Emerging Disease

1
Current Thought on Bioterrorism The Threat,
Preparedness and Response Office of Basic
Energy Sciences Workshop on Basic Research Needs
to Counter Terrorism February 28 - March 1,
2002 Gaithersburg, MD 20878 David R. Franz,
DVM, Ph.D Southern Research Institute University
of Alabama at Birmingham
2
Examples of diseases often mentioned in the
context of biological warfare
Human diseases Smallpox Cholera Shigellosis
Animal diseases African Swine Fever Foot and
Mouth Fowl Plague Newcastle Rinderpest
Zoonoses
Anthrax Brucellosis Coccidioidomycosis EEE / VEE
/ WEE Japanese B Ebola/Marburg Histoplasmosis
Melioidosis Glanders Plague Psittacosis Q
Fever Rabies Tularemia
Botulism SEB intoxication
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B.W. Agents Differ from C.W. Agents
Biological Agents Natural Production
difficult None volatile Many toxins more
toxic Infectious agents replicate Not dermally
active Legitimate medical use Odorless and
tasteless Diverse pathogenic effects Many are
effective immunogens Aerosol delivery Delayed
Onset (Days to Weeks) A few are contagious
Chemical Agents Man-made Production difficult
(industrial) Many volatile Less toxic than many
toxins Do not replicate Many are dermally
active No use other than as weapons Odor or taste
when contaminated Fewer types of effects Poor
immunogens Mist / droplet / aerosol
delivery Rapid Onset (Minutes) Not Contagious
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Implications and Constraints for the Weaponeer

• Must be presented as a respirable aerosol
• Preparation and weaponization may jeopardize
  viability
• Aerosols are dependant on meteorological
  conditions
• However...
• Contagious agents can be delivered without
  weaponization
• Some agents can be spread by vectors

It follows therefore that...
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Implications for Public Health

• Many diseases begin as flu-like illness
• Definitive diagnostics are specific and complex
• Treatment after clinical diagnosis may be too
  late
• Preclinical diagnostics are not generally
  available
• Few antiviral drugs available
• Vaccines are very specific and require years to
  field
• Prophylaxis may be socially or politically
  unacceptable
• Potential for complex psychological response

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Biological Terrorism and Public Health
Chemical Terrorism
HAZMAT EVENT-----------------------------------PUB
LIC HEALTH PROBLEM
Biological Terrorism
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Outbreak or Epidemic ?
Plague
Anthrax (and most others)
Smallpox
Day 0
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Outbreak or Epidemic ?
Plague
Anthrax (and most others)
Smallpox
Day 10
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Outbreak or Epidemic ?
Plague
Anthrax (and most others)
Smallpox
Day 20
10
Outbreak or Epidemic ?
Plague
Anthrax (and most others)
Smallpox
Day 30
11
Outbreak or Epidemic ?
Plague
Anthrax (and most others)
Smallpox
Day 40
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The Unique Threat
Dual-Use Nature Evolving Technology
Political Factors
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Expression of cereolysine AB genes in Bacillus
anthracis vaccine strain ensures protection
against experimental hemolytic anthrax infection
A.P. Pomerantsev, N.A. Staritsin, Yu. V. Mockov
and L.I. Marinin
.results describe the modulation of
immunopathogenic properties of B. anthracis due
to expression of cereolysin AB genes.
Vaccine. Vol 15, 1997
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Technological Change Could Make Biological
Warfare a Moving Target
Genomics Proteomics Automated Sequencing Cloning T
ransfection Polymerase Chain Reaction
Altered agent Tropism Production methods Enhanced
Stability
Access to technologies and information is
getting easier
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The Moscow TimesThursday, January 20, 1994
Yeltsin Names Core of New Government
Ruble Falls and Rush Continues
Funds Disappearing
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Cold-War Solutions

• Vaccines, Drugs and Diagnostics
• Environmental Sensors and Masks
• The Biological Weapons Convention

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The Biological Threat has Changed
Cold War Gulf War Today Tomorrow?
Tactical use on the battlefield .and
strategic use against the U.S.
Terrorist use against the force or our cities
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Why Bioterrorism in the US Today?

• Were the nation to beat
• They cant do it conventionally
• Looking for a great equalizer
• Biological warfare expertise is available
• Dual-use nature makes it hard to detect
• Were still vulnerable
• Biotechnology may make it easier
• But, fortunately, its still not easy to do

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The Biological Terrorist Spectrum
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The Biological Terrorist Spectrum
1997 27 hoaxes Since then ca. 200/yr October
2001 gt Thousands
1987 Salmonella on salad bar.now B. anthracis
None
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Tools for Identification of Biological agents

• Culture and Isolation (1 - 30 days)
• Animal Inoculation (2 - 30 days)
• Immunoassays (2 - 6 hours)
• Nucleic Acid Assays (3 - 5 hours)
• Mass Spectroscopy (1 - 8 hours)

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The Challenge of EnvironmentalDetection

• Logistics (e.g.. power and reagents)
• Sensitivity
• Background Interference
• Timeliness

Detect to Warn or Detect to Treat
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Bill Patricks Relative Aerosol Potency Chart
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Detector Sensitivity Requirements
IF...ID50 is 100 organisms AND..Aerosol
retention is 60 AND..Minute volume is 10
liters AND..Cloud is on site for 10 min 100
org X 60 60 org 10 l /min X 10 min 100
liters Must detect 60 org in 100 liters OR 0.6
org/liter (or 6 organisms / 10 liters)
ID50 Human. Sensor Reqmt. 10 6 org/100 l
10 org/100 l 100 6 org/10 l 10 org/10
l 1,000 6 org/l 10 org/ l 10,000 60
org/ l 100 org/l
Note The human must see 10 orgs to retain 6
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The Challenge of Timely Diagnostics

• Sample collection
• Sample preparation (clean-up)
• Complex matrices/background
• Accurate differentiation
• Miniaturization

• Reasonable Goals
• Sample Prep in lt5min
• Gene Amplification and
• Detection in lt25min

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Complexity of the Problem

• Targets may be military, civilian or both
• Threat footprint may be very small
• It may appear to be a naturally occurring
  disease
• Attribution will not always be possible
• Fundamentally, its a public health problem
• Materiel solutions alone are not enough

Military and Public preparedness is a deterrent
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The New, Multivalent ThreatReducing
Proliferation
NO SINGLE APPROACH FOR ALL SITUATIONS Russia
Current economic weakness provides threat
reduction options China A growing world-power
in biotechnology the great unknown Smaller
threat nations Many may be capable of producing
effective biological weapons Subnational
Groups.or individuals?
The new threat may look like the 1999 West Nile
Outbreak
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What has changed
Since 9-11

• Something related to intent to harm
• New diseases added to physician differentials
• Public understanding of the biological threat
• Funding for Bioterrorism Preparedness
• National...and apparently international...will
• And even, thought of immunizing the population

and what hasnt?

• The technical difficulty of agent preparation
• The importance of meteorology to the attacker
• The difficulty of intelligence collection
• The value of Public Health for preparedness
• The value of our Science and Technology base
• The value of Education

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The Way Ahead

• Surveillance (diagnostics and communication)
• Education
• Proactive Deterrence
• Public Health Infrastructure
• HUMINT
• Biomedical Research

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The Way Ahead

• Surveillance (diagnostics and communication)
• Education
• Proactive Deterrence
• Public Health Infrastructure
• HUMINT
• Biomedical Research

Its not about - Suits - Masks - Decon
Stations Its Public Health
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The Way Ahead

• Surveillance (diagnostics and communication)
• Education
• Proactive Deterrence
• Public Health Infrastructure
• HUMINT
• Biomedical Research

But its not JUST Public Health. Its
Public Health ()
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Bioterrorism Lessons Learned

• Think Public Health (plus)
• Think Dual-use Investments
• Think Tech-base not Materiel
• Think Education
• Think Cost-Benefit
• Think Long-Term

33
The Futurechallenges and potential solutions
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The last 5-6 years Rapid Change

• Nonprolif. Treaties..Cooperative Threat
  Reduction
• Focus Cold-War defense..Domestic Preparedness
• PCMs DoD masksNew clothing technologies
• MCMs Specific Vaccines..Diagnostics, Drugs,
  Generic CMs
• Intel Humint.Masint and Threat Analysis
• Surveillance Nuclear.Bio
• Analysis DoD..DoD/CDC/DoJ/DoEState and
  Local
• Complexity Low...High
• Experts Few..(Many)
• Mgt DoD..HHS, FEMA, DoJ
• Research \ DoD..../ HHS, DoJ, DoD,
  DoE, IC 137M in DoD in 97..11B Nationally in
  03
• Education DoD..DoD, DoJ, HHS, Academia,
  Industry
• The Enemy Soviet Union (80s)..State and
  Non-state actors
• Collaborators Allies..Russian Colleagues
• Hoaxes Almost none.Routine..Overwhelming
• Interest Low....High..Extremely High

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Wish List for the Future

• Nonprolif. Trust pills
• PCMs In-place oro-nasal filter and non-invs.
  Ind. exposure alarm
• Detection Simple, cheap, generic,
  integrated..dual-use
• MCMs Pre-clinical diagnostic, Generic therapeutic
  drugs
• Triage Within-4hr minimally invasive triage
  machine
• Intel Intent meter
• Surveillance Satellite-based, high sensitivity,
  immediate
• Management Educated, objective
• Leadership Mission oriented willing to take
  responsibility/share results
• Education CB M.A.S.H. of Seinfield Series..The
  anthrax letters
• Regulatory Effective FDA teaming..were getting
  there
• Research Risk-benefit based, dual-use, basic
• Hoaxes Airplane hijacking model?.but this is
  more difficult
• Policy Swift retaliation and extreme measures