Tetanus

Epidemiology

  • <100 annual cases of tetanus reported to CDC in USA (94% occur in patients >20/ 68% of cases occur in patients >50)
  • Sporadic: almost always affects nonimmunized or partially immunized patients
  • Common where soil is cultivated/ in males/ during summer months/ in warm climates
  • 800k neonates die annually from neonatal tetanus (rare in USA though)

Etiology

  • Clostridium Tetani tetanospasmin
    • C. tetani: anaerobic motile GPR with oval, colorless terminal spore (“tennis racket” or “drumstick” shape)/ spores are found worldwide in soil, on fomites, in animal and human feces (resistant to disinfectants and boiling x 20 min)
  • Infection source (by spores):
    • Local major or minor wound (abscess/ ulcer/ laceration/ abrasion/ puncture/ gangrene/ burn/ frostbite/ surgical wound): indoors or outdoors
    • Skin popping site:
    • Ear infection:
    • Abortion/ childbirth:
    • Idiopathic (in some cases):

Physiology

  • Tetanus begins when spores of Clostridium tetani enter damaged tissue.
    The spores transform into rod-shaped bacteria and produce the neurotoxin tetanospasmin (also known as tetanus toxin). This toxin is inactive inside the bacteria, but when the bacteria die, the toxin is released and activated by proteases.

Active tetanospasmin enters at neuromascular junction of motor neurons and is carried by retrograde axonal transport[6][8] to cell bodies in the spinal cord and brain stem where it binds irreversibly to receptors at these sites.[6]

It cleaves membrane proteins involved in neuroexocytosis,[9] which in turn blocks neurotransmission.

Ultimately, this produces the symptoms of the disease.

Damaged upper motor neurons can no longer inhibit lower motor neurons (see Renshaw cells), plus they cannot control reflex responses to afferent sensory stimuli.[6]

Both mechanisms produce the hallmark muscle rigidity and spasms.

Similarly, a lack of neural control of the adrenal glands results in release of catecholamines, thus producing a hypersympathetic state and widespread autonomic instability.

C. tetani also produces tetanolysin, another toxin whose role in tetanus is unknown.

Pathogenesis: decreased inhibitory glycine GABA release from SC terminals on alpha motonuerons -> increased alpha motoneuron firing -> muscle spasms
-Occurs only in wounds with low redox potential (devitalized tissue/ foreign body/ active infection)
-C. Tetani itself does not evoke inflammation
-Toxin effect: tetanospasmin neurotoxin (partially homologous to Botulinum neurotoxin) released by spores into wound -> binding to and entry of alpha motoneuron terminal -> retrograde transport to alpha motoneuron body in SC (or brainstem) -> migration across synapse to pre-synaptic terminal -> inhibition of pre-synaptic release of inhibitory GABA and glycine -> increased resting firing of alpha motoneuron -> muscle spasm and rigidity
–Loss of inhibition of preganglionic sympathetic neurons in lateral gray matter of SC -> sympathetic hyperactivity and increased catecholamines
–Tetanospasmin can also block NMJ Ach release (like Botulinum toxin) -> weakness and paralysis may also occur


Diagnosis

  • CBC: leukocytosis
    Wound c/s: not useful, since organism presence does not correlate with presence of Tetanus

LP: normal

EMG: continuous discharge of motor units

EKG: non-specific changes

CK: may be elevated

Serum Anti-Toxin Level: level >0.01 units/mL is considered protective, making tetanus unlikely


Clinical

A) Generalized Tetanus (most common syndrome):
-Occurs when toxin is released into bloodstream, affecting short (head) nerves before long (trunk, extremities) nerves (blood-brain barrier prevents entry into CNS)
-Median Onset of Symptoms After Injury: 7 days (15% occur within 3 days/10% occur after 14 days)

1) Neuro:
a) Trismus (“lockjaw”) -> “risus sardonicus” (facial grimacing), dysphagia -> stiffness or pain in neck, shoulders, back (arching opisthotonos may occur and violent contractions may occur) -> rigid abdomen, stiff proximal limb muscles (relative sparing of hands and feet) -> hyperreflexia, fractures, muscle rupture, rhabdo
b) Normal MS:

2) Pulmonary:
– Respiratory Muscle Involvement
– Apnea
– Laryngospasm
– Aspiration
– Acute/Chronic Hypoventilation (see Acute Hypoventilation, [[Acute Hypoventilation]] and Chronic Hypoventilation, [[Chronic Hypoventilation]])
– Increased Risk of DVT:

3) Cardiac:
a) Autonomic Dysfunction: HTN (due to vasoconstriction and increased catecholamines) or hypo-tension/ tachycardia or bradycardia/ arrhyth-mias/ fever/ hyperhidrosis/ cardiac arrest)

B) Neonatal Tetanus: like generalized tetanus
-Occurs in neonates of non-immunized mothers (unsterile treatment of umbilical cord stump): onset during first 2 weeks of life
-Poor feeding/ rigidity/ muscle spasms
-Fatal in untreated

C) Localized Tetanus: occurs when only the nerves supplying the muscles near the wound are affected (uncommon)
-Excellent prognosis

D) Cephalic Tetanus: rare variant of localized tetanus
-Occurs few days after head injury, ear infection
-Trismus and dysfunction of cranial nerves (especially CN-7)/ typically high mortality


Treatment

Supportive Care:
-Minimal Stimulation: keep in quiet and dark environment
-Debride Wounds:
-Vent Support: may be required for as long as 3 weeks
–Avoid elective/prophylactic intubation, as stimulation (and tracheal suctioning) may worsen reflex spasms
–Elective trach is probably preferred at a later time

Tetanus Vaccination: give acute Td toxoid and also for prevention

Human Tetanus Ig (3-6k ? units IM given anywhere x1/smaller 500 unit dose may be as effective): neutralize circulating toxin and unbound toxin in wound

-Decreases mortality

PCN (10-12 miilion units/day IV x 10 days): questionable benefit, but may eliminate C. Tetani from wound
-Alternatives: Clindamycin/Erythromycin/Metronidazole

Treatment of Muscle Spasm:
-Benzodiazepines: mainstay of therapy for muscle spasms
-Alternatives: Barbiturates/Chlorpromazine
-Paralytics: may be useful in cases with respiratory failure requiring intubation

Treatment of Autonomic Dysfunction:
a) Labetalol (few cases of sudden death have been reported though):
b) Esmolol:
c) Clonidine:
d) Morphine Sulfate:
e) IV Magenesium:
f) Spinal Anesthesia:


Prognosis

  • 10% mortality (some years <2%)
  • Increased tone and minor spasms may last for months (full recovery is usual)
  • Poorer prognosis: neonatal, elderly with short incubation/ short interval from onset of symptoms to first spasm or admission

References

  • Bleck TP. Intravenous immune globulin for passive tetanus prophylaxis. J Infect Dis 1993; 167:498-499
  • Bleck TP. Tetanus: pathophysiology, management and prophylaxis. Dis Mon 1991; 37:545-603