UCLA Center for Public Health and Disasters

Bioterrorism Training for PhysiciansUpdated March 2003

Over 1700 Downloads Since Going Online October 2001

Available at:

http://www.ph.ucla.edu/cphdr/bioterrorism

BIOTERRORISM:

Are You Prepared?

Bioterrorism 101

Why is this a problem?

Who and what are the agencies worrying about?

Biological Terrorism

Intentional or threatened use of

viruses, bacteria, fungi or toxins from

living organisms to produce death or

disease in humans, animals or plants

Anthrax Mail Attacks - 2001

Biological Terrorism – Why?

Small amounts – devastating effectsInvisible, odorless, tastelessEasy to obtain Difficult to detectCivilian populations unprotectedDelayed onset - difficult to tracePublicity, fear, chaos

What Happens in a Bioterrorism Incident?

That depends on whether the attack is:

OVERT

or

COVERT

Overt AttackThreat ValidationCoordinated System Response

Traditional First Responders: Fire, Police, EMSHospitalsCommunity PractitionersPublic Health - Information ManagementLaw Enforcement

Overt Attack

Problems:Verifying if an attack has taken placeFear, chaosLarge numbers of “worried well”DecontaminationLimited supply of treatment, prophylactic drugs, and vaccines

Real or Hoax?Public health and law enforcement will determine credibility, and need for decontamination or prophylaxis

Test results may take 24-48 hours

Covert AttackEMS system may be used by cases (not yet recognized as a bioterrorist event)Likely detected through hospitals, medical care practitionersClinical labs contact local PH departmentPH department refers to State or CDC

Covert Attack

Problems with recognition:Symptoms overlap common illnessesDelayed onset of symptomsVictims present to different centersSecondary spread may occur before attack is recognized

Likely Scenarios

Aerosol releaseMajor city, large event, or key functionVictims presenting to different centersRecognition of attack through symptoms, epidemiologic patterns or microbio lab

Aerosol DeliveryConsidered the most likely route for BTAim is to generate invisible clouds of particles 0.5-10 microns in diameter

Can stay suspended for long periods of timePerfect size to reach the alveoli in lungs

Aerosols of most agents produce systemic disease

Key Indicators of a BT Event

Sudden increase in severity or incidence of illnessAppearance of unusual (non-endemic) illness or syndrome in your communityGeographic and/or temporal pattern of illnessOccurrence of vector-borne disease where there is no vector

Key Indicators of a BT Event

Cluster of sick or dead animalsAtypical seasonalityUnusual expression of endemic diseaseMulti drug-resistant pathogens

Bioterrorism: The AgentsCategory A:

Top PriorityEasily disseminated or transmittedHigh mortalityCauses social disruptionSpecial preparation needed

Category A Agents:AnthraxBotulismPlagueSmallpoxTularemiaViral Hemorrhagic Fevers

Bioterrorism: The Agents

Category BQ FeverBrucellosisViral encephalitidesStaphylococcal enterotoxin BFood/WaterborneRicin

Category CNipah virusHantavirusTickborne hemorrhagic feverYellow feverMultidrug-resistant TB

Overview of the Agents:

Clinical Manifestations and Treatment

Pneumonic Syndromes:

Inhalational AnthraxPneumonic Plague

Pneumonic/Typhoidal Tularemia

Anthrax

Source: Bacillus anthracisBacterial spores and toxinsCutaneous, inhalational and intestinal

Cutaneous Anthrax

Cutaneous AnthraxIncubation 1-12 daysPapule > vesicle or ulcer > black centerover several daysDiagnosis: Gram stain and culture of unroofed vesicle, base of ulcer, under edge of escharUsually responds well to treatment

Inhalational Anthrax

Incubation: 1 - 6 days (rarely up to > 60 days)Prodrome: 1-2 d fever, malaise, dry coughSevere respiratory distress, septic shock, may have meningitis

DiagnosisHemorrhagic mediastinitis – wide on CXR

IsolationStandard; not contagious

Inhalational Anthrax:

Mediastinal Widening

Anthrax vs. Viral Illness Anthrax Flu Other Viral

Elev. Temp 70% 68-77 % 40-73%Cough 90 84-93 72-80SOB 80 6 6Pleuritic Pain 60 35 23Headache 50 84-91 74-89Sore Throat 20 64-84 64-84Rhinorrhea 10 79 68Nausea / Vom. 80 12 12

MMWR Nov 9 2001;50:984

Evaluation of Possible Inhalation Anthrax

History of exposure or risk + Symptoms: WBC (bandemia), Blood culture – highest yield CXR – wide mediastinum, effusion, or infiltrate

Consider CT if CXR normal

If results abnormal or pt. seriously ill:Multi-drug treatmentIf results normal and pt mildly ill:Observe and initiate single-drug prophylaxis

Anthrax - Treatment

Combination Rx for seriously ill:Cipro or Doxy + other drug(s)

Other drugs with activity include:Rifampin, Vancomycin, Clindamycin, Imipenem, Clarithromycin, PCN

Post-Exposure Prophylaxis: Cipro or Doxy X 60 d(X 30 d if given with vaccine)

Anthrax Exposure?Most patients need only reassuranceHigher risk:

Threatening messageSandy brown color powderSuspicious letter or packageHigh-profile person or postal worker

If exposure is credible, contact policeNasal swab NOT sensitive enough to r/o exposure for an individual

PlagueSource

Bacterium: Yersinia pestisForms

Bubonic, septicemic, and pneumonic**

** Suspect Bioterrorism

Pneumonic Plague

Incubation: 2-3 dSymptoms

Fulminant pneumonia, bloody sputum, septic shock, high fever, chills, headache, possible disseminated intravascular coagulation

Diagnosis Laboratory: Gram stain blood, sputum, nodeSmall, Gram-neg, bipolar (‘safety-pin’), poorly staining coccobacilli

Pneumonic Plague

IsolationHighly contagiousStrict respiratory isolation until Rx for 3dFollowed by standard respiratory droplet precautions (masks, gown, gloves, eye protection)

TreatmentStreptomycin, doxycycline, or chloramphenicol

High mortality, but may respond to early treatment

TularemiaSource

Bacterium: Francisella tularensisGram neg. coccobacillusZoonotic (‘rabbit fever’)

FormsUlceroglandular and typhoidal/pneumonic**

**Suspect Bioterrorism

TularemiaIncubation: 2-10 daysProdrome:

Fever, headache, chills, myalgia, cough, nausea, vomiting, diarrheaMay present as pneumonia

DiagnosisLaboratory: Culture/Gram stain blood, sputum, nodeCulture can be difficult and is risky to lab personnel

          

TularemiaIsolation

Standard; not contagiousNo human-human transmission

TreatmentStreptomycin, gentamicin, or doxycycline If exposed: watch for 7 days, treat if fever developsVaccine under review by FDA

Mortality 30% untreated; < 10% treated

Paralytic Syndrome:

Botulism

BotulismSource:Clostridium botulinum neurotoxin

Types A, B, E, and FMost potent toxin known

Lethal dose 1 ng/kg100,000 times more toxic than sarin

BotulismIncubation: 1-5 daysSymptoms

Blocks cholinergic synapsesDry mouth, blurred/diplopia, muscle weakness, dysphagiaDescending flaccid paralysis can last for weeks to months

DiagnosisClinicalA few labs can do serum toxin assay

Death from respiratory failure

BotulismIsolation

Standard; not contagiousNo human-human transmissionDecontaminate clothing, skin with soap and water

TreatmentVentilatory supportBotulinum antitoxin - equine

Skin test for horse serum sensitivityMore effective if given early – will not reverse paralysis that has already occurred

Rash and Fever Syndromes:

SmallpoxViral Hemorrhagic Fevers

Smallpox: Variola major

Smallpox: PresentationIncubation: ~ 12 days (up to 17 days)Early symptoms nonspecific

Fever, malaise, aches for 2-4 days; then severe illnessRash then appears on extremities with uniform appearance

Scabs over in 1-2 weeksContagious until ALL scabs have fallen off

SmallpoxNotify Public Health IMMEDIATELYDiagnosis

LaboratoryRule out chickenpox – PCR

IsolationStrict contact and respiratory isolation (negative pressure)Trace contacts up to 17 days prior to illness

TreatmentNone known effectiveQuestionable effectiveness of Cidofovir

Mortality ~ 30%

Smallpox vs. Chickenpox

Variola VaricellaIncubation 7-17 d 14-21 dProdrome 2- 4 d minimal/noneDistribution extremities trunkProgression similar growth dissimilar growthScab formation 10-14 d p rash 4-7 d p rashScab separation 14-28 d p rash <14 d p rash

Smallpox vs Chickenpox

Rash: extremities, uniform size Rash: trunk, different stages of development

Smallpox Vaccine

Live Vaccinia virusGiven intradermal on bifurcated needlePustule – scab in ~ 1 week, mild feverCan potentially spread to others until scab is gone

Lifelong immunity is questionableVaccinated persons probable reduced risk of mortality

Vaccine is effective up to several days AFTER exposure

Administering the Vaccine

Administering the Vaccine

Vaccinia: Common Reactions

Sore armAdenopathyFever

Up to 1/3 may have reactions severe enough to miss work, school, or usual activities

Smallpox Vaccine - Reactions

Risks for primary vaccinees:Accidental Inoculation: > 500 / millionGeneralized Vaccinia: 242 / millionEczema Vaccinatum: 12 – 39 / millionProgressive Vaccinia: 1 – 2 / millionEncephalitis: 3 – 12 / millionDeath: 1 - 2 / million

Risks are much less if previously vaccinated

Vaccinia Immune Globulin-VIG

Primary treatment for adverse reactionsProduced from plasma of vaccinated individualsStored at CDCIM forms only at present

Indications for useEczema vaccinatumProgressive vacciniaAccidental implantations (extensive lesions)Generalized vaccinia(severe)

Not recommended in vaccinia keratitis

Accidental

Inoculation

Generalized

Vaccinia

Eczema Vaccinatu

m

Progressive Vaccinia

Progressive Vaccinia

Fetal Vaccinia

Viral Hemorrhagic Fever (VHF)

EbolaLassaMarburgSabia: Brazilian HFMachupo: Bolivian HFRift Valley FeverCrimean-Congo HF

Ebola virus

Viral Hemorrhagic Fever

Incubation: 4-21 daysSymptoms vary between virusesFever, myalgia, prostrationPetechiae, hemorrhage, shockNeurologic, pulmonary, hepatic involvementMortality varies: 10 – 90%

Viral Hemorrhagic FeverDiagnosis

Primarily clinicalViral isolation, serology, immunohist. at CDC

IsolationStrict contact isolationStrict respiratory isolationStrict bodily fluid isolation

Viral Hemorrhagic FeverTreatment

SupportiveFluids, transfusionWatch for pulmonary edema

Avoid unnecessary lines, procedures, etc.Ribavirin may be effective for Lassa, Bolivian HF, Crimean-Congo HF, Rift Valley Fever

Risk of Secondary Transmission

Agents to worry about:SmallpoxPlagueViral Hemorrhagic Fever

Isolation is critical if any of these are suspected

Notify hospital infection control immediately

Bioterrorism Agents: Decon

For most agents, it is very unlikely that anyone would be infected from clothing, skin, etc.

Decon when there is:Gross contamination by dust, powders, spray, etc.A body fluid agent, such as in the case of Ebola

Generally, no special equipment neededRemove clothing and seal it in plastic bagShower with soap & water

Laboratory Risks of BT AgentsAgent BSL Laboratory

RiskB. anthracis 2 low

Y. pestis 2 medium

Botulinum toxin 2 medium

F. tularensis 2/3 high

Smallpox 4 high

Viral Hemorrhagic Fever 4 high

Laboratory Response Network for Bioterrorism

LEVEL D: CDC

LEVEL A: Clinical Labs

LEVEL C: Typing Labs, Public Health Labs

LEVEL B: Public Health Labs

Special Problems with BT

Identifying a covert attackSocial disruptionProphylaxis for large populations

National Pharmaceutical Stockpile (NPS)Vaccination plans

Secondary transmission

Special Problems with BT

Specialized labs needed for some agentsRisks to laboratory workersCommunication between agencies

Limited Health Care Resources

Isolation roomsVentilatorsProtective EquipmentMedicationsVaccinesMorgue facilities

Challenges in Recognizing a Bioterrorist Attack

Delayed onset - hours to weeksEarly signs/symptoms nonspecificPhysicians/laboratorians not familiar with rare diseases/organismsCurrent public health surveillance may not be adequate for early detection

Early Detection of a BT Event:

Finding a Zebra Among Horses

Early detection and control of bioterrorism will depend on alert clinicians reporting unusual illnesses or patterns of illness to Public Health

BEFORE definitive diagnosis

When you hear hoof beats, think “zebras” (as well as horses)

Public Health Bioterrorism Surveillance Plan

Enhance traditional surveillance for all potential BT agents and unusual illnessesNovel surveillance methods

Hospital diversion dataMedical examiner dataSyndrome-based ER/ICU admissionsSchool absencesAnimal disease surveillance Pharmacy sales

Agencies Responding to a BT Attack

LocalPublic HealthPolice, Fire, EMS

StatePublic HealthDisaster managementNational Guard

FederalCDCFBI, Dept of JusticeHomeland Security, FEMADept of Defense

BT Hospital Preparedness Issues

Develop plans for:

Infection controlLab supportA large influx of patients: triage, pt placement, pt transportPharmacy inventoriesPsychological aspects of BT

BT Hospital Preparedness Issues

Develop plans for:

Hospital Emergency Incident Command System (HEICS)Internal and external communicationEvidence collectionDischarging or post-mortem careDecon

Preparation for a BT Attack

Familiarize medical staff with BT agentsIncorporate into disaster planning

Infection control and decontaminationCommunication plan with key agencies:

Public Health DeptLaboratory, CDC, police, FBI, etc.

Identify contacts to obtain stockpiled supplies: antibiotics, immune sera, vaccines, antidotes, decon equipment, PPEs, etc.Security preparations

Local Health Department Actions

Determine whether situation is “unusual”Case finding/case investigationLaboratory confirmationAlert medical communityIdentify source of outbreak and at-risk personsCoordinate with State DHS, CDC, FBI, and other authorities

Public Health’s Role in Bioterrorism Event

Incorporation of State Epidemiology BT MaterialsEpi/surveillanceLabsNotificationMedia/Public Information Officer (PIO)Integration with FBIIntegration with CDC

Public Health’s Role in Bioterrorism Event

Infectious Disease/epidemiology tracks infectious diseasesPublic Health Laboratories identify agents (either in-house or through referral to State or CDC)Environmental Health assesses sanitation and safety of food and water

Public Health’s Role in Bioterrorism Event

Health Officer coordinates information for the public and medical providersCommunity Health and PH nurses provide education, information to the public and to community providersTreatment and prophylaxisQuarantine

What To Do if You Suspect a Bioterrorist Disease

IMMEDIATELY NOTIFY:Hospital Infection Control

Isolation: Smallpox, plague, hemorrhagic fevers

LaboratoryHospital AdministrationLocal Public Health Department

Case Studies

Case 1 - Dyspnea, Hypotension

46 year old stock traderFever, malaise, cough 2 days priorAbrupt onset severe dyspnea38.1o 115 86/40 32 O2sat 83%

Diaphoretic, DisorientedCXR - no infiltrate, + small pleural eff.

Mediastinal Widening

Case 1 - Dyspnea, Hypotension

Patient admitted to ICU:Fluids, Intubation, Ceftriaxone, Vanco., Gent.

Later the same day a similar patient presentsAlso a stock trader in the same building

Both patients deteriorate and die the next day

Case 2 - Rapid Progressive Pneumonia

10 y/o boy with fever, dry cough for 1 day8 y/o sister also ill

VS 38.6o 110 96/60 91% sat

Scattered crackles in both lungsCXR - Bilateral infiltratesLater develops severe dyspnea, hemoptysis, shock

Case 3 - Fever

52 y/o male c/o 3 days malaise, fever, vomiting, myalgias

39.1o 92/50 124 28WBC 18 platelets 45 BUN 48 Creatinine 2.9

Within hours becomes confused, vomits blood

Case 4 – Vesicular Rash34 y/o woman with fever, malaise X 2 daysToday, a rash appeared

39.4o 106/78 116 18A & O X 3 Lungs clear

Case 5 - Overt Attack

A terrorist group says they have released 10 kg of botulinum toxin over your city

Clostridium botulinum neurotoxin Lethal dose 1 ng/kg

Bioterrorism Addendum A:

Selected Category B and C Agents

Q Fever

SourceBacterium: Coxiella burnetii Resistant to heat, drying and many common disinfectants

Incubation 10-40 dSx variable - Fever, HA, myalgia, malaiseOcc. cough, rales, CXR infiltrateWBC usually normal, but LFTs common

Low mortality, but malaise may last months

Q FeverDiagnosis

Laboratory: serology, antibody or ELISAIsolation: Standard

TreatmentAntibiotics will shorten course

TetracyclinesErythromycin, azithromycin, quinolones, Chloramphenicol, TMP/SMX

Brucellosis

SourceBrucella species

ZoonoticSlow-growing gram negative rod

Presentation: Incubation 5-60 d or longer

May last weeks or months, but rarely fatal

Brucellosis

DiagnosisSerology; Culture of bone marrow, liver or spleen tissue

IsolationStandardContact if open lesions

TreatmentCombination antibioticsMost recover even without antibiotics

Viral Encephalitis

Alphaviruses: Venezuelan, Eastern, Western Equine EncephalitisPresentation: Incubation 2-14 d

Fever, HA, myalgia, photophobia, vomitingSmall % of VEE progress to neurologic SxDelirium, coma, seizures

Viral EncephalitisDiagnosis

Viral isolation or serology, PCR for some

Isolation: Standard

TreatmentSupportive analgesics, anticonvulsantsVaccines available, but poorly immunogenic

Ricin

RicinSource

Derived from castor beans (Ricinus communis)

1 million tons of castor beans produced annually worldwide5% ricin by weightStable

Inhibits protein synthesis via ribosome Toxic via inhalation, ingestion, injection

RicinRicin was used to assassinate Bulgarian exile Georgi Markov in London in 1978. A weapon disguised as an umbrella was used to implant a ricin-containing pellet

RicinSymptoms begin in 4-8 hours:

Weakness, fever, cough, hypothermia, sweating

InhalationSevere respiratory symptoms from necrosis and edema, hypoxia with respiratory failure in 36-72 hours

IngestionNausea, vomiting, diarrhea, GI hemorrhage, vascular collapse, death in 3 d

May cause DIC, multi-organ failure

RicinDiagnosis

Serum ELISA available in few labs

TreatmentPrimarily supportive:O2, hydration

If ingested:Gastric lavageActivated charcoal

Staphylococcal Enterotoxin B

Presentation: Incubation 1-6 hrsDiagnosis

Clinical and epidemiological

Isolation: StandardTreatment

Supportive

Clostridium perfringens Toxin

SourceEpisilon toxin of Clostridium perfringens Organism ubiquitous in soilPresent in stool of every vertebrate

Can produce gas gangrene, necrotizing enterocolitis, food poisoningSecretes > 12 toxinsCould be toxic if inhaled or ingested

C. perfringens Toxin

Symptoms within hoursGI symptoms prominent, rare feverIf inhaled, could cause resp. distress

MortalityDeath is rareCould result from vascular leaks, lung damage

C. perfringens Toxin

Diagnosis: ClinicalStool tests for enterotoxin are not widely available

TreatmentSupportiveAntibiotics active against organism:

penicillin, clindamycin

Trichothecene MycotoxinsSource

Group of > 40 fungal toxinsProduced by Fusarium, other common fungiStable to heat and UV

Inhibits protein and nucleic acid synthesis affecting rapidly proliferating tissuesIf aerosolized, appears as yellow droplets, “yellow rain”Toxic via inhalation, ingestion, and skin

Trichothecene MycotoxinsSymptoms: onset minutes to 4 hours

Skin blistering, eye irritation, nose/throat pain, Cough, dyspnea, chest pain, hemoptysisAbdominal pain, vomiting, bloody diarrheaBone marrow suppression can lead to diffuse hemorrhageIf severe: prostration, ataxia, shock and death in hours to days

Trichothecene MycotoxinsDiagnosis:

Urine, blood, tissue samples for liquid chromatography-mass spectrometry in specialized labs

Treatment: SupportiveRemove and isolate clothing, irrigate eyes, wash with soap/waterIf ingested, Activated charcoal ? Benefit of ascorbic acid, dexamethasone

Case 1 – Headache, Vomiting

39 y/o woman presents with 2 d worsening HA, nausea, vomiting, fever, malaise

Better after fluids, acetaminophen and is released

Returns following day with confusion, seizure

Case 2 – Vomiting, Diarrhea

Multiple patients present to ER with:Vomiting, diarrhea, headache, myalgias, malaise, fever, chills, cough

All had been at a large outdoor festival

High numbers of people present to ERs and clinics over several weeks in Nov. - Dec.

Fevers, malaise, cough, headachesSome have pneumonia on CXRMost have elevated LFTs

Public health department finds no influenza or other pathogens

Case 3: Malaise

Bioterrorism Addendum B:

Additional Resources and References

Additional Web Resources

Centers for Disease Control and Prevention (CDC)

www.bt.cdc.gov

US Army Medical Research Institute on Infectious Disease (USAMRIID)

www.usamriid.army.mil

World Health Organization (WHO) Communicable Disease Surveillance and Response (CSR)

www.who.int/emc/

Additional Print ResourcesEmergency Medicine Clinics of North America May 2002 (entire issue devoted to bioterrorism)Kortepeter MG and Parker GW. Potential biological weapons threats. Emerging Infectious Diseases. 1999; 5: 523-27.Inglesby TV et al. Anthrax as a Biological Weapon, 2002: Updated Recommendations for Management. JAMA. May 01, 2002;287(17): 2236-2252.Arnon SS et al. Botulinum Toxin as Biological Weapon: Medical and Public Health Management. JAMA. Feb 8, 2001;285(8): 1059-1070, 2081.Inglesby TV et al. Plague as a Biological Weapon: Medical and Public Health Management. JAMA. May 03,2000;283(17): 2281-2290.

Additional Print ResourcesHenderson DA et al. Smallpox as a Biological Weapon: Medical and Public Health Management. JAMA. June 09, 1999; 281(22):2127-2137.Dennis DT et al. Tularemia as a Biological Weapon: Medical and Public Health Management. JAMA. June 02, 2001; 285(21):2763-2773.Borio L et al. Hemorrhagic Fever Viruses as Biological Weapons: Medical and Public Health Management. JAMA. May 08, 2002; 287(18): 2391-2405.Franz DR, Jahrling PB, Friedlander DJ et al. Clinical recognition and management of patients exposed to biological warfare agents. JAMA. 1997;278(5):399-411.

Additional Print ResourcesBryan JL, Fields HF. An ounce of prevention is worth a pound of cure – shoring up the public health infrastructure to respond to bioterrorist attacks. Amer J of Infection Control. 1999;27:465-7.CDC. Biological and Chemical Terrorism: Strategic Plan for Preparedness and Response. Recommendations of the CDC Strategic Planning Workgroup. MMWR. April 21,2000, Vol 49, No. RR-4.Wetter DC, Daniell WE and Treser CD. Hospital preparedness for victims of chemical or biological terrorism. Amer J of Public Health. 2001;91(5):710-16.

Additional Print ResourcesPavlin J. Epidemiology of bioterrorism. Emerging Infectious Diseases. 1999;5:528-530Macintyre AG, Christopher GW, Eitzen E et al. Weapons of Mass Destruction Events with Contaminated Casualties: Effective Planning for Health Care Facilities. JAMA. 2000; 283:242-249.Meltzer MI, Damon I, LeDuc JW, and Millar JD. Modeling potential responses to smallpox as a bioterrorist weapon. Emerging Infectious Diseases. 2001;7(6):959-969.DiGiovanni C Jr . Domestic terrorism with chemical or biological agents: psychiatric aspects. Am J Psychiatry 1999;156:1500-5.

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