Smallpox

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Status Brief
History/Origins:

Developmental Milestones/Developments to Date:

Current Assessment/State of the Field:

Problems/Challenges:

Proposals:

1998

Henderson, D., A., “Bioterrorism as a Public Health Threat,” Emerging Infectious Diseases, vol. 4, No. 3, July-sept 1998.

  1. Admonition & historical accounts.

Russia, Japan, Ebola, Marburg, Hemorrhagic Fever, Smallpox, Anthrax, Germany, Yugoslavia, Vaccination, Iraq, Bioterrorism

1999

Henderson, DA, Inglesby, TV, “Smallpox as a Biological Weapon, Medical and Public Health Management,” JAMA 1999;281:2127-2137.

Smallpox

2000

Benjamin, Georges C. “Chemical and Biological Terrorism: Planning for the WorstPhysician Executive Volume 26 Issue 1. 80. January/February 2000.

  1. Chemical or biological terrorism is the use of pathogenic microbes or toxins derived from plants, animals, microbes, or chemical agents to achieve terror.” – page 80
  2. ”Chemical and biological weapons, like nuclear weapons, are categorized as weapons of mass destruction (WMD) because of the high number of potential victims that can result from their use.” – page 80 *
  3. ”While any chemical can be weaponized, the chemical agents traditionally of concern fall into four categories: nerve agents like sarin, which create an anticholinergic-like syndrome; vesicants like mustard gas, that cause a blistering or burn-like syndrome; cyanide, which interrupts aerobic metabolism; and riot control agents such as mace, which generally cause incapacitation.” – page 80
  4. ”Biological agents act like chemical agents but have a slower onset of action. Agents of concern include Ricin.” – page 81
  5. ”The ideal bioweapon is hard to detect from the usual microbial flora, has person-to-person spread, and is easy to aerosolize. There are two groups of organisms of public health concern: those that cause a high morbidity or a high mortality.” – page 81
  6. ”Examples of high morbidity organisms include salmonella, cholera, or E. coli. The number of highly toxic organisms is fortunately quite low and includes anthrax, smallpox, and the viruses that cause hemorrhagic fevers, plague, brucellosis, and tularemia.” – page 81
  7. “Clues that biological terrorist events have occurred include an unexplained increase in respiratory cases or deaths, or dead and dying animals. Epidemiological clues include diseases with the wrong mode of transmission, which occur in an inappropriate geographic distribution or infect a new or novel population.” – page 81
  8. “Components of a biological/chemical terrorism disaster plan: plan how to identify the threat; develop an effective public health disease surveillance system; link the public health system and the traditional medical care delivery system; develop command and control systems; determine hospital bed availability; define disease containment, isolation, and quarantine procedures; plan how to obtain extra life support equipment such as respirators; plan how to train clinical staff to identify high-risk unusual diseases; ensure non-clinical staff are trained on the management of suspicious packages and mail; identify experts; plan simple handling and transport; plan how to communicate high risk information; manage medical examiner cases; and maintain a crime scene.” – page 81
  9. ”Effective disease control strategies such as case finding, decontamination, prophylaxis and vaccination, and quarantine must be defined.” – page 82

Chemical, WMD, Bioterrorism, Public Health, Military, Sarin, Japan, Ricin, E. coli, Cholera, Salmonella, Anthrax, Smallpox, Hemorrhagic fever, Plague, Brucellosis, Tularemia, Prophylaxis, Vaccination, Quarantine

 2001

Cookson, Clive, “International Economy: Scientists Convert Virus Into Killer Biowarfare Fear,” THE FINANCIAL TIMES LIMITED, Jan 12, 2001. international economy, pg 15.

Plague, Mousepox, Viral Research, Smallpox

 

Fauci, Anthony, S., “Smallpox Vaccination Policy—The Need for Dialogue,” NEJM, Editorial, Vol. 346, No.17, pg. 1319.

  1. “Unfortunately, the threat of an aerosol release of smallpox is real and the potential for a catastrophic scenario is great unless effective control measures can be quickly brought to bear.”
  2. “Ultimately, success in controlling a burgeoning epidemic will depend on the availability of adequate supplies of vaccine and VIG. An adequate stockpile of those commodities would offer a relatively inexpensive safeguard against tragedy.”

Anthrax, Smallpox, Risk, Russia

2002

Powers, Michael and Ban, Jonathan, “Bioterrorism: Threat and Preparedness“, National Academy of Engineering. Spring 2002 http://www.nae.edu/Publications/Bridge/EngineeringandHomelandSecurity/BioterrorismThreatandPreparedness.aspx

  1. Therefore, rather than planning for a narrow range of least-likely, high-consequence contingencies or focusing only on additional mailborne anthrax attacks, we must plan for a variety of future incidents–including incidents that cause mass casualties and mass disruption.”
  2.  “The incidents aroused significant fear and disruptions but not mass casualties. Based on these attacks, some analysts have suggested that terrorists would not be able to orchestrate mass-casualty attacks using biological weapons. Others have considered these attacks as demonstrations of terrorists’ ability to acquire high-quality anthrax”
  3.  “Rather than focusing on vulnerability to a particular organism or looking to history to determine what is to come, policy makers and scientists must recognize that the bioterrorist threat is not uni-dimensional. We must consider four key elements of the threat: the who (the actor), the what (the agent), the where (the target), and the how (the mode of attack).”
  4.  “We do not know how “massive” an attack would have to be to overwhelm the response system, instill fear and panic, or cause serious political or economic fallout.”
    “Every dollar spent preparing for a specific agent, such as building stocks of smallpox or anthrax vaccine or purchasing antidote for botulinum toxin, is a dollar that cannot be spent on preparedness for other organisms.
  5. Given the variety of combinations among actors, agents, targets, and dissemination techniques, a public health system must be capable of rapidly and accurately detecting and assessing a large number of bioterrorism scenarios and addressing most contingencies.”
  6.  “planning should be based on developing the capability of effectively and efficiently responding to a variety of bioterrorist contingencies”
  7.  “We must strike a better balance between hedging our defenses against high-end, mass-casualty events and building a “system of systems” capable of addressing both a wider range of bioterrorist contingencies and natural outbreaks of infectious disease.”
  8.  “In addition, accurate and timely information will be the backbone of the decision making process in times of crisis and will provide credible and consistent information to the general public to reduce panic.”
  9.  “A national surveillance system to provide an early warning of unusual outbreaks of disease, both natural and intentional, will be a critical component of our preparedness. This system will depend on an information infrastructure that includes electronic data networks connecting local public health departments and area health care providers and providing regular analyses of the data for the presence of unusual trends that could indicate a bioterrorist attack”

Public Health, Bioterrorism, WHO, Emergency Response, Smallpox, Anthrax

 

Miriani, Allison, “Hospitals pushed to plan for bioterrorist attacksCapital Service News. Feb. 22, 2004. http://cns.jrn.msu.edu/articles/2002_0222/biohazardplan.html

  1. “Most larger hospitals have a bioterrorism plan. The bill would make sure that all hospitals, including small outstate facilities, will comply, Scott said.”
  2. “Although there are 15 million doses of the vaccine for smallpox in the United States right now, Johnson said, many side effects could even result in death from the vaccine. That is why the Department of Community Health does not advocate a mass vaccination campaign, he said.”
  3. “”We need strict airport precautions, contact isolations. We have to notify public health authorities immediately at the local level and from there the state,” he said. “We need to identify those who have had contact with the person (who was exposed).””

Public Health, Smallpox, Bioterrorism, Emergency Response

 

Barry, John et. al, “Assessing the Threat“, Newsweek, Vol. 140 Issue 16, p52, 14 October 2002.

  1. “Labs in the United States and Russia keep samples under lock and key; whether anyone else has it is the crucial question.”
  2. “No longer found in nature, smallpox can’t be made in a lab and would probably require a suicidal carrier to deliver it.”
  3. “The notion of a black market in smallpox keeps the Bush administration up at night. Homeland Security czar Tom Ridge points to “credible information within the international community at large that some of our enemies have smallpox.” Vice President Dick Cheney thinks so, too.”
  4. “When bioweapons inspectors visited Iraq in the mid-1990s they found no smoking gun, but they did find a disturbing sliver of evidence. They saw the word “smallpox” written in Arabic on a freeze-dryer that could have been used to weaponize the virus; Iraq claimed the dryer was used to make vaccines.”
  5. “When Hussein Kamel, Saddam’s son-in-law and his bioweapons director, defected temporarily to Jordan in 1995, he disclosed much about Iraq’s bioweapons, but he denied any effort to weaponize smallpox.”
  6. “The simplest delivery vehicle would be an infected soldier or terrorist with a hacking cough riding the crowded subways or buses of an American city. Whereas that might initially infect dozens of people, an aerosol bomb that sprayed a virus-laden mist would reach hundreds.
  7. “Iraq and several other countries have the capability of making aerosols.”
  8. “…last month started vaccinating frontline health-care workers. Some Israeli bioweapons experts are convinced that Iraq poses a smallpox threat and advocate vaccinating the entire population. Britain and Australia have been buying vaccines.”

Russia, Iraq, Smallpox, Biosecurity, Vaccination

2003

Vellozi, Claudia, et.al, “Generalized Vaccinia, Progressive Vaccinia, and Eczema Vaccinatum Are Rare following Smallpox (Vaccinia) Vaccination: United States Surveillance,” INVITED ARTICLE: CONFRONTING BIOLOGICAL WEAPONS, 2003.

  1. “military began vaccinating against smallpox in Decemeber 2002 for bioterrorism preparedness.”
  2. dermatological manifestations
  3. “adverse reactions” to the smallpox vaccine

Military, Vaccination, Smallpox

 

Bozzette., Samuel, A., et. al., “A Model for a Smallpox-Vaccination Policy,” n engl j med 348;5, January 30, 2003.

  1. Background: “The new reality of biologic terrorism and warfare has ignited a debate about whether to reintroduce smallpox vaccination.”
  2. Methods: “We developed scenarios of smallpox attacks and built a stochastic model of outcomes under various control policies. We conducted a systematic literature review and estimated model parameters on the basis of European and North American outbreaks since World War II. We assessed the trade-offs between vaccine-related harms and benefits.”

Vaccination, Smallpox

Davis, Jim, “The Looming Biological Warfare StormAir & Space Power Journal, Volume 17, Issue 1. 57. Spring 2003.

  1. ”Until very recently, the lack of focus on this subject (biological warfare) has resulted in a lack of appropriate funding and accountability.” – page 58
  2. ”Unless we focus appropriate dollars and develop a coherent national plant to prepare for and prevent such actions, the United States will likely suffer an enormous economic loss that could even lead to our demise as a superpower.” – page 58
  3. ”A belief in one or more of at least six false assumptions or myths helps explain why individuals, including senior civilian and military leaders, do not believe that a mass-casualty biological warfare (BW) attack will occur.” – page 58
  4. ”Myth one: there never really has been a significant BW attack” – page 58
  5. ”Even before the fall 2001 anthrax terrorism in the United States, incidents of BW and bioterrorism have occurred on multiple occasions.” – page 58
  6. ”Today, more countries have active biological warfare programs than at any other time in history, which increases the likelihood that BW will be used again in the future.” – page 58
  7. ”Myth two: The United States has never been attacked by a BW agent” – page 59
  8. ”Myth three” you have to be extremely intelligent, highly educated, and well-funded to grow, weaponized, and deploy a BW agent” – page 59
  9. ”Dr. Tara O’Toole, deputy director for the Center for Civilian Biodefense Studies at Johns Hopkins University, believes we have probably crossed over the threshold from ‘too difficult’ to accomplish to ‘doable by a determined individual or group’” – page 59
  10. “Much of the technical information is readily available on the internet, in libraries, and through mail order channels that provide ‘how-to’ manuals.” – page 59
  11. ”Myth four: biological warfare must be too difficult because it has failed when it has been tried” – page 59
  12. ”Myth five: there are moral restraints that have kept and will keep BW agents from being used” – page 60
  13. ”Morality can be marshaled as a reason both to limit BW use and to advocate mass killings – depending on the decision maker’s values and perspectives” – page 60
  14. ”Myth six: the long incubation period required for BW agents before onset of symptoms makes BW useless to users” – page 60
  15. ”There have already been multiple BW attacks, and to a savvy weaponeer, the incubation period can be used as an advantage rather than a disadvantage.” – page 60
  16. ”There are two primary motivations that might drive an adversary to attack the United States with a BW agent. The first motivation is to gradually ‘erode US influence’ as a world superpower. The second is categorized as ‘revenge or hate’” – page 61
  17. ”The author believes that there are three most likely BW scenarios the United States and its allies might face in the future: an agroterrorist event against the United States, a BW attack on United States and allied troops in the Middle East, and/or a bioterrorist attack against a large population center in the United States or an allied state.” – page 61
  18. ”Such myths continue to inhibit the adequate funding of US and allied biodefense” – page 66

Military, Anthrax, Plague, Smallpox, Tularemia, Sarin, Japan, Iraq, Iran, Nonproliferation, WMD

2004

Editors, “Assessing The Threat of BW Terrorism”. NTI. 2004. http://www.nti.org/h_learnmore/bwtutorial/chapter04_01.html

  1. “With the exception of the smallpox virus, most bioterrorism threat agents can be isolated from natural sources such as diseased animals, patients, or even contaminated soil in the case of anthrax spores. Nevertheless, more than 85 different strains (varieties) of anthrax bacteria have been identified in nature, and only a few of these strains are highly virulent, or capable of causing disease.”
  2. “Once terrorists acquired a “seed culture” of a virulent pathogen, they would need to cultivate the agent in laboratory glassware or a small stainless steel fermentation tank.”
  3. “The goal of weaponization is to convert the agent into a form in which it can be dispersed as an aerosol cloud of microscopic particles, ranging in size from one to five microns (thousandths of a millimeter). Only particles with these dimensions are small enough to lodge in the tiny air sacs of the victims’ lungs to cause infection.”
  4. “Anthrax spores can survive for decades in soil and for hours in an airborne aerosol. Furthermore, anthrax spores can survive environmental contaminants and potentially become re-aerosolized.”

Bioterrorism, Anthrax, Smallpox, Biosafety, Public Health

 

Kretzschmar, M., “Ring Vaccination and Smallpox Control,” Emerging Infectious Diseases 10, 2004:832-41.

Vaccination, Smallpox

2005

Knauss, Tim, “U.N. to Get Bioterror Agent Decontamination SystemsNTI. Dec. 13, 2005.
http://gsn.nti.org/gsn/GSN_20051213_1084CFA2.php

  1. “Two $60,000 machines capable of cleansing mail of anthrax and other biological agents were completed”
  2. “BioDefense said independent tests confirm that the system, which was created after the September 2001 al-Qaeda attacks, is capable of eliminating anthrax, smallpox, ricin, HIV, influenza, botulism and the plague”

Bioterrorism, Biodefense, Public Health, Anthrax, Smallpox, Ricin, Decontamination, al-Qaeda

2006

Baker, Michael & David Fidler, “Global Public Health Surveillance Under New International Health Regulations,” Emerging Infectious Diseases, Vol. 12, No. 7, pgs. 1058-1065, July 2006.

  1. “IHR (International Health Regulations) 2005 identifies health-related events that each country that agrees to be bound by the regulations must report to WHO.”
  2. “These events include any unexpected or unusual public health events regardless of its origin or source.”
  3. “IHR 2005 also requires state parties …to inform WHO of public health risks identified outside their territories that may cause international disease spread, as manifested by exported or imported human cases, vectors that may carry infection or contamination, or contaminated goods.”
  4. “IHR 2005 defines a ‘public health emergency of international concern’ (PHEIC) as ‘an extraordinary event’ which is determined by the WHO.”
  5. “IHR 2005 contains a ‘decision instrument’ that helps state parties identify whether a health-related event may constitute a PHEIC and therefore requires formal notification to WHO.”
  6. “IHR 2005 includes a list of diseases for which a single case may constitute a PHEIC and must be reported to WHO immediately.  This list consists of smallpox, poliomyelitis, human influenza (flu) caused by new subtypes, and severe acute respiratory syndrome (SARS).”
  7. “IHR 2005 also encourages state parties to consult with WHO over events that do not meet the criteria for formal notification but may still be of public health relevance.”
  8. “IHR 2005’s surveillance strategy, especially the decision instrument, has been specifically designed to make IHR 2005 directly applicable to emerging infectious disease events, which are usually unexpected and often threaten to spread internationally.”
  9. “IHR 2005’s purpose is to prevent, protect against, control, and facilitate public health responses to the international spread of disease.”
  10. “IHR 2005 makes surveillance central to guiding effective public health action against cross-border disease threats.”
  11. “Surveillance needs to be sufficiently sensitive to detect infectious agents that have not yet resulted in large numbers of diagnosed cases.”
  12. “One approach to this challenge is [[Syndromic Surveillance]], but such surveillance has not been effective in detecting emerging infectious diseases early.”

Biosurveillance, Flu, Anthrax, Polio, SARS, Smallpox, Public Health

2007

Collett Marc S. “Impact of Synthetic Genomics on the Threat of Bioterrorism with Viral Agents. In: Working Papers for Synthetic Genomics: Risks and Benefits for Science and Society,” pp. 83-103. Garfinkel MS, Endy D, Epstein GL, Friedman RM, editors. 2007.

  1. “From a bioterrorism perspective, viruses isolated from nature are a sure bet. Their virulence and transmissibility are known. Their effect and impact can be predicted or calculated. Viruses isolated directly from diseased hosts (called “primary isolates”) demonstrate clearly the consequences of their infection. Additionally, the virus’s ability to survive, persist and spread in the environment and among susceptible hosts is generally known. Finally, pathogenic viruses isolated from diseased hosts are typically “hot” viruses; that is, primary isolates of pathogenic viruses tend to cause severe disease in their host.” P87
  2. “Most viral genome sequences deposited in databases are derived from laboratory-passaged viruses. While many sequences may be derived from low-passage viruses, and are therefore more likely to be close to their primary isolates, in some cases the passage history of the virus from which the sequence was derived is unclear, as are the biological attributes associated with that virus. Thus, there can in some cases be uncertainty regarding the biological attributes of a synthetic replica of a gene bank virus sequence.” P88
  3. “[S]ynthetic genomics technology could provide the means for the re-creation of variola virus, and therefore could affect the availability of this agent for malevolent use. Due to the large size of the poxvirus genome, however, it would be anticipated that well-established poxvirus recombination techniques would play a significant supportive or alternative role in producing an entire poxvirus genome.” p 91
  4. “Smaller genome segments of a sequence derived from variola virus may be readily incorporated into a “base” monkeypox virus, resulting in chimeric orthopoxviruses with unknown and unpredictable biological characteristics.” p 91
  5. “Because of their virulence, filoviruses are handled in high containment laboratory facilities to prevent virus release into the environment, and also to protect those working with these highly pathogenic viruses. Consequently, the number of labs in possession of these viruses is limited, as is access to these labs. However, during outbreaks, unsecured local hospitals and medical field teams collect, hold and transport numerous infectious patient specimens. Additionally, there may be covert stores of virus outside known containment laboratories. Hemorrhagic fever viruses were the subject of biowarfare research in the former Soviet Union, where weaponized Marburg virus was produced and research on Ebola was conducted. Upon the dissolution of the Soviet Union and these programs, the disposition of laboratory biological materials was not tracked.” pp 92-93
  6. “While [Australian workers] trying to improve their experimental mouse contraceptive vaccine, they engineered the expression of cytokine IL-4 from ectromelia virus, hoping that infection with this recombinant poxvirus would enhance antibody production by their vaccine. It instead resulted in severe suppression of cellular immune responses in the mice, uncontrolled virus replication, and animal death. Even mice previously immunized against normal ectromelia virus 16 or treated with the antiviral drug cidofovir17 were unable to survive ectromelia-IL-4 virus challenge.” p 95

Synthetic Biology, Bioterrorism, Smallpox, Vaccination, Ebola

2008

 

 

 

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