Clostridium botulinum

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Clostridium botulinum / (Redirected from Botulism)

Background

History

  • Named for sausages (botulus) due to a historical association with improperly-cooked sausages

Microbiology

  • Large Gram-positive anaerobic bacillus with a subterminal spore
    • Lipase positive and lecithin negative on egg yolk agar
  • Diverse species whose defining trait is the production of botulinum toxin
  • Subdivided into four groups based on biochemical tests
    • Group I: proteolytic in culture, and produces toxins A, B, and F
    • Group II: non-proteolytic in culture, and produces toxins B, E, and G
    • Group III: produces toxins C and D
    • Group IV: produces toxin G
  • These strains produce eight toxin types, A through G (and possibly H), that are identified by serology; some strains produce two different toxins
    • A, B, E, and F (and possibly H) cause disease in humans
    • Toxins A and B are used therapeutically (e.g. Botox)
    • Toxin G is the only plasmid-encoded toxin

Pathophysiology

  • Disease is caused by ingestion or inhalation of preformed toxin, or absorption of toxin from localized infections in the GI tract or a wound
    • Absorbed primarily in duodenum and jejunum
  • Botulinum toxins are zinc-dependent metalloproteinases, and inhibit the release of acetylcholine from the presynaptic neuron
    • Affects exclusively cholinergic synapses, including those of the neuromuscular junction and the autonomic nervous system
    • Different toxin types target different specific proteins within the neuro

Life Cycle

  • Circulates primarily in birds and non-human mammals

Epidemiology

  • Spores are found worldwide in soil and water
  • Disease commonly occurs in outbreaks related to contaminated food
    • A is most common in North America and is commonly associate
    • E is associated with marine animals and fish, and is common in outbreaks amongst Inuit people
  • More common in certain areas due to local food practices

Clinical Manifestations

  • Typically involves symmetric descending paralysis, starting with cranial nerves and often involving respiratory muscles
  • Afebrile with normal or slow heart rate despite hypotension, and sparing the sensory nerves
  • This presentation contrasts with polio, which can be asymmetric and often has fever

Foodborne Botulism

  • Symptoms start 12 to 36 hours after ingestion
  • Nausea, diarrhea, and dry mouth
    • Of note, diarrhea is not caused by the toxin but by other ingested contaminants
  • Descending flaccid paralysis, with:
    • Acute onset bilateral cranial neuropathies, causing diplopia, dysphagia, and dysarthria
    • Almost always symmetric, but can rarely be asymmetric
    • Autonomic neuropathies, causing dry mouth, fixed or dilated pupils, blurred vision, and hypotension
    • Upper and lower extremity weakness
    • May appear calm despite significant respiratory distress, due to the paralysis
  • GI symptoms include constipation, nausea, and vomiting; occasionally abdominal cramps and diarrhea
  • Usually fatigue, and occasionally sore throat and dizziness
  • No cognitive or sensory effects (rarely paresthesias)

Wound Botulism

  • Incubation period of 4 to 14 days
  • More commonly caused by toxins A or B
  • Classically associated with injection of "black-tar" heroin, especially those who inject by skin-popping
  • May have fever secondary to an infected wound, although the wound can rarely appear to be healing well
  • Can produce abscesses

Infant Botulism

  • Classically after ingesting unpasteurized honey
  • Most commonly caused by toxins A, B, and F
  • Presents with feeding difficulties, hypotonia, drooling, and weak cry
  • Descending paralysis, including upper airway obstruction that may require intubation
  • Distinguishing features are lack of fever, normal CSF
  • Typically worsens over 1 to 2 weeks, then stabilizes for 2 to 3 weeks, then recovers
  • Relapses are possible

Adult Intestinal Toxemia

  • Rare form of botulism associated with colonisation of the GI tract
  • Most commonly caused by toxin A, but occasionally also B and F
  • Onset is more gradual and disease less severe than foodborne botulism
  • Risk factors are gastrointestinal surgery or illness, such as inflammatory bowel disease

Inhalation Botulism

  • Incubation period of 12 hours to 3 days
  • Rare, associated with insufflation of contaminated cocaine, but also a theoretical bioterrorism agent
  • Typical symptoms of botulism

Iatrogenic Botulism

  • May occur during use of therapeutic botulinum toxin (e.g. Botox)

Prognosis

  • Mortality with appropriate treatment is 5 to 8% in adults and 1% in infants
  • Takes weeks to months to recover (admissions lasting 1 to 3 months) and may have fatigue and weakness for more than one year

Differential Diagnosis

Adults

Infants

Diagnosis

  • Samples should include serum, gastric secretions, stool, or food
  • Gold standard for diagnosis is the mouse bioassay
    • A mouse is injected with a sample and is monitored for paralysis
    • Toxin type is determined by administering type-specific antitoxin and monitoring for improvement
  • Strict anaerobic cultures of serum, stool, or food, though low sensitivity
  • EMG may show small decrement in motor response or brief small abundant motor unit action potentials (BSAP), and may be useful to distinguish botulism from Lambert-Eaton myasthenic syndrome

Management

  • Call the Botulism Reference Service for Canada (or equivalent): office (613) 957-0902; laboratory (613) 957-0885; after-hours (613) 296-1139
  • Supportive care
    • Low threshold for intubation and ventilation
    • If contaminated food still in gastrointestinal tract, may use purgatives to prevent further absorption (unless ileus)
    • Appropriate debridement and wound care, for wound botulism
  • Antitoxin should be given within 2 to 3 days of symptom onset
    • For infants up to 1 year old, BabyBIG (BIG-IV) 50 mg/kg
      • Human-derived
      • Only manufactured in California, so difficult to access urgently
    • For children over 1 year and adults, heptavalent botulinum antitoxin (HBAT)
      • Horse-derived antitoxin to toxins A through G (7,500 U anti-A; 5,500 U anti-B; 5,000 U anti-C; 1,000 U anti-D; 8,500 U anti-E; 5,000 U anti-F; and 1,000 U anti-G)
      • Risk of sensitization or anaphylaxis to horse proteins
  • Antibiotics

Prevention

  • Food safety practices
    • Safe canning and fermentation practices
    • Toxin is heat labile, though, so cooking food will deactivate the toxin
  • Avoiding honey in infants less than 1 year old
    • Possibly also avoiding raw sugar (but not refined sugar), molasses, herbal (chamomile) tea26 and other herbal preparations

Further Reading