Botulism

1
Botulism

• Botulinim toxin

2
History

• Neurologic disease from botulinum toxin
• Most lethal substance known

3
History

• Neurologic disease from botulinum toxin
• Most lethal substance known
• History as bioweapon

4
History

• Neurologic disease from botulinum toxin
• Most lethal substance known
• History as bioweapon
• Japanese in WWII (Unit 731)

5
History

• Neurologic disease from botulinum toxin
• Most lethal substance known
• History as bioweapon
• Japanese in WWII (Unit 731)
• Former US and USSR programs

6
History

• Neurologic disease from botulinum toxin
• Most lethal substance known
• History as bioweapon
• Japanese in WWII (Unit 731)
• Former US and USSR programs
• Iraqi deployed weapons

7
History

• Neurologic disease from botulinum toxin
• Most lethal substance known
• History as bioweapon
• Japanese in WWII (Unit 731)
• Former US and USSR programs
• Iraqi deployed weapons
• Japanese cult in early 1990s

8
Epidemiology

• Found worldwide
• U.S. incidence
• 100 cases annually (1/4 foodborne)

9
Epidemiology

• Mechanisms of intoxication
• No person-to-person transmission

10
Epidemiology

• Mechanisms of intoxication
• No person-to-person transmission
• Toxin ingestion (foodborne)

11
Epidemiology

• Mechanisms of intoxication
• No person-to-person transmission
• Toxin ingestion (foodborne)
• Toxin generated from wound infection (wound)

12
Epidemiology

• Mechanisms of intoxication
• No person-to-person transmission
• Toxin ingestion (foodborne)
• Toxin generated from wound infection (wound)
• Toxin from intestinal colonization (infant,
  intestinal)

13
Epidemiology

• Mechanisms of intoxication
• No person-to-person transmission
• Toxin ingestion (foodborne)
• Toxin generated from wound infection (wound)
• Toxin from intestinal colonization (infant,
  intestinal)
• Toxin inhalation (aerosol release)

14
Epidemiology

• Mechanisms of intoxication
• No person-to-person transmission
• Toxin ingestion (foodborne)
• Toxin generated from wound infection (wound)
• Toxin from intestinal colonization (infant,
  intestinal)
• Toxin inhalation (aerosol release)
• Mortality lt10

15
Microbiology

• Clostridium botulinum

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Microbiology

• Clostridium botulinum
• Large, anaerobic Gram positive bacillus
• Spore-forming

17
Microbiology

• Clostridium botulinum
• Large, anaerobic Gram positive bacillus
• Spore-forming
• Rarely infects humans

18
Microbiology

• Clostridium botulinum
• Large, anaerobic Gram positive bacillus
• Spore-forming
• Rarely infects humans
• Produces potent neurotoxin
• 7 types (A-G)

19
Microbiology

• Clostridium botulinum
• Large, anaerobic Gram positive bacillus
• Spore-forming
• Rarely infects humans
• Produces potent neurotoxin
• 7 types (A-G)
• Types A, E, B most common in U.S.

20
Microbiology

• Clostridium botulinum
• Large, anaerobic Gram positive bacillus
• Spore-forming
• Rarely infects humans
• Produces potent neurotoxin
• 7 types (A-G)
• Types A, E, B most common in U.S.
• Same general mechanism

21
Arnon S, et al. JAMA. 20012851059-70.
22
Clinical Features

• Incubation 12-72 hours
• Probably faster if inhalational exposure

23
Clinical Features

• Classic syndrome

24
Clinical Features

• Classic syndrome
• Acute symmetric cranial nerve palsies

25
Clinical Features

• Classic syndrome
• Acute symmetric cranial nerve palsies
• Blurry vision, ptosis, dysphasia

26
Clinical Features

• Classic syndrome
• Acute symmetric cranial nerve palsies
• Blurry vision, ptosis, dysphasia
• Descending flaccid paralysis

27
Clinical Features

• Classic syndrome
• Acute symmetric cranial nerve palsies
• Blurry vision, ptosis, dysphasia
• Descending flaccid paralysis
• Complete skeletal muscle paralysis

28
Clinical Features

• Classic syndrome
• Acute symmetric cranial nerve palsies
• Blurry vision, ptosis, dysphasia
• Descending flaccid paralysis
• Complete skeletal muscle paralysis
• Respiratory (ventilatory) failure

29
Clinical Features

• Classic syndrome
• Acute symmetric cranial nerve palsies
• Blurry vision, ptosis, dysphasia
• Descending flaccid paralysis
• Complete skeletal muscle paralysis
• Respiratory (ventilatory) failure
• Autonomic urinary retention, orthostasis

30
Clinical Features

• Classic syndrome
• Acute symmetric cranial nerve palsies
• Blurry vision, ptosis, dysphasia
• Descending flaccid paralysis
• Complete skeletal muscle paralysis
• Respiratory (ventilatory) failure
• Autonomic urinary retention, orthostasis
• Afebrile, normal mentation

31
Clinical Features

• Differential Diagnosis

32
Clinical Features

• Differential Diagnosis
• Myasthenia Gravis anticholinesterase response

33
Clinical Features

• Differential Diagnosis
• Myasthenia Gravis anticholinesterase response
• Guillaine-Barre Syndrome - ascending

34
Clinical Features

• Differential Diagnosis
• Myasthenia Gravis anticholinesterase response
• Guillaine-Barre Syndrome - ascending
• Stroke asymmetric, abnormal brain imaging

35
Clinical Features

• Differential Diagnosis
• Myasthenia Gravis anticholinesterase response
• Guillaine-Barre Syndrome - ascending
• Stroke asymmetric, abnormal brain imaging
• Tick paralysis ascending, presence of tick

36
Clinical Features

• Differential Diagnosis
• Myasthenia Gravis anticholinesterase response
• Guillaine-Barre Syndrome - ascending
• Stroke asymmetric, abnormal brain imaging
• Tick paralysis ascending, presence of tick
• Poliomyelitis asymmetric, preceding viral
  illness

37
Clinical Features

• Other features
• Foodborne nausea, diarrhea, dry mouth

38
Clinical Features

• Other features
• Foodborne nausea, diarrhea, dry mouth
• Infant - constipation

39
Diagnosis

• High index of suspicion necessary
• No readily available rapid confirmatory tests

40
Diagnosis

• High index of suspicion necessary
• No readily available rapid confirmatory tests
• Clinical diagnosis

41
Diagnosis

• Laboratory confirmation
• Specimens blood, stool
• At reference labs
• Mouse bioassay
• ELISA

42
Treatment

• Supportive care

43
Treatment

• Supportive care
• Mechanical ventilation, nutritional support
• Prevention of secondary infections

44
Treatment

• Supportive care
• Mechanical ventilation, nutritional support
• Prevention of secondary infections
• Avoid aminoglycosides, clindamycin

45
Treatment

• Passive immunization (antitoxin)

46
Treatment

• Passive immunization (antitoxin)
• Halts paralysis, doesnt reverse

47
Treatment

• Passive immunization (antitoxin)
• Halts paralysis, doesnt reverse
• Must be given ASAP

48
Treatment

• Passive immunization (antitoxin)
• Halts paralysis, doesnt reverse
• Must be given ASAP
• Equine antitoxin (Types A, B and E toxins)
• Serum sickness (9), anaphylaxis (2)

49
Treatment

• Passive immunization (antitoxin)
• Halts paralysis, doesnt reverse
• Must be given ASAP
• Equine antitoxin (Types A, B and E toxins)
• Serum sickness (9), anaphylaxis (2)
• Heptavalent antitoxin (Types A-G)
• Investigational, less hypersensitivity

50
Post-Exposure Prophylaxis

• Antitoxin not recommended
• High incidence hypersensitivity
• Limited supplies

51
Post-Exposure Prophylaxis

• Antitoxin not recommended
• High incidence hypersensitivity
• Limited supplies
• Clinical monitoring
• Extreme vigilance for symptoms
• At least 72 hours
• Antitoxin immediately for any symptoms

52
Vaccination

• Botulinum toxoid
• No role for post-exposure prophylaxis
• Immunity develops over months

53
Vaccination

• Botulinum toxoid
• No role for post-exposure prophylaxis
• Immunity develops over months
• Excellent efficacy
• Not tested versus aerosol exposure
• Few adverse effects

54
Infection Control

• No person-to-person transmission
• Patient handling
• Standard precautions
• Clinical specimens
• Standard precautions