Seminal paper on tetanus,

1. D R M A L L U M C . B
S E N I O R R E G I S T R A R
N E U R O L O G Y U N I T
L U T H
TETANUS

2. HISTORICAL NOTE
 Earliest record dates back to Egyptian civilization.
 In 1890,tetanospasmin was extracted from anaerobic
soil bacteria and found to be responsible for clinical
tetanus.

3. EPIDEMIOLOGY
 Occurs worldwide but more prevalent in developing
countries.
 About 1 million cases (18 per 100,000) are said to
occur annually.
 Case fatality ratio ranges between 20 to over 50
percent.
 Neonatal tetanus is the second leading cause of
death from vaccine preventable disease in children
worldwide.
 Half of the deaths from tetanus occur in children.

4.  Tetanus is rare in developed countries as a result of
immunization.(36 cases of tetanus reported in the
US in 1994)

5. PATHOPHYSIOLOGY
 Clostridium enters the body through a wound.
 Spores germinate in anaerobic conditions.
 Toxins are produced and disseminated through
blood and lymphatics.
 Toxins act at various sites in the nervous system
including the peripheral end plate,spinal cord,brain,
and sympathetic nervous system.

6. PATHOPHYSIOLOGY
 Toxins gain access to the CNS via retrograde axonal
transport in motor nerves.
 Toxins move into the presynaptic inhibitory
interneurons with resulting inhibition of release of
inhibitory neurotransmitters (GABA in the brain,
glycine in the spinal cord).
 This results in heightened muscular activity.
 Loss of glycine inhibition occurs in the
intermediolateral grey matter of the spinal cord
results in increased sympathetic activity.

7. PATHOPHYSIOLOGY
 Reduction of release of acetylcholine from motor
neurons may result in paralysis of cranial nerves in
cephalic tetanus.

8. Clostridium Tetani
 Found primarily in the soil and intestinal tracts of
animals and humans.
 Clostridium tetani is a slender, motile,gram positive,
anaerobic rod that may develop a terminal spore
giving it a drumstick appearance.
 The organism is sensitive to heat and cannot survive
in the presence of oxygen.

9. Clostridium Tetani
 The spores,however, are very resistant to heat and
usual antiseptics.
 Spores may survive several years and are resistant to
various disinfectants and to boiling for 20minutes.
They are relatively resistant to phenol. Spores may
survive autoclaving at 121 degrees C for 10-15 mins.

10.  Spores are found in soil, intestines of animals and on
skin surfaces and contaminated heroin.
 Manure treated soil may contain large numbers of
spores.
 Under anaerobic conditions, spores begin to
germinate and proliferate.
 Spores produce two exotoxins: Tetanolysin and
Tetanospasmin.

11.  The clinical significance of Tetanolysin is still
uncertain.
 Tetanospasmin is a neurotoxin and is responsible for
the clinical manifestations of tetanus.
 The estimated human lethal dose of tetanospasmin is
2.5 ng per kg body weight.

12. MODE OF TRANSMISSION
 Primarily from contaminated wounds.
 May follow elective surgery,burns,deep puncture
wounds, crush wounds,otitis media,dental
infection,animal bites, abortion.
 Tetanus is infectious but not contagious(no person to
person transmission)

13. CLASSIFICATION
 Localized tetanus
 Generalized tetanus
 Neonatal tetanus
 Cephalic tetanus

14. CLINICAL FEATURES
 The hall marks of tetanus are sustained muscular
rigidity, and in severe cases, reflex spasms.
 The interval of time between spore innoculation and
development of the first symptom is the incubation
period .usu 3 and 21 days,range 0-60days
 The time from the first symptom to reflex spasms is
the period of onset.
 Incubation period less than 10-14 days and period of
onset less than 3-6 days is indicative of severe
disease.

15. CLINICAL FEATURES
 The earliest manifestations of generalized tetanus
are rigidity of the masseter muscle (lockjaw or
trismus ) and facial muscles , with straightening of
the upper lip(Grimace or Risus Sardonicus).
 This is soon followed by rigidity of axial muscles with
prominent involvement of the neck and back
muscles(Opisthotonus).
 Rigidity of axial muscles may precede or accompany
trismus.
 Stiffness of the limb muscles may be evident with
sparing of distal muscles.

16. CLINICAL FEATURES
 Reflex spasms are violent, paroxysmal contractions
of the muscles in response to attempts at voluntary
movement and to external and internal(fear,hunger)
stimuli.
 Spasms of the deglutition muscles in severe cases
may result in difficulties in swallowing and verbal
expression.
 Laryngospasm may also occur leading to
asphyxiation.

17. CLINICAL FEATURES
 Disease severity continues for 10-14 days and is
usually followed by recovery.
 Autonomic instability may manifest by fluctuations
of heart rate and blood pressure,arrhythmias,profuse
sweating, hyper salivation,extreme hyperpyrexia.
They reflect a hypersympathetic state and complicate
severe cases.

18. CLINICAL FEATURES(Localized tetanus )
 Localized stiffness near the injury
 Fixed muscular rigidity confined to wound-bearing
extremity may persist for months.
 Localized tetanus usually precedes generalized
tetanus.

19. Cephalic tetanus:
 Usually associated with infections of paracranial
structures eg chronic otitis media and dental
infection.
 Presents as trismus and paralysis of one or more
cranial nerves.
 Facial paresis and dysphagia.
 Abnormal ocular movements – bilateral trochlear
nerve palsy(ophthalmoplegic tetanus) and downbeat
nystagmus.

20. INVESTIGATIONS
 Diagnosis is entirely clinical.
 Clostridium tetani is isolated from the wound in only
30% of patients and may be present in individuals
without tetanus.
 Serum antitoxin levels >0.01u/ml make the
diagnosis unlikely.
 Ancillary investigations like FBC,U&E,CR

21. DIFFERENTIAL DIAGNOSIS
 Strychnine intoxication- trismus is absent,abdominal
muscle is less rigid.
 Neuroleptic Malignant syndrome- lack of reflex
spasms
 Acute dystonic reactions(extrapyramidal side effects
of dopamine blocking agents)- lack of reflex spasms.
 Stiff-person syndrome- insidious onset, less
involvement of face,jaw muscles;muscle rigidity
reduced by sleep.

22. DIFFERENTIAL DIAGNOSIS
 Hypocalcemic tetany- involves extremities more than
trunk;chvostek and trousseau’s sign.
 Meningoencephalitis- also has abnormal tone and
nuchal rigidity but this does not have normal
sensorium as in tetanus.
 Dental abscess- may mimic trismus
 Subarachnoid haemorrhage,
 Hysteria

23. COMPLICATIONS OF TETANUS
 Laryngospasm and/or spasms of muscles of
respiration.
 Fractures of spine and /or long bones from sustained
contraction.
 Hypertension and/or abnormal heart rhythm- due to
hyperactivity of autonomic nervous system.
 Nosocomial infections- sepsis from indwelling
catheters,decubitus ulcers,hospital-aquired
pneumonia.

24. COMPLICATIONS OF TETANUS
 Pulmonary embolism especially in elderly and IV
drug users.
 Aspiration pneumonia-
 Death in 11% of reported cases more common in
persons older 60yrs,unvaccinated persons.
Causes include larygnospasm,cardiac arrest.
 Renal insufficiency

25. MANAGEMENT
 The principles of management are:
1.Elimination of source of toxin
2.Toxin neutralization
3.Control of muscular rigidity and spasms.
4.Supportive care

26. ElIMINATION OF THE SOURCE OF TOXIN
 Wound exploration, cleansing and debridement are
important to reduce the bacterial load.
 Antibiotic therapy is given. Iv metronidazole 500mg
8hrly,
 IV penicillin is usually given but may worsen the
spasm because it has a central GABA antagonistic
effect.

27. TOXIN NEUTRALIZATION
 Neutralization of circulating toxin is done by giving
Sc ATS anti tetanus serum(ATS) at 10,000 IU stat
after a negative test dose
 An alternative is IM Human tetanus Immunoglobin
500 IU stat where available.

28. CONTROL OF SPASMS
 Benzodiazepines such as
diazepam,lorazepam,midazolam
 IV diazepam is given in infusion IV 5% dextrose
water in 0.9%normal saline .
 Dose of diazepam to titrated in response to spasm
frequency and to be reduced in event of any
drowsiness.
 IV diazepam 20mg every 2hours via intravenous
push can be given for breakthrough spasms.

29. CONTROL OF SPASMS
 Barbiturates such as IV phenobarbital are second
line drugs.
 Neuromuscular blockade with
atracurium,vecuronium or pancuronium is required
in severe cases with violent spasms and respiratory
depression.
 Other alternatives are morphine,fentanyl,clonidine,
atropine, continuous spinal anaesthesia.

30. Supportive care
 Autonomic instability has been treated with combined
alpha and beta blockers eg labetalol with varying success
 Patient is to be nursed in a dark, quiet room.
 NPO
 A spasm chart is to be kept.
 DVT prophylaxis with SC clexane or heparin.
 Feeding can be recommenced once patient is spasm free
 Physiotherapy may assist in mobilization once patient is
spasm free.
 ICU admission + tracheostomy may be required in
severe cases

31. IMMUNIZATION SCHEDULE ON DISCHARGE
 IM TT 0.5mls stat is given on presentation
 A Repeat dose is given 6 weeks after the first
 The 3rd dose is given 6 months afterwards.

32. PROGNOSIS
 Poor prognostic factors:
-short incubation period
-short period of onset
-cephalic tetanus
-neonatal tetanus
-poor prior vaccination
-dysautonomia

33. PREVENTION
 Appropriate wound care and immunization
 Especially for wounds with severe tissue
necrosis,suppuration,retained foreign bodies.
 Eg burns,umbilical stumps,compound
fractures,septic abortion,intramuscular injections.
 Antibiotic prophylaxis has no place in the
management of tetanus

34. PREVENTION
 Prophylaxis is antibody dependent and can be either
passive(Tetanus-specific immunoglobulin) or
active(tetanus toxoid)

35.  Patients should receive antitetanus globulin as well
as tetanus toxoid.
 Wounds that are neither clean nor minor
 0-2 prior doses of tetanus toxoid
 Uncertain history of prior doses.

36. IMMUNIZATION
 The only reliable immunity against tetanus is
achieved by vaccination with tetanus toxoid.
 Tetanus toxoid can safely be given in pregnancy and
in immunocompromised individuals.
 1st dose=IgM + small IgG) insufficient protection
2nd dose = 90% protection but after 1 yr drops to 80%
3rd dose = 98% protection and lasts several years

37. IMMUNIZATION
 Length of protection after 5-6 doses = 20-25 yrs.
 WHO recommends that 5 doses of tetanus toxoid be
given over 12-15 yrs , starting at infancy, with a sixth
dose often given in adulthood to ensure long lasting
protection.

38. MCQS
 Regarding spores of causative organism of tetanus ,
which is true?
 - Highly susceptible to heat and disinfectants
 Survive for less than 24 hours
 Require high oxygen tension to grow
 Aquired from contamination of deep wounds by
rusty implements or dust
 Susceptible to autoclaving when present on surgical
instruments

39. MCQS
 Complications of tetanus include the following
 - Acute renal failure
 -fractures
 -Respiratory failure
 Sympathetic overactivity
 Sudden cardiac death

40. MCQS
 In the diagnosis of tetanus, which of the following is
confirmatory?
 ESR
 Serum antitoxin levels
 Serum tetanus toxin levels
 CSF tetanolysin antibody test
 No laboratory test is required

41. MCQS
 The following are poor prognostic features in
tetanus:
-Presence of autonomic features
-short incubation period
-short period of onset
- More cephalic presentation of culprit wound
- Presence of difficulty opening mouth as the first
symptom