Preparing for and Responding to Bioterrorism: Information for Primary Care Clinicians

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

http://www.kcmo.org/health/bioterrorism.jpg

UW Northwest Center for Public Health Practice

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


Diseases of Bioterrorist Potential Diseases of Bioterrorist Potential Tularemia & Viral Hemorrhagic FeversTularemia & Viral Hemorrhagic Fevers

CDC, AFIP


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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Biological Agents of Highest Concern

Tularemia

Viral Hemorrhagic Fevers

Summary and Resources

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

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..

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

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


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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Tularemia




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

http://www.lawestvector.org/tulare3.jpg


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

http://www.lawestvector.org/tulare3.jpg


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


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


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


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


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


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


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


Ulceroglandular TularemiaUlceroglandular Tularemia


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


Pneumonic Tularemia Pneumonic Tularemia

Source: Armed Forces Institute of Pathology


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


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


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


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


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


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

http://jama.ama-assn.org/issues/v285n21/ffull/jst10001.html


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



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



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

http://www.adamshospital.com/images/inf%20control.jpg


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.


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.


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

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5033a2.htm



http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10805829&dopt=Abstract




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Tularemia




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


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


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


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


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


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


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


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


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:


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


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


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


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


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


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


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

http://www.lehigh.edu/~dmr8/ebolavictim.jpg


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


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


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


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


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


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


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.


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.


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)




http://www.cdc.gov/mmwr/PDF/wk/mm5005.pdf




Navigation PageNavigation PageClick on the Section You Wish to Go ToClick on the Section You Wish to Go To


Tularemia




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


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

This link will take you away from the educational site

http://www.usamriid.army.mil/education/instruct.html

http://www.usamriid.army.mil/education/instruct.html


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


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/



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



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



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



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


Preparing for and Responding to Bioterrorism: Information for Primary Care Clinicians

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