Clostridium botulinum: Difference between revisions
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Clostridium botulinum
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===History=== |
===History=== |
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β | *Named for sausages due to a historical association with improperly-cooked sausages |
+ | *Named for sausages (botulus) due to a historical association with improperly-cooked sausages |
===Microbiology=== |
===Microbiology=== |
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β | *[[Stain::Gram-positive]] [[Cellular respiration::anaerobic]] [[ |
+ | *Large [[Stain::Gram-positive]] [[Cellular respiration::anaerobic]] [[Shape::bacillus]] with a subterminal spore |
+ | **Lipase positive and lecithin negative on egg yolk agar |
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*Diverse species whose defining trait is the production of botulinum toxin |
*Diverse species whose defining trait is the production of botulinum toxin |
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*Subdivided into four groups based on biochemical tests |
*Subdivided into four groups based on biochemical tests |
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+ | **Group I: proteolytic in culture, and produces toxins A, B, and F |
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⚫ | |||
+ | **Group II: non-proteolytic in culture, and produces toxins B, E, and G |
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+ | **Group III: produces toxins C and D |
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+ | **Group IV: produces toxin G |
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⚫ | |||
+ | **A, B, E, and F (and possibly H) cause disease in humans |
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+ | **Toxins A and B are used therapeutically (e.g. Botox) |
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+ | **Toxin G is the only plasmid-encoded toxin |
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===Pathophysiology=== |
===Pathophysiology=== |
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+ | *Disease is caused by ingestion or inhalation of preformed toxin, or absorption of toxin from localized infections in the GI tract or a wound |
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+ | **Absorbed primarily in duodenum and jejunum |
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*Botulinum toxins are zinc-dependent metalloproteinases, and inhibit the release of acetylcholine from the presynaptic neuron |
*Botulinum toxins are zinc-dependent metalloproteinases, and inhibit the release of acetylcholine from the presynaptic neuron |
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β | *Affects cholinergic |
+ | **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 |
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===Life Cycle=== |
===Life Cycle=== |
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*Circulates primarily in birds and non-human mammals |
*Circulates primarily in birds and non-human mammals |
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+ | |||
+ | ===Epidemiology=== |
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+ | |||
+ | *Spores are found worldwide in soil and water |
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+ | *Disease commonly occurs in outbreaks related to contaminated food |
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+ | **A is most common in North America and is commonly associate |
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+ | **E is associated with marine animals and fish, and is common in outbreaks amongst Inuit people |
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+ | *More common in certain areas due to local food practices |
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==Clinical Manifestations== |
==Clinical Manifestations== |
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*Descending flaccid paralysis, with: |
*Descending flaccid paralysis, with: |
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**Acute onset bilateral cranial neuropathies, causing diplopia, dysphagia, and dysarthria |
**Acute onset bilateral cranial neuropathies, causing diplopia, dysphagia, and dysarthria |
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+ | **Almost always symmetric, but can rarely be asymmetric |
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**Autonomic neuropathies, causing dry mouth, fixed or dilated pupils, blurred vision, and hypotension |
**Autonomic neuropathies, causing dry mouth, fixed or dilated pupils, blurred vision, and hypotension |
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**Upper and lower extremity weakness |
**Upper and lower extremity weakness |
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+ | **May appear calm despite significant respiratory distress, due to the paralysis |
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*GI symptoms include constipation, nausea, and vomiting; occasionally abdominal cramps and diarrhea |
*GI symptoms include constipation, nausea, and vomiting; occasionally abdominal cramps and diarrhea |
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*Usually fatigue, and occasionally sore throat and dizziness |
*Usually fatigue, and occasionally sore throat and dizziness |
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*Incubation period of 4 to 14 days |
*Incubation period of 4 to 14 days |
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+ | *More commonly caused by toxins A or B |
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+ | *Classically associated with injection of "black-tar" heroin, especially those who inject by skin-popping |
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*May have fever secondary to an infected wound, although the wound can rarely appear to be healing well |
*May have fever secondary to an infected wound, although the wound can rarely appear to be healing well |
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*Can produce abscesses |
*Can produce abscesses |
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*Classically after ingesting unpasteurized honey |
*Classically after ingesting unpasteurized honey |
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+ | *Most commonly caused by toxins A, B, and F |
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β | * |
+ | *Presents with feeding difficulties, hypotonia, drooling, and weak cry |
*Descending paralysis, including upper airway obstruction that may require intubation |
*Descending paralysis, including upper airway obstruction that may require intubation |
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*Distinguishing features are lack of fever, normal CSF |
*Distinguishing features are lack of fever, normal CSF |
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*Rare form of botulism associated with colonisation of the GI tract |
*Rare form of botulism associated with colonisation of the GI tract |
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+ | *Most commonly caused by toxin A, but occasionally also B and F |
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*Onset is more gradual and disease less severe than foodborne botulism |
*Onset is more gradual and disease less severe than foodborne botulism |
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*Risk factors are gastrointestinal surgery or illness, such as inflammatory bowel disease |
*Risk factors are gastrointestinal surgery or illness, such as inflammatory bowel disease |
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β | === |
+ | ===Inhalation Botulism=== |
β | * |
+ | *Incubation period of 12 hours to 3 days |
+ | *Rare, associated with insufflation of contaminated cocaine, but also a theoretical bioterrorism agent |
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β | * |
+ | *Typical symptoms of botulism |
+ | |||
+ | ===Iatrogenic Botulism=== |
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+ | |||
+ | *May occur during use of therapeutic botulinum toxin (e.g. Botox) |
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+ | |||
+ | ===Prognosis=== |
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+ | |||
⚫ | |||
⚫ | |||
==Differential Diagnosis== |
==Differential Diagnosis== |
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+ | === Adults === |
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⚫ | |||
+ | |||
⚫ | |||
β | *[[Guillain-BarrΓ© syndrome]] (acute inflammatory demyelinating polyneuropathy): asymmetric, ascending, and involves sensory nerves; or ataxia, in the Miller-Fisher variant that involves cranial nerves |
+ | * [[Guillain-BarrΓ© syndrome]] (acute inflammatory demyelinating polyneuropathy): asymmetric, ascending, and involves sensory nerves; or ataxia, in the Miller-Fisher variant that involves cranial nerves |
⚫ | |||
⚫ | |||
⚫ | |||
⚫ | |||
β | * |
+ | * [[Stroke]], especially [[brainstem stroke]] |
+ | * Bacterial or chemical [[food poisoning]] |
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⚫ | |||
+ | * Chemical intoxication: [[carbon monoxide poisoning]], [[organophosphate toxicity]] |
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+ | * [[Mushroom poisoning]] |
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⚫ | |||
+ | * Psychiatric illness |
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+ | |||
+ | === Infants === |
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+ | |||
+ | * [[Sepsis in children|Sepsis]] |
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+ | * [[Meningitis in children|Meningitis]] |
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+ | * Electrolyte imbalance |
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+ | * [[Reye syndrome]] |
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+ | * [[Congenital myopathy]] |
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+ | * [[Werdnig-Hoffman disease]] |
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+ | * [[Leigh disease]] |
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==Diagnosis== |
==Diagnosis== |
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+ | *Samples should include serum, gastric secretions, stool, or food |
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β | *Gold standard is the '''mouse bioassay''' |
+ | *Gold standard for diagnosis is the '''mouse bioassay''' |
β | **A mouse is injected with a sample |
+ | **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 |
**Toxin type is determined by administering type-specific antitoxin and monitoring for improvement |
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β | * |
+ | *Strict anaerobic cultures of serum, stool, or food, though low sensitivity |
β | *EMG may show small decrement in motor response or brief small abundant motor unit action potentials (BSAP) |
+ | *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== |
==Management== |
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*Call the [https://www.canada.ca/en/health-canada/services/science-research/activity-highlights/microbial-research-activities/botulism-reference-service-canada.html Botulism Reference Service for Canada] (or equivalent): office (613) 957-0902; laboratory (613) 957-0885; after-hours (613) 296-1139 |
*Call the [https://www.canada.ca/en/health-canada/services/science-research/activity-highlights/microbial-research-activities/botulism-reference-service-canada.html Botulism Reference Service for Canada] (or equivalent): office (613) 957-0902; laboratory (613) 957-0885; after-hours (613) 296-1139 |
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*Supportive care |
*Supportive care |
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+ | **Low threshold for intubation and ventilation |
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β | **Intubation and ventilation if necessary |
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+ | **If contaminated food still in gastrointestinal tract, may use purgatives to prevent further absorption (unless ileus) |
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β | **Bowel routine including enemas if constipated but without severe ileus |
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+ | **Appropriate debridement and wound care, for wound botulism |
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β | *Antitoxin |
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+ | *Antitoxin should be given within 2 to 3 days of symptom onset |
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**For infants up to 1 year old, BabyBIG (BIG-IV) 50 mg/kg |
**For infants up to 1 year old, BabyBIG (BIG-IV) 50 mg/kg |
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***Human-derived |
***Human-derived |
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+ | ***Only manufactured in California, so difficult to access urgently |
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**For children over 1 year and adults, heptavalent botulinum antitoxin (HBAT) |
**For children over 1 year and adults, heptavalent botulinum antitoxin (HBAT) |
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+ | ***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) |
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β | ***Horse-derived |
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β | ***Including antitoxins to toxin types A through G |
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***Risk of sensitization or anaphylaxis to horse proteins |
***Risk of sensitization or anaphylaxis to horse proteins |
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*Antibiotics |
*Antibiotics |
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+ | **Unclear benefit, but often [[penicillin G]] or [[metronidazole]] are used for wound botulism |
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β | **May cause more toxin to be released from dying bacteria, so generally avoided |
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β | **Aminoglycosides and tetracyclines can worsen the paralysis of infant botulism |
+ | **[[Aminoglycosides]] and [[tetracyclines]] can worsen the paralysis of infant botulism, possibly by lysis of ''Clostridium botulinum'' in the gut |
β | == |
+ | == Prevention == |
+ | * Food safety practices |
||
⚫ | |||
+ | ** Safe canning and fermentation practices |
||
⚫ | |||
+ | ** Toxin is heat labile, though, so cooking food will deactivate the toxin |
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+ | * Avoiding honey in infants less than 1 year old |
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+ | ** Possibly also avoiding raw sugar (but not refined sugar), molasses, herbal (chamomile) tea26 and other herbal preparations |
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==Further Reading== |
==Further Reading== |
Latest revision as of 09:49, 15 October 2020
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
- Guillain-BarrΓ© syndrome (acute inflammatory demyelinating polyneuropathy): asymmetric, ascending, and involves sensory nerves; or ataxia, in the Miller-Fisher variant that involves cranial nerves
- Lambert-Eaton myasthenic syndrome
- Myasthenia gravis: lacks autonomic features
- Stroke, especially brainstem stroke
- Bacterial or chemical food poisoning
- Tick paralysis: Dermacentor tick still attached
- Chemical intoxication: carbon monoxide poisoning, organophosphate toxicity
- Mushroom poisoning
- Poliomyelitis: typically febrile and asymmetric
- Psychiatric illness
Infants
- Sepsis
- Meningitis
- Electrolyte imbalance
- Reye syndrome
- Congenital myopathy
- Werdnig-Hoffman disease
- Leigh disease
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
- For infants up to 1 year old, BabyBIG (BIG-IV) 50 mg/kg
- Antibiotics
- Unclear benefit, but often penicillin G or metronidazole are used for wound botulism
- Aminoglycosides and tetracyclines can worsen the paralysis of infant botulism, possibly by lysis of Clostridium botulinum in the gut
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