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Botulism

Presented by B.Khodabakhshi

2009 B.Khodabakhshi

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Introduction:

Botulism results from protein neurotoxin Similar to tetanus toxin Cost of care was estimated ,340,000 $ 1989 Have 5 clinical form: A -food born in B -intestinal botulism B 1 -infantile B 2 -adult type C D E - wound botulism – Inhalation ,(bioterrorism) – Iatrogenic ,(cosmetic ) B.Khodabakhshi

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Botulinum Toxin

Very potent • 1 microgram • 250 grams   kill 10 people 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

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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 as now described botulism B.Khodabakhshi

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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 B.Khodabakhshi

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Neurotoxin Human Horses Cattle Sheep Dogs Avian Mink & Ferret

Neurotoxins

A B C D E X X X X X X X X X X X X X X X X F X G

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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 100 º c/1 atm/several hours, but not in pressure cooker For non proteolytic food appearance activity isn't changing B.Khodabakhshi

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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 B.Khodabakhshi

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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

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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 7.5 -30 %(>60yr) Inhalation botulism doesn’t occur in nature It’s bioterrorism weapon B.Khodabakhshi

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110 100 90 80 70 60 50 40 30 20 10 0 1982 1987 1992 1997 2002 Year MMWR B.Khodabakhshi

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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 B.Khodabakhshi

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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

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Clinical manifestations:

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Acute bilateral cranial neuropathies with

symmetrical descending

weakness

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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

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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 21

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

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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 B.Khodabakhshi

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Clinical Manifestations

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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 B.Khodabakhshi

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Clinical manifestations (con..)

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Infant botulism

Feeding difficulties Hypotonia Increased drooling Weak cry Upper airway obstruction maybe initial sign B.Khodabakhshi

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Infant Clinical Signs

      Constipation Lethargy Poor feeding Weak cry Bulbar palsies Failure to thrive B.Khodabakhshi

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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 B.Khodabakhshi

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Inhalation botulism

    Bioterrorism Non communicable No obvious food source Multiple simultaneous outbreaks B.Khodabakhshi

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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 B.Khodabakhshi

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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

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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???

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Prevention:

Do not feed honey to children <1 yr of age Proper food preservation methods  Proper time, temperature and pressure • • 80 o C for 30 min or 100 o C 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 B.Khodabakhshi

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