View source for Clostridium botulinum

==Background==

===History===

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

===Microbiology===

*Large [[Stain::Gram-positive]] [[Cellular respiration::anaerobic]] [[Shape::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
* [[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 in children|Sepsis]]
* [[Meningitis in children|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 [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
*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
**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

==Further Reading==

*[https://www.canada.ca/en/health-canada/services/food-nutrition/legislation-guidelines/guidance-documents/botulism-guide-healthcare-professionals-2012.html Botulism Reference Service for Canada]
{{DISPLAYTITLE:''Clostridium botulinum''}}
[[Category:Gram-positive bacilli]]