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Bioterrorism:
Getting the Big Picture
Texas Society of Infection
Control Practitioners
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 prophylaxis
Discuss appropriate laboratory support
systems for dealing with bioterrorism
events
Describe key concepts of Mental Health
in Disasters/Bioterrorism
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
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 hundreds
Features of most likely agents
Availability
Ease of production
Lethality
Stability
Infectivity
Saint Louis Unversity School of
Public Health
Bioterrorism: A Legitimate Threat
Most agents relatively easy to produce
Availability of information on the Internet
Access to dual use equipment
Relatively inexpensive
1970 study–cost of 50% casualty rate per km2
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•
•
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 release
Symptoms occur days or weeks later
Some have secondary spread
Saint Louis Unversity School of
Public Health
Bioterrorism: A Legitimate
Threat
Use can cause panic
Users able to protect selves
Users can escape before effect
Saint Louis Unversity School of
Public Health
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 terrorists
State sponsorship of terrorism
At 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 exposed
Most contagious route of infection
Food / Waterborne less likely
Only effective for some agents
Saint Louis Unversity School of
Public Health
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
Saint Louis Unversity School of
Public Health
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
Saint Louis Unversity School of
Public Health
Bioterrorism-Diseases
Risk Category A
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
Centers for Disease Control
Category A Biological Agents
Anthrax
Botulism
Plague
Smallpox
Tularemia
Viral 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
Brucellosis
Epsilon toxin of Clostridium perfringens
Food safety threats
Salmonella
E. coli O157:h7
Shigella
Centers for Disease Control
Category B Biological Agents
Glanders
Melioidosis
Psittacosis
Q Fever
Ricin toxin
Staphylococcal enterotoxin B
Centers for Disease Control
Category B Biological Agents
Typhus fever
Viral encephalitis
Water safety threats
Vibrio cholerae
Cryptosporidium
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:
availability
ease 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
Centers for Disease Control
Common Clinical Manifestations
of Bioterrorism Agents
Skin lesions w/fever
Acute respiratory distress w/fever
Influenza-like illness
Neurologic syndromes
Skin Lesions w/Fever
Smallpox
Cutaneous Anthrax
Acute Respiratory Distress
w/Fever
Inhalation Anthrax
Pneumonic Plague
Flu-like Illnesses
Tularemia
Inhalational Anthrax
Viral Hemorrhagic Fever
Smallpox
(Pretty much everything except the
kitchen sink!)
Neurologic Illnesses
Ricin
VX
Sarin gas
Mustard gas
Botulism
Smallpox
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
Saint Louis Unversity School of
Public Health
Photo: National
Archives
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
Saint Louis Unversity School of
Public Health
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
Saint Louis Unversity School of
Public Health
Smallpox: Bioweapon Potential
Nonimmune population
<20% 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
Saint Louis Unversity School of
Public Health
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
Saint Louis Unversity School of
Public Health
Smallpox: Epidemiology
All ages and genders affected
Incubation period
From infection to onset of prodrome
Range 7-17 days
Typical 12-14 days
Saint Louis Unversity School of
Public Health
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
• <10 virions sufficient to cause infection
• Aerosol exposure <15 minutes sufficient
Saint Louis Unversity School of
Public Health
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
Saint Louis Unversity School of
Public Health
Smallpox: Epidemiology
Transmission via fomites
Contaminated hospital linens/laundry
May have been successfully used as
weapon in French-Indian War
Saint Louis Unversity School of
Public Health
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
Saint Louis Unversity School of
Public Health
Smallpox: Epidemiology
Infectious Materials
Saliva
Vesicular fluid
Scabs
Urine
Conjunctival fluid
Possibly blood
Saint Louis Unversity School of
Public Health
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)
Saint Louis Unversity School of
Public Health
Smallpox: Epidemiology
Mortality
25-30% overall in unvaccinated population
Infants, elderly greatest risk (>40%)
Higher in immunocompromised
May be dependent on ICU facilities
Dependent on virus strain
Dependent on disease variant
Saint Louis Unversity School of
Public Health
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
Saint Louis Unversity School of
Public Health
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
Saint Louis Unversity School of
Public Health
Smallpox: Microbiology
Variola major
Classic smallpox
Predominant form in Asian epidemics
Highest mortality (~30%)
Saint Louis Unversity School of
Public Health
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
Saint Louis Unversity School of
Public Health
Smallpox: Microbiology
Environmental survival
Longest (>24hr) in low temp/low humidity
Inactive within few hours in high
temp/humidity
Dispersed aerosol
• completely inactivated within 2 days of release
Saint Louis Unversity School of
Public Health
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
Saint Louis Unversity School of
Public Health
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
Saint Louis Unversity School of
Public Health
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
Saint Louis Unversity School of
Public Health
Smallpox: Clinical Features
Three stages of disease
Incubation
• Asymptomatic
Prodromal
• Nonspecific febrile illness, flu-like
Eruptive
• Characteristic rash
Saint Louis Unversity School of
Public Health
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
Saint Louis Unversity School of
Public Health
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
Saint Louis Unversity School of
Public Health
Smallpox: Clinical Features
Eruptive Stage (Rash)
May start with transient defervescence
Characteristic rash
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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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Public Health
Classic Centrifugal Rash of Smallpox Involving Face and
Extremities,
Photo: National
Archives
Including the Soles.
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Public Health
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
Saint Louis Unversity School of
Public Health
Classic Smallpox
Rash, Demonstrating
Same Development
Stage (Pustular) of
All Lesions in a
Region
Photo: National
Archives
Smallpox
Smallpox: Clinical Features
Scarring
From separated scabs
Fibrosis, granulation in sebaceous glands
Pink, depressed pock marks
Prominent on face, usually >5 lesions
Permanent
Saint Louis Unversity School of
Public Health
Smallpox: Clinical Features
Rash variations
Sine eruptione variant
• Prodrome without rash
• Clinically less severe
Saint Louis Unversity School of
Public Health
Smallpox: Clinical Features
Modified variant
Previously vaccinated
with partial immunity
Milder rash, better
outcome, faster
resolution
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of
Photo: National Archives
Public Health
Smallpox: Clinical Features
Rash variations
Ordinary (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
Saint Louis Unversity School Photo:
of National Archives
Public Health
Saint Louis Unversity School of
Public Health
Photo: National Archives
Smallpox: Clinical Features
Rash variations
Flat (Malignant) variant
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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 Features
Rash variations
Hemorrhagic
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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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Public Health
Smallpox: Clinical Features
In an outbreak setting atypical or
variant rashes must be considered
smallpox until proven otherwise
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Public Health
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
Saint Louis Unversity School of
Public Health
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
Saint Louis Unversity School of
Public Health
Smallpox: Diagnosis
Clinical diagnosis
Sufficient in outbreak setting
>90% have classical syndrome
• Prodrome followed by rash
Rarely, variants can be difficult to recognize
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Hemorrhagic – mimics meningococcemia
Malignant – more rapidly fatal
Sine eruptione – prodrome without rash
Partially immune – milder, often atypical
Saint Louis Unversity School of
Public Health
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
Saint Louis Unversity School of
Public Health
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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Public Health
Smallpox
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
Chickenpox
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
Smallpox
Chickenpox
Smallpox: Treatment
Management of cases
Supportive
Post-exposure prophylaxis
Vaccine
Vaccinia immunoglobulin
Primary prophylaxis
Vaccine
Saint Louis Unversity School of
Public Health
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)
Saint Louis Unversity School of
Public Health
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)
Saint Louis Unversity School of
Public Health
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
Saint Louis Unversity School of
Public Health
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
Saint Louis Unversity School of
Public Health
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
Saint Louis Unversity School of
Public Health
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
Saint Louis Unversity School of
Public Health
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
Saint Louis Unversity School of
Public Health
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 > 38.0º C
Saint Louis Unversity School of
Public Health
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
Saint Louis Unversity School of
Public Health
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
Saint Louis Unversity School of
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Smallpox: Decontamination
Original aerosol release setting
Likely 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 release
HEPA filtration
Sterilization of surfaces
• Standard disinfectants such as bleach
Saint Louis Unversity School of
Public Health
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
Saint Louis Unversity School of
Public Health
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
Saint Louis Unversity School of
Public Health
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 >38.0
Saint Louis Unversity School of
Public Health
Smallpox Essential Pearls
Report any suspected smallpox cases to
your State and Local Health
Departments
Saint Louis Unversity School of
Public Health