Botulism

Clostridium botulinum
1. Gram Positive rod
2. Anaerobic
3. Spore forming Bacteria

Botulinum Toxin is heat labile (inactivated at high Temperature)
Botulinum Toxin has 7 different serotypes
1. Botulinum Toxins A, B and E are pathogenic in humans
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
Botulinum Toxin binds to presynaptic nerve terminal
1. Neuromuscular terminal
2. Cholinergic autonomic site
Receptor binding is irreversible
1. Receptors are replaced however over time
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
Botulinum Toxin medical uses (Botox)
1. Treatment for oculomotor disorders
  1. Strabismus
  2. Blepharospasm
2. Treatment for Dystonias
  1. Torticollis
  2. Hemifacial spasm

Not spread from person to person
Aerosol spread as warfare Biological Toxin
1. Incubation: 1 to 5 days
Wound Infection
1. Associated with Trauma and IV Drug Abuse (e.g. Heroin use)
2. Course differs from Foodborne Illness
  1. Longer Incubation Period: 4 to 14 days
  2. Minimal gastrointestinal symptoms
Foodborne Illness (ingestion of Bacteria or preformed toxin)
1. Incubation: 12-72 hours (median 24 hours)
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. Spores germinate in Stomach, grow and produce toxin (incubates over weeks)
  2. Infants (See Infant Botulism)
  3. Altered Gastrointestinal Tract (e.g. Gastric Bypass surgery, Proton Pump Inhibitors)
4. Improperly preserved pickled or canned foods (e.g. tomatoes)
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

Sudden onset symptoms
1. Symptoms follow ingestion or exposure by 12-72 hours, or inhalation by 12-80 hours
2. No associated fever
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%)
Anticholinergic Symptoms
1. Dry Mouth
2. Decreased tears
3. Blurred Vision
4. Dizziness
5. Urinary Retention
6. Abdominal Pain or cramping (ileus)
7. Constipation
Other symptoms
1. Nausea or Vomiting (56%)
2. Headache
3. Fever (Wound Botulism)

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
Later signs
1. Symmetrical descending Flaccid Paralysis
2. Hyporeflexia
3. Incoordination
4. Irregular respirations to Respiratory Failure
Distinguishing features from other causes
1. Mentation clear
2. Patient is usually afebrile
3. Neurologic changes are bilateral, descending and motor (not sensory)

Precautions
1. Labs are sent, but typically delayed, and diagnosis and management is started empirically
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
Test suspected food source for toxin
Classic testing (historical)
1. Lab mice die after ingesting suspected food source
2. Illness reversed by type specific antitoxin
Other testing to consider
1. Lumbar Puncture (evaluate differential diagnosis)

Contact Centers for Disease Control for suspected cases
Supportive care
Ventilator support often required
1. Follow Vital Capacity on serial Pulmonary Function Testing
Gastric Decontamination if recent ingestion in foodborne Botulism
1. Consider even in delayed presentation
2. If no ileus, may give Laxatives and enemas
Surgical Wound Debridement in Wound Botulism
1. Indicated even in benign appearing wounds
Antibiotic precautions
1. Antibiotics are only recommended in Wound Botulism
2. First-Line
  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
Antitoxin
1. Indicated in both food-borne and Wound Botulism in adults and children over age 1 year
2. See below
Other measures
1. Tetanus Toxoid booster

May shorten disease course if used early
Does not reverse paralysis, but stops progression
Indicated in both food-borne and Wound Botulism in adults and children over age 1 year
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
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

Avoid honey in infants under 1 year of age
1. See Infant Botulism
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