1 What happened in Tokyo on March 20, 1995?

On March 20, 1995, at the height of morning rush hour, members of the Japanese Aum Shinrikyo religious cult placed containers of the deadly nerve agent sarin in various downtown locations of the Tokyo subway system and unleashed a new era in terrorism. This same group attempted unsuccessfully to deploy anthrax and botulinum toxin weapons on several occasions. The chemical warfare attack on Tokyo affected more than 5000 victims and caused 12 deaths.

Henretig FM, Cieslak TJ, Madsen JM, et al: Emergency department awareness and response to incidents of biological and chemical terrorism. In Fleisher GF, Ludwig S, Henretig FM (eds): Textbook of Pediatric Emergency Medicine, 5th ed. Philadelphia, Lippincott Williams & Wilkins, 2006, pp 135–162.

Rotenberg JS, Newmark J: Nerve agent attacks on children: Diagnosis and management. Pediatrics 112:648–658, 2003.

2 How is the Tokyo incident typical of recent terrorism?

Prior decades had witnessed numerous attacks targeted at military installations, government officials or representatives, or, on occasion, relatively small groups of ordinary civilians in highly visible circumstances. In the 1990s a new threshold was crossed, however, with the rise of religious terrorism that allows violence as a seemingly justifiable means to accomplish a sacred theological imperative. Several terrorist incidents over the past decade, such as the Oklahoma City bombing and, of course, the attacks of September 11, 2001, on the World Trade Center and the Pentagon have highlighted this new willingness to kill large numbers of innocent people indiscriminately. An especially disturbing scenario in terms of the medical management challenges posed is that of the use of biologic and chemical weapons as a means of terrorism. In 1984, the Rajneeshee cult sickened 750 citizens of The Dalles, a town in Oregon, by intentionally contaminating restaurant salad bars with Salmonella typhimurium. More recently, persons linked to white-supremacist militias have obtained anthrax, stockpiled the highly toxic substance ricin (a biotoxin extracted from castor beans), and have been arrested for transporting the bacterium Yersinia pestis, the etiologic agent of bubonic plague. In 1995, the FBI thwarted an attempt to release a chlorine gas bomb in Disneyland, an attack obviously targeted particularly at children. And then came the mysterious epidemic of illness that began in October 2001.

3 What did we learn from the anthrax outbreak of 2001?

This outbreak was characterized by 22 confirmed or suspected cases (11 inhalational, 11 cutaneous), with five deaths, resulting from presumed or known exposure to anthrax-contaminated mail. At least five letters containing highly weaponized anthrax spores were sent to government and business offices in Florida, Washington, DC, and New York City from Trenton, New Jersey. This means of dispersal represents one mode of attack, but many bioterrorism defense experts fear even more a widespread aerosol release (e.g., from a small crop duster–type airplane) that could potentially sicken hundreds of thousands. As it was, even the 2001 attack resulted in enormous public anxiety and major demands for medical care and public health resources. Antibiotic prophylaxis was prescribed for over 30,000 persons, and decontamination of just the Hart Senate Office Building alone took months and cost more than $20 million.

Centers for Disease Control and Prevention: Update: investigation of bioterrorism-related anthrax and interim guidelines for exposure management and antimicrobial therapy, October 2001. MMWR Morb Mortal Wkly Rep 50:909–919, 2001.

4 Why are such incidents of particular importance to emergency department (ED) personnel?

Such incidents illustrate the potential for biologic or chemical terrorist attacks, thus the imperative that health care workers, particularly first-responders and ED personnel, be familiar with the expedient diagnosis and management of chemical and biologic terrorist events.

5 What are the four basic phases of disaster response?

Agency for Healthcare Research and Quality: Pediatric Terrorism and Disaster Preparedness: A Resource for Pediatricians: www.ahrq.gov./research/pedprep/resource.htm

6 Why do terrorists use biologic and chemical weapons?

The term weapons of mass destruction (WMD) has been used to denote weapons using nuclear, biologic, or chemical agents in devices intended to kill and injure large numbers of victims. Biologic and chemical weapons are believed by U.S. military and counterterrorism experts to constitute a likely mode of WMD attack on civilian populations by terrorist groups. These agents are relatively inexpensive and technically less difficult to produce and deploy than nuclear weapons, the raw materials for their production are less regulated, and there is wide access to biologic and chemical agent information via the Internet.

Chemical and biologic weapons can be deployed easily, using relatively simple devices, such as garden sprayers, aerial crop dusting equipment, or insect control vehicles. In addition, a conventional attack on factories, chemical production facilities, or tank cars may result in the release of toxic industrial chemicals, with effects similar to those of an attack by military chemical warfare agents. Biologic agents may involve aerosol dispersal or possible contamination of food or water supplies.

7 What are the potential medical consequences of a chemical attack?

Chemical attacks probably would combine elements of traditional mass disasters (e.g., earthquakes), in which large numbers of casualties occur almost immediately, and traditional hazardous materials (HAZMAT) incidents. However, they may be more catastrophic for several reasons:

Henretig FM, Cieslak TJ, Eitzen EM Jr: Biological and chemical terrorism. J Pediatr 141:311–326, 2002.

8 Which of these features were observed in the 1995 Tokyo sarin attack?

One ED close to the scene received more than 500 patients, including three in cardiopulmonary arrest. Citywide, over 5000 persons sought emergency medical treatment at more than 200 facilities within a few hours, and about 25% required hospitalization. Of note, 90% of victims went to hospitals by taxi, private vehicles, or on foot rather than by formal EMS transport, further compounding the initial chaos. Until the identity of the agent was known, significant efforts at patient decontamination were lacking, resulting in many symptomatic exposures to hospital staff, although most were mild.

Okumura T, Suzuki K, Fukuda A, et al: The Tokyo subway sarin attack: Disaster management Part 2: Hospital response. Acad Emerg Med 5:618–624, 1998.

9 How would a biologic attack differ from a chemical attack?

Because of incubation periods, attacks with biologic agents must be viewed differently than conventional and chemical terrorist attacks. The scenario is more like that of a public health crisis than an EMS or HAZMAT emergency. Exposed persons may well be unaware of the attack, and disperse from the site of initial exposure. Many diseases caused by high-threat agents begin with nonspecific febrile syndromes. The first indication of a biologic attack is likely to be an epidemic of an unusually large number of persons presenting to diverse locations, possibly several days after exposure, with either early nonspecific clinical findings or later findings of severe disease. Thus, patients may present to various medical offices and EDs in piecemeal fashion, reporting, for example, flulike symptoms. This was clearly illustrated by the mail-borne anthrax outbreak in the fall of 2001.

10 What clues suggest a biologic attack?

Pediatricians and emergency physicians must maintain an index of suspicion if a biologic attack is to be diagnosed in time for useful measures to be undertaken. Several epidemiologic features may suggest a bioagent attack:

The earliest suspicion of such an attack should be reported at once to appropriate public health authorities.

Henretig FM, Cieslak TJ, Madsen JM, et al: Emergency department awareness and response to incidents of biological and chemical terrorism. In Fleisher GF, Ludwig S, Henretig FM (eds): Textbook of Pediatric Emergency Medicine 5th, ed. Philadelphia, Lippincott Williams & Wilkins, 2006, pp 135–162.

11 Why may children be disproportionately affected by both chemical and biologic agents?

Henretig FM, Cieslak TJ, Eitzen EM Jr: Biological and chemical terrorism. J Pediatr 141:311–326, 2002.

Henretig FM, Cieslak TJ, Madsen JM, et al: Emergency department awareness and response to incidents of biological and chemical terrorism. In Fleisher GF, Ludwig S, Henretig FM (eds): Textbook of Pediatric Emergency Medicine 5th, ed. Philadelphia, Lippincott Williams & Wilkins, 2006, pp 135–162.

Rotenberg JS, Newmark J: Nerve agent attacks on children: Diagnosis and management. Pediatrics 112:648–658, 2003.

12 What are the principal biologic agent threats?

See Table 68-1. In most circumstances patients will present after a significant time interval from their exposure. In the event of an announced attack, some consideration to decontamination issues is appropriate. In most cases, simple disrobement of outer garments and soap and water washing is sufficient for biologic agents.

13 What is the most important biologic threat?

The most important biologic threat is believed to be inhalational anthrax. This disease is caused by aerosol exposure to anthrax spores, which were weaponized by the United States (before 1969, when the United States renounced the use of biologic weapons and destroyed all existing stockpiles) and more recently by Russia and Iraq. The causative bacterium is Bacillus anthracis, a sporulating gram-positive rod. Endemic anthrax occurs in cutaneous and gastrointestinal as well as inhalational forms; generally it is contracted by close contact with hides, wool, or meat of infected herbivores (especially sheep, cattle, and goats).

14 What are the signs and symptoms of inhalational anthrax exposure?

After inhalation of anthrax spores, infection begins with pulmonary macrophage uptake and subsequent carriage to mediastinal lymph nodes, where necrotizing lymphadenitis and sepsis ensue. Inhalational anthrax has an incubation period of 1–6 days, and then begins with a flulike illness characterized by fever, myalgia, headache, cough, and chest “tightness.” A brief period of improvement sometimes is seen 1–2 days later, but it is followed by rapid deterioration with high fever, dyspnea, cyanosis, and shock. Hemorrhagic meningitis is present in up to 50% of cases. Chest radiographs obtained late in the course of illness may demonstrate a widened mediastinum or prominent mediastinal lymphadenopathy; infiltrates or pleural effusions may also be present. Death is universal in untreated cases and may occur in as many as 95% of treated cases if therapy is begun more than 48 hours after symptom onset (even with modern intensive care). The diagnosis should be considered with this clinical picture and a chest radiograph demonstrating widened mediastinum and may be confirmed with positive blood cultures.

15 What are the signs and symptoms of cutaneous anthrax exposure?

Cutaneous anthrax occurs when organisms gain entry into skin, particularly through abrasions or cuts. It is characterized by the development of a papule at the inoculum site, which then progresses over days to a vesicle, then an ulcer, and finally to a depressed, black eschar. The surrounding tissue becomes markedly edematous, but not particularly tender, distinguishing this infection from more typical staphylococcal or streptococcal cellulitis. It is quite amenable to therapy with a variety of antibiotics; with timely institution of treatment, it is rarely fatal. In the fall 2001 outbreak, all 11 patients with cutaneous anthrax survived. The only pediatric victim of that attack was a 7-month-old boy with cutaneous anthrax on his arm, presumably contracted after a brief visit to a New York City television news studio that had received contaminated mail. He was initially suspected of having a brown recluse spider bite, and the correct diagnosis was confirmed only after the discovery of anthrax contamination at another television studio. Of note, he also developed hemolysis, thrombocytopenia, and renal insufficiency, features not usually observed in otherwise uncomplicated cases of cutaneous disease, thus raising the possibility of a particular vulnerability in infancy.

16 What problems are associated with management of children exposed to anthrax?

First, the anthrax vaccine is approved only for adults. Second, both quinolones and tetracyclines have relative contraindications in children, although dental staining seen with tetracyclines usually requires multiple courses, and the risk of cartilage problems associated with quinolones is theoretical. Current experience with the use of both classes of antibiotics in children suggests that short-term use is safe. It seems reasonable that the extreme danger posed by anthrax exposure warrants use of any or all of these modalities in exposed children. Anthrax has little potential for person-to-person transmission; thus, standard precautions are adequate for health care workers.

17 Why is smallpox of special concern?

Because smallpox is highly contagious, protection of health care workers and prevention of secondary transmission are important factors. Smallpox was globally eradicated in 1980, and children are no longer vaccinated. Most American adults and all children are susceptible. Smallpox produces a febrile prodrome followed by a characteristic centrifugal vesicular rash; fatality rates approach 30% in unimmunized patients. Smallpox mandates the use of airborne isolation technique. Treatment is primarily symptomatic.

18 What are the concerning features of plague?

Like smallpox, plague is highly contagious. Inhalational exposure causes a severe, hemorrhagic pneumonia (pneumonic plague) characterized by respiratory distress and hemoptysis. Plague is highly lethal in untreated patients. Antibiotics, including aminoglycosides and doxycycline, are effective if begun within 24 hours of onset of illness. Droplet precautions are necessary in managing patients with plague.

19 What are the primary chemical threats? Describe the general approach to their management.

See Table 68-2.

20 Which chemical weapons are most feared?

Nerve agents are the most feared chemical weapons. These potent organophosphate compounds, similar to many pesticides, are toxic by inhalation, ingestion, and topical absorption and can result in profound muscarinic (cholinergic syndrome), nicotinic (initial muscle fasciculations, then paralysis), and central nervous system effects (seizures, coma, apnea). The clinical picture varies slightly by route of exposure, as noted in Table 68-2. Severe cases require antidotal therapy with atropine (adults, 2–5 mg; children, 0.02–0.05 mg/kg), pralidoxime (adults, 1–2 gm; children, 25–50 mg/kg), and usually diazepam for seizure control (adults, 5–10 mg; children, 0.1–0.3 mg/kg).

Rotenberg JS, Newmark J: Nerve agent attacks on children: Diagnosis and management. Pediatrics 112:648–658, 2003.

21 What are the principal components of the federal response plan?

The 1996 Defense Against Weapons of Mass Destruction Act lays out the federal response plan for management of chemical or biologic attacks. The lead federal agencies are the FBI and the Federal Emergency Management Administration. The Public Health Service may activate the National Disaster Medical System, which can deploy disaster medical assistance teams from military bases or coordination centers, such as the Centers for Disease Control and Prevention. Regionally, local EMS systems and hospitals need to coordinate planning and provide adequate training, protective gear, antidote and antibiotic availability, triage systems, protocols for isolation or quarantine, and potential utilization of alternative secondary care sites (e.g., schools, nursing homes as communal infectious disease wards).

22 How does the federal plan apply to children?

As noted earlier, many exposure and treatment issues are not settled in regard to children, and many EMS concerns would specifically relate to the provision of adequate care to pediatric mass casualties. Recently, the American Academy of Pediatrics has turned attention to many of these logistical and research issues as they pertain to children and has recommended extensive involvement of the pediatric emergency medicine community in this effort.

American Academy of Pediatrics: Chemical-biological terrorism and its impact on children: A subject review. Pediatrics 105:662–670, 2000.