an evidence-based approach to emergency medicine

July 2002Volume 4, Number 7

Authors

Sarah D. McNutt, MDResearch Associate, Department of EmergencyMedicine, Center for Disaster Preparedness, University ofAlabama at Birmingham, Birmingham, AL.

Steven M. Becker, PhDAssistant Professor of Public Health and Scientist, Centerfor Disaster Preparedness, University of Alabama atBirmingham, Birmingham, AL.

David R. Franz, DVM, PhDDeputy Director, Center for Disaster Preparedness,University of Alabama at Birmingham, Birmingham, AL.

Peer Reviewers

Robert G. Darling, MD, FACEPCaptain, Medical Corps, United States Navy; U.S. ArmyMedical Research Institute of Infectious Diseases(USAMRIID), Fort Detrick, MD.

Edward N. Barthell, MD, MSExecutive Vice President, Infinity HealthCare; AssociateClinical Professor, Medical College of Wisconsin;Milwaukee, WI.

Stephen Karas, Jr., MD, FACEPClinical Professor, UCSD Department of Medicine, SanDiego, CA.

CME Objectives

Upon completing this article, you should be able to:1. describe the complexity of the bioterrorist threat and

the need for the preparation and development of acoordinated response plan;

2. describe the clinical presentation of Category Aagents (according to the CDC); and

3. explain the appropriate diagnostic and treatmentapproaches for patients who are exposed to orinfected with Category A agents.

Date of original release: July 1, 2002.Date of most recent review: June 3, 2002.

See “Physician CME Information” on back page.

EMERGENCY MEDICINE PRACTICEA N E V I D E N C E - B A S E D A P P R O A C H T O E M E R G E N C Y M E D I C I N E

Editor-in-Chief

Stephen A. Colucciello, MD, FACEP,Assistant Chair, Department ofEmergency Medicine, CarolinasMedical Center, Charlotte, NC;Associate Clinical Professor,Department of EmergencyMedicine, University of NorthCarolina at Chapel Hill, ChapelHill, NC.

Associate Editor

Andy Jagoda, MD, FACEP, Professorof Emergency Medicine; Director,International Studies Program,Mount Sinai School of Medicine,New York, NY.

Editorial Board

Judith C. Brillman, MD, ResidencyDirector, Associate Professor,Department of EmergencyMedicine, The University ofNew Mexico Health SciencesCenter School of Medicine,

Albuquerque, NM.

W. Richard Bukata, MD, AssistantClinical Professor, EmergencyMedicine, Los Angeles County/USC Medical Center, Los Angeles,CA; Medical Director, EmergencyDepartment, San Gabriel ValleyMedical Center, San Gabriel, CA.

Francis M. Fesmire, MD, FACEP,Director, Chest Pain—StrokeCenter, Erlanger Medical Center;Assistant Professor of Medicine,UT College of Medicine,Chattanooga, TN.

Valerio Gai, MD, Professor and Chair,Department of EmergencyMedicine, University of Turin, Italy.

Michael J. Gerardi, MD, FACEP,Clinical Assistant Professor,Medicine, University of Medicineand Dentistry of New Jersey;Director, Pediatric EmergencyMedicine, Children’s MedicalCenter, Atlantic Health System;Vice-Chairman, Department ofEmergency Medicine, MorristownMemorial Hospital.

Michael A. Gibbs, MD, FACEP,Residency Program Director;Medical Director, MedCenter Air,Department of EmergencyMedicine, Carolinas MedicalCenter; Associate Professor ofEmergency Medicine, Universityof North Carolina at Chapel Hill,Chapel Hill, NC.

Gregory L. Henry, MD, FACEP,CEO, Medical Practice RiskAssessment, Inc., Ann Arbor,MI; Clinical Professor, Departmentof Emergency Medicine,University of Michigan MedicalSchool, Ann Arbor, MI; President,American Physicians AssuranceSociety, Ltd., Bridgetown,Barbados, West Indies; PastPresident, ACEP.

Jerome R. Hoffman, MA, MD, FACEP,Professor of Medicine/EmergencyMedicine, UCLA School ofMedicine; Attending Physician,UCLA Emergency Medicine Center;Co-Director, The DoctoringProgram, UCLA School of Medicine,

Los Angeles, CA.

Francis P. Kohrs, MD, MSPH, AssociateProfessor and Chief of the Divisionof Family Medicine, Mount SinaiSchool of Medicine, New York, NY.

John A. Marx, MD, Chair and Chief,Department of EmergencyMedicine, Carolinas MedicalCenter, Charlotte, NC; ClinicalProfessor, Department ofEmergency Medicine, Universityof North Carolina at Chapel Hill,Chapel Hill, NC.

Michael S. Radeos, MD, MPH,Attending Physician, Departmentof Emergency Medicine,Lincoln Medical and MentalHealth Center, Bronx, NY;Assistant Professor in EmergencyMedicine, Weill College ofMedicine, Cornell University,New York, NY.

Steven G. Rothrock, MD, FACEP, FAAP,Associate Professorof Emergency Medicine, Universityof Florida; Orlando RegionalMedical Center; Medical Director of

Orange County EmergencyMedical Service, Orlando, FL.

Alfred Sacchetti, MD, FACEP,Research Director, Our Lady ofLourdes Medical Center, Camden,NJ; Assistant Clinical Professorof Emergency Medicine,Thomas Jefferson University,Philadelphia, PA.

Corey M. Slovis, MD, FACP, FACEP,Professor of Emergency Medicineand Chairman, Department ofEmergency Medicine, VanderbiltUniversity Medical Center;Medical Director, Metro NashvilleEMS, Nashville, TN.

Mark Smith, MD, Chairman,Department of EmergencyMedicine, Washington HospitalCenter, Washington, DC.

Charles Stewart, MD, FACEP,Colorado Springs, CO.

Thomas E. Terndrup, MD, Professorand Chair, Department ofEmergency Medicine, Universityof Alabama at Birmingham,Birmingham, AL.

Bioterrorism And TheEmergency Physician:On The Front Lines

“…and he that will not apply new remedies must expect new evils; for time is thegreatest innovator…”—Sir Francis Bacon, “The Essays,” 1601

September 20, 2002, 7:40 p.m.: A 32-year-old white male presents with “theflu.” This is the second case of flu-like illness you’ve seen tonight. The patientcomplains of sudden-onset diffuse myalgias and chills. His physical examination isunremarkable aside from a temperature of 102.4°F. No runny nose or sneezing, buthe does complain of some shortness of breath. Seems strange to see flu this time ofyear. Laboratory and radiological examinations are all unremarkable. I guess it’sjust an “off-season” viral illness. Motrin and Tylenol should be all he needs.

September 23, 2002, 5:30 p.m.: This flu epidemic is getting out of hand—theED is swamped. Now, EMS brings in a patient with severe respiratory distress. Asyou prepare to intubate him, your stomach tightens in a sickening knot; it’s thesame “32-year-old white male” you saw three days before. Now, he presents withmassive hemoptysis and shock. He gets it all: intubation, crystalloids, pressors, andbroad-spectrum antibiotics. Two hours later, he’s dead. This lethal pattern repeatsitself throughout the shift, again, and again, and again…

IN domestic warfare, the casualties are no longer on a battlefield. Becauseterrorist attacks using aerosolized biological agents can occur without

warning, the first sign of such an attack might be hundreds or thousands ofill or dying patients. The front-line responders in a biological weaponsattack are members of the healthcare community.

Emergency medicine will play a leading role in disaster response,training of first responders, and the initial care of patients. In the anthraxattacks of late 2001, nine of the 11 patients with inhalational anthraxinitially presented to EDs, while the other two eventually sought carein the ED as their illness progressed. The emergency physician is uniquelypoised to detect the outbreak, identify the pathogen, and alert the public

Emergency Medicine Practice 2 www.empractice.net • July 2002

health community.A bioterror event raises a unique set of questions:

• Is this incident really due to bioterrorism?• Who should be notified?• What resources are available to assist in this crisis?• How do I diagnose and treat diseases I have never

seen before?• Do these patients need to be decontaminated,

isolated, or quarantined?• What can be done to protect the hospital staff from

potential exposure?• How should we handle the psychological conse-

quences of exposure or potential exposure?• Am I safe?

This issue of Emergency Medicine Practice providesanswers to these and other pressing questions.

Critical Appraisal Of The Literature

“In the arts of life, man invents nothing;but in the arts of death, he outdoes Nature herself,

and produces by chemistry and machinery all the slaughterof plague, pestilence, and famine.”

—George Bernard Shaw (1856–1950),Anglo-Irish playwright, critic.

The Devil, in Man and Superman, act 3.1

For most potential bioterrorist agents, there is a notablelack of evidence in the scientific literature. Many of thesediseases have been functionally eradicated in the devel-oped world, and their alien characteristic makes themeven more dangerous. In other instances, outbreaks ofthese pathogens involve a handful of cases seen in

faraway lands, perhaps decades ago. Because there is solittle evidence on which to base medical decisionsregarding bioterrorist agents, public health experts haveformed consensus-based guidelines. These guidelinesand references to other information may be found athttp://www.bt.cdc.gov/.2

Epidemiology Of A Bioterrorist Attack

History Of Biological WarfareThe concept of using naturally occurring organisms as aweapon is not new. Indeed, history has documentednumerous instances of biological warfare. (See Table 1.)Only recently have we come to realize the lasting effectsof some of these agents. During World War II, to competewith German and Japanese bio-weapons research, theBritish used anthrax to infect a herd of sheep on GruinardIsland, off the coast of Scotland. The island, now referredto as “Anthrax Island,” remained contaminated with thelethal spores for decades. A military report on thisexperiment suggested that anthrax could render citiesuninhabitable “for generations.”3

The latter portion of the 20th century is termed the“modern era” of biological warfare. During this period,nation-states developed biological weapons for use on atraditional battlefield. Even after the ratification of theBiological Weapons Convention of 1972, the mostimpressive bio-weapons program in the history ofmankind continued for 20 years—cloaked in secrecy inthe former Soviet Union. This program may never besurpassed in scale or offensive capability.

With the Soviet economic implosion of the 1990s,concern turned to the fate of tens of thousands ofunemployed Russian scientists and engineers whopreviously worked in the bio-weapons program. Fear

Table 1. Historical Bioterrorism Events.

Year Incident

400 B.C. Scythian archers use arrows dipped in blood, manure, or decomposing bodies

190 B.C. Hannibal hurls venomous snakes onto enemy ships

1346 Mongols hurl plague-infected corpses over enemy walls

1405 The Spanish contaminate wine drunk by French soldiers with blood of leprosy patients

1650 Polish soldiers place saliva from rabid dogs into hollow shell casings

1710 Russians invading Estonia hurl plague-infected corpses over enemy walls

1763 British officers give blankets used by smallpox victims to American Indians in Pennsylvania, resulting in adevastating smallpox outbreak

1860s Confederate sympathizers during the American Civil War attempt to ship garments and bedding used byyellow fever victims to New York

1863 Confederate soldiers during the American Civil War leave dead animals in wells and ponds to contaminateUnion soldiers’ water supply

Sources: Smart JK. History of chemical and biological warfare: an American perspective. In: Zajtchuk R, Bellamy RF, eds. Medical Aspects of Chemicaland Biological Warfare. Bethesda, MD: Office of the Surgeon General, Department of the Army, USA; 1997:12; and Hayward W. Bermuda Past andPresent. New York: Dodd Mead; 1911.

3 Emergency Medicine PracticeJuly 2002 • www.empractice.net

grew that weak nations or terrorist organizations mightuse jobless bio-engineers to build their “great equalizer.”

In response, the United States redirected millions ofdollars toward domestic preparedness. Similarly, theemergency medicine community recognized that it mightbe faced with the consequences of a biological weaponsattack—that EDs would become the “front line” in sucha conflict. In the wake of 9/11, emergency plannersanxiously began to review disaster plans and preparefor bioterrorism.

Incidents involving biological weapons during thelatter half of the 20th century were rare. The MontereyDatabase, which tracks chemical, biologic, and nuclearattacks worldwide, noted that there were only 66criminal events and 55 terrorist events involving biologicagents over the 40-year period from 1960 to 1999.4 Mostattacks were small and fatalities few.

This changed in October 2001. The United States wasattacked through its postal system, and to date, sevencases of cutaneous anthrax and 11 cases of inhalationalanthrax have been confirmed, with five fatalities.Thousands of other potentially exposed individuals wereprovided with antibiotics.5

Awareness And Recognition: Making The DiagnosisAttacks may be either overt (announced) or covert(unannounced). In either case, awareness of the event isthe first step in incident management. Overt attacksrequire rapid assessment of the veracity of the claim andthen an appropriate and measured response as indicated.A covert attack will be recognized only after victimspresent for medical care—after the incubation period haspassed and clinical signs become manifest.

Kaufmann et al have published an economic modelof a large-scale anthrax attack demonstrating that rapidimplementation of a post-attack prophylaxis program isthe single most important means of reducing lossesfollowing a bioterrorist attack.6 Pivotal to the implemen-tation of post-attack measures is identification of theagent and the attack. However, before the diagnosis oridentification can be made, an astute clinician must thinkoutside the routine differentials. We must consideremerging infectious disease and biological terrorism. Theattack may be a hoax, a small foodborne outbreak, alethal aerosol cloud moving silently through a city at

night, or the reintroduction of smallpox. Emergencyphysicians who think like epidemiologists, understandterror pathogens, and are familiar with the diagnosticand treatment options can mitigate the attack.

Making the index diagnosis in a bioterrorism eventmight be a long shot, but the chances are increasing inthis new era. With each missed diagnosis, more peoplewill become ill or die. As emergency physicians, we mustadd the exotic and nefarious to our differential diagnosis.

Unique Challenges Of Bio-weapons:Conventional vs. Chemical vs. Biological AttacksThe results of a biological attack differ from the destruc-tion seen with conventional explosives or with chemicalweapons. (See Table 2.) Biologic weapons can be deadly,inexpensive to manufacture, and produce contagion andgrowing fear as the epidemic spreads. The cost to affect asquare kilometer with a biological weapon is approxi-mately $1, compared to $2000 using a conventionalweapon.7 Dispersal agents may involve water, food, cropdusters, and even the U.S. mail. A piece of fruit couldbecome a weapon of terror if sprayed with a potentagent. Biological weapons are easily smuggled and weigh105-106 times less than chemical weapons of the same“yield” in regard to the number of casualties.8

Biological weapons can cause syndromes nearlyindistinguishable from naturally occurring illnesses, andpatients might not become ill until well after exposure.For these reasons, the HAZMAT model rarely applies tobioterrorism. In contrast to chemical warfare, victims ofbiological weapons initially might be encountered in theED rather than the street. The first victims may fall illdays to weeks after an attack. Even then the diagnosismay be delayed, allowing time for hundreds or eventhousands of people to become infected before prophy-lactic measures are instituted. Containment of theoutbreak is difficult, and decontamination (other thanremoval of clothing, plus soap-and-water removal ofdermal debris) usually is not helpful. During theresultant disease outbreak following a biological attack,isolation and quarantine—concepts that are rarelynecessary with chemical attacks—may be necessary.Because of the insidious nature of these attacks, publicfear can be more pervasive than in an attack by conven-tional weapons with a similar number of casualties.

Table 2. Comparison Of Weapons: Conventional vs. Chemical vs. Biological.

Conventional Chemical Biological

Onset of illness Instantaneous Rapid Often delayed

Exposure source Obvious Obvious Often covert

Mimics naturally occurring illness No No Yes

First victim encounter Prehospital Prehospital Hospital

Containment Easy Relatively easy Difficult

Decontamination helpful Usually not Yes Usually not


General Principles

While each biological agent requires different diagnosticand treatment approaches, certain principles apply to allbioterror incidents.

PlanningThe best time to plan a response to a mass casualty disasteris weeks, months, or years before it happens. Disaster drillsthat specifically address a bio-weapons attack are especiallyuseful. The Association for Professionals in Infection Controland Epidemiology (APIC) and the Centers for DiseaseControl and Prevention (CDC) have published a documentto help prepare hospitals for such events. This electronicpublication, titled “Bioterrorism Readiness Plan: ATemplate for Healthcare Facilities,” is available at:http://bioterrorism.slu.edu/key_references/BioPlan.doc.9

Facilities need to ensure a proper chain of command,adequate communications, efficient triage procedures,and the ability to provide more doctors, nurses, andancillary staff on short notice. During the planning stage,hospitals should determine whether they have adequatemedications—for both patients and staff—in the event ofa biological attack. This would include vaccines, immu-noglobulins, antitoxins, antibiotics, and antidotes.Sufficient amounts of personal protective gear are alsoimportant. Information sheets regarding the variousagents and instructions on when to seek medical care areuseful as patient handouts.

A disaster-planning book located in the ED shouldidentify who plays what role in the event of a masscasualty incident. A separate chapter on bioterrorism willbe invaluable in a time of crisis.

Patient Triage, Placement, And PrecautionsAs in any disaster, efficient triage is essential inmanaging large numbers of patients. One of the mostemotionally straining triage principles in a disaster isthat of “the greatest good for the greatest number.” Thismeans that in a mass casualty incident, the moribundpatient may receive only palliative care, while criticalcare resources are reserved for those with a better chanceof surviving. In a large-scale disaster, it will also beessential to distinguish the “walking worried” from thetruly symptomatic.

Precautions to prevent transmission depend on theparticular biologic agent. Some agents, like anthrax, haveminimal or no potential for human-to-human transmis-sion. Handwashing should be routine for all patients,while gloves, face protection, and gowns should beutilized if procedures or healthcare activities will causecontact with blood, body fluids, excretions, or secretions.9

For more transmissible diseases (such as smallpoxand pneumonic plague), quarantine and a negativepressure room may be necessary to reduce the likelihoodfor transmission. (Infection control measures are de-scribed in further detail later in the text.)

Bioterrorism will also require different interactionswith the laboratory and pathology department. Some

clinical specimens may be highly infectious and requirespecial handling and processing by a state or regionallaboratory. The most dangerous specimens (such asthose possibly contaminated with smallpox or Ebola)must be processed in a special Bio-Safety Laboratory(also known as the “Hot Zone”). These Bio-Safety Level(BSL) 4 labs are located at the CDC and at the UnitedStates Army Medical Research Institute of InfectiousDiseases (USAMRIID).

Remember the risk posed by casualties. Therecently deceased may be teeming with infectiousorganisms, and the pathology department and/orfuneral homes should be warned if certain high-riskdiseases, such as Ebola, are suspected so that specialprotective measures may be implemented throughthe assistance of the CDC.

Decontamination, Prophylaxis, And ImmunizationUnless the patient is grossly contaminated with abiological weapon, decontamination usually is notnecessary. If patients are directly exposed to a powderor spray, they should remove contaminated clothing,place them in an impervious bag, and immediatelyshower with soap and water. Patients should not bedoused in bleach or solvents. Irrigate eyes in the usualmanner with water or saline. While the subsectionsbelow discuss postexposure management, local healthdepartments can provide additional details regardingdecontamination procedures.

Postexposure prophylaxis and immunizationdepend on the agent, type of exposure, and the patient’sclinical status. Clear guidelines regarding who needsprophylaxis will assist both patients and physicians inavoiding adverse drug events and conserving valuableresources. Some well-prepared hospitals print an infor-mation sheet for patients who want but do not receiveprophylaxis; this explains why they do not need antibiot-ics or vaccines and under what circumstances theyshould return to the ED.

Differential Diagnosis

Syndrome RecognitionIn theory, any biological agent could be used as aterrorist weapon; therefore, it is important to think“epidemiologically” and recognize disease patternsas possible bioterrorist attacks. For example, one caseof rapidly progressive influenza-like illness may notherald a bioterrorist attack, but multiple patients withan unusual syndrome of influenza-like illness shouldraise the suspicion for bioterrorism. Most bioterroristagents initially induce an influenza-like prodrome,including fever, chills, myalgias, or malaise. One ormore of four syndromic patterns then follow thenonspecific prodrome:

• Rapidly progressive pneumonia• Fever with rash• Fever with altered mental status• Bloody diarrhea


When outbreaks of any of these syndromic diseasepatterns are identified, suspect bioterrorism. (See Table 3.)

The CDC has issued a list of high-likelihood poten-tial bioterrorist agents. They are prioritized according toease of dissemination, transmissibility, mortality, publichealth impact, potential to cause fear and social disrup-tion, and need for special preparedness.11 (See Table 4 onpage 6.) Category A agents are most likely to cause masscasualties if deliberately disseminated as small-particleaerosols and require broad-based public health prepared-ness. These agents, therefore, are seen as a priority forpreparation and training. This article discusses theepidemiology, pathophysiology, evaluation, and manage-ment of these diseases.

Anthrax

“The explosion of anthrax bombsis hardly louder than the popping of a paper bag.”—Aldous Huxley, in “Brave New World,” 1932

EpidemiologyFor centuries, anthrax has infected animals and occasion-ally humans throughout the world. Bacillus anthracis, thecausative organism of anthrax, is a gram-positive spore-forming bacillus that is naturally found in the soil and isdistributed worldwide.12,13 The hardy spores formed bythe bacterium can survive harsh environmental condi-tions and remain viable for decades—perhaps evencenturies. When exposed to a nurturing environmentsuch as a host animal or human, the vegetative bacillusdevelops from the spore. Animals such as sheep, cattle,goats, and horses acquire the bacillus spore whilegrazing. In the natural environment, humans acquire thedisease via inoculation of minor skin lesions from contact

with infected animals, their hides, wool, or other prod-ucts. Other vectors include ingesting contaminated meat,inhaling spores during the processing of wool, andpossibly flies that bite.12 The drastic reduction in anthraxin the developed world has been attributed to aggressiveanimal vaccination programs.14

Anthrax can be “weaponized” by milling spores to1-5 micron size. These small spores remain aerosolizedfor long periods of time (and are also small enough toleach through the 20-micron pores that may be found inenvelopes). Other weaponized features may includegreater virulence or antibiotic resistance.15 The strainresponsible for the most recent outbreak, the Ames strain,is noted for its high toxin production.16 The strain datesback to a 1981 anthrax-infected Texas cow, bacteria fromwhich were studied by USAMRIID.

Anthrax infection in humans manifests in threeforms: cutaneous, gastrointestinal, and inhalational. Thecutaneous form is by far the most common. Between 1944and 1994, 224 cases of cutaneous anthrax were reportedin the United States.17 Gastrointestinal anthrax is rare,and outbreaks are usually associated with the ingestionof contaminated, undercooked meat.18,19 Prior to October4, 2001, the last known case of inhalational anthrax in theUnited States was in 1978. The accidental release in 1979of aerosolized anthrax spores by a military microbiologylaboratory in Sverdlovsk, a city of the former SovietUnion, resulted in 79 cases of anthrax infection and 68deaths, mostly attributable to inhalational infection.20

Since the catastrophe at Sverdlovsk, there were no deathsreported from cutaneous disease alone.

PathophysiologyAnthrax infection begins when spores are introducedthrough a break in the skin (cutaneous anthrax), the

Table 3. Distinguishing A Natural Disease Outbreak From A Bioterrorist Attack.

Natural outbreak Bioterrorist attack

Gradual presentation of victims with no readily Sudden presentation of large numbers of victims with a similar diseaseidentifiable common exposure or syndrome (e.g., many cases of rapidly progressive pneumonia) who

may have a readily identifiable common exposure

Cases present at varying stages of disease progression Many cases present at a similar stage in disease epidemiology due tocommon source of exposure

Usual expected disease course for that specific pathogen, More severe disease than is usually expected for that specificwith appropriate response to standard therapy pathogen, or failure to respond to standard therapy

Slowly progressive disease with prodromal symptoms Rapidly progressive disease, suggesting an unusual form of disease(e.g., natural progression of bubonic plague to transmission (e.g., primary pneumonic plague with rapidly progressivepneumonic plague) fulminant pneumonia and no prodromal bubonic form of the disease)

Normal antibiotic sensitivities Highly virulent strains, possibly with antibiotic resistance

No announcement of attack Possible announcement of bioterrorist attack

Presentation of common illnesses (such as influenza) Presentation of a single case of any disease caused by CDCCategory A, B, or C agent

Presentation of disease in the usual geographic area Presentation of disease in an unusual geographic area orduring the usual transmission season transmission season


mucosa (gastrointestinal anthrax), or through depositionin alveolar spaces with subsequent lymphatic transportto mediastinal lymph nodes (inhalational anthrax). Aftergerminating, anthrax produces a variety of toxins, two ofwhich are suitably termed edema factor and lethal factor.These toxins perform their noxious duties even ifantibiotics kill all of the bacteria.

The cutaneous form is characterized by a pruriticmacule or papule that progresses to a round ulcer within48 hours. The central lesion may have a superimposedvesicle up to 2 cm in diameter and is often surrounded bysmaller satellite vesicles that contain serosanguineousfluid laden with gram-positive bacilli. (See Figure 1.) Thelesion then develops a painless, depressed black eschar.(The Greek derivation of the word “anthrax” is “char-coal” or “coal,” referring to this characteristic lesion.) Theeschar dries, loosens, and falls off within 1-2 weeks,leaving little if any scar.

Localized edema, erythema, and lymphadenopathy areimportant clues to the diagnosis. Without antibiotic therapy,cutaneous anthrax can lead to bacteremia, with mortalityrates as high as 20%. With antibiotics, death due tocutaneous anthrax is rare.21 Recognition of cutaneousanthrax infection is important because its presenceindicates exposure to anthrax spores and could possiblyherald other cases of the more serious inhalationalanthrax. The differential diagnosis of cutaneous anthraxincludes furuncles (usually painful), ecthyma (usuallywithout edema or systemic signs), ecthyma gangrenosum(usually in neutropenic patients), and brown reclusespider bite (painful necrotic lesion).22 Another unusualpossibility is orf, or ecthyma contagiosum, a viralzoonosis of sheep and goats, in which gelatinous edemais rare and the scab forms without eschar.

Gastrointestinal anthrax symptoms (nausea, vomit-ing, fever, and abdominal pain) appear 2-5 days after theingestion of vegetative bacilli (usually in undercookedmeat). The disease progresses rapidly to bloody diarrhea,with ulceration of the gastrointestinal tract, hemorrhagic

Table 4. Critical Biological Agents.

Category AHigh-priority agents include organisms that pose a risk tonational security because they can be easily disseminated ortransmitted person-to-person; cause high mortality, withpotential for major public health impact; might cause publicpanic and social disruption; and require special action forpublic health preparedness.

• Variola major (smallpox)• Bacillus anthracis (anthrax)• Yersinia pestis (plague)• Clostridium botulinum toxin (botulism)• Francisella tularensis (tularemia)• Viral hemorrhagic fevers

• Filoviruses• Ebola virus (Ebola hemorrhagic fever)• Marburg virus (Marburg hemorrhagic fever)

• Arenaviruses• Lassa fever virus (Lassa fever)• Junin virus (Argentine hemorrhagic fever) and

related viruses

Category BSecond-highest-priority agents include those that aremoderately easy to disseminate; cause moderate morbidityand low mortality; and require specific enhancements of theCDC’s diagnostic capacity and enhanced disease surveillance.

• Coxiella burnetii (Q fever)• Brucella species (brucellosis)• Burkholderia mallei (glanders)• Alpha viruses

• VEE virus (Venezuelan encephalomyelitis)• EEE and WEE viruses (Eastern and Western equine

encephalomyelitis)• Ricin toxin from Ricinus communis (castor beans)• Epsilon toxin of Clostridium perfringens• Staphylococcus enterotoxin B

A subset of Category B agents includes pathogens that arefood- or waterborne. These pathogens include but are notlimited to:

• Salmonella species• Shigella dysenteriae• Escherichia coli 0157:H7• Vibrio cholerae• Cryptosporidium parvum

Category CThird-highest-priority agents include emerging pathogensthat could be engineered for mass dissemination in thefuture because of availability; ease of production anddissemination; and potential for high morbidity and mortalityand major health impact.

• Nipah virus• Hanta viruses• Tickborne hemorrhagic fever viruses• Tickborne encephalitis viruses• Yellow fever• Multidrug-resistant tuberculosis

Source: Khan AS, Levitt AM, Sage MJ, et al. Biological and chemicalterrorism: strategic plan for preparedness and response. Recommen-dations of the CDC Strategic Planning Workgroup. April 21, 2000.Source: Centers for Disease Control and Prevention.

Figure 1. Early cutaneous anthrax.


mesenteric lymphadenitis, and formation of markedascites. Mortality can be greater than 50%.19,23

Classic inhalational anthrax is a biphasic illness.After up to six days of incubation, the first phase appearsas a nonspecific, flu-like illness characterized by mildfever, malaise, myalgias, nonproductive cough, andoccasional chest or abdominal pain. Rhinorrhea and nasalcongestion usually are not associated with inhalationalanthrax. Such symptoms suggest an etiology other thananthrax in patients presenting with influenza-likedisease.24-26 (See Table 5.) Shortness of breath appears tobe common in anthrax but unusual in influenza andinfluenza-like illness.26 The second phase of the illnessappears 2-3 days later and is characterized by the abruptonset of high fever, dyspnea, chest or abdominal pain,diaphoresis, cyanosis, and shock. The recent inhalationalcases in the United States have manifested with sweatsand gastrointestinal symptoms.5,27-29 Hemorrhagicmeningitis and altered mental status may be seen inup to 50% of cases as the disease progresses to thecentral nervous system.30,31 Death occurs within 24-36hours. The case-fatality estimates for inhalationalanthrax are based on incomplete information; however,the mortality is approximately 75%, even with aggressivecare including antibiotics.2

ED EvaluationWith the possible exception of Gram’s stain and culture,most readily available laboratory tests are not helpful inthe diagnosis of anthrax. While a complete blood countand chemistry panel may show hemoconcentration orleukocytosis, such findings are clearly nonspecific.Gram’s stain and culture of fluid from cutaneous vesicles,blood, or cerebrospinal fluid will often show gram-positive bacilli, which grow in bamboo-like chains. (See

Figure 2.) Blood cultures may become positive in as fewas 14 hours.32

Viral testing is generally unhelpful. While point-of-carerapid influenza tests may occasionally help differentiateinfluenza from other influenza-like illnesses, the sensitivityof the rapid influenza tests is relatively low (45%-90%). Anegative test does not add any diagnostic certainty, and apositive test could occur in someone unfortunate enough tohave both influenza and anthrax (a situation that couldoccur during the flu season, when as many as one-quarter ofthe population could test positive). Because viral cultureresults are not immediately available, they are not generallyuseful in the ED setting.

In asymptomatic patients with suspected exposure to

Table 5. Distinguishing Inhalational Anthrax From Influenza.

Sign or symptom Anthrax Influenza or other influenza-like illness

Fever or chills +++++ +++

Fatigue or malaise +++++ +++++

Cough ++++ ++++

Shortness of breath ++++ 0

Chest discomfort or pleuritic chest pain +++ +

Headache ++ ++++

Myalgias ++ ++++

Sore throat 0 ++++

Rhinorrhea 0 ++++

Nausea or vomiting ++++ +

Abdominal pain + +

Adapted from: Centers for Disease Control and Prevention. Considerations for distinguishing influenza-like illness from inhalational anthrax. MMWRMorb Mortal Wkly Rep 2001;50(44):984-986.

Figure 2. Bacillus anthracis, gram-positive bacilliin chains.

Source: Jernigan JA, Stephens DS, Ashford DA, et al. Bioterrorism-related inhalational anthrax: the first 10 cases reported in theUnited States. Emerg Infect Dis 2001;7(6):933-944.


inhalational anthrax, public health authorities have usednasal swab culture as an epidemiologic screening tool toconfirm exposure to B. anthracis. The predictive value ofthis tool is not known and, at present, the CDC does notrecommend the routine use of nasal swab culture to rule outinfection with B. anthracis.33

Chest radiography in patients with inhalationalanthrax often exhibits mediastinal widening, occasionalinfiltrates, and pleural effusion. (See Figure 3.) Allpatients in the recent bioterror event had mediastinalabnormalities early in the course of the illness. Incontrast, most cases of influenza-like illness are notassociated with chest radiographic abnormalities.Computed tomography (CT) of the chest should stronglybe considered in any patient with influenza-like illnesswho presents with mediastinal abnormalities or pleuraleffusions.34-36 CT of the chest in cases of inhalationalanthrax was first reported with the outbreak of October2001 and seems to be an important diagnostic tool.Findings included prominent mediastinal lymphaden-opathy, pleural effusion, mediastinal edema, and basilarair space disease.27-30 (See Figure 4.) With the developmentof hemorrhagic meningitis, contrast-enhanced CT of thehead may show diffuse meningeal enhancement.37,38

Treatment And ProphylaxisIn any suspected case of inhalational anthrax or in casesof cutaneous anthrax with signs of systemic involvement,

extensive edema, or head and neck lesions, intravenousmultidrug antimicrobial therapy should be startedimmediately. Based on animal and in vitro studies,the recommended agents include ciprofloxacin 400 mgevery 12 hours or doxycycline 100 mg every 12 hours plusone of the following drugs: rifampin, vancomycin,penicillin, ampicillin, chloramphenicol, imipenem,clindamycin, or clarithromycin. For uncomplicated casesof cutaneous anthrax that do not involve the head orneck, the CDC suggests that oral ciprofloxacin 500 mgevery 12 hours or doxycycline 100 mg every 12 hoursalone is sufficient therapy.33

To date, there are no controlled human trialsthat validate current treatment recommendations forinhalational anthrax. The clinical experience is likewiselimited. Studies in monkeys show that death may occurup to 58 days after inhalation of anthrax spores, hencethe origin for the recommendation that antibioticprophylaxis for inhalational exposure should be contin-ued for 60 days.39 This concept of prolonged prophylaxisis supported by the Sverdlovsk inhalational anthraxoutbreak, where all cases occurred within six weeks ofthe release of the spores.20,31

Promptly initiate prophylactic therapy for patientswith confirmed exposure to B. anthracis. The CDCrecommends that, as with uncomplicated cutaneousanthrax, oral ciprofloxacin 500 mg every 12 hours ordoxycycline 100 mg every 12 hours is sufficient prophy-lactic therapy.40 Children or breastfeeding mothers maytake amoxicillin at the appropriate dosage for prophy-laxis only, but confirmed cases should be treated withciprofloxacin or doxycycline and the other antibioticdespite their known adverse effects in children.41 In anysuspected or confirmed exposure to anthrax, publichealth authorities should be notified and involved in case

Figure 3. Chest radiography of a patient with inhalationalanthrax, demonstrating a widened mediastinum.

Source: Centers for Disease Control and Prevention.

Source: Jernigan JA, Stephens DS, Ashford DA, et al. Bioterrorism-related inhalational anthrax: the first 10 cases reported in theUnited States. Emerg Infect Dis 2001;7(6):933-944.

Figure 4. Chest computed tomography of a patientwith inhalational anthrax, demonstrating hemorrhagicmediastinal lymphadenopathy.

➤

➤


management in order to assist with epidemiologicinvestigation. At present, there is no vaccine for B.anthracis available to the public. The U.S. governmentmaintains a limited supply of a licensed anthrax vaccinefor use by at-risk military personnel.

Because toxins released from the bacteria cause themajor complications of systemic anthrax, corticosteroidtherapy may be of some benefit in treating cases ofinhalational anthrax.42,43 However, no empirical dataregarding this intervention are available.

Infection ControlAnthrax is not transmissible through person-to-personcontact, and private rooms are unnecessary. Universalprecautions are generally sufficient to protect contactsfrom exposure to the disease. Decontamination with asoap-and-water bath is sufficient for gross exposures.

Smallpox

“The small pox was always present,filling the church-yards with corpses,

tormenting with constant fears all whom it hadnot yet stricken, leaving on those whose lives it sparedthe hideous traces of its power, turning the babe into

a changeling at which the mother shuddered,and making the eyes and cheeks of the betrothed maiden

objects of horror to the lover.”—Thomas Babington Macaulay, in “History of England,” 184844

EpidemiologyThe last known naturally occurring case of smallpox wasin Somalia in 1977. After a monumental vaccinationcampaign, in 1980 the World Health Organization (WHO)declared smallpox officially eradicated.45,46 There is nonatural animal reservoir or vector for variola, the virusresponsible for smallpox infection. Variola virus isconsidered a potential biological weapon threat becauseof its aerosol infectivity, high mortality, transmissibility,and relative stability in the environment. Further, thereare reports of efforts by the former Soviet Union to mass-produce the virus and adapt it for use as a bio-weapon.47

Some experts fear that some nations retained stocks ofthe variola virus instead of placing them in the WHOrepositories as requested in the late 1970s. The reintro-duction of smallpox would no doubt lead to deadlyepidemics. During the 1960s and 1970s in Europe, asmany as 10-20 second-generation cases were oftenreported as infected from an index case.45,48 During the20th century, smallpox infection was associated with a 1%mortality rate in the vaccinated and a 30% mortality ratein the unvaccinated.45

Smallpox is spread from person to person primarilyvia airborne particles and direct contact. Contaminatedclothing and bed linens also spread the virus.49,50

PathophysiologyInfection occurs through direct contact with mucous

membranes or through aerosol exposure. When inhaled,the virus travels from the respiratory tract to regionallymph nodes, where it replicates after an incubationperiod of 7-17 days. The resulting viremia causes aprodrome characterized by high fever, malaise, vomiting,headache, and myalgias. Two to three days later, acharacteristic macular rash erupts about the face, hands,and forearms. As the rash spreads across the body, themacules morph into papules and eventually to pustularvesicles. (See Figure 5.) Lesions are most prominent aboutthe extremities and face and tend to develop synchro-nously, a characteristic that aids in discriminating variolainfection from varicella infection, as chickenpox tends toshow lesions in various stages of evolution. By the timethe rash occurs, patients are usually toxic-appearing.Within 7-10 days, the rash begins to form scabs (if thepatient lives that long), leaving depressed, depigmentedscars. Scabs contain readily recoverable virus throughoutthe entire healing period; therefore, all patients should beconsidered infectious until all scabs are shed.51

ED EvaluationThere is no widely available laboratory test to confirmsmallpox infection; therefore, clinical presentation is thekey to early diagnosis. The presence of a centrifugal,synchronous rash in the appropriate clinical settingsuggests the diagnosis of smallpox.

In the first several days of the rash, it may beimpossible to distinguish between smallpox andchickenpox. However, smallpox lesions are “deep,”develop at the same pace, and rapidly diffuse. In con-trast, chickenpox lesions are superficial, appear invarious stages of evolution, and develop in crops.Chickenpox is more dense over the trunk instead of theextremities (as in the case of smallpox)—and, unlikesmallpox, chickenpox lesions almost never appear on thepalms or soles.52

Because the discovery of even a single case ofsmallpox is an international emergency, it is imperative toinvolve public health officials early when the diagnosis issuspected. (Re-read the section on distinguishingsmallpox from chickenpox before calling the President.)

Figure 5. Pustular rash of smallpox.



In this instance, the patient must be placed in isolationand held, even if against his or her will, until publichealth authorities complete their assessment. Electronmicroscopy can confirm the presence of smallpoxvirions. Definitive techniques such as cell culture andnucleic-acid based diagnostic techniques can also beused to identify variola virus, but currently they areneither widely nor rapidly available in the ED setting.53,54

Sampling of pustular fluid should be performed only bypeople who are recently vaccinated against smallpox,and samples are to be handled by a Bio-Safety Level 4(BSL-4) laboratory.

Prophylaxis And TreatmentAlthough animal trials with cidofovir are promising,there is currently no treatment for smallpox.55

In the United States, routine smallpox vaccinationceased in 1972. The immune status for those vaccinatedbefore 1972 is unclear. A limited emergency supply ofsmallpox vaccine and vaccina immune globulin (VIG) isunder the control of the CDC. Efforts to increase thenational stockpile of smallpox vaccine are under way.

Infection ControlSmallpox is extremely infectious. Diagnosis of smallpoxrequires immediate respiratory isolation of the patient.Place a mask on the patient when he or she is beingtransported and even while he or she is in the treatmentroom. All healthcare providers who enter the room mustbe gowned and wear a National Institute for Occupa-tional Safety and Health (NIOSH) particulate respirator(N95). The gown must be removed before leaving thepatient’s room. All household and face-to-face contactsshould be vaccinated and placed under surveillance.Because smallpox is rapidly spread via aerosol transmis-sion, it poses a particular threat in hospitals that have alimited number of negative pressure isolation facilities.Given the serious nature of this disease, home care andquarantine are a likely and reasonable alternative toinpatient hospital treatment, especially in a masscasualty instance.

Plague

“At the onset of the disease both men and womenwere afflicted by a sort of swelling in the groin

or under the armpits, which sometimes attainedthe size of a common apple or egg. Some of these swellings

were larger and some smaller, and all were commonly calledboils….Afterwards, the manifestation of the disease changed

into black or livid spots on the arms, thighs and the wholeperson….Like the boils, which had been and continued

to be a certain indication of coming death, these blotcheshad the same meaning for everyone on whom they appeared.”

—Giovanni Boccaccio, “Preface to the Ladies,”in “The Decameron”

EpidemiologyPlague, also known as the Black Death, has killed

millions of victims over the ages—often in catastrophicpandemics. There have been three pandemics recorded,beginning in 541 A.D., 1346, and in China in 1855, killingup to 30%-60% of the population of the infected countries(or continents).56 With advances in living conditions,public health, and antibiotic therapy, the rare naturaloutbreaks are now small and quickly contained.57,58

However, plague has been used as a biological weapon inthe past and has potential for causing devastating diseaseif released as an aerosol.47,59,60

Naturally occurring plague manifests when infectedfleas bite humans, who then develop bubonic plague. Afew people infected in this manner will develop systemicdisease, known as primary septicemic plague. A percent-age of patients with bubonic or septicemic plague willdevelop secondary pneumonic plague, which can bespread via droplet transmission. In turn, people contract-ing the disease by this route develop primary pneumonicplague. Between 1947 and 1996 in the United States, therewere 390 cases of plague reported. Of these cases, 84%were bubonic, 13% septicemic, and 2% pneumonic.60

While it is possible that the release of infected fleascould be used as a biological weapon, the most deadlybio-weapons scenario is the release of aerosolized plague,leading to outbreaks of primary pneumonic plague.61

PathophysiologyYersinia pestis, a gram-negative coccobacillus, causesplague. When viewed under the microscope, the bacteriahave a characteristic bipolar appearance that is com-monly referred to as the “safety-pin” pattern. (See Figure6.) When a human is infected by the bite of an infectedflea, symptoms of bubonic plague develop within 2-8days. These include the sudden onset of flu-like symp-toms and the development of acutely swollen, painfullymphadenopathy, typically in the groin, axilla, orcervical regions. The infected lymph nodes, known asbuboes, can be up to 10 cm in diameter. They are warm,exquisitely tender, non-fluctuant, and are associated withconsiderable edema.

Figure 6. Yersinia pestis, gram-negative coccobacilli in a“safety-pin” pattern.



Septicemic plague can occur de novo from the bite ofan infected flea or secondarily from untreated bubonicplague. It is characterized by disseminated intravascularcoagulation, necrosis of small blood vessels, purpuricskin lesions, and gangrene to acral regions such as thedigits and nose.62

Pneumonic plague develops secondarily frombubonic or septicemic plague, or primarily when aero-solized bacilli are inhaled. After a two- to four-dayincubation period, initial symptoms include fever,hemoptysis, and dyspnea.63,64 Other complaints includenausea, vomiting, abdominal pain, and diarrhea.65,66

As the disease progresses, a fulminant pneumoniaensues with pulmonary infiltrates and lobar consolida-tion, respiratory failure, sepsis, and death. Primarypneumonic plague infection, as would be expected from theaerosolized release of Y. pestis, typically does not cause theclassic buboes that are seen with the naturally occurring formof the disease.

ED EvaluationThere are two recent cases of primary pneumonicplague (which were contracted after handling infectedcats). Both patients had pulmonary symptoms as wellas nausea, vomiting, abdominal pain, and diarrhea;both died.63,65

There is no widely available rapid diagnostic test forplague. Gram’s stain and culture of blood, cerebrospinalfluid (CSF), sputum, or lymph node aspirate may revealgram-negative bacilli or coccobacilli. Giemsa stainingreveals bipolar “safety-pin”-appearing bacilli. Culturesshould demonstrate growth within 24-48 hours. Defini-tive laboratory diagnosis of Y. pestis can be made viaantigen detection, immunoassay, immuno-staining, orpolymerase chain reaction (PCR) at the CDC and othergovernment-operated laboratories.67,68

Radiologic evaluation with chest radiography andcomputed tomography may reveal evidence of pulmo-nary infiltrate or lobar consolidation.62 Obtain a chestx-ray on any patient in whom the plague is suspected.

Prophylaxis And TreatmentIn the past, a vaccine protective against naturallyoccurring plague was produced; however, the vaccinewas ineffective against primary pneumonic plagueand is no longer available. New vaccines are currentlyunder development.69

Antibiotic therapy with streptomycin 15 mg/kggiven intramuscularly twice a day for 10 days has beenconsidered first-line therapy for pneumonic plague in thepast. Small numbers of human cases and animal datasuggest that gentamicin or doxycycline given intrave-nously are effective treatments as well. Animal modelssuggest that quinolones may also be efficacious, but nohuman data exist for treatment of plague with this classof drugs.70 In addition, laboratory and animal studiesindicate that doxycycline or fluoroquinolone antibioticsgiven orally for seven days is adequate prophylaxis forthose potentially exposed to plague.

Infection ControlBecause plague is readily transmissible via droplets,strict isolation for the first 48 hours of treatment isrequired to prevent secondary spread of the disease.Patients with the pneumonic form of the disease mustremain in isolation for four days after the initiation ofantibiotic therapy.62

Botulism

EpidemiologyBotulinum toxin is a neurotoxic protein produced by theanaerobic bacterium Clostridium botulinum. The naturallyoccurring form of the disease is seen with ingestion ofimproperly prepared or canned foods or with absorptionof the toxin from an infected wound. In the United States,fewer than 200 cases are reported annually.71 As abiological weapon, botulinum toxin could be released asan aerosol or used as a food contaminant. After the GulfWar, Iraq admitted to producing 19,000 liters of concen-trated botulinum toxin, which are still unaccounted for.72

Based on primate studies, the lethal dose of inhaledbotulinum toxin for a 70 kg human is approximately0.21-0.90 mcg, making it the most toxic substance knownto man.73-75 Botulinum toxin has already been used as abio-weapon in Japan on at least three occasions between1990 and 1995 by a Japanese cult.76 These attacks failedfor a variety of reasons, none of which were due to thelimitations of the toxin.

PathophysiologyBotulinum toxin acts by binding to the presynaptic nerveterminal at the neuromuscular junction and at cholinergicautonomic sites. In doing so, the toxin prevents presyn-aptic release of the neurotransmitter acetylcholine,thereby blocking neurotransmission. Symptoms developwithin 1-3 days after inhalational exposure, beginningwith bulbar palsies. Victims demonstrate dysarthria,dysphagia, blurred vision, and ptosis. As the diseaseprogresses, skeletal muscles are affected, and the patientdevelops descending, symmetrical, flaccid paralysis thatmay culminate in respiratory failure.

ED EvaluationPatients with botulism are alert, oriented, and afebrile.Upon neurologic examination, they exhibit bulbar palsiesand flaccid paralysis, while sensation remains intact.Look for the “four Ds”: diplopia, dysarthria, dysphonia,and dysphagia.77

In the ED, the diagnosis is clinical, and laboratorytests are not generally helpful. Electrophysiologic studies(such as electromyogram) may be helpful (but not readilyavailable during an outbreak).78 Definitive testing withmouse toxicity assay or immunoassay is availablethrough the CDC and other government labs. While themouse assay is the most sensitive test, it requires severaldays to complete. The differential diagnosis includesGuillain-Barré syndrome (and its Miller-Fisher variant),

Continued on page 14


The evidence for recommendations is graded using the following scale. For complete definitions, see back page. Class I: Definitely recommended.Definitive, excellent evidence provides support. Class II: Acceptable and useful. Good evidence provides support. Class III: May be acceptable,possibly useful. Fair-to-good evidence provides support. Indeterminate: Continuing area of research.

This clinical pathway is intended to supplement, rather than substitute for, professional judgment and may be changed depending upon apatient’s individual needs. Failure to comply with this pathway does not represent a breach of the standard of care.

Copyright ©2002 EB Practice, LLC. 1-800-249-5770. No part of this publication may be reproduced in any formatwithout written consent of EB Practice, LLC.

Clinical Pathway: ED Management Of Bioterrorism• Unusual diseases?• Abnormal presentation of disease?• Unexplained fatalities?• Atypical clustering of disease?

Influenza-type illness with:• suspicious circumstances?• shortness of breath?• no sore throat or rhinorrhea?

Unexplained skin lesion with:• significant local erythema and edema?• central vesicle with satellite vesicles?• painless, black, central eschar?

• Papules or pustular vesicles in samestage of evolution?

• “Deep” lesions?• Toxic-appearing patient?

➤Yes

➤➤

No

• Consider bioterrorism (Class I)• Notify local health department and FBI (Class I-II)

Possible inhalational anthrax• Chest x-ray (Class I)• Consider blood culture (Class I-II)• Consider CT of chest (especially if pleural effusion,

mediastinal widening) (Class I-II)• Determine the need for empirical treatment* of

presumed anthrax (Class I-II)

* IV ciprofloxacin 400 mg every 12 hours or doxycycline 100 mgevery 12 hours plus one of the following: rifampin, vancomycin,penicillin, ampicillin, chloramphenicol, imipenem, clindamycin,or clarithromycin

➤Yes

➤

No

Possible cutaneous anthrax• Gram’s stain of lesion looking for gram-positive bacilli

(Class I-II)• Culture/biopsy of lesion (Class II)• Determine the need for empirical treatment* of

presumed anthrax (Class I-II)

*Oral ciprofloxacin 500 mg or doxycycline 100 mg BID (notadequate for head or neck infections)

➤Yes

➤

No

➤Yes

➤

No

Possible smallpox• Respiratory isolation (Class I)• Gown, gloves, mask (Class I)• Notify health department about possible smallpox

(Class I)• Samples of pustular fluid to be collected and handled

by BSL-4 lab (Class I-II)

Go to top of next page


Clinical Pathway: ED Management Of Bioterrorism (continued)

The evidence for recommendations is graded using the following scale. For complete definitions, see back page. Class I: Definitely recommended.Definitive, excellent evidence provides support. Class II: Acceptable and useful. Good evidence provides support. Class III: May be acceptable,possibly useful. Fair-to-good evidence provides support. Indeterminate: Continuing area of research.

This clinical pathway is intended to supplement, rather than substitute for, professional judgment and may be changed depending upon apatient’s individual needs. Failure to comply with this pathway does not represent a breach of the standard of care.

Copyright ©2002 EB Practice, LLC. 1-800-249-5770. No part of this publication may be reproduced in any formatwithout written consent of EB Practice, LLC.

• Fever, hemoptysis, and dyspneafollowed by fulminant pneumoniaand respiratory failure OR

• Huge and painful lymphadenopathy,typically in the groin, axilla, or cervicalregions OR

• Purpuric skin lesions, and gangreneto acral regions?

• Dysarthria, dysphagia, blurred vision,and ptosis OR

• These symptoms followedby descending, symmetrical,flaccid paralysis

Flu-like illness followed by:• Bronchitis, bronchopneumonia,

pneumonitis, hilar lymphadenitis,or sepsis OR

• Massive lymphadenopathy?

• High fever, headache, fatigue,myalgias, abdominal pain, andmalaise, followed by:

• Gastrointestinal bleeding, general-ized mucous membrane hemor-rhage, petechial or ecchymoticrash, conjunctival injection,nondependent edema, andhypotension?

➤Yes

➤

No

Possible plague• Gram’s stain and culture of blood, CSF, sputum, or

lymph node aspirate for gram-negative bacilli orcoccobacilli (Class II)

• Giemsa staining for bipolar “safety-pin”-appearingbacilli (Class II)

• Chest x-ray or CT of chest (Class II)• Determine the need for empirical treatment* of

presumed plague (Class I-II)

* IM streptomycin 15 mg/kg BID for 10 days OR IV ciprofloxacinor IV gentamicin

Possible botulism• Anticipate and determine the need for mechanical

ventilation (Class I-II)• Contact CDC to determine the need for botulism

antitoxin (Class I-II)

➤Yes

➤

No

➤Yes

➤

No

Possible tularemia• Gram’s stain for small, faint-staining gram-negative

coccobacilli (Class II)• Blood cultures (Class II)• Chest x-ray or CT of chest (Class II)• Determine the need for empirical treatment* of

presumed tularemia (Class I-II)

* IM streptomycin 15 mg/kg BID for 10 days OR IV ciprofloxacinor IV gentamicin

➤Yes Possible viral hemorrhagic fever

Supportive care:• Crystalloids, blood products, and pressors as

indicated (Class II)• Gown, gloves, NIOSH 95 mask (Class I)• Respiratory isolation (Class II)• Intravenous ribavirin if presumed Lassa fever or

Argentine hemorrhagic fever (Class II-III)


myasthenia gravis, poliomyelitis, Eaton-Lambert syn-drome, tick paralysis, hypokalemia, and hysteria.

Prophylaxis And TreatmentDespite its frightening lethality, the botulinum toxin isheat labile, and it is easily destroyed by heating contami-nated food or drink to an internal temperature of 85°C(185°F) for five minutes.79 A limited supply of antitoxin isavailable through the CDC. USAMRIID holds an investi-gational antitoxin product. This antitoxin is effective inanimals if administered after exposure but before thedevelopment of serious symptoms.73 Early administrationof the antitoxin may prevent further deterioration butwill not reverse existent paralysis.80 Likewise, a limitedsupply of an investigational toxoid preparation, used formore than 30 years to immunizeat-risk laboratory workers and military troops, is avail-able through USAMRIID.81 Recombinant vaccines arecurrently in the development phase.82

Respiratory failure is the most common cause ofdeath due to botulinum toxin; carefully monitor patientsfor evidence of respiratory muscle weakness. Assess theadequacy of gag and cough reflexes, look for the danger-ous sign of drooling, and monitor respiratory parameterssuch as oxygen saturation, vital capacity, and inspiratoryforce. Mechanical ventilation is the most importanttreatment, as antibiotics have no effect on the diseasecourse.77 Avoid aminoglycosides and clindamycin, asthey may worsen the neuromuscular blockade.

Recovery may take weeks or months; prolongednursing care is required.

Infection ControlBotulism is not transmissible from person to person;therefore, no special isolation procedures are required.Contaminated surfaces should be washed with0.1% bleach.

Tularemia

“The horseman on the pale horse is Pestilence.He follows the wars.”

—The General (Boris Karloff), in “Isle of the Dead”

EpidemiologyTularemia is a zoonotic disease caused by Francisellatularensis, a small facultative intracellular gram-negativecoccobacillus. The clinical disease is known by a varietyof names, including “rabbit fever” and “deer fly fever.”Naturally occurring disease is seen when humans areinoculated through the bite of an infected insect. Thisulceroglandular form of the disease causes flu-likesymptoms, fever, and massive lymphadenopathy. Thereare also reports, including a recent series of 11 patients, ofnaturally occurring primary pneumonic tularemia due toinhalation of contaminated dust.83 The mortality rate ofuntreated pneumonic tularemia is over 60%.84 In a

biological weapons scenario, the aerosolization ofF. tularensis is most likely, leading to outbreaks ofprimary pneumonic tularemia. The bio-warfare potentialof tularemia has been studied since the 1930s,85 and theformer Soviet Union reportedly developed strainsresistant to antibiotics and vaccines.47

PathophysiologyAfter a three- to five-day incubation period, peopleexposed to aerosolized tularemia present with an acute,nonspecific febrile illness. Initial symptoms includefever, headache, myalgias, coryza, sore throat, and drycough. Nausea, vomiting, and diarrhea are sometimesnoted. Shortly thereafter, the disease progresses tobronchitis, bronchopneumonia, pneumonitis, hilarlymphadenitis, sepsis, and death.86 When compared toother threat agents, such as anthrax or plague, illness dueto tularemia progresses more slowly and has a lowercase-fatality rate.

ED EvaluationTularemia as an aerosolized bio-weapon would presentas an outbreak of acute febrile illness. Clinical symptomsvary considerably depending on the portal of entry, andpatients may demonstrate pharyngitis, bronchitis,pneumonitis, pleuritis, hilar lymphadenitis, or sepsis.Others may have fever with no identifiable source.87

Chest radiography or CT may reveal peribronchialinfiltrates, multilobar pneumonia, pleural effusion, andhilar lymphadenopathy.88,89

As with many other potential bioterror agents, rapiddiagnostic testing is not widely available. In public healthlaboratories, confirmatory diagnosis is made by directfluorescent antibody or immunohistochemical stains.90-92

Routine Gram’s stain reveals small, faint-staining gram-negative coccobacilli. Growth of F. tularensis by culture ofbody fluids is the definitive means of diagnosis. Serumantibody titers are not diagnostic until 10 or more daysafter the onset of illness and are not valuable during theacute phase of the illness.93

Prophylaxis And TreatmentIn a contained casualty situation, current recommenda-tions for the treatment of tularemia include a 10-daycourse of streptomycin given intramuscularly, gentamicingiven intravenously or intramuscularly, or ciprofloxacingiven intravenously.94 Tetracyclines or chloramphenicolmay also be used but are less effective and must beadministered for at least 14 days to prevent relapse.95,96

Patients exposed to tularemia should receivedoxycycline 100 mg orally twice a day or ciprofloxacin500 mg orally twice a day for 14 days as prophylaxis.97 Inthe setting of a mass casualty situation, this oral form oftherapy is also recommended.

A limited supply of live-attenuated vaccine is availablefrom the CDC as an investigational new drug. The vaccineimproves immunity to aerosolized F. tularensis but does notprovide complete protection from the disease when largenumbers of the bacteria are inhaled.98,99

Continued from page 11


Infection ControlTularemia is not transmissible from person to person;therefore, standard precautions should be adequate toprevent the spread of the disease. No special isolationmeasures are necessary.

Viral Hemorrhagic Fevers

“Ebola is called a ‘slate wiper’ for humans.There is no known cure.

Once infected, the virus kills its host in seven days.”—Richard Preston, in “The Hot Zone”

EpidemiologyViral hemorrhagic fevers (VHFs) include a group ofillnesses caused by RNA viruses. These highly infectiousagents cause high fever, flu-like symptoms, increasedvascular permeability, and bleeding from multiple sites.All of the four viral families known to cause VHF arepossible bioterrorist agents. Of particular concern are theEbola, Marburg, Lassa, and Junin viruses. The mortalityrate for the Zaire subtype of Ebola is 90%.100

Infected rodents or arthropods transmit some ofthese diseases in the natural environment to humans.Notably, the natural reservoir of the Ebola virus remainsunknown. Once the human host is infected, the virus isreadily transmissible from person to person through directcontact with body fluids. This accounts for the high numberof fatalities among healthcare workers who care forpatients infected with these viruses. Cases of VHF in theUnited States are extremely rare and are usually seen intravelers who have visited endemic areas. Because oftheir highly infectious nature, diagnosis of a single caseshould be considered a public health emergency.101

Some have speculated that the Plague of Athens(430-427/425 B.C.) was actually the first outbreak of theEbola virus.102

PathophysiologyFollowing a two- to 21-day incubation period, earlyinfection with VHFs is marked by high fever, headache,fatigue, myalgias, abdominal pain, and malaise. As thedisease progresses, the more worrisome clinical findingsinvolve increased vascular permeability. These includegastrointestinal bleeding, generalized mucous membranehemorrhage, petechial or ecchymotic rash, conjunctivalinjection, nondependent edema, and hypotension. Thedisease rapidly progresses to shock and death.103

ED EvaluationThe clinical presentation of hemorrhagic fever dependson the particular agent. Patients will present with feverand toxicity and some constellation of headache,myalgias, rash or jaundice, bleeding, and disseminatedintravascular coagulation. Physical findings includepetechiae, mucous membrane and conjunctival hemor-rhage, hematuria, hematemesis, and melena. Delirium,seizures, ataxia, and coma are ominous signs.

There are no widely available rapid tests for hemor-rhagic fever. Antibody and nucleic acid-based assays areavailable through the CDC in Atlanta and USAMRIID inFort Detrick, MD. Because of the highly infectious natureof these diseases, great care should be taken in handlingall body fluid specimens.

Routine laboratory testing may indicate leukopenia,thrombocytopenia, elevated hepatic transaminases, andprolonged prothrombin time (PT) and partial thrombo-plastin time (PTT).104

Prophylaxis And TreatmentAn investigational vaccine available in limited quantitieshas been effective in preventing the Junin virus (Argen-tine hemorrhagic fever). Other vaccines are currentlyunder development.105 Intravenous ribavirin has beenused to treat some cases of Lassa fever and Argentinehemorrhagic fever. Postexposure prophylaxis with orallyadministered ribavirin also seems to be effective.106,107

Otherwise, treatment is supportive and includesadministration of crystalloids, blood products, andpressors as indicated.

Infection ControlThere have been numerous infections among healthcareworkers in Africa secondary to contact with victimsof hemorrhagic fever. During a 2000 outbreak of Ebolain Uganda, 14 of 22 medical personnel (64%) wereinfected despite the use of isolation wards and infectioncontrol measures including gowns, gloves, shoe covers,standard surgical masks, and either goggles or eye-glasses.108 It is not clear if this was due to breaks intechnique or airborne transmission (for which a standardsurgical mask is inadequate protection). Contact anddroplet precautions, including the use of HEPA filtermasks, should be employed when caring for patientswith VHFs, particularly in cases with respiratory involve-ment. In patients with prominent cough, vomiting,diarrhea, or hemorrhage, a negative pressure room isrecommended to prevent aerosol transmission of thedisease. Decontamination of infected materials withhousehold bleach is adequate.109,110

Psychosocial Consequences Of Bioterrorism

“If it’s a 50-pound package of a white, powdery substancebeing delivered to a bakery, assume it is flour.”

—Recent notice to UPS drivers117

An often overlooked—but crucially important—dimen-sion of ED bioterrorism preparedness concerns themanagement of psychological consequences.111,112 ManyEDs have special provisions for addressing psychologicalissues after mass casualty incidents (e.g., a buildingcollapse or bus accident).

A bioterrorism attack, however, is anything but“normal” and differs from other mass casualty incidents.The psychological effects of such an attack could be


enormous, often dwarfing the usual scope of hospitaltraining exercises or disaster plans. EDs at the center of abioterrorism response will face at least two majorchallenges: identifying and managing large numbers ofpsychological casualties, and managing extraordinarystresses on staff.

Psychological CasualtiesLarge numbers of psychological casualties—possibly farexceeding the toll of direct illness and fatalities—can resultfrom incidents involving invisible agents (biological agents,chemicals, radiation). Following the sarin attack on theTokyo subway system, which killed 12 individuals, over5000 people sought care from area hospitals. The vastmajority did not wait for ambulances or other emergencyvehicles; instead, they drove or walked to the nearestmedical facility. One of the most common problems wasanxiety and stress related to the attack.113 Similarly, in theaftermath of a radiological accident in Goiania, Brazil, astaggering 112,000 concerned people sought medicalexaminations. In some cases, even individuals who lived farfrom the affected area requested such exams.114,115 During theanthrax outbreak of 2001, a HAZMAT team was mobilizedwhen a man thought there was something suspicious abouthis M&Ms.116

In the aftermath of a large-scale bioterrorismincident, people can be expected to stream into areaEDs seeking assistance. Significant numbers may besuffering from acute mental effects such as shock, horror,grief, confusion, and irritability. Others will complainof sleep disturbance, loss of trust, social isolation, fearof contagion, paranoia, and anger. More may sufferfrom subacute or chronic psychological effects. Insituations involving invisible agents, significantnumbers experience stress-induced physical symptomsthat mimic the effects of exposure. During the Goianiaexperience, large numbers of people waited in line fortheir medical examinations. The fear was “so intense thatsome people fainted in the queues as they approachedtheir moment of monitoring. Many complained ofvomiting and diarrhea.”115

Thus, ED staff dealing with a bioterrorism incidentwill face a challenging triage situation involving acomplicated mix of people: some with signs of havingbeen infected by an agent, others with psychogenicsymptoms, and some with both. Effective triage protocolswill be vital. The response team must distinguishpsychological casualties from medical ones and differen-tiate the more serious psychological problems from lessserious ones.118

For people with transient symptoms, responsemanagers may facilitate recovery by creating respitelocations. Such locations should be removed fromareas of high-tempo triage activity, but they shouldalso be close enough to permit symptoms to be observedand monitored and to enable return for re-evaluationshould symptoms worsen.119 It will also be importantto have appropriate materials and assistance availablefor children.120

Sustained Stress On ED PersonnelDealing with a bioterrorism situation will subject EDpersonnel to levels of sustained psychological stressgreater than anything they have ever known. Healthcareproviders may encounter dead bodies on a daily basisover a significant period of time. They may also seegruesome deaths, numerous dead children, and dead ordying colleagues. Such grim experiences are especiallytraumatic.121-123 Over time, some physicians may sufferpsychosomatic symptoms.115

In a bioterrorism situation, ED personnel can alsoexpect to have to deal with large numbers of worriedpatients, parents, and so on asking for tests anddemanding antibiotics. During the anthrax letter situa-tion in late 2001, emergency rooms in the Washington,DC, area saw substantial numbers of people reportingheadaches, nasal congestion, and coughs who fearedthey had anthrax. Parents, worried about their children,were flooding doctors with requests for Cipro.124,125

After a 2001 outbreak of meningococcal disease in Ohiokilled two students, hundreds of people reportedlytraveled to local hospitals seeking testing or treatment.Several days later, thousands of people reportedly stoodin the rain outside one hospital awaiting the arrival ofadditional antibiotics.126,127

Clinicians will be bombarded by patients, familymembers, and members of the press. We will be ques-tioned about isolation, quarantine, contamination,symptomatology, and treatments. Education of cliniciansmust include ways of addressing these questions and,more broadly, strategies for dealing effectively withpeople’s concerns and anxieties.

Wearing personal protective clothing/equipment canbe a significant psychological stressor. Studies of militarytraining exercises have seen significant personnelattrition (up to 10%) due to anxiety, claustrophobia, orpanic related to protective gear.128-130 Among civilianhealthcare personnel, figures could be even higher.

Of course, it is not only medical doctors who aresubject to enormous stresses in a hospital dealing with abioterrorism incident. Every staff member would be atrisk. As DiGiovanni notes: “There is little reason tobelieve that medical personnel (including ancillarystaff, e.g., housekeepers, central supply workers),inexperienced and perhaps untrained in chemical andbiological incidents, will be spared from the anxiety andother distresses that will afflict the rest of the community,particularly if the offending agent threatens their ownfamilies.”131 While no one can be certain, it is quitepossible that some staff members, fearful of exposureor concerned about the well-being of their families,may opt out of hospital operations. This, in turn,would add further to the stresses on the remaininghealthcare workers.

In short, even well-prepared healthcare facilities willface unprecedented challenges in dealing with a large-scale bioterrorism situation, while less adequatelyprepared facilities could easily be overwhelmed andrendered ineffective. At a minimum, therefore, EDs need


to have the following in place:• a bioterrorism incident triage protocol that integrates

ED personnel and behavioral health staff;• mechanisms for identifying and managing large

numbers of psychological casualties;• respite areas for people experiencing transient

mental health effects;• materials and assistance for children and worried

parents who arrive at the hospital;• bioterrorism education and training for all ED staff

(including support/ancillary staff);• pre-briefing for ED personnel who are expected to

have to deal with unusually grotesque scenes outside

of their usual experience; and• adequate psychological support for ED personnel.

The unique psychological issues posed bybioterrorism should also be addressed in hospital disasterplans, training courses, and training exercises.

Preparation For Bioterrorism

The best deterrent and response to the unknowns ofbioterrorism is preparation. In contrast to preparationfor chemical terrorism, where preparation relies largelyon HAZMAT equipment, immediate treatment in the

Ten Assumptions A Bioterrorist Wants You To Make1. “I don’t have to consider rare diseases; the infectious

disease specialists can worry about that.”

The earlier a rare pathogen is identified, the more effective

the public health response. Failure to consider a rare

disease will lead to inevitable delays and possibly extend

the epidemic.

2. “There’s no reason for me to notify public health

authorities—it would just mean a lot of extra phone calls

and paperwork.”

Coordination of the medical community by public health

authorities is essential in rare disease outbreaks. Failure to

notify public health authorities can lead to fatal delays in

appropriate civic response.

3. “I think I’ll call the local radio station and tell them about

this suspected case of anthrax. They can handle the

distribution of information to the public.”

This is a sure way to cause panic in the streets (and

prompt a call from an enraged hospital administrator).

Appropriate delivery of accurate information is essential

to conserve limited medical resources. Work directly with

public health and media authorities at your hospital before

notifying others.

4. “I’m not sure this is smallpox. Putting him in negative

pressure isolation might cause panic.”

Failure to properly isolate patients who are suspected

to be infected with highly transmissible diseases such

as smallpox can be a deadly mistake—for you and

your staff.

5. “Sure, this patient has a flu-like illness and a widened

mediastinum on chest radiography—but it will take two

hours to get a CT scan of his chest, and he really wants to

go home.”

If we are to detect bioterrorist attacks, we must think of rare

diseases and recognize suspicious patterns. Failure to order

appropriate diagnostic testing can delay critical treatment

and have deadly consequences.

6. “Even though this case could be inhalational anthrax, I

don’t want to expose the patient to all of those antibiotics

before we have a definitive diagnosis.”

In many bioterror situations, early, aggressive antibiotic

therapy is essential to survival. Delays in treatment may

lead to unnecessary morbidity and mortality.

7. “None of these patients were in the building when

the suspicious envelope arrived, but we’re going to

decontaminate them anyway. We want everyone to

know we’re taking this seriously.”

In cases of potential exposure, the public turns to you as a

healthcare provider for advice on decontamination

procedures. Unnecessary decontamination can cause

unwarranted stress for patients and can overburden the

emergency healthcare system.

8. “This patient doesn’t have any signs or symptoms of

plague and has not been near anyone with the disease, but

he is asking for antibiotics, so I’ll give them to him anyway.”

Reserve antibiotic prophylaxis for those patients who

genuinely warrant treatment. This will prevent unnecessary

side effects. In some cases, conservation of antimicrobials

may be important.

9. “All of the employees in the office said they were covered

in this powder that tested positive for anthrax, but we

decontaminated them and they don’t look sick now. They

can wait to get antibiotics if they develop symptoms.”

Patients who are genuinely at high risk for exposure to

deadly infectious agents should certainly receive antibiotic

prophylaxis. All suspected threat agent exposures should

be discussed with local or state public health officials.

10. “In the ED, my role is just to stabilize the patients, not to

diagnose rare diseases.”

The emergency physician is likely to be the first-line

responder in a bioterrorist attack. ED diagnosis of rare

diseases can and must be done in order to rapidly

recognize and respond to the threat of bioterrorism. ▲


streets, and cordoned-off crime scenes, preparation forbiological terrorism relies much more on education, arobust public health system, and broad inter-agencycollaboration. The integrated system must includeintelligence and forensics, disease surveillance, medicaland physical countermeasures, and a strong public healthinfrastructure, all bound together by vigorous inter-agency collaboration and effective educational programs.Fortunately, much of what should be done in anticipationof a biological terrorist attack is also applicable to anypublic health disaster or infectious disease outbreak,making these expensive but necessary preparations“dual use” in nature.

In a recent survey of 30 hospitals within a localregion, none of the hospitals believed they were fullyprepared to handle a biological incident, and only 27% ofthe hospitals surveyed had incorporated weapons ofmass destruction (WMD) preparedness into their hospitaldisaster plans. Of the hospitals that had performed WMDdrills, only one had conducted a drill specifically ad-dressing biological weapons.132 A large-scale bioterrorism

drill performed in Denver that simulated aerosolizedplague attacks resulted in over 3000 simulated casualtieswithin four days.133 One of the most valuable insightsfrom this drill was that the systems and resourcescurrently in place are inadequate to manage the stress ofa large-scale bio-weapons attack. Based on these observa-tions, it is clear that in order to treat victims ofbioterrorism, we must augment our diagnostic capabili-ties and surveillance programs and make infrastructuremodifications to prepare adequately for the consequencesof an epidemic of infectious disease.

Today, rapid progress in the development andenrichment of our public health infrastructure isongoing, and multiple parties have called for improvedsurveillance systems both before and after the events ofthe U.S. anthrax attack.134,139-141 But the system is not yetwhere it needs to be. Currently there is no unifiedsurveillance system in place, leaving multiple fragmentedsystems that rely on widely varying methodology andtechnology to function. The complexities of diseasereporting and the lack of consistent feedback have led to

Table 6. Patient Isolation Precautions.

Standard Precautions• Wash hands after patient contact.• Wear gloves when touching blood, body fluids, secretions,

excretions, and contaminated items.• Wear a mask and eye protection, or a face shield, during

procedures likely to generate splashes or sprays of blood,body fluids, secretions, or excretions.

• Handle used patient-care equipment and linen in amanner that prevents the transfer of microorganisms topeople or equipment.

• Use care when handling sharps, and use a mouthpiece orother ventilation device as an alternative to mouth-to-mouth resuscitation when practical.

Standard precautions are employed in the care of all patients.

Airborne PrecautionsStandard Precautions plus:

• Place the patient in a private room that has monitorednegative air pressure, a minimum of six air changes/hour,and appropriate filtration of air before it is dischargedfrom the room.

• Wear respiratory protection when entering the room.• Limit movement and transport of the patient. Place a

mask on the patient if he or she needs to be moved.

Conventional diseases requiring Airborne Precautions:measles, varicella, pulmonary tuberculosis.

Biothreat diseases requiring Airborne Precautions: smallpox.

Droplet PrecautionsStandard Precautions plus:

• Place the patient in a private room or cohort him or herwith someone with the same infection. If this is notfeasible, maintain at least three feet between patients.

• Wear a mask when working within three feet ofthe patient.

• Limit movement and transport of the patient. Place amask on the patient if he or she needs to be moved.

Conventional diseases requiring Droplet Precautions: invasiveHaemophilus influenzae and meningococcal disease, drug-resistant pneumococcal disease, diphtheria, pertussis,mycoplasma, GABHS, influenza, mumps, rubella, parvovirus.

Biothreat diseases requiring Droplet Precautions: pneu-monic plague.

Contact PrecautionsStandard Precautions plus:

• Place the patient in a private room or cohort him or herwith someone with the same infection if possible.

• Wear gloves when entering the room. Change glovesafter contact with infective material.

• Wear a gown when entering the room if contact withpatient is anticipated or if the patient has diarrhea, acolostomy, or wound drainage not covered by a dressing.

• Limit the movement or transport of the patient fromthe room.

• Ensure that patient-care items, bedside equipment, andfrequently touched surfaces receive daily cleaning.

• Dedicate use of noncritical patient-care equipment (suchas stethoscopes) to a single patient or cohort of patientswith the same pathogen. If this is not feasible, adequatedisinfection between patients is necessary.

Conventional diseases requiring Contact Precautions:MRSA, VRE, Clostridium difficile, RSV, parainfluenza,enteroviruses, enteric infections in the incontinent host,skin infections (SSSS, HSV, impetigo, lice, scabies), hemor-rhagic conjunctivitis.

Biothreat diseases requiring Contact Precautions: Viralhemorrhagic fevers.

Source: USAMRIID’s Medical Management of Biological CasualtiesHandbook, 4th ed. See: http://www.usamriid.army.mil/education/bluebook.html.

For more information, see: Garner JS. Guideline for infection controlpractices in hospitals. Infect Control Hosp Epidemiol 1996;17:53-80.


physician frustration and poor compliance with currentpublic health reporting mechanisms.135,136

Given the impact of delays in detecting bioterrorism,new approaches to surveillance that emphasize the earlydetection of specific syndromes and reporting casesthrough real-time communication systems are beingimplemented.137 The government recognizes that EDs willplay an increasingly important role in bioterrorismsurveillance, and standard approaches to data sharing arelikely to emerge in the near future.138

Summary

The emerging threat of bioterrorism is an inescapablereality. All EDs should prepare for this eventuality.Emergency physicians must be alert to unusual presenta-tions and, in particular, clusters of unusual presentationsthat could result from biological weapons. ED personnelshould participate in bioterrorism surveillance systems.When bioterrorism is suspected, ED personnel mustwork closely with the public health and behavioral healthcommunity to appropriately triage, rapidly diagnose, and

effectively treat patients. This system will not workefficiently without planning and preparation for theunusual contingencies presented by a bioterrorist attack.We can act rapidly and effectively if we pay closeattention to epidemiologic patterns and remember thepotential for biological weapons. ▲

References

Evidence-based medicine requires a critical appraisal ofthe literature based upon study methodology andnumber of subjects. Not all references are equally robust.The findings of a large, prospective, randomized, andblinded trial should carry more weight than a case report.

To help the reader judge the strength of eachreference, pertinent information about the study, such asthe type of study and the number of patients in the study,will be included in bold type following the reference,where available. In addition, the most informativereferences cited in the paper, as determined by theauthors, will be noted by an asterisk (*) next to thenumber of the reference.

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Table 7. Discussion Of Investigational Information.

Anthrax: Doxycycline, ciprofloxacin, and penicillin Gprocaine are all FDA-approved for the treatment ofanthrax. The anthrax vaccine is FDA approved forindividuals at high risk of infection with B. anthracis.The use of rifampin, vancomycin, ampicillin, chloram-phenicol, imipenem, clindamycin, clarithromycin, orcorticosteroids for the treatment of anthrax would beconsidered off-label.

Smallpox: The smallpox vaccine and vaccinia immuneglobulin are both FDA-approved for the prevention andtreatment of smallpox. Cidofovir is not FDA-approved forthe treatment of smallpox, and the use of the drug in thissetting would be considered off-label.

Plague: Doxycycline and gentamicin are both FDA-approved for the treatment of plague. Streptomycin andthe quinolone drugs are not FDA-approved for thetreatment of plague, and the use of these drugs to treatplague would be considered off-label.

Botulism: Botulism antitoxin is FDA-approved for thetreatment of patients with botulism. The botulism toxoidis approved by the FDA as an Investigational New Drug.

Tularemia: The Live Vaccine Strain (LVS) for tularemia isapproved by the FDA as an Investigational New Drug.Streptomycin and doxycycline are both FDA-approved forthe treatment of tularemia. Gentamicin and ciprofloxacinare not FDA-approved for the treatment of tularemia, andthe use of these drugs for the treatment of tularemiawould be considered off-label.

Viral Hemorrhagic Fevers: The vaccine for Argentinehemorrhagic fever is approved by the FDA as an Investi-gational New Drug. Ribavirin is not FDA-approved for thetreatment of viral hemorrhagic fevers, and the use of thedrug to treat viral hemorrhagic fevers would be consid-ered off-label.


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72. United Nations Security Council. Tenth Report of theExecutive Chairman of the Special Commission Establishedby the Secretary-General Pursuant to Paragraph 9(b)(I) ofSecurity Council Resolution 687 (1991), and Paragraph 3 ofResolution 699 (1991) on the Activities of the SpecialCommission. New York: United Nations Security Council;1995. S/1995/1038.

73. Franz DR, Pitt LM, Clayton MA, et al. Efficacy of prophylac-tic and therapeutic administration of antitoxin for inhalationbotulism. In: Das-Gupta BR, ed. Botulinum and TetanusNeurotoxins: Neurotransmission and Biomedical Aspects. NewYork: Plenum Press; 1993:473-476. (Textbook chapter)

74. Herrero BA, Ecklung AE, Street CS, et al. Experimentalbotulism in monkeys: a clinical pathological study. Exp MolPathol 1967;7:84-95. (Animal study)

75. Schantz EJ, Johnson EA. Properties and use of botulinumtoxin and other microbial neurotoxins in medicine. MicrobiolRev 1992;56:80-99. (Review)

76. Tucker JB, ed. Toxic Terror: Assessing the Terrorist Use ofChemical and Biological Weapons. Cambridge, MA: MIT Press;2000. (Book)

77.* Arnon SS, Schechter R, Inglesby TV, et al. Working Groupon Civilian Biodefense. Botulinum toxin as a biologicalweapon: medical and public health management. JAMA2001 Feb 28;285(8):1059-1070. (Consensus developmentconference; review)

78. Cherington M. Clinical spectrum of botulism. Muscle Nerve1998 Jun;21(6):701-710. (Review)

79. Burrows WD, Renner SE. Biological warfare agents as threatsto potable water. Environ Health Perspect 1999Dec;107(12):975-984. (Review)

80. Tacket CO, Shandera WX, Mann JM, et al. Equine antitoxinuse and other factors that predict outcome in type Afoodborne botulism. Am J Med 1984 May;76(5):794-798.(Retrospective; 132 patients)

81. Siegel LS. Human immune response to botulinum pentava-lent (ABCDE) toxoid determined by a neutralization test andby an enzyme-linked immunosorbent assay. J Clin Microbiol1988;26:2351-2356. (Prospective, cohort; 77 patients)

82. Byrne MP, Smith LA. Development of vaccines for preven-tion of botulism. Biochimie 2000;82:955-966. (Review)

83. Feldman KA, Enscore RE, Lathrop SL, et al. An outbreak ofprimary pneumonic tularemia on Martha’s Vineyard. N Engl JMed 2001;345(22):1602-1601. (Case series; 15 patients)

84. Hornick RB. Tularemia. In: Evans AS, Brachman PS, eds.Bacterial Infections of Humans: Epidemiology and Control. 3rded. New York: Plenum Medical Book; 1998:823-837.(Textbook chapter)

85. Harris S. Japanese biological warfare research on humans: acase study of microbiology and ethics. Ann N Y Acad Sci 1992Dec 31;666:21-52. (Review)

86. McCrumb FR Jr. Aerosol infection in man with Pasteurellatularensis. Bacteriol Rev 1961;25:262-267. (Review)

87.* Dennis DT, Inglesby TV, Henderson DA, et al. Working Groupon Civilian Biodefense. Tularemia as a biological weapon:medical and public health management. JAMA 2001 Jun6;285(21):2763-2773. (Review)

88. Avery FW, Barnett TV. Pulmonary tularemia: a report of fivecases and consideration of pathogenesis and terminology. AmRev Respir Dis 1967;95:584-591. (Case series; 5 patients)

89. Stuart BM, Pullen RL. Tularemic pneumonia: Review ofAmerican literature and report of 15 additional cases. Am J MedSci 1945;210:223-236. (Review, case series; 15 patients)

90. White JD, McGavran MH. Identification of Pasteurella tularensisby immunofluorescence. JAMA 1965 Oct 18;194(3):294-296.

91. Guarner J, Greer PW, Bartlett J, et al. Immunohistochemicaldetection of Francisella tularensis in formalin-fixed paraffin-embedded tissue. Appl Immunohistochem Mol Morphol1999;7:122-126.

92. Centers for Disease Control and Prevention. Basic laboratoryprotocols for the presumptive identification of Francisellatularensis, at: http://www.bt.cdc.gov/Agent/Tularemia/Tularemia20010417.pdf.

93. Bevanger L, Maeland JA, Naess AI. Agglutinins and antibodiesto Francisella tularensis outer membraneantigens in the early diagnosis of disease during an outbreak oftularemia. J Clin Microbiol 1988 Mar;26(3):433-437. (57 patients)

94. Mason WL, Eigelsbach HT, Little SF, et al. Treatmentof tularemia, including pulmonary tularemia, withgentamicin. Am Rev Respir Dis 1980;121:39-45. (Prospective,cohort; 10 patients)

95.* Enderlin G, Morales L, Jacobs RF, et al. Streptomycin andalternative agents for the treatment of tularemia: review of theliterature. Clin Infect Dis 1994;19:42-47. (Review)

96. Evans ME, Gregory DW, Schaffner W, et al. Tularemia:a 30-year experience with 88 cases. Medicine 1985;64:251-269. (Review)

97. Sawyer WD, Dangerfield HG, Hogge AL, et al. Antibioticprophylaxis and therapy of airborne tularemia. Bacteriol Rev1966;30:542-548. (Prospective; 34 patients)

98. Saslaw S, Eigelsbach HT, Wilson HE, et al. Tularemia vaccinestudy, II: respiratory challenge. Arch Intern Med 1961;107(5):702-714. (Prospective, randomized, controlled; 28 patients)

99. Burke DS. Immunization against tularemia: analysis ofthe effectiveness of live Francisella tularensis vaccine inprevention of laboratory-acquired tularemia. J Infect Dis1977;135(1):55-60. (Retrospective)

100.* Borio L, Inglesby T, Peters CJ, et al. Hemorrhagic fever virusesas biological weapons: medical and public health management.JAMA 2002 May 8;287(18):2391-2405. (Review)

101. Suresh V. The enigmatic haemorrhagic fevers. J R Soc Med1997;90(11):622-624. (Review)

102. Olson PE, Hames CS, Benenson AS, et al. The Thucydidessyndrome: Ebola déjà vu? (or Ebola reemergent?) Emerg InfectDis 1996 Apr;2(2):155-156. (Historical article; letter)

103. Jahrling PB. Viral hemorrhagic fevers. In: Zajtchuk R, BellamyRF, eds. Medical Aspects of Chemical and Biological Warfare.Bethesda, MD: Office of the Surgeon General, Department ofthe Army, USA; 1997:591-602. (Textbook chapter)

104. Pigott DC, Shope RE, McGovern TW. Viral hemorrhagic fevers.In: eMedicine 2001:2(10).

105. Sullivan NJ, Sanchez A, Rollin PE, et al. Development of apreventive vaccine for Ebola virus infection in primates. Nature2000 Nov 30;408(6812):605-609. (Animal study)


106. Enria DA, Maiztegui JI. Antiviral treatment of Argentinehemorrhagic fever. Antiviral Res 1994;23(1):23-31. (Review)

107. McCormick JB, King IJ, Webb PA, et al. Lassa fever: effectivetherapy with ribavarin. N Engl J Med 1986;314(1):20-26. (Casecontrol, 70 patients; Prospective, randomized, 62 patients)

108. No authors listed. Outbreak of Ebola hemorrhagic fever,Uganda, August 2000–January 2001. MMWR Morb Mortal WklyRep 2001;50:73-77. (Epidemiologic data)

109. Peters CJ, LeDuc JW. Ebola: the virus and the disease. J InfectDis 1999;179 (suppl 1):ix-xvi. (Review)

110. Speed BR, Gerrard MP, Kennett ML, et al. Viral hemorrhagicfevers: current status, future threats. Med J Aust 1996;164(2):79-83. (Review)

111.* Becker SM. Are psychosocial aspects of WMD incidentsaddressed in the Federal Response Plan: summary of an expertpanel. Mil Med 2001;166,S2:66-68. (Consensus statement)

112.* Becker SM. Meeting the threat of weapons of mass destructionterrorism: Toward a broader conception of consequencemanagement. Mil Med 2001;166, S2:13-16. (Policy analysis)

113. Lillibridge S, Liddle J, Leffingwell S, et al. Report of the AmericanMedical Delegation to Japan. Atlanta: Centers for Disease Controland Prevention; 1995. (Case report)

114. International Atomic Energy Agency. The Radiological Accidentin Goiania. Vienna: International Atomic Energy Agency; 1988.(Case report)

115. de Carvalho AB. Psychological aspects of a radiologicalaccident. Paper presented at the Ninth Annual NationalRadiological Preparedness Conference, Baton Rouge, LA;March 29-31, 1999. (Case report)

116. Chicago Sun Times. October 17, 2001.117. Personal communication, Peter Viccellio, MD.118.* Institute of Medicine. Chemical and Biological Terrorism: Research

and Development to Improve Civilian Medical Response. Institute ofMedicine/National Research Council. Washington, DC:National Academy Press; 1999. (Policy analysis)

119. Benedek DM, Holloway HC, Becker SM. Emergency mentalhealth management of bioterrorism events. Emerg Med ClinNorth Am (in press).

120. Pynoos RS, Goenjian AK, Steinberg AM. A public mental healthapproach to the postdisaster treatment of children andadolescents. Child Adolsesc Psychiatr Clin North Am 1998;7:195-210. (Review)

121. Fullerton CS, Ursano RJ. The other side of chaos: Understand-ing the patterns of posttraumatic responses. In: Fullerton CS,Ursano RJ, eds. Posttraumatic Stress Disorder: Acute and Long-Term Responses to Trauma and Disaster. Washington, DC:American Psychiatric Press; 1997:3-18. (Textbook chapter)

122. Ursano RJ, Fullerton CS, McCaughey BG. Trauma and disaster.In: Ursano RJ, McCaughey BG, Fullerton CS, eds. Individual andCommunity Responses to Trauma and Disaster: The Structure ofHuman Chaos. Cambridge, MA: Cambridge University Press;1994:3-27. (Textbook chapter)

123. Burns C, Harm NJ. Emergency nurses’ perceptions of criticalincidents and stress debriefing. J Emerg Nurs 1993;19:431-436.(Survey; 682 nurses)

124. Tucker N. Emergency rooms overrun by the “worried butwell.” Washington Post. November 1, 2001.

125. Elias M. Parents’ anthrax, smallpox worries deluge doctors.USA Today. October 22, 2001.

126. Higgins J. Thousands wait in rain for antibiotics. Akron BeaconJournal. June 3, 2001.

127. Cardwell J. Students’ deaths frighten community. Akron BeaconJournal. May 29, 2001.

128.* Carter BJ, Cammermeyer RN. Emergence of real casualtiesduring simulated chemical warfare training under high heatconditions. Mil Med 1985:150;657-665. (Qualitative; 195medical personnel)

129. Fullerton CS, Ursano RJ. Health care delivery in the high-stressenvironment of chemical and biological warfare. Mil Med1994;159:524-528. (Preliminary report)

130. Stokes JW, Banderet LE. Psychological aspects of chemicaldefense and warfare. Mil Psychol 1997;9(4):395-415. (Review)

131.* DiGiovanni C Jr. Domestic terrorism with chemical or

biological agents: Psychiatric aspects. Am J Psychiatr1999;156:1500-1505. (Review)

132.* Treat KN, Williams JM, Furbee PM, et al. Hospital prepared-ness for weapons of mass destruction incidents: an initialassessment. Ann Emerg Med 2001 Nov;38(5):562-565. (Evalua-tion; 30 respondents)

133.* Inglesby TI, Grossman R, O’Toole T. A plague on your city:observations from TOPOFF. Biodefense Quarterly 2000;2(2):1-10.(Retrospective exercise summary)

134. Garrison HG, Runyan CW, Tintinalli JE, et al. Emergencydepartment surveillance: an examination of issues anda proposal for a national strategy. Ann Emerg Med1994;24(5):849-856.

135. Elliott VS. Public health reporting flaws spell trouble.Am Med News 2002:45(16);1-4.

136. No authors listed. Reporting of laboratory-confirmedchlamydial infection and gonorrhea by providers affiliatedwith three large managed care organizations—UnitedStates, 1995-1999. MMWR Morb Mortal Wkly Rep2002;51(12):256-259. (Retrospective)

137.* Lober WB, Karras BT, Wagner MM, et al. Roundtable onbioterrorism detection: information system-based surveillance.J Am Med Inform Assoc 2002 Mar;9(2):105-115. (Review)

138. Barthell EN, Cordell WH, Moorhead JC, et al. The Frontlines ofMedicine Project: a proposal for the standardized communica-tion of emergency department data for public health usesincluding syndromic surveillance for biological and chemicalterrorism. Ann Emerg Med 2002 Apr;39(4):422-429. (Descriptive)

139.* Bowles LT, Sirica C, eds. The Role of Emergency Medicine inthe Future of American Medical Care: Proceedings of aConference Chaired by L. Thompson Bowles, MD, PhD. NewYork: Josiah Macy, Jr. Foundation, 1995.

140. U.S. Department of Health and Human Services. HealthyPeople 2010: Understanding and Improving Health. 2000.(Position statement)

141.* Brennan PF. AMIA Recommendations for national healththreat surveillance and response. JAMIA 2002;9:204-206.(Position statement)

Physician CME Questions

1. All of the following are true of biological warfareattacks except:a. They are a new phenomenon.b. They may be either overt or covert.c. Victims are most likely to present to the

ED initially.d. They require rapid diagnosis and containment.

2. Most bioterrorist agents initially induce aninfluenza-like prodrome, including fever, chills,myalgias, or malaise. After this prodrome, whichof the following is/are a “red flag” that a bioterroragent may be involved?a. Rapidly progressive pneumoniab. Fever with rashc. Fever with altered mental statusd. Bloody diarrheae. All of the above

3. Of the following Category A bioterror agents, theone that is the most transmissible is:a. anthrax.b. botulism.c. tularemia.d. viral hemorrhagic fevers.


4. Measures that can ease the challenges in dealingwith a potential bioterrorist attack include:a. a bioterrorism incident triage protocol that

integrates ED personnel and behavioralhealth staff.

b. mechanisms for identifying and managing largenumbers of psychological casualties.

c. written materials for worried parents who arriveat the hospital.

d. bioterrorism education and training for all EDstaff (including support/ancillary staff).

e. all of the above.

5. During bioterror mass casualty incidents:a. triage should proceed as usual, with the worst

cases treated first.b. healthcare providers must differentiate

the “walking worried” from the trulysymptomatic.

c. healthcare providers should provideprophylactic antibiotics to anyone whorequests them.

d. healthcare providers should collect and sendlaboratory samples to their local labs.

6. All of the following tend to indicate a naturaldisease outbreak, rather than a bioterroristattack, except:a. Cases present to the ED at varying stages of

disease progressionb. Usual expected disease course for that

specific pathogen, with appropriate responseto standard therapy

c. Slowly progressive disease course, withprodromal symptoms

d. Sudden presentation of large numbers of victimswith a similar disease or syndrome who mayhave a readily identifiable common exposure

7. All of the following are true regarding cutaneousanthrax except:a. Localized edema, erythema, and lymphaden-

opathy are important clues to the diagnosis.b. Without antibiotic therapy, cutaneous anthrax

can lead to bacteremia, with mortality rates ashigh as 20%.

c. With antibiotics, death due to cutaneousanthrax is rare.

d. Cutaneous anthrax is not caused by the samespores as inhalational anthrax.

8. The recommended prophylactic therapy forpatients with confirmed exposure to B. anthracis is:a. oral ciprofloxacin 500 mg every 12 hours, or

doxycycline 100 mg every 12 hours, for 60 days.b. the anthrax vaccine.c. prophylactic therapy is unnecessary.d. there is no prophylactic therapy.

9. All of the following are true regarding inhalationalanthrax except:a. It begins as a nonspecific, flu-like illness.b. Rhinorrhea and nasal congestion usually are not

associated with inhalational anthrax.c. Shortness of breath is rare in anthrax but

common in influenza and influenza-like illness.d. Chest radiography in patients with inhalational

anthrax often exhibits mediastinal widening,occasional infiltrates, and pleural effusion.

10. Patients who are diagnosed with smallpox:a. require the standard precautions.b. should receive aggressive antibiotic therapy.c. should be questioned so that recent contacts can

be vaccinated and placed under surveillance.d. are expected to have a 95% mortality rate.

11. Smallpox:a. is not very contagious.b. begins with high fever, malaise, vomiting,

headache, and myalgias; the characteristicrash appears 2-3 days later.

c. lesions rarely develop on the extremitiesand face.

d. lesions are superficial, appear in various stagesof evolution, and develop in crops.

12. All of the following are true regardingplague except:a. The bacteria have a characteristic bipolar

appearance that is commonly referred toas the “safety-pin” pattern.

b. Septicemic plague can occur de novo fromthe bite of an infected flea or secondarilyfrom untreated bubonic plague.

c. Pneumonic plague develops secondarily frombubonic or septicemic plague, or primarilywhen aerosolized bacilli are inhaled.

d. Primary pneumonic plague infectiontypically does not cause the classic buboesthat are seen with the naturally occurringform of the disease.

e. Isolation is not required, because the plague isnot very contagious.

13. By weight, the most toxic substance known to man is:a. anthrax spores.b. inhaled botulinum toxin.c. ricin toxin.d. epsilon toxin.

14. Patients with botulism exhibit:a. diplopia.b. dysarthria.c. dysphonia.d. dysphagia.e. all of the above.


Emergency Medicine Practice is not affiliated with anypharmaceutical firm or medical device manufacturer.

Class I• Always acceptable, safe• Definitely useful• Proven in both efficacy and

effectiveness

Level of Evidence:• One or more large prospective

studies are present (withrare exceptions)

• High-quality meta-analyses• Study results consistently

positive and compelling

Class II• Safe, acceptable• Probably useful

Level of Evidence:• Generally higher levels

of evidence• Non-randomized or retrospec-

tive studies: historic, cohort, orcase-control studies

• Less robust RCTs• Results consistently positive

Class III• May be acceptable• Possibly useful• Considered optional or

alternative treatments

Level of Evidence:• Generally lower or intermediate

levels of evidence

• Case series, animal studies,consensus panels

• Occasionally positive results

Indeterminate• Continuing area of research• No recommendations until

further research

Level of Evidence:• Evidence not available• Higher studies in progress• Results inconsistent,

contradictory• Results not compelling

Significantly modified from: TheEmergency Cardiovascular CareCommittees of the American HeartAssociation and representativesfrom the resuscitation councils ofILCOR: How to Develop Evidence-Based Guidelines for EmergencyCardiac Care: Quality of Evidenceand Classes of Recommendations;also: Anonymous. Guidelines forcardiopulmonary resuscitation andemergency cardiac care. EmergencyCardiac Care Committee andSubcommittees, American HeartAssociation. Part IX. Ensuringeffectiveness of community-wideemergency cardiac care. JAMA1992;268(16):2289-2295.

Class Of Evidence Definitions

Each action in the clinical pathways section of Emergency Medicine Practicereceives an alpha-numerical score based on the following definitions.

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Emergency Medicine Practice (ISSN 1524-1971) is published monthly (12 times per year) by EB Practice, LLC, 305 Windlake Court, Alpharetta, GA 30022. Opinions expressed are not necessarilythose of this publication. Mention of products or services does not constitute endorsement. This publication is intended as a general guide and is intended to supplement, rather thansubstitute, professional judgment. It covers a highly technical and complex subject and should not be used for making specific medical decisions. The materials contained herein are notintended to establish policy, procedure, or standard of care. Emergency Medicine Practice is a trademark of EB Practice, LLC. Copyright 2002 EB Practice, LLC. All rights reserved. No part of thispublication may be reproduced in any format without written consent of EB Practice, LLC. Subscription price: $249, U.S. funds. (Call for international shipping prices.)

Publisher: Robert Williford. Executive Editor: Heidi Frost.

15. Tularemia typically presents:a. after a three-week incubation period.b. as an acute, nonspecific febrile illness.c. without a sore throat or cough.d. with nausea and vomiting, but not fever.

16. Viral hemorrhagic fevers:a. present with fever and toxicity and some

constellation of headache, myalgias, rashor jaundice, bleeding, and disseminatedintravascular coagulation.

b. can be detected by a rapid bedside test.c. are rarely lethal.d. require no special infection control measures

other than handwashing.

This work was funded in part by a grant fromthe Agency for Healthcare Research and Quality,

Contract #290-00-0022.

Physician CME InformationThis CME enduring material is sponsored by Mount Sinai School of Medicineand has been planned and implemented in accordance with the Essentialsand Standards of the Accreditation Council for Continuing MedicalEducation. Credit may be obtained by reading each issue and completingthe printed post-tests administered in December and June or online single-issue post-tests administered at www.empractice.net.

Target Audience: This enduring material is designed for emergencymedicine physicians.

Needs Assessment: The need for this educational activity wasdetermined by a survey of medical staff, including the editorial boardof this publication; review of morbidity and mortality data from theCDC, AHA, NCHS, and ACEP; and evaluation of prior activities foremergency physicians.

Date of Original Release: This issue of Emergency Medicine Practice waspublished July 1, 2002. This activity is eligible for CME credit throughJuly 1, 2005. The latest review of this material was June 3, 2002.

Discussion of Investigational Information: As part of the newsletter, facultymay be presenting investigational information about pharmaceuticalproducts that is outside Food and Drug Administration approved labeling.Information presented as part of this activity is intended solely ascontinuing medical education and is not intended to promote off-labeluse of any pharmaceutical product. Disclosure of Off-Label Usage: Off-labeluses mentioned in this article are disclosed in Table 7, page 19. (See text.)

Faculty Disclosure: In compliance with all ACCME Essentials, Standards, andGuidelines, all faculty for this CME activity were asked to complete a fulldisclosure statement. The information received is as follows: Dr. Franz ownsstock in Pfizer and Merck. Dr. McNutt, Dr. Becker, Dr. Darling, Dr. Barthell, andDr. Karas report no significant financial interest or other relationship withthe manufacturer(s) of any commercial product(s) discussed in thiseducational presentation.

Accreditation: Mount Sinai School of Medicine is accredited by theAccreditation Council for Continuing Medical Education to sponsorcontinuing medical education for physicians.

Credit Designation: Mount Sinai School of Medicine designates thiseducational activity for up to 4 hours of Category 1 credit toward theAMA Physician’s Recognition Award. Each physician should claim onlythose hours of credit actually spent in the educational activity.Emergency Medicine Practice is approved by the American Collegeof Emergency Physicians for 48 hours of ACEP Category 1 credit (perannual subscription). Emergency Medicine Practice has also been approvedfor 48 Category 2B credit hours by the American Osteopathic Association.

Earning Credit: Two Convenient Methods• Print Subscription Semester Program: Physicians with current and

valid licenses in the United States who read all CME articles duringeach Emergency Medicine Practice six-month testing period, completethe post-test and the CME Evaluation Form distributed with theDecember and June issues, and return it according to the publishedinstructions are eligible for up to 4 hours of Category 1 credit towardthe AMA Physician’s Recognition Award (PRA) for each issue. You mustcomplete both the post-test and CME Evaluation Form to receivecredit. Results will be kept confidential. CME certificates will bedelivered to each participant scoring higher than 70%.

• Online Single-Issue Program: Physicians with current and validlicenses in the United States who read this Emergency Medicine PracticeCME article and complete the online post-test and CME EvaluationForm at www.empractice.net are eligible for up to 4 hours of Category1 credit toward the AMA Physician’s Recognition Award (PRA). Youmust complete both the post-test and CME Evaluation Form to receivecredit. Results will be kept confidential. CME certificates may be printeddirectly from the Web site to each participant scoring higher than 70%.

an evidence-based approach to emergency medicine

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