoretically may exacerbate spasms.
• Failure to remove pockets of ongoing infection may result in
recurrent or prolonged tetanus.
Treatment
27. • Control of Autonomic disturbance
• Cardiovascular instability in severe tetanus is notoriously
difficult to treat.
• Rapid fluctuations in blood pressure and heart rate can
occur.
• Cardiovascular stability is improved by
• Increasing sedation with IV magnesium sulfate (plasma
concentration, 2–4 mmol/L), morphine, or other sedatives.
• Drugs acting specifically on the cardiovascular system (e.g.,
esmolol, calcium antagonists, and inotropes) may be required*.
Treatment
28. • Prevention of VTE
• In some centers, prophylaxis against deep-vein thrombosis
and thromboembolism is routine
Treatment
29. • Thrombophlebitis associated with diazepam injection,
• Ventilator-associated pneumonia,
• Central-line infections, and
• Septicemia.
Complications of Treatment
30. • Tetanus is one of the few bacterial diseases that does not
confer immunity following recovery from acute illness
• All patients with tetanus should receive active
immunization with a total of three doses of tetanus and
diphtheria toxoid (Td) spaced at least two weeks apart,
commencing immediately upon diagnosis
• It should be assumed that anyone who is not adequately
vaccinated or protected against tetanus is also inadequately
protected against diphtheria
Active Immunization
31. • The tetanus-diphtheria-acellular pertussis vaccine (TdaP)
may be used instead of Td, but if used, recommendations
are for this formulation to be used only once in adults
• Subsequent tetanus doses, in the form of Td, should be
given at 10-year intervals throughout adulthood.
• Tetanus toxoid alone should be given only to those
patients with documented allergy or untoward reactions to
diphtheria toxoid
Active Immunization
32. Previous
doses of
tetanus
toxoid*
Clean and minor wound All other woundsΔ
Tetanus
toxoid-
containing
vaccine◊
Human tetanus
immune globulin
TT-containing
vaccine◊
Human
TIG§
<3 doses or
unknown
Yes¥ No Yes¥ Yes
≥3 doses
Only if last
dose given
≥10 years ago
No
Only if last dose
given ≥5 years
ago‡
No
Active Immunization
33. • Case-fatality rates for non-neonatal tetanus in developing
countries range from 8 to 50 percent, whereas the
majority of patients with tetanus recover when modern
supportive care is available
Prognosis
34. Factors associated with Poorer Prognosis
Adult Tetanus
Age >70 years
Incubation period <7 days
Short time from first symptom to admission
Puerperal, IV, postsurgery, burn entry site
Period of onseta <48 h
Heart rate >140 bpmb
Systolic blood pressure >140 mmHgb
Severe disease or spasmsb
Temperature >38.5°Cb
Prognosis
35. • The WHO guidelines for tetanus vaccination consist of a
primary course of three doses in infancy, boosters at 4–7
and 12–15 years of age, and one booster in adulthood.
• In the United States, the CDC suggests an additional
dose at 14–16 months and boosters every 10 years.
Prevention
36. • "Catch-up" schedules recommend a three-dose primary
course for unimmunized adolescents followed by two
further doses.
• For persons who have received a complete primary
course in childhood but no further boosters, two doses at
least 4 weeks apart are recommended.
Prevention
37. • Standard WHO recommendations for prevention of
maternal and neonatal tetanus call for administration of
two doses of TT at least 4 weeks apart to the previously
unimmunized pregnant woman.
• Ethiopia
• 1st dose: 1st ANC visit
• 2nd dose: after 4 weeks (1month)
• 3rd dose: after another 6 months
Prevention
38. • Individuals sustaining tetanus-prone wounds should be
immunized if their vaccination status is incomplete or
unknown or if their last booster was given >10 years
earlier.
• Patients sustaining wounds not classified as clean or
minor should also undergo passive immunization with
TIG.
Prevention
39. Prevention after trauma
• There are well-established guidelines for the prevention of
tetanus after wounds are sustained.
• The need for tetanus toxoid or TIG depends on the nature
of the wound and the patient's immunization status.
40. Prevention after trauma
• TIG, which confers short-term passive immunity, is
reserved for cases in which the following criteria are met:
1. The patient has received fewer than three doses of tetanus
toxoid or the patient's immunization status is unknown, and
2. The injury is not a clean, minor wound (e.g., there is
contamination with dirt, or the injury is a puncture wound or
is an avulsion injury)
41. Prevention after trauma
• If a patient's immunity is insufficient or the patient's
immune status is unknown but the wound is minor,
tetanus toxoid alone (in the form of Td) provides sufficient
protection.
• Patients who have received more than three doses of
tetanus toxoid previously, and who have a contaminated
wound or a puncture wound will require Td if the last
booster was given more than 5 years ago
• Patients who have received three doses of tetanus toxoid
previously and who have a clean, minor wound will
require Td if the last booster was given more than 10
Preganglionic sympathetic activity Sympathetic hyperactivity and circulating catecholamine level Blockade of neurotransmitter release at the NMJ Paralysis
* Strychnine is a competitive antagonist of glycine, an important inhibitory neurotransmitter in the spinal cord, brainstem, and higher centers [9]. Strychnine's toxicity is attributed to action at the postsynaptic receptor in the motor neurons of the spinal cord's neural horn. There, it antagonizes inhibitory tone, resulting in powerful and uncontrollable muscle contractions. Additional mechanisms have been proposed, including agonism of excitatory NMDA receptors and antagonism of gamma amino butyric acid (GABA), another inhibitory neurotransmitter
* (diazepam in 5-mg increments, or lorazepam in 2-mg increments)
* A significant problem with all these treatments is that the doses necessary to control spasms also cause respiratory depression; thus, in resource-limited settings without mechanical ventilators, controlling spasms while maintaining adequate ventilation is problematic, and respiratory failure is a common cause of death.
In locations with ventilation equipment, severe spasms are best controlled with a combination of sedatives or magnesium and relatively short-acting, cardiovascularly inert, nondepolarizing neuromuscular blocking agents that allow titration against spasm intensity.
Intrathecal baclofen given as an initial bolus in a dose ranging from 40 to 200 mcg followed by a continuous infusion of 20 mcg/hour was found to control spasms and rigidity in 21 out of 22 patients with grade III tetanus in a retrospective outcome study from a single medical center in Portugal. One of 22 patients developed meningitis secondary to infection of the intrathecal catheter despite the fact that most patients required such therapy for at least three weeks (range 8 to 30 days) [ 33 ]. In some cases, baclofen has been used without the need for artificial ventilation [ 34 ].
* However, there is evidence that intrathecal administration of TIG inhibits disease progression and leads to a better outcome. The results of a randomized controlled trial have been supported by a meta-analysis of trials involving both adults and neonates, with TIG doses of 50–1500 IU administered intrathecally.
* Short-acting drugs that allow rapid titration are preferred; particular care should be taken when longer-acting antagonists are administered, as their use has been associated with hypotensive cardiac arrest.
Appropriate tetanus prophylaxis should be administered as soon as possible following a wound, but should be given even to patients who present late for medical attention. This is because the incubation period is quite variable; most cases occur within eight days, but the incubation period can be as short as one day or as long as several months.* Tetanus toxoid may have been administered as diphtheria-tetanus toxoids adsorbed (DT), diphtheria-tetanus-whole cell pertussis (DTP, DTwP; no longer available in the United States), diphtheria-tetanus-acellular pertussis (DTaP), tetanus-diphtheria toxoids adsorbed (Td), booster tetanus toxoid-reduced diphtheria toxoid-acellular pertussis (Tdap), or tetanus toxoid (TT). Δ Such as, but not limited to, wounds contaminated with dirt, feces, soil, or saliva; puncture wounds; avulsions; wounds resulting from missiles, crushing, burns, or frostbite. ◊ The preferred vaccine preparation depends upon the age and vaccination history of the patient: <7 years: DTaP.
Underimmunized children ≥7 and <11 years who have not received Tdap previously: Tdap. Children who receive Tdap between age 7 and 11 years do not require revaccination at age 11 years.
≥11 years: A single dose of Tdap is preferred to Td for all individuals in this age group who have not previously received Tdap.
Td is preferred to TT for those who received Tdap previously and when Tdap is not available.
§ 250 units intramuscularly at a different site than tetanus toxoid; intravenous immune globulin should be administered if human tetanus immune globulin is not available. ¥ The vaccine series should be continued through completion as necessary. ‡ Booster doses given more frequently than every five years are not needed and can increase adverse effects.
aTime from first symptom to first generalized spasm.
bAt hospital admission
* However, in high-risk areas, a more intensive approach has been successful, with all women of childbearing age receiving a primary course along with education on safe delivery and postnatal practices.
