Bioterrorism Preparedness:

January 1, 2006
David A. Relman, MD

,
Jed E. Olson, MD

Until recently, the specter of biologicwarfare or bioterrorism was infrequentlydiscussed by most physicians,despite the attention it had receivedfrom novelists, screenplay writers,politicians, and military defense strategists.Thankfully, most physicians havestill never encountered the malevolentuse of biologic agents, nor have theytreated a victim of a biologic attack. Infact, despite their occasional occurrencein a “natural setting,” as well asin recent events, clinical cases involvingany of the classic biothreat agentsare rarely encountered even by mostinfectious disease physicians.

Until recently, the specter of biologicwarfare or bioterrorism was infrequentlydiscussed by most physicians,despite the attention it had receivedfrom novelists, screenplay writers,politicians, and military defense strategists.Thankfully, most physicians havestill never encountered the malevolentuse of biologic agents, nor have theytreated a victim of a biologic attack. Infact, despite their occasional occurrencein a 'natural setting,' as well asin recent events, clinical cases involvingany of the classic biothreat agentsare rarely encountered even by mostinfectious disease physicians.For these and many other reasons,the intentional use of biologicagents has represented an exceedinglyunlikely hypothetical scenario formost clinicians. Yet, evidence mountsthat the use of biologic agents asweapons is increasingly feasible andplausible in a civilian population setting.The events of September-October2001 involving the deliberate deliveryof anthrax spores through the USpostal system provide an introductionto the issues and potential scenariosthat can arise from the intentional useof biologic agents as weapons or astools of fear. And nearly all predictedscenarios of intentional biothreat agentuse place physicians at the leadingedge of exposure and management.Despite international bans suchas the 1972 Biological and ToxinWeapons Convention, signed by morethan 140 countries'including theUnited States1'and heightened defensiveplanning on the part of the US military,the facts remain that lethal andhighly noxious biologic agents are relativelyinexpensive. They are also easyto obtain (with more than 400 strainrepositories around the world, in additionto clinical microbiology laboratories),easy to produce (most undergraduate,graduate, and postdoctoralstudents in microbiology and relatedfields have the necessary background),easy to conceal, and are becomingincreasingly easy to deliver.Arguments have been made thatbiologic agents are the weaponry of thefuture; they represent the 'poor man'satomic bomb.' While the goal in statesponsoredwarfare may be to kill substantialnumbers of people, a terroristorganization or individual may employbiologic agents for less 'ambitious' reasons:to incapacitate local populations,to cause social or political disruption, orsimply to generate fear and mistrust. Althoughthe concept is loathsome, thethreat is nevertheless a real one.2In this and in coming issues ofCONSULTANT, we will examine somecommonly acknowledged agents of biologic warfare. These include smallpox,plague, tularemia, staphylococcalenterotoxin B, and ricin. Throughoutthe series, our focus will be on naturallyoccurring agents that may causeunusual syndromes when employedintentionally and on agents with whichclinicians may be unfamiliar. Becausea review on anthrax appeared in lastmonth's issue of CONSULTANT (December2001, page 1797),3we will notaddress it here.Our goal with this series is to addressthe needs of health care practitionersas they are forced to confrontthis problem and to suggest that thetopic of biologic warfare and bioterrorismrequires their involvement.We will begin with an overview ofbiologic weapons and associated disease.In the accompanying 'PrimaryCare Updates,' pages 33 and 56, wewill present brief overviews of theplague and tularemia, respectively.WHY THE CONCERN?
Continuing political and militaryinstability focuses sharp attention onthe known capabilities and assets ofnations such as North Korea, Syria,Iraq, and Iran. Iraq, for example, admittedto the development of nearly400 missile warheads, bombs, androckets armed with botulinum toxin,anthrax, and aflatoxin, which were releasedfor use by forward-deployedcommanders during the 1990-1991Persian Gulf War. The fate and whereaboutsof these weapons and evenlarger stockpiles of weaponized agentsremain uncertain. Certainly, the combinationof an unstable and despoticIraqi leadership with ties to well-organizedterrorist organizations, and recurrentIraqi military humiliation bythe United States increases the level ofconcern, as do recent political developmentsin the wake of the events ofSeptember 11, 2001.Of even more concern is the recentlypublicized history of massive biologicweapons development in Russiabeginning in the early 1970s and continuinginto the 1990s. The agents purportedlystockpiled included Bacillusanthracis; variola virus (smallpox); variousviral hemorrhagic fever agents;and a variety of nontraditional agents,including biologic response modifiers.The disintegration of the Russian stateinfrastructure may have led to the defectionof key personnel to hostile nationsand organizations.Japan's Aum Shinrikyo cult remindsus of the potential capabilities oforganizations devoted to non'statesponsoredbiologic and chemical terrorism.The Aum cult produced botulinumtoxin, B anthracis spores, andCoxiella burnetii, in addition to thenerve gas sarin and a wide array ofother biologic and chemical weaponry.4,5 This cult visited Zaire during the1992 Ebola fever outbreak, in an attemptto obtain Ebola virus samplesfor cultivation and weapon development.The cult's terrorist activitiescaused the deaths of 12 people fromsarin gas exposure; anthrax was alsoused, but unsuccessfully.Closer to home, in 1984, the devoteesof Bhagwan Shree Rajneesh in-fected 751 people in Oregon with Salmonellatyphimurium by intentionallycontaminating local self-service saladbars.6 In 1996, a disgruntled hospitalmicrobiology laboratory technician inDallas intentionally infected 12 coworkerswith Shigella dysenteriae.7 Thedeliberate distribution of B anthracisspores through the US mail system in2001 and associated cases of anthraxhighlight the vulnerability of modernsociety and the difficulties in definingthe origins and scope of the act. In fact,the history of the intentional use ofnoxious biologic agents stretches backto antiquity.Table 1 highlights some events inthe modern history of documenteduse of biologic weapons.4,8Small-scale terrorist attacks aremore difficult to predict and detect.Such attacks may only be recognizedwell into the course of the epidemic,and perhaps long after the resolution ofall clinical cases. Some of the potentialagents (mentioned above) cause naturallyoccurring disease with some regularity.It is possible that other bioterroristevents in this country have goneunrecognized. Because these eventsare usually unannounced and becauseof the prolonged and variable incubationperiod of most biologic agents, it islikely that emergency department staffand physicians will be among the firstto encounter and treat the victims.We clinicians need to heightenour awareness of irregular disease patternsand features and question themechanism of disease emergenceBIOLOGIC WEAPONS ANDASSOCIATED DISEASE
Some commonly acknowledgedagents of biologic warfare, includingintact microorganisms as well as purifiedtoxins, are listed in Table 2. Thislist is by no means complete, nor doesit include nontraditional agents such asgenetically engineered organisms,their products, or other biologically activemolecules.Few randomized, blinded studieshave been performed on which tobase recommendations for treatmentand prophylaxis of diseases caused bynaturally occurring agents that are intentionallyemployed. This point hasbeen emphasized repeatedly duringthe 2001 US anthrax bioterroristevents. For detailed information, readersshould consult references 9 and 10and their state health departments.9,10(Contact information for your statehealth department appears on page1809 of the December 2001 issue ofCONSULTANT.)The Box on page 30 lists a seriesof Internet sites that offer valuable informationabout biologic warfare.

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