Botulism

Aka: Botulism, Clostridium botulinum, C. botulinum, Botulinum Toxin, Wound Botulism, Foodborne Botulism

advertisement

II. Epidemiology

  1. Mean Incidence: 110 per year in U.S.
  2. Foodborne Botulism accounts for 25% of cases
  3. No gender predisposition
  4. Age
    1. Infant Botulism is most common (accounts for 70% of cases)
      1. Intestinal Botulism (spore ingestion and intestinal colonization)
    2. Child and Adult mean age: 46 years (range 3 to 78 years old)
      1. Primarily Foodborne Botulism from preformed Toxin Ingestion (esp. improper canning)
  5. U.S. Regional concentration of 50% of cases in western states
    1. California
    2. Washington
    3. Colorado
    4. Oregon
    5. Alaska (esp. native Alaskan)
  6. References
    1. Botulism: Epidemiological Overview for Clinicians (CDC, accessed 10/24/2024)
      1. https://www.emergency.cdc.gov/agent/botulism/clinicians/epidemiology.asp

III. Pathophysiology: Toxin mediated disease

  1. Source: Clostridium botulinum
    1. Gram Positive rod
    2. Anaerobic
    3. Spore forming Bacteria
  2. Botulinum Toxin is heat labile
    1. Toxin is inactivated at high Temperature (boiled water for 5 minutes at 85 C, or 185 F)
    2. Clostridium botulinum spores are, in contrast, heat resistant
  3. Botulinum Toxin has 7 different serotypes
    1. Botulinum Toxins A, B and E are pathogenic in humans
  4. Botulinum Toxin is typically cleaved into active heavy chains and light chains
    1. Heavy chains irreversibly bind Acetylcholine containing Neurons
    2. Light chains interfere with Acetylcholine exocytosis
  5. Botulinum Toxin binds to presynaptic nerve terminal
    1. Neuromuscular terminal
    2. Cholinergic autonomic site
  6. Receptor binding is irreversible
    1. Receptors are replaced however over time
  7. Affects Neuromuscular Junction only
    1. Prevents presynaptic Acetylcholine release
    2. Results in bulbar palsy (CN 9-12), Autonomic Dysfunction and skeletal Muscle Weakness
    3. Does not cause sensory deficit or pain
  8. Botulinum Toxin medical uses (Botox)
    1. Treatment for oculomotor disorders
      1. Strabismus
      2. Blepharospasm
    2. Treatment for Dystonias
      1. Torticollis
      2. Hemifacial spasm

IV. Transmission

  1. Not spread from person to person
  2. Aerosol spread as warfare Biological Toxin
    1. See Biological Weapon
    2. Incubation: 1 to 5 days
  3. Wound Infection
    1. Epidemiology
      1. More common in adults, esp. women (mean 41 years old, range 23 to 58 years old)
      2. More common in western United States (esp. California)
    2. Causes
      1. Trauma with a wound contaminated with soil has historically caused Wound Botulism
      2. Substance Abuse related Botulism has become more common
        1. IV Drug Abuse (e.g. Heroin use)
        2. Chronic Cocaine Abuse may result in nasal or sinus Wound Botulism
    3. Clostridium botulinum spores germinate and colonize the wound
      1. Leads to local production of Botulinum Toxin that is absorbed systemically
      2. Incubation Period: 10 days
    4. Course differs from Foodborne Illness
      1. Longer Incubation Period: 4 to 14 days
      2. Minimal gastrointestinal symptoms
  4. Foodborne Illness (ingestion of Bacteria or preformed toxin)
    1. Incubation: 12-72 hours (median 24 hours, but may be up to 2 weeks)
    2. Toxin types A and B in the United States
      1. West of the Mississippi: Type A toxins
      2. East of the Mississippi: Type B toxins
    3. Ingested spores (esp. from honey) may also cause Botulism in high risk patients
      1. Primary cause of Infantile Botulism (Intestinal Botulism)
      2. May also occur with altered GI Tract (e.g. Gastric Bypass surgery, Proton Pump Inhibitors)
      3. Spores germinate in Stomach, colonize and produce toxin in colon (incubates over weeks)
    4. Improperly preserved pickled or canned foods (e.g. tomatoes)
      1. Most common cause of adult Botulism
    5. In-ground vegetables (potatoes, onions, Garlic)
      1. Potatoes baked in aluminum foil
    6. Meat products in Europe (Toxin Type B)
    7. Vegetable products in China (Toxin Type A)
    8. Preserved fish (Toxin type E)
      1. Found in Alaska, Japan, Russia, Scandinavia

V. Precautions

  1. Keep Botulism in the differential diagnosis of weakness and Anticholinergic Symptoms despite its rarity
  2. Missed diagnosis of Botulism or Infant Botulism are associated with high morbidity and mortality

VI. Symptoms

  1. Sudden onset symptoms
    1. Symptoms follow ingestion or exposure by 12-72 hours, or inhalation by 12-80 hours
    2. Dysphagia, Diplopia and Dry Mouth are among the most common presenting complaints
    3. No associated fever
  2. Descending symmetric paralysis
    1. Early changes: Cranial Nerve palsy occurs first
      1. Diplopia with Blurred Vision (90%)
      2. Dysphagia (76%)
      3. Dysarthria
      4. Dysphonia (55%)
    2. Later changes
      1. Progressive, bilateral descending Flaccid Paralysis
      2. Generalized Weakness (58%)
  3. Anticholinergic Symptoms
    1. Dry Mouth
    2. Decreased tears
    3. Blurred Vision
    4. Dizziness (Postural Hypotension)
    5. Urinary Retention
    6. Constipation with Abdominal Pain or cramping (Paralytic Ileus)
  4. Other symptoms
    1. Nausea or Vomiting (56%)
    2. Headache
    3. Fever (Wound Botulism)

VII. Signs

  1. Early signs
    1. Bilateral Cranial Nerve 6 (Abducens Nerve) paralysis
    2. Ptosis
    3. Mydriasis with sluggish pupil reaction
    4. Nystagmus
    5. Diminished Gag Reflex
    6. Swollen Tongue
  2. Later signs
    1. Symmetrical descending Flaccid Paralysis
    2. Hyporeflexia
    3. Incoordination
    4. Irregular respirations to Respiratory Failure
  3. Distinguishing features from other causes
    1. Mentation clear
    2. Patient is usually afebrile
    3. Neurologic changes are bilateral, descending and motor (not sensory)

VIII. Differential Diagnosis

  1. See Floppy Infant
  2. Myasthenia Gravis
  3. Guillain Barre Syndrome
  4. Eaton-Lambert Syndrome
  5. Trichinosis
  6. Cerebrovascular Accident
  7. Electrolyte disturbance
    1. Hypocalcemia
    2. Hypermagnesemia
  8. Tick Paralysis or Tick Toxicosis (ascending paralysis)
  9. Other toxin exposure
    1. Organophosphate Poisoning
    2. Atropine Poisoning
    3. Shellfish Poisoning or puffer fish Poisoning

IX. Labs

  1. Precautions
    1. Labs are sent, but typically delayed, and diagnosis and management is started empirically
  2. Patient sources
    1. Serum for Botulinum Toxin (positive in 1/3 of cases)
    2. Gastric contents for Botulinum Toxin
    3. Stool for Botulinum Toxin (positive in 1/3 of cases)
    4. Stool for culture (positive in 60% of cases)
    5. Wound culture (if present) for organisms
  3. Test suspected food source for toxin
  4. Classic testing (historical)
    1. Lab mice die after ingesting suspected food source
    2. Illness reversed by type specific antitoxin
  5. Other testing to consider
    1. Lumbar Puncture (evaluate differential diagnosis)

X. Diagnostics

  1. Negative Inspiratory Force
  2. Electromyogram (EMG)
    1. Protocol
      1. Initial supramaximal single nerve stimulation
      2. Repetitive stimulation at 40 to 50 hz
    2. Differentiates from other neuromuscular conditions
      1. Single maximal stimulus: Diminished Action Potentials
      2. Repetitive stimuli: Facilitation of Action Potentials
      3. Hypermagnesemia may give similar EMG
  3. Other testing
    1. Edrophonium Testing

XI. Management: General

  1. Contact Centers for Disease Control for suspected cases
  2. Supportive care
  3. Ventilator support often required
    1. Admit to Intensive Care
    2. Follow Vital Capacity or Negative Inspiratory Flow on serial Pulmonary Function Testing
    3. Ventilator support is often needed for weeks until Botulinum Toxin affects subside
  4. Gastric Decontamination if recent ingestion in Foodborne Botulism
    1. Consider even in delayed presentation
    2. If no ileus, may give Laxatives and enemas
  5. Surgical Wound Debridement (source control) in Wound Botulism
    1. Indicated even in benign appearing wounds
  6. Antibiotic precautions
    1. Indications
      1. Antibiotics are only recommended in Wound Botulism
      2. However, even in isolated Wound Botulism, Antibiotic use is not typically recommended
        1. No evidence that Antibiotics speed paralysis recovery
    2. First-Line Antibiotics
      1. Penicillin G 3 million units IV q4 hours
    3. Alternative (if Penicillin allergic)
      1. Metronidazole (Flagyl) 500 mg IV every 8 hours
    4. Avoid Aminoglycosides and Clindamycin
  7. Antitoxin
    1. Indicated in both food-borne and Wound Botulism in adults and children over age 1 year
    2. See below
  8. Other measures
    1. Tetanus Toxoid booster

XII. Management: Antitoxin (from CDC)

  1. May shorten disease course if used early
  2. Does not reverse paralysis, but stops progression
  3. Indicated in both food-borne and Wound Botulism in adults and children over age 1 year
  4. Depreciated Heptavalent equine antitoxin (preferred)
    1. Available from CDC and from state department
    2. Covers types A, B, C, D, E, F, G
    3. Reduced risk of Serum Sickness
    4. Effective if given prior to or early in symptoms
  5. Trivalent equine antitoxin (replaced by heptavalent Vaccine)
    1. Risk of Serum Sickness and Anaphylaxis
    2. Skin Test for Horse Serum Sensitivity first
    3. Do not use in Infant Botulism

XIII. Prevention

  1. Avoid honey in infants under 1 year of age
    1. See Infant Botulism
  2. DOD Pentavalent toxoid Vaccine
    1. Covers types A, B, C, D, E
    2. Dose: 0.5 SC at 0, 2, and 12 weeks, then annually
    3. Protective Antibody >90% after 1 year

XIV. Prognosis

  1. Untreated: Mortality 60% from Respiratory Failure
  2. Treated with intensive support: Mortality <7%

XV. References

  1. (2019) Sanford Guide, acccessed 6/5/2019
  2. Bartlett in Goldman (2000) Cecil Medicine, p. 1673-4
  3. Della-Giustina (2024) Crit Dec Emerg Med 38(10): 27-34
  4. Schechter in Behrman (2000) Nelson Pediatrics, p. 875-8
  5. Seeyave (2015) Crit Dec Emerg Med 29(5): 13-21
  6. Shearer in Marx (2002) Rosen's Emergency Med, p. 1525
  7. Sun and Tomaszewski (2017) Crit Dec Emerg Med 31(6): 24
  8. Arnon (2001) JAMA 285:1059-70 [PubMed]
  9. Rathjen (2021) Am Fam Physician 104(4): 376-85 [PubMed]
  10. Rao (2021) MMWR Recomm Rep 70(2):1-30 +PMID: 33956777 [PubMed]

Images: Related links to external sites (from Bing)

These images are a random sampling from a Bing search on the term "Botulism." Click on the image (or right click) to open the source website in a new browser window. Search Bing for all related images

Related Studies

Related Topics in Neurology

advertisement