Botulism

Botulism is a life-threatening condition of neuroparalysis that is caused by a potent neurotoxin produced by the spore-forming bacteria Clostridium botulinum. Botulinum toxin blocks the release of acetylcholine from presynaptic axon terminals into the synaptic cleft, irreversibly inhibiting neurotransmission. There are three main types of botulism: foodborne botulism, infant botulism, and wound botulism. Foodborne botulism results from the ingestion of a food product already contaminated with botulinum toxin (typically home-canned foods). Infant botulism represents the majority of cases and is caused by the ingestion of spores (commonly from honey or soil), which then germinate and produce neurotoxins within the intestinal tract. In wound botulism, which typically occurs in IV drug users, C. botulinum spores germinate in contaminated wounds. All three types present with neuroparalysis, while foodborne and infant botulism are sometimes also associated with gastrointestinal symptoms (e.g., discomfort, nausea, constipation). Clinical suspicion of botulism may be confirmed by quickly identifying the toxin in bodily fluids (e.g., serum, vomit, gastric acid, stool) and/or food. Foodborne botulism is best treated with an antitoxin and medically-induced bowel emptying. Treatment of infant botulism consists of the administration of botulism immune globulin. Wound botulism requires surgical debridement in addition to antitoxin administration.

Pathogen

• Clostridium botulinum
  • Gram-positive rod
  • Spore-forming
  • Obligate anaerobe
  • Produces heat-labile neurotoxin

Pathophysiology

• Botulinum toxin: protease that cleaves SNARE proteins and prevents fusion of transmitter-containing vesicles with the presynaptic membrane → inhibition of acetylcholine release from the presynaptic axon terminals ^[1]

Clinical features

• Neurological symptoms
  • Descending paralysis
    • Peripheral flaccid muscle paralysis that descends caudally (typically begins in frequently used muscles)
    • Pupils: accommodation paralysis, mydriasis, diplopia
    • Pharynx: dysarthria, dysphagia
  • Autonomic nervous system: xerostomia
  • Infantile hypotonia (see “Infant botulism” below)
• Gastrointestinal symptoms
  • Gastrointestinal discomfort, nausea, and vomiting, later followed by constipation
  • Only present in 30% of cases of foodborne botulism; absent in wound botulism
  • Constipation is often the first symptom of infant botulism.

4 D's of botulism: Dysarthria, Diplopia, Dysphagia, and Dyspnea.

Diagnostics

• Rapidly identify botulinum toxin in samples from serum, vomit, gastric acid, stool, or suspicious foods.
• Pathological EMG findings in affected muscles support the diagnosis. ^[2]

Treatment

• Secure airways.
• See the corresponding sections for specific treatment measures.

Therapeutic/cosmetic botulinum toxin use

• Local injection of botulinum toxin A (Botox) can be used to treat various conditions, including:
  • Muscle spasms
  • Focal dystonia
  • Hyperhidrosis
• Also used to reduce facial wrinkles

References:^[3][4]

• Etiology
  • Ingestion of preformed botulinum toxin via contaminated foods
    • The anaerobic spores survive in poorly pasteurized canned foods (e.g., vegetables with soil contact, meat, home-fermented tofu) ^[5]
    • Germination of the spores produces dangerous toxins (botulinum toxins = enterotoxins A-F) and gas → bulging cans
• Incubation period: 12–36 hours
• Specific treatment
  • Horse-derived heptavalent botulism antitoxin
  • Eradication of toxin through bowel emptying (induced by medication)
• Prevention
  • Sterilize food through autoclaving.
  • Food should be boiled twice before being canned to kill spores that may have germinated after the first round of boiling.

References:^[4]

• Etiology: ingestion of spores
  • Spores may be present in honey, juice, and contaminated soil.
  • Germination of the spores in intestinal tract → synthesis of botulinum toxin
• Incubation period: days to 4 weeks
• Clinical features: Infants may present with infantile hypotonia
  • Ptosis
  • Floppy movements
  • General weakness
  • Poor feeding (weak sucking)
• Differential diagnosis:

• Specific treatment: IV human botulism immune globulin (BIG-IV)
• Prevention: Avoid exposure of < 1-year-old infants to potentially contaminated material (e.g., raw honey, dust, soil).

A stool sample should be obtained for culture and toxin testing, because serum studies in infants often yield false negative results. ^[7]

Treatment should not be delayed if there is a high clinical suspicion of infant botulism. ^[8]

References:^[4]

• Etiology: germinating spores in contaminated wounds (most common among IV drug users)
• Incubation period: 10 days (ranges from 4–14 days)
• Specific treatment
  • Administration of horse-derived botulism antitoxin
  • Surgical debridement
  • Antibiotics are only used to treat secondary bacterial infections.
• Prevention
  • Government-sponsored sterile needle and syringe programs
  • Avoidance of IV drug use
  • Seek medical attention for infected wounds.

• Guillain-Barré syndrome
• Myasthenia gravis
• Lambert-Eaton syndrome
• Tick paralysis

References:^[2]

The differential diagnoses listed here are not exhaustive.