The Johns Hopkins University, Center for Civilian Biodefense Strategies

Biodefense Quarterly, June 1999
Volume 1, Number 1

Director's Greetings   Smallpox Destruction   WHA Resolution
Role of Emergency Medicine   Smallpox Facts   REVIEW: Biohazard
Recent Publications   Events   Editorial Board   Editorial Staff & Disclaimer

Greetings from the Director

D.A. Henderson, M.D., M.P.H.

This quarterly newsletter represents an effort by the Johns Hopkins Center for Civilian Biodefense Studies (CCBS) to disseminate information on the myriad issues related to bio-defense, and to help establish ties among the diverse members of the bio-defense community. We are pleased to make this inaugural issue available. Within the next eight pages and in future editions, readers can expect to find columns that:

  1. explore diverse viewpoints regarding major biodefense issues,
  2. report coordination and collaboration efforts among key sectors of the response community,
  3. provide resources for professionals to consult for developing planning initiatives,
  4. highlight recent news coverage of bio-defense topics,
  5. offer annotated bibliographies and other resources for self-education, and
  6. provide information on related events such as conferences and symposia. It is our hope that this newsletter will be a useful resource to our readership. We also invite your contributions to making this an effective communication and education tool.

This newsletter grows out of the CCBS desire to help develop medical and public health policies and structures -- at home and abroad -- to protect civilians from bioterrorism.

The Biodefense Quarterly manifests the Center's commitment to preventing the use of biological weapons, and our strategies are diverse. By articulating the horrific consequences of organic weapons in the in timate terms of disease and epidemic , we hope to augment the legal, political and moral prohibitions against their use.

Moreover, by identifying the microbiological, clinical and epidemiological attributes of bioweapons, and engaging health professionals in response planning, we hope to facilitate preparedness that diminishes the power of biological agents as instruments of terror.

Many readers will recognize The Johns Hopkins Center for Civilian Bio-defense Studies as a major sponsor of the National Symposium on Medical and Public Health Response to Bioterrorism. Convened this February in Crystal City, Virginia, this event brought together, for the first time, medical, public health, law enforcement and public safety officials for the purpose of examining the many issues surrounding an intentional release of a biological agent. For those who were unable to attend, an audio version of the program is available on our website at www.hopkins-id.edu/bioterror/index.html. Additionally, the written proceedings will be published in the July/August issue of CDC's journal, Emerging Infectious Diseases, and will be available online at www.cdc.gov/ncidod/eid.

With the symposium behind us, we are now laying out a detailed agenda that involves a number of components. Specifically, white papers for the main threats are being authored by our Working Group. Consensus statements on anthrax and smallpox have appeared in recent issues of The Journal of the American Medical Association, and a consensus statement on plague is due to be published later this summer. Our website is being regularly updated as new developments arise, and several projects are underway that focus on different facets of biodefense and epi demic management. Through these endeavors and through our quarterly newsletter, we shall continue to explore linkages and facilitate dialog among scientific, medical, public health, and law enforcement communities in order to support U.S. biodefense preparedness.

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Smallpox Virus Destruction: Why Change Direction?

Based on an op ed article published May 6,1999 in the Baltimore Sun.

Washington had done a turnabout, and the world followed. On May 22, the World Health Assembly passed a resolution postponing the destruction of the last known repositories of the smallpox virus until 2002. This decision came in the wake of the Clinton Administration's startling reversal of policy on April 22. Rather than move ahead with destruction as planned, the White House decided to retain the virus indefinitely for possible research.

Despite the action by the World Health Assembly (WHA), the debate is far from over. Do we relegate the smallpox virus to history and prevent its accidental or intentional release by destroying it? Or, do we safeguard the virus so that we may learn from it? And, what if any thing remains to be learned? The WHA has, in the end, taken the position of Solomon. In its resolution (see page 3), the assembly decided to retain the virus for further research until 2002 -- while at the same time strongly reaffirming the need to destroy remaining repositories.

It was only three years ago that member nations of the WHA had agreed by consensus to destroy the virus on June 30 of this year. The policy had been firmly supported by the United States since 1990, when the idea was first proposed to the WHA by Louis Sullivan, the U.S. secretary of health and human services. The Soviet Union, the only other country apart from the U.S. with known stocks of the virus, supported the proposal, as did virtually all other nations.

It is difficult to find anyone who knows personally the horrors of epidemic smallpox and who favors retaining the virus. The disease kills 30 percent; there is no treatment. Those who survive are left severely pock-marked, and some are blinded. It is no wonder that before its eradication in 1979, smallpox was the most feared of all the pestilential diseases.

Mass immunity to the disease is only a memory. Vaccination was discontinued in the U.S. in 1972 and throughout the world by 1980. Thus many, perhaps most, of those who were vaccinated are no longer protected. Stocks of vaccine both in the U.S. and globally are small, and there are no manufacturers now equipped to produce more.

Some virologists have insisted that the virus be retained for further research, arguing that studies may shed light on the cause of disease virulence or immunity. However, it should be noted that research requiring the use of the intact smallpox virus has long been of low priority. Worldwide, only one laboratory is now conducting such research: a former Soviet bioweapons facility, which began working with the virus in May 1996 (according to their official report). Elsewhere, very little work has been done for nearly 20 years. Moreover, other poxviruses such as monkeypox -- which is 95 per cent identical to smallpox -- are far easier to work with and should provide information with regard to the basic biology of the virus.

Others say that retaining the virus could aid development of a new vaccine or therapeutic drug. Neither product is likely or practical. In the first place, expenditures of several hundred million dollars would be needed for either a drug or a vaccine, and even then success would not be guaranteed. Secondly, a new antiviral drug is impractical, in part because of the difficulties in developing a successful drug against any virus disease, and in part because the smallpox virus in afflicted individuals is found primarily in pustules which are all but impermeable to drug penetration.

As for vaccine development, we should keep in mind that the vaccine in use is not derived from the smallpox virus, but originally came from cows and was called "cowpox." Thus, for purposes of vaccine development, the smallpox virus itself would not be needed. We should also remember that the smallpox virus does not produce disease in animals. Since there are no human cases, it would be impossible to determine whether a new vaccine was truly effective. Thus, we could never be certain that a vaccine was protective until actually used. Then, it could well be too late.

Editorial note: The Center for Civilian Biodefense Studies welcomes alternative view-points.

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World Health Assembly's May 22, 1999
Resolution on Destruction of Variola Virus

The Fifty-second World Health Assembly,

Recalling that resolution WHA49.10 recommended that the remaining stocks of variola virus should be destroyed on 30 June 1999 after a final decision had been taken by the Health Assembly;

Having considered the report of the Secretariat on destruction of the variola virus stocks, as well as the report of the January 1999 meeting of the WHO ad hoc Committee on Orthopox Virus Infections;

Affirming that the final elimination of all variola virus remains the goal of the World Health Organization and all Member States;

Noting that recent scientific reviews of the smallpox issue have presented arguments that retention of the variola virus stocks for the present would permit research for public health purposes, including the development of antiviral agents as well as an improved and safer vaccine;

Having noted a lack of consensus among Member States as to whether the Assembly should proceed to authorize destruction of the variola virus stocks on 30 June 1999 as proposed by the Assembly in 1996,

  1. STRONGLY AFFIRMS the decision of previous Assemblies that the remaining stocks of variola virus should be destroyed;

  2. DECIDES to authorize temporary retention up to not later than 2002 and subject to annual review by the World Health Assembly of the existing stocks of variola virus at the current locations - the Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America, and the Russian State Centre for Research on Virology and Biotechnology, Koltsovo, Novosibirsk Region, Russian Federation - for the purpose of further international research into antiviral agents and improved vaccines, and to permit high-priority investigations of the genetic structure and pathogenesis of smallpox;

  3. FURTHER DECIDES that any such research shall be funded by Member States or by other national or international bodies and shall be conducted in an open and transparent manner only with the agreement and under the control of WHO;

  4. REQUESTS the Director-General:

    1. to appoint a new group of experts which will establish what research, if any, must be carried out in order to reach global consensus on the timing for the destruction of existing variola virus stocks, and will:

        (a) advise WHO on all actions to be taken with respect to variola;
        (b) develop a research plan for priority work on the variola virus;
        (c) devise a mechanism for reporting of research results to the world health community;
        (d) outline an inspection schedule to confirm the strict containment of existing stocks and to assure a safe and secure research environment for work on the variola virus, and make recommendations on these points;

    2. to facilitate the full participation in the work of the new group of experts of a limited number of scientists and public health experts from Member States of each of the WHO regions;

    3. to report the initial recommendations and plans of the group of experts, including relevant costs for WHO, to the Executive Board at its 106th session in May 2000, providing that external funding has been made available for this purpose;

    4. to present a detailed report, including progress of the research programme on the smallpox virus, to the Executive Board and Health Assembly as soon as possible, but in any event not later than 2002, and to make recommendations to the Executive Board and Health Assembly regarding their proposals for the date of final destruction of the remaining stocks of variola virus.

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The Role of Emergency Medicine in Responding
to a Bioterrorist Attack

Christina L. Catlett, M.D.

Editorial note: This column is designed to highlight effective coordination efforts -- either planned or practiced -- that can serve as models for thebioterrorism response community. Moreover, this column is dedicated to fostering mutual understanding of the roles, responsibilities and authorities of diverse members of the response community. To that end, we invite contributions from the field. Our first contributor is Christina Catlett, Assistant Chief of Service at the Johns Hopkins Hospital, Department of Emergency Medicine.

Emergency physicians face significant hurdles to delivering effective care in the unique, crisis situation posed by a bioterrorist attack. The prolonged state of distress associated with a willfully created epidemic has the potential to tax the resources of the emergency department (ED) severely, most especially its personnel. At the same time, how ever, self-reflection on these challenges now provides an unparalleled opportunity for emergency medicine to develop greater sophistication in collaboration and coordination across disciplines, departments, and institutions -- an organizational outlook essential to staying bioterrorism's potential consequences.

Emergency physicians are trained in disaster medicine and in dealing with mass casualties; yet, a large-scale biological attack would result in a catastrophe the likes of which no disaster course or tabletop exercise could prepare one for. New and unusual problems would arise for the ED. First, natural disasters and chemical terrorist attacks generally result in a finite number of patients acutely affected. These types of incidents usually overwhelm resources for 12 to 24 hours but allow the ED to recover within 1 to 2 days. A biological attack with a contagious agent, however, would have long-term implications. Not only will EDs be inundated with large numbers of acutely ill patients, but numbers will continue to grow over succeeding hours and days. Further more, with some biological agents, future waves or generations of cases can be expected weeks after the initial assault.

Second, several of the biological agents are not only highly lethal but highly contagious as well. Most EDs, however, have very limited isolation capabilities and personal protective equipment. ED staff will be especially vulnerable to infection with communicable agents and should be considered a priority when the vaccination schedule is established. Lastly, life in the ED must go on, even in the midst of crisis. In addition to the influx of attack victims and the "worried well," the emergency department must continue to treat heart attacks, strokes, shootings, etc. It is possible that panic will set in among employees once the first case is disclosed, depleting the ED of desperately needed staff. It is likely that health care staff will need emotional support to cope with a devastating crisis. Further, effective use of scarce resources will probably necessitate communication and cooperation among different hospitals in a community or region.

The issue of scarce resources under lines the importance for emergency physicians and others in the response community to envision an ED not as a self-contained, functioning unit, but as a locale embedded in larger institutions. They include the hospital, the community and the society, and they represent additional expertise, provisions, and obligations. Responding to bioterrorism, the emergency department will need to interface with multiple specialties and agencies, including first responders, infectious control specialists, the public health department, the F.B.I, and others.

As sentinel professionals, for example, emergency physicians have a responsibility to alert the proper public health and law enforcement authorities at the onset of an epidemic. Learning to recognize the disease complexes associated with the biological weapons of greatest concern is a first step in assuming this responsibility. Given the vague symptomatology common to the initial phase of exposure, it is unrealistic to think that an emergency physician will be the first to say, "We have an anthrax attack," or "This is undoubtedly smallpox." It is completely reasonable, however, to expect the emergency physician to recognize an epidemic of acutely ill patients. An unusual number of previously healthy patients requiring intubation may be the only clue that an attack has occurred.

Moreover, other specialty groups within the hospital, including infectious disease specialists and hospital epidemiologists, are important collaborators with the emergency department in the context of a bioterrorist incident. Hospital disaster policies to cope with the unique aspects of a biological attack require the contributions of all these professional groups. Hospital preparedness must include an efficient system for notification of the proper public health authorities and a well-defined communication structure.

Faced with the overwhelming task of bioterrorism readiness, the emergency medicine community is already displaying greater awareness and expertise in biodefense. The American College of Emergency Physicians, under the leadership of Dr. Joe Waeckerle, has been developing biodefense curricula for emergency professionals; moreover, the August 1999 issue of Annals of Emergency Medicine will address the issue of bioterrorism planning and response.

Interfacing with other specialties and agencies will make emergency professionals more effective in their own realm as well as advance a strong, collective counter-measure to bioterrorism.

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Facts about Smallpox and Its Frightful Potential

Editorial note: Readers are encouraged to review the full consensus statement of the Working Group on Civilian Biodefense, published in the June 9, 1999 issue of The Journal of the American Medical Association, Volume 281, Number 22, pp. 2127-2137.

Smallpox, because of its high case-fatality rates and transmissibility, now represents one of the most serious bioterrorist threats to the civilian population. Over the centuries, naturally occurring smallpox, with its case-fatality rate of 30 percent or more and its ability to spread in any climate and season, has been universally feared as the most devastating of all the infectious diseases.

Smallpox was once worldwide in scope; before vaccination was practiced, almost everyone eventually contracted the disease. In 1980, the World Health Assembly announced that smallpox had been eradicated and recommended that all countries cease vaccination. That same year, the Soviet government embarked on an ambitious program to grow small pox in large quantities and adapt it for use in bombs and intercontinental ballistic missiles. They succeeded.

Russia still possesses an industrial facility that is capable of producing tons of smallpox virus annually and also maintains a research program that is thought to be seeking to produce more virulent and contagious strains.

An aerosol release of smallpox virus would disseminate readily, given its considerable stability in aerosol form and epidemiological evidence suggesting the infectious dose is very small. Even as few as 50-100 cases would likely generate widespread concern or panic and a need to invoke large-scale, perhaps national emergency control measures.

Smallpox spreads directly from person to person, primarily by droplet nuclei expelled from the oropharynx of the infected person or by aerosol. Natural infection occurs following implantation of the virus on the oropharyngeal or respiratory mucosa.

Contaminated clothing or bed linen could also spread the virus. Special precautions need to be taken to insure that all bedding and clothing of patients are autoclaved. Disinfectants such as hypochlorite and quaternary ammonia should be used for washing contaminated surfaces.

A smallpox outbreak poses difficult problems because of the ability of the virus to continue to spread through out the population unless checked by vaccination and/or isolation of patients and their close contacts.

Between the time of an aerosol release of smallpox and diagnosis of the first cases, an interval of as much as two weeks is apt to occur. This is because there is an average incubation period of 12 to 14 days.

After the incubation period, the patient experiences high fever, malaise, and prostration with headache and backache. Severe abdominal pain and delirium are sometimes present.A mascopapular rash then appears, first on the mucosa of the mouth and pharynx, face and forearms, spreading to the trunk and legs. Within one or two days, the rash becomes vesicular and later pustular. The pustules are characteristically round, tense and deeply embedded in the dermis; crusts begin to form about the eighth or ninth day. When the scabs separate, pigment-free skin remains, and eventually pitted scars form.

Approximately 140,000 vials of vaccine are in storage at the Centers for Disease Control and Prevention, each with doses for 50-60 people, and an additional 50-100 million doses are estimated to exist worldwide. This stock cannot be immediately replenished, since all vaccine production facilities were dismantled after 1980, and renewed vaccine production is estimated to require at least 24-36 months.

Treatment of smallpox is limited to supportive therapy and antibiotics as required for treating secondary bacterial infections. There are no proven antiviral agents effective in treating smallpox.

Recommendations of the Working Group on Civilian Biodefense include testing and ultimate consideration for FDA approval of a vaccinia strain grown in tissue culture rather than on calves, finding a rapid diagnostic test for smallpox virus in the asymptomatic early stages, and developing a more attenuated strain of vaccine.

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Biohazard
by Ken Alibek
Random House, 1999

Reviewed by Tim Scott, M.H.S.

Biohazard is Dr. Ken Alibek's autobiographical account of his life in the former Soviet Union, his rise to power as a high-ranking official in Biopreparat -- the secret civilian component to the Soviet biological weapons program -- and the moral interrogations to which he subjected himself and the institution he helped create. Within Biohazard are two integrated narratives. The first provides a history of the world's most comprehensive bioweapons program, whose geographic reach, scientific agenda and production capacity astound. The second narrative shows the life of a complex man, whose desires to practice medicine, serve his country, and achieve a measure of social and political authority (as an ethnic minority among a Russian majority) propelled him through a successful career in mass destruction.

From the time before the Biological Weapons Convention, to the early 1990s when Dr. Alibek defected to the United States, the Soviets explored the use of biologics for weaponry. The author describes the relentless drive and the vast government resources used to design and perfect biological weapons slated for use against the West. Readers encounter chilling details of biological weapons tests, accidents involving deadly organisms, and confrontations with Russian officials as well as inspectors from the West. Dr. Alibek recounts, for instance, a time when he had to answer to KGB and military officials when caught standing -- literally -- in a puddle of deadly Tularemia bacteria after an accident at Omutninsk. Although the exact mechanisms cannot be revealed for reasons of security, the Soviet weapons are described in a relatively straightforward manner that is easily understood by the average reader.

Dr. Alibek spent much of his career in the Soviet military and was quickly promoted through the ranks of the Biopreparat system during its rapid expansion in the 1980s. Alibek him self is amazed at how his career as a bioweaponeer could diverge so greatly from his youthful desire to practice medicine. As his story unfolds, read ers discover how loyalty, fear and deceit were central to sustaining the Soviet program. Propagated by Soviet leadership, images of a robust and expanding American offensive program served as strong motivation to work for Biopreparat.

The Soviets' ability to build, maintain and keep secret a program of this enormity is extremely alarming. Equally unnerving is the delicate yet resilient set of beliefs shoring up the work of political leaders and bioweaponeers behind the program. Biohazard instructs its readers well in the technical, organizational, and emotional dimensions of the largest bioweapons program in the world.

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Recent Publications about Biodefense

  1. Annals of Emergency Medicine. To be published Aug. 1999.

    • Kiem, M., and A. Kaufmann. The Anthrax Hoax Phenomenon: Principles for Emergency Response to Bioterrorism. Presents an overview of anthrax hoaxes and their impact on the emergency response system.
    • Kiem, M., et. al. Do U.S. Emergency Medicine Residency Programs Provide Adequate Training for Bioterrorism? Provides results of a survey administered to 118 emergency medicine program or residency directors on program BW preparedness, and the availability of BW training.

  2. Proceedings from the National Symposium on Medical and Public Health Response to Bioterrorism. Emerging Infectious Diseases. Jul./Aug. 1999. 5(4). Speakers include Health Secretary Donna Shalala; Assistant Health Secretary Margaret Hamburg; Richard Clarke, National Security Council; Dr. Christopher Davis, Former Senior Intelligence Analyst for CBW Matters; and Dr. D. A. Henderson, Director, Johns Hopkins Center for Civilian Biodefense Studies.

  3. Henderson, D.A., et. al. Smallpox as a Biological Weapon: Medical and Public Health Management. Journal of the American Medical Association. June 9, 1999, pp. 2127-37. Outlines specific consensus recommendations regarding smallpox vaccination, postexposure isolation and infection control, hospital epidemiology and infection control, home care, environmental decontamination, and additional research needs.

  4. Inglesby, T.V., et.al. Anthrax as a Biological Weapon: Medical and Public Health Management. Journal of the American Medical Association. May 12, 1999, pp. 1735-45. Outlines specific consensus recommendations regarding diagnosis, vaccination, therapy, postexposure prophylaxis, environmental decontamination and additional research needs.

  5. Christopher, G. W., and E. M. Eitzen, Jr. Air Evacuation under High-level Biosafety Containment: The Aeromedical Isolation Team. Emerging Infectious Diseases. Mar.-Apr. 1999. 5(2): 241-6. Describes in great detail the military response to a lethal,contagious disease outbreak

  6. Henderson, D.A. The Looming Threat of Bioterrorism. Science. Feb. 26, 1999, pp. 1279-82. Provides an overview of the emerging threat of bioweapons and the need for strong national preparedness and response measures.

  7. Drugs and Vaccines against Biological Weapons. The Medical Letter on Drugs and Therapeutics. May 12, 1999, pp. 1735-45. Feb. 12, 1999. 41(1046): 15-16. Outlines symptoms, treatment, and prevention of Plague, Tularemia, Brucellosis and Smallpox.

  8. World Health Organization. Destruction of the Smallpox Virus. Weekly Epidemiological Record. Jan. 29, 1999, pp. 27-8. Summary of the WHO Orhtopox Virus Committee, Jan. 1999.

  9. Biological Weapons. Critical Reviews in Microbiology (entire issue). Feb. 1998. 24(3).

    • Atlas, R. M. The Medical Threat of Biological Weapons. pp. 157-68. Presents a comprehensive overview of the biological threat and what it means for the general public. Also focuses on public health response.

    • Roberts, B. Export Controls and Biological Weapons: New Roles, New Challenges. Presents the problems and possible solutions regarding international trade of biologics with respect to biological warfare. Issues include defense research and proprietary rights.

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Editorial Board

D.A. Henderson, M.D., M.P.H.
Director

Tara O'Toole, M.D., M.P.H.
Senior Fellow

Tom Inglesby, M.D.
Assistant Professor

Monica Schoch-Spana, Ph.D.
Research Coordinator

Molly D'Esopo
Newsletter Coordinator

Tim Scott
Research Assistant

 

Back to Smallpox Virus Destruction Page

Threat of Bioterrorism

Smallpox Virus Destruction

Meeting of the WHO Variola Research Committee

The Research Agenda Utilizing Variola Virus:
A Public Health Perspective

Biodefense Quarterly, June 1999

Risk of a Deliberate Release of Smallpox Virus;
Its Impact on Virus Destruction

Deliberations Regarding the Destruction of Smallpox Virus: A Historical Review, 1980-1998

Confronting Biological Weapons: a special section in Clinical Infectious Diseases

Smallpox as a Biological Weapon

Recent Events and Observations Pertaining to Smallpox Virus Destruction in 2002

Bioterrorism and the People: How to Vaccinate a City against Panic