An overview of food

intoxications

Andrew Bayat, PGY-2

3/30/2015, 3/31/2015

Topics

Staphylococcus aureus Bacillus cereus Clostridium perfringens Clostridium botulinum Ciguatera Scombroid Tetrodotoxin Amnesic shellfish poisoning Other shellfish poisonings Safe foods?

Other topics to consider

Clostridium difficile

EIEC, EHEC, STEC, Shigella

ETEC

Salmonella

Vibrio cholera and parahaemolyticus

Camypylobacter jejuni

Bacillus anthracis

Yersinia enterocolitica

Mushroom intoxications

Heavy Metal ingestions

Radioactive ingestions

Tyramine, MSG, Metabisulfate, preservatives, flavoring

Common Plant toxins: hemlock, nightshade, wisteria, fox-glove, hydrangea, oleander, etc

Solvents, paints, industrial exposures, pesticides

Staphylococcus aureus

One of the most common causes of food poisoning and the most common toxin-mediated form of food poisoning

Bacteria is colonized on the food source, can replicate at 10-40 °C.

Forms one of several heat stable (120 °C) Exotoxins, prior to ingestion.

◦ Believed to be >10 toxins, commonest being Exotoxin B

Common food sources are milk, cream, meats, egg, mushrooms.

Staphylococcus aureus

Onset of symptoms is rapid: 1-6 hours Resolution is rapid: ~24 hours Treatment is supportive care Mechanism for producing symptoms is

unclear◦ Thought to be increased intestinal serotonin

release, possibly increased vagal tone, and/or direct irritation/inflammation to the mucosa

Symptoms:

Bacillus cereus

Gm + rod, motile, non encapsulated, spore-forming

Spores can survive up to 100 °C

Commonly on foods that have been improperly cooked below 100 °C, thus endospores survive.

#1 vector is fried rice, then non-fried rice, then meat

Bacillus cereus Two forms of illness are caused by B.

cereus Treatment for both is supportive◦ 1. Diarrheal form: 6-24 hours incubation then

nausea, abdominal cramps and watery diarrhea. Due to germination of endospores in the small

intestine making heat labile toxin, tripartite hemolysin B similar to heat labile toxin of ETEC.

◦ 2. Emetic form: similar to Staph enterotoxin in character: 1-6 hour incubation then nausea, vomiting and abdominal pain/cramps Due to germination of spores during ambient

temperatures (classically a buffet), these then make heat-stable (and acid-stable) toxin, cereulide.

Syndrome Usually lasts <10 hours.

Toxin cellular targets

5-HT3 Receptor

Beta-Barrel

Clostridium perfringens Anaerobic Gm + spore forming rod. Several

strains exist.◦ Forms heat resistant spores that when deposited

on food, survive normal cooking/heating temperature (100 °C)

◦ Spores germinate during preparation between 12°C - 60°C

◦ Proliferates very rapidly between 30°C -50°C

◦ Symptoms start 6-24 hours after ingestion

◦ Once ingested, forms several toxins in the intestine

◦ No defined food vehicle but usually meat, poultry, gravy

◦ Also responsible for gas gangrene

Clostridium perfringens

Strain A:

Most common strain causing enteral disease in Industrialized countries.◦ Toxin, which may be encoded via plasmid or

chromosomal.

◦ Creates 46kDa “CPE” enterotoxin. Binds extracellular Claudin 3 and Claudin 4 on

extracellular domain.

Causes: 1) Cellular pore formation and 2) disassembly of tight junctions and thus the paracellular pathway.

Heat labile at 74 °C

◦ Leads to cell death and increased cellular/membrane permeability

Treat with IVF, no antibiotics recommended for enteral infection

CPE mechanism

Calpain

Apoptosi

s

CPE mechanismTight Junction

Clostridium perfringens

Strain B and C

Forms 34 kDa Beta-toxin, which is similar to Staphylococcal alpha toxin. ◦ Heat labile, normally digested by trypsin-> disease

predisposed by malnutrition

◦ Beta strands, heptamerize into a Beta-barrel which causes a pore in the cell membrane

◦ Result is K efflux, Ca influx, cellular swelling and cell death

May infect small bowel namely jejunum (occasionally ileum) and result in Clostridialnecrotizing enteritis, AKA: Pigbel, Darmbrand.◦ Characterized by bloody diarrhea, small bowel

ulceration, perforation, peritonitis.

Usually treat with abx: Metronidazole, Pen G

Clostridium botulinum

Anaerobic gm + spore forming rod. Motile.◦ 4 (I-IV) major groups with groups I and II

causing human disease.

◦ In adult disease, toxins are pre-formed by the bacteria then released upon bacterial death. Formed in anaerobic environment with suitably low

acidity and salinity

Toxin is heat labile and destroyed at 85 °C

◦ Usually in association with eating canned foods that are not properly heated/prepared.

Clostridium botulinum

There are at least 7 types of neurotoxin, all somewhat similar in size, structure and function 150kDa. ◦ Absorbed through the intestinal M cell, utilizing

hemagglutinin

◦ Heavy chain one portion of the molecule is responsible for binding a nerve cell another portion is responsible for inserting the light chain into the nerve cell.

◦ The light chain is a Zinc peptidase that cleaves SNAP, and VAMP

◦ SNAP and VAMP are molecules that are responsible for exocytosis of neurotransmitter containing vesicles at the neuromuscular junction.

◦ Result is that neurotransmitter (Ach) is not released into the synapse

Clostridium botulinum toxin

Clostridium botulinum

Symptoms delayed 12-72 hours: Symptoms include: nausea and vomiting evolving into descending paralysis involving cranial nerves: dysphagia, dysphonia, dysarthria, facial weakness/droop (usually bilateral), and respiratory failure.

Death rate is 5-10%

Treatment is supportive care and Heptamericdespeciated (no Fc portion) equine IgG to the toxin

Scombroid poisoning

Most common cause of fish-related

food poisoning in the US.

Associated with improperly prepared

Scombridae family of fish: mackerel,

tuna, blue-fish, tuna, bonito.

Sometimes caused by non-

scombroids: mahi-mahi, amberjack

Scombroid poisoning

Presents 30-60 minutes after ingestion with flushing, diaphoresis, abdominal pain/cramping, nausea, vomiting, diarrhea headache, urticaria, tachycardia, bronchospasm/wheezing, and angioedema.◦ Essentially resembles allergic reaction

◦ Lasts 10-24 hours if untreated

◦ Treatment is usually histamine blockade

◦ Severe cases can require IM epinephrine, steroids, ventilator support

Scombroid poisoning

Cause is Histidine in the muscle content of the fish:◦ Histidine is converted to Histamine by E. coli,

Klebsiella pneumoniae, Morganella morganiiusing Histidine decarboxylase.

◦ Occurs at temperatures >18 °C; thus predominates in fish that is improperly frozen

◦ Because Histamine is heat stable, once formed smoking, cooking or canning the meat will not eliminate the toxin

Histadine decarboxylase

Ciguatera

Name of the common cause of food intoxication caused by eating predatory reef fish including Red Snapper, Grouper, Jack, Barracuda, etc contaminated with Ciguatoxin.◦ Toxin is formed by Diflagellate sp (namely

Gambierdiscus toxicus) which are eaten along with algae by herbivorous fish and biomagnifyup the food chain

◦ Concentrates in head, roe, and viscera

Ciguatoxin

Onset of symptoms 1-30 hours, usually within 12h; may last months to years.◦ Symptoms usually start with GI: nausea,

vomiting, weakness.

◦ Progress to neurological: paresthesia, dysuria, blurred vision, hot-cold sensation reversal, loose/painful teeth, cold allodynia, and rarely dyspareunia

◦ May occasionally have bradycardia, hypotension.

Several toxins may be present but the predominant toxin is Ciguatoxin◦ Heat stable, acid stable, tasteless and

odorless

◦ Not modified by handling or cooking process

Ciguatoxin

Mechanism is lowering the potential for voltage-gated sodium channels in the CNS, predisposing neurons to depolarization.◦ Toxin is lipid soluble and able to cross the BBB

◦ No completely effective treatment; no validated treatments

◦ Calcium channel blockers including nifedipine, TCAs, mannitol have been used with variable success

◦ Lethal in concentrations of 0.45 ug/kg

Tetrodotoxin Pre-formed toxin present in puffer-fish, trigger-fish,

porcupine-fish, blue-ringed octopus among others.◦ Formed by commensal bacteria, usually Vibrio sp.

◦ Toxin usually concentrated in liver, ovaries, eyes, with much lower concentrations if at all in the flesh and skin of fish.

◦ Fugu is the Japanese dish of puffer-fish, prepared but a specially trained chef- usually requiring 2-3 years of specialized training. Available in ~17 restaurants in the US.

◦ Poisoning happens in the setting of inappropriately prepared foods.

◦ Toxin is heat-stable and potentiated by some cooking temperatures, thus soups are frequently associated with worse cases of toxicity

Tetrodotoxin

Symptoms start within 30 minutes of ingestion◦ Lip/Tongue paresthesia, abdominal pain,

nausea, vomiting, weakness, tremor, ataxia, dysphagia, dysphonia, ascending paralysis, bronchospasm, hypotension, bradycardiaand respiratory failure/ arrest

◦ LD50 is roughly 300 ug/kg= 25-30mg would kill 50% average adults

◦ Death occurs at ~4-6 hours, most those who survive 24 hours go on to survive.

◦ No antidote available, although there is research on a monoclonal Ab.

Tetrodotoxin

Mechanism is inhibition of voltage-

gated sodium channels, inhibiting

depolarization in nerve and muscle

cells.

Amnesic Shellfish Poisoning

Caused by eating filter-feeding shellfish contaminated by the toxin, domoic acid.◦ Shellfish include bivalve mollusks: mussels,

clams, oysters, scallops. Also can be found in anchovies.

◦ Toxin is formed by diatomaceous phytoplankton (type of algae) and biomagnifyin shellfish

◦ First seen 1987 in Prince Edward Island, Canada

◦ Toxin is heat stable and not inactivated by routine cooking

Amnesic Shellfish poisoning

Symptoms can start 15 minutes-38

hours after ingestion (usually delayed

by 24h)

◦ Symptoms usually begin with GI: Nausea,

vomiting, diarrhea, abdominal pain

◦ Then develop Headache, dizziness,

weakness, seizure, altered mental status.

◦ 10% develop antegrade memory loss

◦ Treatment is supportive care, no known

antidote

Amnesic Shellfish poisoning

Domoic acid

◦ Structurally similar to glutamate

◦ Causes toxicity by binding and exciting

AMPA/KA subset of Glutamate receptors

in the neurons and astrocytes of the CNS,

especially the Amygdala and

Hippocampus.

Binding of the receptor causes increased

intracellular calcium, activation of caspases

and ultimately apoptosis

Neurotoxic Shellfish poisoning

Also in Bivalves

Caused by eating shellfish

contaminated by toxin formed by

dinoflagellate and associated

temporally with red-tides.

◦ Toxin is coined “brevetoxin” and is

structurally and functionally similar to

Ciguatoxin (increased excitability) with

similar symptoms

Paralytic Shellfish poisoning

Also in Bivalves Caused by toxin, Saxitoxin made by

dinoflagellates, again associated with red-tides.◦ Inhibits neuronal voltage-gated sodium channels

in a similar fashion to tetrodotoxin, causing inhibition of neuronal action potential

◦ Similar symptoms to tetrodotoxin: nausea, vomiting followed by tingling lips, weakness, ataxia and ascending paralysis

◦ Deadly in doses estimated ~5 ng/kg

Voltage gated sodium

receptor

In summary, what is safe to

eat?

Well maybe not completely

safe…

Amazon reviews…

Thanks

Chief residents

Dr. Kleinschmidt

Dr. Cutrell

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