bioterrorism: getting the big picture texas society of infection control practitioners

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


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.


Bioterrorism Agents

Potentially hundredsFeatures of most likely agents

AvailabilityEase of productionLethalityStabilityInfectivity


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



Dissemination may cover large area Difficult to detect releaseSymptoms occur days or weeks laterSome have secondary spread



Use can cause panicUsers able to protect selvesUsers can escape before effect



Former Soviet scientists successfully weaponized many agents Active research was undertaken to engineer more virulent strains



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


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


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


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


Category A Biological Agents

AnthraxBotulismPlagueSmallpoxTularemiaViral Hemorrhagic Fever


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



BrucellosisEpsilon toxin of Clostridium perfringensFood safety threats

SalmonellaE. coli O157:h7Shigella



GlandersMelioidosisPsittacosisQ FeverRicin toxinStaphylococcal enterotoxin B



Typhus feverViral encephalitisWater safety threats

Vibrio choleraeCryptosporidium


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


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


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


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


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



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



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


Smallpox: Epidemiology

All ages and genders affectedIncubation period

From infection to onset of prodromeRange 7-17 daysTypical 12-14 days



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


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



Transmission via fomitesContaminated hospital linens/laundryMay have been successfully used as weapon in French-Indian War


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



Infectious MaterialsSalivaVesicular fluidScabsUrineConjunctival fluidPossibly blood



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)



Mortality25-30% overall in unvaccinated populationInfants, elderly greatest risk (>40%)Higher in immunocompromisedMay be dependent on ICU facilitiesDependent on virus strainDependent on disease variant


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


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


Smallpox: Microbiology

Variola majorClassic smallpoxPredominant form in Asian epidemicsHighest mortality (~30%)



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



Environmental survivalLongest (>24hr) in low temp/low humidityInactive within few hours in high temp/humidityDispersed aerosol • completely inactivated within 2 days of

release


Smallpox: Pathogenesis

Virus lands on respiratory/oral mucosaMacrophages carry to regional nodesPrimary viremia on Day 3Invades reticuloendothelial organsSecondary viremia on Day 8


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


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


Smallpox: Clinical Features

Three stages of diseaseIncubation• Asymptomatic

Prodromal• Nonspecific febrile illness, flu-like

Eruptive• Characteristic rash



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



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



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


Classic Centrifugal Rash of Smallpox Involving Face and Extremities,Including the Soles.

Photo: National Archives



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


Smallpox



ScarringFrom separated scabsFibrosis, granulation in sebaceous glandsPink, depressed pock marksProminent on face, usually >5 lesionsPermanent



Rash variationsSine eruptione variant• Prodrome without rash• Clinically less severe



Modified variantPreviously vaccinated with partial immunityMilder rash, better outcome, faster resolution




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)


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


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%



In an outbreak setting atypical or variant rashes must be considered smallpox until proven otherwise



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



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


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


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


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


Smallpox Chickenpox


Smallpox: Treatment

Management of casesSupportive

Post-exposure prophylaxisVaccineVaccinia immunoglobulin

Primary prophylaxisVaccine


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)


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)


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


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


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



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



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


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



Handling of specimensBSL4 laboratory containment only

Handling of linens/laundryPlace in leak-proof containersAutoclave before launderingLaunder in hot water & bleach

Cremation recommended for corpses



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


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


Smallpox: Decontamination

If known recent releaseHEPA filtrationSterilization of surfaces• Standard disinfectants such as bleach


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


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


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


Smallpox Essential Pearls

Report any suspected smallpox cases to your State and Local Health Departments

bioterrorism: getting the big picture texas society of infection control practitioners

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