B.Khodabakhshi 1. B.Khodabakhshi 2 Botulism Presented by B.Khodabakhshi2009.

B.KhodabakhshiB.Khodabakhshi 11


BotulismBotulismPresented by Presented by

B.KhodabakhshiB.Khodabakhshi

20092009


Introduction:Introduction: Botulism results from protein neurotoxinBotulism results from protein neurotoxin Similar to tetanus toxinSimilar to tetanus toxin Cost of care was estimated ,340,000Cost of care was estimated ,340,000$ $ in in

19891989 Have 5 clinical form: Have 5 clinical form: AA-food born-food born BB-intestinal botulism-intestinal botulism BB11-infantile-infantile BB22-adult type-adult type CC - wound botulism - wound botulism DD – Inhalation ,(bioterrorism) – Inhalation ,(bioterrorism) EE – Iatrogenic ,(cosmetic ) – Iatrogenic ,(cosmetic )


Botulinum ToxinBotulinum Toxin

Very potent Very potent • 1 microgram 1 microgram kill kill 10 people10 people• 250 grams 250 grams kill all the people on earth kill all the people on earth• 1 gram aerosolized will kill potentially 1 gram aerosolized will kill potentially 1 million people1 million people

Acts at the Neuromuscular Junction Acts at the Neuromuscular Junction • Prevents release of acetylcholine from Prevents release of acetylcholine from

alpha motor neuronsalpha motor neurons• Muscles cannot receive signals telling to Muscles cannot receive signals telling to

contract contract Flaccid ParalysisFlaccid Paralysis



Hx :Hx :

Botulism derives from latin Botulism derives from latin word ,botulus or sausageword ,botulus or sausage

In 1820 In 1820 KenerKener diagnosed relation diagnosed relation between sausage and paralytic between sausage and paralytic illness of 230 pt in Germanyillness of 230 pt in Germany

1897 1897 ErmengerErmenger described botulism described botulism as nowas now


Toxicology:Toxicology:

Toxin A-G but only A, B, E, F produce Toxin A-G but only A, B, E, F produce human diseasehuman disease

C ,D animal diseaseC ,D animal disease C2 cytotoxin, not neurotoxinC2 cytotoxin, not neurotoxin G no natural diseaseG no natural disease


NeurotoxinsNeurotoxins

NeurotoxinNeurotoxin AA BB CC DD EE FF GG

HumanHuman XX XX XX XX

HorsesHorses XX XX

CattleCattle XX XX XX

SheepSheep XX

DogsDogs XX XX

AvianAvian XX XX

Mink & FerretMink & Ferret XX XX XX


Microbiology:Microbiology: G+ ,strict anaerobe, with sub terminal G+ ,strict anaerobe, with sub terminal

spore.spore. C .Boyulinum, C.Botyricum, C.BaratiiC .Boyulinum, C.Botyricum, C.Baratii Create spore that can remain dormant 30 Create spore that can remain dormant 30

year or moreyear or more C. botulinum spore is distributed C. botulinum spore is distributed

worldwide, marine & soil environment worldwide, marine & soil environment It tolerated 100ºc/1 atm/several hours, but It tolerated 100ºc/1 atm/several hours, but

not in pressure cookernot in pressure cooker For For non proteolyticnon proteolytic activity isn't changing activity isn't changing

food appearancefood appearance


EpidemiologyEpidemiology

In U.S., average 110 cases each yearIn U.S., average 110 cases each year• Approximately 25% food-borneApproximately 25% food-borne• Approximately 72% infant formApproximately 72% infant form• Remainder wound formRemainder wound form

Infective dose- few nanogramsInfective dose- few nanograms All forms fatal and a medical All forms fatal and a medical

emergencyemergency


Epidemiology:Epidemiology:

A is more common in west USAA is more common in west USA B is more common in east USAB is more common in east USA Type E have fish sourceType E have fish source Wound botulism ,A or BWound botulism ,A or B Infant A ,B ,F (honey)Infant A ,B ,F (honey) Unknown origin A ,B, FUnknown origin A ,B, F Foodborn is in outbreak Foodborn is in outbreak


Epidemiology (con..)Epidemiology (con..) Home canned vegetable and fruit and fish are Home canned vegetable and fruit and fish are

more source ,condiment, green beans, beets, more source ,condiment, green beans, beets, corn, baked potatoes, chopped garlic in oil, corn, baked potatoes, chopped garlic in oil, Chile peppers, tomatoes; type AChile peppers, tomatoes; type A

In Alaskan native & ( torkman ) ,fish In Alaskan native & ( torkman ) ,fish fermentedfermented

In china bean fermentedIn china bean fermented Ph of implicated food is Ph of implicated food is > 4.6> 4.6 Case fatality rate is from 7.5 -30 %(>60yr)Case fatality rate is from 7.5 -30 %(>60yr) Inhalation botulism Inhalation botulism doesn’t occurdoesn’t occur in nature in nature It’s bioterrorism weaponIt’s bioterrorism weapon


Year

1982 1987 1992 1997 2002

Report

ed C

ase

s

110

100

90

80

70

60

50

40

30

20

10

0

MMWR



Pathogenesis:Pathogenesis: Toxin after adsorbing in duodenum & Toxin after adsorbing in duodenum &

jejunum with blood stream reaches jejunum with blood stream reaches to peripheral cholinergic synapses to peripheral cholinergic synapses including neuromuscular junctionsincluding neuromuscular junctions

In synapses :toxin prevents the In synapses :toxin prevents the release of acetylcholinerelease of acetylcholine

This process results for flaccid This process results for flaccid paralysis of motor neurons & paralysis of motor neurons & autonomic dysfunctionautonomic dysfunction

This process is irreversible This process is irreversible


Pathogenesis (con..)Pathogenesis (con..) No CNS involvementNo CNS involvement Peripheral cholinergic nerve terminals,Peripheral cholinergic nerve terminals,

A- N.M.JA- N.M.J

B- post ganglionic parasympatheticB- post ganglionic parasympathetic 1 – binding with heavy chain1 – binding with heavy chain 2 – internalization in endocytic vesicle2 – internalization in endocytic vesicle 3 – translocation to cytosole3 – translocation to cytosole 4 – proteolysis 4 – proteolysis 5 – blockage of acetylcholine realease5 – blockage of acetylcholine realease


This figure, "Mechanism of Action of Botulinum Toxin," from the



Clinical manifestations:Clinical manifestations:

Acute bilateral cranial Acute bilateral cranial neuropathies with neuropathies with symmetrical symmetrical descendingdescending weakness weakness


Clinical manifestations (con..)Clinical manifestations (con..)

No fever No fever Symmetrical [ difference with polio]Symmetrical [ difference with polio] Pt is responsivePt is responsive PR is normal or slowPR is normal or slow NO sensory deficit (difference with NO sensory deficit (difference with

GBS )GBS )


Clinical manifestations (con..)Clinical manifestations (con..) Incubation period 18 – 36 hrIncubation period 18 – 36 hr Nausea, dry mouth , diarrhea or Nausea, dry mouth , diarrhea or

constipation constipation Symmetric descending neuropathySymmetric descending neuropathy Cranial neuropathy that begin with eyesCranial neuropathy that begin with eyes Blurred vision (pupillary dysfunction & 3,4,6 Blurred vision (pupillary dysfunction & 3,4,6

nerve paralysis nerve paralysis ptosisptosis Dysphagia, dysarthria, diplopia ,hypoglossal Dysphagia, dysarthria, diplopia ,hypoglossal

weaknessweakness Respiratory failure [glot and diaphragm]Respiratory failure [glot and diaphragm]



Pt need to mechanical ventilation for Pt need to mechanical ventilation for mean period 58 daysmean period 58 days

Autonomic problems, gastrointestinal Autonomic problems, gastrointestinal dysfunction ,alteration in heart rate, dysfunction ,alteration in heart rate, hypothermia & urinary retentionhypothermia & urinary retention

Fixed mid dilated or dilated pupil Fixed mid dilated or dilated pupil occur in < 50% and doesn’t R/O occur in < 50% and doesn’t R/O botulismbotulism



Recovery begin after mean 50 day, Recovery begin after mean 50 day, progress up to 3 month and progress up to 3 month and complete up to 1 yrcomplete up to 1 yr

Some pshychological dysfunctions Some pshychological dysfunctions maybe remainmaybe remain

DTR normal or few decreasedDTR normal or few decreased Requires the sprouting of new nerve Requires the sprouting of new nerve

terminalsterminals


Clinical ManifestationsClinical Manifestations


Infant BotulismInfant Botulism

Most common form in U.S.Most common form in U.S. Spore ingestionSpore ingestion

• Germinate then toxin released Germinate then toxin released and colonize large intestine and colonize large intestine

Infants < 1 year oldInfants < 1 year old• 94% < 6 months old94% < 6 months old

Spores from varied sourcesSpores from varied sources• Honey, food, dust, corn syrupHoney, food, dust, corn syrup



Infant botulismInfant botulism Feeding difficultiesFeeding difficulties HypotoniaHypotonia Increased droolingIncreased drooling Weak cryWeak cry Upper airway obstruction maybe Upper airway obstruction maybe

initial signinitial sign


Infant Clinical SignsInfant Clinical Signs

ConstipationConstipation LethargyLethargy Poor feedingPoor feeding Weak cryWeak cry Bulbar palsiesBulbar palsies Failure to thriveFailure to thrive



Wound botulismWound botulism Without prodromal gastrointestinal Without prodromal gastrointestinal

disturbancedisturbance Botulism has been reported after Botulism has been reported after

clostridial sinusitis after clostridial sinusitis after cocainecocaine inhalationinhalation

Incubation period is from 4 – 14 daysIncubation period is from 4 – 14 days


Inhalation botulismInhalation botulism

BioterrorismBioterrorism Non communicableNon communicable No obvious food source No obvious food source Multiple simultaneous outbreaksMultiple simultaneous outbreaks


Differential diagnosis:Differential diagnosis:Myasthenia gravisMyasthenia gravisEaton lambert Eaton lambert myasthenia myasthenia syndrome(LEMS)no syndrome(LEMS)no pupil involvementpupil involvementTick paralysisTick paralysisGuillian- barre synGuillian- barre syn

-sensory complaint-sensory complaint -ascending-ascending -not alter pupil-not alter pupil -areflexia-areflexia

Miller-fisher (ataxia)Miller-fisher (ataxia)PoliomyelitisPoliomyelitisMagnesium Magnesium intoxicationintoxicationOrganophosphate Organophosphate poisoningpoisoningBrain stem infarctBrain stem infarctPsychiatric illnessPsychiatric illness


Diagnosis:Diagnosis:Hx is the important diagnostic testHx is the important diagnostic testDiagnosis is clinicalDiagnosis is clinicalAnaerobic culture Anaerobic culture andand toxin assay toxin assay

-serum-serum -stool-stool -food-food

Most sensitiveMost sensitive toxin assay is mouse toxin assay is mouse bioassaybioassayElisa test and gel hydrolysisElisa test and gel hydrolysis


treatment:treatment:

Elective intubation (decrease 30% Elective intubation (decrease 30% vital capacity)vital capacity)

PurgativesPurgatives Antitoxin ,1 vial im,1vial ivAntitoxin ,1 vial im,1vial iv Human botulinum immune globulin Human botulinum immune globulin

50mg/kg iv for 50mg/kg iv for infant botulisminfant botulism Antibiotic for wound botulismAntibiotic for wound botulism Antibiotic for infant botulism???Antibiotic for infant botulism???


Prevention:Prevention: Do not feed honey to children <1 yr of ageDo not feed honey to children <1 yr of age Proper food preservation methods Proper food preservation methods

Proper time, temperature and pressureProper time, temperature and pressure• 8080ooC for 30 min or 100C for 30 min or 100ooC for 10 minC for 10 min• 85˚C for 5 min (NEW)85˚C for 5 min (NEW)

Prompt refrigeration of foodsPrompt refrigeration of foods Boil foods for > 10 minutesBoil foods for > 10 minutes DecontaminationDecontamination

• Boil suspected food before discardingBoil suspected food before discarding• Boil or chlorine disinfect utensils usedBoil or chlorine disinfect utensils used



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