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Organisms that make botulism

Bacteria


Clostridium botulinum and other Clostriums (baratii, butyricum, argentinense)

Root of word botulism

Latin: botulism-> sausage

Pediatric vs adult botulism inoculatilm

Peds: bacterial growth in gut


Adult: ingestion of toxin from food



Other: wound botulism and aerosolized terrorism

Main population that gets wounds botulism

IV drug users

Spore factors: temp, ph


Toxin stability

Survive 100c for hours, 120 less than 30 mins.


Germinate pH>4.5, NaCl<3.5%, low nitrite


Produce toxin >27c (one strain down to 5c (E)


Toxin: destroyed 80c for 30 mins, 100c for 10 mins

Food smell if contaminated

A and B: putrified smell and appearance due to proteolytic


E: normal due to sacchrolytic

Toxin path in gut

Bound to hemagglutinin and other proteins to get past stomach. Alkaline intestines favours release and absorption


Symptoms usually within 1 day, but up to 7 days

Bacteria path in gut and risk factors

Alkaline stomach of infants and people on ppis, hx of bypass doesnt kill it. Immature gut flora allows replication.


Symptoms 1-2 months

Toxin structure

Single polypeptide 900 dalton's


Gets cleaved to 150 dalton active piece that has a heavy 100 dalton chain and 50 dalton light chain

Mechanism of toxin

Heavy chain facilitates entry into.presynaptic cholinergic neurons in peripheral system


Light chain cleaves SNARE proteins responsible for exocytosis of acetylcholine

Differences between toxin subtypes

All cleave different SNARE proteins, likely given variable toxicity

Other effects of BoNT

At high [ ] can impair release of norepi and serotonin centrally

Does botulism affect central acetylcholine neurons?

No.

Which proteins does each botulism subtype target?

All SNARE proteins

Botulism s/s

Early: nausea, vomiting, abdo distension and pain


Usually within 24 hours: weakness starting in facial nerves down, blurred vision, horizontal nystagmus, inability to accommodate


Constipation from smooth muscle effect


Anticholinergic effects EXCEPT the tachycardia and AMS


Dysarthria, dysphonia (nasally)


Decreased to abscent reflexes


Hypotension and brady


Normal sensation and MS

Botulism vs GBS vs Miller Fisher Variant

Presentation of infant botulism

<1 year


Constipation, feeble cry, difficulty feeding, decreased tone (mainly neck and arms, floppy baby). Mydriasis, ophthalmoplegia, diminished gag, poor sphincter tone


Usually gradual due to gradual absorption

Risk factors doe infant botulism

Breast feeding (formula get colonized by protective organisms).


Children of people who work with soil (construction, farming, nurseries, plumbers)


Deficiencies in immune systems

Risks of botulinum antitoxin

Equine derived: so serum sickness(9-17%), hypersensitivity and anaphylaxis (2%)

Pre-treatment for botulinum antitoxin

Histamine blockers


Steroids

How does botulinum antitoxin work?

Binds to UNBOUND butulism toxin. DOES NOT FIX ALREADY AFFECTED MUSCLES

Botulism antitoxin for infant botulism?



Different from the other one


BabyBIG, human derived IG.

Antitoxin definition

Antibody or antibody fragment against a toxin

Toxoid definition

Inactivated form of a bacterial toxin

Current heptavalent botulism antitoxin is produced how?

Immunizing horses for months with toxoids. Pooling horses Ig from different stereotypes of antitoxin. Pepsin enzymatic cleavage to despeciate achieving 98% FAB and only 2% intact.

Differences between FAB and intact Ig?

FAB is despeciated and so less immunogenic. Less likely to get serum sickness or anaphylactic reactions.


FAB has shorter half life due to improved renal clearance and uptake by vascular endothelium and surrounding tissues

Dose of heptavalent botulism antitoxin?

1 vial is 10-100x the amount needed for typical food borne illness. A second vial can be needed to due nonlinear interactions and ongoing absorption of toxin, or in cases of colonization.

Pharmacokinetics and dynamic of babying botulism antitoxin

Half life of 28 days. Can neutralize 20-500x the normal oral dose of botulism out to 20 days (20x). Thus. One infusion generally enough to treat

BabyBIG botulism antitoxin efficacy

Only against A and B now, need heptavalent Ig for others

Adverse effects of babyBIG botulism antitoxin

None reported, but lots theoretical


Main: loss of live vaccine efficacy within 3 months


Main:IgA deficient patient may develop immune response to subsequent IgA containing products.



Other: Trali, hemolytic anemia, aseptic meningitis

Heptavalent BAT botulism antitoxin dosing

Adult: 1 vial at a very slow rate increased every 30 mins


Children: weight based as a calculated percentage of adult dose


Infant: 10% of adult dose.

BabyBIG botulism antitoxin dosing

1.5ml/kg. 0.5ml/kg/hour x 15 mins then 1 ml/kg/hour until done.