Bioterrorism:%20Getting%20the%20Big%20Picture

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Bioterrorism Getting the Big Picture

• Texas Society of Infection
• Control Practitioners

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This program has been created and made possible
through a grant from the Texas Department of
Health.
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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

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Objectives

• Name the 6 Category A Biological Agents,
  treatment and prophylaxis
• Discuss appropriate laboratory support systems
  for dealing with bioterrorism events
• Describe key concepts of Mental Health in
  Disasters/Bioterrorism

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Objectives

• List appropriate infection control precautions
  for Category A biological agents
• Identify security, transportation and
  communication needs in your facility
• Identify roles of external agencies in a disaster
  event

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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.

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Bioterrorism Agents

• Potentially hundreds
• Features of most likely agents
• Availability
• Ease of production
• Lethality
• Stability
• Infectivity

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Bioterrorism A Legitimate Threat

• Most agents relatively easy to produce
• Availability of information on the Internet
• Access to dual use equipment
• Relatively inexpensive
• 1970 studycost of 50 casualty rate per km2
• conventional - 2,000
• nuclear - 800
• anthrax - 1

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Bioterrorism A Legitimate Threat

• Dissemination may cover large area
• Difficult to detect release
• Symptoms occur days or weeks later
• Some have secondary spread

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Bioterrorism A Legitimate Threat

• Use can cause panic
• Users able to protect selves
• Users 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

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Bioterrorism A Legitimate Threat

• With the collapse of the Soviet Union, microbe
  stock technology has possibly landed in hands
  of terrorists
• State sponsorship of terrorism
• At least 17 nations are known to have offensive
  biological weapons programs

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Delivery Mechanisms

• Aerosol likely route for most agents
• Easiest to disperse
• Highest number of people exposed
• Most contagious route of infection
• Food / Waterborne less likely
• Only effective for some agents

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Epidemiology

• Clues suggesting a bioweapon release
• Large numbers present at once (epidemic)
• Previously healthy persons affected
• High morbidity and mortality
• Unusual syndrome or pathogen for region
• Recent terrorist claims or activity
• Unexplained epizootic of dead, sick animals

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Role of Primary Care Physician

• Have a high level of suspicion
• Keep BT agents in differential diagnosis
• Recognize typical BT disease syndromes
• Be aware of unusual epidemiologic trends
• Know treatment/prophylaxis of BT agents
• Know how to report suspected BT cases

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Bioterrorism-DiseasesRisk Category A
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Category A Biological Agents

• Can be easily disseminated or transmitted from
  person to person
• Result in high mortality rates and have the
  potential for major public health impact
• Might cause public panic and social disruption
• Require special action for public health
  preparedness

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Category A Biological Agents

• Anthrax
• Botulism
• Plague
• Smallpox
• Tularemia
• Viral Hemorrhagic Fever

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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

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Category B Biological Agents

• Brucellosis
• Epsilon toxin of Clostridium perfringens
• Food safety threats
• Salmonella
• E. coli O157h7
• Shigella

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Category B Biological Agents

• Glanders
• Melioidosis
• Psittacosis
• Q Fever
• Ricin toxin
• Staphylococcal enterotoxin B

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Category B Biological Agents

• Typhus fever
• Viral encephalitis
• Water safety threats
• Vibrio cholerae
• Cryptosporidium

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Category C Biological Agents

• Third highest priority agents include emerging
  pathogens that could be engineered for mass
  dissemination in the future because of
• availability
• ease of production and dissemination and
• potential for high morbidity and mortality rates
  and major health impact

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Category C Biological Agents

• Emerging infectious diseases
• Nipah virus
• Hantavirus

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Common Clinical Manifestations of Bioterrorism
Agents

• Skin lesions w/fever
• Acute respiratory distress w/fever
• Influenza-like illness
• Neurologic syndromes

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Skin Lesions w/Fever

• Smallpox
• Cutaneous Anthrax

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Acute Respiratory Distress w/Fever

• Inhalation Anthrax
• Pneumonic Plague

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Flu-like Illnesses

• Tularemia
• Inhalational Anthrax
• Viral Hemorrhagic Fever
• Smallpox
• (Pretty much everything except the kitchen sink!)

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Neurologic Illnesses

• Ricin
• VX
• Sarin gas
• Mustard gas
• Botulism

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Smallpox
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Smallpox History

• Caused by variola virus
• Most deaths of any infectious disease
• 500 million deaths in 20th Century
• 2 million deaths in 1967
• Known in ancient times
• Described by Ramses
• Natural disease eradicated
• Last U.S. case 1949 (imported)
• Last international case 1978
• Declared eradicated in 1979

Photo National Archives
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Smallpox Bioweapon Potential

• Features making smallpox a likely agent
• Can be produced in large quantities
• Stable for storage and transportation
• Known to produce stable aerosol
• High mortality
• Highly infectious
• Person-to-person spread
• Most of the world has little or no immunity

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Smallpox Bioweapon Potential

• Current concerns
• Former Soviet Union scientists have confirmed
  that smallpox was successfully weaponized for use
  in bombs and missiles
• Active research was undertaken to engineer more
  virulent strains
• Possibility of former Soviet Union virus stock in
  unauthorized hands

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Smallpox Bioweapon Potential

• Nonimmune population
• lt20 of U.S. with substantial immunity
• Availability of virus
• Officially only 2 stocks (CDC and Russia)
• Potential for more potent attack
• Combined with other agent (e.g. VHF)
• Engineered resistance to vaccine

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Smallpox Bioweapon Potential

• Delivery mechanisms
• Aerosol
• 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 affected
• Incubation period
• From infection to onset of prodrome
• Range 7-17 days
• Typical 12-14 days

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Smallpox Epidemiology

• Transmission
• Airborne route known effective mode
• Initially via aerosol in BT attack
• Then person-to-person
• Hospital outbreaks from coughing patients
• Highly infectious
• lt10 virions sufficient to cause infection
• Aerosol exposure lt15 minutes sufficient

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Smallpox Epidemiology

• Person-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

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Smallpox Epidemiology

• Transmission via fomites
• Contaminated hospital linens/laundry
• May have been successfully used as weapon in
  French-Indian War

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Smallpox Epidemiology

• Infectiousness Rash is marker
• Onset approx one day before rash
• Peaks 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

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Smallpox Epidemiology

• Infectious Materials
• Saliva
• Vesicular fluid
• Scabs
• Urine
• Conjunctival fluid
• Possibly blood

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Smallpox Epidemiology

• Role of index case severity
• Does not predict transmissibility
• Does not predict severity of 2 cases
• Role of prior vaccination
• Immunity wanes with time
• Maintain partial immunity for many years
• Partial immunity reduces disease severity
• Reduces transmissibility (less virus shed)

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Smallpox Epidemiology

• Mortality
• 25-30 overall in unvaccinated population
• Infants, elderly greatest risk (gt40)
• Higher in immunocompromised
• May be dependent on ICU facilities
• Dependent on virus strain
• Dependent on disease variant

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Smallpox Epidemiology

• Factors that allowed smallpox eradication
• Slow spread
• Effective, relatively safe vaccine
• No animal/insect vectors
• No sig. carrier state (infected die or recover)
• Infectious only with symptoms
• Prior infection gives lifelong immunity
• International cooperation

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Smallpox Microbiology

• Variola 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 major
• Classic smallpox
• Predominant form in Asian epidemics
• Highest mortality (30)

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Smallpox Microbiology

• Variola minor
• Same incubation period, mode of transmission,
  clinical presentation
• Causes milder disease
• Less severe prodrome and rash
• Mortality 1
• Discovered in 20th century
• Started in S. Africa
• Was most predominant form in N. America

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Smallpox Microbiology

• Environmental survival
• Longest (gt24hr) in low temp/low humidity
• Inactive within few hours in high temp/humidity
• Dispersed aerosol
• completely inactivated within 2 days of release

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Smallpox Pathogenesis

• Virus lands on respiratory/oral mucosa
• Macrophages carry to regional nodes
• Primary viremia on Day 3
• Invades reticuloendothelial organs
• Secondary viremia on Day 8

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Smallpox Pathogenesis

• White Blood Cells infected
• WBCs migrate capillaries, invade dermis
• Infects dermal cells
• Influx of WBCs, mediators cause vesicle
• Systemic inflammatory response
• Triggered by viremia
• Sepsis, multiorgan failure, often DIC

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Smallpox Pathogenesis

• Severity of disease
• Not influenced by severity of source case
• Probably 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

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Smallpox Clinical Features

• Three stages of disease
• Incubation
• Asymptomatic
• Prodromal
• Nonspecific febrile illness, flu-like
• Eruptive
• Characteristic rash

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Smallpox Clinical Features

• Incubation Stage
• From time of infection to onset of symptoms
• Average 12-14 days (range 7-17)
• Important for epidemiologic investigation
• Considered non-infectious during this stage
• Virus sometimes culturable

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Smallpox Clinical Features

• Prodromal Stage
• Common 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

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Smallpox Clinical Features

• Eruptive Stage (Rash)
• May start with transient defervescence
• Characteristic 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 development
• All lesions in one region at same stage
• Starts macular, then papular
• Deep, tense vesicles by Day 2 of rash
• Turns to round, tense, deep pustules
• Pustules dry to scabs by Day 9
• Scabs separate

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Classic Smallpox Rash, Demonstrating Same
Development Stage (Pustular) of All Lesions in a
Region
Photo National Archives
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Smallpox
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Smallpox Clinical Features

• Scarring
• From separated scabs
• Fibrosis, granulation in sebaceous glands
• Pink, depressed pock marks
• Prominent on face, usually gt5 lesions
• Permanent

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Smallpox Clinical Features

• Rash variations
• Sine eruptione variant
• Prodrome without rash
• Clinically less severe

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Smallpox Clinical Features

• Modified variant
• Previously vaccinated with partial immunity
• Milder rash, better outcome, faster resolution

Photo National Archives
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Smallpox Clinical Features

• Rash variations
• Ordinary (Classic presentation) variant
• gt90 all cases
• Subdivided based on confluence of lesions
• Discrete (lt10 mortality)
• Semi-confluent (25-50 mortality), most common
• Confluent (50-75 mortality)

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Photo National Archives
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Photo National Archives
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Smallpox Clinical Features

• Rash 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
• gt90 mortality

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Smallpox Clinical Features

• Rash 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

• Complications
• Sepsis/toxemia
• Usual cause of death
• Associated with multiorgan failure
• Usually occurs during 2nd week of illness
• Encephalitis
• Occasional
• Similar to demyelination of measles, varicella

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Smallpox Clinical Features

• Complications
• Secondary 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

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Smallpox Diagnosis

• Clinical diagnosis
• Sufficient in outbreak setting
• gt90 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 methods
• Electron microscopy of vesicle fluid
• Rapidly confirms if orthopoxvirus
• Culture on chick membrane or cell culture
• Slow, specific for variola
• Newer rapid tests
• Available only at reference labs (e.g. CDC)
• PCR, RFLP

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Smallpox Diagnosis

• Differential Diagnosis
• Chickenpox (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

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Smallpox Chickenpox

• Physical 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 exam
• Central distribution
• Peaks at 3-5 days
• Lesions in different stages of evolution
• 2-4 mm diameter
• Oval shape
• Desquamation in 6-14 days
• Uncommon to have lesions on palms and sole

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Smallpox Chickenpox
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Smallpox Treatment

• Management of cases
• Supportive
• Post-exposure prophylaxis
• Vaccine
• Vaccinia immunoglobulin
• Primary prophylaxis
• Vaccine

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Smallpox Treatment

• Managing confirmed or suspected cases
• No specific effective antiviral treatment
• Supportive care is critical
• Electrolytes / Volume / Ventilation / Pressors
• Antibiotics only for secondary infections
• e.g. S. aureus cellulitis
• Isolation
• Vaccinate (in case diagnosis is wrong)

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Smallpox Post-Exposure Prophylaxis

• Vaccine
• Protective 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 mortality
• Passive immunity for 2 weeks
• Very limited supply (at CDC)

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Smallpox Infection Control

• Vital component of outbreak management
• Transmission is key
• No animal/arthropod vectors
• No known asymptomatic reservoirs
• carrier state hypothetical but not confirmed
• Higher rate in cool, dry conditions

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Smallpox Infection Control

• Transmission
• Overall secondary attack rate 25-40
• Historically 3-4 cases per index patient
• Outbreak in mostly nonimmune population
• Anticipate 10-20 cases per contact
• All body fluids infectious
• Respiratory secretions main culprit
• Cough dramatically increases transmission

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Smallpox Infection Control

• Period of infectiousness
• Onset usually 1 day before rash
• associated with mucosal lesions
• sometimes transient defervescense at end of
  prodromal stage
• Lasts until all lesions scabbed over
• Longer duration with more severe cases

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Smallpox Infection Control

• Isolation of Cases
• Home 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 Contacts
• Carefully 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 Control

• Management of Case Contacts
• Vaccination
• Proven benefit given within 3-4 days of exposure
• Observation for 17 days
• Twice daily temperature check
• Isolation if fever gt 38.0º C

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Smallpox Infection Control

• Handling of specimens
• BSL4 laboratory containment only
• Handling of linens/laundry
• Place in leak-proof containers
• Autoclave before laundering
• Launder in hot water bleach
• Cremation recommended for corpses

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Smallpox Infection Control

• Surveillance and containment critical
• Correct identification of those at risk
• Conservation of vaccine
• Target only those with true risk
• Limited national supply
• Components
• Aggressive case-seeking
• Aggressive contact-seeking observation

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Smallpox Decontamination

• Original aerosol release setting
• Likely no decontamination applicable
• Rapid dispersion of virus
• lt6 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

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Smallpox Decontamination

• If known recent release
• HEPA filtration
• Sterilization of surfaces
• Standard disinfectants such as bleach

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Smallpox Essential Pearls

• Smallpox has been weaponized
• Case fatality will likely approach 30
• Clinical diagnosis
• Asymptomatic incubation period 7-17 days
• Prodrome with high fever 3-5 days
• Eruptive phase with typical rash
• Centrifugal (head, face, hands/palms, feet/soles)
• Vesicles all same stage of development

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Smallpox Essential Pearls

• Highly infectious
• Not infectious prior to fever onset
• Infectiousness starts one day before rash
• Lasts until all lesions scabbed over
• Secondary attack rate 25-40
• Expect 10-20 2º cases per index case
• No specific treatment, only supportive

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Smallpox Essential Pearls

• Case 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 gt38.0

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Smallpox Essential Pearls

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