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BIOTERRORISM: Are You Prepared? By By Gregg S. Silberg, D.O., R.Ph., Gregg S. Silberg, D.O., R.Ph., F.A.C.O.I., F.A.O.C.R. F.A.C.O.I., F.A.O.C.R. Executive Director Executive Director Wisconsin Association of Osteopathic Physicians and Wisconsin Association of Osteopathic Physicians and Surgeons Surgeons Chair, Department of Internal Medicine Chair, Department of Internal Medicine Professor of Biosciences, Medicine and Professor of Biosciences, Medicine and Radiology Radiology

BIOTERRORISM: Are You Prepared? By Gregg S. Silberg, D.O., R.Ph., F.A.C.O.I., F.A.O.C.R. Executive Director Wisconsin Association of Osteopathic Physicians

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BIOTERRORISM: Are You Prepared?

By By

Gregg S. Silberg, D.O., R.Ph., F.A.C.O.I., F.A.O.C.R.Gregg S. Silberg, D.O., R.Ph., F.A.C.O.I., F.A.O.C.R.Executive DirectorExecutive Director

Wisconsin Association of Osteopathic Physicians and SurgeonsWisconsin Association of Osteopathic Physicians and Surgeons

Chair, Department of Internal MedicineChair, Department of Internal MedicineProfessor of Biosciences, Medicine and RadiologyProfessor of Biosciences, Medicine and RadiologyWilliam Carey University College of Osteopathic MedicineWilliam Carey University College of Osteopathic Medicine

Bioterrorism

The use, or threatened use, The use, or threatened use, of a micro-organism or the of a micro-organism or the product of a micro-organism product of a micro-organism in order to generate fear, in order to generate fear, morbidity or mortality in a morbidity or mortality in a population.population.

Delivery MechanismsAerosol routeAerosol route

Easiest to disperse Easiest to disperse

Highest number of people exposedHighest number of people exposed

Most infectiousMost infectious

Undetectable to humansUndetectable to humans

Food / Waterborne less likelyFood / Waterborne less likelyLarger volumes requiredLarger volumes required

More technically difficultMore technically difficult

Roles of Clinicians

General ConceptsGeneral ConceptsHigh level of suspicionHigh level of suspicion

Hoofbeats could be a zebraHoofbeats could be a zebra

Unusual epidemiologic trendsUnusual epidemiologic trendsCase clusteringCase clustering

Severe, fulminant disease in Severe, fulminant disease in otherwise healthyotherwise healthy

Unusual for the regionUnusual for the region

Similar disease in animalsSimilar disease in animals

Roles of Clinicians

For specific Bioterrorism (BT) diseasesFor specific Bioterrorism (BT) diseasesRecognize typical BT disease syndromesRecognize typical BT disease syndromes

Perform appropriate diagnostic testingPerform appropriate diagnostic testing

Initiate appropriate treatment/prophylaxisInitiate appropriate treatment/prophylaxis

Report suspected cases to proper authoritiesReport suspected cases to proper authorities

1) Local health department1) Local health department

2) Hospital epidemiologist2) Hospital epidemiologist

3) Infectious Disease consultants3) Infectious Disease consultants

CASES

Case 1 - Dyspnea, Hypotension

• 46 year old stock trader46 year old stock trader

• Fever, malaise, cough 2 days priorFever, malaise, cough 2 days prior

• Abrupt onset severe dyspneaAbrupt onset severe dyspnea

• 38.138.1oo 115 86/40 115 86/40 32 O 32 O22sat 83%sat 83%

• Diaphoretic, DisorientedDiaphoretic, Disoriented

• CXR - no infiltrate, + small pleural eff.CXR - no infiltrate, + small pleural eff.

Case 1 - Dyspnea, Hypotension

• Patient admitted to ICU:Patient admitted to ICU:

Fluids, Intubation, Ceftriaxone, Vanco., Gent.Fluids, Intubation, Ceftriaxone, Vanco., Gent.

• Later the same day a similar patient presentsLater the same day a similar patient presents- Also a stock trader in the same building- Also a stock trader in the same building

• Both patients deteriorate and die the next dayBoth patients deteriorate and die the next day

Case 2 – Vesicular Rash34 y/o woman with fever, malaise X 2 days34 y/o woman with fever, malaise X 2 days

Today rash appeared on face & armsToday rash appeared on face & arms

39.439.4o o 106/78106/78 116 116 1818

A & O X 3 A & O X 3 Lungs clear

• Scattered macules and vesicles noted

• Dx – Chicken pox

• Rx – po Acyclovir, recheck in 2 days

Case 3 - Rapid Progressive Pneumonia

10 y/o boy with fever, dry cough for 1 day10 y/o boy with fever, dry cough for 1 day8 y/o sister also ill8 y/o sister also illVSVS 38.638.6 oo 110110 96/60 96/60 91% sat 91% satScattered crackles in both lungsScattered crackles in both lungsCXR - Bilateral infiltratesCXR - Bilateral infiltrates

Later develops severe dyspnea, hemoptysis, Later develops severe dyspnea, hemoptysis, shockshock

Case 4 - Overt Attack

A terrorist group says they have released A terrorist group says they have released 10 Kg of botulinum toxin over your city10 Kg of botulinum toxin over your city

Clostridium botulinumClostridium botulinum neurotoxin neurotoxin Lethal dose 1 ng/kg Lethal dose 1 ng/kg

Case 5 - Fever• 52 y/o male c/o 3 days malaise, fever, 52 y/o male c/o 3 days malaise, fever,

vomiting, myalgiasvomiting, myalgias

• 39.139.1o o 92/5092/50 124124 2828

• WBC 18WBC 18 platelets 45platelets 45 BUN 48BUN 48

• Creatinine 2.9Creatinine 2.9

• Within hours becomes confused, vomits Within hours becomes confused, vomits bloodblood

Case 6 – Flu-like syndrome• 40 y/o with development of a painful ulcer on 40 y/o with development of a painful ulcer on

the left thumb 2 days after flu-like symptoms the left thumb 2 days after flu-like symptoms beganbegan

OVERVIEW OF BIOTERRORISM AGENTS

ObjectivesObjectivesIdentify the six major biological threat agents Identify the six major biological threat agents

classified as Category A by the Center for classified as Category A by the Center for Disease Control (CDC)Disease Control (CDC)

Describe the natural transmission of Category Describe the natural transmission of Category A biological agentsA biological agents

Know the epidemiology, microbiology clinical Know the epidemiology, microbiology clinical features of Category A biological agentsfeatures of Category A biological agents

Describe methods of diagnosis, available Describe methods of diagnosis, available treatments and prophylaxis options for treatments and prophylaxis options for Category A biological agents Category A biological agents

Overview of Bioterrorism Agents

Ideal Qualities for a Biologic Terrorist Agent Ideal Qualities for a Biologic Terrorist Agent

High rate of illness among those exposed High rate of illness among those exposed High attack rate High attack rate

High rate of death among those who get ill High rate of death among those who get ill High case fatality rateHigh case fatality rate

Short time between onset of illness and deathShort time between onset of illness and deathSmall window to start treatmentSmall window to start treatment

Low level of immunity in the populationLow level of immunity in the population

Overview of Bioterrorism Agents

Ideal Qualities for a Biologic Terrorist AgentIdeal Qualities for a Biologic Terrorist Agent (cont)(cont)

No effective or available treatmentNo effective or available treatment

Can be transmitted person to personCan be transmitted person to person

Easy to produce and disseminateEasy to produce and disseminate

Difficult to diagnosis either clinically or Difficult to diagnosis either clinically or diagnostically (i.e. laboratory identification)diagnostically (i.e. laboratory identification)

Overview of Bioterrorism Agents

Epidemiological CluesEpidemiological CluesWhat we look for…What we look for… Large outbreak with high illness and death rateLarge outbreak with high illness and death rate

Single case of uncommon disease (e.g., Smallpox)Single case of uncommon disease (e.g., Smallpox)

Unusual symptoms or severity of illnessUnusual symptoms or severity of illness

Infection is non-endemic to regionInfection is non-endemic to region

Unusual seasonal distributionUnusual seasonal distribution

Multiple simultaneous outbreaks in non-contiguous Multiple simultaneous outbreaks in non-contiguous areasareas

Sick or dying animalsSick or dying animals

Overview of Bioterrorism Agents

BioterrorismThreatsBioterrorismThreats::

Priority Biological AgentsPriority Biological Agents

BacterialBacterialAnthraxAnthraxPlaguePlagueTularemiaTularemiaBrucellosisBrucellosisQ feverQ feverOtherOther

food borne pathogensfood borne pathogenswaterborne pathogenswaterborne pathogens

ViralViralSmallpoxSmallpox

Viral Hemorrhagic Viral Hemorrhagic FeversFevers

Viral EncephalitisViral Encephalitis

ToxinsToxinsBotulismBotulism

Staph Enterotoxin BStaph Enterotoxin B

Ricin toxinRicin toxin

Tricothecene mycotoxinsTricothecene mycotoxins

Overview of Bioterrorism Agents

AnthraxAnthraxGram positive spore forming Gram positive spore forming bacterium bacterium Bacillus anthracisBacillus anthracis

Primarily disease of herbivores Primarily disease of herbivores which are infected by ingesting which are infected by ingesting spores in soilspores in soil

Natural transmission to humans by Natural transmission to humans by contact with infected animals or contact with infected animals or contaminated animal productscontaminated animal products

““Woolsorter’s disease”Woolsorter’s disease”

Three forms of diseaseThree forms of diseaseCutaneousCutaneous

Gastrointestinal (GI)Gastrointestinal (GI)

InhalationalInhalational

CDC: Gram stain of B. anthracis

Overview of Bioterrorism Agents

Infected herbivores and soil are reservoir

Direct contact Cutaneous anthrax

IngestionGastrointestinal anthrax

InhalationPulmonary/mediastinal

anthrax

Epidemiology of Transmission

Overview of Bioterrorism Agents

Day 2-4 Day 6

Day 10

Eschar formation

Anthrax: Cutaneous Accounts for 80% of

naturally occurring Anthrax cases

Enters through openings in skin from abrasions, lacerations

20% progress to systemic form if untreated

Most cases recover

Overview of Bioterrorism Agents

Anthrax: Inhalational Inhalation of spores Incubation, 2-3 days (range up to 60 days) Spores engulfed by macrophages and

transported to mediastinal and peribronchial lymph nodes

Insidious onset: malaise, low grade fever, nonproductive cough

Abrupt development of respiratory distress Hemorrhagic mediastinitis Hematogenous spread Meningitis in 50%, usually fatal

Overview of Bioterrorism Agents

Anthrax: Pulmonary/Mediastinal

Mediastinal widening from anthrax Normal chest x-ray

                                                       

Overview of Bioterrorism Agents

Ciprofloxacin400 mg intravenous every 12 hours for adults

10 -15 mg/kg intravenous every 12 hours for children

Ciprofloxacin400 mg intravenous every 12 hours for adults

10 -15 mg/kg intravenous every 12 hours for children

Doxycycline100 mg intravenous every 12 hours for adults and children > 8 yr and > 45 kg

2.2mg/kg every 12 hours for children < 8 yr (up to 200 mg/day)

Doxycycline100 mg intravenous every 12 hours for adults and children > 8 yr and > 45 kg

2.2mg/kg every 12 hours for children < 8 yr (up to 200 mg/day)

PLUS One or two additional anti-microbial agents effective against anthrax (e.g. imipenem,

clindamycin, rifampin, macrolides) Additional issues Penicillin should never be used as a monotherapy If meningitis is suspected, an antibiotic with good CSF penetration should also be

administered (e.g. rifampin or chloramphenicol) Supportive therapy for shock, fluid volume deficit and airway management may be

needed. Drainage of pleural effusions may improve clinical outcome

AND/OR

Anthrax Immune Globulin (AIG) can be used to neutralize anthrax toxin.

Patient Care Inhalational Anthrax

Overview of Bioterrorism Agents

Anthrax: Post-Exposure Prophylaxis Anthrax: Post-Exposure Prophylaxis Start 60 days of oral antibiotics ASAP after Start 60 days of oral antibiotics ASAP after

exposureexposureCiprofloxacin or Levofloxacin Ciprofloxacin or Levofloxacin

OROR

DoxycyclineDoxycyclineOROR

Amoxicillin or Penicillin (if known PCN sensitive)Amoxicillin or Penicillin (if known PCN sensitive)

VaccineVaccine

Can be given post-exposure in conjunction with Can be given post-exposure in conjunction with

antibioticsantibiotics

Overview of Bioterrorism Agents

SmallpoxSmallpoxVariola Variola virus, two forms of the disease: minor and virus, two forms of the disease: minor and

majormajorSpread via respiratory droplets or aerosols expelled Spread via respiratory droplets or aerosols expelled

from the oropharynxfrom the oropharynxMay also spread via direct contactMay also spread via direct contactPatients are most contagious during the time at which Patients are most contagious during the time at which

the skin rash is presentthe skin rash is presentApprox. 30% of patients exposed go on to develop the Approx. 30% of patients exposed go on to develop the

diseasediseaseApprox. 30% mortality with ordinary smallpoxApprox. 30% mortality with ordinary smallpox

Overview of Bioterrorism Agents

Overview of Bioterrorism Agents

Smallpox CharacteristicsSmallpox CharacteristicsFebrile SyndromeFebrile Syndrome – occurring 1-4 days prior to rash. – occurring 1-4 days prior to rash.

Classic Smallpox lesionClassic Smallpox lesion – deep-seated, firm/hard, round, well- – deep-seated, firm/hard, round, well-circumscribed; lesion may become umbilicated or confluent. circumscribed; lesion may become umbilicated or confluent.

Smallpox Rash

Overview of Bioterrorism AgentsChickenpox Rash

Overview of Bioterrorism Agents

Smallpox CharacteristicsSmallpox CharacteristicsFebrile SyndromeFebrile Syndrome – occurring 1-4 days prior to rash. – occurring 1-4 days prior to rash.

Classic Smallpox lesionClassic Smallpox lesion – deep-seated, firm/hard, round, well- – deep-seated, firm/hard, round, well-circumscribed; lesion may become umbilicated or confluent. circumscribed; lesion may become umbilicated or confluent.

Lesion in Same Stage of Development Lesion in Same Stage of Development – Evolve from macules – Evolve from macules → → papules → pustules at the same time.papules → pustules at the same time.

Centrifugal distribution Centrifugal distribution – First lesion on oral mucosa, face, or – First lesion on oral mucosa, face, or forearms. forearms.

Overview of Bioterrorism AgentsSmallpox vs. Chickenpox: Distribution

Overview of Bioterrorism Agents

Smallpox CharacteristicsSmallpox CharacteristicsFebrile SyndromeFebrile Syndrome – occurring 1-4 days prior to rash. – occurring 1-4 days prior to rash.

Classic Smallpox lesionClassic Smallpox lesion – deep-seated, firm/hard, round, well- – deep-seated, firm/hard, round, well-circumscribed; lesion may become umbilicated or confluent. circumscribed; lesion may become umbilicated or confluent.

Lesion in Same Stage of Development Lesion in Same Stage of Development – Evolve from macules – Evolve from macules → → papules → pustules at the same time.papules → pustules at the same time.

Centrifugal distribution Centrifugal distribution – First lesion on oral mucosa, face, or – First lesion on oral mucosa, face, or forearms. forearms.

Lesion on palms and solesLesion on palms and soles

Prodrome phase (2 - 4 days) Abrupt onset of fever

>38.3°C Malaise/myalgia Headache Nausea/vomiting Backache

Usually NOT Infectious

Incubation period 12 days

(range 7-19 days)NOT

Infectious

Incubation period 12 days

(range 7-19 days)NOT

Infectious

Rash Phase(21 days)

1) macules2) papules3) vesicles4) pustules5) scabsInfectious until all scabs

fall off

 

Early Rash Phase Mucous membrane lesions Small red spots on the tongue

and throat Lesions enlarge, ulcerate, then

shed virusInfectious 24 hours before visible skin rash

ExposureExposure

Clinical Timeline for SmallpoxOverview of Bioterrorism Agents

Smallpox Progression

Day 4

Day 6

Day 8

Day 13

Overview of Bioterrorism Agents

Papules

Vesicles

Pustules“pocks”

Scabs

Smallpox: Medical ManagementSmallpox: Medical ManagementStrict respiratory/contact isolation of patientStrict respiratory/contact isolation of patient

Patient infectious until all scabs have Patient infectious until all scabs have separatedseparated

Treatment is supportive care onlyTreatment is supportive care onlyAntivirals are under evaluationAntivirals are under evaluation

CidofovirCidofovirST246ST246

Overview Bioterrorism Agents

Smallpox: Prevention and ControlSmallpox: Prevention and ControlImmediate vaccination of Immediate vaccination of ALLALL

close contacts (close contacts (< < 6 ft) and 6 ft) and ALL ALL contacts of patients contacts contacts of patients contacts (Ring vaccination)(Ring vaccination)

Vaccination within 4 days of Vaccination within 4 days of exposure exposure maymay prevent or lessen prevent or lessen disease disease

Mass vaccination may be Mass vaccination may be necessary and/or everyone may necessary and/or everyone may want to be vaccinatedwant to be vaccinated

Case(s)

Contacts of Case(s)

Contacts of Contacts

Overview of Bioterrorism Agents

Smallpox: Current VaccineSmallpox: Current VaccineLive Live vacciniavaccinia virus virusBecause it is a live virus, Because it is a live virus, there can be adverse events there can be adverse events from vaccinationfrom vaccination

Occurs mostly in Occurs mostly in immunologically suppressed immunologically suppressed personspersons

Immunity is Immunity is notnot life-long, but life-long, but having been vaccinated in the having been vaccinated in the past may reduce morbidity past may reduce morbidity and mortalityand mortality

WHO

Overview of Bioterrorism Agents

PlaguePlague is a severe bacterial disease of humans and animals produced by the gram negative nonsporulating bacillus Yersinia pestis

•Bite of a rodent flea that is carrying the plague bacterium, or by handling an infected animal•Hundreds of millions of people died

when human dwellings were inhabited

by flea-infested rats•Modern antibiotics are effective, but without prompt treatment the disease can likely cause illness or death

Overview of Bioterrorism Agents

Types of PlagueTypes of PlagueThree types:Three types:

BubonicBubonic

SepticemicSepticemic

PneumonicPneumonic

Overview of Bioterrorism Agents

Secondary plague cases

Primary pneumonic plague

AA Flea vector such as

Xenopsylla cheopis

Animal Reservoirs

Primary bubonic plague

Primary septicemic plague

AA

BB

BB

CCCC

DDDD

Routes of Plague TransmissionA= Bite of Flea

B = Contact with animal or carcass

C = Inhalation of respiratory droplets

D = Contact with sputum or fluid

Plague: Epidemiology of Natural Transmission

Overview of Bioterrorism Agents

Early Presentation Abrupt onset of fever, malaise, headache, myalgia Chest pain and dyspnea Tachypnea (particularly in young children) Productive cough (sputum may be purulent or watery, frothy, blood-tinged) Hemoptysis

 

IncubationPeriod

1-6 days

IncubationPeriod

1-6 days

Late Presentation Rapid progression to pulmonary disease/ARDS Pulmonary edema, dyspnea, cyanosis Meningitis may be a complication Hypotension, DIC, septicemia, and death Lab findings -- bacterial infection and sepsis Organism usually seen on sputum gram stain Mortality approaches 100% if untreated in 24 hours

Antibiotictherapy in the first 24

hours can prevent septicemia, cardio-respiratory failure, shock, and death!

ExposureExposure

Clinical Presentation of Pneumonic Plague

Overview of Bioterrorism Agents

Plague: Patient Care

Early antibiotic treatment* is paramount to patient survival

Adults: Streptomycin 1 gm IM b.i.d. for 10 days;

Chloramphenicol 25 mg/kg IM or IV 4 times daily for 10 days Gentamicin 5 mg/kg IM or IV once daily for 10 days;

Doxycycline 100 mg IV b.i.d. or 200 mg IV once daily for 10 days; Ciprofloxacin 400 mg IV b.i.d. for 10 days;

Children: Streptomycin 15 mg/kg IM twice daily for 10 days (max 2 gm/day); Chloramphenicol 25 mg/kg IV 4 times daily for 10 days (max 4 gm/day) Gentamicin 2.5 mg/kg IM or IV 3 times daily for 10 days; Doxycycline 2.2 mg/kg IV twice daily for 10 days (max dose 200mg/day); Ciprofloxacin 15 mg/kg IV twice daily for 10 days (max 1 gm/day)

*CDC recommends initiating treatment with two drugs believed effective against Y. pestis until antimicrobial susceptibility data is available on isolates.

Overview of Bioterrorism Agents

Plague: ProphylaxisPlague: Prophylaxis

Pneumonic plague contacts (transmitted Pneumonic plague contacts (transmitted

via droplets)via droplets)Oral Doxycycline or Ciprofloxacin Oral Doxycycline or Ciprofloxacin

For 7 days after last exposureFor 7 days after last exposure

Vaccine no longer manufacturedVaccine no longer manufactured

Overview of Bioterrorism Agents

Botulism Botulism

Caused by toxin from Caused by toxin from Clostridium Clostridium botulinumbotulinum

Colorless, odorless and tastelessColorless, odorless and tasteless

Lethal dose for 70kg human is 1ng/kgLethal dose for 70kg human is 1ng/kgBotulinum toxin is the most lethal neurotoxin known to manBotulinum toxin is the most lethal neurotoxin known to man

Dispersal of aerosolized toxin, 1 gm of aerosolized toxin Dispersal of aerosolized toxin, 1 gm of aerosolized toxin could kill up to 1.5 million peoplecould kill up to 1.5 million people

Seven toxin typesSeven toxin typesHuman disease: A, B, E, and FHuman disease: A, B, E, and F

Animal disease: C, D, and GAnimal disease: C, D, and G

Overview of Bioterrorism Agents

Toxin production in foods prepared or stored at ambient temperature

Intestinal colonization and toxin production in susceptible

infants and adults

Colonization and toxin production in an open

wound

C. botulinum in the soil,

flora and fauna

Botulism:Acute, symmetric, descending flaccid

paralysis with bulbar palsies

Botulism: Epidemiology of Natural Transmission

Overview of Bioterrorism Agents

DescendingFlaccid Paralysis

Symmetric ParalysisVoluntary Muscles

1. Neck2. Shoulders3. Upper extremities4. Lower extremities

BP often normal; Mental status normal

 

Cranial Nerve Palsies

Cranial Nerves III, IV, VI, VII, IX

Blurry vision Diplopia Ptosis Expressionless Facies Regurgitation Dysarthria/Dysphagia

IncubationPeriod

Inhalational 24-72 hours

Foodborne 18-36 hours

(range 2 hours to 8 days) Dependent on toxin dose

IncubationPeriod

Inhalational 24-72 hours

Foodborne 18-36 hours

(range 2 hours to 8 days) Dependent on toxin dose

ExposureExposureClinical Presentation of Botulism

Overview of Bioterrorism Agents

Botulism: Medical Botulism: Medical ManagementManagement

Early administration of Early administration of antitoxinantitoxin

Supportive careSupportive careMonitoring respiratory functionMonitoring respiratory function

Providing mechanical ventilationProviding mechanical ventilationMay be needed for weeks or monthsMay be needed for weeks or months

Overview of Bioterrorism Agents

Botulism: AntitoxinBotulism: AntitoxinPreferably within 24 hours of Preferably within 24 hours of

symptom onsetsymptom onset

Type of antitoxin based on type of botulismType of antitoxin based on type of botulismBivalent antitoxin specific to serotype A and B,Bivalent antitoxin specific to serotype A and B,

Monovalent antitoxin specific to serotype E, and Monovalent antitoxin specific to serotype E, and

Heptavalent antitoxin specific against serotypes A, Heptavalent antitoxin specific against serotypes A, B, C, D, E, F, and GB, C, D, E, F, and G

1 vial per person1 vial per person

Acts by binding free systemic toxinActs by binding free systemic toxinDoes Does notnot reverse paralysis already present reverse paralysis already present

Overview of Bioterrorism Agents

Viral Hemorrhagic Fevers (VHF)Viral Hemorrhagic Fevers (VHF)Hemorrhagic fever viruses (RNA) belong to Hemorrhagic fever viruses (RNA) belong to

four taxonomic families: four taxonomic families: Filoviridae (Ebola/Marburg)Filoviridae (Ebola/Marburg)Arenaviridae (Bolivian HF))Arenaviridae (Bolivian HF))Bunyaviridae (Congo-Crimean HF)Bunyaviridae (Congo-Crimean HF)Flaviviridae (Dengue)Flaviviridae (Dengue)

Natural vectors – virus dependentNatural vectors – virus dependentRodents, mosquitoes, ticksRodents, mosquitoes, ticks

Natural occurrences have been seen in TexasNatural occurrences have been seen in Texas

Overview of Terrorism Agents

VHF as a Biological Weapon These viruses are considered

suitable weapons because:

— they have a low infectious dose

— they cause high morbidity and mortality

— they cause fear and panic in the general public

—effective vaccines are either not available, or supplies are limited

Overview of Bioterrorism Agents

Later Manifestations

External /Internal Hemorrhage• Ecchymosis• Petechiae• Bleeding from puncture site• Bleeding from nose and gums• Hemorrhagic conjunctivitis• Gastrointestinal bleeding• Severe vaginal bleeding• Pleural effusion• Renal Failure• Shock Laboratory Findings• Leukopenia or leukocytosis • Thrombocytopenia• Elevated Liver Function Tests• Anemia or Hemoconcentration• Prolonged PT, PTT

 

Early Manifestations

In general:• High fever• Headache• Myalgia• Arthralgia• Anorexia• Varying degrees of nausea, vomiting and diarrhea

IncubationPeriod

2-21 days (depending on

the virus)

IncubationPeriod

2-21 days (depending on

the virus)

ExposureExposure

Overview of Bioterrorism Agents

Clinical Timeline for VHF

Aggressive supportive care with Aggressive supportive care with intravenous fluids, colloids, blood intravenous fluids, colloids, blood products as neededproducts as needed

Specific therapy (ribavirin) may be Specific therapy (ribavirin) may be helpful in bunyaviruses and helpful in bunyaviruses and arenaviruses arenaviruses

Avoid IM injections or invasive Avoid IM injections or invasive procedures (due to bleeding)procedures (due to bleeding)

Strict aerosol precautions (i.e. Strict aerosol precautions (i.e. respiratory isolation)respiratory isolation)

VHF Clinical Management

Overview of Bioterrorism Agents

Tularemia

• Francisella tularensisFrancisella tularensis - Intracellular gram - Intracellular gram neg. coccobacillusneg. coccobacillus

• Zoonotic - usually ulceroglandular disease Zoonotic - usually ulceroglandular disease but also can be pneumonic diseasebut also can be pneumonic disease

• Presentation: Incubation 2-10 dPresentation: Incubation 2-10 d

• Mortality 35% untreated; < 10% treatedMortality 35% untreated; < 10% treated

Tularemia• Diagnosis: Culture/Gram’s stain blood, sputum, Diagnosis: Culture/Gram’s stain blood, sputum,

nodenode

• Isolation: Standard – No human-human Isolation: Standard – No human-human transmissiontransmission

• Treatment: Treatment:

StreptomycinStreptomycin Gentamicin Gentamicin Tetracycline Tetracycline

• If exposed: watch for 7 days, treat if fever developsIf exposed: watch for 7 days, treat if fever develops

Sources of InformationSources of InformationCenters for Disease Control Centers for Disease Control

(CDC)(CDC)www.cdc.govwww.cdc.gov

CDC Emergency Preparedness CDC Emergency Preparedness www.emergency.cdc.govwww.emergency.cdc.gov

CDC Quarantine and IsolationCDC Quarantine and Isolationwww.cdc.gov/ncldod/dp/index.htmwww.cdc.gov/ncldod/dp/index.htm

Overview of Bioterrorism Agents

CATEGORY B AGENTS

Definition

Second highest priority agents including those thatSecond highest priority agents including those that

are moderately easy to disseminateare moderately easy to disseminate

result in moderate morbidity rates and low mortality result in moderate morbidity rates and low mortality ratesrates

and require specific enhancements of the CDC’s and require specific enhancements of the CDC’s diagnostic capacity and enhanced disease diagnostic capacity and enhanced disease surveillance surveillance

Q FeverCoxiella burnetiiCoxiella burnetii

Presentation: Incubation 10-40 dPresentation: Incubation 10-40 d

• Sx variable - Fever, HA, myalgia, malaiseSx variable - Fever, HA, myalgia, malaise

• Occ. cough, rales, CXR infiltrateOcc. cough, rales, CXR infiltrate

• WBC usually normal, but WBC usually normal, but LFTs commonLFTs common

Low mortality, but malaise may last monthsLow mortality, but malaise may last months

Q FeverDiagnosis: Serology, Antibody or ELISADiagnosis: Serology, Antibody or ELISA

Isolation: StandardIsolation: Standard

Treatment: Antibiotics will shorten courseTreatment: Antibiotics will shorten course

TetracyclinesTetracyclines

Erythromycin, Azithromycin, Erythromycin, Azithromycin,

Quinolones, chloramphenicol, TMP/SMXQuinolones, chloramphenicol, TMP/SMX

Brucellosis

• Zoonotic, slow-growing gram neg. rodZoonotic, slow-growing gram neg. rod

• Presentation: Incubation 5-60 d or longerPresentation: Incubation 5-60 d or longer

• May last weeks or months, but rarely fatalMay last weeks or months, but rarely fatal

BrucellosisDiagnosis: Serology; Culture of blood, marrowDiagnosis: Serology; Culture of blood, marrow

• Isolation: Standard. Contact if open lesionsIsolation: Standard. Contact if open lesions

• Treatment: Combination antibioticsTreatment: Combination antibiotics

Most recover even without Most recover even without antibioticsantibiotics

Case 7 – Headache, Vomiting

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

• Better after fluids, acetaminophen -Released Better after fluids, acetaminophen -Released

• Returns following day with confusion, Returns following day with confusion, seizureseizure

Viral Encephalitis• Venezuelan, Eastern, Western Equine Venezuelan, Eastern, Western Equine

Encephalitis Encephalitis

• Presentation: Incubation 2-14 dPresentation: Incubation 2-14 d

• Fever, HA, myalgia, photophobia, vomitingFever, HA, myalgia, photophobia, vomiting

• Small % of VEE progress to neurologic sxSmall % of VEE progress to neurologic sx

• Delirium, coma, seizuresDelirium, coma, seizures

Viral Encephalitis• Diagnosis: Viral isolation or serologyDiagnosis: Viral isolation or serology

PCR for somePCR for some

• Isolation: StandardIsolation: Standard

• Treatment: SupportiveTreatment: SupportiveAnalgesics, AnticonvulsantsAnalgesics, Anticonvulsants

• Vaccines available, but poorly immunogenicVaccines available, but poorly immunogenic

Cases 8 – Vomiting, Diarrhea

• Multiple patients present to ER with Multiple patients present to ER with vomiting, diarrhea, headache, myalgias, vomiting, diarrhea, headache, myalgias, malaise, fever, chills, coughmalaise, fever, chills, cough

• All had been at a large outdoor festivalAll had been at a large outdoor festival

Staphylococcal Enterotoxin B

• Presentation: Incubation 1-6 hrsPresentation: Incubation 1-6 hrs

• Diagnosis: Clinical and epidemiological. Diagnosis: Clinical and epidemiological.

• Isolation: StandardIsolation: Standard

• Treatment: SupportiveTreatment: Supportive

Other Category B Agents• Epsilon toxin of Clostridium perfringensEpsilon toxin of Clostridium perfringens• Food safety threats (e.g., Salmonella species, Escherichia coli Food safety threats (e.g., Salmonella species, Escherichia coli

O157:H7, Shigella)O157:H7, Shigella)• Glanders (Burkholderia mallei)Glanders (Burkholderia mallei)• Melioidosis (Burkholderia pseudomallei)Melioidosis (Burkholderia pseudomallei)• Psittacosis (Chlamydia psittaci) Psittacosis (Chlamydia psittaci) • Q fever (Coxiella burnetii) Q fever (Coxiella burnetii) • Ricin toxin from Ricinus communis (castor beans)Ricin toxin from Ricinus communis (castor beans)• Typhus fever (Rickettsia prowazekii)Typhus fever (Rickettsia prowazekii)• Water safety threats (e.g., Vibrio cholerae, Cryptosporidium Water safety threats (e.g., Vibrio cholerae, Cryptosporidium

parvum)parvum)

CATEGORY C AGENTS

Definition

Third highest priority agents include emerging Third highest priority agents include emerging pathogens that could be engineered for mass pathogens that could be engineered for mass dissemination in the future because ofdissemination in the future because of

availabilityavailability

ease of production and disseminationease of production and dissemination

and potential for high morbidity and mortality and potential for high morbidity and mortality rates and major health impact rates and major health impact

Agents

• Emerging infectious diseases such as Emerging infectious diseases such as Nipah virus and hantavirusNipah virus and hantavirus

QUESTIONS…

…THE END