SMALLPOX

1. SMALLPOX Terrorism, Science, Values, Choice, Public Health and Public Policy The US Health System Faces UNCERTAINTY William J. Bicknell, MD, MPH School of Public Health Boston University

2. The Issues • The Risk of Attack? • If an attack, the magnitude? • If an attack, can ring containment & quarantine work? • Vaccine risks? • Liability issues? • Are there responsible alternative options? • Who should decide what?

3. Challenges • 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

4. The Risk of Attack • Let’s address this first and get off the table • 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 • And there are reports of vaccination of N.Korean and Iraqi troops • My bottom line - Unknown but non-trivial risk of terrorist attack • Therefore, we need to know something about smallpox, let’s get some basics

5. Off the Wall? • Dr. Fenner: No errors and “A good case, reasonable for America” • Dr. Fauci: “….excellent and hopefully will generate some frank and needed discussion. The stepwise approach that you recommend makes sense and is quite reasonable….”

6. 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 American population not immune • ~ 50% may have some residual immunity • How much immunity ? No one really knows

7. 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 throat • 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

8. Smallpox transmission 2 • Close contacts are “best” - within 6 feet • Think of the morning metro or many other places • How easy is it to transmit? • Let’s consider some historical examples

9. 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 in another train…. Something like a hundred cases being infected from a single case.” • 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

10. More Examples • Other documented examples • Yugoslavia 1972 “..denied (having a) rash..no evidence of skin lesions” 11 secondary cases • Tripoli 1946 “…a highly modified attack..unrecognized… gives rise to… fatal attacks ” A smuggler infects wife and child • 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

11. Possible Attack Rates in Terrorist Contacts Something between 10% & 50% may be a reasonable assumption Dixon, p310

12. 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 • Much anecdotal evidence from the eradication years that the disease is less severe if vaccination within 4 days of contact • Vaccination within the window may/probably prevent death but not 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 a terrorist situation, finding initial contacts within 4 days is impossible

13. “The Race to Trace”* • “Contact identification is the most urgent task when investigating smallpox cases since vaccination of close contacts as soon as possible following exposure but preferably within 3-4 days may prevent or modify disease. This was the successful strategy used for the global eradication of smallpox.” CDC Interim Plan, Guide A, p. A-10 • A race that cannot be won in a terrorist scenario *Kaplan, Craft & Wein

14. A Recent Mathematical Model(Kaplan -Yale, Craft - MIT, Wein - Stanford) • Clearly demonstrates the limits and inadequacies of the current CDC recommendation for ring containment. • Also shows that, for any significant exposure, immediate mass vaccination is far superior. • Ratio of cases and deaths: Ring/Mass ~ 180/1

15. 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 days • Also demonstrates limited value and great difficulties with quarantine and isolation of susceptibles and the asymptomatic

16. Kaplan Unpublished

17. Plausible Case after 40 days(Play with the model ask wbicknel@bu.edu) • 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

18. Very Bad/Extreme Case ScenarioFirst 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

19. Ring Containment, Isolation & Quarantine • Excellent for eradication with high and growing population immunity, relatively low mobility and without malicious intent - A great achievement • 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 • The 4 day window - Exists but 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 probably cannot work

20. Ring Containment - Summary • Excellent for residual cases in an environment with high population immunity • Good for an isolated exposure, particularly if there is some population immunity • Inadequate for a mobile population, with low to absent immunity and a malicious exposure in multiple cities

21. The Magnitude of an Attack • Plan for the worst, hope for the best • Malicious and well executed • Multiple terrorists, Multiple cities

22. The Vaccine • It works and works well • There is plenty for everyone 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 seem very rare (Israel & US military n ~ > 1,000,000) • Semi-permeable membrane dressing prevents 99+% of viral shedding (Dr. Belshe, 5/8/01 at CDC) • Atopic dermatitis tricky (avoiding children helps a lot) • New and old vaccine probably similar complications • VIG good for many but not all complications

23. Dilute Vaccine Lasts 180+ Days From Dr. Belshe ACIP CDC Presentation May 8, 2002

24. RATIONING AND WHO DECIDES Federal control of the only effective tool

25. AND FEDERAL SUPPORT WILL BE MINIMAL “..quickly overwhelm..” is realistic and reasonable. BUT CDC HAS THE VACCINE AND THE STATES ARE LEFT HOLDING THE CONTROL BAG!

26. IF YOU WERE THE STATE HEALTH OFFICER • What would you do? • I’d call CDC and get access to my own supply of vaccine before the fact

27. The State Role • In addition to the constitutional responsibility of the states consider: • Risk may vary by state & city • Washington, New York, Boston, Chicago, Atlanta, Seattle, Los Angeles, San Jose vs. • Butte, Sioux Falls, Burlington, Boise, and either Portland • The states and the people in them may perceive risk differently • State by state options 1) to expand definition of first responders with 2) individuals given the right to opt for voluntary pre-exposure vaccination make considerable sense • States may give differ in risk recommendations given to citizens

28. Who should Decide? • 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

29. Why Voluntary Pre-Exposure Vaccination? • 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

30. Possible Objections • 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 methods • 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

31. 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 decreased: • 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 immunocompromised

32. Vaccine Issues - 2 • Accidental vaccination of contacts of vaccinees • Non-immunocompromised • Immunocompromised • Very rare • Mostly 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 • Use semi-permeable membrane dressings (Dr. Belshe) • Post-exposure drop to age 1 (and below if risk of exposure is high)

33. 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 (~ 5.5 million people) • The definition of first responder & priority for vaccination should be determined by each state: • Which health workers? • Who in the executive branch? • Fire and police? • Essential public service providers? • Media crews? • The Federal Government decides for itself

34. Liability Issues • Action needed whether pre- or post-exposure • New federal law specific for smallpox that: • Protects manufacturers and everyone in the delivery chain • Transfers liability to the federal government • Limits liability • Provides for fair compensation, within limits, to individuals • A Congressional initiative is needed now

35. First - a Measured Trial • Federal liability legislation • Careful guidelines to protect immunocompromised • Vaccinate 100,000 first responders (We’ve already vaccinated over 11,000 civilians since 1983, plus many military in the US until ‘90 and Israel until ‘96) • Use first responder volunteers to donate blood for VIG production • Observe vaccine complications very carefully • Revise guidelines and approach as indicated • Repeat with 250,000 to 500,000 first responders • Observe with care and revise as indicated • Vaccinate balance of first responders, a number in the low millions.

36. 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

37. Details • Dilute existing stock • Educate providers in technique using web technologies, CME, journals, in-service education • Deliver through all normal primary care sites - doctors’ offices, OPDs, health centers, ERs and health departments. • Federal government provides at no cost to states and states arrange for distribution within their borders

38. More Details • Consider limiting the charge for administration to $5 or $10 • Urge providers to administer for no charge • Offer during the course of ongoing medical care • Vaccine days as for flu shots are also an option • Those who wish to wait for a new vaccine may do so

39. Likely Results of Pre-Exposure Vaccination • Based on survey data, 50% to 70% of population will opt for vaccination • 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

40. Roles & Responsibilities • CDC • Safety guidelines for pre- and post-exposure vaccination - NOT the societal or individual risk decision • 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

41. Illustrative Control Options 1 - Post-exposure ring containment, isolation and quarantine 2 - Pre-exposure vaccination of first responders, post-exposure ring containment, isolation and quarantine 3 - Post-exposure mass vaccination 4 - Pre-exposure vaccination of first responders and general population, post-exposure ring containment 5 - Pre-exposure vaccination of first responders, post-exposure mass vaccination 6 - Pre-exposure vaccination of first responders and general population, post-exposure residual mass vaccination

42. Post Exp Ring Pre 1st Resp, Post Ring Post Exp Mass Vac Pre 1st Resp + Vol All. PostRing Pre 1st Resp, Post* MassVac Pre 1st + Vol All, Post* MassVac Vaccine Complications High High High Low Moderate Lowest Smallpox Most Deaths High Low Low Lower Lowest Deaths Benefit/Cost C >>B C>>B B>C B>C B>>C B>>>C Preferred -- + ++ ++ +++ ++++ Illustrative Smallpox Control Options * In the areas where There are cases

43. 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 health • 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

44. 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 rests with those who have the risk - Citizens • This 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 is all about

45. Thank You Email <wbicknel@bu.edu>