Microbiology · Year 2 · from Microbiology

Case 1: Tetanus

Presentation

A 52-year-old man presents to the emergency department with jaw stiffness and difficulty swallowing that began yesterday. He also reports painful muscle spasms that are triggered by loud noises. Two weeks ago, he sustained a puncture wound to his right foot while working in his garden without shoes. He cleaned the wound himself but did not seek medical attention. He immigrated to the United States from a rural area 5 years ago and is unsure of his vaccination history.

Physical examination reveals a patient in visible distress. He has marked trismus (lockjaw) and cannot open his mouth more than 1 cm. His facial muscles are contracted in a grimacing expression. While being examined, a door slams in the hallway, triggering severe generalized muscle spasms causing him to arch his back dramatically. Vital signs show temperature 38.2°C, heart rate 125 bpm, and blood pressure 165/95 mmHg.

Clinical Image

Gram-positive rods with spore formation - characteristic features of Clostridium species showing endospore development.

Image Source: Lecture image - Clostridium morphology

Questions

  1. What is the diagnosis, and what organism is responsible?
  1. Describe the mechanism of action of the toxin causing this patient's symptoms. Why does it cause spastic rather than flaccid paralysis?
  1. The patient's wound appeared trivial and well-healed on examination. Why does the wound appear unremarkable despite causing systemic disease?
  1. What are the components of treatment for this condition?

Answers

  1. Diagnosis and organism: The diagnosis is tetanus caused by Clostridium tetani. The classic clinical features present in this case include:
  • Trismus (lockjaw): Masseter muscle spasm - often the first symptom
  • Risus sardonicus: Sustained contraction of facial muscles producing a grimacing expression
  • Opisthotonus: Severe back arching due to paraspinal muscle spasms
  • Reflex spasms: Triggered by stimuli (noise, light, touch)
  • Autonomic dysfunction: Hypertension, tachycardia (can also cause hypotension, diaphoresis)

Risk factors include the puncture wound from gardening (soil contamination with C. tetani spores) and uncertain vaccination history.

  1. Mechanism of tetanospasmin:

Structure: Tetanospasmin is an A-B toxin

  • B (binding) fragment binds to ganglioside receptors on motor nerve terminals
  • A (active) fragment is a zinc metalloprotease

Pathway to CNS:

  • Toxin is released at the wound site when C. tetani bacteria lyse
  • Binds to motor nerve terminals at the neuromuscular junction
  • Undergoes retrograde axonal transport to the spinal cord (takes days - explains incubation period)

Mechanism of action:

  • Cleaves synaptobrevin (VAMP-2), a SNARE protein essential for neurotransmitter vesicle fusion
  • Specifically affects inhibitory interneurons (Renshaw cells) in the spinal cord
  • Blocks release of glycine and GABA (inhibitory neurotransmitters)

Why spastic paralysis?

  • Normally, inhibitory interneurons dampen motor neuron firing
  • Without glycine/GABA release, motor neurons receive unopposed excitatory input
  • Results in sustained muscle contraction (spastic paralysis)

This contrasts with botulism, where the same SNARE protein is cleaved but at the neuromuscular junction, blocking acetylcholine release and causing flaccid paralysis.

  1. Why the wound appears unremarkable:
  • C. tetani does not invade tissues - it remains localized at the wound site
  • The bacteria may be present in very small numbers
  • Wound may have healed superficially while anaerobic conditions persist deeper
  • Deep puncture wounds are ideal because they create anaerobic environment without extensive tissue destruction
  • All disease manifestations are due to toxin action at distant sites (CNS), not local infection
  • The wound may appear completely healed by the time symptoms appear (incubation 3-21 days)
  1. Treatment components (all should be initiated simultaneously):
  1. Human tetanus immune globulin (TIG): 3000-6000 units IM
  • Neutralizes circulating toxin
  • Cannot reverse toxin already bound to neurons
  • Must be given early before more toxin binds
  1. Wound debridement: Remove source of toxin production
  • Even if wound appears healed, debridement is indicated
  1. Antibiotics: Kill vegetative bacteria to stop toxin production
  • Metronidazole (preferred) - 500mg IV q6h
  • Penicillin is alternative but may theoretically enhance GABA antagonism
  1. Muscle relaxation: Benzodiazepines (diazepam, midazolam)
  • Enhance GABA activity at remaining receptors
  • Provide anticonvulsant effect
  1. Supportive care: Often requires ICU
  • Mechanical ventilation (severe cases)
  • Dark, quiet room to reduce stimulus-triggered spasms
  • Treatment of autonomic instability
  • May require weeks of intensive care
  1. Vaccination: Patients do not develop immunity from disease
  • Give Tdap after recovery

All cases for this lecture as Markdown