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      Terrorism & Science
      What Do We Know
      What Should We Do
Values, Choice, Public Health and
         Public Policy
   Grand Rounds Cambridge Hospital

      William J. Bicknell, MD, MPH
         School of Public Health
            Boston University
               Let’s start with a clinical look

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                                        Day Zero
                     In the mouth and throat. You don‟t see it. And,
                                    very infectious

                                     Bottom Line
           Days 0, 1 and 2 missed                 3 unrecognized infectious
           Day 3 maybe                            days for sure
           Day 4 probably                         Maybe 4 or 5
           DaY 5 Almost for sure
                             Confirmation - Add 12 to 24 hours
                             Begin vaccinating - Add 1 to 3 days
                                      Earliest Vaccination
                              5 days after the first case is infectious
W Bicknell 10/23/02 BU SPH
                   Context & The US Issues
              The Risk of Attack?
              If an attack, the magnitude?

              If an attack, can ring containment & quarantine
              Vaccine risks?

              Liability issues?

              Are there responsible alternative options?

              Who should decide what?

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                              Facts

                              Myths and controversies
                              What the US is doing
                                Where it was just after 911
                                Where it is today

                             Q   &A

W Bicknell 10/23/02 BU SPH
                             Off the Wall?
               Dr. Fenner: No errors and “A good case,
                reasonable for America”

               Dr. Fauci: With regard to the US “….excellent and
                hopefully will generate some frank and needed
                discussion. The stepwise approach that you
                recommend makes sense and is quite

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           Very  limited current knowledge &
            experience about smallpox
           No one has epidemic control in a non-
            immune population experience
           Relevance of lessons from eradication
            experience (characterized by very different
            circumstances) is likely to be more limited
            than realized

W Bicknell 10/23/02 BU SPH
                             The Risk of Attack
              What was our estimate of 9/11 on 9/10?
              I have never heard any informed person state with
               confidence that smallpox has not been disseminated
               outside the two repositories
              There are reports of vaccination of N.Korean and Iraqi
              US, UK, Israel, Germany & Australia and perhaps others
               are acquiring vaccine.
              Israelis vaccinating first responders
              The US has enough for vaccine for all residents
              US is vaccinating first responders (more later)
              Bottom line - Unknown but non-trivial risk of terrorist
              Therefore, we need to know something about smallpox,
               let‟s get some basics
W Bicknell 10/23/02 BU SPH
                             Smallpox Disease
         Highly Infectious
               It is dangerous and in error to say or believe otherwise
     Mortality5% to > 50% - usually ~25%
     60% - 80% of survivors disfigured
     Highest in young children
     No specific treatment
     ~ 50% of US and most populations not immune
     ~ 50% may have some residual immunity
            How much immunity ? No one really knows
         An historical note: The Aztecs & Incas, immunologically &
          genetically naïve, lost to smallpox not the Spanish &

          *F. Fenner 10/11/02
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                  Smallpox Transmission 1
         Incubation - not infectious 10 -12 days
         Last days of incubation you feel lousy with Fever
         Then fever drops and you feel better but not well
          and are infectious
         Usually no visible rash yet - just inside mouth and
         Classic rash still 2 to 4 days away
         Message - Highly infectious, not very visible or
          obvious and not necessarily very sick
         Remember terrorists are motivated folks and can
          be expected to walk and disseminate even though
          feeling ill
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                    Smallpox transmission 2
           Close  contacts are “best” - within 6 feet
           Think of the morning metro or many other
           How easy is it to transmit?

           Let‟s consider some historical examples

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                             A Chilling Scenario
        “One person with smallpox arriving in the country traveled by
         train….he was apparently in the initial phase of the disease, as
         nobody noticed a rash on his face…Almost everyone who
         traveled with him in the compartment from Queensborough to
         Manchester contracted smallpox, the ticket collector...and those
         who traveled with him to Stalybridge in another train,
         something like a hundred people being infected from one single

        Not so different from flying in from Europe, traveling
         downtown by public transport and taking a train to the next city
        And terrorists are very motivated, so expect them to travel even
         if feeling quite ill

    Wanklyn (1913) cited in Dixon p311
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                              More Examples
               Other documented examples
                   Yugoslavia 1972 “..denied (having a) evidence
                    of skin lesions” 11 secondary cases
                   Tripoli 1946 “…a highly modified attack..unrecognized…
                    gives rise to… fatal attacks ” A smuggler infects wife and
                   Walking by a window and similar examples are found in
                    the literature
                   Also true this is not always the case - but should we count
                    on good luck?
               Worse yet, aerosol by immune disseminators.
                     Experts I have spoken with feel, technically, this is very
                      feasible and is reasonable to expect in a terrorist attack.
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                             Possible Attack Rates in Terrorist Contacts

                             Something between 10% & 50% may be
W Bicknell 10/23/02 BU SPH          a reasonable assumption                Dixon, p310
                             The four day window
         Evidence fromTripoli in 1946 (Dixon 12/48, 369-
          370) 21 non-immunes vaccinated within 5 days,
          all acquired smallpox, most mild, none died
         Anecdotal evidence from the eradication years that
          the disease is less severe if vaccination within 4
          days of contact
         Vaccination within the window may prevent death
          and perhaps may prevent some disease
         But the vaccinator has to find and vaccinate the
          infected persons
         Contact tracing not likely to begin until 14 to 17
          days after first exposure. In most situations,
          finding initial contacts within 4 days is impossible
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                             A Recent Mathematical Model
                       (Kaplan -Yale, Craft - MIT, Wein - Stanford)

           Clearly demonstrates the limits and inadequacies of
            the CDC recommendation for ring containment.*
               CDC has not yet adequately acknowledged and needs to
                update and change their website to reflect reality.
               Also shows that, for any significant exposure, immediate
                mass vaccination is far superior.
           Ratio of cases and deaths:
                       Ring/Mass ~ 180/1

       * Identify and vaccinate contacts then contacts of contacts in
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              A Recent Mathematical Model - Details
                       (Kaplan -Yale, Craft - MIT, Wein - Stanford)

          New York City
          1000 Persons initially infected
          Compares Trace Vaccination (Ring Containment)
           and Immediate Mass Vaccination
          Ring Containment: 324,000 cases, 97,000 deaths,
           control slow, epidemic still growing at 100 days
          Mass Vaccination: 1,720 cases, 525 deaths,
           control fast, epidemic essentially over in 30 to 45
          Also demonstrates limited value and great
           difficulties with quarantine and isolation of
           susceptibles and the asymptomatic
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                Ring Is Be More Myth than Reality
               Kaplan, Wein & Craft - (Epidemiology in Press)
                     Central & West Africa eradication data recalculated.
                     Growing levels of population immunity fully explain the decline in
                      new cases.
               Bicknell Conversations with Lane, Margolis and Bloem
                     “We went into a village where there was a case and assumed
                      everyone was a contact”
                     That‟s local mass vaccination
               Prof. Fenner - Surveillance, finding new cases, was
                critical. Then the response was local mass vaccination.
               Conclusion: Contact tracing, isolation, quarantine and ring
                vaccination seems to have been more the exception than
                the rule.

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                       But CDC still on 4 day window!
          “If contacts can be vaccinated within 4 days of their
           contact with the smallpox case, they may be protected
           from developing the disease or may at least develop a less
           severe illness. Since smallpox is usually transmitted by
           close contact except under special circumstances (to be
           discussed later in this section), people with face-to-face or
           household contact with a smallpox case are the ones at
           greatest risk for developing the disease and should be
           prioritized for vaccination.” CDC Interim Plan, Guide B,
          In people exposed to smallpox, the vaccine can lessen the
           severity of or even prevent illness if given within 4 days
           after exposure. CDC “Facts About Smallpox”
          Paucity of data. Therefore: Delphi of believers
          An excellent example of DO NOT ALWAYS
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             Plausible US Scenario after 40 days
            (Play with the model ask
           5 terrorists each travel to 3 urban areas
           200 close contacts per city
           20% of contacts infected (40 cases/site)
           20% mortality
           5% of infected contacts travel to other cities
           1ary contacts infect 9 others, 2ary 5, 3ary 3
           Cities & Towns - 1,600 (21 by day 11)
           Smallpox Cases - 114,000
           Smallpox Deaths - 22,000

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                         Very Bad/Extreme Case Scenario
                                  First 40 days
     10 terrorists each travel to 5 different urban areas
     500 close contacts per city
     40% of contacts infected (200 cases/site)
     30% mortality
     5% of infected contacts travel to other cities
     1ary contacts infect 10 others, 2ary 7, 3ary 4
     Cities & Towns - 40,000 (100 by day 11, then 1000s)
     Smallpox Cases - 3,600,000
     Smallpox Deaths - 1,000,000

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        Ring Containment, Isolation & Quarantine
          Eradication was accomplished in populations with high and
           growing population immunity, relatively low mobility and
           without malicious intent - A MAGNIFICANT ACHIEVMENT.
          Terrorism today is different
                 Malicious intent
                 Low to absent immunity
                 Highly mobile terrorists and a more mobile population
          Transmission to 2 or 3 - unrealistically low (Meltzer, et al)
          The 4 day window - may not exist and not really relevant
          Vaccination within the window not likely
          Widespread isolation & quarantine - A near hopeless task,
           chaos and possible national shutdown
          In brief - A plan that cannot work in a terrorist scenario and saw
           far less use in the eradication years than is commonly believed.

W Bicknell 10/23/02 BU SPH
                       Ring Containment - Summary
           Today, to the extent possible, with the first case or
            two, vaccinate probable contacts as soon as
            possible as you prepare for local or wider mass
           Consider contact tracing, isolation and quarantine
            ONLY if:
                   residual cases in an environment with high population
                   an isolated exposure, particularly if there is high
                    population immunity
               Inadequate for a mobile population, with low to
                absent immunity and malicious exposure.

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               The Magnitude of an Attack
                 Plan  for the worst, hope for
                  the best
                 Malicious and well executed
                 Multiple terrorists, Multiple

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                              The Vaccine
              It works and works well
              There is plenty for everyone in the US and will be lots more
              It is has more side effects including deaths than other vaccines
               currently in wide use
              Who dies and who has the most severe side effects? Children 9 and
               under (NEJM, p1202, 11/27/69.
              Accidental inoculation most common kid to kid
              About 80% of the serious complications and deaths (1968 data)
               avoided if children not vaccinated
              Teen and adult deaths extremely rare (CDC, Israel & US military &
               1968 data)
              Semi-permeable membrane dressing prevents 95 to 99% of viral
               shedding (Dr. Belshe, 5/8/01 at CDC)
              Atopic dermatitis tricky (avoiding children helps a lot)
              Could contact lens wearers have a problem? (AAFP 10/17)
              New and old vaccine probably similar complications
              VIG good for many but not all complications

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                              New Vaccines
               Acambis -Replicating, not attenuated
                   Intended to mimic NYBH
                   Expect similar side effects
                   License on a fast track

               Japanese LC16m8 - Replicating, attenuated
                   Fewer & less severe side effects
                   Still not OK for immunocompromised
                   Earliest, if developed 2005+

               Modified Vaccinia Ankara (MVA), Live non-
                   Intention is OK for everyone
                   Earliest 2005+

               LC16m8 & MVA - Can we be really sure they
                will be effective in humans? How to know?
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                             Vaccine Issues - 1
       Immunocompromised are at the highest risk of vaccine
        complications and of death from smallpox
       Pre-exposure vaccination done with forethought provides
        a calm atmosphere where education and precautions can
        be assured
                 And if an attack, counseled to self isolate with selective
                  vaccination based on well thought out criteria
          Post-exposure will be in crisis with ability to protect the
           immunocompromised from complications greatly
              Many will want to be vaccinated and not reveal their status
              Our ability to identify and protect very limited when in crisis
              Deaths from vaccine complications can be expected to exceed
               pre-exposure PLUS more smallpox deaths in the
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                             Vaccine Issues - 2
           Accidental vaccination of contacts of vaccinees
               Non-immunocompromised
               Immunocompromised

        Extremely rare
        Almost exclusively in household contacts
        Mostly children to children
        Vaccine complications including deaths most common
         and most severe in children
        Solution:
               Pre-exposure do not immunize under age 9
               Screen with care
               Use semi-permeable membrane dressings (Dr. Belshe)
               Post-exposure drop to age 1 (and below if risk of exposure
                is high)
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                             Vaccine Issues - 3
           1968  data - Vaccination deaths in >15 all (2
            of 14 million) would (should) be screened
            out today (aplastic anemia and leukemia)
           If children <10 not vaccinated pre-exposure,
            careful screening and use of semi-
            permeable membrane dressing:
                   Severe   complications and deaths should (my
                      opinion) be at or below historical rates

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          Dilute Vaccine Lasts 180+ Days

           From Dr. Belshe ACIP CDC Presentation May 8, 2002
W Bicknell 10/23/02 BU SPH
           Bifurcated Needle or Jet Injector?
              Jet is faster
              Jet can be difficult to maintain

              Some evidence of inadvertent disease
              US currently off the table

              CDC is developing a new, safer jet injector

              Dr. Bruce Weniger is the US expert at CDC

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          US Position - Fall 01 to Mid 02
           Reality - Limited Vaccine, have to prioritize
           Did not say this, rather gave false assurances that
            Ring, etc.would work
           State Health Officers silent
           Substantial federal and state bad judgment
                   Believe public must be reassured - WRONG
                   Know it won‟t work but don‟t want to rock the boat -
                   Fear of Loosing federal funds
                          Possibly  realistic and, to the extent it is true, reveals a
                             dangerous perversity in the federal process

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         Who should decide in the US?
                Attack risk is unknowable
                Personal risk can be illuminated
                Citizens make decisions about everything from
                 participating in research protocols to deciding between
                 vaginal delivery and C-section, angioplasty and open heart
                 surgery on a daily basis
                Smallpox vaccination is no more difficult, arguably much
                 simpler with far lower risks than many other choices
                Let the citizen decide within the framework of thoughtful
                 pre-exposure guidelines
                Unfortunately, we have seen that relying on PH
                 professionals in the US may not be safe - more reason to
                 let individuals decide for themselves

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             Why Voluntary Pre-Exposure Vaccination in the US?
              Decreases consequences of an attack
              May decrease likelihood of attack
              Provides the best protection for the immunocompromised
              Is low cost and relatively easy to do as part of ongoing care
              Recognizes the limited surge capacity of US hospitals and
               near impossibility of quarantine
              In case of attack
                    Makes containment & control much easier, whatever the strategy
                    Decreases panic and maintains order
                    Minimizes interruption of the nation‟s normal business
              Is realistic, has face validity and is easily understood by the
               professional and lay public
              By decreasing the likelihood and severity of an attack may
               benefit the rest of the world
              Will protect the most people at the lowest cost
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          The known risk exceeds the unknown risk and benefit
          Our overall medical care delivery system is inequitable.
           Therefore pre-exposure vaccination will unfairly protect those
           with health insurance
                 We cannot solve all social problems before protecting against terrorism
          Wait for newer safer vaccines and/or better, simpler diagnostic
                 The country needs protection today. We must plan for and use tools we
                  have while developing better tools
          We can‟t vaccinate unless we are prepared to vaccinate the rest
           of the world
                 US vaccination, to the extent it decreases the likelihood of our being
                  attacked , deceases risk to other countries. Many other countries have or
                  are acquiring vaccine. This is fundamentally a foreign policy and
                  foreign assistance question
                 A rational terrorist won‟t use smallpox as it will boomerang. Let‟s hope
                  this is correct. However, it is irrational to apply our logic to terrorists

W Bicknell 10/23/02 BU SPH
     Inhibit the epidemiologic pump & first protect
                    those most at risk
         First responders, at a minimum, should include
          ALL staff of hospitals, clinics and physicians‟
          offices, EMS (~ 5.5 million people)
         Enough police, fire, transport, media, public
          health, water, power, phone to maintain core
          functions of civil society
                   An additional ~ 5 million
         Total ~ 10 million
         The Federal Government decides for itself -
          1,000,000 doses going to the army (NYT Oct 5)

W Bicknell 10/23/02 BU SPH
                        First - a Measured Trial
        Resolve liability issues
        Careful guidelines to protect immunocompromised
        Vaccinate 500,000 first responders (We‟ve already
         vaccinated over 11,000 civilians since 1983, plus
         many military in the US until „90, IDF until „96 and
         Israeli first responders >9,000 now)
        Ramp up VIG production (Cangene)
        Observe vaccine complications very carefully
        Revise guidelines and approach as indicated
        Repeat with 1 to 2,000,000 first responders
        Observe with care and revise as indicated
        Vaccinate balance of first responders

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      Then - Expand to the general population
             VIG now widely available
             Public education as to risks and benefits of vaccination
              taking care to honestly and carefully distinguish between
              very serious/very rare and not so serious and far more
              common complications
             Informed consent
             Greatly reduce complications and deaths by restricting
              vaccination to:
                   Persons older than 9 years
                   Persons who are not immunocompromised and do not have other
                    disqualifying conditions
             Urge vaccinees to:
                   Announce their intent to family, friends and co-workers
                   Use appropriate dressing
                   Possibly consider avoiding crowds

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                                Roles & Responsibilities
                CDC
                    Safety guidelines for pre- and post-exposure
                     vaccination - NOT the societal or individual risk
                    Technical assistance on request
                    Guidelines for pre- and post-exposure state action

                States
                    Determine risk for their state
                    Make state-specific plans and recommendations
                              Who  are first responders?
                              Pre-exposure guidance for general public
                              Post-exposure planning

                Individuals
                    Assess their own risk
                    Opt or decline pre-exposure vaccination

W Bicknell 10/23/02 BU SPH
                             Recommendations & Conclusions
          CDC guidance for
                 Pre-exposure vaccination
                 Post-exposure vaccination
                 State planning frameworks
          CDC technical assistance (as capacity allows)
          State control
          Individual choice
          Assessment of risk and benefit in the US should rest with those
           who have the risk - Citizens
          Provides the most protection, at the lowest cost, with the least
           chaos, and recognizes that response will and must primarily be a
           local and state responsibility
          Pre-exposure voluntary vaccination protects against a specific
           threat and puts prevention first. This is what public health and
           responsible government are all about
W Bicknell 10/23/02 BU SPH
 Likely Results of Pre-Exposure Vaccination
          Based on survey data, 50% to 70% of population will opt for
          Very rare serious complications and deaths
          Decreased risk to the immunocompromised from vaccination
           and smallpox
          Trained vaccinators and supplies in place in case of attack
          Possible decreased likelihood of attack
          Containment and control far easier in case of attack
          Hospitals and the health care system not overwhelmed
          Panic, disorder and the interruption of essential services and
           activities minimized
          Known specific preventive steps taken before a terrorist attack
          The public has an example of sound proactive public health

W Bicknell 10/23/02 BU SPH
                               Public Trust
              Whatever is done, it is vital that actions, including
               discussions, take place in a way that builds public trust
              Inappropriate secrecy, silence or recommendations that do
               not make sense erode public trust
              The responses of the federal government and state health
               departments to bioterrorism provide an opportunity to
               build trust and understanding of the importance of public
              Our response to smallpox and bioterrorism, if done with
               humility, openly and non-defensively, can be a win for
               everyone, protecting the public‟s health and strengthening
               the public health system
              So far, as a nation, we have done no better than a mediocre
               job. The pieces are in place for a good job. Will we do it?

W Bicknell 10/23/02 BU SPH
                         Take Away Messages
          The first cases will be missed
          4 day window – more myth than reality
          Ring containment – not for terrorism and not
           much else
          The old vaccine, calf lymph or tissue culture, is
           what we know works
          Other vaccines not yet ready, may work, but can
           we be certain?
          The more that is done pre-exposure, the easier it is
           to contain disease post-exposure
          Slight but near certain risk today to avoid possible
           huge individual & societal risk tomorrow.
W Bicknell 10/23/02 BU SPH
               Hope - Smallpox will never return
               Smallpox is the worst bioterrorism threat
               The US is on the verge of being well prepared
                     Minimum well prepared (opinion) 10 million pre-exposure
                     Mass vaccination systems exercised and tested
                     Vaccine supplies at the state level
               Systems and coordination pre and post attack remain a
                very large issue
               The Acute Care System is complimented by Public Health
                not vice-versa
               Furlough - I doubt if needed
               Liability - Seems like moving ahead
               Adequate preparation - Still a very open question
               I look forward to Al‟s Comments

W Bicknell 10/23/02 BU SPH
                             Thank You
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W Bicknell 10/23/02 BU SPH

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