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Botulism
Botulism
Infectious Diseases, AIDS & Clinical
Infectious Diseases, AIDS & Clinical
Immunology Research Center Tbilisi
Immunology Research Center Tbilisi
Definition
Definition
 Botulism is a paralytic disease
caused by potent protein neurotoxins
elaborated by clostridium botulinum.
 Botulism is characterized by
symmetrical, descending, flaccid
paralysis of motor and autonomic
nerves usually beginning with cranial
nerves
Etiologic Agent
Etiologic Agent
 C. botulinum is an anaerobic gram-
positive organism that form spors;
 C. botulinum
C. botulinum is in soil and marine
environments throughout the world.
 C. botulinum
C. botulinum elaborates the most
potent bacterial toxin.
– Spores
Spores
 Ubiquitous
Ubiquitous
 Resistant to heat, light, drying and radiation
Resistant to heat, light, drying and radiation
 Spores may survive boiling for several hours
Spores may survive boiling for several hours
at 100
at 100 o
o
C
C
 Specific conditions for germination
Specific conditions for germination
– Anaerobic conditions
Anaerobic conditions
– Warmth (10-50
Warmth (10-50o
o
C)
C)
– Mild alkalinity
Mild alkalinity
Neurotoxins
Neurotoxins
 Seven different types: A through G
Seven different types: A through G
– Different types affect different species
Different types affect different species
– All cause flaccid paralysis
All cause flaccid paralysis
– Only a few nanograms can cause illness
Only a few nanograms can cause illness
– Binds neuromuscular junctions
Binds neuromuscular junctions
 Toxin: Destroyed by boiling
Toxin: Destroyed by boiling
 Spores: Higher temperatures to be
Spores: Higher temperatures to be
inactivated
inactivated
Neurotoxins
Neurotoxins
– toxins A, B, E and F cause illness in humans
toxins A, B, E and F cause illness in humans
– toxins C and D cause illness in birds and
toxins C and D cause illness in birds and
mammals
mammals
– toxin G has been associated with sudden death,
toxin G has been associated with sudden death,
but not with neuroparalytic illness, in a few
but not with neuroparalytic illness, in a few
patients in Switzerland.
patients in Switzerland.
– Toxin type A produces the most severe
Toxin type A produces the most severe
syndrome, with the greatest proportion of
syndrome, with the greatest proportion of
patients requiring mechanical ventilation. Toxin
patients requiring mechanical ventilation. Toxin
type B appears to cause milder disease than
type B appears to cause milder disease than
type A.
type A.
Neurotoxins
Neurotoxins
Neurotoxin A B C D E F G
Human X X X X
Horses X X
Cattle X X X
Sheep X
Dogs X X
Avian X X
Mink & Ferret X X X
Epidemiology
Epidemiology
 Ingestion
Ingestion
– Organism
Organism
– Spores
Spores
– Neurotoxin
Neurotoxin
 Wound contamination
Wound contamination
 Inhalation
Inhalation
Epidemiology
Epidemiology
 Foodborne botulism
Foodborne botulism
– caused by eating foods that contain
caused by eating foods that contain
botulism toxin
botulism toxin
 Intestinal botulism
Intestinal botulism (infant and child/adult)
(infant and child/adult)
– caused by ingesting spores of the bacteria
caused by ingesting spores of the bacteria
which germinate and produce toxin in the
which germinate and produce toxin in the
intestines.
intestines.
 Wound botulism
Wound botulism
– C. botulinum spores germinate in the
C. botulinum spores germinate in the
wound.
wound.
Epidemiology
Epidemiology
 The highest incidence rate is reported from the
The highest incidence rate is reported from the
Republic of Georgia and Armenia, where illness is
Republic of Georgia and Armenia, where illness is
associated with risky home-canning practices.
associated with risky home-canning practices.
 In the United States during 1990–2000, the median
In the United States during 1990–2000, the median
number of foodborne cases of botulism per year
number of foodborne cases of botulism per year
was 23 (range, 17–43).
was 23 (range, 17–43).
 Since the early1990s, cases in the United States
Since the early1990s, cases in the United States
have occurred almost exclusively in injection drug
have occurred almost exclusively in injection drug
users.
users.
Pathogenesis
Pathogenesis
 Toxin enters bloodstream from mucosal surface or
Toxin enters bloodstream from mucosal surface or
wound
wound
 Binds to peripheral cholinergic nerve endings
Binds to peripheral cholinergic nerve endings
 Inhibits release of acetylcholine, preventing
Inhibits release of acetylcholine, preventing
muscles from contracting
muscles from contracting
 Symmetrical, descending paralysis occurs
Symmetrical, descending paralysis occurs
beginning with cranial nerves and progressing
beginning with cranial nerves and progressing
downward
downward
 Can result from airway obstruction or paralysis of
Can result from airway obstruction or paralysis of
respiratory muscles
respiratory muscles
 Secondary complications related to prolonged
Secondary complications related to prolonged
ventilatory support and intensive care
ventilatory support and intensive care
Clinical Manifestations
Clinical Manifestations
Food-borne botulism
Food-borne botulism
 Incubation period
Incubation period -
- 18-36 h (depending
18-36 h (depending
on toxin dose can range from a few hours to
on toxin dose can range from a few hours to
several days).
several days).
 Home-canned goods (foodborne)
Home-canned goods (foodborne)
– particularly low-acid foods such as
particularly low-acid foods such as
asparagus, beets, and corn
asparagus, beets, and corn
 Nausea, vomiting, diarrhea
Nausea, vomiting, diarrhea
 Diplopia, dysarthria, dysphonia,
Diplopia, dysarthria, dysphonia,
dysphagia
dysphagia
 Descending weakness or paralysis
Descending weakness or paralysis
– Shoulders to arms to thighs to calves
Shoulders to arms to thighs to calves
 Symmetrical flaccid paralysis
Symmetrical flaccid paralysis
 No fever
No fever
 Respiratory muscle paralysis
Respiratory muscle paralysis
Wound botulism
Wound botulism
 Incubation period –
Incubation period – 10 days.
10 days.
 Gastrointestinal symptoms are lacking
Gastrointestinal symptoms are lacking
 Wound botulism has been documented:
Wound botulism has been documented:
 After traumatic injury involving contamination with
After traumatic injury involving contamination with
soil;
soil;
 After cesarean delivery
After cesarean delivery
 After antibiotics have been given to prevent wound
After antibiotics have been given to prevent wound
infection.
infection.
 (When present, fever is probably attributable to
(When present, fever is probably attributable to
concurrent infection with other bacteria).
concurrent infection with other bacteria).
Intestinal (infant)
Intestinal (infant)
botulism
botulism
 May be one cause of sudden infant death.
May be one cause of sudden infant death.
 Honey can contain
Honey can contain C. botulinum
C. botulinum spores
spores
– not recommended for infants <12 months old
not recommended for infants <12 months old
 Constipation
Constipation
 Lethargy
Lethargy
 Poor feeding
Poor feeding
 Weak cry
Weak cry
 Bulbar palsies
Bulbar palsies
 Failure to thrive
Failure to thrive
Diagnosis
Diagnosis
 A diagnosis of botulism must be
A diagnosis of botulism must be
considered in patients with symmetric
considered in patients with symmetric
descending paralysis who are afebrile
descending paralysis who are afebrile
and mentally intact.
and mentally intact.
A 14-year-old with botulism. Note the weakness of his
A 14-year-old with botulism. Note the weakness of his
eye muscles and the drooping eyelids in the image to
eye muscles and the drooping eyelids in the image to
the left, and the large and non moving pupils in the
the left, and the large and non moving pupils in the
right image.
right image.
Laboratory diagnosis
Laboratory diagnosis
 Toxin in serum, stool, gastric aspirate,
Toxin in serum, stool, gastric aspirate,
suspected food
suspected food
 Culture of stool or gastric aspirate
Culture of stool or gastric aspirate
– Takes 5-7 days
Takes 5-7 days
 Electromyography also diagnostic
Electromyography also diagnostic
 Mouse neutralization test
Mouse neutralization test
– Results in 48 hours
Results in 48 hours
Laboratory diagnosis
Laboratory diagnosis
Botulinum toxin can be detected by a
Botulinum toxin can be detected by a
variety of techniques, including:
variety of techniques, including:
Enzyme-linked immunosorbent assays
Enzyme-linked immunosorbent assays
(ELISAs);
(ELISAs);
Electrochemiluminescent (ECL) tests
Electrochemiluminescent (ECL) tests
Botulism Differential
Botulism Differential
Diagnoses
Diagnoses
 Guillain-Barré syndrome
Guillain-Barré syndrome
 Myasthenia gravis
Myasthenia gravis
 Stroke
Stroke
 Tick paralysis
Tick paralysis
 Lambert-Eaton syndrome
Lambert-Eaton syndrome
 Psychiatric illness
Psychiatric illness
 Poliomyelitis
Poliomyelitis
 Diabetic Complications
Diabetic Complications
 Drug intoxication
Drug intoxication
 CNS infection
CNS infection
 Overexertion
Overexertion
Treatment
Treatment
 Persons of all ages (including infants) in whom
Persons of all ages (including infants) in whom
botulism is suspected should be hospitalized
botulism is suspected should be hospitalized
immediately in an intensive care setting, with
immediately in an intensive care setting, with
frequent monitoring of vital capacity and
frequent monitoring of vital capacity and
mechanical ventilation if required.
mechanical ventilation if required.
 In adults, botulism can be treated by passive
In adults, botulism can be treated by passive
immunization with a horse-derived antitoxin,
immunization with a horse-derived antitoxin,
which blocks the action of the toxin circulating
which blocks the action of the toxin circulating
in the blood
in the blood
Treatment
Treatment
 Intensive care immediately
Intensive care immediately
– Ventilator for respiratory failure
Ventilator for respiratory failure
 Botulinum antitoxin
Botulinum antitoxin
– Derived from equine source
Derived from equine source
– CDC distributes
CDC distributes
– Used on a case-by-case basis
Used on a case-by-case basis
 Botulism immune globulin
Botulism immune globulin
– Infant cases of types A and G
Infant cases of types A and G
 Equine antitoxin
Equine antitoxin
– Trivalent and bivalent antitoxins available
Trivalent and bivalent antitoxins available
through the CDC
through the CDC
– Licensed trivalent antitoxin neutralizes type A,
Licensed trivalent antitoxin neutralizes type A,
B, and E botulism toxins
B, and E botulism toxins
– Effective in the treatment of foodborne,
Effective in the treatment of foodborne,
intestinal, and wound botulism
intestinal, and wound botulism
– Effectiveness for inhalation botulism has not
Effectiveness for inhalation botulism has not
been proven
been proven
– Does not reverse current paralysis, but may limit
Does not reverse current paralysis, but may limit
progression and prevent nerve damage if
progression and prevent nerve damage if
administered early
administered early
 Hypersensitivity to equine antitoxin
Hypersensitivity to equine antitoxin
– 9% of people experience some hypersensitivity
9% of people experience some hypersensitivity
Botulism Vaccine
Botulism Vaccine
 A toxoid vaccine (antigen types A, B,
A toxoid vaccine (antigen types A, B,
C, D, and E) is available for laboratory
C, D, and E) is available for laboratory
workers at high risk of exposure
workers at high risk of exposure
 Limited supplies of this vaccine
Limited supplies of this vaccine
available
available
Therapeutic Uses of
Therapeutic Uses of
Botulism Toxin
Botulism Toxin
 There is a vaccine for botulism that
There is a vaccine for botulism that
protects against type A, B, C, D, and E
protects against type A, B, C, D, and E
available for those at high risk of
available for those at high risk of
exposure. In the event of a bioterrorist
exposure. In the event of a bioterrorist
attack of botulism toxin, however,
attack of botulism toxin, however,
reserves would quickly be depleted.
reserves would quickly be depleted.

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botulismgshsbdvdbdbebehejz-161205091721.pdf

  • 1. Botulism Botulism Infectious Diseases, AIDS & Clinical Infectious Diseases, AIDS & Clinical Immunology Research Center Tbilisi Immunology Research Center Tbilisi
  • 2. Definition Definition  Botulism is a paralytic disease caused by potent protein neurotoxins elaborated by clostridium botulinum.  Botulism is characterized by symmetrical, descending, flaccid paralysis of motor and autonomic nerves usually beginning with cranial nerves
  • 3. Etiologic Agent Etiologic Agent  C. botulinum is an anaerobic gram- positive organism that form spors;  C. botulinum C. botulinum is in soil and marine environments throughout the world.  C. botulinum C. botulinum elaborates the most potent bacterial toxin.
  • 4. – Spores Spores  Ubiquitous Ubiquitous  Resistant to heat, light, drying and radiation Resistant to heat, light, drying and radiation  Spores may survive boiling for several hours Spores may survive boiling for several hours at 100 at 100 o o C C  Specific conditions for germination Specific conditions for germination – Anaerobic conditions Anaerobic conditions – Warmth (10-50 Warmth (10-50o o C) C) – Mild alkalinity Mild alkalinity
  • 5. Neurotoxins Neurotoxins  Seven different types: A through G Seven different types: A through G – Different types affect different species Different types affect different species – All cause flaccid paralysis All cause flaccid paralysis – Only a few nanograms can cause illness Only a few nanograms can cause illness – Binds neuromuscular junctions Binds neuromuscular junctions  Toxin: Destroyed by boiling Toxin: Destroyed by boiling  Spores: Higher temperatures to be Spores: Higher temperatures to be inactivated inactivated
  • 6. Neurotoxins Neurotoxins – toxins A, B, E and F cause illness in humans toxins A, B, E and F cause illness in humans – toxins C and D cause illness in birds and toxins C and D cause illness in birds and mammals mammals – toxin G has been associated with sudden death, toxin G has been associated with sudden death, but not with neuroparalytic illness, in a few but not with neuroparalytic illness, in a few patients in Switzerland. patients in Switzerland. – Toxin type A produces the most severe Toxin type A produces the most severe syndrome, with the greatest proportion of syndrome, with the greatest proportion of patients requiring mechanical ventilation. Toxin patients requiring mechanical ventilation. Toxin type B appears to cause milder disease than type B appears to cause milder disease than type A. type A.
  • 7. Neurotoxins Neurotoxins Neurotoxin A B C D E F G Human X X X X Horses X X Cattle X X X Sheep X Dogs X X Avian X X Mink & Ferret X X X
  • 8. Epidemiology Epidemiology  Ingestion Ingestion – Organism Organism – Spores Spores – Neurotoxin Neurotoxin  Wound contamination Wound contamination  Inhalation Inhalation
  • 9. Epidemiology Epidemiology  Foodborne botulism Foodborne botulism – caused by eating foods that contain caused by eating foods that contain botulism toxin botulism toxin  Intestinal botulism Intestinal botulism (infant and child/adult) (infant and child/adult) – caused by ingesting spores of the bacteria caused by ingesting spores of the bacteria which germinate and produce toxin in the which germinate and produce toxin in the intestines. intestines.  Wound botulism Wound botulism – C. botulinum spores germinate in the C. botulinum spores germinate in the wound. wound.
  • 10. Epidemiology Epidemiology  The highest incidence rate is reported from the The highest incidence rate is reported from the Republic of Georgia and Armenia, where illness is Republic of Georgia and Armenia, where illness is associated with risky home-canning practices. associated with risky home-canning practices.  In the United States during 1990–2000, the median In the United States during 1990–2000, the median number of foodborne cases of botulism per year number of foodborne cases of botulism per year was 23 (range, 17–43). was 23 (range, 17–43).  Since the early1990s, cases in the United States Since the early1990s, cases in the United States have occurred almost exclusively in injection drug have occurred almost exclusively in injection drug users. users.
  • 11. Pathogenesis Pathogenesis  Toxin enters bloodstream from mucosal surface or Toxin enters bloodstream from mucosal surface or wound wound  Binds to peripheral cholinergic nerve endings Binds to peripheral cholinergic nerve endings  Inhibits release of acetylcholine, preventing Inhibits release of acetylcholine, preventing muscles from contracting muscles from contracting  Symmetrical, descending paralysis occurs Symmetrical, descending paralysis occurs beginning with cranial nerves and progressing beginning with cranial nerves and progressing downward downward  Can result from airway obstruction or paralysis of Can result from airway obstruction or paralysis of respiratory muscles respiratory muscles  Secondary complications related to prolonged Secondary complications related to prolonged ventilatory support and intensive care ventilatory support and intensive care
  • 13. Food-borne botulism Food-borne botulism  Incubation period Incubation period - - 18-36 h (depending 18-36 h (depending on toxin dose can range from a few hours to on toxin dose can range from a few hours to several days). several days).  Home-canned goods (foodborne) Home-canned goods (foodborne) – particularly low-acid foods such as particularly low-acid foods such as asparagus, beets, and corn asparagus, beets, and corn
  • 14.  Nausea, vomiting, diarrhea Nausea, vomiting, diarrhea  Diplopia, dysarthria, dysphonia, Diplopia, dysarthria, dysphonia, dysphagia dysphagia  Descending weakness or paralysis Descending weakness or paralysis – Shoulders to arms to thighs to calves Shoulders to arms to thighs to calves  Symmetrical flaccid paralysis Symmetrical flaccid paralysis  No fever No fever  Respiratory muscle paralysis Respiratory muscle paralysis
  • 15. Wound botulism Wound botulism  Incubation period – Incubation period – 10 days. 10 days.  Gastrointestinal symptoms are lacking Gastrointestinal symptoms are lacking  Wound botulism has been documented: Wound botulism has been documented:  After traumatic injury involving contamination with After traumatic injury involving contamination with soil; soil;  After cesarean delivery After cesarean delivery  After antibiotics have been given to prevent wound After antibiotics have been given to prevent wound infection. infection.  (When present, fever is probably attributable to (When present, fever is probably attributable to concurrent infection with other bacteria). concurrent infection with other bacteria).
  • 16. Intestinal (infant) Intestinal (infant) botulism botulism  May be one cause of sudden infant death. May be one cause of sudden infant death.  Honey can contain Honey can contain C. botulinum C. botulinum spores spores – not recommended for infants <12 months old not recommended for infants <12 months old
  • 17.  Constipation Constipation  Lethargy Lethargy  Poor feeding Poor feeding  Weak cry Weak cry  Bulbar palsies Bulbar palsies  Failure to thrive Failure to thrive
  • 18. Diagnosis Diagnosis  A diagnosis of botulism must be A diagnosis of botulism must be considered in patients with symmetric considered in patients with symmetric descending paralysis who are afebrile descending paralysis who are afebrile and mentally intact. and mentally intact.
  • 19. A 14-year-old with botulism. Note the weakness of his A 14-year-old with botulism. Note the weakness of his eye muscles and the drooping eyelids in the image to eye muscles and the drooping eyelids in the image to the left, and the large and non moving pupils in the the left, and the large and non moving pupils in the right image. right image.
  • 20. Laboratory diagnosis Laboratory diagnosis  Toxin in serum, stool, gastric aspirate, Toxin in serum, stool, gastric aspirate, suspected food suspected food  Culture of stool or gastric aspirate Culture of stool or gastric aspirate – Takes 5-7 days Takes 5-7 days  Electromyography also diagnostic Electromyography also diagnostic  Mouse neutralization test Mouse neutralization test – Results in 48 hours Results in 48 hours
  • 21. Laboratory diagnosis Laboratory diagnosis Botulinum toxin can be detected by a Botulinum toxin can be detected by a variety of techniques, including: variety of techniques, including: Enzyme-linked immunosorbent assays Enzyme-linked immunosorbent assays (ELISAs); (ELISAs); Electrochemiluminescent (ECL) tests Electrochemiluminescent (ECL) tests
  • 22. Botulism Differential Botulism Differential Diagnoses Diagnoses  Guillain-Barré syndrome Guillain-Barré syndrome  Myasthenia gravis Myasthenia gravis  Stroke Stroke  Tick paralysis Tick paralysis  Lambert-Eaton syndrome Lambert-Eaton syndrome  Psychiatric illness Psychiatric illness  Poliomyelitis Poliomyelitis  Diabetic Complications Diabetic Complications  Drug intoxication Drug intoxication  CNS infection CNS infection  Overexertion Overexertion
  • 23. Treatment Treatment  Persons of all ages (including infants) in whom Persons of all ages (including infants) in whom botulism is suspected should be hospitalized botulism is suspected should be hospitalized immediately in an intensive care setting, with immediately in an intensive care setting, with frequent monitoring of vital capacity and frequent monitoring of vital capacity and mechanical ventilation if required. mechanical ventilation if required.  In adults, botulism can be treated by passive In adults, botulism can be treated by passive immunization with a horse-derived antitoxin, immunization with a horse-derived antitoxin, which blocks the action of the toxin circulating which blocks the action of the toxin circulating in the blood in the blood
  • 24. Treatment Treatment  Intensive care immediately Intensive care immediately – Ventilator for respiratory failure Ventilator for respiratory failure  Botulinum antitoxin Botulinum antitoxin – Derived from equine source Derived from equine source – CDC distributes CDC distributes – Used on a case-by-case basis Used on a case-by-case basis  Botulism immune globulin Botulism immune globulin – Infant cases of types A and G Infant cases of types A and G
  • 25.  Equine antitoxin Equine antitoxin – Trivalent and bivalent antitoxins available Trivalent and bivalent antitoxins available through the CDC through the CDC – Licensed trivalent antitoxin neutralizes type A, Licensed trivalent antitoxin neutralizes type A, B, and E botulism toxins B, and E botulism toxins – Effective in the treatment of foodborne, Effective in the treatment of foodborne, intestinal, and wound botulism intestinal, and wound botulism – Effectiveness for inhalation botulism has not Effectiveness for inhalation botulism has not been proven been proven – Does not reverse current paralysis, but may limit Does not reverse current paralysis, but may limit progression and prevent nerve damage if progression and prevent nerve damage if administered early administered early
  • 26.  Hypersensitivity to equine antitoxin Hypersensitivity to equine antitoxin – 9% of people experience some hypersensitivity 9% of people experience some hypersensitivity
  • 27. Botulism Vaccine Botulism Vaccine  A toxoid vaccine (antigen types A, B, A toxoid vaccine (antigen types A, B, C, D, and E) is available for laboratory C, D, and E) is available for laboratory workers at high risk of exposure workers at high risk of exposure  Limited supplies of this vaccine Limited supplies of this vaccine available available
  • 28. Therapeutic Uses of Therapeutic Uses of Botulism Toxin Botulism Toxin  There is a vaccine for botulism that There is a vaccine for botulism that protects against type A, B, C, D, and E protects against type A, B, C, D, and E available for those at high risk of available for those at high risk of exposure. In the event of a bioterrorist exposure. In the event of a bioterrorist attack of botulism toxin, however, attack of botulism toxin, however, reserves would quickly be depleted. reserves would quickly be depleted.