GOOD
Hello and welcome to Recognition of Illness Associated With Chemical Exposure.
Im
This
program is sponsored by the
The goal
of todays program is to increase the likelihood that physicians and public
health professionals will recognize chemical-release-related illness so that
public health authorities can implement the appropriate emergency response and
public health actions.
Upon
successful completion of the program, participants will be able to describe:
Epidemiologic
clues that might suggest the covert release of a chemical agent and . . .
the importance of reporting and surveillance in recognizing outbreaks of
illness resulting from exposure to chemicals and toxins.
If youd
like to register and evaluate this program, you can do so from August 5th
through
The Webcast
and Web on Demand registration and evaluation begins
If you have
any questions about registration please call 1-800-41-TRAIN or you can
e-mail us
at ce@cdc.gov
And though
your evaluation is appreciated, it is not required.
Now it's my
great pleasure to introduce our two distinguished panelists. They are:
Dr. Manish
Patel, Medical Toxicologist, Division of Environmental Hazards and Health
Effects,
Dr. Martin
Belson, Medical Toxicologist, Division of Environmental Hazards and Health
Effects,
Welcome,
gentlemen.
Since the
September
11th was an obvious or an overt attack but future terrorist attacks
may not be so obvious and may be more covert.
Martin, can
you distinguish between covert and overt events and how they relate to chemical
terrorism, commonly referred to as a CT event?
BELSON
Thank you,
Cynthia. We would first like to give a
very brief background on the two types of chemical events.
The
intentional release of a chemical agent into the environment may be an overt or
covert event. An overt event, which
receives most of the national focus, is one in which the nature of the event
reveals itself.
Examples of
an overt event include a large explosion of a chemical container or a release
of a nerve agent in a subway, such as the
PATEL
And as
Martin mentioned, terrorism also can be covert, that is, an unrecognized
release in which the presentation of sick patients might be the first sign of
an exposure, such as deliberate contamination of food, water, or a consumer product.
An example
of a recent covert event would include the ricin incidents where castor beans
were ground up and ricin was extracted and put into the mail system with the
specific intent of harming individuals.
BELSON
Previous
events, some very recent, involving intentional or inadvertent contamination of
food or product tampering with chemicals have highlighted the need for
physicians and public health officials to be at heightened alert for patients
in their communities who have signs and symptoms consistent with chemical
exposures.
PATEL
Lets begin
with our first example of how the presence of ill people might be the first
sign of a deliberate contamination or a terrorist event.
In January
2003, 18 people from four families became ill after eating ground beef that was
purchased either on Dec 31st or Jan 1st.
Symptoms included nausea, vomiting and a burning sensation in the mouth;
one person developed atrial fibrillation.
None of the patients required hospitalization.
Since
ground beef was the only commonality, the supermarket, in conjunction with the
Michigan Department of Agriculture and the USDA issued a recall of
approximately 1700 pounds of ground beef. 120 people returned the recalled
product and 36 more people reported being ill.
Company officials submitted samples of ground beef provided by the ill
families to a private lab where they found high concentrations of nicotine in
the beef.
The
supermarket issued multiple press releases and recall notices. It was eventually discovered that the product
was contaminated at a single store rather than at the processing plant. The local health department alerted hospital
EDs and local medical practices in the area.
In all, 92 people had an illness consistent with nicotine poisoning
after eating the contaminated beef.
An employee
of the supermarket intentionally poisoned 200 pounds of beef with a nicotine
containing insecticide. He was
subsequently arrested and indicted for this event.
BELSON
Prevention
of potential future events, such as the example given by Manish, are a real challenge because of the large number of toxins
and chemical agents and the infinite combination of agents and dissemination
scenarios.
Despite
some difficulties in recognizing illness from a covert exposure, there are ways
to overcome the challenges. We will
focus on what health care workers and public health professionals can do to
improve recognition of covert illness from intentional contamination through
food, water, or medications. We will
offer epidemiologic clues and clinical signs or patterns of illness that might
suggest covert release of a chemical agent.
Early recognition of illness associated with these types of exposures is
vital because early detection of an outbreak has the greatest potential for
limiting the scope of the illness.
PATEL
We will
also discuss public health strategies for responding to intentional chemical
releases and emphasize the importance of reporting and surveillance so that
public health authorities can implement the appropriate emergency response and
public health actions.
GOOD
Okay
Manish, why dont you start us off with a discussion of why a covert release of
a chemical agent might be difficult to identify?
PATEL
I will be
glad to. The way we see it, there are six obstacles that might delay the
recognition of a chemical-related illness. We will discuss each one of these in
detail.
These
obstacles include the potential for delayed health effects that might occur
with certain chemicals; the outbreak may occur over an extended period of time
with gradual presentation of cases following certain exposures; in a terrorist
scenario, there also is a potential for exposure to multiple agents; some
chemicals are also notorious for causing non-specific illness resembling other
common natural illnesses; and lastly, many chemical-related illnesses are not
encountered that often and this lack of familiarity may make it difficult to
recognize and treat these illnesses.
Lets
discuss our first obstacle. Chemicals do
not always cause acute and obvious health effects. Immediate symptoms of chemical exposures
might be nonexistent or mild despite the risk for long-term effects. Because of this lag time, it may be difficult
for us to recognize the exposure source leading to the illness.
BELSON
Some
examples include pharmaceutical agents such as digitalis, which can cause toxic
effects at very small doses and symptoms may not be evident for up to several
hours.
Depending
on the dose and the chronicity of exposure, symptoms from heavy metal poisoning
such as dimethylmercury or lead poisoning may not be evident for weeks to
months.
Warfare
agents such as phosgene may result in pulmonary edema up to 48 hours after
exposure.
Carcinogens
such as aflatoxin may not result in a detectable illness for years.
Reproductive
toxins such as isotretinoin or Accutane are also examples of agents leading to
delayed health effects.
Chemical
toxicity also depends on dose-gradient or dose-response. In other words, those further away from a
source, inhalational for example, or those who consumed less of a contaminated
product will be affected less.
Physicians
and public health professionals will need to try innovative approaches and
think outside the box to detect these illnesses and prevent further morbidity
and mortality.
PATEL
Thats
right, Martin.
As you can
see in this graphic,
the
second possible obstacle to recognition could be from contamination of food,
water, or consumer products, especially at a location such as a distribution
facility. Unless detected early, the
ongoing community-wide exposure may continue through the distribution
chain. This might result in reports of
illness to physicians over a long period and in various locations, such as
grocery stores and pharmacies, through the city, state, or possibly across the
country.
GOOD
What are
your thoughts on that, Martin?
Can you
give us an example to demonstrate that point?
BELSON
Yes,
Cynthia, I do have a good example of an incident involving the adulteration of
medication that caused illness over a couple of days in different areas of a
city.
In 1983,
seven sudden deaths occurred over a two-day period in several different suburbs
of
At first,
the deaths appeared to be unrelated as the first patient was initially believed
to die of a stroke and the second appeared to have suffered a massive heart
attack. But an astute physician at a
The
physician reported the cases to the regional poison control center and based on
the signs and symptoms, cyanide was suspected and subsequently confirmed. Also, an investigation into these deaths
progressed when two observant off-duty firefighters made the connection of the
deaths to Tylenol.
Subsequent
investigation by law enforcement and public health agencies revealed that eight
bottles of Extra-Strength Tylenol had been removed from six different
Two lots of
Extra-Strength Tylenol were recalled from the market when the link was
made. This recall involved over 250,000
bottles. FDA issued a national warning
not to take any Extra-Strength Tylenol.
As you would expect, there was nationwide concern.
Within days
FDA had inspected more than a million Tylenol capsules from across the nation
and fortunately no additional cyanide-laced capsules were found outside of the
A priority
in the investigation was to determine the location of the tampering. Was it during the manufacturing process,
during shipping, or at the retail level?
Because the
cyanide-laced Tylenol was discovered in shipments from more than one plant and
had only turned up near
For years
following this incident, a wave of copycat tamperings with cyanide occurred in
the
GOOD
Thats a
frightening story. Manish, what are some other obstacles in recognizing a
chemical-related illness?
PATEL
Another
obstacle that could lead to difficulty in recognition might be exposure to
multiple chemical agents.
For
instance, simultaneous exposure to a nerve agent and arsenic would result in
obvious clinical effects that would likely resemble a cholinergic syndrome . .
. in other words, patients are likely to have
excessive salivation, lacrimation, sweating, vomiting, diarrhea, and pulmonary
secretions.
In the
setting of a chemical terrorism event, the likely diagnosis will be nerve agent
poisoning and providers will institute the appropriate therapy . . . atropine
and pralidoxime. However, in this scenario,
arsenic is likely to be overlooked.
Arsenic most likely will cause vomiting and diarrhea but will not result
in an obvious toxidrome leading to a rapid diagnosis in this setting.
BELSON
So Manish,
as a physician if it is already difficult for me to recognize an illness
related to a single covert exposure, how do I recognize an exposure that
potentially involves more than one chemical agent?
PATEL
Good
question Martin. We are often taught the
principle of Occams Razor, which states that even things
which seemingly do not fit together well can be explained by ONE unifying
theory, or in other words, one cause typically explains the entire clinical
picture. Although this may be true with
a naturally occurring disease, with a malicious event keep in mind that more
than one agent may be introduced into the environment.
So, in
answer to your question, initially, I would recommend treating the patients
signs and symptoms at hand, however, for admitting physicians and public health
officials, it may be prudent to consider a wider differential and make use of
available environmental & biological screening tests to rule out other
reasonable causes of illness.
BELSON
Thanks,
Manish. That really makes sense.
You know,
chemical poisoning also is notorious for resulting in nonspecific signs or
symptoms that resemble other common diseases.
For
instance, arsenic is very likely to resemble viral gastroenteritis.
Inhalation
of ricin will result in a non-specific illness with generalized fatigue,
malaise, and constitutional symptoms.
Acute lead
poisoning may lead to neurologic emergencies such as status-epilepticus or
encephalopathy that may be misdiagnosed initially as meningitis.
Cyanide, a
potent cellular poison, will lead to shock and acidosis which could easily be
mistaken for more common causes of shock such as acute cardiac failure and
sepsis.
PATEL
Finally,
physicians might be less familiar with recognition and treatment of illness
related to chemical agents simply because illness from most chemicals is just
not that common or at least not recognized as often as it occurs.
Take for
example:
Paraquat .
. . a toxic herbicide still available across the world;
cyanide .
. . another commonly found potent poison;
and then
there is ricin. There are very few clinicians
in this world, much less this country, who have ever seen a case of ricin
poisoning. However, ricin is a potential
agent of chemical terrorism.
Poisoning
from metals such as thallium, mercury and arsenic also is not commonly seen.
BELSON
And one
last obstacle I should mention is that some chemicals and toxins such as ricin,
present unique advantages for deliberate contamination because they tend to be
odorless, colorless, and tasteless.
PATEL
Let me give
you an example that nicely illustrates the non-specific illness caused by
certain chemicals and the difficulties encountered even after these illnesses
are recognized.
On a Sunday
afternoon during the spring of 2003, there was a church bake sale in the small
town of
During the
church function, sixteen adults became acutely ill with gastroenteritis like
symptoms. Most people had vomiting, some
had diarrhea, and a few became hypotensive.
After these patients arrived at the local ED, a relatively small
facility, the staff immediately recognized the cluster of illness and called
the hospital infection control nurse.
Rightfully so, the initial concern was that this cluster was an
infectious or a typical food borne illness.
The regional
poison control center was also called.
At this point one person was in the ICU with the diagnosis of sepsis and
five patients were hypotensive. The PCC
staff and toxicologist immediately recognized the unusual nature of the
clinical course for people with typical food borne gastroenteritis. They suggested a chemical as the cause of the
illness.
Preliminary
epidemiology suggested coffee as the source of illness. The state laboratory
was immediately prepared for wide-screen testing of chemicals and biologic
agents. The following morning, on
Monday, biological samples were couriered to the state lab, maintaining chain
of custody. Samples arrived at the state
lab at
High levels
of arsenic were identified in the coffee and the biologic samples within 24
hours of patients presentation to the ED.
By any
standard, this was a phenomenal response by the health care workers, public
health and law enforcement agencies of
GOOD
Manish, I
know you are an emergency physician, but were there any ongoing treatment
issues or follow-up considerations for these patients?
PATEL
Yes
Cynthia, but recognition was only part of the battle.
As we
discussed, lack of familiarity with treatment of illness related to chemical
agents is also likely to be a problem, simply because we do not see these
outbreaks frequently. Beyond
recognition, there were many difficulties with regards to the appropriate
treatment of arsenic poisoning, the availability and shipment of antidotes, how
long to observe patients, how long to pursue cardiac monitoring, the frequency
of laboratory analysis, and the expected prognosis of the patients.
In
addition, illness from chemical exposures is typically thought to be
short-lived; in other words, a misperception might be that patients usually
survive without complications or die shortly after a chemical exposure.
However,
arsenic is a perfect example of how certain chemicals are also notorious for
causing long-term complications such as skin cancer and cardiac arrhythmias.
GOOD
All of this
really sounds overwhelming and fatalistic.
But are there ways to prepare ourselves for the challenges posed by
these chemicals?
Martin,
what can we do to recognize these potentially covert events?
BELSON
That is
exactly what we are going to spend the remainder of the hour on . . . specific
strategies to recognize illness associated with the covert release of a
chemical agent into the environment.
Despite
some difficulties in recognizing illness from a covert exposure, there are ways
to overcome the challenges. Ultimately,
it involves familiarity with the epidemiologic clues and the syndromic
presentations of chemical agents exposures.
First,
lets discuss the epidemiologic clues that might suggest the covert release of
a chemical agent. The first clue is an unusual increase in the number of
patients seeking medical care. These
patients may seek care in clusters all in the same day, or may be spread out
over time, such as over a period of weeks.
An excellent
example of an increased number of patients seeking medical care is the arsenic
poisoning outbreak in
This event
was detected by national poison control center surveillance because astute
health care workers recognized the event as a possible noninfectious poisoning
and reported the cases to their regional poison control center.
The
poisoning surveillance system detected an increase in the number of poison
exposures for the hour that the cases were called into the Northern New England
PCC. Based on the surveillance methods,
the expected number of poisoning calls for this center between
Obviously,
the regional poison center was aware of this cluster and helped manage the
patients involved;
however,
its important to not only recognize this on the local level but also on a
national level in order to identify trends or patterns of illness at other
locations throughout the country. This
would be crucial in a potential widespread terrorist act.
Another
very useful epidemiologic clue is the cluster of illness in people who have a
common exposure, such as drinking water or eating food from the same source:
PATEL
The
As it
turned out, all of the ill people ate beef purchased from the same store prior
to becoming ill.
GOOD
Martin, it
appears that a detailed historical evaluation is crucial in this type of
circumstance.
BELSON
Yes
Cynthia, you are correct. This really
points out the importance of what we have all been taught early in our training
. . . to ask and record the food and beverages consumed by the patient prior to
a GI illness.
Another
epidemiologic clue is the rapid onset of symptoms after an exposure to a
potentially contaminated medium.
PATEL
Both the
Again, this
points out the importance of a detailed epidemiologic investigation.
BELSON
Unexplained
death of plants, fish, or animals, either domestic or wild, is an additional
epidemiologic clue that might suggest the covert release of a chemical agent.
PATEL
Absolutely! For example, just this past spring CDC and
state and local health officials investigated the death of several dogs shortly
after the dogs swam in a lake in
Fortunately,
no significant illness occurred in humans living around the lake, but the death
of the dogs alerted public health officials to a potential human health threat.
BELSON
Lastly,
unexplained deaths among young or healthy people may alert you to a covert
Chemical illness.
PATEL
I have an
example that nicely illustrates your point.
During a six-month period between November of 1995 and July of 1996, 109
previously healthy children were admitted to the University hospital in
Members of
multiple international agencies collaborated with the hospital and the Ministry
of Health of
Subsequent
laboratory analysis of the product revealed high concentrations of diethylene
glycol, a known human toxicant.
Traceback investigation revealed that DEG contaminated a shipment of
glycerin imported to
Withdrawal
of the glycerin-containing products from the market resulted in an abrupt
cessation of cases.
GOOD
Thanks
Manish, for your description of that unfortunate, but educational,
outbreak. Martin, I believe you have
some information about the recognition of a chemical event.
BELSON
Yes,
Cynthia. I would like to turn our
attention to toxicologic syndromes, another useful tool in the recognition of a
chemical event.
A toxic
syndrome can be defined as a constellation of clinical signs and symptoms
typical for a given chemical exposure.
The photos
seen here represent the clinical syndrome for a vesicant, or blistering agent,
exposure, in which large bullae are present along with eyelid edema and
conjunctivitis.
Many
chemical agents could be used as covert weapons, and the actual clinical
syndrome will vary depending on the type of agent, the amount and concentration
of the chemical, and the route of the exposure.
Also, some
syndromes can be caused by many different agents. For example, caustics and corrosive chemicals
can also cause a syndrome similar to the vesicants syndrome shown in the
previous graphic.
In general,
treating exposed people by clinical syndrome rather than by specific agent
probably is the most pragmatic approach to the treatment of illness caused by
chemical exposures.
PATEL
As Martin
mentioned, the list of chemical agents is exhaustive. The bright side, however, is that because
many agents have similar chemical properties, there are a limited number of
clinical syndromes. Certain of these
clinical syndromes are more likely to occur than others based on factors such
as high toxicity and ease of availability and dispersal of certain chemicals.
In
recognizing covert CT events, the KEY message to remember is that, it will
really involve recognition of patterns rather than individual cases . . . the
pattern to recognize will involve a combination of epidemiologic clues and
clinical syndromes.
One classic
example of a clinical syndrome that we should be aware of is cellular
hypoxia. When we talk of agents that
cause cellular hypoxia, we are talking about chemicals that impair the ability
of our bodys cells to utilize oxygen.
Signs and symptoms are typically nonspecific and, depending on the dose,
may be mild, such as nausea, vomiting, and headache, or severe such as
delirium, dyspnea, hypotension, seizures, and metabolic acidosis.
The
hallmark of toxicity in this syndrome is acidosis, particularly unexplained
acidosis.
Again, an
isolated case of unexplained acidosis is not something that would tip off
clinicians; however, if combined with the epidemiologic patterns we discussed
earlier, a CT event should be considered.
BELSON
Manish, let
me mention here that one reason that the cyanide outbreak in
PATEL
Thanks
Martin.
Toxins
causing cellular hypoxia include:
Cyanide,
the most likely CT agent in this group;
carbon
monoxide,
hydrogen
sulfide,
sodium
monofluoroacetate, which is an agent used as a rat poison in the past;
and
sodium azide, an industrial chemical.
Another
clinical syndrome is one with a combination of peripheral neuropathy and CNS
effects.
Signs and
symptoms of peripheral neuropathy may include:
muscle weakness, sensory loss in the glove and stocking pattern, and
depressed deep tendon reflexes.
CNS signs
and symptoms include memory loss, delirium, ataxia, and encephalopathy. Examples of toxins responsible for this
syndrome are lead, thallium, organic mercury, acrylamide, hexane, carbon
disulfide and inorganic arsenic.
Although
this syndrome can present after an acute exposure to these agents, the signs
and symptoms may develop days to weeks . . . and even months . . . after the
initial exposure.
We will
really have to be hypervigilant about recognizing these presentations. I believe Martin has an excellent example for
this syndrome.
BELSON
Yes. In 1988, three members of the same family
became ill with an unknown disease.
They
acutely developed parasthesias,
extremity
weakness, blurred vision, dry mouth, and cranial nerve abnormalities followed
by psychosis.
Initially,
botulism was the suspected diagnosis.
However, all three developed alopecia or hair loss This
finding prompted urinary screening for heavy metals. Thallium poisoning was confirmed in all three
patients.
The mother
died two months later of an acute respiratory arrest and her two sons survived
but suffered from persistent upper and lower muscle weakness.
Following
an exhaustive epidemiologic and environmental investigation, it was determined
that the source of the thallium was the contents of soft drink bottles found in
the home.
The
evidence that thallium was introduced into the bottles after purchase from a
store included the fact that cases were only within one family, evidence of
bottle tampering existed, and an anonymous death threat against the family six
months before the illnesses had occurred.
Ultimately, a neighbor was arrested for the crime one year later.
PATEL
Good
example! Lastly, the classic syndrome
that we have all heard about is cholinergic crisis.
The typical
signs and symptoms leading to diagnosis of this syndrome will be excess
secretions such as salivation, lacrimation, diarrhea, diaphoresis,
bronchorrhea, and urination. Other signs
and symptoms include miosis, fasciculations, weakness, bradycardia or
tachycardia, hypotension or hypertension, delirium, and convulsions. Toxins resulting in the cholinergic crisis
might include nicotine, organophosphates, nerve agents, and carbamates.
BELSON
Let me give
you an example of an outbreak involving signs and symptoms consistent with
cholinergic crisis.
On
Two nights
later, on July 1st, a second incident occurred
involving two people who consumed striped watermelon. Symptoms were similar to those of the first
group. These incidents were reported to
the Health Division which determined all the watermelons were linked to the
same distributor. The distributor
voluntarily recalled the watermelons.
Surveillance
was initiated after the second group of cases in which five area emergency
departments were alerted and asked to report cases. Over the July 4th holiday, additional cases
were reported from
Both
striped and green watermelons were implicated from multiple distributors, and
residues of the pesticide Aldicarb, a potent carbamate, was detected in some
watermelons. Consequently, all
watermelons were recalled on July 5th by the Health Division and the Oregon
Department of Agriculture. Similar
action took place in
GOOD
Wow. Let me
ask you guys another question. I have
heard that patients or their clothing may have a particular odor after a
chemical exposure. Is this true and do
you have any specific examples?
PATEL
Yes, for
example, the smell of tobacco suggesting nicotine or the smell of garlic
suggesting arsenic or organophosphates.
A description of rotten eggs odor suggests hydrogen sulfide, and the
smell of freshly cut hay suggests phosgene.
However, we
must admit that chemical odors have not traditionally been a sensitive method
of detecting poisonings. If you smell
it, great, you may have a diagnosis.
But, don't expect an odor on every patient exposed to a chemical.
GOOD
The
watermelon-Aldicarb outbreak just discussed exemplifies some important points
that we would like to turn our attention to.
Up until now, we have talked about how critical it is for health care
providers to recognize illness related to a possible CT event. Now
Manish,
lets switch our focus to the reporting of events . . . a critical step for
improving and protecting public health.
PATEL
Thank you,
Cynthia. There are surveillance programs that are undertaken by state and
federal public health agencies to recognize CT events. However, the Achilles heel for these
surveillance programs is reporting.
For
example, when Im working in the ED, I may not consider one or two suspicious
cases to be important to report; however,
one or
two cases at each of the ten EDs in a city might add up to a significant public
health event. And for covert CT events,
time is of the essence! The earlier an
event is recognized and reported, the sooner we will be able to implement the
measures to limit further disease.
BELSON
I can see
myself in the ED hesitant to report a case unless I have laboratory
confirmation. How would you advise the
emergency physician on that point?
PATEL
Well, we
want to hear about cases as soon as possible.
I would recommend not to delay reporting for
laboratory confirmation but to report based on clinical suspicion or
presumptive diagnosis. Remember,
surveillance was initiated at the onset of the watermelon-aldicarb outbreak
because of the initial report filed by the physician who recognized the index
case. This probably led to an earlier
identification of the outbreak than would otherwise have occurred over a
holiday weekend.
BELSON
One
misconception that may discourage me from reporting is that my notification may
lead to unnecessary and unfruitful investigations.
PATEL
That is
also a very important point. I think
its crucial to note that reporting does not necessarily mean that some serious
action must take place. Beyond data
gathering, other steps of surveillance include data analysis and interpretation
before any action takes place. Going
back to our analogy, one or two cases from a single ED may not cast any further
suspicion by the public health agency other than logging the cases in a
database. However, if more similar cases
are detected, from other EDs in the area for instance, then a detailed
investigation may be warranted.
It is
important to re-emphasize that reporting should be burden-free and replete with
redundancies . . . for example, clinicians should not have to take a great deal
of time out of their busy workload to decide who to report to. Just getting the ball rolling by calling any
of the following agencies such as the PCC, local or state health department, or
even the hospitals infection control nurse, will be enough to mobilize the
necessary resources.
GOOD
Good
point. Now, Martin can we take a look at
how reporting potential chemical exposures to your regional poison control
center not only will assist you with patient management but also have a
potential impact on poisoning surveillance on a local and national level?
BELSON
Of course Cynthia.