Not all disasters are easily recognized in their earliest stages. Although disasters caused by weather events (e.g., tornadoes, hurricanes, lightning), geologic events (e.g., earthquakes, volcanic eruptions), and some technological events (e.g., bomb explosions, nuclear reactor accidents, structural failures) are quickly attributable to a physical source, other disasters such as acts of biological, chemical, or radiological terrorism, or even some vehicular collisions or accidents, may not be readily recognized or characterized. Recognizing and responding to these types of disasters require patience, a high level of awareness, clinical astuteness, and rapid epidemiological assessment and response. Disasters that manifest as physical illness in a population may go unrecognized over a period of time and not become apparent until many persons become ill or die, or the contaminating or infectious agent is identified as one that does not commonly occur or does not appear to be a plausible natural finding (such as smallpox anywhere on Earth or anthrax in Washington, DC).
When an illness is attributed to an unexpected biological, chemical, or radiological agent, information from a detailed patient clinical and epidemiological history is the most effective tool to distinguish “accidental” or “natural” outbreaks from “intentional” or “terrorism-related” outbreaks. Local and state public health authorities also will engage law enforcement agencies to begin concurrent criminal investigations, although in the United States, once a terrorist event has occurred, the Federal Bureau of Investigation (FBI) will take the lead and have ultimate responsibility for managing the event.
Biological, chemical or radiological terrorism is the deliberate use of any of these agents against people, animals, water sources, or agriculture to cause disease, death, destruction, or panic for political or social gains. The only factor differentiating an accidental event from a terrorist event may be the malicious intent. Historically, there have been serious outbreaks that have been mistaken for intentional terrorist attacks, outbreaks for which terrorism was quickly ruled out, and an outbreak that was presumed to be a natural food-borne outbreak and was not discovered to have been an act of terrorism for nearly a year.
Two naturally occurring infectious disease outbreaks in the United States were initially feared to be the result of terrorist attacks: the Hantavirus pulmonary syndrome outbreak of 1994 and the West Nile virus outbreak of 1999. Both were caused by newly emergent infectious diseases and required careful evaluation of both clinical and epidemiological data to assign causality. In each case, a viral pathogen was identified that was not previously endemic to the United States. Both outbreak investigations yielded reasonable alternative explanations that refuted the terrorism hypothesis.
The smallpox outbreak of 1978 in England, is an example of an accidental outbreak that today would certainly raise suspicions of a terrorist attack. The last case of naturally occurring smallpox anywhere in the world was diagnosed in Somalia in 1977, and naturally occurring smallpox had not been seen in England since 1975. Ten months after the world’s last case, a 40-year-old woman in Birmingham, England, was diagnosed with smallpox. She died 3 weeks later, but not before infecting her mother, who recovered, and perhaps her father, who though febrile died of a myocardial infarction within the incubation period of the disease. Prompt vaccination of contacts and isolation of febrile contacts quickly extinguished the outbreak. (Similar isolation techniques were used in the Ebola case in Dallas, Texas, in 2014, albeit without the benefit of having a vaccine available.) Public health investigators concluded that the source of the outbreak was most likely the smallpox laboratory at the University of Birmingham. The index patient was a medical photographer who worked in an office immediately above the laboratory. Matching strains of smallpox confirmed the source, although the route of virus transmission is less certain. This was the last outbreak of smallpox in the world. In May 1980, the World Health Assembly declared smallpox to be eradicated from the planet. Any smallpox outbreaks that occur posteradication most likely will be first investigated as a terrorist event, even if a laboratory accident is suspected.
During the anthrax attacks of 2001, the first case of anthrax was initially suspected to be naturally occurring. The index patient, a resident of Florida, traveled through rural North Carolina 3 days prior to becoming ill with inhalational anthrax, an uncommon diagnosis even in animal handlers, and an even more unusual diagnosis in an office worker. As anthrax spores are regularly found in soil, and cases can occur sporadically among persons who have been exposed to animal products such as animal skin blankets and goatskin drums that have been contaminated by soil, this particular person did not have any sources of animal exposure. When further epidemiological investigation revealed anthrax spores in the patient’s workplace and a co-worker became ill with inhalational anthrax, terrorism was recognized. In this attack, 21 persons were infected via the postal system, intentionally contaminated by spores that had leaked out of envelopes going through a highspeed mail-processing machine. The envelopes had been used to mail anthrax spores to prominent Congressional and media personalities. This case study illustrates the importance of considering terrorism when investigating outbreaks that occur in unusual geographic locations (e.g., anthrax in urban or suburban Florida instead of a rural area), among unusual populations (e.g., office workers with no animal contact, when typical cases are in handlers of goats and other animal skins), inhalational form of the infection (when 95% of naturally acquired cases are of the cutaneous type), and in clusters (e.g., more than one person in the same office). It also illustrates that more advanced microbiological techniques are usually required in order to process and possibly weaponize biological agents, so trained lab technicians involved in such cases may be the recipients of extra scrutiny.
A final example is that of the Salmonella outbreak in The Dalles, Oregon, in 1984. A total of 751 cases of Salmonella typhimurium , the largest outbreak of food-borne gastroenteritis in the United States that year, were linked to restaurant salad bars, 10 of which had been intentionally contaminated, in secret, by members of the Rajneeshee religious cult, in an attempt to affect a Wasco County election by limiting the turnout. The event was initially felt to be a food-borne outbreak. The link to the cult was only identified more than a year later when definitive evidence was found. , In this setting, a number of restaurants had less than adequate food management practices, and isolation of the same organism from multiple sites suggested a common food-borne bacterial source. In retrospect, further cases of intentional poisoning of individuals by the same group were identified. The additional significance of this case is that not all terrorism or intentional transmission of infectious agents will involve organisms with high mortality, and the fact that this outbreak was from an organism commonly encountered in food-borne outbreaks in the United States may have played a role in the delay in identifying it as an intentional act of terrorism.
A review of all Centers for Disease Control (CDC) outbreak investigations around the world from 1988 to 1999 found that 44 of the 1099 investigations (4.0%) involved organisms considered to have bioterrorism potential. Intentional use of infectious agents was considered in six of these investigations. In the early stages of the 2014 Ebola outbreak in West Africa, there was some concern it may have been intentional because it occurred outside of the virus’s normal geographic pattern, as well as the remarkably small number of viral units needed to cause illness. As of this writing there has been no definitive evidence pointing to this being an intentional event.
Disease outbreaks have occurred and been investigated for many years. However, recent events such as the 2001 anthrax attacks in the United States and the 1994 and 1995 Sarin gas attacks in Japan make it necessary to consider terrorism when evaluating clusters of infectious and noninfectious diseases. A terrorist agent may be a very common organism, such as influenza or Salmonella, or may be a more exotic organism such as variola virus, Q fever, or Ebola virus, which is more easily obtainable during the current epidemic in West Africa.
Unusual clusters of illness may signal terrorist events that require prompt public health and law enforcement responses. Although most clusters of disease will have a source other than a deliberate act of criminal intent, terrorism should be considered in the differential diagnosis. The evaluation of each situation must be based on its specific context.
As noted above, today a single case of smallpox would be immediately investigated as a case of biological terrorism; however, some events may be subtler. When investigating a disease outbreak, there are a number of clues that should heighten the suspicions of the clinician and epidemiologist that a terrorist attack has occurred. Because no list of clues can be all-inclusive, all health care providers should be alert for the possibility that a patient’s condition may not have occurred through natural means.
Although terrorist attacks could ultimately affect large numbers of people, disease in a single patient may be the first clue. Disease caused by an uncommon organism, such as smallpox, anthrax, or viral hemorrhagic fever, may signal a sentinel event of bioterrorism. Suspicion may be further heightened by a less common presentation of one of these organisms. For example, whereas a small number of cases of cutaneous anthrax occur naturally each year in the United States, cases of inhalational anthrax are highly unusual. Furthermore, should a disease present in a geographic location where it is not usually seen, such as anthrax in a nonrural area or plague in the northeastern United States, further investigation into the possibility of bioterrorism is needed. Unexpected seasonal distribution of disease, such as influenza in the summer (which, however, can occur with pandemic influenza strains), or antiquated, genetically engineered, or unusual strains of infectious agents, may also be clues. Multiple unusual or unexplained diseases in the same patient may indicate that multiple organisms or substances were used in an intentional act, as could disease presenting in an atypical age group or population, such as anthrax in children or varicella-like rashes in adults. Additionally, a single case of an unusual infection may in fact be that of the perpetrator himself who may have accidentally exposed himself to the causative agent or may be an intentional carrier on a suicide mission.
When a disease strikes more than one person, additional clues may arise. Large numbers of cases of unexplained disease or death may signal bioterrorism, as may an unexplained increase in the incidence of an endemic disease that previously had a stable rate. If an unusual condition strikes a disparate population, such as respiratory illness in a large population, this may signal the release of a chemical or biological agent, as would a large number of people seeking medical care the same time, signaling they may have been present at a common site when an agent was released. Likewise, large numbers of persons presenting with similar illnesses in noncontiguous regions may be a sign that there have been simultaneous releases of an agent at multiple sites. Finally, animal illness or die-off that is temporally related with human illness or death may signify the release of an agent that affects both humans and animals. When there is no other explanation for an outbreak of illness, it may be reasonable to investigate terrorism as a possible source. Common sources of exposure to an infectious agent may include food and water that has been deliberately contaminated, respiratory illness due to proximity to a ventilation source, or the absence of illness among those in geographic proximity but not directly exposed to the contaminated food, water, or air.
Each event must be evaluated in context. Terrorism is still the least common explanation for disease, and other more frequent explanations should be evaluated and ruled out. Clues that may raise the suspicion that an intentional event has occurred can be broken down into some general categories: epidemiological, unusual variations in disease outbreaks, unusual characteristics of disease, and animal signals.
A single case of an unusual disease, such as plague, smallpox, or anthrax, without an acceptable epidemiological explanation
Illness among persons with exposure to a common ventilation source and absence of disease among persons not exposed to that ventilation source (potential intentional aerosol release of an agent)
Large numbers of persons seeking care for a similar condition at the same time (may indicate a point source)
Clusters of similar disease outbreaks in disparate geographic locations (potential of multiple attacks)
Large numbers of cases of unexplained diseases or deaths
Unusual Variations in Disease Outbreaks
Unexplained increases in an endemic illness, such as an increase in plague cases in the southwestern United States
Disease occurring outside of its usual geographic distribution, such as plague or Hantavirus occurring in the northeastern United States
Disease that appears to be transmitted via common exposure to an aerosol, food, or water that may have been intentionally contaminated
Unusual Characteristics of Disease or Agents
Isolation of a genetically engineered, antiquated, or laboratory-manufactured form of an agent, which may have unusual or unexpected characteristics
Isolation of a weapons-grade form of an agent
Isolation of a known organism with an unusual antibiotic microbial-resistance pattern
Unusual presentations of clinical disease, such as pneumonic plague (rather than bubonic plague usually caused by bites from infected fleas) or inhalational anthrax (rather than the more common cutaneous presentation, which is seen 95% of the time)
Common disease with a higher than expected mortality, or decreased patient response to usual treatments
Several conditions or clinical syndromes occurring in the same patient, which may indicate genetically engineered or artificially combined agents
Disease or syndromes occurring in unusual populations, such as outbreaks of chickenpox-like rash in adults or anthrax among office workers
Unusual disease outbreaks that occur across a large geographic area, suggesting the aerosol release of an agent
Similar genetic types of a pathogen identified across disparate geographic locations or at different times in the same location
Other Species Signals
An unusual pattern of animal disease or death preceding human disease or death, or an unusual pattern of animal disease or death that follows human disease or death; either may indicate a large-scale release of an agent, with differing susceptibilities between animals and humans
Insect die-off or plant die-off associated with human illness may indicate an environmental chemical release in which the symptoms of human poisoning syndromes may be nonspecific
Physical findings in the environment such as liquid droplets or puddles, powders or dusts, vapors or clouds, or unusual odors in the vicinity of human or animal cases may indicate a release of a biological, chemical, or radiological agent.
Radiological and Chemical Agents
Although these examples focus mostly on biological terrorism, the tenets presented apply to radiological and chemical events too. Covert radiological events, such as intentionally hiding a cobalt or cesium source stolen from a medical or veterinary facility, may expose many unsuspecting people. With accidental exposure, involved persons again may not realize that they have been exposed, such as in the 1987 Goiania incident in Brazil in which a canister of cesium-137 was inappropriately discarded by a cancer treatment facility. One family brought home the sealed radioactive element and unwittingly exposed multiple family members, who then became ill. Neighboring families came to look at the fluorescent blue substance, some covering their skin with it. Although clinicians did not make the link to radiation exposure in this cluster of illness, the family’s grandmother realized that her family became ill shortly after the radioactive canister entered their home. She surrendered the canister to health authorities, though not before an estimated 244 people in the community were exposed.
With sufficient exposure, whether intentional or accidental, multiple persons may present with acute radiation syndrome, which during its prodromal phase is characterized by nausea, vomiting, and diarrhea that last for several days after exposure. This is followed by a latent phase, during which a patient feels well for a few weeks until obvious radiation illness begins. This spectrum of clinical illness can easily be confused with a self-limited gastrointestinal illness, particularly if a number of people attend the same event during which the exposure occurs and then present with gastrointestinal symptoms. A thorough epidemiological investigation may rule out a common food source. A high index of suspicion for a radiation event should be maintained, especially when an infectious pathogen is not readily identifiable from clinical specimens. Patients with acute radiation syndrome may also experience cutaneous radiation syndrome, a dermatological condition consisting of erythema, pruritus, and desquamation. These cutaneous symptoms and findings, accompanied by gastrointestinal symptoms and the absence of an infectious pathogen in a cluster of patients, may indicate a radiation exposure, whether accidental or intentional. Hidden sources of exposure usually lead to diagnostic delays. Concealed sources of exposure usually lead to diagnostic delays; again, prompt epidemiological investigation of unusual cases can hasten the identification of a source, while criminal investigation is needed to determine possible intent.
Likewise, recognizing exposures to chemical agents can be challenging, even though the epidemiological clues listed above still apply. Chemical exposures may be overt and quickly recognized, as in the 1984 industrial chemical release in Bhopal, India, in which a release of methyl isocyanate killed 2500 people during the first week, and an estimated 3500 more over the following 10 years. Conversely, a chemical incident may be as covert as contamination of food, water, or consumer products. Some exposures may cause delayed health effects, making it more difficult to identify an exposure source or prove a cause and effect. Chemical exposures often cause nonspecific illnesses or syndromes of illness that are less familiar to many clinicians. Additionally, if chemicals are mixed, classic toxicological syndromes such as anticholinergic poisoning may not be apparent because patients may experience a broad array of symptoms rather than a single recognizable syndrome.
There are many case reports that illustrate these diagnostic and investigative challenges. In the United States, in the Tylenol tampering cases of 1982 and other medicine tampering cases like it, otherwise healthy patients who ingested cyanide-laced over-the-counter medications became seriously ill and multiple deaths occurred. In the Tylenol incident, the first two deaths were thought to be due to stroke and myocardial infarction. But an astute clinician linked the unexplained syndromes of hypotension and acidosis in multiple family members of the first victim, and subsequent toxicological testing revealed the presence of cyanide. This case report demonstrates the importance of considering chemical exposures when a cluster of patients presents with illness that is sudden, unexpected, and without a prodrome. When clinical information does not indicate a naturally occurring disease, toxicology screening for poisoning is a reasonable next step (however, a comprehensive toxicological screen may take days to perform and may still miss the offending toxin).
Similarly, unexplained deaths or serious illness in an otherwise healthy population may indicate a chemical exposure. Over a 6-month period in 1985, 109 children were diagnosed with anuric renal failure at a single hospital in Haiti. This condition had not been seen at the hospital in the prior 5 years. A trace-back investigation revealed that these children had ingested an acetaminophen syrup preparation that was locally manufactured from glycerin that was contaminated with diethylene glycol, the chemical used as automotive antifreeze. Ninety-nine of the children died. A criminal investigation ensued and determined that the poisoning was not intentional, but rather was caused by a departure from manufacturing quality control measures.
Pesticides are a group of toxic chemicals that are readily available to terrorists and also can accidentally contaminate the food supply, sickening large numbers of people in disparate geographic areas. In Oregon in 1985, a physician reported five cases of organophosphate poisoning resulting in cholinergic crises to the state Health Division. Epidemiological investigation revealed that the patients had become ill after eating watermelon. Additional cases were reported in Oregon, Washington, and California. Over a 3-month period, more than 700 cases were identified in seven states, and 483 cases occurred in Canada. The outbreak was linked to aldicarb sulfoxide poisoning. Aldicarb sulfoxide is a toxic metabolite of Aldicarb, the systemic pesticide that was used on the watermelons originating from California. The rapid notification of public health authorities led to timely identification of the poison, although the outbreak was protracted due to the far-reaching shipping network of the global food supply. The contamination was not found to be intentional. Aldicarb was banned by the Food and Drug Administration (FDA) in 2010 and is being phased out over a 7-year period. But this will not dissuade terrorist organizations or lone-wolf renegades from using it.
In another pesticide-related case in Michigan in 2003, 92 people became ill and 1700 pounds of ground beef were recalled due to nicotine-based pesticide contamination. However, in this case, the epidemiological investigation identified a single supermarket source of the contaminated meat, and the concurrent criminal investigation led to the arrest of a supermarket employee who intentionally contaminated 200 pounds of ground beef with Black Leaf 40 insecticide, which contains nicotine.
These pesticide contamination case studies illustrate the following: ( ) clinicians should consider chemical poisoning in outbreaks of unexpected serious illnesses; ( ) prompt reporting to authorities can lead to more rapid initiation of public health response and investigation by linking distant outbreaks to a common source; and (3) accidental and criminal events may involve the same clinical appearance of illness but can be distinguished by epidemiological and criminal investigations.