1. IN THE NAME OF GOD
B.Khodabakhshi

2. Presented by B.Khodabakhshi 2009
Botulism
Presented by
B.Khodabakhshi
2009
B.Khodabakhshi

3. Introduction: Botulism results from protein neurotoxin
Similar to tetanus toxin
Cost of care was estimated ,340,000$ in 1989
Have 5 clinical form:
A-food born
B-intestinal botulism
B1-infantile
B2-adult type
C - wound botulism
D – Inhalation ,(bioterrorism)
E – Iatrogenic ,(cosmetic )
B.Khodabakhshi

4. Botulinum Toxin Very potent Acts at the Neuromuscular Junction
1 microgram kill 10 people
250 grams  kill all the people on earth
1 gram aerosolized will kill potentially
1 million people
Acts at the Neuromuscular Junction
Prevents release of acetylcholine from alpha motor neurons
Muscles cannot receive signals telling to contract  Flaccid Paralysis
B.Khodabakhshi

5. B.Khodabakhshi

6. Hx : Botulism derives from latin word ,botulus or sausage
In 1820 Kener diagnosed relation between sausage and paralytic illness of 230 pt in Germany
1897 Ermenger described botulism as now
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7. Toxicology: Toxin A-G but only A, B, E, F produce human disease
C ,D animal disease
C2 cytotoxin, not neurotoxin
G no natural disease
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8. Neurotoxins Neurotoxin A B C D E F G Human X Horses Cattle Sheep Dogs
Avian
Mink & Ferret
This table summarizes the most common neurotoxin type affecting the various species affected by C. botulinum. All types of botulinum toxins produce the same clinical signs; however, the toxin type is important if antiserum is used for treatment. Type G has been isolated from soil and autopsy specimens but an etiologic role has not been established. Type E outbreaks are usually related to fish, seafood and meat from marine mammals.
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9. Microbiology: G+ ,strict anaerobe, with sub terminal spore.
C .Boyulinum, C.Botyricum, C.Baratii
Create spore that can remain dormant 30 year or more
C. botulinum spore is distributed worldwide, marine & soil environment
It tolerated 100ºc/1 atm/several hours, but not in pressure cooker
For non proteolytic activity isn't changing food appearance
B.Khodabakhshi

10. Epidemiology In U.S., average 110 cases each year
Approximately 25% food-borne
Approximately 72% infant form
Remainder wound form
Infective dose- few nanograms
All forms fatal and a medical emergency
In the US, there are on average 110 cases of botulism per year. Typically about 25% are food-borne related illnesses. Approximately 72% are the infant botulism form and the remainder are wound related. In 1995, the reported case-fatality rate for botulism cases was 5-10%.
B.Khodabakhshi

11. Epidemiology: A is more common in west USA
B is more common in east USA
Type E have fish source
Wound botulism ,A or B
Infant A ,B ,F (honey)
Unknown origin A ,B, F
Foodborn is in outbreak
B.Khodabakhshi

12. Epidemiology (con..)
Home canned vegetable and fruit and fish are more source ,condiment, green beans, beets, corn, baked potatoes, chopped garlic in oil, Chile peppers, tomatoes; type A
In Alaskan native & ( torkman ) ,fish fermented
In china bean fermented
Ph of implicated food is > 4.6
Case fatality rate is from %(>60yr)
Inhalation botulism doesn’t occur in nature
It’s bioterrorism weapon
B.Khodabakhshi

13. 110
100 90 80 70 60 50 40 30 20 10
Reported Cases
This graph depicts the trends of foodborne botulism cases in the U.S. from In 1983, 28 persons in Illinois obtained food-borne botulism from a batch of sautéed onions. Twelve required ventilator support, however no deaths occurred (MMWR 1984:33(2):22-23). During , Alaska recorded 226 cases of food-borne botulism from 114 outbreaks. All were Alaska Natives and were associated with eating fermented foods. In 1994, an outbreak at a Greek restaurant in Texas affected 30 persons from improperly stored foil-wrapped baked potatoes. The 2001 Texas outbreak resulted in 39 cases of foodborne botulism from persons eating commercially produced chili sauce that had been improperly stored. Overall botulism is a rare disease, but it can be fatal and every case of botulism is treated as a public health emergency. Graph from the Summary of Notifiable Diseases 2002, CDC website.
Year
MMWR
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14. B.Khodabakhshi

15. Pathogenesis:
Toxin after adsorbing in duodenum & jejunum with blood stream reaches to peripheral cholinergic synapses including neuromuscular junctions
In synapses :toxin prevents the release of acetylcholine
This process results for flaccid paralysis of motor neurons & autonomic dysfunction
This process is irreversible
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16. Pathogenesis (con..) No CNS involvement
Peripheral cholinergic nerve terminals,
A- N.M.J
B- post ganglionic parasympathetic
1 – binding with heavy chain
2 – internalization in endocytic vesicle
3 – translocation to cytosole
4 – proteolysis
5 – blockage of acetylcholine realease
B.Khodabakhshi

17.                                                                                                                                                                                                                                                                                                                                                  
This figure, "Mechanism of Action of Botulinum Toxin," from the
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18. B.Khodabakhshi

19. Clinical manifestations:
Acute bilateral cranial neuropathies with symmetrical descending weakness
B.Khodabakhshi

20. Clinical manifestations (con..)
No fever
Symmetrical [ difference with polio]
Pt is responsive
PR is normal or slow
NO sensory deficit (difference with GBS )
B.Khodabakhshi

21. Clinical manifestations (con..)
Incubation period 18 – 36 hr
Nausea, dry mouth , diarrhea or constipation
Symmetric descending neuropathy
Cranial neuropathy that begin with eyes
Blurred vision (pupillary dysfunction & 3,4,6 nerve paralysis
ptosis
Dysphagia, dysarthria, diplopia ,hypoglossal weakness
Respiratory failure [glot and diaphragm]
B.Khodabakhshi

22. Clinical manifestations (con..)
Pt need to mechanical ventilation for mean period 58 days
Autonomic problems, gastrointestinal dysfunction ,alteration in heart rate, hypothermia & urinary retention
Fixed mid dilated or dilated pupil occur in < 50% and doesn’t R/O botulism
B.Khodabakhshi

23. Clinical manifestations (con..)
Recovery begin after mean 50 day, progress up to 3 month and complete up to 1 yr
Some pshychological dysfunctions maybe remain
DTR normal or few decreased
Requires the sprouting of new nerve terminals
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24. Clinical Manifestations
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25. Infant Botulism Most common form in U.S. Spore ingestion
Germinate then toxin released and colonize large intestine
Infants < 1 year old
94% < 6 months old
Spores from varied sources
Honey, food, dust, corn syrup
The most common form of human botulism occurs in infants. Annual incidence in the US is two cases per 100,000 live births. Spores are ingested, germinate, then release their toxin and colonize the large intestine. It occurs predominantly in infants less than 1 year old (94% are less than 6 months old). The spores are obtained from various sources such as honey, food, dust, and corn syrup.
B.Khodabakhshi

26. Clinical manifestations (con..)
Infant botulism
Feeding difficulties
Hypotonia
Increased drooling
Weak cry
Upper airway obstruction maybe initial sign
B.Khodabakhshi

27. Infant Clinical Signs Constipation Lethargy Poor feeding Weak cry
Bulbar palsies
Failure to thrive
Children less than 1 year of age with the following clinical signs should be suspected of infant botulism. Constipation, lethargy, poor feeding, weak cry, bulbar palsies, failure to thrive, and progressive weakness. This can lead to impaired respiration and sometimes death if not treated promptly. The child in this picture is too weak to hold up its head as noted by the limp appearance of the neck and arms. It was an infant case of botulism. 72% of natural botulism cases occur in children under 1 year of age. California Department of Health Services
B.Khodabakhshi

28. Clinical manifestations (con..)
Wound botulism
Without prodromal gastrointestinal disturbance
Botulism has been reported after clostridial sinusitis after cocaine inhalation
Incubation period is from 4 – 14 days
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29. Inhalation botulism Bioterrorism Non communicable
No obvious food source
Multiple simultaneous outbreaks
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30. Differential diagnosis:
Myasthenia gravis
Eaton lambert myasthenia syndrome(LEMS)no pupil involvement
Tick paralysis
Guillian- barre syn
-sensory complaint
-ascending
-not alter pupil
-areflexia
Miller-fisher (ataxia)
Poliomyelitis
Magnesium intoxication
Organophosphate poisoning
Brain stem infarct
Psychiatric illness
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31. Diagnosis: Hx is the important diagnostic test Diagnosis is clinical
Anaerobic culture and toxin assay
-serum
-stool
-food
Most sensitive toxin assay is mouse bioassay
Elisa test and gel hydrolysis
B.Khodabakhshi

32. treatment: Elective intubation (decrease 30% vital capacity)
Purgatives
Antitoxin ,1 vial im,1vial iv
Human botulinum immune globulin 50mg/kg iv for infant botulism
Antibiotic for wound botulism
Antibiotic for infant botulism???
B.Khodabakhshi

33. Prevention: Do not feed honey to children <1 yr of age
Proper food preservation methods
Proper time, temperature and pressure
80oC for 30 min or 100oC for 10 min
85˚C for 5 min (NEW)
Prompt refrigeration of foods
Boil foods for > 10 minutes
Decontamination
Boil suspected food before discarding
Boil or chlorine disinfect utensils used
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34. Any Question??
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35. B.Khodabakhshi