Bioterrorism: Getting the Big Picture
Texas Society of Infection Control Practitioners
Saint Louis Unversity School of Public Health
This program has been created and made possible through a grant from the Texas Department of Health.
Goal
At the end of this workshop Infection Control Practitioners will be able to describe various components necessary to develop and implement a successful bioterrorism preparedness program
Objectives
Name the 6 Category A Biological Agents, treatment and prophylaxisDiscuss appropriate laboratory support systems for dealing with bioterrorism eventsDescribe key concepts of Mental Health in Disasters/Bioterrorism
Objectives
List appropriate infection control precautions for Category A biological agentsIdentify security, transportation and communication needs in your facilityIdentify roles of external agencies in a disaster event
Saint Louis Unversity School of Public Health
Definition of Bioterrorism
The unlawful use, or threatened use, of microorganisms or toxins derived from living organisms to produce death or disease in humans, animals, or plants. The act is intended to create fear and/or intimidate governments or societies in the pursuit of political,religious, or ideological goals.
Saint Louis Unversity School of Public Health
Bioterrorism Agents
Potentially hundredsFeatures of most likely agents
AvailabilityEase of productionLethalityStabilityInfectivity
Saint Louis Unversity School of Public Health
Bioterrorism: A Legitimate Threat
Most agents relatively easy to produce
Availability of information on the InternetAccess to dual use equipment
Relatively inexpensive1970 study–cost of 50% casualty rate per km2
• conventional - $2,000• nuclear - $800• anthrax - $1
Saint Louis Unversity School of Public Health
Bioterrorism: A Legitimate Threat
Dissemination may cover large area Difficult to detect releaseSymptoms occur days or weeks laterSome have secondary spread
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Bioterrorism: A Legitimate Threat
Use can cause panicUsers able to protect selvesUsers can escape before effect
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Bioterrorism: A Legitimate Threat
Former Soviet scientists successfully weaponized many agents Active research was undertaken to engineer more virulent strains
Saint Louis Unversity School of Public Health
Bioterrorism: A Legitimate Threat
With the collapse of the Soviet Union, microbe stock & technology has possibly landed in hands of terroristsState sponsorship of terrorismAt least 17 nations are known to have offensive biological weapons programs
Saint Louis Unversity School of Public Health
Delivery Mechanisms
Aerosol likely route for most agents
Easiest to disperse Highest number of people exposedMost contagious route of infection
Food / Waterborne less likelyOnly effective for some agents
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Epidemiology
Clues suggesting a bioweapon releaseLarge numbers present at once (epidemic)Previously healthy persons affectedHigh morbidity and mortalityUnusual syndrome or pathogen for regionRecent terrorist claims or activityUnexplained epizootic of dead, sick animals
Saint Louis Unversity School of Public Health
Role of Primary Care Physician
Have a high level of suspicionKeep BT agents in differential diagnosis
Recognize typical BT disease syndromesBe aware of unusual epidemiologic trendsKnow treatment/prophylaxis of BT agentsKnow how to report suspected BT cases
Bioterrorism-DiseasesRisk Category A
Centers for Disease Control
Category A Biological AgentsCan be easily disseminated or transmitted from person to personResult in high mortality rates and have the potential for major public health impactMight cause public panic and social disruptionRequire special action for public health preparedness
Centers for Disease Control
Category A Biological Agents
AnthraxBotulismPlagueSmallpoxTularemiaViral Hemorrhagic Fever
Centers for Disease Control
Category B Biological Agents
Are moderately easy to disseminate
Result in moderate morbidity rates and low mortality rates
Require specific enhancements of CDC's diagnostic capacity and enhanced disease surveillance
Centers for Disease Control
Category B Biological Agents
BrucellosisEpsilon toxin of Clostridium perfringensFood safety threats
SalmonellaE. coli O157:h7Shigella
Centers for Disease Control
Category B Biological Agents
GlandersMelioidosisPsittacosisQ FeverRicin toxinStaphylococcal enterotoxin B
Centers for Disease Control
Category B Biological Agents
Typhus feverViral encephalitisWater safety threats
Vibrio choleraeCryptosporidium
Centers for Disease Control
Category C Biological Agents
Third highest priority agents include emerging pathogens that could be engineered for mass dissemination in the future because of:
availabilityease of production and dissemination and potential for high morbidity and mortality rates and major health impact
Centers for Disease Control
Category C Biological Agents
Emerging infectious diseases Nipah virus Hantavirus
Common Clinical Manifestations of Bioterrorism Agents
Skin lesions w/fever Acute respiratory distress w/feverInfluenza-like illness Neurologic syndromes
Skin Lesions w/Fever
SmallpoxCutaneous Anthrax
Acute Respiratory Distress w/Fever
Inhalation AnthraxPneumonic Plague
Flu-like Illnesses
TularemiaInhalational AnthraxViral Hemorrhagic FeverSmallpox
(Pretty much everything except the kitchen sink!)
Neurologic Illnesses
RicinVXSarin gasMustard gasBotulism
Smallpox
Saint Louis Unversity School of Public Health
Smallpox: HistoryCaused by variola virusMost deaths of any infectious disease
~500 million deaths in 20th Century~2 million deaths in 1967
Known in ancient timesDescribed by Ramses
Natural disease eradicatedLast U.S. case – 1949 (imported)Last international case – 1978Declared eradicated in 1979 Photo: National
Archives
Saint Louis Unversity School of Public Health
Smallpox: Bioweapon Potential
Features making smallpox a likely agent
Can be produced in large quantitiesStable for storage and transportationKnown to produce stable aerosolHigh mortalityHighly infectiousPerson-to-person spreadMost of the world has little or no immunity
Saint Louis Unversity School of Public Health
Smallpox: Bioweapon PotentialCurrent concerns
Former Soviet Union scientists have confirmed that smallpox was successfully weaponized for use in bombs and missilesActive research was undertaken to engineer more virulent strainsPossibility of former Soviet Union virus stock in unauthorized hands
Saint Louis Unversity School of Public Health
Smallpox: Bioweapon Potential
Nonimmune population<20% of U.S. with substantial immunity
Availability of virusOfficially only 2 stocks (CDC and Russia)
Potential for more potent attackCombined with other agent (e.g. VHF)Engineered resistance to vaccine
Saint Louis Unversity School of Public Health
Smallpox: Bioweapon Potential
Delivery mechanismsAerosol• Easiest to disperse • Highest number of people exposed• Most contagious route of infection• Most likely to be used in bioterrorist
attack
Fomites• Theoretically possible but inefficient
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Smallpox: Epidemiology
All ages and genders affectedIncubation period
From infection to onset of prodromeRange 7-17 daysTypical 12-14 days
Saint Louis Unversity School of Public Health
Smallpox: Epidemiology
TransmissionAirborne route known effective mode• Initially via aerosol in BT attack• Then person-to-person• Hospital outbreaks from coughing
patients
Highly infectious• <10 virions sufficient to cause infection• Aerosol exposure <15 minutes sufficient
Saint Louis Unversity School of Public Health
Smallpox: EpidemiologyPerson-to-person transmission
Secondary Attack Rate (SAR)• 25-40% in unvaccinated contacts
Relatively slow spread in populations (compared to measles, etc.)
• Higher during cool, dry conditions
Historically 3-4 contacts infected• May be 10-20 in unvaccinated population
Very high potential for nosocomial spread Usually requires face-to-face contact
Saint Louis Unversity School of Public Health
Smallpox: Epidemiology
Transmission via fomitesContaminated hospital linens/laundryMay have been successfully used as weapon in French-Indian War
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Smallpox: EpidemiologyInfectiousness – Rash is marker
Onset approx one day before rashPeaks during first week of rash? Carrier state possible• Some data show virus detectable in
saliva of contacts who never become infected
• Unclear if they can transmit infection, but theoretically possible
Saint Louis Unversity School of Public Health
Smallpox: Epidemiology
Infectious MaterialsSalivaVesicular fluidScabsUrineConjunctival fluidPossibly blood
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Smallpox: Epidemiology
Role of index case severityDoes not predict transmissibilityDoes not predict severity of 2° cases
Role of prior vaccinationImmunity wanes with time• Maintain partial immunity for many years• Partial immunity reduces disease severity
Reduces transmissibility (less virus shed)
Saint Louis Unversity School of Public Health
Smallpox: Epidemiology
Mortality25-30% overall in unvaccinated populationInfants, elderly greatest risk (>40%)Higher in immunocompromisedMay be dependent on ICU facilitiesDependent on virus strainDependent on disease variant
Saint Louis Unversity School of Public Health
Smallpox: EpidemiologyFactors that allowed smallpox eradication
Slow spreadEffective, relatively safe vaccineNo animal/insect vectorsNo sig. carrier state (infected die or recover)Infectious only with symptomsPrior infection gives lifelong immunityInternational cooperation
Saint Louis Unversity School of Public Health
Smallpox: MicrobiologyVariola virus – the agent of smallpox
Orthopoxviridae family• 2 strains of variola
– Variola major– Variola minor
• Vaccinia– Used for current vaccine– Namesake of “vaccine”
• Cowpox – used by Jenner in first vaccine• Monkeypox – rare but serious disease from
monkeys in Africa
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Smallpox: Microbiology
Variola majorClassic smallpoxPredominant form in Asian epidemicsHighest mortality (~30%)
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Smallpox: Microbiology
Variola minorSame incubation period, mode of transmission, clinical presentationCauses milder disease • Less severe prodrome and rash• Mortality ~1%
Discovered in 20th centuryStarted in S. AfricaWas most predominant form in N. America
Saint Louis Unversity School of Public Health
Smallpox: Microbiology
Environmental survivalLongest (>24hr) in low temp/low humidityInactive within few hours in high temp/humidityDispersed aerosol • completely inactivated within 2 days of
release
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Smallpox: Pathogenesis
Virus lands on respiratory/oral mucosaMacrophages carry to regional nodesPrimary viremia on Day 3Invades reticuloendothelial organsSecondary viremia on Day 8
Saint Louis Unversity School of Public Health
Smallpox: Pathogenesis
White Blood Cells infectedWBCs migrate capillaries, invade dermisInfects dermal cellsInflux of WBCs, mediators cause vesicle
Systemic inflammatory responseTriggered by viremiaSepsis, multiorgan failure, often DIC
Saint Louis Unversity School of Public Health
Smallpox: PathogenesisSeverity of disease
Not influenced by severity of source caseProbably related to degree of viremia
• Inoculation dose– Longer exposure, higher concentration at
release
• Virulence of variola– strain, engineered resistance
• Host immune status
Type of rash predictive of outcome• More severe rashes = poorer outcomes
Saint Louis Unversity School of Public Health
Smallpox: Clinical Features
Three stages of diseaseIncubation• Asymptomatic
Prodromal• Nonspecific febrile illness, flu-like
Eruptive• Characteristic rash
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Smallpox: Clinical Features
Incubation StageFrom time of infection to onset of symptomsAverage 12-14 days (range 7-17)Important for epidemiologic investigationConsidered non-infectious during this stage• Virus sometimes culturable
Saint Louis Unversity School of Public Health
Smallpox: Clinical Features
Prodromal StageCommon symptoms• High fever, prostration, low back
myalgias, HA
Occasional symptoms• Vomiting, abdominal pain, delirium
Duration typically 3-5 days• End of stage heralded by mucosal lesions• Mucosal lesions onset of infectiousness
Saint Louis Unversity School of Public Health
Smallpox: Clinical Features
Eruptive Stage (Rash)May start with transient defervescenceCharacteristic rash
• Centrifugal (in order of appearance & severity)• Initially oral mucosa– borders pre-eruptive stage• Head, face• Forearms, hands, palms• Legs, soles, +/- trunk
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Classic Centrifugal Rash of Smallpox Involving Face and Extremities,Including the Soles.
Photo: National Archives
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Smallpox: Clinical Features
Rash stages of developmentAll lesions in one region at same stage Starts macular, then papularDeep, tense vesicles by Day 2 of rashTurns to round, tense, deep pustulesPustules dry to scabs by Day 9Scabs separate
Classic Smallpox Rash, Demonstrating Same Development Stage (Pustular) of All Lesions in a Region
Photo: National Archives
Smallpox
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Smallpox: Clinical Features
ScarringFrom separated scabsFibrosis, granulation in sebaceous glandsPink, depressed pock marksProminent on face, usually >5 lesionsPermanent
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Smallpox: Clinical Features
Rash variationsSine eruptione variant• Prodrome without rash• Clinically less severe
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Smallpox: Clinical Features
Modified variantPreviously vaccinated with partial immunityMilder rash, better outcome, faster resolution
Photo: National Archives
Saint Louis Unversity School of Public Health
Smallpox: Clinical Features
Rash variationsOrdinary (Classic presentation) variant• >90% all cases• Subdivided based on confluence of
lesions– Discrete (<10% mortality)– Semi-confluent (25-50% mortality), most
common– Confluent (50-75% mortality)
Saint Louis Unversity School of Public Health
Photo: National Archives
Saint Louis Unversity School of Public Health
Photo: National Archives
Saint Louis Unversity School of Public Health
Smallpox: Clinical FeaturesRash variations
Flat (Malignant) variant• Uncommon• Prodrome more sudden, severe• More likely severe abdominal pain• Rash never forms pustules/scabs• Leathery in appearance• Sometimes hemorrhagic or exfoliating• DDX – acute abdomen, hemorrhagic
varicella• >90% mortality
Saint Louis Unversity School of Public Health
Smallpox: Clinical FeaturesRash variations
Hemorrhagic• Rare• Prodrome more acute and severe• Bleeding diathesis before onset of rash• Rash is also hemorrhagic• Pregnant women at highest risk (?immune
state)• Higher risk of transmission (more fluid
shedding)• DDX – meningococcemia, DIC• Mortality 100%
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Smallpox: Clinical Features
In an outbreak setting atypical or variant rashes must be considered smallpox until proven otherwise
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Smallpox: Clinical Features
ComplicationsSepsis/toxemia• Usual cause of death• Associated with multiorgan failure• Usually occurs during 2nd week of illness
Encephalitis• Occasional• Similar to demyelination of measles,
varicella
Saint Louis Unversity School of Public Health
Smallpox: Clinical Features
ComplicationsSecondary bacterial infections uncommon • Staphylococcus aureus cellulitis
– Responds to appropriate antibiotics
• Corneal ulcers– A leading cause of blindness before 20th Century
Conjunctivitis rare• During 1st week of illness
Saint Louis Unversity School of Public Health
Smallpox: Diagnosis
Clinical diagnosisSufficient in outbreak setting>90% have classical syndrome
• Prodrome followed by rash
Rarely, variants can be difficult to recognize• Hemorrhagic – mimics meningococcemia• Malignant – more rapidly fatal• Sine eruptione – prodrome without rash• Partially immune – milder, often atypical
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Smallpox: Diagnosis
Traditional confirmatory methodsElectron microscopy of vesicle fluid• Rapidly confirms if orthopoxvirus
Culture on chick membrane or cell culture• Slow, specific for variola
Newer rapid testsAvailable only at reference labs (e.g. CDC)PCR, RFLP
Saint Louis Unversity School of Public Health
Smallpox: Diagnosis
Differential DiagnosisChickenpox (varicella)• Vesicles shallow, in crops, varied stages• Centripetal, spares palms/soles
Other orthopox viruses• Monkeypox – only in Africa, monkey
contact• Vaccinia – after exposure to vaccine• Cowpox – rare, only in UK
Smallpox ChickenpoxPhysical exam
Centrifugal distribution
Peaks at 7 to 10 days
Lesions in same stage of evolution
4-6 mm diameter
Round shape
Desquamation in 14-21 days
Lesions on palms and sole
Physical examCentral distributionPeaks at 3-5 daysLesions in different stages of evolution2-4 mm diameterOval shapeDesquamation in 6-14 daysUncommon to have lesions on palms and sole
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Smallpox Chickenpox
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Smallpox: Treatment
Management of casesSupportive
Post-exposure prophylaxisVaccineVaccinia immunoglobulin
Primary prophylaxisVaccine
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Smallpox: Treatment
Managing confirmed or suspected cases
No specific effective antiviral treatmentSupportive care is critical• Electrolytes / Volume / Ventilation / Pressors
Antibiotics only for secondary infections• e.g. S. aureus cellulitis
IsolationVaccinate (in case diagnosis is wrong)
Saint Louis Unversity School of Public Health
Smallpox: Post-Exposure Prophylaxis
VaccineProtective if given within 3-4 days exposure
• Reduces incidence 2-3 fold• Decreases mortality by ~50%
Vaccinia immune globulin (VIG)3 fold decrease in incidence and mortalityPassive immunity for 2 weeksVery limited supply (at CDC)
Saint Louis Unversity School of Public Health
Smallpox: Infection ControlVital component of outbreak managementTransmission is key
No animal/arthropod vectorsNo known asymptomatic reservoirs• carrier state hypothetical but not
confirmed
Higher rate in cool, dry conditions
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Smallpox: Infection ControlTransmission
Overall secondary attack rate 25-40%Historically 3-4 cases per index patientOutbreak in mostly nonimmune population• Anticipate 10-20 cases per contact
All body fluids infectiousRespiratory secretions main culprit• Cough dramatically increases transmission
Saint Louis Unversity School of Public Health
Smallpox: Infection Control
Period of infectiousnessOnset usually 1 day before rash• associated with mucosal lesions • sometimes transient defervescense at
end of prodromal stage
Lasts until all lesions scabbed overLonger duration with more severe cases
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Smallpox: Infection Control
Isolation of CasesHome isolation is preferable• Avoids nosocomial spread
Droplet and inoculation protection • Contact precautions – glove, gown, face
shield
Aerosol protection• Negative pressure room, HEPA filter
Assign immune persons for care
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Smallpox: Infection Control
Management of Case ContactsCarefully identify true contacts• Exposure to a case patient after fever onset• Contact with secretions OR• Face-to-face contact OR• In nosocomial setting with a case
– Includes ALL hospital patients and staff
• Except for nosocomial, large group exposure unlikely – usually bedridden by fever onset
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Smallpox: Infection ControlManagement of Case Contacts
Vaccination• Proven benefit given within 3-4 days
of exposure
Observation for 17 days• Twice daily temperature check• Isolation if fever > 38.0º C
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Smallpox: Infection Control
Handling of specimensBSL4 laboratory containment only
Handling of linens/laundryPlace in leak-proof containersAutoclave before launderingLaunder in hot water & bleach
Cremation recommended for corpses
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Smallpox: Infection Control
Surveillance and containment criticalCorrect identification of those at riskConservation of vaccine• Target only those with true risk• Limited national supply
ComponentsAggressive case-seekingAggressive contact-seeking & observation
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Smallpox: Decontamination
Original aerosol release settingLikely no decontamination applicable• Rapid dispersion of virus
– <6 hours in higher heat, humidity– Most gone by 24 hours even under ideal
conditions– Completely dissipated by 2 days
• Delayed onset of symptoms (at least 1 week)
Virus long gone by time of index case recognition in covert release
Saint Louis Unversity School of Public Health
Smallpox: Decontamination
If known recent releaseHEPA filtrationSterilization of surfaces• Standard disinfectants such as bleach
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Smallpox Essential PearlsSmallpox has been weaponizedCase fatality will likely approach 30%Clinical diagnosis
Asymptomatic incubation period 7-17 daysProdrome with high fever 3-5 daysEruptive phase with typical rash
• Centrifugal (head, face, hands/palms, feet/soles)
• Vesicles all same stage of development
Saint Louis Unversity School of Public Health
Smallpox Essential Pearls
Highly infectiousNot infectious prior to fever onsetInfectiousness starts one day before rashLasts until all lesions scabbed over
Secondary attack rate 25-40%Expect 10-20 2º cases per index case
No specific treatment, only supportive
Saint Louis Unversity School of Public Health
Smallpox Essential PearlsCase identification & isolation essential
Droplets / secretions (contact isolation)Aerosols (negative pressure isolation)Isolate at home if possible (quarantine)
Post-exposure prophylaxis for contacts
Vaccine (with VIG for hi-risk groups)Fever observation x 17days, isolate if >38.0
Saint Louis Unversity School of Public Health
Smallpox Essential Pearls
Report any suspected smallpox cases to your State and Local Health Departments