Botulism

Epidemiology

  • Occurs worldwide
  • Type A toxin: west of Rocky Mountains
  • Type B toxin: Eastern USA
  • Type E toxin (associated with fish products): Pacific Northwest/Alaska/Great Lakes area
  • Wound Botulism Outbreak (reported in JAMA, 1998): associated with black-tar heroin injection (usually due to skin-popping with associated SQ or IM infections)

Etiology

  • Clostridium botulinum
    • Anaerobic Gram positive, spore-forming rod
    • Found in soil and water
    • Botulinum Neurotoxin (types A through G) is the most potent bacterial toxin known
      • Toxin is inactivated by 100°C x 10 min (routine home cooking)
    • Spores are inactivated only by 120°C (steam or pressure cooking)

Physiology

Botulinum Neurotoxin

  • One of the most powerful known toxins: about one microgram is lethal to humans.
  • It acts by blocking nerve function and leads to respiratory and musculoskeletal paralysis.
  • In all cases illness is caused by the toxin made by Clostridium botulinum, not by the bacterium itself.
  • The pattern of damage occurs because the toxin affects nerves that are firing more often
  • In peripheral nervous system, toxin exhibits irreversible presynaptic inhibition (interference with calcium release) of Ach release at neuromuscular junction
    • Sprouting of new terminals -> cure

Pathogenesis by Clinical Syndrome

  • Food-Borne Botulism: contaminated food ingestion (especially anaerobically preserved home-canned foods, like vegetables, fruit, condiments/ less common with meats, fish)
    • Certain type of C. Botulinum with proteolytic activity can spoil food/ others leave food appearance unchanged
  • Wound Dotulism (rare): spores in wound -> germination into vegetative organisms -> toxin produced in wound
    • Reported with soil contamination of wounds/ IVDA/ post-C-section
    • May even occur when antibiotics were given to prevent wound infection
  • Infant Botulism: due to ingestion of spores -> germination into vegetative organism -> toxin production in intestine
    • Reported to occur with spore-contaminated honey (avoid feeding honey to infants <12 months old)
    • Resistance may occur with development of normal intestinal flora
  • Adult Infant Botulism: similar to mechanism in infant botulism, except cases occur in older children and adults

Diagnosis

  • CBC: normal
  • ESR: normal
  • LP: normal
  • PFT’s: restriction
    • Decreased VC (due to muscle weakness, de-creased lung compli-ance, and decreased CW compliance):
    • Decreased TLC, MVV
    • Increased RV (due to inability to overcome recoil of chest wall outward at volume less than FRC)
    • Decreased MIP/MEP
    • Decreased Compliance (due to chronically low volumes: microatelectasis/reduced surface tension/altered lung interstitial elastic fibers)
  • CXR
    • Aspiration Pneumonia: may occur in some cases
    • Low Lung Volumes:
  • EMG/NCV (normal NCV): repeated nerve stimulation -> incremental response (distinguishes Botulism from MG
  • Serum Assay for Botulinum Toxin (in mice): definitive (may be negative in infant and wound cases), but takes 24-86 hrs to complete
    • Detection in gastric fluid/stool is suggestive (intestinal carriage is rare)
  • Wound C/S: suggestive if positive
  • Tensilon Test: may be weakly positive

Clinical

  • Food-borne Botulism
    • Incubation: 18-36 hrs (range: hrs-several days)
    • Variable Symptoms: range from mild illness to death within 24 hrs
      • Symmetric (usually) Descending Paralysis:
        • Cranial Nerve Weakness (diplopia/dysarthria/dysphagia/dizziness/dry mouth/dry sore throat/ptosis/decreased gag/fixed or dilated pupils): seen in 50% of cases -> progresses to neck/extermities/thorax
        • Absence of Sensory Findings: distinguishes Botulism from GBS
        • Normal-Hyporeflexia:
        • Normal MS (usually): occasionally lethargic
      • Dyspnea (common)
      • N/V/Abdominal Pain/Ileus/Constipation: may precede or follow paralysis
      • Urinary Retention:
      • Absence of Fever:
  • Wound Botulism: rare
    • Clinically resembles food-borne Botulism: cranial nerve (especially CN-6) findings, mydriasis, ptosis, tongue weakness, UE weakness (75% of cases) are common
    • Incubation: 10 days (Range: 4-14 days) -> symptoms usually develop soon after the wound appears to be infected
    • Absence of GI Symptoms (usually)
    • Wound: may appear relatively benign
    • Fever (not usually seen in food-borne Botulism): when present, is usually due to wound infection by other bacteria
  • Infant Botulism (most common type): most cases in infants <6 months old/ variable symptoms (range: mild illness-sudden infant death)
  • Adult Infant Botulism (adult enteric infectious botulism/adult infectious botulism of unknown source):
    • Organisms and toxin may be found in stools for prolonged periods
    • May occur after surgery, with GI disease

Treatment

  • Ventilatory Support: indicated for cases with FVC <30% predicted
    • MIP: predicts need for vent support
  • Trivalent (type A/B/E) Equine Anti-Toxin: test for sensitivity to horse serum -> give 2 vials IV ASAP (may be repeated in 2-4 hrs)
    • Not beneficial in infant Botulism cases
    • Neutralizes circulating toxin in serum
  • Human Botulism Ig: experimental for infant cases
  • GI Decontamination: to purge GI tract of toxin
  • Antibiotics (to eliminate organism): unproven
    • PCN: high-dose
  • Wound Debridement: for wound cases
  • Guanidine: unproven (may be useful for ocular muscles)

Prognosis

  • 7.5% mortality currently
  • Type A disease is more severe/ higher mortality in cases >60 y/o
  • Residual decreased exercise tolerance and autonomic dysfunction (may persist for years after recovery even when PFT’s normalized): tachypnea/dyspnea/rapid shallow breathing/ decreased VO2max

References

  • Werner SB, Passaro D, McGee J, et al. Wound botulism in California, 1951-1998: recent epidemic in heroin injectors. Clin Infect Dis 2000; 31:1018-1024
  • Sandrock CE, Murin S. Clinical predictors of respiratory failure and long-term outcome in black tar heroin-associated wound botulism. Chest 2001; 120:562-566
  • Shapiro RL, Hatheway C, Swerdlow DL. Botulism in the United States: a clinical and epidemiologic review. Ann Intern Med 1998; 129:221-228
  • Passaro DJ, Werner SB, McGee J, et al. Wound botulism associated with black tar heroin among injecting drug users. JAMA 1998; 280:1479-1480