Biological Threats and Terrorism Assessing the Science and Response Capabilities: Workshop Summary (2002) / Chapter Skim
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2 Assessing Our Understanding of the Threats
2 Assessing Our Understanding of the Threats
Pages 43-84
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From page 43... ...
However, these are not the only credible bioterrorist agents out there. For example, the former Soviet Union is known to have weaponized at least thirty biological agents, including several vaccine- or drug-resistant strains.
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From page 44... ...
Since the 1950s, one of these strains has been used as a live attenuated strain in humans in countries of the former Soviet Union. The molecular pathogenesis of anthrax, including the exact target of its lethal factor, is largely unknown.
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From page 45... ...
More effort needs to be directed toward other therapeutics, such as immunomodulators. Plague Plague a deadly and highly contagious disease was weaponized in the former Soviet Union for aerosol delivery and engineered for antimicrobial resistance and possibly enhanced virulence.
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From page 46... ...
Antibodies have several distinct advantages as bioweapons defense agents: they induce immediate immunity, they can be produced in unlimited quantities, and they are highly potent. In fact, an unlimited supply of human recombinant antitoxin is probably the best defensive measure against Botulinum toxin.
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From page 47... ...
Senior Military Research Scientist, United States Army Medical Research Institute of Infectious Diseases "It has now prevailed and been recognized in this neighborhood about forty years, and notwithstanding all that has been done to prevent it, by ventilation, the use of respirators and other means, it still continues, as severe and Sequent as it ever was, overclouding the life of the sorter." (Bell, 1880) 47 Anthrax has a long history: apocryphal accounts describe it as the fifth and sixth plagues in Exodus, when dust was cast into Pharaoh's eyes, it was the first disease for which a microbial etiology was determined by Robert Koch, and the anthrax vaccine was one of the first live vaccines, developed by Pasteur and one of the first examples of attenuation of a fully virulent organism for use as a vaccine.
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From page 48... ...
Since the late 1930's and early 1940's, the Sterne strain and others similar to it have been used throughout the world as live veterinary spore vaccines that have proven to be highly effective in controlling disease in domesticated animals. Since the 1950's, a similar strain has been used as a live attenuated vaccine for humans in the former Soviet Union.
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From page 49... ...
Only when protective antigen combines with lethal factor does it constitute lethal toxin, and only when it binds with edema factor does it constitute edema toxin. From cell culture studies, it appears that the anthrax toxins function as outlined in Figure 2-1.
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From page 50... ...
The Department of Health and Human Services, with input from the Department of Defense, is currently focusing on three therapeutic issues: testing licensed antibiotics that could be used to treat anthrax, developing human antibodies against the current vaccine, which has been administered to about 500,000 individuals, and assessing combined vaccine and antibiotic use. Other issues that need to be addressed include: identifying near-term, mid-term, and long-term research goals, identifying new protective antigens that are effective against modified strains, producing vaccines that work more quickly, particularly from the perspective of a post-exposure scenario, and, critical to all of these efforts, developing a large-scale central animal testing facility as evaluation of new treatments in humans will likely be extremely difficult.
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From page 51... ...
Senior Research Scientist, United States Army Medical Research Institute of Infectious Diseases 51 The recent bioterrorist attacks involving anthrax have increased awareness that biological agents are truly weapons of mass destruction. Unlike anthrax, the smallpox virus is a contagious disease with fairly high rates of human to human transmission.
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Subsequent inoculation of four monkeys with 109 PFU India 7124 via the intravenous route alone yielded uniform rapid lethality. In subsequent attempts to obtain a more slowly evolving disease course, lower doses produced systemic infections and more protracted disease courses, but no deaths.
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This capability should improve the likelihood of successful intervention using antiviral drugs. The production of these clinical samples is a significant byproduct of animal model development.
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Division of Vector-Borne Infectious Diseases Centers for Disease Control and Prevention 55 Yersinia pestis and Francisella tularensis are category A critical biological agents that pose a risk to national security because they could be easily disseminated (both agents) or transmitted person-to-person (Y.
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From page 56... ...
pestis and F tularensis strain typing, using multiplelocus, variable-number tandem repeat analyses are expected to provide rapid tracking of outbreak strains as well as providing a foundation for deciphering global genetic relationships of these organisms that could be useful in the event of a BT attack (Johansson et al., 2000, Klevytska et al.,2001, Farlow et al., 2001~.
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From page 57... ...
Botulinum toxin is considered a plausible prime bioweapon threat because of its extreme potency and lethality, its ease of transport and misuse, and its profound impact on victims and the health care infrastructure. Botulinum toxin is the only non-replicating member of the six Centers for Disease Control and Prevention (CDC)
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From page 58... ...
Botulinum toxin is produced by the spore-forming anaerobic bacterium Clostridium botulinum, whose natural home worldwide is the soil and dust, from which it can be isolated with undue difficulty. Botulinum toxin exists in seven different serotypes arbitrarily assigned the letters A-G, antibody that neutralizes one toxin type does not neutralize any other serotypes (e.g., anti-A antitoxin does not neutralize toxins B-G, etch.
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From page 59... ...
Death results either from obstruction of the upper airway by unswallowable secretions and flaccid pharyngeal muscles or from complications of mechanical ventilation and intensive care. Production and Delivery of Botulinum Toxin as a Bioweapon Botulinum toxin is readily available as a bioweapon because of the relative ease with which its source, C
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From page 60... ...
Immunization of either civilian or military populations with botulinum toxoid is not a practical defense against weaponized botulinum toxin for several reasons. The existing pentavalent botulinum toxoid contains only A-E toxoids (i.e., it lacks F and G)
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From page 61... ...
Treatment with human botulism antitoxin is effective as well as safe. In a randomized, placebo-controlled, double-blinded clinical trial, use of BIG-IV to treat infant botulism patients shortened their mean hospital stay by over 50%, from 5.7 weeks to 2.6 weeks, and reduced their mean hospital charges from approximately $130,000 to approximately $60,000 per case (California Department of Health Services, presently unpublished data)
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The phage-display technology that underlies the development of these recombinant human antitoxin antibodies also enables neutralizing human antibodies to the remaining six (B-G) botulinum toxin types to be rapidly created.
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; both laboratory and epidemiology · Develop rapid in vitro toxin detection methods · Produce human recombinant antitoxin for stockpiling as well as current use Clinical Medicine · Improve communications with public health colleagues for early detection · Ensure adequate surge capacity for ventilators and mobile intensive care units and their staffing · Produce human recombinant antitoxin for stockpiling as well as current use Research · Begin development of human recombinant antibodies against toxin serotypes B-F · Begin scale-up production of existing human recombinant anti-A antibodies to establish pathways and capabilities · Obtain intelligence on toxin-derived bioweapons research in other countries to enable defensive recombinant human antitoxin development
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From page 64... ...
Distinguished Professor of Medical Microbiology and Executive Director, Center for Biodefense George Mason University President Advanced Biosystems, Inc., a subsidiary of Hadron, Inc. Because they are our best protection against infectious disease, it is necessary that we continue to develop, approve, and introduce new vaccines against many naturally occurring infectious diseases and against some biological weapons threat agents.
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From page 65... ...
However, though vaccines have proven extremely effective against infectious diseases in general, they are of limited utility in the defense against infections caused by biological weapons. Vaccination is a successful defense only when the target population is well-defined and can be identified well in advance of an attack, when the biological threat agents in the enemy's biological weapons arsenal are known, when vaccines for those agents have already been developed, and when the biological agents used are not genetically altered strains capable of circumventing a vaccine.
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It is very important that we re-evaluate our knowledge of pathogenesis and identify what we have missed in the field of protection and treatment of infectious diseases caused by biological weapons.
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From page 67... ...
This complacency was reinforced by the large number of "anthrax" powder hoaxes that have occurred over the last few years, a social phenomenon worthy of study in itself. This short essay attempts to outline why we should be concerned about use of biological weapons in terrorism, why some scenarios are more dangerous than others, and some general observations concerning what we could do to combat bioterrorism.
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From page 68... ...
Direct inoculation, infection of natural vectors or reservoirs and loosing them on the target population, or infection of a few persons and counting on their spreading the infection even further are some possibilities. If we focus on terrorist strategies that can inflict mass casualties none of these possibilities is highly feasible today with the exception of the use of smallpox, a virus that is well-known to spread from human to human after a long and successful career in that evolutionary niche.
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From page 69... ...
Open air dissemination was mimicked using a surrogate organism, Serratia marscens, and this confirmed that an organism with the aerosol stability and infectivity of Francisella tularensis could cause mass casualties over large geographic areas provided attention was given to metrological conditions. The areas affected could reach thousands of square kilometers.
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From page 70... ...
. The additional impact that might be possible through modification of naturally occurring organisms by methods well within the reach of simple biotechnology including induction of antimicrobial resistance, enhancement of viruTABLE 2-4 Some diseases and their causative agents considered to be aerosol biological warfare threats capable of causing mass casualties (CDC Category A Biological Agents/Diseases)
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From page 71... ...
The dry powders are difficult to manufacture, but they are extremely dangerous because they can be prepared so as to aerosolize with minimal energy input and can be manufactured in very fine particle sizes. If the skills to prepare these particles are availTABLE 2-5 Some agents often mentioned as potential aerosol biological warfare or biological terrorist threats Tick-borne flaviviruses Typhus and other Rickettsiae Glanders Alphaviral encephalitidies Brucellosis Q fever Melioidosis Nipah virus Staph Enterotoxin B Ricin Tricothecene mycotoxins
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From page 72... ...
When these aerosol clouds are generated, there is a period of instability and larger particles or agglomerates fall out near the dissemination device with considerable surface contamination possible. Once the small particle aerosols are formed, they will move with wind currents and traverse the landscape, being gradually diluted by mixing and decay.
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From page 73... ...
There is little experience with transfer of infectious powders from one solid surface to another or with the deposit of larger clumps of highly aerosolizable particles on hard solid surfaces. Surrogate infectious agents, fluorescent tracers or radioactive particles predict that highly concentrated biological agents (titers >109/g and perhaps as much as 10~2/g)
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From page 74... ...
Fortunately, attention to the worst case is a step toward the more general solution, although the lesser eventuality should also be in the mind of planners. It is also important to note that biodefense efforts meld with the general struggle against infectious diseases.
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The viral hemorrhagic fevers are essentially without therapy, have severe psychological impact, and carry a high mortality. Their production is still more difficult, but the technology is readily accessible to an experienced microbiologist (Peters, 2000~.
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However, limiting access to certain agents such as Ebola, Marburg, and smallpox viruses should be pursued. The equipment needed to produce limited amounts of biological agents is readily available and
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From page 77... ...
and B ala Swaminath an Foodborne and Diarrheal Diseases Branch Division of Bacterial and Mycotic Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Estimates of Foodborne Illness in the United States The spectrum of illnesses caused by consumption of contaminated foods may range from self-limiting mild gastroenteritis to life-threatening neurologic, hepatic and renal syndromes (Mead et al., 1999~.
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Large Foodborne Disease Outbreaks Examples illustrating large-scale (several thousands of cases) foodborne outbreaks are listed in Table 2-6.
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Unlike some potential threat agents (i.e., smallpox) for which the sources are limited, many foodborne agents such as Salmonella, E
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From page 80... ...
Capacity for early detection of intentional contamination of the nation's food and water supply is vital to minimize the impact on community health. Challenges to Rapid Response There are a number of challenges to providing a rapid response to intentional or unintentional widespread foodborne outbreaks (Mead et al., 1999~.
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From page 81... ...
In: Remington JS and Swartz MM, eds. Current Clinical Topics in Infectious Diseases, Maiden, MA: Blackwell Scientific Publications 20:335.
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From page 82... ...
Emerging Infectious Diseases 7(6)
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From page 83... ...
ed. Biological Weapons.
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From page 84... ...
1999. Emerging Infectious Diseases 5, 607-625.
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