Clostridium botulinum

Background

History

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

Microbiology

• Gram-positive anaerobic bacillus with a subterminal spore
• Diverse species whose defining trait is the production of botulinum toxin
• Subdivided into four groups based on biochemical tests
• These strains produce eight toxin types, A through H, that are identified by serology; some strains produce two different toxins

Pathophysiology

• Botulinum toxins are zinc-dependent metalloproteinases, and inhibit the release of acetylcholine from the presynaptic neuron
• Affects cholinergic nerve terminals, including neuromuscular junction and the autonomic nervous system

Life Cycle

• Circulates primarily in birds and non-human mammals

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
  • Autonomic neuropathies, causing dry mouth, fixed or dilated pupils, blurred vision, and hypotension
  • Upper and lower extremity weakness
• 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
• 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
• 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
• 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
• Typical symptoms of abotulism

Differential Diagnosis

• Myasthenia gravis: lacks autonomic features
• Lambert-Eaton myasthenic syndrome
• Guillain-Barré syndrome (acute inflammatory demyelinating polyneuropathy): asymmetric, ascending, and involves sensory nerves; or ataxia, in the Miller-Fisher variant that involves cranial nerves
• Tick paralysis: Dermacentor tick still attached
• Polio: febrile and asymmetric
• Others: diphtheria, organophosphate toxicity, brainstem stroke

Diagnosis

• Gold standard is the mouse bioassay
  • A mouse is injected with a sample (serum, gastric secretions, stool, or food) and are monitored for paralysis
  • Toxin type is determined by administering type-specific antitoxin and monitoring for improvement
• 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)

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
  • Intubation and ventilation if necessary
  • Bowel routine including enemas if constipated but without severe ileus
• Antitoxin
  • For infants up to 1 year old, BabyBIG (BIG-IV) 50 mg/kg
    • Human-derived
  • For children over 1 year and adults, heptavalent botulinum antitoxin (HBAT)
    • Horse-derived
    • Including antitoxins to toxin types A through G
    • Risk of sensitization or anaphylaxis to horse proteins
• Antibiotics
  • May cause more toxin to be released from dying bacteria, so generally avoided
  • Aminoglycosides and tetracyclines can worsen the paralysis of infant botulism

Prognosis

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

Further Reading

• Botulism Reference Service for Canada