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CONTROVERSIES • CONTROVERSES

Bioterrorism: an emerging threat

Eric Grafstein, MD; Grant Innes, MD

rior to the 1998 Vancouver Asian participated in a chemical arms race BWC, bringing an end to widespread PPacific Economic Summit, emer- that culminated in the development of research. gency physicians were briefed on the mustard gas by the Germans. By possibility of terrorist-related biolog- 1918, over 100,000 men had died The modern era ical or chemical weapons incidents. from exposure to chemical weapons.2 As part of a training exercise, the After the war, a backlash of moral Recent events in the former Soviet “victim” of a chemical weapon attack revulsion led to the development of Union, Iraq, Japan, and have was brought to our ED. Because of the (1925), which led industrialized countries to become confusion and ignorance, the “vic- prohibited future use of chemical or increasingly concerned about the risk tim,” the physician, several members biological agents. of bioterrorism. of the ED staff, and a number of other Between 1932 and 1945, Japan con- Despite signing the BWC, the Soviet patients also became “casualties.” ducted biological weapons research in Union continued a vast biological occupied Manchuria. At least 10,000 weapons program,1,3,4 producing and A history of biological warfare prisoners died after being infected stockpiling several agents, including with , meningitis, cholera or anthrax and . A former deputy Biological warfare is not just a twenti- plague. During this period, Japan chief of research for the biological eth century phenomenon. During the launched biological attacks on at least weapons program reported that the French and Indian War (1754–1767), 11 Chinese cities. Infectious agents Russian military had mounted small- Sir Jeffery Amherst, commander of were deployed by directly contaminat- pox in bombs and intercontinen- the British forces in North America, ing water and food supplies, by spray- tal ballistic missiles for strategic use.5 devised the plan of using smallpox ing cultures from aircraft, by dropping In a related event on April 3rd, 1979, against hostile Native Indian tribes.1 -filled bombs, or by releasing Soviet technicians at a Sverdlovsk mil- On June 24, 1763, one of Amherst’s clouds of plague-infected over itary installation failed to activate criti- officers acquired several contaminat- major cities.2 In a single attack on cal air filters. Up to a gram of anthrax ed blankets from a smallpox hospital Changteh in 1941, 10,000 Chinese cit- spores was inadvertently released, and presented them, as a gift, to a izens and 1700 Japanese troops died, killing 68 people and rendering a 4000- group of Native Americans. Shortly predominately from cholera. square-mile area uninhabitable.1,3,6 This thereafter, smallpox decimated tribes During the 1950s and 1960s, nuclear, event is testimonial to the hazards of along the Ohio River Valley. This out- biological and chemical weapons pro- working with biological agents. break may or may not have been relat- liferated, primarily in the arsenals of the Iraq remains a major concern. It is ed to Amherst’s gift.2 United States and the Soviet Union. But the only country since World War II Almost 2 centuries later, on a sunny the concept of biological weapons that has deliberately released biologi- spring afternoon in 1915, German remained abhorrent to individuals and cal weapons against its enemies (Iran) troops at Ypres deployed chlorine gas governments alike. This general disdain and its own people (the Kurds). against the French. Within minutes, ultimately spawned an international Between 1985 and 1991, Iraq accu- thousands were overcome. During the treaty, the Biological Weapons Con- mulated a variety of biological agents next 3 years, all of the major powers vention (BWC), which proscribed the including botulinum, , development, production, storage, or dengue virus, anthrax, and smallpox.1,2 St. Paul’s Hospital, Vancouver, BC This article has been peer reviewed. acquisition of biological weapons. On The Iraqis claim to have produced April 10, 1972, 79 nations signed the 90,000 litres of botulinum , 8300

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litres of anthrax, and to have distrib- anthrax threats has increased from 1 agencies as part of a plan. uted 200 bombs and warheads con- in 1997 to 37 in 1998. There were 10 Biological events are different. taining these agents to various mili- additional threats during the first 2 They may be clandestine; there may tary bases.4,5 Iraq has complied mini- months of 1999 alone.10 While none be no recognition that an attack has mally with United Nations (UN) have been associated with actual occurred. Because biological agents requests for nuclear and chemical spore release, these incidents generate have incubation periods, an immedi- weapons site inspections, and has fear among the general population, ate deluge of casualties is unlikely. resisted all attempts to locate biologi- strain resources, and Rather, victims are likely to present cal weapons factories. Despite defeat undermine the urgency of response over a period of weeks with flu-like in the Gulf War, Iraq’s development required by the medical, public health, illnesses (anthrax) or chickenpox-like facilities, scientific personnel, and municipal and provincial agencies. rashes (smallpox). Patients may be biological warfare capability remain Bioterrorism is a growing threat as spread over wide areas and present at essentially intact.7 we approach the millennium.4 Today diverse health care facilities. Since During the 1990s, a fanatical reli- at least 17 countries are believed to few physicians have seen smallpox, gious group, Aum Shinrikyo, made have active biological weapons pro- anthrax or plague, recognition will be several attempts to aerosolize anthrax grams.3 Recipes for biological agents delayed. Days or weeks may pass and botulism are available on the before public health agencies become throughout Internet, and groups aware of the biological attack, during .2,3,5 In Biological with basic scienti- which time the outbreak can spread 1992, group is a low probability, fic knowledge can widely.5 The potential for casualties is members trav- high consequence develop deadly bio- huge. Whereas conventional terrorist elled to Zaire, logicals at low cost. activities like bombings kill dozens or the site of an event. Several dissident hundreds, a single act of bioterrorism virus groups have the may kill thousands or millions.11 outbreak, to acquire samples for use skills necessary to cultivate lethal Initial cases will present to emer- as biological weapons.2,8 In 1995, in pathogens8 and the will to deploy gency departments, and ED physi- one of the most notorious terrorist them. Biological weapons will be cians will constitute the first line of attacks in history, Aum Shinrikyo deployed again, but we have no ability defense.5,11 Because biological agents placed sarin nerve gas in 5 subway to predict or prevent an attack, little threaten not only the lives of the pri- cars converging on central Tokyo. ability to detect one when it occurs, mary victims, but also those of physi- This attack affected over 5000 people, and limited ability to manage the con- cians and hospital staff, rapid diagno- causing 1000 hospitalizations and 12 sequences. sis is important; therefore emergency deaths.2 physicians, particularly those in large Biological incidents have also Bioterrorism and the cities, should be trained to recognize occurred in North America. In emergency department the syndromes caused by the most September of 1984, the Rajneeshee likely biological warfare agents.11 religious cult contaminated 10 restau- It is crucial to understand the differing Early syndrome recognition facilitates rant salad bars in the Dalles, Oregon, nature of biological and chemical life-saving vaccination of high-risk area with typhimurium.9 agents (Table 1), since these differ- populations (e.g., ED staff) and allows Subsequently, 751 community mem- ences mandate different public health, for early post-exposure therapy for bers developed salmonella gastroen- first responder, and medical responses. victims. In the event of a smallpox teritis, demonstrating the ease with Chemical agents produce immedi- release, rapid recognition and re- which a motivated group can perpe- ate dramatic effects. In the Tokyo sponse could mitigate the effects by trate an act of bioterrorism. Six years sarin gas attack, symptoms appeared 100-fold, but only if initiative is ago, in April of 1993, Canadian cus- within hours and thousands of people shown. Early identification of a dead- toms agents stopped an Arkansas man were affected. In such incidents, the ly may mean the difference carrying weapons, ammunition, neo- key health care responders are fire- between life and death for ED staff Nazi literature, and enough to fighters, paramedics, police and mili- and patients, and could prevent thou- kill 30,000 people.4 tary.5 This medical response is typical- sands or tens of thousands of casual- In the United States, the number of ly practised and promoted by local ties over the ensuing months.

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Epidemiology of bioterrorism can take months, as it did with the and botulism. Of these, smallpox and Pacific Northwest Salmonella out- anthrax are the greatest threats.5 Knowledge of basic epidemiological break, to confirm that an incident was, principles is important in dealing in fact, an act of bioterrorism. Smallpox with biological warfare threats. The The last natural case of smallpox first requirement is to maintain a Biological weapons of mass occurred 20 years ago in Ethiopia. high level of suspicion, looking for destruction Although it is difficult to obtain, the following clues: smallpox virus is considered a high • large epidemics of acutely ill An ideal is easily risk for use as a biological weapon. patients and rapidly produced, is environmen- Smallpox is spread person–person • unexplained animal deaths tally stable, and can be concentrated by droplets or aerosol (e.g., cough- • diseases that are unusual for the or dried. Agents should be highly ing). It is highly infectious and region infectious (but not necessarily conta- contagious at low doses. After a 10- • multiple or simultaneous epidemics • increased utilization of pharmacies, medications, ambulance services, Bioterrorism will demand the expertise emergency departments, physicians of emergency medical staff and public and funeral homes. Claims by terrorist groups or prior health clinicians. intelligence about attacks may sim- plify the public health investigation. gious) in low doses, properly sized to to 12-day incubation period, victims The steps required to deal with a cause (2 to 6 microns) by develop a flu-like illness with fever, bioterrorism attack are the same as for the aerosol route, and cause severe joint pains, headache, and a pustular, any infectious outbreak. They include disease. In addition, it is advanta- chickenpox-like rash. Unlike chicken- verifying that an alleged disease event geous if vaccines and toxoids are pox, the rash is centrifugally distrib- has occurred, developing an objective available to protect those working uted and pustules develop on the case definition based on signs and with or deploying the agent. There palms and soles. The case fatality symptoms, searching for unreported are thousands of possible rate is 30% to 80%, and treatment cases, describing the outbreak and but only a few meet the criteria listed is limited to and vaccina- comparing it to expected disease rates above (Table 2). The 4 most likely to tion. Vaccination within 3 days of and other epidemics. Unfortunately it be used are smallpox, plague, anthrax exposure can prevent disease, and vaccination within 4 to 5 days may Table 15 prevent death. Existing vaccine Parameter Chemical agent Biological agent stores, in the United States, are Onset of illness Rapid: usually minutes to hours Delayed: days to weeks adequate to immunize 6 to 7 million people, but further large-scale vac- Patient distribution Downwind; near release point Widespread; perhaps international cine production would take at least First response Paramedics, firefighters, police ED physicians and nurses 36 months. Decontamination Critically important Usually unnecessary Treatment Chemical antidotes Vaccines and Anthrax Isolation No need after decontamination Crucial for communicable diseases Anthrax, primarily a disease of graz- ing animals, is caused by gram-posi- Table 2. Biological agents tive rods that may survive up to 40 Bacteria years in spore form. Anthrax is trans- Plague Smallpox mitted to humans who are exposed to Anthrax Viral hemorrhagic fevers Ricin animal products in agricultural or occupational settings. Aerosolized Viral encephalitides Marine toxins anthrax disseminates easily over large Venoms areas, making it a dangerous biologi- Staph enterotoxin B cal agent. For example, while it takes 8

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tons of ricin to cover a 10-square-mile ray is a classic finding of anthrax. The against smallpox. Vaccine availability battlefield and achieve a 50% death diagnosis is confirmed by history of is very limited,3 and there are no plans rate, a few kilograms of anthrax will exposure, a positive Gram stain of to vaccinate the general public. In the have the same effect. Although blood, nasal swabs, or environmental event of a bioterrorism attack, prefer- anthrax can be acquired via the aerosol samples, and a positive culture or ential vaccination would be provided route, the risk of secondary anthrax polymerase chain reaction (PCR) for for those exposed without symptoms, through re-aerosolization or person-to- anthrax DNA. A suspicion of anthrax contacts of anthrax victims, first person contact is low. should prompt immediate notification responders, laboratory workers, and of public health authorities so that (probably) government officials. On- definitive testing can be arranged. going research is focused on the We should consider Pre-exposure prophylaxis involves development of vaccines against small- how our local and 6 doses of anthrax vaccine at 0, 2 and pox (second generation), tularemia, regional disaster 4 weeks, and at 6, 12 and 18 months.3 Q fever, botulinum and viral equine Post-exposure therapy, which should . plans will address begin within 48 hours of exposure, the issue of biological includes or doxycycline Planning for biological terrorism. for 30 to 60 days in addition to incidents anthrax vaccine at 0, 2 and 4 weeks. Cutaneous anthrax, the most com- Unfortunately, in a typical anthrax Proactive mitigation is crucial to dis- mon form, begins as a dermal vesicle scenario, victims would develop non- aster planning. Recognizing that ter- that breaks down to form an eschar, specific symptoms 2 to 3 days after rorist action can rarely be predicted or sometimes with associated edema. It exposure and physicians would not prevented, the greatest payoff will is easily recognized, susceptible to think of anthrax. By the time definitive come from improving our response to treatment, and carries a identification was made, treatment biological attacks and the emergency low mortality.3 Gastrointestinal an- would likely be futile.8 Infected indi- medical community will play a criti- thrax, most common after ingestion viduals would become critically ill cal role in this process.11 of contaminated meat, produces within 24 to 48 hours and die rapidly. It is likely that a biological weapons hemorrhagic gastroenteritis followed The for non-vaccinated incident would overwhelm communi- by anthrax septicemia, which is gen- civilians after pneumonic anthrax ty and medical resources, and many erally fatal. exposure would approach 100%. questions need to be considered. Who Inhalational anthrax is rare except There have been several recent will coordinate outbreak investigation after a biological weapon exposure.3 hoaxes where individuals claim to and control? How will communica- Aerosolized anthrax spores penetrate have mailed anthrax in a letter. In such tion occur between organizations, the terminal alveoli and are taken up by situations, “exposed” persons should media and the public? How will emer- pulmonary macrophages. Nonspecific remove their clothing and personal gency health services, police, military, symptoms, including fever, malaise, effects, place them in plastic bags and emergency medicine and ancillary headache and cough, occur 1 to 3 days shower copiously with soap and medical personnel be coordinated? after exposure. Spore germination water. Personal effects and anything How will local disaster teams set up (which may be delayed up to 2 that contacted the letter should be containment and command centres? months) leads to toxin production, decontaminated with a 0.5% hypo- Who will designate hospitals and how edema, and tissue necrosis. Rapid chlorite solution. will they contain infection? How will deterioration ensues, characterized by hospitals obtain antibiotics and anti- dyspnea, stridor (if tracheal nodes are Vaccines toxins for large numbers of patients? involved), and the sine qua non, hem- What are the plans to distribute vac- orrhagic mediastinitis. Hemorrhagic Vaccines exist for anthrax, smallpox, cine? Who will authorize quarantines meningitis is seen in up to 50% of cholera and plague, although the latter or martial law? Who will authorize the cases, and death frequently occurs is only effective against -borne closure of airports and borders if nec- within 3 days of symptom onset. plague. The US military vaccinates its essary? How will panic be controlled Given a compatible clinical presenta- entire armed forces against anthrax, within the population at large? tion, a wide mediastinum on chest x- but there are no plans to vaccinate

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But wait! This is Canada References health threat. Emerg Infect Dis 1998:4. www.cdc.gov/ncidod/eid/vol4no3/hen 1. Christopher GW, Cieslak TJ, Pavlin JA, drsn.htm. The cash-strapped Canadian health Eitzen EM. Biological warfare: a historical perspective. JAMA 1997;278(5):412-7. 9. Torok TJ, Tauxe RV, Wise RP, Liven- care system can barely cope with “nor- good JR, Sokolow R, Mauvais S, et al. 2. Cole LA. The Eleventh Plague, New mal” health care problems. In most A large community outbreak of salmo- York: W.H. Freeman and Co.; 1997. p. Canadian cities, public health budgets nellosis caused by intentional contami- 1-10; 79-102. are stretched to the limit and probably nation of restaurant salad bars. JAMA 3. Ingelsby TV, Henderson DA, Bartlett 1997;278:389-95. inadequate. Few funds are available to JG, Ascher MS, Eitzen E, Friedlander 10. Proceedings of the National Symposium address emerging . Yet AM, et al. Anthrax as a biological on Medical and Public Health Response bioterrorism is an emerging reality we weapon: medical and public health man- to Bioterrorism. www.cdc.gov/ncidod agement. JAMA 1999;281:1735-45. cannot ignore. The Clinton administra- /eid/index.htm tion appears ready to assign $2.2 bil- 4. Stephenson J. Confronting a biological 11. Jeffrey S. Biological terrorism: prepar- . JAMA 1996;276:349-51. lion dollars in the 1999 and 2000 bud- ing to meet the threat. JAMA 1997; gets toward preparing for this threat. 5. Henderson DA. The looming threat of 278:428-30. More realistic goals in Canada are to bioterrorism. Science 1999;283:1279-82. develop appropriate plans to deal with 6. Meselson M, Guillemin J, Hugh-Jones Further information about bioterrorism is M, Langmuir A, Popova I, Shelokov A, available at the Johns Hopkins Infectious this potentially devastating occurrence et al. The Sverdlovsk anthrax outbreak Disease Web page (www.hopkins-id.edu) and to increase the awareness of key of 1979. Science 1994;266:1202-7. and at The Center for Civilian Web site (www.hopkins-biodefense.org). health care providers, managers and 7. Zilinskas RA. Iraq’s biological weapons: administrators — especially those The past as future? JAMA 1997;278: involved with disaster plans and their 418-24. Correspondence to: Dr. Eric Grafstein; egrafstein implementation. 8. Henderson DA. Bioterrorism as a public @stpaulshosp.bc.ca

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