Clostridium botulinum

Background

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

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

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

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

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, and hypotension
No cognitive or sensory effects

Incubation period of t to 14 days
May have fever secondary to an infected wound, although the wound can rarely appear to be healing well
Can produce abscesses

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

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

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

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)

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