1. Smallpox Lessons Learned and Future Challenges

2. 2 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%)

3. 3 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

4. 4 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)

5. 5 How Vaccination Works Herd Immunity Smallpox Spreads to the Non-immune Immunization Slows the Spread Dramatically Epidemics Die Out Naturally Herd Immunity Protects the Unimmunized

6. 6 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

7. 7 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?

8. 8 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

9. 9 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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11. 11 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

12. 12 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

13. 13 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

14. 14 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?

15. Smallpox Vaccination Campaign Fall 2002 - Spring 2003

16. 16 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

17. 17 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

18. 18 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

19. 19 CDC Plan Voluntary vaccinations No screening or medical records review Self-deferral

20. 20 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

21. 21 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?

22. 22 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?

23. 23 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?

24. 24 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?

25. 25 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)."

26. 26 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

27. 27 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

28. 28 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

29. 29 The Real Problem Lack 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?

30. 30 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

31. Modeling Smallpox and the CDC, Post Smallpox Immunization Campaign

32. 32 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

33. 33 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.”

34. 34 Decomposing the Models – Common Factors Population at risk Initial seed Transmission rate Control measures under study

35. 35 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

36. 36 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

37. Where do the Models Differ?

38. 38 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

39. 39 What is the Data on Transmission Rate? Appendix I http://whqlibdoc.who.int/smallpox/9241561106_ chp23.pdf 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

40. What are the Policy Implications of the Transmission Rate?

41. 41 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

42. 42 Kaplan - Risk of 5 Mass immunization on case detection Best to pre-immunize health care workers

43. 43 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

44. What are the Politics?

45. 45 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

46. 46 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

47. 47 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

48. 48 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?

49. 49 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

50. 50 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?

51. What does this tell us about Pan Flu?