Transcript 31. Biological Warfare

DETECTING AND RESPONDING
TO A BIOTERRORIST AGENT
INFECTING YOUR PATIENT(S)
Panel Discussion
Outline
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Brief history of biowarfare
Potential impact and effects of BT
Transmission of BT agents
Clues to BT
“Most likely BW agents”
Rational perspectives
Management
Overview of potential pre-exposure prophylaxis,
post-exposure prophylaxis and therapy
BIOLOGIC WARFARE:
HISTORY
• 14TH century, Kaffa: Attacking Tatar force
catapulted cadavers of plague victims into city –
outbreak of plague led to defeat
• 18th century, Fort Pitt, North America: Blankets
from smallpox hospital provided to Native
Americans – resulted in epidemic of smallpox
among tribes in Ohio River valley
• 1932-45, Manchuria: Japanese military physicians
infected 10,000 prisoners with biological agents (B.
anthracis, N. meningitidis, Y. pestis, V. cholerae) –
11 Chinese cities attacked via food/water
contamination, spraying via aircraft
USE OF BIOLOGICAL
AGENTS: US
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Site: The Dalles, Oregon, 1984
Agent: Salmonella typhimurium
Method of transmission: Restaurant salad bars
Number ill: 751
Responsible party: Members of a religious
community had deliberately contaminated the
salad bars on multiple occasions (goal to
incapacitate voters to prevent them from voting
and thus influence the outcome of the election)
Torok TJ, et al. JAMA 1997;278:389-395
USE OF BIOLOGICAL
AGENTS: US
• Site: Large medical center, Texas, 1996
• Agent: Shigella dysenteriae
• Method of transmission: Ingestion of
muffins/doughnuts
• Number ill: 12 (27% attack rate)
• Responsible party: Disgruntled lab employee? S.
dysenteriae identical by PFGE from stock culture
stored in laboratory
Kolavic S, et al. JAMA 1997;278:396-398.
International Biological Weapons
Programs
Known
Iraq
Russia
Probable
China
Iran
North Korea
Libya
Syria
Taiwan
Possible
Cuba
Egypt
Israel
Source: Committee on Armed Services, House of Representatives. Special Inquiry into the Chemical and Biological Threat. Countering the Chemical and
Biological Weapons Threat in the Post-Soviet World. Washington, D.C.: U.S. Government Printing Office; 23 Feb 1993. Report to the Congress.
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BIOTERRORISM: IMPACT
• Direct infection: Mortality, morbidity
• Indirect infection: Person-to-person
transmission, fomite transmission
• Environmental impact: Environmental
survival, animal infection
• Other: Social, political, economic
EFFECTS OF A BIOLOGICAL
WEAPONS RELEASE
Siegrist, Emerging Infectious Diseases 1999
BIOLOGICAL WARFARE:
IMPACT
[release of 50 kg agent by aircraft along a 2 km line
upwind of a
population center of 500,000 – Christopher et al., JAMA 278;1997:412]
Agent
Downwind No. dead
No.
reach, km
incapacitated
Rift Valley fever
1
400
35,000
Tick-borne encephalitis
Typhus
Brucellosis
Q fever
1
5
10
>20
9,500
19,000
500
150
35,000
85,000
125,000
125,000
Tularemia
Anthrax
>20
>20
30,000
95,000
125,000
125,000
TRENDS FAVORING BIOLOGICAL
WEAPONS
• Biological weapons have an unmatched destructive
potential
• Technology for dispersing biologic agents is
becoming more sophisticated
• The lag time between infection and appearance of
symptoms generally is longer for biological agents
than with chemical exposures
• Lethal biological agents can be produced easily and
cheaply
• Biological agents are easier to produce clandestinely
than are either chemical or nuclear weapons
TRENDS FAVORING BIOLOGICAL
WEAPONS
• Global transportation links facilitate the potential for
biological terrorist strikes to inflict mass casualties
• Urbanization provides terrorists with a wide array of
lucrative targets
• The Diaspora of Russian scientists has increased the
danger that rogue states or terrorist groups will accrue
the biological expertise needed to mount catastrophic
terrorist attacks
• The emergence of global, real-time media coverage
increases the likelihood that a major biological
incident will induce panic
DEVELOPING A RISK
ASSESSMENT OF BIOLOGIC
WARFARE AGENTS
General difficulties in weaponizing a biologic
agent
• Ability to procure a virulent strain (e.g., anthrax,
tularemia)
• Ability to culture large amounts of the agent
• Ability to process agent into a suitable form (e.g.,
anthrax spores)
• Ability to safely handle and store the agent (may
be difficult for hemorrhagic fever viruses)
DEVELOPING A RISK
ASSESSMENT OF BIOLOGIC
WARFARE AGENTS
General difficulties in weaponizing a biologic
agent
• Ability to disseminate the agent as an aerosol
• Ability to generate aerosol particles of the proper
size (1-10 u)
• Ability to assess climatic effects in order to
disseminate agent effectively
• Different Federal agencies have reached different
conclusions regarding the likelihood of an attack
using a biologic agent
CHARACTERISTICS OF
BIOWARFARE
• Potential for massive numbers of casualties
• Ability to produce lengthy illnesses requiring
prolonged and intensive care
• Ability of certain agents to spread via contagion
• Paucity of adequate detection systems
• Diminished role for self-aid and buddy aid,
thereby increasing sense of helplessness
CHARACTERISTICS OF
BIOWARFARE
• Presence of an incubation period, enabling victims
to disperse widely
• Ability to produce non-specific symptoms,
complicating diagnosis
• Ability to mimic endemic infectious diseases,
further complicating diagnosis
US Army, Biologic Casualties Handbook, 2001
Bioterrorism: Modes of Spread
Aerosol Sprays
Particle size of agent
Stability of agent
Wind Speed
Wind direction
Atmospheric stability
Explosives
Tend to inactivate biological agents
Food and Water
Contamination
Fairly self-limited
Epidemiologic Clues to
Bioterrorism
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Multiple simultaneous patients with
similar clinical syndrome
Severe illness among healthy
Predominantly respiratory symptoms
Unusual (nonendemic) organsims
Unusual antibiotic resistance patterns
Atypical clinical presentation of
disease
Unusual patterns of disease such as
geographic co-location of victims
Intelligence information
Reports of sick or dead animals or
plants
Soviet BW Priorities
“Agents Likely to be Used”
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Smallpox
Plague
Anthrax
Botulism
VEE
Tularemia
Q Fever
Marburg
Influenza
Melioidosis
Typhus
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Category A: Highest Priority
• Can be easily disseminated or
transmitted person-to-person
• Cause high mortality, with
potential major public health
impact
• Might cause public panic and
social disruption
• Require special action for
public health prepardeness
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Smallpox
Anthrax
Yersinia pestis
Botulism
Tularaemia
Filoviruses (Ebola and
Marburg)
• Arenaviruses (Lassa and Junin)
Category B: Second Highest Priority
• Moderately easy to disseminate
• cause moderate morbidity and
low mortality
• Require specific enhancements
of CDC’s diagnostic capacity
and enhanced disease
surveillance
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Coxiella burnetti (Q fever)
Brucella
Burkholderia mallei (glanders)
Alphaviruses (Venezuelan
encephalomyelitis and Eastern
and Western equine)
Ricin toxin from Ricinus
communis
Epsilon toxin of C. perfringes
Staph enterotoxin B
Salmonella
Shigella
E. coli O157:H7
Vibrio cholerae
Cryptosporidium parvum
Category C: Third Highest Priority
• Pathogens that could be
engineered for mass destruction
because of availability, ease of
production and dissemination
and potential for high morbidity
and mortality and major health
impact
• Nipah virus
• Hantavirus
• Tickborne hemorrhagic fever
viruses
• Tickborne encephalitis viruses
• Yellow fever
• MDR TB
RISK OF DYING (US, per year)
Other risks
Major risks
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Heart disease: 1 in 400
Cancer: 1 in 600
Stroke: 1 in 2,000
Flu & pneumonia: 1 in 3,000
MVA: 1 in 7,000
Being shot by a gun: 1 in
10,000
USA Today: October 16, 2001
• Falling down: 1 in 20,000
• Crossing the street: 1 in
60,000
• Drowning: 1 in 75,000
• House fire: 1 in 100,000
• Bike accident:1 in 500,000
• Commercial plane crash: 1
in 1 million
• Lightening strike: 1 in 3
million
• Shark attack: 1 in 100
million
• Roller coaster accident: 1 in
300 million
PERSON-TO-PERSON
ACQUISITION
Disease
Transmission
Risk
Andes virus
Undefined
Low
Anthrax
Contact with skin lesions
Rare
Ebola, Lassa, Marburg,
Congo-Crimean, AHF, BHF
Smallpox
Contact with infective fluid,
droplet?
Contact, droplet, airborne
High
Plague (pneumonic)
Droplet
High
Q fever
Contact with infected placenta
Rare
High
Airborne
Contact
Lassa Fever
Ebola
Marburg virus
Smallpox
Pneumonic plague
Inhalational anthrax
Venezuelan equine encephalitis
Botulism
Brucellosis
Cholera
Q fever
Pulmonary tularemia
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C
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Droplet
Standard
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Precautions
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FOMITE ACQUISITION
• Agents acquired from contaminated clothes
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Variola major (smallpox)
Bacillus anthracis (anthrax)
Coxiella burnetii (Q fever)
Yersinia pestis (plague)
• Management
– Remove clothing, have patient shower
– Place contaminated clothes in impervious bag, wear
PPE
– Decontaminate environmental surfaces with EPA
approved germicidal agent or 0.5% bleach (1:10
dilution)
BW AGENTS
CHARACTERISTICS
Disease
ID
Incubation
Anthrax** 8,000-50,000 spores 1-6 d
Duration Mortality
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3-5 d
High
Smallpox 1-10 organisms
~12 (7-17d) 4 wks
Mod-High
Plague** 100-500 organisms 2-3 d
1-6 d
High
Q fever
1-10 organisms
10-40 d
2-14 d
Very low
Tularemia 10-50 organisms
3-5d (2-10d) >2 wks Mod
VHF-viral hemorrhagic
fevers
US Army,
Biological
Casualties
2001
VHF
1-10 organisms
4-21
d
7-16Handbook,
d
Mod-High
* Untreated, ** Pneumonic form
BW AGENT PROPHYLAXIS
AND TREATMENT
Disease
Anthrax**^
Smallpox
Plague**^
Q fever#
Tularemia#
VHF+
Vaccine Efficacy*
Effective, 1,000 LD50 monkeys
Effective, high dose primates
Ineffective, 118 LD50 monkeys
94%, 3500 LD50 guinea
80%,1-10 LD50
No vaccine
PEP
Antibiotics
Vaccine, VIG
Antibiotics
Antibiotics
Antibiotics
None
Treatment
Antibiotics
Cidofovir?
Antibiotics
Antibiotics
Antibiotics
Ribavirin@
VHF-viral hemorrhagic fevers, PEP-postexposure prophylaxis
*Aerosol exposure; **Pneumonic form; ^FDA approved vaccine (not available); #IND
+ IND BHF, RVF; @ CCHF, Lassa
US Army, Biological Casualties Handbook, 2001
STEPS IN MANAGEMENT
1. Maintain an index of suspicion
2. Protect thyself
3. Assess the patient
4. Decontaminate as appropriate
5. Establish a diagnosis
6. Render prompt therapy
7. Practice good infection control
STEPS IN MANAGEMENT
8. Alert the proper authorities
9. Assist in the epidemiologic investigation
10. Maintain proficiency and spread the
gospel
US Army, Biologic Casualties Handbook, 2001