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Clostridium tetani
• Gram positive spore forming anaerobic rod
• Reservoir – soil
• Transmission – puncture wounds, trauma, human bites
• The incubation period of tetanus is approximately 8 days but ranges from 3 to 21 days
• Pathogenesis
Spores germinate in tissues with low oxygen and produce tetanus toxins
C. tetani produces two exotoxins
Tetanospasmin – neurotoxic and causes the clinical manifestations of tetanus
Tetanolysin – haemolytic , tissue lysis
2/7/2023 DEREBE ASSEFA 1
• Although tetanus is now rare in the developed world, the disease remains a threat
to all unvaccinated people, particularly in developing countries.
• Persons >60 years of age are at greater risk of tetanus because antibody levels
decrease over time.
2/7/2023 DEREBE ASSEFA 2
Predisposing factors
• Absence of antibodies (ie, from inadequate vaccination) + plus ≥2 of the following
A penetrating injury resulting in the inoculation of C. tetani spores
Coinfection with other bacteria
Devitalized tissue
A foreign body
Localized ischemia
• Cryptogenic(unknown cause)-10% = may be due to unnoticed skin abrasions
2/7/2023 DEREBE ASSEFA 3
pathogenesis
•  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 terminalsresting firing rate of motor neurons  rigidity 
Simultaneous recruitment of agonist and antagonistic muscles 20 to limited
glycinegic activity Spasm
2/7/2023 DEREBE ASSEFA 4
• Preganglionic sympathetic activity Sympathetic hyperactivity and 
circulating catecholamine level
• Blockade of neurotransmitter release at the NMJ paralysis
2/7/2023 DEREBE ASSEFA 5
• Toxins are produced and disseminated via blood and lymphatics.
• Toxins act at several sites within the central nervous system, including peripheral
motor end plates, spinal cord, and brain, and in the sympathetic nervous system
• Seizures may occur
2/7/2023 DEREBE ASSEFA 6
Tetanus
• Forms: generalized, localized, cephalic, neonatal
• Defn of terms:
IP – time gap b/n injury and first symptom (trismus)
Onset time – time b/n trismus and first spasm
Risus sardonicus – recession of the lips backward and a grinning like grimace
Opisthotonus – backward arched posture
Trismus (lockjaw) 20 to masseter muscle hypertonicity
2/7/2023 DEREBE ASSEFA 7
Generalized tetanus(80%)
• 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
2/7/2023 DEREBE ASSEFA 8
• The disease usually presents with a descending pattern.
• The first sign is trismus or lockjaw, followed by stiffness of the neck, difficulty in
swallowing, and rigidity of abdominal muscles.
• Other symptoms include elevated temperature, sweating, elevated blood pressure,
and episodic rapid heart rate.
• Spasms may occur frequently and last for several minutes. Spasms continue for
3–4 weeks.
2/7/2023 DEREBE ASSEFA 9
Severity of generalized tetanus
2/7/2023 DEREBE ASSEFA 10
Complications
• Aspiration pneumonia
• Vertebral fracture
• Muscle rupture
• DVT+PE (VTE)
• Decubitus ulcer
• Rhabdomyolysis (pigment-induced nephropathy)
• Autonomic dysfunction - Labile or sustained HTN, Tachycardia, Hyperpyrexia,
Profuse sweating, Bradycardia and hypotension episodes, Sudden cardiac arrest
2/7/2023 DEREBE ASSEFA 11
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(typically occurs 5 to 7 days following
birth)
• Manifests with poor feeding, rigidity and spasm
• High rate of mortality
2/7/2023 DEREBE ASSEFA 12
Local tetanus
• Uncommon form of tetanus
• Manifests with localized muscle contraction near the wound
• good prognosis
Cephalic tetanus : Rare form of local tetanus
• Follows head injury or ear infection
• Manifests with trismus and CN palsy (often CN VII), but involvement of cranial nerves
VI, III, IV, and XII may also occur
• High mortality
2/7/2023 DEREBE ASSEFA 13
Clinical and pathologic progression of tetanus
2/7/2023 DEREBE ASSEFA 14
Diagnosis
• Entirely on clinical findings
• Spatula test – gag stimulation causes masseter muscle spasm
• The WHO definition of adult tetanus requires at least one of the following signs:
Trismus (inability to open the mouth) or
Risus sardonicus (sustained spasm of the facial muscles); or
Painful muscular contractions.
2/7/2023 DEREBE ASSEFA 15
DDx: -
Strychnine poisoning, Dystonic drug reaction (phenothiazines, metoclopramide),
Hypocalcemic tetany, Malignant neuroleptic syndrome
Rabies, Stiff-person syndrome (SPS)
Meningitis /encephalitis,
Acute intraabdominal process ,Alveolar abscess, Dental infection
2/7/2023 DEREBE ASSEFA 16
Duration of illness
• Tetanus toxin-induced effects are long lasting because recovery requires the
growth of new axonal nerve terminals.
• The usual duration of clinical tetanus is 4-6 weeks
2/7/2023 DEREBE ASSEFA 17
Treatment
• Principle
Cardiorespiratory support
Eliminate the source of toxin
Neutralize unbound toxin
Prevent muscle spasms
2/7/2023 DEREBE ASSEFA 18
goals of treatment
• The goals of treatment include:
Halting the toxin production
Neutralization of the unbound toxin
Airway management
Control of muscle spasms
Management of dysautonomia
General supportive management
2/7/2023 DEREBE ASSEFA 19
1. General measures
• Admit in a quiet ICU with a possibility for continuous monitoring but minimal
disturbance
• Hydration
• Nutritional support (IV/PO)
spasms result in high metabolic demands and a catabolic state.
• Physiotherapy to prevent contracture
• psychological support, analgesia
• Treatment of superimposed infection eg aspiration pneumonia
2/7/2023 DEREBE ASSEFA 20
2. Treatment of source infection
• Wound debridement
• Antibiotic therapy to eradicate vegetative C.Tetani; choice are:
Metronidazole 500mg IV TID or QID , Penicillin 2 -4 million units IV Q4-6hrs
lower dose of penicillin should be used as high dose has a GABA inhibitory effect
Others Clindamycin, vancomycin ,chloramphenicol, Tetracyclines, macrolides,
cephalosporins can be used .
We suggest a treatment duration of 7 to 10 days.
2/7/2023 DEREBE ASSEFA 21
3. Neutralization of unbound toxin
Antitoxin
• Since tetanus toxin is irreversibly bound to tissues, only unbound toxin is available
for neutralization
• Human tetanus immune globulin (HTIG)
A dose of 3000 to 6000 units IM should be given as soon as the diagnosis of
tetanus is considered, with part of the dose infiltrated around the wound .
HTIG should be administered at different sites than tetanus toxoid
• Pooled IV Ig and equine antitoxin are used as alternative to HTIG
2/7/2023 DEREBE ASSEFA 22
4. Active immunization
• Since 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.
• Subsequent tetanus doses, in the form of Td, are recommended at 10-year intervals
throughout adulthood
Tetanus toxoid should be administered at a different site than tetanus immune
globulin.
It should be assumed that anyone who is not adequately vaccinated or protected
against tetanus is also inadequately protected against diphtheria (not Tdap)
2/7/2023 DEREBE ASSEFA 23
2/7/2023 DEREBE ASSEFA 24
2. Control of muscle spasm
• Generalized muscle spasms are life threatening since they can cause respiratory failure,
lead to aspiration, and induce generalized exhaustion
• Benzodiazepines (Diazepam, midazolam), Barbiturates, chlorpromazine, propofol,
dantrolene, baclofen
Diazepam 10 to 30 mg IV and repeated as needed every 1 to 4 hours; total daily
doses as high as 500 mg may be required for an adult
Chlorpromazine 50–150 mg IM injection every 4–8 hours
• Neuromuscular blocking agents- Vecuronium is less likely to cause autonomic problems
than Pancuronium
2/7/2023 DEREBE ASSEFA 25
Respiratory care
• Intubation / Tracheostomy + mechanical ventilation for adequate oxygenation
2/7/2023 DEREBE ASSEFA 26
Management of autonomic dysfunction
• Magnesium sulfate -acts as a presynaptic neuromuscular blocker, blocks catecholamine release
from nerves,
5 gm (75mg/kg) IV loading dose, then 2–3 grams/hour until spasm control is achieved
Can control the autonomic dysfunction and spasm
• Labetalol – both α and β blockers are preferred.
Beta blockade alone with propranolol, for example, should be avoided because of reports of
hypotension and sudden death.
• Esmolol (short acting B blocker), verapamil, clonidine, morphine can be used.
• Continuous spinal anesthesia can also be used- epidural bupivacaine-20 to 50 mL of 0.25%
2/7/2023 DEREBE ASSEFA 27
prognosis
 Case-fatality rates for non-neonatal tetanus in developing countries range from 8
to 50 percent
2/7/2023 DEREBE ASSEFA 28
Reference
• Harrison 20th edition
• Uptodate 2018
2/7/2023 DEREBE ASSEFA 29

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Tetanus.pptx

  • 1. Clostridium tetani • Gram positive spore forming anaerobic rod • Reservoir – soil • Transmission – puncture wounds, trauma, human bites • The incubation period of tetanus is approximately 8 days but ranges from 3 to 21 days • Pathogenesis Spores germinate in tissues with low oxygen and produce tetanus toxins C. tetani produces two exotoxins Tetanospasmin – neurotoxic and causes the clinical manifestations of tetanus Tetanolysin – haemolytic , tissue lysis 2/7/2023 DEREBE ASSEFA 1
  • 2. • Although tetanus is now rare in the developed world, the disease remains a threat to all unvaccinated people, particularly in developing countries. • Persons >60 years of age are at greater risk of tetanus because antibody levels decrease over time. 2/7/2023 DEREBE ASSEFA 2
  • 3. Predisposing factors • Absence of antibodies (ie, from inadequate vaccination) + plus ≥2 of the following A penetrating injury resulting in the inoculation of C. tetani spores Coinfection with other bacteria Devitalized tissue A foreign body Localized ischemia • Cryptogenic(unknown cause)-10% = may be due to unnoticed skin abrasions 2/7/2023 DEREBE ASSEFA 3
  • 4. pathogenesis •  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 terminalsresting firing rate of motor neurons  rigidity  Simultaneous recruitment of agonist and antagonistic muscles 20 to limited glycinegic activity Spasm 2/7/2023 DEREBE ASSEFA 4
  • 5. • Preganglionic sympathetic activity Sympathetic hyperactivity and  circulating catecholamine level • Blockade of neurotransmitter release at the NMJ paralysis 2/7/2023 DEREBE ASSEFA 5
  • 6. • Toxins are produced and disseminated via blood and lymphatics. • Toxins act at several sites within the central nervous system, including peripheral motor end plates, spinal cord, and brain, and in the sympathetic nervous system • Seizures may occur 2/7/2023 DEREBE ASSEFA 6
  • 7. Tetanus • Forms: generalized, localized, cephalic, neonatal • Defn of terms: IP – time gap b/n injury and first symptom (trismus) Onset time – time b/n trismus and first spasm Risus sardonicus – recession of the lips backward and a grinning like grimace Opisthotonus – backward arched posture Trismus (lockjaw) 20 to masseter muscle hypertonicity 2/7/2023 DEREBE ASSEFA 7
  • 8. Generalized tetanus(80%) • 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 2/7/2023 DEREBE ASSEFA 8
  • 9. • The disease usually presents with a descending pattern. • The first sign is trismus or lockjaw, followed by stiffness of the neck, difficulty in swallowing, and rigidity of abdominal muscles. • Other symptoms include elevated temperature, sweating, elevated blood pressure, and episodic rapid heart rate. • Spasms may occur frequently and last for several minutes. Spasms continue for 3–4 weeks. 2/7/2023 DEREBE ASSEFA 9
  • 10. Severity of generalized tetanus 2/7/2023 DEREBE ASSEFA 10
  • 11. Complications • Aspiration pneumonia • Vertebral fracture • Muscle rupture • DVT+PE (VTE) • Decubitus ulcer • Rhabdomyolysis (pigment-induced nephropathy) • Autonomic dysfunction - Labile or sustained HTN, Tachycardia, Hyperpyrexia, Profuse sweating, Bradycardia and hypotension episodes, Sudden cardiac arrest 2/7/2023 DEREBE ASSEFA 11
  • 12. 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(typically occurs 5 to 7 days following birth) • Manifests with poor feeding, rigidity and spasm • High rate of mortality 2/7/2023 DEREBE ASSEFA 12
  • 13. Local tetanus • Uncommon form of tetanus • Manifests with localized muscle contraction near the wound • good prognosis Cephalic tetanus : Rare form of local tetanus • Follows head injury or ear infection • Manifests with trismus and CN palsy (often CN VII), but involvement of cranial nerves VI, III, IV, and XII may also occur • High mortality 2/7/2023 DEREBE ASSEFA 13
  • 14. Clinical and pathologic progression of tetanus 2/7/2023 DEREBE ASSEFA 14
  • 15. Diagnosis • Entirely on clinical findings • Spatula test – gag stimulation causes masseter muscle spasm • The WHO definition of adult tetanus requires at least one of the following signs: Trismus (inability to open the mouth) or Risus sardonicus (sustained spasm of the facial muscles); or Painful muscular contractions. 2/7/2023 DEREBE ASSEFA 15
  • 16. DDx: - Strychnine poisoning, Dystonic drug reaction (phenothiazines, metoclopramide), Hypocalcemic tetany, Malignant neuroleptic syndrome Rabies, Stiff-person syndrome (SPS) Meningitis /encephalitis, Acute intraabdominal process ,Alveolar abscess, Dental infection 2/7/2023 DEREBE ASSEFA 16
  • 17. Duration of illness • Tetanus toxin-induced effects are long lasting because recovery requires the growth of new axonal nerve terminals. • The usual duration of clinical tetanus is 4-6 weeks 2/7/2023 DEREBE ASSEFA 17
  • 18. Treatment • Principle Cardiorespiratory support Eliminate the source of toxin Neutralize unbound toxin Prevent muscle spasms 2/7/2023 DEREBE ASSEFA 18
  • 19. goals of treatment • The goals of treatment include: Halting the toxin production Neutralization of the unbound toxin Airway management Control of muscle spasms Management of dysautonomia General supportive management 2/7/2023 DEREBE ASSEFA 19
  • 20. 1. General measures • Admit in a quiet ICU with a possibility for continuous monitoring but minimal disturbance • Hydration • Nutritional support (IV/PO) spasms result in high metabolic demands and a catabolic state. • Physiotherapy to prevent contracture • psychological support, analgesia • Treatment of superimposed infection eg aspiration pneumonia 2/7/2023 DEREBE ASSEFA 20
  • 21. 2. Treatment of source infection • Wound debridement • Antibiotic therapy to eradicate vegetative C.Tetani; choice are: Metronidazole 500mg IV TID or QID , Penicillin 2 -4 million units IV Q4-6hrs lower dose of penicillin should be used as high dose has a GABA inhibitory effect Others Clindamycin, vancomycin ,chloramphenicol, Tetracyclines, macrolides, cephalosporins can be used . We suggest a treatment duration of 7 to 10 days. 2/7/2023 DEREBE ASSEFA 21
  • 22. 3. Neutralization of unbound toxin Antitoxin • Since tetanus toxin is irreversibly bound to tissues, only unbound toxin is available for neutralization • Human tetanus immune globulin (HTIG) A dose of 3000 to 6000 units IM should be given as soon as the diagnosis of tetanus is considered, with part of the dose infiltrated around the wound . HTIG should be administered at different sites than tetanus toxoid • Pooled IV Ig and equine antitoxin are used as alternative to HTIG 2/7/2023 DEREBE ASSEFA 22
  • 23. 4. Active immunization • Since 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. • Subsequent tetanus doses, in the form of Td, are recommended at 10-year intervals throughout adulthood Tetanus toxoid should be administered at a different site than tetanus immune globulin. It should be assumed that anyone who is not adequately vaccinated or protected against tetanus is also inadequately protected against diphtheria (not Tdap) 2/7/2023 DEREBE ASSEFA 23
  • 25. 2. Control of muscle spasm • Generalized muscle spasms are life threatening since they can cause respiratory failure, lead to aspiration, and induce generalized exhaustion • Benzodiazepines (Diazepam, midazolam), Barbiturates, chlorpromazine, propofol, dantrolene, baclofen Diazepam 10 to 30 mg IV and repeated as needed every 1 to 4 hours; total daily doses as high as 500 mg may be required for an adult Chlorpromazine 50–150 mg IM injection every 4–8 hours • Neuromuscular blocking agents- Vecuronium is less likely to cause autonomic problems than Pancuronium 2/7/2023 DEREBE ASSEFA 25
  • 26. Respiratory care • Intubation / Tracheostomy + mechanical ventilation for adequate oxygenation 2/7/2023 DEREBE ASSEFA 26
  • 27. Management of autonomic dysfunction • Magnesium sulfate -acts as a presynaptic neuromuscular blocker, blocks catecholamine release from nerves, 5 gm (75mg/kg) IV loading dose, then 2–3 grams/hour until spasm control is achieved Can control the autonomic dysfunction and spasm • Labetalol – both α and β blockers are preferred. Beta blockade alone with propranolol, for example, should be avoided because of reports of hypotension and sudden death. • Esmolol (short acting B blocker), verapamil, clonidine, morphine can be used. • Continuous spinal anesthesia can also be used- epidural bupivacaine-20 to 50 mL of 0.25% 2/7/2023 DEREBE ASSEFA 27
  • 28. prognosis  Case-fatality rates for non-neonatal tetanus in developing countries range from 8 to 50 percent 2/7/2023 DEREBE ASSEFA 28
  • 29. Reference • Harrison 20th edition • Uptodate 2018 2/7/2023 DEREBE ASSEFA 29

Hinweis der Redaktion

  1. Penicillin G (100,000–200,000 IU/kg/day intravenously, given in 2–4 divided doses
  2. In 1897, Nocard demonstrated the protective effect of passively transferred antitoxin, and passive immunization in humans was used for treatment and prophylaxis during World War I.
  3. 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, except in pregnant women, who should receive Tdap during each pregnancy Tetanus toxiod - Age <7 yrs – DPT vaccine; Age> 7 yrs –DT Vaccine TT vaccination should receive a second dose 1–2 months after the first dose and a third dose 6–12 months later TT-containing vaccine, 0.5 cc by intramuscular injection
  4. Other agents used for spasm control include baclofen, dantrolene (1–2 mg/kg intravenous or by mouth every 4 hours), barbiturates, preferably short-acting (100–150 mg every 1–4 hours in adults; 6–10 mg/kg in children; by any route), and chlorpromazine (50–150 mg by intramuscular injection every 4–8 hours in adults;
  5. Magnesium sulphate can be used alone or in combination with benzodiazepines to control spasm and autonomic dysfunction: 5 gm (or 75mg/kg) intravenous loading dose, then 2–3 grams per hour until spasm control is achieved To avoid magnesium sulphate overdose, monitor patellar reflex as areflexia (absence of patellar reflex) occurs at the upper end of the therapeutic range (4mmol/L). If areflexia develops, dose should be decreased.