Smallpox
Lessons Learned and Future Challenges
Why Smallpox Bioterrorism?
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Stable aerosol Virus
Easy to Produce
Infectious at low doses
Human to human transmission
10 to 12 day incubation period
High mortality rate (30%)
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Co-Evolution
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Smallpox infects humans only
 Could not survive until agriculture
 No non-human reservoir
 If at any point no one in the world is infected,
then the disease is eradicated
Infected persons who survive are immune,
allowing communities to rebuild after epidemics
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Small Pox Vaccine History
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1000 AD - China, deliberate inoculation of smallpox into
skin or nares resulting in less severe smallpox infection.
Vaccinees could still transmit smallpox
1796 - Edward Jenner demonstrated that skin inoculation
of cowpox virus provided protection against smallpox
infection
1805 - Italy, first use of smallpox vaccine manufactured
on calf flank
1864 - Widespread recognition of utility of calf flank
smallpox vaccine
1940’s - Development of commercial process for freezedried vaccine production (Collier)
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How Vaccination Works
Herd Immunity
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Smallpox Spreads to the Non-immune
 Immunization Slows the Spread Dramatically
 Epidemics Die Out Naturally
Herd Immunity Protects the Unimmunized
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Smallpox Vaccine
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Live Virus Vaccine (Vaccinia Virus)
 Not Cowpox, Might be Extinct Horsepox
 Must be Infected to be Immune
Crude Preparation We Have Now
 Prepared from the skin of infected calves
 Filtered, Cleaned (some), and Freeze-dried
New Vaccine is Clean, but still Live
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Complications of Vaccination
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Local Lesion
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Progressive
(Disseminated) Vaccina
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Can be Spread on
the Body and to
Others
Deadly Like
Smallpox, but Less
Contagious
Encephalitis
Heart Disease?
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Historic Probability of Injury
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Small Risk from Bacterial and Viral Contaminants
Small Risk of Allergic Reaction
35 Years Ago
5.6M New and 8.6M Revaccinations a Year
 9 deaths, 12 encephalitis/30-40%
permanent
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Death or Severe Permanent Injury - 1/1,000,000
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Mostly among immunsupressed persons
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Global Eradication Program
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1950 - Pan American Sanitary Organization initiated
hemisphere-wide eradication program
1967 - Following USSR proposal (1958) WHO initiated
Global Eradication Program
Based on Ring Immunization
 Vaccinate All Contacts and their Contacts
 Isolate Contacts for Incubation Period
 Involuntary - Ignore Revisionist History
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1977 - Oct. 26, 1977 last known naturally occurring
smallpox case recorded in Somalia
1980 - WHO announced world-wide eradication
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Eradication Ended Vaccinations
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Cost Benefit Analysis
 Vaccine was Very Cheap
 Program Administration was Expensive
 Risks of Vaccine Were Seen as Outweighing
Benefits
 Restatement of Torts 2nd - Products Liability
Stopped in the 1970s
Immunity Declines with Time
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Post Eradication
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50%+ in the US have not been vaccinated
Many fewer have been vaccinated in Africa
Immunity fades over time
 Everyone is probably susceptible
 Perhaps enough protection to reduce the
severity of the disease
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Role of Medical Care
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Smallpox
 Can Reduce Mortality with Medical Care
 Huge Risk of Spreading Infection to Others
 Very Sick Patients - Lots of Resources
 Cannot Treat Mass Casualties
Vaccinia
 VIG - more will have to be made
 Less sick patients - longer time
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The Danger of Synchronous Infection
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The whole world may be like Hawaii before the
first sailors
If everyone gets sick at the same time, even nonfatal diseases such as measles become fatal
A massive smallpox epidemic would be a national
security threat
Is a massive epidemic possible?
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Smallpox Vaccination Campaign
Fall 2002 - Spring 2003
Why Did White House Wait so Long?
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Key year for bioterrorism – 1993
 Credible information that the Soviet Union
had tons of smallpox virus it could not
account for
 CIA did not tell CDC
 Still Debating Destruction of the Virus in 1999
Should have started on a new vaccine
Should have worked out a vaccination program
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Vaccinating the Military
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Required of Combat Ready Troops
Combat ready personnel are medically screened
and discharged if they have conditions that would
complicate vaccination
All are young and healthy
Not a good control group
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Vaccinating Health Care Workers
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All ages
Many have chronic diseases that compromise the
immune system or otherwise predispose to
complications
Have not been medically screened
ADA makes medical screening legally
questionable
Political concerns make it impossible
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CDC Plan
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Voluntary vaccinations
No screening or medical records review
Self-deferral
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Problems in the CDC Plan
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Conflicting information on removing vaccinated
workers from the workplace
No focus on who should be vaccinated - random
volunteers do not produce a coherent emergency
team
Assumed patients would walk into the hospital
Ignored Securing ERs to prevent this
No attention paid to hospital and worker concerns
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Liability for Primary Vaccine Injuries
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Informed Consent
 Was the Patient Warned of the Risk?
 Is it 1/1,000,000 or is it 1/10 for the
Immunosuppressed?
Negligent Screening
 Is it reasonable to rely on self-screening when
the clinical trials demanded medical testing and
records review?
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Liability for Secondary Spread
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Spread to Family Members
 Is a Warning to the Vaccinee Enough?
 Should there be investigation of the health
status of family members?
Spread to Patients by Health Care Providers
 Should Vaccinated Persons be in the Workplace
while Healing?
 Should Patients be Warned?
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Employment Discrimination Issues
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What Happens When Health Care Providers and
Others Refuse Vaccination?
What if they Cannot be Immunized?
Must they be Removed from Emergency
Preparedness Teams?
What about Other Workplace Sanctions?
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Costs to Hospitals and Workers
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Is a vaccine injury a worker's compensation
injury?
 Should be, but many comp carriers baulked at
assuring they would pay
Who pays for secondary spread injuries?
Who pays for time off work and replacing
workers?
Does the worker have to take sick leave?
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Homeland Security Act Solution
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"For purposes of this section, and subject to other
provisions of this subsection, a covered person
shall be deemed to be an employee of the Public
Health Service with respect to liability arising out
of administration of a covered countermeasure
against smallpox to an individual during the
effective period of a declaration by the Secretary
under paragraph (2)(A)."
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What Triggers This?
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Secretary of HHS Must Make a Declaration
Must Specify the Covered Actions
 Immunity Only Extends to Covered Use of
Vaccine
 Does Not Apply to Unauthorized Use or
Blackmarket
Includes People and Institutions
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What is Excluded?
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Probably Worker’s Comp
 Not a Liability Claim
 If Included, then the Injured Worker has no
Compensation
Black-market and direct person to person
inoculation
Only injuries, not costs of lost time and other
hospital costs
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Effect on Injured Workers, Their Families,
and Patients
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No compensation beyond comp
Questions about whether comp would pay
Might have to use vacation and sick leave
Smallpox compensation act was eventually
passed but not implemented and is too limited
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The Real Problem
Lack of Information
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What is the real risk of complications?
 Never clarified the risk to immunosuppressed
persons
Why now?
 Has something really changed?
Is this just Swine Flu all over again?
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The End Result
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Less than 35,000 vaccinated out of a target of
500,000
Many of those were reservists who were
vaccinated outside the hospital setting
Smallpox vaccination has been discredited
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Modeling Smallpox and the CDC, Post
Smallpox Immunization Campaign
The Dark Winter Model
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Johns Hopkins Model - 2001
Simulation for high level government officials
Assumed terrorists infected 1000 persons in
several cities
Within a few simulated months, all vaccine was
gone, 1,000,000 people where dead, and the
epidemic was raging out of control
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Response to the Dark Winter Model
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Koopman – worked in the eradication campaign
 “Smallpox is a barely contagious and slowspreading infection.”
Lane – ex-CDC smallpox unit director
 Dark Winter was “silly.” “There’s no way that’s
going to happen.”
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Decomposing the Models – Common
Factors
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Population at risk
Initial seed
Transmission rate
Control measures under study
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Population at Risk
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Total number of people
 Compartments - how much mixing?
Immunization status
 Most assume 100% are susceptible
Increasing the % of persons immune to smallpox
 Reduces the number of susceptibles
 Dilutes the pool, reducing rate of spread
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Transmission Rate
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Mixing Coefficient X Contact Efficiency
Mixing Coefficient
 The number of susceptible persons an index
case comes in contact with
Contact Efficiency (Infectivity)
 Probably of transmission from a given contact
 Can be varied based on the type of contact
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Where do the Models Differ?
Transmission Rate is the Key
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< 1 - epidemic dies out on its own
1 - 3 - moves slowly and can be controlled without
major disruption
> 5 - fast moving, massive intervention needed for
control
> 10 - overwhelms the system - Dark Winter
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What is the Data on Transmission Rate?
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Appendix I
 http://whqlibdoc.who.int/smallpox/9241561106_
chp23.pdf
 This is all the data that exists
 The data is limited because of control efforts
This data supports any choice between 1 and 10
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What are the Policy Implications of the
Transmission Rate?
Dark Winter - Risk of 10
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Can only be prevented by the reinstituting routine
smallpox immunization
Terrible parameters for policy making
 Huge risk if there is an outbreak
 Low probability of an outbreak
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Kaplan - Risk of 5
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Mass immunization on case detection
Best to pre-immunize health care workers
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Metzler/CDC - Risk of 2-3
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Contact tracing and ring immunization
 Trace each case and immunize contacts
 Immunize contacts of contacts
 Takes a long time to get the last case
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What are the Politics?
Reinstituting Routine Vaccinations
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We cannot even get people to get flu shots, which
is perfectly safe
No chance that any significant number of people
will get the smallpox vaccine after the failure of
the campaign to vaccinate health care workers
Would require a massive federal vaccine
compensation program
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Mass Vaccinations Post-Outbreak
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Pros
Limits the duration of the outbreak to the time
necessary to do the immunizations, could be
two weeks with good organization
 Eliminates the chance of breakout
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Cons
Lots of complications and deaths from the
vaccine
 Requires massive changes in federal vaccine
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Contract Tracing and Ring Immunizations
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Pros
Limits the vaccine complications
 Does not require hard policy choice to
immunize everyone
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Cons
Requires lots of staff
 Requires quarantine
 Requires lots of time
 Chance of breakout
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Contact Tracing Model and Lessons from
Katrina
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National Security Administration Course Problem
How much do the feds depends on the states to
do their part?
 What is the risk if the states do not do their
part?
 How can the feds know in time?
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No one was interested
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Of course the states will do what they are
required to do
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Political Choices are Hidden in the Models
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Federal policy is based on a low transmission rate
 Is that justified by the data?
 Is the potential upside risk too great with this
assumption?
Dark Winter is based on a high rate
 Do anything and pay anything to avoid
bioterrorism
 Convenient for bioterrorism industries
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The Problem
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Smallpox is still a real threat
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Or is it?
The CDC plans for dealing with an outbreak are
completely unrealistic
Should we start vaccinating the population?
 Vaccinating health care workers alone is not
epidemiologically sound or politically
acceptable
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How do we resolve the uncertainty?
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What does this tell us about Pan Flu?