\[GOOD\]

Hello and welcome to

**"Recognition of Chemical Associated Gastrointestinal Foodborne
Illness".**

I\'m Cynthia Good,

your moderator for this program which is originating from the studios of
the Centers for Disease Control and Prevention in Atlanta, Georgia.

This program is sponsored by the National Center for Environmental
Health,

Agency for Toxic Substances and Disease Registry and CDC's Public Health
Training Network.

The goal of this program is to enhance early recognition, reporting,

and clinical management of chemical associated gastrointestinal
foodborne illness by clinicians and healthcare providers.

Upon successful completion of the program,

participants will be able to:

\* Distinguish features of chemical associated foodborne illness

\* Describe epidemiologic clues of a covert chemical associated
foodborne illness

\* Describe a structured approach to guide the generation of a
differential diagnosis targeting various chemical etiologies

\* Describe appropriate reporting strategies for suspected covert
chemical associated foodborne illness, and\...

\* Discuss the clinical course and general management of poisoning from
various chemicals

So, now that we've gotten the business part of the program behind us,

let's meet our program guests.

I'd like to welcome Dr. Helen

Schurz Rogers,

Research Scientist with the National Center for Environmental Health at
CDC \...

\...and Lieutenant Commander

Joshua Schier of the United States Public Health Service, Medical
Toxicologist with the National Center for Environmental Health at the
CDC.

Welcome to the program.

Let's begin with you, Dr. Rogers.

\[ROGERS\]

Thank you, Cynthia.

The etiologies of a large majority of foodborne gastrointestinal

illness, or

GI illness outbreaks are never identified or confirmed by the
laboratory.

GI illness refers to the presence of

GI signs and symptoms including nausea,

vomiting,

abdominal discomfort and diarrhea.

Chemicals are seldom considered early in the differential diagnosis of
foodborne

GI illness since the majority of these illnesses in which an etiology is
identified are caused by biological organisms, such as bacteria, viruses
or parasites.

Since the most commonly identified etiologies of

GI foodborne illnesses are due to biological organisms, these are much
more commonly considered early in an outbreak.

The wide variety of possible chemicals that can induce

GI illness hinders accurate recognition and diagnosis.

When chemicals are finally considered, biologic specimens such as urine
and blood often have to be re-collected and may not show evidence of the
chemical due to the body's normal elimination mechanisms. Furthermore,

stool samples,

which are commonly used for analysis of infectious foodborne illness are
often not the ideal specimen to identify chemical etiologies.

Chemical agents have been used in the deliberate contamination of food
with the intention of causing illness in the past. We will discuss
several examples during the course of this webcast.

Since the terrorist attacks of 2001, concern has grown about the use of
chemical agents in future attacks. Contamination of the nation's food
supply is one major area of concern.

This webcast has been structured to assist clinicians and public health
officials in the recognition of chemical associated GI foodborne

illness.

It is also intended to raise awareness and recognition of how many
commonly available chemicals could be used in a covert chemical
terrorism event. Most chemicals tend to produce

GI symptoms within a short time frame, less than 12 hours, after
ingestion.

Chemicals that do not produce

GI symptoms within that time frame or those agents that do not produce

GI symptoms at all after ingestion will NOT be discussed.

No etiologic agent was identified in

62 percent of the 1073 foodborne disease outbreaks reported to the

CDC in 2003.

Many of these outbreaks had illness characterized by the onset of

GI symptoms such as nausea,

vomiting,

diarrhea and abdominal discomfort of less than 12 hours, classifying
them as short incubation outbreaks.

Possible etiologic agents in these short incubation outbreaks include
industrial chemicals,

drugs,

pesticides,

and plant toxins - most of which could be identified and quantified in
specialized laboratories if specimens were collected and stored
correctly until analysis was able to be completed. Detection of these
agents,

however,

requires

agent-dependent specific biologic specimen collection,

prompt collection methods,

and testing techniques that are not routinely included in the
investigation of many foodborne outbreaks.

\[GOOD\]

Thank you,

Dr. Rogers.

Allow me to interject some information concerning the background for
this program.

This webcast will provide clinicians and public health officials with
the following information related to chemical etiologies of
unintentional and intentional covert chemical associated foodborne GI
illness:

\* background information on chemical poisoning

\* the general differences between biological and chemical foodborne
illnesses

\* epidemiologic clues of chemical foodborne illnesses

\* how to recognize a possible covert chemical terrorism foodborne
poisoning event

\* a structured approach to guide the generation of a differential
diagnosis targeting chemical etiologies

\* discussion of possible chemical etiologies and their management

AND, how to report chemical associated GI foodborne

illness.

To continue with this background information,

let's go to Dr. Schier.

\[SCHIER\]

Thanks, Cynthia.

The rapid and accurate identification of a chemical etiology in
foodborne illness outbreaks is necessary for many reasons.

These includeing proper patient management,

risk assessment for long-term adverse health effects and outbreak
control.

In a true chemical terrorism event this is even more important.

Accurate identification of a chemical etiology in a foodborne illness
outbreak is done through good investigative work, early consideration of
a possible chemical etiology and prompt collection of biologic samples.

Historically,

most chemical associated foodborne

GI illnesses have been unintentional. However,

there have been several notable cases of intentional poisoning through
food contamination. When an intentional poisoning occurs,

it may be overt or covert.

In an overt foodborne illness, the contamination of food is often
obvious, that is,

it may have been announced in some way such as by the discovery of an
overturned chemical container into foodstuffs prior to processing.

In a covert foodborne illness;

however,

it may not be immediately apparent that a food or meal is responsible
for the illness.

An example of a covert event would be the intentional or inadvertent
contamination of food in a restaurant with a harmful agent that is
unknown to the restaurant patrons and not immediately identifiable.

The presence of ill persons at an emergency department,

or even at the restaurant,

may be the first indication of a common source of exposure.

If there is a highly suspected or known exposure,

or a concurrent credible threat of poisoning,

then a clinical diagnosis can be much more easily made.

However,

if illness is occurring as a result of a covert event,

clinical diagnosis will be much more difficult.

\[GOOD\]

That's very interesting.

Could you discuss some historical examples of chemical foodborne GI
illness . . . examples that would differ in scope, etiology of
contamination and severity . . .

perhaps to illustrate the various ways chemical contamination of
foodstuffs may occur?

\[SCHIER\]

Sure.

In March 2002,

a man and woman in NJ became ill after eating a meal of pufferfish they
had prepared at home.

A relative had caught the fish in Florida and shared part of the catch
with family.

Shortly after eating the fish,

they both began to feel tingling in the mouth and around the lips.

During the next two hours,

the woman began vomiting and experiencing chest pain.

The local poison control center was contacted and they were both advised
to proceed to the closest hospital.

At the hospital,

the woman had a mild tachycardia,

an elevated blood pressure and began to develop an ascending paralysis.

A test of her respiratory function indicated she had less than 20
percent of a normal vital capacity for a woman her age.

She was electively intubated and placed on a mechanical ventilator.

Over the next several days she recovered and was able to be successfully
extubated 72 hours later.

The examination of Florida state poison control center records and the
national poison center reporting database back to January of 2002
indicated that these pufferfish poisoning cases were not the first.

From January to July, a total of 23 cases of pufferfish poisoning
sporadically occurred in four states including,

New Jersey,

New York,

Virginia and

Florida,

although all of the fish had been harvested in Florida. Only one case
was from store-bought fish;

all others were from recreational fishers.

Fish tissue specimens and urine samples from patients were collected for
laboratory analysis.

Tetrodotoxin was initially considered as the etiologic agent due to its
known presence in pufferfish. Tetrodotoxin was not identified in the
fish tissue samples; however,

additional analysis confirmed the presence of saxitoxin.

Saxitoxin is a similar toxin that is found in certain types of
shellfish.

In these cases of illness,

presumptive diagnosis of pufferfish poisoning was made based on the
neurologic symptoms the patients experienced,

the latency of the symptoms and the type of food consumed.

What was important in these events, however,

was the rapid consideration and identification of the type of toxin most
consistent with their symptoms.

This greatly assisted in the management and treatment of their clinical
findings. Helen....

\[ROGERS\]

Thanks Josh.

In July 2004,

ten people reported that they became ill at a restaurant. They were not
part of a large group that ate together at the restaurant,

and local hospitals did not report any rise in community illness.

Some of the people who became ill had consumed food, while others had
only consumed fountain drinks.

Nausea and vomiting were the most common symptoms, and,

the average incubation period was 10 minutes.

Two people also developed diarrhea the following day.

A health inspection of the restaurant did not indicate any obvious
etiologies or health code violations.

Further investigation, however,

found that seven out of the 10 cases had consumed fountain drinks.

Ice,

water and carbonated beverages from the fountain machine were collected
for testing.

Test results indicated that copper was almost seven times higher in the
fountain drinks than the acceptable limit for human consumption. This
was ultimately determined to be the etiology of the illnesses.

Copper may leach out into the water when acidic solutions enter copper
pipes.

In a post-dispensing soda machine,

like those found in fast-food restaurants, carbonation of the water
occurs after the water leaves the copper piping. Regulations require a
functional

back-flow prevention valve at the end of the copper-pipe. This valve
prevents the carbonated water or carbonic acid from back flowing back
into the copper pipe. A faulty valve canwill allow the carbonated water
to enter the copper-pipe.

Leaching of the copper from the pipe may occur after prolonged contact
with carbonic acid.

Most often,

the leaching occurs overnight when the dispenser is not operated;

the first users in the morning,

typically the restaurant workers, are the ones who become ill -

hence copper poisoning has been called the

"restaurant worker syndrome".

Luckily all individuals that were affected by this contamination
recovered.

Josh....

\[SCHIER\]

In April of 2003,

27 people stayed after church services for a council meeting.

During the meeting, refreshments, including pastries and beverages,

were served. Approximately 16 people became ill with nausea, vomiting
and diarrhea after consuming

bitter-tasting coffee.

The ill parishioners were taken to an area hospital where they were
evaluated. An infectious etiology was initially suspected;

however, as the clinical course of several of the ill parishioners
worsened,

a possible chemical etiology was considered.

The rapid progression of illness and the failure to respond to basic
supportive care prompted consultation with the New England Poison
Control Center as well as the local and state health departments.

Sixteen people were ultimately hospitalized and some were seriously ill.

Even with prompt recognition and treatment of this illness,

tragically,

one person died.

The collaboration between clinicians, local and state public health
officials and the poison control center targeted several likely
etiologies,

including arsenic.

The identification of a clinical course which was atypical for most
infectious foodborne illness and subsequent laboratory analysis for
chemical agents led to the rapid identification of arsenic as the
etiologic agent. Antidotal chelation therapy was then initiated in
conjunction with continued supportive care.

\[ROGERS\]

GI illnesses can be broken down into two categories based on GI tract
symptoms. These include upper GI illnesses and lower GI illnesses.

Upper GI illnesses usually include nausea and vomiting.

Lower GI illnesses usually include abdominal cramps and diarrhea.

The latency and presence of upper

GI and/or lower

GI symptoms as well as which ones occur first or predominate, are
important clues in determining if a biological or chemical foodborne
illness is occurring.

Although poisoning without GI symptoms may occur after consumption of
some contaminated foodstuffs,

most chemicals do cause GI symptoms if significant amounts are ingested,

and only those agents will be discussed in this presentation.

In general,

infectious foodborne illnesses have mean incubation periods that are at
least

12 hours long although shorter incubation periods are the norm for
illness resulting from the ingestion of certain pre-formed toxins from
Staphyloccus aureus and Bacillus cereus.

The incubation period,

however,

may not be definitively known until an investigation pinpoints the
actual source.

Depending on the agent, upper GI or lower GI symptoms may predominate.

In chemical foodborne illnesses, symptoms may be similar to some aspects
of the flu, namely the GI ones. Upper GI symptoms are more likely to
predominate.

The most important indicator of chemical contamination is the latency of
the illness onset,

which is often very short.

Indeed,

symptoms from many agents such as metals,

detergents and pesticides

can start within minutes of ingestion. Others such as ricin poisoning
may take several hours.

Chemicals should be strongly considered in the differential diagnosis of

GI foodborne illness when:

\* The latency period is very short.

Most GI manifestations of chemical illnesses will occur within

30 to 60 minutes of ingestion.

There are some exceptions,

however,

such as Amanita mushroom poisoning or ricin which may take several hours
before they begin to cause symptoms\...

\* Symptoms do not resolve over time with standard supportive therapy,
or they rapidly worsen over the next 12 to 24 hours despite this
therapy\...

\* There are reports that the food had a metallic taste, or unusual odor
or appearance\...

\* The predominant GI symptom is often vomiting;

however,

case-patients may have other symptoms such as neurologic findings,
depending on the type of toxin.

\[GOOD\]

Thank you Dr. Rogers.

Those were some of the symptom clues.

Dr. Schier,

what are some examples of clinical manifestations that go along with
chemical poisining?

\[SCHIER\]

Chemical poisoning may result in a rapid progression of illness and
cause a variety of clinical manifestations and laboratory abnormalities.

Some examples include:

\* Metabolic acidosis

\* Hypoglycemia

\* Tachycardia

\* Hypotension

and\...

\* Tachypnea

When present,

these manifestations may occur in conjunction with multiple system organ
dysfunction and rapid progression of illness that may be unresponsive to
traditional therapies.

Neurologic symptoms are more indicative of a chemical or biological
toxin exposure than a bacterial one.

These symptoms may include parasthesias, numbness, weakness in
extremities,

visual disturbances or dizziness.

Flushing,

diaphoresis or a burning sensation may occur.

The presence of symptoms like these can be an important clue that a
chemical exposure has occurred.

Similarly, organoleptic comments,

or comments that describe a quality of the food having to do with taste,

smell or visual appearance,

can be important clues.

For example:

\* Did the food have an odd taste?

Was it metallic, acidic,

burning,

alcoholic or bitter? Was there an excessive amount of flavor,

such as sweet,

salty or sour?

\* Were there any strange odors associated with the food,

such as a chemical or metallic odor?

\* Did the food look different,

was there a strange color or texture,

was it oily or viscous?

Another factor which complicates the accurate identification of a
chemical etiology is possible exposure to multiple agents.

This may result in clinical findings that do not make up an easily
recognizable pattern.

Healthcare providers are generally less familiar with clinical
presentations of chemical poisonings than they are with signs and
symptoms resulting from infectious gastroenteritis.

The severity and duration of symptoms depends on the type and amount of
exposure to a given chemical or toxin.

Depending on the toxin,

specific antidotal therapy,

supportive treatment and hospital observation may be necessary to ensure
a good outcome. Helen...

\[ROGERS\]

Once a chemical exposure is suspected,

it's vitally important to collect proper samples so that the agent can
be identified.

This may mean that several types of samples need to be collected
initially.

Laboratory analysis for a particular agent usually involves measuring
the agent itself,

a metabolite or a surrogate marker.

If a chemical foodborne illness is suspected,

it is best to collect appropriate biological specimens as soon as
possible and preferably within the first 24 hours.

If chemical analysis is not immediately available or the differential
diagnosis is too broad to enable efficient analysis,

samples can usually be stored in a freezer.

In the laboratory workup of chemical foodborne illness, the emphasis is
often placed on prompt collection of a urine specimen,

whereas in most biologic foodborne illnesses,

emphasis is placed on the collection of stool samples.

An early or first vomitus sample may sometimes be very helpful in
identifying the chemical.

Some agents are also identifiable in blood samples.

Stool samples are generally not useful for identification of chemical
etiologies.

Many chemicals have a short-half life, which refers to the amount of
time it takes for half of a dose to be eliminated. If too much time
passes before a urine sample is collected,

there won't be enough of the agent left for identification.

It's also important to collect urine samples from

non-symptomatic people that shared in the meal or food item.

The reason for this is that these individuals provide an important
control sample that is helpful when evaluating laboratory results.

Whenever possible, samples of the implicated food or beverage should
also be obtained for analysis.

Sometimes,

if a method does not exist for the laboratory confirmation of a chemical
in a biological specimen, like urine,

there may be a method available that can be utilized for food samples.

Unused collection containers, preferably from the same lot, should also
be stored.

These containers are used to help the laboratory evaluate for any
background contamination.

It is important to also mention that collection procedures and
guidelines are similar for chemical agents that do not cause early onset

GI symptoms.

A useful resource for the proper collection of biological materials is
located on the CDC website.

Details about proper sample collection techniques and storage are also
given.

A vital part of the investigative process in a foodborne outbreak is a
standardized food history questionnaire. One of the goals of such a
questionnaire is to seek commonalities among the ill.

These questions may be essential to implicate a particular foodstuff.

Once a food or meal has been implicated, pertinent questions to ask
include:

\* What were the predominant symptoms?

\* What was the latency of illness?

\* What food items were available to the patient,

which ones were consumed and how was the food prepared?

For chemical foodborne illnesses, it is helpful to keep in mind the
following questions,

and then include these in the final questionnaire:

\* Were there neurologic symptoms in addition to GI complaints?

\* Were there other types of symptoms not commonly associated with
foodborne illness, such as sore throat?

\* Did the food have a bitter or metallic taste,

was there an abnormal smell,

an unusual appearance?

And\...

\* What does the patient think made them ill?

\[GOOD\]

Those are good questions to ask,

but are there any conditions or circumstances that may make it difficult
to recognize contamination?

\[SCHIER\]

Yes.

In fact,

an intentional or unintentional contamination of foodstuffs is likely to
be covert or an unrecognized incident in which the presence of sick
persons might be the first sign of an exposure.

There are four reasons why such an event may not be easily recognized.
These include the following:

\* Initial symptoms of illness resulting from chemical exposure may
mimic those of more common

non-chemical etiologies such as an infectious gastroenteritis\...

\* Exposure to contaminated foodstuffs and/or water may occur over a
broad geographical area and time course.

For example,

a large-scale event may not be rapidly identified if patients present to
different health care facilities in multiple states over the course of
several weeks\...

\* Exposures to two or more chemical agents may result in symptoms of
illness from both agents and therefore complicate identification\...

\* Finally,

infectious gastroenteritidies are seen much more commonly by health care
workers than chemical induced

GI illness; therefore, chemicals may not be high on a provider\'s
differential diagnoses.

This may delay identification of the actual etiologic agent in a
chemical release.

There are certain epidemiologic clues the health care worker and public
health official can use to assist in identifying a possible chemical
release. These guidelines may be especially helpful in a covert chemical
terrorism foodborne event.

These include:

\* An unusual increase in the number of patients seeking care for
potential chemical associated illness\...

\* Unexplained deaths among young or healthy persons

\*Emission of unexplained odors by patients from their clothing or skin

\* Clusters of illness in persons who have common characteristics,

such as drinking water or eating foodstuffs from the same source

\* Rapid onset of symptoms after an exposure to a potentially
contaminated medium.

An example would be the rapid development of parasthesias and vomiting
following the consumption of a meal.

The following discussion is presented in what is hoped to be a more
useable format for the health care provider and public health official
in developing a chemical based differential diagnosis in the
undifferentiated patient.

We will discuss differential diagnosis based on the clinical
presentation of the individual patient.

This discussion is not meant to be

all-inclusive and should not be used as a restrictive flow diagram.

Significant overlap of signs and symptoms may occur depending on the
route of exposure, concentration of agent,

exposure to more than one agent, certain individual differences such as
age and

ultimately the severity of toxicity. The following format is to be used
as a guide in formulating a differential diagnosis and applying a
logical approach toward identification of chemical associated GI
foodborne illness.

CDC has developed the following suggested clinical presentation-based
approach to identify the etiologic agent in a suspected
chemical-associated GI foodborne illness event.

Classification is based on the **primary** presence or absence of
certain clinical manifestations in conjunction with expected GI signs
and symptoms

such as nausea,

vomiting and abdominal discomfort.

The major categories of agents that we will be talking about include
those agents with GI signs and symptoms AND:

\* Neurologic findings

\* Cardiotoxic findings

\* Multi-system Organ Failure

And\...

\* Localized GI Effects

Health care workers and public health officials should initially
determine the presence or absence of neurologic signs and symptoms.

\* Are cholinergic signs present?

\* Does the patient have any type of parasthesias and weakness?

\* Is there a history of a rapid onset of severe agitation, seizures or
status epilpeticus?

Cholinergic signs and symptoms result from the overstimulation of
cholinergic receptors.

This may occur due to:

\* Excessive or increased synaptic concentrations of acetylcholine,

OR\...

\* A separate agent which has acetylcholine-like activity.

These latter compounds can be referred to as cholinergic agonists.

There are two types of cholinergic receptors:

nicotinic and muscarinic.

There are a variety of agents which may interact with one or both
receptors. Clinical effects vary depending on which type of cholinergic
receptor is stimulated.

Organic phosphorous compounds and carbamates are most commonly used as
insecticides.

These agents inhibit the enzyme which normally degrades the
neurotransmitter, acetylcholine.

If enough of this enzyme is inhibited, an enormous increase in synaptic
acetylcholine can occur which results in overstimulation of cholinergic
receptors.

These agents differ in that organic phosphorous compounds can bind
irreversibly to acetylcholinesterase; however, carbamates spontaneously
disassociate,

usually within

24 hours.

Clinical findings may include both nicotinic and muscarinic effects such
as toxicity resulting from numerous types of organic phosphorous
insecticides. However,

other agents may produce predominantly either nicotinic OR muscarinic
symptoms. We will discuss these signs and symptoms separately, with the
understanding that a mix of both may occur, depending on the agent.

Agents which may cause muscarinic symptoms include toxins and toxicants
such as:

\* Organic phosphorous compounds

\* Carbamates

\* Muscarine- containing mushrooms

Toxicity from organic phosphorous and carbamate compounds results from
an excess of acetylcholine since these agents inhibit the enzyme
acetylcholinesterase, which breaks down acetylcholine. Muscarine is a
natural ligand for the muscarinic receptor and can stimulate the
receptor directly.

The stimulation of muscarinic receptors results in the expected GI
manifestations of vomiting and diarrhea as well as several other
clinical findings.

They can be remembered by the pneumonic, "DUMBELS".

This stands for:

Diarrhea,

Urination,

Miosis,

Bradycardia, Bronchorrhea, Bronchospasm, Emesis,

Lacrimation, Salivation,

Secretion and Sweating.

The onset of symptoms usually follows exposure very rapidly,

and medical treatment should be sought immediately. Supportive care such
as assisted ventilation, intravenous fluids and antidotal therapy should
be given as needed.

The antidotes for this type of poisoning include atropine, which is a
competitive muscarinic receptor antagonist,

and pralidoxime, which regenerates inactivated acetylcholinesterase.

Muscarine- containing mushrooms may also produce a similar clinical
picture.

Examples include numerous members of the

Clitocybe and

Inocybe genus. The mushroom Amanita muscaria also contains muscarine,

but in much smaller amounts.

Treatment is usually supportive,

as toxicity is usually limited.

In cases of severe toxicity,

small amounts of atropine may be considered depending on the situation.

Pralidoxime is not used in muscarinic toxicity, resulting from
muscarine, since there is no acetylcholinesterase inhibition.

Stimulation of nicotinic receptors results in different clinical
findings.

These include:

\* Mydriasis, Tachycardia, Weakness, Hypertension and Hyperglycemia

and\...

Fasciculations

They can be remembered by taking the first letter of each day of the
week except for Thursday,

in which you remember the H instead of the T.

Agents that are able to cause

nicotinic-type signs and symptoms after exposure include:

\*Organic phosphorous compounds and carbamates

\* Certain plants that contain nicotine, such as those from the genus
Nicotiana, or the tobacco plant

\* Tobacco-containing products

\* And other plants with compounds that possess nicotinic-like activity,

such as those listed on the screen.

Treatment for toxicity resulting from nicotine or nicotine- like
compounds is generally supportive in nature.

Atropine only functions at muscarinic receptors and is therefore not
helpful in selective

nicotinic-type toxicity. Nicotinic symptoms resulting from agents such
as organic phosphorous compounds CAN be treated with preladoxine to
regenerate inactivated acetylcholinesterase.

Benzodiazepines can be used as

anti-anxiety,

anti-agitation and anti-convulsive medications if needed.

\[ROGERS\]

The next

sub-category I would like to talk about includes those agents that cause
the relatively rapid onset of parasthesias and weakness,

in addition to GI manifestations. Cardiac dysrhythmias such as
bradycardia, although not frequent,

may also occur.

These include the seafood toxins:

\* Ciguatoxin

\* Tetrodotoxin

\* Saxitoxin

and\...

\* Brevetoxin

Treatment for these marine toxins are primarily supportive and
symptomatic in nature.

There are no known antidotes.

Illness from these agents usually results from the consumption of
seafood that contains the toxins. A thorough history from the patient or
the patient's family and/or friends will often elucidate a history of
recent suspicious seafood consumption.

Ciguatoxin is a

heat-stable,

lipid-soluble, odorless and tasteless toxin.

It is produced by bacteria within certain dinoflagellates such as
Gambierdiscus toxicus.

These dinoflagellates serve as the major food source for small fish.

As these fish are eaten by larger, carnivorous species, bioaccumulation
of the toxin occurs.

Ciguatera poisoning most often occurs after consumption of warm-water,

bottom-dwelling shore reef fish

such as barracuda,

sea bass,

amber jack,

kingfish and

red snapper.

Most poisoning in the United States occurs in Hawaii and Florida.

Ciguatoxin causes its effects through binding to the sodium channel and
interfering with normal ion conduction across the cell. Poisoning
usually occurs several hours after ingestion and includes an abrupt
onset of:

\* Nausea

\* Vomiting

\* Watery diarrhea

and\...

\* Neurologic symptoms

The neurologic symptoms can include:

\* Paresthesias

\* A reversal of hot and cold sensation such that hot objects feel cold
and cold objects are perceived as hot

and\...

\* Headaches

In severe toxicity, ciguatoxin may interfere with ion conduction in
myocardial cells. Cardiac dysrhythmias such as bradycardia and
orthostatic hypotension may occur.

Other manifestations of poisoning include vertigo,

diaphoresis and seizures.

GI symptoms typically resolve in one-to-two days but neurologic and
cardiac toxicity may last longer.

Tetrodotoxin is also a heat-stable,

water-soluble compound.

This toxin is primarily found in puffer fish and puffer-like fish such
as the globefish, balloonfish,

blowfish and toadfish.

It is also found in the blue-ringed Octopus, horseshoe crab eggs and the
gastropod mollusk.

A specific variety of pufferfish known as fugu is considered a delicacy

but can cause tetrodotoxin poisoning,

especially if improperly prepared.

Tetrodotoxin also interferes with normal sodium ion conductance in cells
and in neuromuscular transmission.

Signs of poisoning appear within minutes of ingestion. Neurologic signs
and symptoms predominate and include:

\* Headache

\* Diaphoresis

and\...

\* Parasthesias -- especially in the perioral area.

GI symptoms such as nausea,

vomiting and diarrhea often rapidly follow.

Patients are at risk of developing an ascending paralysis within several
hours of consumption of tetrodotoxin containing foodstuffs.

Death by respiratory paralysis or cardiac dysfunction may occur.

Another type of marine toxin poisoning\...

Saxitoxin poisoning\... usually occurs after consumption of certain
shellfish, including clams, oysters,

mussels and scallops.

It has also recently been identified in some species of pufferfish in
waters off the coasts of Japan and Florida.

Neurologic symptoms such as perioral and extremity parasthesias
predominate. Patients may also exhibit a sensation of floating,

weakness,

paralysis and

cranial nerve dysfunction including:

\* Dysphagia

\* Dysarthria

and\...

\* Dysphonia

GI symptoms such as nausea, abdominal pain, vomiting and diarrhea are
less common but can still occur.

Respiratory failure may occur in severe toxicity.

Lastly,

Brevetoxin can cause Neurotoxic Shellfish Poisoning which is
characterized by

GI and neurologic symptoms similar to those mentioned previously,

except it usually does not cause paralysis.

Its mechanism of action is also similar to tetrodotoxin and saxitoxin.

The GI and neurologic symptoms usually occur simultaneously and within a
few hours of ingestion.

Cardiac effects such as bradycardia may also be seen.

Brevetoxin toxicity has tends to have more pronounced

GI effects than saxitoxin,

and a reversal of hot and cold temperature sensation may also be
occasionally seen.

\[GOOD\]

That's fascinating, Dr. SchierRogers. You've talked about a lot of
different marine toxins, perhaps Dr Schier, you could discuss other
environmental toxins, such as plant toxins, that present a potential
hazard?

\[SCHIER\]

Of course.

The third

sub-category of agents with neurologic effects,

in addition to

GI signs and symptoms,

consists of those agents that produce agitation,

confusion and/or seizures.

Examples include:

\* Gyromitra mushrooms

\* Tetramine-type compounds

\* Organochlorine compounds

And\...

\* Camphor

The gyromitrin group of mushrooms includes Gyromitra esculenta,

or the false morel,

as well as several others.

The false morel is often mistaken for the true morel,

or Morchella esculenta,

by amateur mushroom hunters because it is very similar in appearance.

Toxicity from consumption of the false morel typically begins about five
hours after consumption. GI symptoms such as nausea,

vomiting,

abdominal pain and diarrhea are common,

and patients may complain of headaches and myalgias.

Most patients recover;

however,

severe toxicity may result in confusion, refractory seizures and coma.

Tetramine has been traditionally used as a rodenticide, particularly in
China. Although it was banned by the Chinese government,

it may still be found and imported or manufactured elsewhere. Tetramine
has been implicated in several mass poisonings in China and cases of
poisoning exist in the United States, although they are rare.

Although tetramine ingestion may cause traditional GI symptoms such as
nausea,

vomiting,

diarrhea and abdominal pain,

\...its most concerning toxicity is its propensity to cause seizures.

Patients may present with seizures and progress to status epilepticus
after ingestion of very small amounts.

Treatment is primarily supportive in nature.

If seizures and/or status epilepticus is present as a result of
tetramine poisoning, treatment should include anti-seizure medications
and drug-induced status epilepticus protocols. The benzodiazepine and
barbiturate classes of

anti-convulsant drugs are better agents for control of seizures
resulting from chemical poisoning.

There is no known specific antidote.

Treatment for Gyromitra poisoning is primarily supportive and
symptomatic; however,

it is important to note that refractory seizures or status epilepticus
should be rapidly treated with pyridoxine in conjunction with typical

anti-convulsant drugs such as benzodiazepines. This is because
gyromitrin,

found within some Gyromitra species such as the false morel,

interferes with the pyridoxine- dependent metabolism of GABA or gamma

amino-butyric acid. GABA is the major inhibitory neurotransmitter of the
central nervous system.

Other examples of agents that may also cause central nervous system
hyperstimulation, altered mental status and even seizures include
camphor and the organochlorine pesticides.

Both of these agents are likely to cause a rapid onset of concurrent

GI symptoms such as nausea,

vomiting and abdominal pain

after ingestion. Camphor-induced seizures are often brief and
self-limited. Organochlorine ingestion may also cause recurring seizures
and even status epilepticus depending on the class and overall dose.

Benzodiazepines and barbiturates should be used to control seizures if
needed.

Supportive and symptomatic treatment should be instituted and

GI decontamination considered.

The second major category of agents which can cause rapid onset of

GI symptoms and also present with severe symptoms from another organ
system are the cardioactive glycosides.

The prescription medication Digoxin, is an example of a purified
cardioactive glycoside,

but similar compounds exist throughout nature.

Examples of plants in which cardioactive glycosides can be extracted
include:

\* Oleander

\* Lily of the Valley

\* Foxglove

\* Red Squill

\* Dogbane

and\...

\* Siberian ginseng

The ingestion of toxic amounts of these compounds may result in nausea,
vomiting and abdominal pain.

The patient may also be somewhat drowsy or confused.

The cardioactive glycosides are aptly named since they interfere with
the normal electrolyte flux in and out of myocardial cells. This can
result in myocardial ectopy and dysrhythmias.

Just about any kind of dysrthymia,

from bradydysrhythmias to tachydysrhythmias, can be seen in cardioactive
glycoside poisoning. These patients also tend to have evidence of
myocardial conduction delays, such as an

atrio-ventricular conduction block, due to their pronounced effects on
the vagus nerve.

Toxicity is dependent on dose and type of compound,

as severity of illness varies with the particular agent. Although a
serum digoxin level may be helpful in the identification of poisoning,

the absence of a detectable digoxin level or a low but non-toxic level
does not exclude cardioactive glycoside toxicity in the appropriate
clinical setting. Cross-reactivity may occur between the digoxin assay
and the various cardioactive glycosides,

however,

the assay is designed to look for digoxin.

Therefore the absence of a detectable digoxin level or a non-toxic
digoxin level does not necessarily indicate a

non-exposure.

In fact,

cardioactive glycoside poisoning should be highly suspected if a patient
has a clinical picture consistent with Digoxin poisoning, and a low but
detectable digoxin level is found,

and the patient does not have access to the medication Digoxin.

Definitive treatment is through the administration of Digoxin-specific
antibodies. Treatment should also include supportive care as needed.

Calcium is

contra-indicated for cardioactive glycoside-induced hyperkalemia due to
an inherent risk of worsening cardiotoxicity.

\[GOOD\]

How serious can some of these agents be?

\[ROGERS\]

Actually,

the third major category of agents is known for its ability to cause
multisystem organ dysfunction and ultimately organ failure.

Sometimes only very small amounts of these agents are needed to cause
poisoning.

Some well known examples of these agents include:

\* the Amanita Phalloides mushroom

\* Ricin toxin from Ricinus communis, or castor bean plant

\* Abrin toxin from Abrus precatorius,

or the jequirty pea

And\...

\* multiple forms of inorganic metals.

Poisoning from select Amanita species such as

Amanita Phalloides does not occur until five or six hours after
ingestion. Severe watery diarrhea and other GI symptoms such as nausea
are common.

Initial iImprovement usually occurs with supportive care such as
replacement fluid therapy.

However, approximately

24 to 36 hours after consumption,

the patient's condition can worsen considerably as manifested by hepatic
and renal toxicity.

Death is common after severe poisoning.

Treatment should include supportive and symptomatic therapies.

Multiple doses of activated charcoal should be considered in conjunction
with a clinical toxicologist and/or the local poison center.

If amanita poisoning is confirmed and presentation to a health care
facility is within four hours, charcoal hemoperfusion should be strongly
considered.

There are various other suggested but unproven treatments which may also
be considered.

Ricin is one of several types of toxalbumins which exert their toxicity
by inhibiting protein synthesis in eukaryotic cells and therefore can
cause cell death.

It is a compound derived from Ricinus communis,

or the castor bean plant.

All of the information available on oral ricin poisoning comes from
people who have eaten castor beans.

There are no reports of anyone who has ingested purified ricin.

The information that follows is based on ricin consumed in the form of
masticated castor beans and may vary somewhat if purified ricin is used.

Signs and symptoms are likely to be the same, however.

There are hundreds of reported cases of toxicity,

and several fatalities, from castor bean mastication and ingestion.

If enough ricin is ingested,

the potential for significant morbidity and mortality exists.

Symptoms of mild toxicity include: nausea,

vomiting,

diarrhea,

and/or

abdominal cramping.

These symptoms are invariably present in people who chew and swallow a
significant amount of castor beans. Oropharyngeal irritation may also
follow ingestion.

Bloody diarrhea and systemic effects, such as hypotension, hemolysis and
renal failure,

are NOT present and symptoms typically resolve within

24 hours.

Onset of

GI symptoms typically occurs in less than 10 hours. Delayed presentation
of GI symptoms, beyond ten hours after ingestion,

is unlikely to occur.

Moderate to severe toxicity may include: GI symptoms such as persistent
vomiting and voluminous diarrhea . . . bloody or

non-bloody . . .

which typically leads to significant fluid losses.

This may result in dehydration and hypovolemic shock, which would
manifest as tachycardia, hypotension, decreased urine output,

and possibly altered mental status,

such as confusion or disorientation.

In severe poisoning, hepatic and renal failure and even death are
possible within 36 to 72 hours of exposure.

Treatment is primarily symptomatic and supportive in nature.

Abrin is a closely related type of toxalbumin that is derived from Abrus
precatorius,

or the jequirty pea. The seeds of this plant are commonly used in
jewelry and in ornaments due to their colorful appearance.

Abrin poisoning can result from mastication and ingestion of Abrus
precatorious seeds and from ingestion of purified abrin. Toxicity,

symptoms of poisoning and treatment are similar to ricin poisoning.

Other agents often implicated in chemical-associated multisystem organ
failure include metals.

There are numerous metals that may cause GI illness once ingested. These
include the inorganic salts of:

\* Arsenic

\* Mercury

\* Iron

\* Lead

\* Copper

\* Cadmium,

and\...

\* Numerous others

Patients who ingest metal salts in foodstuffs or beverages may complain
that the food had a bitter or metallic taste. Symptoms of inorganic
metal poisoning often begin within 30 to 60 minutes of ingestion and can
rapidly progress over the next several hours.

The ingestion of significant amounts of inorganic metal salts is usually
rapidly followed by GI symptoms such as nausea,

vomiting,

abdominal pain and diarrhea.

The severity is directly dependent on the amount and form ingested.

An important clue to metal toxicity in the clinical course is a rapid
progression, over 12 to 36 hours, of symptoms that include multiple
organs and organ systems,

depending on the agent.

This may include renal failure, hepatotoxicity and pulmonary toxicity.
The widespread damage done by metals is usually due to their nonspecific
binding of functional groups,

such as sulfhydryl moieties,

on numerous enzymes and proteins.

Binding can cause irreparable damage to the protein and cell to which it
is attached.

Another clue to metal poisoning is severe GI fluid loss due to
widespread damage to the GI tract.

This fluid loss may require large amounts of intravenous fluid
replacement and even intravenous vasopressor therapies to maintain
adequate blood pressure.

This is not likely to happen with a typical viral or bacterial
gastroenteritis other than cholera.

Metal salt poisoning may,

however,

be hard to distinguish clinically from ricin or abrin poisoning.

Laboratory testing is needed to definitively confirm metal poisoning.

Blood and urine testing is available for most metals. This is dependent,
however,

on the individual agent.

It is important to note that many metals, such as arsenic and mercury,

can exist in nature and in the body in organic and inorganic forms.
Often, interpretation of laboratory results needs to take into account
the amount in each form with the patient's clinical presentation.

The ingestion of seafood can substantially increase total blood arsenic
and mercury levels.

When certain metals such as these are analytically measured in biologic
specimens like blood and urine,

the results often represent a summation of the levels of both inorganic
and organic forms.

Therefore, interpretation of the results must take into account whether
these different forms were measured,

or speciated,

during the analysis. Ideally,

and in non-acute cases,

patients should abstain from eating any kind of seafood for at least

three-to-five days prior to testing for some metals, especially arsenic
and mercury,

since this could affect the results.

In acutely ill patients, this delay is unacceptable and specialized
testing may be needed.

\[GOOD\]

That's good advice Dr. Rogers.

Dr. Schier,

I believe you have something to add concerning localized GI illness.

\[SCHIER\]

Yes I do, Cynthia. Many agents may simply cause a limited clinical
picture consistent with a severe gastroenteritis. Chemicals and
biological toxins that may cause this include:

\* Hydrocarbons

\* Detergents

\* Caustics

\* Certain mushrooms

And\...

\* some pre-formed toxins from Staphylococcus aureus,

Clostridium perfringens,

and Bacillus cereus

Hydrocarbons,

if ingested,

generally produce

GI symptoms but little else.

Their biggest risk is if the patient aspirates after vomiting,

which can result in a hydrocarbon-induced pneumonitis. Treatment is
supportive and symptomatic in nature with a careful evaluation for
aspiration.

Some hydrocarbons may have a significantly greater risk of additional
toxicity and are commonly remembered by the pneumonic, CHAMP. This
stands for:

\* Camphor

\* Halogenated hydrocarbons

\* Aromatic hydrocarbons

\* Hydrocarbons associated with metals

and\...

\* Hydrocarbons associated with pesticides

Treatment and management may vary considerably for patients who ingest
these compounds.

Caustics include compounds with extreme pHs such as acids or alkalis.
Common household products include toilet bowl cleaner, commercial drain
blockage removal formulations and other products. Caustics may also
include agents corrosive by nature of their oxidative state such as
chlorates, permanganates and chromates.

These agents are extremely irritating to the GI tract and can cause
severe damage,

including perforation and scarring.

Generally,

acute toxicity is limited to the GI tract, however,

airway burns may sometimes occur, necessitating emergent airway control.

Ingested acids may cause a resultant metabolic acidosis due to systemic
absorption in severe cases.

Endoscopy is often used to assess damage resulting from symptomatic
caustic ingestion. Charcoal should NOT be given in caustic ingestions
since the damage is usually done within minutes of the ingestion and may
obscure visualization on endoscopy later.

As with any poison, the dose ingested determines severity.

The ingestion of detergents and soaps generally cause limited

GI signs and symptoms.

This usually resolves with time,

although supportive therapy and fluid replacement may be needed in
severe cases.

However,

some detergents, such as powdered dishwasher detergent,

are inherently caustic,

and closer evaluation along with endoscopy may be needed.

A large variety of mushrooms from multiple genera can cause nausea,
vomiting and diarrhea after ingestion. Symptoms are due to a wide
variety of poorly understood GI toxins with limited toxicity.

Patients poisoned by mushrooms from these groups manifest symptoms
within three hours of ingestion.

This distinguishes the toxin class from the much more deadly Amanita
phalloides toxin, which does not induce symptoms until five-to-six hours
after ingestion. Treatment is supportive,

and symptoms generally resolve within 12-24 hours.

A small number of bacterial species may cause

GI foodborne illness by consumption of pre-formed toxin. These species
primarily include Staphylococcus aureus,

Bacillus cereus,

and Clostridium perfringens.

Clinical illness includes nausea, vomiting,

abdominal pain, diarrhea,

and occasionally fever.

The presence of some of these symptoms depends heavily on which organism
is present and which toxins are being produced. Treatment is with
supportive care and fluid replacement when indicated.

Numerous other agents may cause GI symptoms if ingested.

A few are worth briefly mentioning due to historical use, ease of
availability or inherent toxicity. These include syrup of ipecac and
various pharmaceuticals.

Syrup of ipecac can cause nausea and vomiting within half an hour of
ingestion. Symptoms commonly resolve after two-to-three hours.

Ipecac has been historically used as an emetic in the treatment of
poisoning,

as well as abused in those trying to lose weight.

There are numerous drugs that can cause a clinical picture similar to
those agents already described.

The sheer number of agents precludes their comprehensive review in this
webcast;

however,

clinicians and public health officials are advised to at least consider
the possibility. The identification of foodstuffs contaminated with
pharmaceuticals in a foodborne illness event is unlikely to be
unintentional.

If enough of any drug is ingested,

some degree of GI irritation may be expected.

Some examples of drugs which tend to cause more GI signs and symptoms
include:

\* Acetaminophen, salicylates and nonsteroidal

anti-inflammatory drugs

\* Theophylline

\* Lithium

\* Digoxin

\* Colchicine

and\...

\* Podophyllum resin

..Helen\...

\[ROGERS\]

Thank you for your attention during this webcast.

We have attempted to provide you with an organized template from which
you can develop a differential diagnosis of possible chemical etiologies
based on a patient's clinical presentation.

The classification scheme includes many of the more common

GI presentations that may occur with chemical agents. The list of agents
discussed is not comprehensive,

but rather includes many examples of the aforementioned categories.

We have also tried to emphasize certain clues in the patient's history
and clinical presentation,

as well as epidemiologic clues that may alert the astute clinician or
public health official that a foodborne illness event may have a
chemical etiology.

The regional poison control center should always be contacted in any
case of suspected or known chemical associated foodborne illness by
calling

1-800-222-1222.

This will automatically connect the caller to the closest poison center.

Clinicians and health care workers should also contact their local and
state departments of health for assistance.

Local and state health officials are also encouraged to call the Rapid
Onset of Gastroenteritis with Unknown Etiology,

or R.O.G.U.E., hotline to obtain epidemiological assistance.

In addition, CDC may be able to provide specialized laboratory
capabilities if needed and the circumstances require it.

We hope that this

presentation will help clinicians and public health officials
understand, diagnose and manage chemical-associated GI foodborne
illness.

\[GOOD\]

Thank you,

Dr. Rogers.

The many questions that we have received concerning today's program will
be posted,

with their answers, on our website at

w-w-w-

dot-

p-h-p-p-o-

dot-

c-d-c-

dot-

g-o-v-

slash-

p-h-t-n-

slash-

g-a-s-t-r-o-

hyphen-

zero-

five.

You can also view the archived version of this program at the same
website.

In addition, videotapes and

CD-ROMs of this program will soon be available for purchase through the
Public Health Foundation.

To order,

you can call

1-877-252-1200

or visit their online bookstore at

www

dot

p-h-f

dot

org.

Finally, I'd like to thank our guests . . . Doctors

Helen

Schurz Rogers

and

Joshua Schier, \...and I'd also like to thank our viewing audience for
submitting your thoughtful questions concerning today's program.

And so,

that brings us to the close of

**"Recognition of Chemical Associated Gastrointestinal Foodborne
Illness".**

I'm Cynthia Good, and it has been my pleasure to be your moderator
today.

Good-bye.

\#######

DRAFT 4.3 - PAGE #21