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
Guillain-Barré syndrome (acute inflammatory demyelinating polyneuropathy): asymmetric, ascending, and involves sensory nerves; or ataxia, in the Miller-Fisher variant that involves cranial nerves
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
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
