Smallpox

Lessons Learned and Future Challenges

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Why Smallpox Bioterrorism?

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

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

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 freeze-dried vaccine production (Collier)

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How Vaccination WorksHerd Immunity

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

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

Local Lesion Can be Spread on

the Body and to Others

Progressive (Disseminated) Vaccina Deadly Like

Smallpox, but Less Contagious

Encephalitis Heart Disease?

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Historic Probability of Injury

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 Death or Severe Permanent Injury - 1/1,000,000

Mostly among immunsupressed persons

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Global Eradication Program 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

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

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

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

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

The whole world may be like Hawaii before the first sailors

If everyone gets sick at the same time, even non-fatal diseases such as measles become fatal

A massive smallpox epidemic would be a national security threat

Is a massive epidemic possible?

Smallpox Vaccination Campaign

Fall 2002 - Spring 2003

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Why Did White House Wait so Long?

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

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

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

Voluntary vaccinations No screening or medical records review Self-deferral

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Problems in the CDC Plan

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

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

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

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

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

"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?

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?

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

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 ProblemLack of Information

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

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

Modeling Smallpox and the CDC, Post Smallpox Immunization Campaign

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The Dark Winter Model

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

Koopman – worked in the eradication campaign “Smallpox is a barely contagious and slow-

spreading 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

Population at risk Initial seed Transmission rate Control measures under study

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Population at Risk

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

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

Where do the Models Differ?

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Transmission Rate is the Key

< 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?

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

What are the Policy Implications of the Transmission Rate?

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Dark Winter - Risk of 10

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

Mass immunization on case detection Best to pre-immunize health care workers

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Metzler/CDC - Risk of 2-3

Contact tracing and ring immunization Trace each case and immunize contacts Immunize contacts of contacts Takes a long time to get the last case

What are the Politics?

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Reinstituting Routine Vaccinations

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

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 Cons

Lots of complications and deaths from the vaccine Requires massive changes in federal vaccine plans

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Contract Tracing and Ring Immunizations

Pros Limits the vaccine complications Does not require hard policy choice to

immunize everyone 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

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?

No one was interested Of course the states will do what they are required to

do What else can the states say when they depend on

federal money?

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Political Choices are Hidden in the Models

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

Smallpox is still a real threat 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 How do we resolve the uncertainty?

What does this tell us about Pan Flu?