Preparing for and Responding to Bioterrorism: Information for Primary Care Clinicians
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Transcript of Preparing for and Responding to Bioterrorism: Information for Primary Care Clinicians
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Northwest Center for Public Health PracticeUniversity of Washington School of Public Health and Community Medicine, July 2002
Preparing for and Responding to Preparing for and Responding to Bioterrorism: Information for Bioterrorism: Information for
Primary Care CliniciansPrimary Care Clinicians
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Acknowledgements Acknowledgements This presentation, and the accompanying instructor’s manual (current as of 7/02), were prepared by Jennifer Brennan Braden, MD, MPH, at the Northwest Center for Public Health Practice in Seattle, WA, and Jeff Duchin, MD with Public Health – Seattle & King County and the Division of Allergy & Infectious Diseases, University of WA, for thepurpose of educating primary care clinicians in relevant aspects of bioterrorism preparedness and response. Instructors are encouragedto freely use all or portions of the material for its intended purpose.
The following people and organizations provided information and/or support in the development of this curriculum. A complete list of resources can be found in the accompanying instructor’s guide.
Patrick O’Carroll, MD, MPH The Centers for Disease Control and Prevention Project Manager
Judith YarrowHealth Policy & Analysis, University of WADesign and Editing
Jane Koehler, DVM, MPHCommunicable Disease Control, Epidemiology and Immunization section, Public Health - Seattle & King County
Ed Walker, MD; University of WADepartment of Psychiatry
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Diseases of Bioterrorist Potential Diseases of Bioterrorist Potential Tularemia & Viral Hemorrhagic FeversTularemia & Viral Hemorrhagic Fevers
CDC, AFIP
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Diseases of BT Potential Diseases of BT Potential Learning ObjectivesLearning Objectives
Be familiar with the agents most likely to be Be familiar with the agents most likely to be used in a biological weapons attack and the used in a biological weapons attack and the most likely mode of disseminationmost likely mode of dissemination
Know the clinical presentation(s) of the Know the clinical presentation(s) of the Category A agents and features that may Category A agents and features that may distinguish them from more common diseases distinguish them from more common diseases
Be familiar with diagnosis, treatment Be familiar with diagnosis, treatment recommendations, infection control, and recommendations, infection control, and preventive therapy for management of infection preventive therapy for management of infection with or exposure to Category A agents. with or exposure to Category A agents.
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Navigation PageNavigation PageClick the Section to Which You Want to GoClick the Section to Which You Want to Go
Biological Agents of Highest Concern
Tularemia
Viral Hemorrhagic Fevers
Summary and Resources
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Biological Agents of Highest ConcernBiological Agents of Highest ConcernCategory A AgentsCategory A Agents
Easily disseminated, infectious via aerosolEasily disseminated, infectious via aerosol Susceptible civilian populationsSusceptible civilian populations Cause high morbidity and mortality Cause high morbidity and mortality Person-to-person transmission Person-to-person transmission Unfamiliar to physiciansUnfamiliar to physicians – – difficult to difficult to
diagnose/treatdiagnose/treat Cause panic and social disruptionCause panic and social disruption Previous development for BWPrevious development for BW
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Biological Agents of Highest ConcernBiological Agents of Highest Concern Category A AgentsCategory A Agents
Variola major (Smallpox)Variola major (Smallpox) Bacillus anthracisBacillus anthracis (Anthrax) (Anthrax) Yersinia pestisYersinia pestis (Plague) (Plague) Francisella tularensisFrancisella tularensis (Tularemia) (Tularemia) Botulinum toxin (Botulism)Botulinum toxin (Botulism) Filoviruses & Arenaviruses (Viral hemorrhagic Filoviruses & Arenaviruses (Viral hemorrhagic
fevers)fevers) Report ANY Report ANY suspected suspected illness due to these illness due to these
agents to Public Health agents to Public Health immediatelyimmediately..
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Biological Agents of 2nd Highest ConcernBiological Agents of 2nd Highest ConcernCategory B AgentsCategory B Agents
Coxiella burnettiCoxiella burnetti (Q-fever) (Q-fever) BrucellaBrucella species (brucellosis) species (brucellosis) Burkholderia malleiBurkholderia mallei (glanders) (glanders) Alphaviruses (Venezuelan, Western and Alphaviruses (Venezuelan, Western and
Eastern encephalomyelitis viruses)Eastern encephalomyelitis viruses) Ricin toxin from Ricin toxin from Ricinus communisRicinus communis (castor (castor
bean)bean) Epsilon toxin from Epsilon toxin from Clostridium perfringensClostridium perfringens StaphlococcusStaphlococcus enterotoxin B enterotoxin B
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Biological Agents of 2nd Highest ConcernBiological Agents of 2nd Highest ConcernFood- or Water-borne Category B AgentsFood- or Water-borne Category B Agents
Salmonella speciesSalmonella species
Shigella dysenteriaeShigella dysenteriae
Escherichia coli Escherichia coli 0157:H70157:H7
Vibrio choleraVibrio cholera
Cryptosporidium parvumCryptosporidium parvum
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Biological Agents of 3rd Highest ConcernBiological Agents of 3rd Highest ConcernCategory C AgentsCategory C Agents
Emerging pathogens that could be Emerging pathogens that could be engineered for mass dissemination in the engineered for mass dissemination in the futurefuture Nipah virus Nipah virus Hantaviruses Hantaviruses Tick-borne hemorrhagic fever virusesTick-borne hemorrhagic fever viruses Tickborne encephalitis viruses Tickborne encephalitis viruses Yellow fever Yellow fever Multidrug-resistant tuberculosisMultidrug-resistant tuberculosis
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Navigation PageNavigation Page Click the Section to Which You Want to GoClick the Section to Which You Want to Go
Biological Agents of Highest Concern
Tularemia
Viral Hemorrhagic Fevers
Summary and Resources
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Francisella TularensisFrancisella Tularensis
Causative agent of tularemia Causative agent of tularemia Non-motile, non-spore-forming gram negative Non-motile, non-spore-forming gram negative
cocco-bacillus found in diverse animal hostscocco-bacillus found in diverse animal hosts Studied by U.S. and others as potential BW Studied by U.S. and others as potential BW
weapon weapon Resistant to freezing temperatures, sensitive to Resistant to freezing temperatures, sensitive to
heat and disinfectantsheat and disinfectants
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Francisella TularensisFrancisella Tularensis
Biovar type ABiovar type A - may be highly virulent in - may be highly virulent in humans and animals, most common biovar in N. humans and animals, most common biovar in N. AmericaAmerica
Biovar type BBiovar type B - relatively avirulent, thought to - relatively avirulent, thought to cause all human tularemia in Europe and Asia cause all human tularemia in Europe and Asia
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Francisella TularensisFrancisella TularensisEpidemiologyEpidemiology
Humans infected by various modes:Humans infected by various modes: Handling contaminated animal tissues or fluids Handling contaminated animal tissues or fluids Bite of infective deer flies, mosquitoes, or ticksBite of infective deer flies, mosquitoes, or ticks Direct contact with or ingestion of contaminated Direct contact with or ingestion of contaminated
water, food, or soilwater, food, or soil Inhalation of infective aerosols (most likely BT Inhalation of infective aerosols (most likely BT
route)route) About 200 cases of tularemia/year in U.S.About 200 cases of tularemia/year in U.S.
Most in south-central and western statesMost in south-central and western states Most in rural areas Most in rural areas Majority of cases in summerMajority of cases in summer
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Francisella TularensisFrancisella TularensisEpidemiologyEpidemiology
Low infectious dose: 10-50 organisms Low infectious dose: 10-50 organisms produce diseaseproduce disease
Incubation period: probably 3-5 days Incubation period: probably 3-5 days following aerosol exposure (range 1-21 days)following aerosol exposure (range 1-21 days)
Case fatality rateCase fatality rate Treated: <1-3% Treated: <1-3% Untreated: 30-60% (pneumonic), 5% Untreated: 30-60% (pneumonic), 5%
(ulceroglandular)(ulceroglandular) Recovery followed by permanent immunityRecovery followed by permanent immunity No person-to-person transmissionNo person-to-person transmission
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Francisella TularensisFrancisella Tularensis Pathogenesis Pathogenesis
Intracellular pathogen: multiplies within Intracellular pathogen: multiplies within macrophagesmacrophages
Major target organs - lymph nodes, lungs and Major target organs - lymph nodes, lungs and pleura, spleen, liver, kidneypleura, spleen, liver, kidney
Focal suppurative necrosis Focal suppurative necrosis granulomas granulomas
Inhalational exposures can cause hemorrhagic Inhalational exposures can cause hemorrhagic inflammation of airwaysinflammation of airways
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TularemiaTularemiaClinical FormsClinical Forms
Ulceroglandular - Ulcer at inoculation site Ulceroglandular - Ulcer at inoculation site with regional adenopathywith regional adenopathy
Glandular - Regional adenopathy without skin Glandular - Regional adenopathy without skin lesionlesion
Oculoglandular - Painful purulent Oculoglandular - Painful purulent conjunctivitis with regional adenopathyconjunctivitis with regional adenopathy
Pneumonic (most likely BT presentation)Pneumonic (most likely BT presentation) Primary from aerosol exposure or Primary from aerosol exposure or
secondary from bacteremia secondary from bacteremia
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TularemiaTularemiaClinical FormsClinical Forms
Typhoidal (possible BT presentation) Typhoidal (possible BT presentation) Septicemia, no adenopathySepticemia, no adenopathy
Oropharyngeal – pharyngitis/tonsillitis with or Oropharyngeal – pharyngitis/tonsillitis with or without ulcer; cervical and/or oropharyngeal without ulcer; cervical and/or oropharyngeal adenopathy; stomatitis adenopathy; stomatitis
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TularemiaTularemiaClinical FeaturesClinical Features
General – high fever, malaise, myalgia, General – high fever, malaise, myalgia, headache, chills and rigors, sore throatheadache, chills and rigors, sore throat
Respiratory - coryza, dry/slightly productive Respiratory - coryza, dry/slightly productive cough, substernal pain/tightnesscough, substernal pain/tightness
Gastrointestinal - nausea, vomiting, diarrheaGastrointestinal - nausea, vomiting, diarrhea Lab evaluation nonspecific:Lab evaluation nonspecific:
WBC’s increased with normal differential WBC’s increased with normal differential Mild increase in LDH, transaminases, alkaline Mild increase in LDH, transaminases, alkaline
phosphatasephosphatase
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Ulceroglandular TularemiaUlceroglandular Tularemia
75-85% of naturally occurring cases 75-85% of naturally occurring cases Cutaneous papule appears at inoculation site Cutaneous papule appears at inoculation site
concurrent with generalized symptomsconcurrent with generalized symptoms Papule --> pustule --> tender indolent ulcer with Papule --> pustule --> tender indolent ulcer with
or without eschar or without eschar Tender regional lymphadenopathyTender regional lymphadenopathy
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Ulceroglandular TularemiaUlceroglandular Tularemia
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Pneumonic Tularemia Pneumonic Tularemia Initial clinical picture: systemic illness with Initial clinical picture: systemic illness with
prominent signs of respiratory disease prominent signs of respiratory disease Abrupt onset of fever, chills, headaches, Abrupt onset of fever, chills, headaches,
myalgia, non-productive cough, sore throatmyalgia, non-productive cough, sore throat Radiographic signs Radiographic signs
Often minimal early in diseaseOften minimal early in disease May include peribronchial infiltrates, typically May include peribronchial infiltrates, typically
advancing to bronchopneumonia and often advancing to bronchopneumonia and often accompanied by pleural effusions and hilar accompanied by pleural effusions and hilar lymphadenopathylymphadenopathy
Mortality 30% untreated; < 10% treatedMortality 30% untreated; < 10% treated
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Pneumonic Tularemia Pneumonic Tularemia
Source: Armed Forces Institute of Pathology
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When to Think (BT) Tularemia? When to Think (BT) Tularemia? History/Epi CluesHistory/Epi Clues
Other recent cases of tularemia in the Other recent cases of tularemia in the community community
Claims* by a terrorist or aggressor of a Claims* by a terrorist or aggressor of a release of tularemiarelease of tularemia
Comparable illness in persons with common Comparable illness in persons with common ventilation system or other exposureventilation system or other exposure
Cluster of similar or unusual syndromeCluster of similar or unusual syndrome More severe disease than is usually expected More severe disease than is usually expected
or failure to respond to standard therapyor failure to respond to standard therapy Unusual season for pneumonia in presenting Unusual season for pneumonia in presenting
age groupage group*a “credible threat” as determined by law enforcement and/or public health officials
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Pneumonic TularemiaPneumonic TularemiaDifferential DiagnosisDifferential Diagnosis
Community acquired pneumonia (CAP)Community acquired pneumonia (CAP) Atypical CAP (Legionella, Mycoplasma)Atypical CAP (Legionella, Mycoplasma) Streptococcal pneumonia, Influenza, Streptococcal pneumonia, Influenza, H. influenzaH. influenza
Inhalational AnthraxInhalational Anthrax Other ZoonosesOther Zoonoses
BrucellosisBrucellosis Q FeverQ Fever Pneumonic plaguePneumonic plague HistoplasmosisHistoplasmosis Hantavirus pulmonary syndromeHantavirus pulmonary syndrome
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TularemiaTularemiaLaboratory DiagnosisLaboratory Diagnosis
Laboratory testing important in establishing Laboratory testing important in establishing diagnosis diagnosis
Alert lab personnel of suspicion for tularemiaAlert lab personnel of suspicion for tularemia Risk of infection to laboratory staffRisk of infection to laboratory staff Need for special culture mediaNeed for special culture media
IHC stains of secretions, exudates, tissueIHC stains of secretions, exudates, tissue Small size, pleomorphism, faint staining Small size, pleomorphism, faint staining
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TularemiaTularemiaLaboratory DiagnosisLaboratory Diagnosis
Culture of exudates, secretions, bloodCulture of exudates, secretions, blood Requires cysteine supplementation Requires cysteine supplementation Hold 5-7 days (if pt was given antibiotics)Hold 5-7 days (if pt was given antibiotics)
Direct fluorescent antibody stain, PCR, and Direct fluorescent antibody stain, PCR, and antigen detection = rapid testsantigen detection = rapid tests Performed by designated reference labs (e.g., WA Performed by designated reference labs (e.g., WA
PHL) PHL) Antibodies detectable beginning 10 days Antibodies detectable beginning 10 days
post-onset post-onset
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Tularemia Tularemia ProphylaxisProphylaxis
Vaccine: live attenuated vaccine under FDA Vaccine: live attenuated vaccine under FDA review – availability uncertainreview – availability uncertain
For known aerosol exposures, 14d oral For known aerosol exposures, 14d oral antibiotics recommended antibiotics recommended
If covert attack, observe for development of If covert attack, observe for development of fever for 14 days and treat with antibiotics if fever for 14 days and treat with antibiotics if febrile febrile
Post-exposure antibiotics – most effective when Post-exposure antibiotics – most effective when given within 24 hours of exposuregiven within 24 hours of exposure
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Treatment of Patients With Tularemia in a Contained Treatment of Patients With Tularemia in a Contained Casualty Setting*Casualty Setting*
Adults Adults Streptomycin 1gm IM BID x 10dStreptomycin 1gm IM BID x 10d GentamicinGentamicin**** 5mg/kg IM/IV qd x 10d 5mg/kg IM/IV qd x 10d
ChildrenChildren Streptomycin 15mg/kg IM BID x 10d (should Streptomycin 15mg/kg IM BID x 10d (should
not exceed 2 gm/d) not exceed 2 gm/d) GentamicinGentamicin**** 2.5mg/kg IM/IV TID x 10d 2.5mg/kg IM/IV TID x 10d
Pregnant Women - gentamicin preferred over Pregnant Women - gentamicin preferred over streptomycinstreptomycin
*Working Group on Civilian Biodefense consensus-based recommendations Source: JAMA. 2001;285:2763-2773 **Not an FDA-approved useThis link will take you away from the educational site
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Treatment of Patients With Tularemia in a Contained Treatment of Patients With Tularemia in a Contained Casualty Setting*Casualty Setting*
Alternate choices: Doxycycline, chloramphenicol Alternate choices: Doxycycline, chloramphenicol (contraindicated in pregnant women), (contraindicated in pregnant women), ciprofloxacin ciprofloxacin
Can switch to oral antibiotics when clinically Can switch to oral antibiotics when clinically indicatedindicated
*Working Group on Civilian Biodefense consensus-based recommendations Source: JAMA. 2001;285:2763-2773This link will take you away from the educational site
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Treatment of Tularemia in a Mass Casualty Setting Treatment of Tularemia in a Mass Casualty Setting and for Post-exposure Prophylaxis*and for Post-exposure Prophylaxis*
Adults Adults Doxycycline 100mg po BID x 14dDoxycycline 100mg po BID x 14d CiprofloxacinCiprofloxacin**** 500mg po BID x 14d 500mg po BID x 14d
Children (45kg or less)Children (45kg or less) Doxycycline 2.2mg/kg po BID x 14d Doxycycline 2.2mg/kg po BID x 14d
(if 45+kg, give adult dosage) (if 45+kg, give adult dosage) CiprofloxacinCiprofloxacin**** 15mg/kg po BID x 14d, should 15mg/kg po BID x 14d, should
not exceed 1g/daynot exceed 1g/day Pregnant Women - ciprofloxacin preferred over Pregnant Women - ciprofloxacin preferred over
doxycycline doxycycline *Working Group on Civilian Biodefense consensus-based recommendations Source: JAMA. 2001;285:2763-2773
**Not an FDA-approved useThis link will take you away from the educational site
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TularemiaTularemiaInfection ControlInfection Control
Standard precautionsStandard precautions No patient isolation No patient isolation
necessary due to lack necessary due to lack of human-to-human of human-to-human transmissiontransmission
Alert lab of suspicion Alert lab of suspicion for tularemiafor tularemia
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TularemiaTularemiaSummary of Key PointsSummary of Key Points
In naturally occurring tularemia, infection In naturally occurring tularemia, infection virtually always occurs in a rural setting. virtually always occurs in a rural setting. Infection in an urban setting with no known risk Infection in an urban setting with no known risk factors or contact with infected animals factors or contact with infected animals suggests a possible deliberate source. suggests a possible deliberate source.
Tularemia is not transmitted person to person.
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TularemiaTularemiaSummary of Key PointsSummary of Key Points
The most likely presentations of tularemia in a BT attack are pneumonic and typhoidal disease, as opposed to cutaneous disease in naturally occurring cases.
Tularemia can be treated and prevented with antibiotics.
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TularemiaTularemiaCase Studies and ReportsCase Studies and Reports
MMWR Morb Mortal Wkly Rep 2001;50(33)
N Engl J Med 2000 May 11;342(19):1430-8 (abstract)
These links will take you away from the educational site
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Navigation PageNavigation PageClick the Section to Which You Want to GoClick the Section to Which You Want to Go
Biological Agents of Highest Concern
Tularemia
Viral Hemorrhagic Fevers
Summary and Resources
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Viral Hemorrhagic FeversViral Hemorrhagic Fevers
Diverse group of illnesses caused by RNA Diverse group of illnesses caused by RNA viruses from 4 families:viruses from 4 families: Arenaviridae, Bunyaviridae, Filoviridae, FlaviridaeArenaviridae, Bunyaviridae, Filoviridae, Flaviridae Differ by geographic occurrence and vector/reservoirDiffer by geographic occurrence and vector/reservoir Share certain clinical and pathogenic features Share certain clinical and pathogenic features
Potential for aerosol dissemination, with human Potential for aerosol dissemination, with human infection via respiratory route (except dengue)infection via respiratory route (except dengue)
Target organ: vascular bedTarget organ: vascular bed Mortality 0.5 - 90%, depending on agentMortality 0.5 - 90%, depending on agent
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Viral Hemorrhagic FeversViral Hemorrhagic Fevers
Category A agents Category A agents FilovirusesFiloviruses ArenavirusesArenaviruses
Category C agents Category C agents HantavirusesHantaviruses Tick-borne Tick-borne
hemorrhagic fever hemorrhagic fever virusesviruses
Yellow fever Yellow fever
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Viral Hemorrhagic Fevers Viral Hemorrhagic Fevers TransmissionTransmission
Zoonotic diseasesZoonotic diseases Rodents and arthropods main reservoirRodents and arthropods main reservoir Humans infected via bite of infected arthropod, Humans infected via bite of infected arthropod,
inhalation of rodent excreta, or contact with infected inhalation of rodent excreta, or contact with infected animal carcassesanimal carcasses
Person-to-person transmission possible with Person-to-person transmission possible with several agentsseveral agents Primarily via blood or bodily fluid exposurePrimarily via blood or bodily fluid exposure Rare instances of airborne transmission with Rare instances of airborne transmission with
arenaviruses and filovirusesarenaviruses and filoviruses Rift Valley fever has potential to infect domestic Rift Valley fever has potential to infect domestic
animals following a biological attackanimals following a biological attack
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UW Northwest Center for Public Health Practice
Viral Hemorrhagic FeversViral Hemorrhagic Fevers Summary of AgentsSummary of Agents
Virus Family Virus/Syndrome Geographic occurrence
Reservoir or Vector
Human-human transmission?
Arenaviridae Junin (Argentine HF) S.America Rodents Lassa Fever – yes, via body fluids; others – not usually
Machupo (Bolivian HF) S.AmericaGuanarito (Brazilian HF)
S.America
Sabia (Venezuelan HF) S.AmericaLassa (Lassa Fever) West Africa
Flaviridae Yellow Fever Tropical Africa,Latin America
Mosquitoes Yellow Fever – blood infective up to 5d of illness; Others - No
Dengue Fever Tropical areas
Kyanasur Forest Disease
India Ticks
Omsk HF Siberia
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UW Northwest Center for Public Health Practice
Viral Hemorrhagic FeversViral Hemorrhagic FeversSummary of AgentsSummary of Agents
Virus Family Virus/Syndrome Geographic occurrence
Reservoir or Vector
Human-human transmission?
Bunyaviridae Congo-Crimean HF
Crimea, parts of Africa, Europe & Asia
Ticks Congo-Crimean Hemorrhagic Fever – yes, through body fluids; Rift Valley Fever, Hantaviruses – no
Rift Valley Fever Africa MosquitoesHantaviruses (Hemorrhagic Renal Syndrome/Hantavirus Pulmonary Syndrome)
Diverse Rodents
Filoviridae Ebola HF Africa Unknown Yes, body fluid transmissionMarburg HF Africa
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UW Northwest Center for Public Health Practice
Viral Hemorrhagic FeversViral Hemorrhagic FeversPathogenesisPathogenesis
Destruction of infected cellsDestruction of infected cells Occurs in filovirus, Rift Valley fever, and yellow fever Occurs in filovirus, Rift Valley fever, and yellow fever
infectionsinfections
Coagulopathy from hepatic dysfunction and Coagulopathy from hepatic dysfunction and disseminated intravascular coagulation (DIC)disseminated intravascular coagulation (DIC) Most prominent in Rift Valley fever and yellow feverMost prominent in Rift Valley fever and yellow fever
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UW Northwest Center for Public Health Practice
Viral Hemorrhagic FeversViral Hemorrhagic FeversPathogenesisPathogenesis
HemorrhageHemorrhage FilovirusesFiloviruses
From direct damage to vascular endothelial cells From direct damage to vascular endothelial cells and platelets and platelets impaired microcirculation impaired microcirculation
Through immunological and inflammatory Through immunological and inflammatory mediatorsmediators
DIC characteristicDIC characteristic ArenavirusesArenaviruses
Via stimulation of inflammatory mediators by Via stimulation of inflammatory mediators by macrophagesmacrophages
ThrombocytopeniaThrombocytopenia Inhibition of platelet aggregationInhibition of platelet aggregation DIC not characteristicDIC not characteristic
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Viral Hemorrhagic FeversViral Hemorrhagic FeversClinical PresentationClinical Presentation
Clinical manifestations nonspecific, vary by Clinical manifestations nonspecific, vary by agent agent
Incubation period 2-21 days, depending on Incubation period 2-21 days, depending on agentagent
Onset typically abrupt with filoviruses, Onset typically abrupt with filoviruses, flaviviruses, and Rift Valley feverflaviviruses, and Rift Valley fever
Onset more insidious with arenavirusesOnset more insidious with arenaviruses
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UW Northwest Center for Public Health Practice
Viral Hemorrhagic FeversViral Hemorrhagic FeversInitialInitial SymptomsSymptoms
High feverHigh fever Headache Headache Malaise Malaise WeaknessWeakness ExhaustionExhaustion
DizzinessDizziness MyalgiasMyalgias ArthralgiasArthralgias NauseaNausea Non-bloody diarrheaNon-bloody diarrhea
Prodromal illness lasting < 1 week may include:Prodromal illness lasting < 1 week may include:
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UW Northwest Center for Public Health Practice
Viral Hemorrhagic FeversViral Hemorrhagic FeversClinical SignsClinical Signs
Flushing, conjunctival Flushing, conjunctival injectioninjection
PharyngitisPharyngitis Petechiae, bleeding Petechiae, bleeding
(with some agents)(with some agents)
EdemaEdema Hypotension Hypotension Positive tourniquet Positive tourniquet
testtest ShockShock
Reflect vascular damage and increased capillary permeability
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Clinical Identification of Clinical Identification of Suspected VHFSuspected VHF
Clinical criteria: Clinical criteria: Temperature 101Temperature 101F(38.3F(38.3C) for <3 weeksC) for <3 weeks Severe illness and no predisposing factors for Severe illness and no predisposing factors for
hemorrhagic manifestations hemorrhagic manifestations 2 or more of the following:2 or more of the following:
Hemorrhagic or purple rashHemorrhagic or purple rash Epistaxis Epistaxis Hematemesis Hematemesis HemoptysisHemoptysis Blood in stools Blood in stools Other hemorrhagic symptoms Other hemorrhagic symptoms No established alternative diagnosis No established alternative diagnosis
JAMA 2002;287Adapted from WHO
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Clinical Identification of Clinical Identification of Suspected VHFSuspected VHF
Inquire about potential natural exposuresInquire about potential natural exposures Travel, insect bites, exposure to animals or ill Travel, insect bites, exposure to animals or ill
personspersons
Report suspected cases immediately to: Report suspected cases immediately to: Local and state health departmentLocal and state health department Hospital infection control professional and Hospital infection control professional and
laboratory personnellaboratory personnel
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Viral Hemorrhagic FeversViral Hemorrhagic FeversDifferential Diagnosis Differential Diagnosis
Severe systemic illness due to other agents: Severe systemic illness due to other agents: BacterialBacterial
Typhoid fever, meningococcemia, rickettsioses, Typhoid fever, meningococcemia, rickettsioses, leptospirosis, toxic shock syndrome, borreliosis, leptospirosis, toxic shock syndrome, borreliosis, psittacosis, septicemic plague, gram neg sepsispsittacosis, septicemic plague, gram neg sepsis
ProtozoaProtozoa Falciparum malaria, trypanosomiasis Falciparum malaria, trypanosomiasis
Viral and OtherViral and Other Measles, rubella, hemorrhagic smallpox, Measles, rubella, hemorrhagic smallpox,
vasculitis, TTP, Hemolytic Uremic Syndrome vasculitis, TTP, Hemolytic Uremic Syndrome (HUS), acute leukemia (HUS), acute leukemia
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UW Northwest Center for Public Health Practice
Viral Hemorrhagic FeversViral Hemorrhagic FeversLaboratory SignsLaboratory Signs
Thrombocytopenia (except LF)Thrombocytopenia (except LF) Leukopenia (except LF, HV, & some severe Leukopenia (except LF, HV, & some severe
CCHF)CCHF) Proteinuria and hematuria commonProteinuria and hematuria common Elevated liver function testsElevated liver function tests Anemia or hemoconcentrationAnemia or hemoconcentration
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Viral Hemorrhagic Fevers Viral Hemorrhagic Fevers Laboratory DiagnosisLaboratory Diagnosis
Antigen detection (ELISA)Antigen detection (ELISA) RT-PCRRT-PCR Viral isolation Viral isolation
Requires level D (BSL-4) laboratoryRequires level D (BSL-4) laboratory Later phases: 4-fold IgG titer rise between acute Later phases: 4-fold IgG titer rise between acute
and convalescent seraand convalescent sera Contact local or state public health to facilitate Contact local or state public health to facilitate
confirmatory testing confirmatory testing
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Medical Management of Medical Management of Viral Hemorrhagic FeversViral Hemorrhagic Fevers
Supportive care Supportive care Correct coagulopathies as neededCorrect coagulopathies as needed No antiplatelet drugs or IM injectionsNo antiplatelet drugs or IM injections Investigational treatments, available under Investigational treatments, available under
protocol:protocol: Ribavirin for arenaviridae and bunyaviridaeRibavirin for arenaviridae and bunyaviridae Convalescent plasma within 8d of onset for AHFConvalescent plasma within 8d of onset for AHF
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Medical Management of Medical Management of Viral Hemorrhagic FeversViral Hemorrhagic Fevers
Initiate supportive and ribavirin therapyInitiate supportive and ribavirin therapy If arenavirus or bunyavirus confirmed, If arenavirus or bunyavirus confirmed,
continue 10 day coursecontinue 10 day course If VHF excluded, or other VHF confirmed, If VHF excluded, or other VHF confirmed,
discontinue ribavirin discontinue ribavirin
JAMA 2002;287
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UW Northwest Center for Public Health Practice
Recommendations for Recommendations for Ribavirin Therapy in VHF*Ribavirin Therapy in VHF*
Contained Casualty Contained Casualty SettingSetting
Mass Casualty SettingMass Casualty Setting
AdultsAdults Loading dose: Loading dose: 30mg/kg IV (max 2g) 30mg/kg IV (max 2g) Then 16 mg/kg IV Then 16 mg/kg IV (max 1g/dose) (max 1g/dose) Q 6hr x 4 daysQ 6hr x 4 daysThen 8 mg/kg IV Then 8 mg/kg IV (max 500 mg/dose) (max 500 mg/dose) Q 8 hrs x 6 days Q 8 hrs x 6 days
Loading dose: 2000 Loading dose: 2000 mg PO mg PO Then 1200 mg/d PO QD in 2 Then 1200 mg/d PO QD in 2 divided doses (if > divided doses (if > 75 kg) or 1000 75 kg) or 1000 mg/d PO (if mg/d PO (if 75 kg) 75 kg) in 2 divided doses x 10 days in 2 divided doses x 10 days
Pregnant Pregnant WomenWomen
Same as adultsSame as adults Same as adults Same as adults
Children Children Same as adults, dosed Same as adults, dosed by weightby weight
Loading dose: 30 Loading dose: 30 mg/kg PO mg/kg PO Then 15 mg/kg po QD in Then 15 mg/kg po QD in 2 divided doses x 10 d 2 divided doses x 10 d
*VHF of unknown etiology, or secondary to arenaviruses or bunyaviruses
JAMA 2002;287
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Viral Hemorrhagic Fevers Viral Hemorrhagic Fevers Management of Exposed PersonsManagement of Exposed Persons
Medical surveillance for all potentially exposed Medical surveillance for all potentially exposed persons, close contacts, and high-risk contacts persons, close contacts, and high-risk contacts (I.e., mucous membrane or percutaneous (I.e., mucous membrane or percutaneous exposure) x 21 days exposure) x 21 days Report hemorrhagic symptoms (slide 47) Report hemorrhagic symptoms (slide 47) Record fever 2x/dayRecord fever 2x/day
Report temperatures Report temperatures 101 101F(38.3F(38.3C) C) Initiate presumptive ribavirin therapyInitiate presumptive ribavirin therapy
Percutaneous/mucocutaneous exposure to Percutaneous/mucocutaneous exposure to blood or body fluids of infected: blood or body fluids of infected: Wash thoroughly with soap and water, irrigate Wash thoroughly with soap and water, irrigate
mucous membranes with water or salinemucous membranes with water or saline
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UW Northwest Center for Public Health Practice
Viral Hemorrhagic FeversViral Hemorrhagic Fevers Management of Exposed PersonsManagement of Exposed Persons
Patients convalescing should refrain from Patients convalescing should refrain from sexual activity for 3 months post-recovery sexual activity for 3 months post-recovery (arenavirus or filovirus infection) (arenavirus or filovirus infection)
Only licensed vaccine: Yellow FeverOnly licensed vaccine: Yellow Fever Investigational vaccines: AHF, RV, HVInvestigational vaccines: AHF, RV, HV Possible use of ribavirin to high risk contacts of Possible use of ribavirin to high risk contacts of
CCHF & LF patients CCHF & LF patients
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UW Northwest Center for Public Health Practice
Viral Hemorrhagic FeversViral Hemorrhagic Fevers Infection ControlInfection Control
Airborne & contact precautions for health care, Airborne & contact precautions for health care, environmental, and laboratory workers environmental, and laboratory workers
Negative pressure room, if availableNegative pressure room, if available 6-12 air changes/hour6-12 air changes/hour Exhausted outdoors or through HEPA filterExhausted outdoors or through HEPA filter
Personal protective equipmentPersonal protective equipment Double glovesDouble gloves Impermeable gowns, leg and shoe coveringsImpermeable gowns, leg and shoe coverings Face shields and eye protectionFace shields and eye protection N-95 mask or PAPR N-95 mask or PAPR
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UW Northwest Center for Public Health Practice
Viral Hemorrhagic FeversViral Hemorrhagic Fevers Infection Control Infection Control
Dedicated medical equipment for patientsDedicated medical equipment for patients If available, point-of-care analyzers for routine If available, point-of-care analyzers for routine
laboratory analyses laboratory analyses If unavailable, pretreat serum w/Triton X-100If unavailable, pretreat serum w/Triton X-100 Lab samples double-bagged and hand-Lab samples double-bagged and hand-
carried to lab carried to lab Prompt burial or cremation of deceased with Prompt burial or cremation of deceased with
minimal handling minimal handling Autopsies performed only by trained Autopsies performed only by trained
personnel with PPEpersonnel with PPE
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UW Northwest Center for Public Health Practice
Viral Hemorrhagic FeversViral Hemorrhagic FeversSummary of Key PointsSummary of Key Points
A thorough travel and exposure history is key to A thorough travel and exposure history is key to distinguishing naturally occurring from distinguishing naturally occurring from intentional viral hemorrhagic fever cases.intentional viral hemorrhagic fever cases.
Viral hemorrhagic fevers can be transmitted via Viral hemorrhagic fevers can be transmitted via exposure to blood and bodily fluids. exposure to blood and bodily fluids.
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UW Northwest Center for Public Health Practice
Viral Hemorrhagic FeversViral Hemorrhagic FeversSummary of Key PointsSummary of Key Points
Contact and airborne precautions are Contact and airborne precautions are recommended for health care workers caring for recommended for health care workers caring for infected patients. infected patients.
Diagnostic laboratory testing for viral hemorrhagic fevers must be done in a bio-safety level 4 lab (i.e., CDC); contact the local or state health department before specimen collection in suspected cases.
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Viral Hemorrhagic FeversViral Hemorrhagic FeversCase Studies and ReportsCase Studies and Reports
Crit Care Med 2000 Jan;28(1):240-4 (abstract)
MMWR Morb Mortal Wkly Rep 2001;50(5)
These links will take you away from the educational site
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Navigation PageNavigation PageClick on the Section You Wish to Go ToClick on the Section You Wish to Go To
Biological Agents of Highest Concern
Tularemia
Viral Hemorrhagic Fevers
Summary and Resources
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Summary - Category A Critical AgentsSummary - Category A Critical Agents
Disease Transmit Man to Man
Infective Dose* (Aerosol)
Incubation Period
Duration of Illness Approx. case fatality rate
Inhalation anthrax
No
8,000-50,000 spores
1-6 days 3-5 days (usually fatal if untreated)
High
Pneumonic Plague
High 100-500 organisms
2-3 days 1-6 days (usually fatal)
High unless treated within 12-24 hours
Tularemia No 10-50 organisms
2-10 days (average 3-5)
> 2 weeks Moderate if untreated
Smallpox High Assumed low (10-100 organisms)
7-17 days (average 12)
4 weeks High to moderate
Viral Hemorrhagic Fevers
Moderate 1-10 organisms 2-21 days Death between 7-16 days
High for Zaire strain, moderate with Sudan
Botulism No 0.001 g/kg is LD50 for type A
1-5 days Death in 24-72 hours; lasts months if not lethal
High without respiratory support
Modified from: USAMRIID’s Medical Management of Biological Casualties Handbook
*infectious dose may be less in certain circumstances
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SummarySummaryCategory A Critical AgentsCategory A Critical Agents
Decontamination of exposed persons Decontamination of exposed persons Showering or washing thoroughly with soap and Showering or washing thoroughly with soap and
water adequate for most; bleach not necessary water adequate for most; bleach not necessary
Infection controlInfection control Standard precautions – all cases Standard precautions – all cases Airborne and contact precautions – smallpox and Airborne and contact precautions – smallpox and
viral hemorrhagic feversviral hemorrhagic fevers Droplet precautions – pneumonic plagueDroplet precautions – pneumonic plague
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Resources Resources Centers for Disease Control and Prevention Centers for Disease Control and Prevention
Bioterrorism Web page: Bioterrorism Web page: CDC Office of Health and Safety Information System CDC Office of Health and Safety Information System
(personal protective equipment)(personal protective equipment)
USAMRIID USAMRIID –– includes link to online version of Medical includes link to online version of Medical Management of Biological Casualties HandbookManagement of Biological Casualties Handbook
Johns Hopkins Center for Civilian Biodefense Johns Hopkins Center for Civilian Biodefense Studies Studies fact fact sheets and links to other info, including JAMA series sheets and links to other info, including JAMA series from Working Group on Civilian Biodefense and BT-from Working Group on Civilian Biodefense and BT-related anthrax case studiesrelated anthrax case studies
http://www.hopkins-biodefense.org
http://www.usamriid.army.mil/
http://www.bt.cdc.gov/
http://www.cdc.gov/od/ohs/
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Resources Resources
Office of the Surgeon General: Medical Office of the Surgeon General: Medical Nuclear, Biological and Chemical InformationNuclear, Biological and Chemical Information
St. Louis University Center for the Study of St. Louis University Center for the Study of Bioterrorism and Emerging Infections Bioterrorism and Emerging Infections –– fact fact sheets and links sheets and links
Public Health - Seattle & King CountyPublic Health - Seattle & King County
http://www.nbc-med.org
http://www.metrokc.gov/health
http://bioterrorism.slu.edu
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Resources Resources
American College of Physicians – links to BT American College of Physicians – links to BT resources, including decision support tools and resources, including decision support tools and palm documents palm documents
Self-Assessment (case scenarios – chemical Self-Assessment (case scenarios – chemical and biological)and biological)
MMWR Rec. and Rep. Case definitions under MMWR Rec. and Rep. Case definitions under public health surveillance.public health surveillance.
http://www.acponline.org
http://www.acponline.org/bioterro/self_assessment.htm
1997;46(RR-10):1-55
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In Case of An Event…In Case of An Event…Web Sites with Up-to-Date Information and Web Sites with Up-to-Date Information and
InstructionsInstructions
Centers for Disease Control and Prevention Centers for Disease Control and Prevention Saint Louis University, CSB & EISaint Louis University, CSB & EI WA State Local Health Departments/DistrictsWA State Local Health Departments/Districts
Level A Lab Protocols: Presumptive Agent IDLevel A Lab Protocols: Presumptive Agent ID
http://www.bt.cdc.gov/EmContact/index.asphttp://www.bt.cdc.gov/EmContact/index.asp
http://bioterrorism.slu.edu/hotline.htmhttp://bioterrorism.slu.edu/hotline.htm
http://www.bt.cdc.gov/LabIssues/index.asphttp://www.bt.cdc.gov/LabIssues/index.asp
http://www.doh.wa.gov/LHJMap/LHJMap.htmhttp://www.doh.wa.gov/LHJMap/LHJMap.htm
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In Case of An Event…In Case of An Event…Web Sites with Up-to-Date Information and Web Sites with Up-to-Date Information and
InstructionsInstructions FBI Terrorism Web PageFBI Terrorism Web Page
WA State Emergency Mgt Division – Hazard WA State Emergency Mgt Division – Hazard Analysis UpdateAnalysis Update
Mail Security Mail Security
Links to your state health departmentLinks to your state health department
NIOSH – Worker Safety and Use of PPE NIOSH – Worker Safety and Use of PPE
http://www.fbi.gov/terrorism/terrorism.htmhttp://www.fbi.gov/terrorism/terrorism.htm
http://www.usps.com/news/2001/press/serviceupdates.htmhttp://www.usps.com/news/2001/press/serviceupdates.htm
http://www.cdc.gov/niosh/emres01.htmlhttp://www.cdc.gov/niosh/emres01.html
http://www.wa.gov/wsemhttp://www.wa.gov/wsem
http://www.astho.org/state.htmlhttp://www.astho.org/state.html
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