Hello and welcome to “Recognition of Illness Associated With Chemical Exposure”.
I’m Cynthia Good, your moderator for this program which is originating from 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 the Public Health Training Network.
The goal of today’s 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. thIf you’d like to register and evaluate this program, you can do so from August 5 through thSeptember 4, 2004 at www.phppo.cdc.gov/phtnonline. thThe Webcast and Web on Demand registration and evaluation begins September 5, 2004. The
course numbers are WC0061 for the webcast and WD0049 for Web on Demand.
If you have any questions about registration please call 1-800-41-TRAIN or you can e-mail us at firstname.lastname@example.org
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, National Center for Environmental Health, CDC and . . .
Dr. Martin Belson, Medical Toxicologist, Division of Environmental Hazards and Health Effects, National Center for Environmental Health, CDC
Since the September 11, 2001 attacks, there is increasing concern in the United States about other potential terrorist attacks such as those involving the use of chemical agents. thSeptember 11 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?
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 Tokyo sarin attacks in the 1990s.
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.
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.
Let’s 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.
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.
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.
Okay Manish, why don’t you start us off with a discussion of why a covert release of a chemical agent might be difficult to identify?
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
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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. Let’s 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.
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.
That’s 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.
What are your thoughts on that, Martin?
Can you give us an example to demonstrate that point?
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 Chicago. Three of these deaths occurred in one family and one death involved a 12-year-old child.
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 Chicago area hospital grew suspicious when two family members of the first victim were admitted to the hospital with severe hypotension and unexplained acidosis. 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 Chicago area stores over a
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period of weeks to months, and placed back on the shelves of five different Chicago area stores, as shown on the map. Five Tylenol bottles involved in the seven deaths were purchased at these five stores.
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 Chicago area. 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 Chicago, investigators concluded that any tampering occurred at the retail level. To this day, the perpetrator has not been identified.
For years following this incident, a wave of copycat tamperings with cyanide occurred in the United States including Lipton Cup-A-Soup in 1986, Excedrin and Tylenol in 1986, and Sudafed in 1991.
That’s a frightening story. Manish, what are some other obstacles in recognizing a chemical-
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.
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?
Good question Martin. We are often taught the principle of Occam’s 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 patient’s 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.
Thanks, Manish. That really makes sense.
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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.
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.
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.
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 New Sweden, Maine, which has a population of less than a thousand.
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 5:00 PM and were analyzed within two to three hours.
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 Maine.
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Manish, I know you are an emergency physician, but were there any ongoing treatment issues or follow-up considerations for these patients?
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.
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?
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, let’s 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 Maine, which involved 16 people. Reporting of such a large number of illnesses to the proper authorities is important for a number of reasons but there is one I would like to emphasize now.
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 6 to 7 PM is 13. On the day of the church poisonings, 17 calls took place to the poison center during this one-hour period. This resulted in an alert at the national level.
Obviously, the regional poison center was aware of this cluster and helped manage the patients involved;
however, it’s 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:
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The Michigan ground beef incident we discussed earlier is a perfect example. In this outbreak, there were four families with 18 people that initially became ill over a two-day period. As it turned out, all of the ill people ate beef purchased from the same store prior to becoming ill.
Martin, it appears that a detailed historical evaluation is crucial in this type of circumstance.
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.
Both the Michigan beef outbreak and the Maine arsenic event are perfect examples. In the arsenic outbreak, there were many reports of a “funny” taste to the coffee, and the onset of illness was within an hour of drinking the coffee.
Again, this points out the importance of a detailed epidemiologic investigation.
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.
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 Nebraska. Their deaths were attributed to a toxin released from Microcystins, a blue-green algae, found on autopsy and in the lake water.
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.
Lastly, unexplained deaths among young or healthy people may alert you to a covert Chemical illness.
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 Port-au-Prince, Haiti, with acute renal failure. 99 of the 109 children died. At this hospital, no children had been admitted with this diagnosis in the preceding five years. Members of multiple international agencies collaborated with the hospital and the Ministry of Health of Haiti to determine the cause of the outbreak, institute control measures, and evaluate their effectiveness. The epidemiologic investigation revealed that a locally manufactured acetaminophen syrup was highly associated with the illness.
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 Haiti from China.
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Withdrawal of the glycerin-containing products from the market resulted in an abrupt cessation of cases.
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.
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.
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 body’s 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.
Manish, let me mention here that one reason that the cyanide outbreak in Chicago was detected early was because an astute clinician recognized the unusual pattern of unexplained acidosis in two family members.
Toxins causing cellular hypoxia include:
Cyanide, the most likely CT agent in this group;
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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.
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.
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.
Let me give you an example of an outbreak involving signs and symptoms consistent with cholinergic crisis.
On June 29, 1985, in Oregon an astute physician reported to the State Health Division illness in five people occurring 30 minutes after eating striped watermelon. Two families were involved, and watermelon was the only food eaten in common. Symptoms included vomiting, diarrhea, salivation, blurred vision and fasciculations. This symptom complex initially led the reporting physician to suspect organophosphate poisoning.
stTwo nights later, on July 1, 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.
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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 Oregon, Washington, and California.
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 California and Washington.
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?
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.
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, let’s switch our focus to the reporting of events . . . a critical step for improving and protecting public health.
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 I’m 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.
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?
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.
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