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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