Epidemiologic clues, alert clinicians key to detect covert chemical attack

But many obstacles still hinder early detection

Drawing upon a real-world lesson from the past, medical toxicologists recently recalled the 1983 Tylenol poisoning case in Chicago as an example of how a bioterrorism attack involving chemicals may begin to unfold. Though product-tampering protections have been improved, disturbing aspects of the case include how easy it was to accomplish and the fact that the perpetrator was never caught.

In 1983, seven sudden deaths occurred over a two-day period in several different suburbs of Chicago. At first, the deaths appeared to be unrelated. It was thought the first patient died 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," said Martin Belson, MD, a medical toxicologist at the Centers for Disease Control and Prevention (CDC) at a CDC satellite training broadcast. ". . . The physician reported the cases to the regional poison control center; and based on the signs and symptoms, cyanide was suspected and subsequently confirmed. The investigation into the 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 Tylenol had been removed from six different Chicago area stores over a period of weeks to months, and then placed back on the shelves of five different Chicago area stores. "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." Belson said.

A priority in the Tylenol investigation was to determine the location where the tampering took place. 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. More problematic would be a chemical poisoning of food, water, or consumer products at a location such as a distribution facility. "Unless detected early, the ongoing community-wide exposure may continue through the distribution chain," said Manish Patel, MD, MSc, a medical toxicologist at the CDC. "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."

Patel and Belson were the principal faculty in the broadcast on recognizing and responding to an intentional release of a chemical agent. Such an attack may be a covert or overt event.

"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." Belson said.

More insidious would be an unrecognized release in which the presentation of sick patients might be the first sign of an exposure. "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," Patel said.

Another real-world example described during the program occurred in Michigan in January 2003, when 18 people from four families became ill after eating ground beef. Symptoms included nausea, vomiting, and a burning sensation in the mouth. One patient developed atrial fibrillation, but none had to be hospitalized. Officials recalled approximately 1,700 pounds of ground beef. Overall, 120 people returned the recalled product, and 36 more people reported being ill. It eventually was discovered that the product was contaminated at a single store rather than at the processing plant. The local health department alerted hospital emergency departments and local medical practices. 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," Patel noted. "He was subsequently arrested and indicted."

Prevention of such attacks is a challenge because of the large number of toxins and chemical agents and the infinite combination of agents and dissemination scenarios, Belson said.

"Despite some difficulties in recognizing illness from a covert exposure, there are ways to overcome the challenges. 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."

Obstacles to early detection

However, there are many obstacles to early detection of a chemical attack, including the possibility that initial symptoms will not be dramatic. "Chemicals do not always cause acute and obvious health effects," Patel added. "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."

By the same token, some chemicals can cause nonspecific illness resembling other common natural illnesses. Chemical poisoning is notorious for resulting in signs or symptoms that resemble other common diseases, Belson noted. For example, arsenic is very likely to resemble viral gastroenteritis, he said.

"Acute lead poisoning may lead to neurologic emergencies such as status-epilepticus or encepha-lopathy that may be misdiagnosed initially as meningitis," Belson said. "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."

Many clinicians are not familiar with chemical-related illnesses, making initial diagnosis all the more problematic. "There are very few clinicians in the world, much less this country, who have ever seen a case of ricin poisoning," Patel said. "However, ricin is a potential agent of chemical terrorism. Poisoning from metals such as thallium, mercury, and arsenic also is not commonly seen."

Given that it is difficult to recognize an illness related to a single covert exposure, an attack involving more than one chemical agent might be all the more confounding. "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 and biological screening tests to rule out other reasonable causes of illness," Patel said.

Despite some difficulties in recognizing illness from a covert exposure, there are ways to overcome the challenges, Belson said. "Ultimately, it involves familiarity with the epidemiologic clues and the syndromic presentations of chemical agents exposures," he said. For example, the first clue suggesting a covert release of a chemical agent might be an 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," Belson said. Establishing thresholds of poison reports and other trigger mechanisms can be used in public health to sound the alarm.

"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," he said. "This would be crucial in a potential widespread terrorist act."

Look for common exposure

Another epidemiologic point of investigation is determining whether a cluster of illness is occurring in people who have a common exposure. "The Michigan ground beef incident we discussed earlier is a perfect example," Patel said. "In this outbreak, there were four families with 18 people who 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."

An epidemiologic clue suggesting covert release of a chemical agent is the unexplained death of plants, fish, or animals, either domestic or wild. "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," Belson said. "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."

Another clue that immediately should raise suspicions is death among young or healthy people. "In recognizing covert CT (chemical terrorism) events, the key message to remember is that it will really involve recognition of patterns rather than individual cases," Patel said. "The pattern to recognize will involve a combination of epidemiologic clues and clinical syndromes."

One classic example of a clinical syndrome that clinicians should be aware of is cellular hypoxia, he said. "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," Patel said. "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."

Indeed, Belson added, one reason the Tylenol cyanide outbreak in Chicago was detected early was because an astute clinician recognized the unusual pattern of unexplained acidosis in two family members.