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Countering Bioterrorism: The Role of Science and Technology 3 Prevention, Response, and Recovery We can never create a perfect system to safeguard against terrorist use of a biological agent. But conscientious preparation—to the greatest extent that budgets and available methods allow—will reduce anxiety and greatly mitigate the consequences of an actual attack. Part of that preparation should involve research and development on needed tools and approaches. These include modeling techniques, bioforensics, methods for defining threats, specific and broad-spectrum antibiotic and novel antiviral agents, and means for rapid vaccine fielding. Once an attack has occurred, a better prepared and reinforced health and agriculture response system will be needed, as will be a reliable and consistent communications plan. For those exposed, protocols for treatment and decontamination must be available. And for animal and plant exposures, an effective disposal and decontamination plan must be in place. For communicable diseases in particular, given the potential for initial exponential growth in the number of cases from a single diseased individual, it is crucial that a variety of methodologies, both prophylactic and reactive, be developed for limiting spread. These include vaccination, treatment, quarantine, movement restrictions, isolation and, in the case of nonhuman populations, culling. Because the potential for spread is determined by the number of secondary infections per primary infection, success in management can be achieved by a combination of reducing the infectious period and reducing transmission. Studies must be done to develop decision rules and procedures for quarantine. These studies must be conducted with the goal of ultimately involving active participation of communities well before any event occurs. This will help reduce panic and irrational behavior in the case of an actual or suspected bioterrorism event. Quarantined communities must know where they will get medical care, antibiotics and vaccines, clean water, food, and mortuary service if the need arises.
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Countering Bioterrorism: The Role of Science and Technology A systems-level approach to dealing with bioterrorism threats, especially those involving communicable diseases, is needed. This approach must consider the integration of multiple modes of management, risk analysis in the face of inherent uncertainties concerning what agents will be introduced, and potential interactions among multiple biological agents. Such research is likely to rely heavily on the techniques of operations research, especially models that can be used for scenario development and training, for rapid response following detection of infected individuals, and for redesigning current systems (including possible patterns of movement) in order to make societies less susceptible to catastrophic outbreaks. Indeed, all of this argues for major development of modeling capabilities. UNCERTAIN UNDERSTANDING OF THE EFFECTS OF BIOLOGICAL WEAPONS Modeling the likely outcomes of different bioterrorism attacks is important for two reasons. It provides insight into the severity of the threat posed by the proliferation of biological weapons, and it allows one to estimate the effectiveness of different defensive responses (and hence the priority one should assign to each). Modeling efforts over the past decade, at least those publicly available, tend to emphasize worst-case scenarios—broadscale attacks involving millions of human casualties, if not fatalities. While such scenarios may be possible under the right circumstances, they probably are less likely than localized threats. In any case, a wider range of simulations is required to capture the range of possible outcomes. Here there is a major need for training; a critical mass of competent scientific expertise in epidemiological modeling has not to date been adequately supported. Such efforts should become major responsibilities of NIH, CDC, and DOD. Constructing models may be easier, however, than supplying them with meaningful data. There are gaps in our understanding of the factors that affect biological agents’ dispersal and uptake by humans, animals, and plants. For example, uncertainties of a factor of 10 or more in the LD50 values and a factor of 2 or more in the probit slopes (i.e., the dose-response curves) for different agents are common. These uncertainties are even greater if strain type is not known or the mechanism and magnitude of environmental decay rates for different agents are not well understood. Moreover, the incubation period (and its dose dependence) for different agents can vary by factors of 2 or more; and diurnal and weather variations can easily affect the contaminated area by an order of magnitude or more for open-air releases (typically the highest-casualty scenarios). Finally, uncertainties surrounding the amount and purity of the agent, the aerosolization efficiency for 1- to 5-micron particles, reaerosolization for agents that have settled onto the ground versus other surfaces, protection factors associated with buildings, and breathing rates can easily affect the inhaled dose by an order of magnitude or more.
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Countering Bioterrorism: The Role of Science and Technology These factors produce an irreducible uncertainty of several orders of magnitude in the number of people who will be infected in an open-air release. Moreover, the onset of disease may occur several times faster or more slowly than predicted, and this can have a significant impact on the efficacy of medical prophylaxis administered at a specific time after release. When bounds on these uncertainties are taken into account, the mean and variance of different attack outcomes may yield a different picture of the magnitude of the medical response required to cope with attacks—it is possible, in other words, that response options may be relatively insensitive to these uncertainties. However, the psychosocial consequences of a biological warfare attack (i.e., the disruption and terror caused by the event) will likely remain very large and difficult to quantify. Other transmission modes (water, food, animal vectors) create similar uncertainties, as do attacks directed at livestock or crops. Nonetheless, modeling and scenario building will be essential for cities and states to evaluate and improve their capacity to respond. Recommendation 6: Agencies with relevant expertise (such as NIH, CDC, and DOD) should develop and support the development of models—taking into account a range of incubation periods, transmission dynamics, and variables of climate, population, and migration—to simulate the release of contagious and noncontagious agents. Such modeling may resolve many of the uncertainties about the effects of biological weapons. Substantial uncertainties regarding mechanisms of pathogenesis would still remain, however; the only way to resolve them is through new experiments that involve virulent organisms and animal models of human disease. This fundamental work, which has been neglected in the age of molecular biology, underlies much of what must be done to develop new vaccines, broad-spectrum antibiotics and antivirals, and preclinical and traditional diagnostics. And, work must proceed in parallel on nonpathogenic bacteria and viruses, where many of the molecular mechanisms essential to our understanding of pathogenic organisms can most readily be deciphered. For example, new antibiotic discovery is dependent on an understanding of fundamental cellular mechanisms that are held in common among bacterial pathogens and nonpathogens. Careful oversight of experiments with pathogenic organisms is essential to ensure that they are not in violation of the Biological Weapons Convention of 1972.3 3 From the Web site of the Harvard Sussex Program on CBW Armament and Arms Limitation: “The Harvard Sussex Program on CBW Armament and Arms Limitation, with advice from an international group of legal authorities, has prepared a draft convention that would make it a crime under international law for any person knowingly to develop, produce, acquire, retain, transfer or use biological or chemical weapons or knowingly to order, direct or render substantial assistance to those activities or to threaten to use biological or chemical weapons.” More information is available online at <http://www.fas.harvard.edu/~hsp/cbwcrim.html>.
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Countering Bioterrorism: The Role of Science and Technology Recommendation 7: Expand investigations into the pathogenesis of infectious agents. Review the state of knowledge on the mechanisms of pathogenesis of all bioterrorist agents and of host responses to them, and initiate an action plan to conduct laboratory research using the latest molecular biology tools. This research will enhance understanding of the points at which these threats are most susceptible to useful intervention and will help identify new targets for developing diagnostics, drugs, and vaccines. MICROBIAL FORENSICS AND ANALYSIS OF TRACE EVIDENCE The overall lack of knowledge about how to respond to a given attack, together with the lack of intelligence information to help identify the organisms or chemical agents used in an attack, presents major vulnerabilities. But the importance of microbiological forensics in reducing these vulnerabilities was largely overlooked until the recent outbreak of anthrax. Its importance is that the sophisticated scientific and organizational mechanisms of forensics can be the means for determining the states or persons responsible for the attack and for formulating strategies to deter future attacks (Cummings and Relman, 2002). The U.S. criminal justice, national security, public health, and agricultural communities have more than adequately demonstrated that physical evidence and subsequent forensic investigations are crucial to the investigation of a crime. Similarly, preventing the use of biological weapons, responses to their use, and adequate defenses against them depend in large part on the ability of forensic analyses to attribute (or exclude) the source of a material with a high degree of scientific certainty. The ability to characterize biological weapons might also contribute to deterrence. But although advances have been made in forensics for specific biological agents that may pose a threat, a far more aggressive, comprehensive, and coordinated R&D program is needed. Such a program could then lead to fully tested forensic capabilities for all known biological agents that might be used in an attack. Lessons should be drawn from the forensic community’s experience with human DNA over the past few decades, and alternative approaches to microbial forensics should also be explored. For example, knowledge of microorganisms, the methods used to profile them, and the responses of mammals (particularly humans, domesticated species, and sentinel species) to infections with these microorganisms can be used to determine whether an attack with a biological agent can be effectively correlated with a particular place, event, process, or time. Biological trace evidence, microchemical analysis (analysis of information about the agent carried along with the biological weapon during manufacture, storage, handling, and release), and the feasibility of using tagged organisms should be comprehensively investigated to determine their value in the characterization and comparison of the biological agents used in different weapons. Many in the
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Countering Bioterrorism: The Role of Science and Technology biological warfare defense community believe that it should be possible to use a combination of DNA sequence information (occurring naturally) and/or deliberately introduced additional DNA sequences (stegnographic tags) to uniquely mark and identify all known pathogenic species. In this way, it may eventually prove possible to assign a unique code to every strain and variant, which would help in forensics, attribution, and defense. Such tags might even be encrypted. Recommendation 8: Develop and coordinate bioterrorism forensics capabilities. Federal agencies with missions in defense and national security should lead in establishing this new multidisciplinary, multilayered field. A comprehensive study should be performed to determine the capabilities of and needs for bioterrorism forensics, and an integrated national strategy and plan formulated. Investments and outcomes in the new field of bioterrorism forensics should be fully coordinated among agencies, with the program design, implementation, management, and oversight involving those agencies that actually have expertise in relevant sciences—including, of course, forensic science. The new field should cover human, animal, and plant pathogens. The information resident in the genomes and proteomes of organisms should be fully exploited, as should trace materials and chemical evidence associated with those organisms. The strategic objective of a bioterrorism forensics program is to establish systems for the high-resolution analysis and specific identification of all materials and substances used (or intended for use) in bioterrorism. Although the committee recognizes the extreme difficulty of the task, the desired outcome is the absolute attribution of a biological weapon to its source—the identification of persons, places, processes, or instruments involved in the attack. The ability to substantially reduce the number of possible sources or individuals involved in bioterrorism, and the ability to completely exclude the possibility of an act of bioterrorism, are equally important. So is the ability to understand the limits of the bioterrorism forensics process at any given moment and to accurately interpret and communicate results. AN APPROACH TO DEFINING BIOTERRORIST THREATS Pathogenic microorganisms and the toxins produced by living organisms pose a threat to national security whether they occur in their natural state or are released in bioterrorism attacks. In either case, the greatest threats to human health in the United States come from emerging and reemerging infectious agents that sporadically occur in nature. The population is highly susceptible to such infectious agents, and the mortality rates among infected individuals can be high. Such agents in a bioterrorism attack could easily be spread to large numbers of individuals (Peters, 2002). As part of a risk analysis, one can classify infectious agents and diseases in
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Countering Bioterrorism: The Role of Science and Technology relation to these sorts of factors. Thus an eradicated disease agent to which there is currently a high degree of susceptibility, for which there is a high rate of mortality among infected individuals, that can be spread as an aerosol, and that can continue to be spread via contagion—in effect, a worst-case disease—could inflict the most casualties. Smallpox is such a disease, and it is at the top of the list of biological agents that may pose a threat. Once measles is eliminated (Hilleman, 2001) it will join smallpox in this category if immunization against measles is halted (as was done for smallpox) and the population becomes highly susceptible. This has important policy implications for the continuation of immunization against a disease agent after elimination of its natural occurrences. Previously circulating pandemic influenza strains, most notably the 1918 Spanish influenza (Taubenberger, 2000) and the 1957 Asian influenza (Cox and Subbarao, 2000), and influenza strains of novel subtypes—e.g., the 1997 H5N1 strains from Hong Kong—have pandemic potential in humans. Ebola and hemorrhagic fevers (the causative viruses of which, however, are less easily spread from person to person than influenza viruses) would also have the characteristics of rare diseases that are communicable, to which there is a high degree of susceptibility, and for which there is a high rate of mortality among infected individuals. A genetically engineered pathogen could also have these characteristics and would need to be viewed as being among the most serious potential biological threats. The difficulty is that such genetically engineered pathogens could be created from virtually any biological pathogen or even vaccine strain; thus it will be challenging to develop vaccines or therapeutic antimicrobial agents in advance of a bioterrorism attack. Because eradiated or genetically engineered agents often do not occur naturally or are difficult to obtain from nature, the best source for terrorists is a research facility. It is thus appropriate to impose significant restrictions in terms of oversight and apply stringent security precautions for biological agents that pose high-level risks. Security guards, surveillance systems, personnel checks, and testing of personnel can be used to ensure that such biological agents are not removed from research facilities. In contrast, biological agents with the potential to damage U.S. agriculture most often occur naturally in some part of the world. These agents can easily be obtained (domestically or overseas) and can readily be released, given the general lack of security on farms and fields and their formidable size. For example, foot-and-mouth disease was widespread in the United Kingdom in 2001. A shoe from someone who walked on an infected farm would have been able to carry enough of the agent into the United States to cause an outbreak. Although U.S. border inspections for such potential introductions were heightened during the outbreak in the United Kingdom, the methods used were heavily dependent on the honest answers and voluntary compliance of the traveling public. It is likely that a determined terrorist could circumvent such an interdiction approach. Similar issues arise for plant pathogens and pests. For example, citrus canker
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Countering Bioterrorism: The Role of Science and Technology is a bacterial disease of woody perennials that is endemic in several parts of the world where citrus is grown. It has recently been reintroduced into the United States, in Florida, and has had significant adverse impacts on the state’s citrus industry. For agriculture, given that would-be terrorists have access to various naturally occurring threats, it will also be important to consider the possibility of the intentional release of multiple types of agents at multiple sites. For biological agents that may be used by terrorists and that occur naturally, it is appropriate to use lower levels of security and less direct oversight. The level of such oversight may still be significant and should be designed to offer real protection against the acquisition of biological agents that may be used as weapons. Significantly higher levels of security should be applied to any weaponized biological agents—for example, anthrax spores that have been treated to make them easily aerosolized. DEVELOPING ANTIMICROBIALS AND ANTIVIRALS The diversity of existing biological weapons and the ever-increasing number of possibilities through use of genetic recombination preclude simple therapeutic countermeasures to bioterrorism. The Soviets are known to have developed at least 30 biological agents. While it might only take 1 to 3 years to develop a new biological weapon, the average development time of a new drug or vaccine is 8 to 10 years. Thus with respect to development of countermeasures for biological weapons, a great need exists for broad-spectrum antibiotics and antivirals. Based on current knowledge, technology, and genomic databases, the goal of broad-spectrum anti-infectives is achievable. Existing countermeasures for known threats are limited. For the potential biological weapons on the CDC “A” list, there are only two vaccines available or in production (anthrax and smallpox), one antiviral, and a limited number of classes of antibiotics. Supplies of both vaccines are currently limited. While smallpox vaccination is effective, it elicits dangerous and potentially lethal complications in a number of individuals, and because it is a live-attenuated vaccine, it poses a significant risk for all immunocompromised individuals. The limited antibiotic armamentarium is an even greater concern with respect to future threats, especially in light of an increase in the number of new and reemerging infectious diseases and a marked rise in resistance to existing antibiotics. When the issue of resistance is laid against the dearth of new classes of antibiotics being developed and commercialized today, it becomes clear that no public health response to bioterrorism is likely to prove effective without a wider range of antimicrobials to draw on. Work must proceed in parallel on nonpathogenic bacteria in the same class as the pathogen. New antibiotic discovery is dependent on an understanding of fundamental cellular mechanisms that are held in common among pathogens and nonpathogens. In most cases, the nonpathogenic cousin has far superior genetics
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Countering Bioterrorism: The Role of Science and Technology and a deeper database of gene function and regulatory networks allowing discovery and development to proceed at a faster pace. Most antibiotic discovery is, in fact, based on work in nonpathogens that is then directly applicable to the pathogens on the list of biological warfare agents. An Interagency Task Force on Antimicrobial Resistance has set forth recommendations for judicious use of existing antibiotics; they appeared in the Federal Register almost 2 years ago.4 Although the recommendations were widely endorsed, funds have yet to be appropriated by Congress to implement the plan. Given the long lead time required for development of new antibiotics, we must preserve those we have. Thus it is essential that the recommendations of the task force be implemented without further delay. Unfortunately, the complacency associated with infectious diseases in the 1960s and the general confidence in existing antibiotics largely arrested the production of new classes of antimicrobials. There has been only one new class in the past three decades, and resistant strains emerged prior to its launch. But the situation may be changing for the better. The public attention to the antibiotic crisis in the early 1990s, coupled with the potential for discovering new antibiotics using genomics, high-throughput screening, microarrays, combinatorial chemistry, and structural biology, has resulted in industry’s reinvestment in antibiotic research. At first glance, the current antibiotic pipeline looks encouraging. There are more than 18 antibiotics in Phases I through III of clinical development. However, there are no new classes or targets for antibiotics. In particular, there are no new classes of broad-spectrum antibiotics, and the outlook for antivirals, particularly broad-spectrum agents, seems even more distant. These deficiencies are critical, as the chances for use of a multi-drug-resistant recombinant organism in future attacks is high. Here again, the deciphering of the genomes of major pathogens and the analysis of their function by the new field of bioinformatics will reveal new potential drug targets—most notably, targets that are present only in bacteria or viruses and not in human cells (such that broad-spectrum drugs can be developed that are likely to have few adverse effects on the human host). The need has never been greater for research, in both the public and private sectors, aimed at development of novel antimicrobials. However, recent analysis indicates that most, if not all, major pharmaceutical companies have over the past 3 to 5 years decreased their investments in drug discovery related to antibiotics, and few are exploring antiviral agents. These changes have resulted from higher regulatory hurdles, competing priorities, and a shrinking market. Thus, new 4 A Public Health Action Plan to Combat Antimicrobial Resistance appeared in the Federal Register on June 22, 2000 (Volume 65, Number 121). The report is available online at <http://www.cdc.gov/drugresistance/actionplan/html/index.htm>.
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Countering Bioterrorism: The Role of Science and Technology classes of antimicrobials will not emerge in the next decade without a major strategic shift. RAPID VACCINE DEVELOPMENT Bioterrorism attacks might not be restricted to the dissemination of known pathogens. Variants that have been engineered by current molecular-biology-based methods to alter or mask surface antigens—so as to avoid detection by the immune system—could also be used in such attacks. The following question arises: How quickly and by what means could a new vaccine be developed and deployed to protect against a novel pathogen? Before that need is upon us, we should act now to tackle several challenges to overcome the critical shortfall of research in vaccinology: The genome sequences of all plausible organisms that could potentially be used in a bioterrorism attack, including naturally occurring variants, need to be determined. This information will greatly facilitate the identification of any engineered variations in a weaponized strain. DNA-based vaccines (including vaccines that use defective viruses as carriers) should be more fully investigated for human application, as their use represents a potential quick path from determination of the genome sequence to the availability of a vaccine. Recombinant human antibody technologies should be explored, including novel delivery systems. Recombinant protein expression provides another pathway for the development of relevant antigens, but more research is needed to determine ways to make recombinant proteins as effective as immunogens. More effective adjuvants are needed. The development of vaccines against toxins, as opposed to pathogenic organisms, should also be explored. Better surrogate animal models are needed for testing vaccines against novel pathogens. Improved vaccines against known agents (like smallpox virus) are necessary if immunocompromised subjects are to be safely protected. A low cost per dose and stability at ambient temperature are important goals if vaccines are to be shipped to troops in remote locations or to populations in developing countries. Antibodies produced for medical use may provide an effective way to ameliorate the effects of a toxin or an infectious agent. The regulatory, legal (liability), and ethical issues associated with new vaccines are complex and must be addressed. Could vaccines developed by certain standard protocols be preapproved by the Food and Drug Administration (FDA) to streamline vaccine deployment, even if only at times when a certain high threshold of infection or mortality had been surpassed?
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Countering Bioterrorism: The Role of Science and Technology Vaccines must be produced and stored in multiple secure locations, as the vaccine itself could be a target in a terrorist attack to disable our ability to respond. The possibility of using vaccines effective against combinations of antigens from different viral pathogens needs to be investigated. Further work in basic immunology needs to be done to obtain an understanding of whether it will be possible to develop drugs that will up-regulate an immune response to pathogens, including organisms used for bioterrorism (immune modulation). The application of microbial genomics to the development of a novel meningococcal vaccine is one instructive model to consider here (Pizza et al., 2000). In addition, over the past several decades there has been an explosion of basic knowledge about virus structure, the genetic organization of viral genomes, and the mechanisms of viral replication. This knowledge presents us with many potential targets for antiviral therapy. Only a tiny fraction of such targets has been exploited to date. An informative example of success in this area is development of protease inhibitors, such as anti-HIV drugs. The discovery that processing of certain HIV proteins by the protease is essential for virus multiplication came out of basic research on viral proteins. The demonstration that the protease is essential for infectivity was published in 1988. The first protease inhibitor was approved by FDA in 1995. It is highly likely that similar approaches would result in useful therapeutics to counter viruses that might be used for bioterrorism. Recommendation 9: Increase research and development on therapeutics and vaccines. Support basic and clinical research to discover molecular targets in bacteria and viruses, develop broad-spectrum antivirals and antibiotics, and devise treatments that enhance or stimulate protective host responses (both innate and acquired). Similarly, continue to expand and deploy the capability to use genomics to rapidly identify engineered mutations or altered virulence factors, create a generic platform to develop a vaccine against recombinant pathogens, and employ streamlined testing and regulatory processes to assure adequate efficacy and safety while expediting delivery. IMPROVEMENT AND TESTING OF ENVIRONMENTAL AND PERSONAL PROTECTIVE EQUIPMENT As described in Chemical and Biological Terrorism (IOM, 1999), personal protective equipment (PPE) includes clothing and respiratory apparatus designed to shield an individual from chemical, biological, and physical hazards. Availability (and even knowledge of availability) of such devices can reduce anxiety
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Countering Bioterrorism: The Role of Science and Technology among first responders, health-care providers, and potential victims. In general, PPE is more effective against chemical agents, because biological agent incidents are not likely to be evident until well after release of the agent. Protective methods aimed at preventing the pathogen from entering the body are usually physical rather than biological and do not depend on the detailed structure of the pathogen. Available filtering methods depend only on particle size. Like most physical methods, filtering methods available today have the characteristic that they are not 100 percent effective, but they are able to sharply reduce the number of casualties. What is remarkable is that a capability exists based on existing products that can be put into service rapidly. HVAC filters in large buildings can be upgraded at minimal cost; other similar filtering devices can be used in the home. Simple cheap masks, about the size of a folded handkerchief, are available and probably provide a high degree of protection. These devices must be tested by government agencies and information must be provided to citizens about their effectiveness. An array of equipment currently exists (e.g., gloves, gowns, masks, eye protectors, respirators, protective suits), but technical problems remain—for example, heat stress in suits, permeable respirators, and difficulty of use. Also, there is no uniform testing standard for some of this equipment. In particular, testing is needed for antipathogen devices in order to distinguish personal protective equipment that is truly protective from items that generate a false sense of security (and that could increase people’s risks by unknowingly putting them in harm’s way). There is also a need for research on environmental protection devices that safeguard buildings and homes from biological and chemical-aerosol threats. For example, less expensive HEPA (high-efficiency particulate-arresting) filters for heating, ventilating, and air-conditioning systems could provide a real defense against terrorist attack on buildings and landmarks; they could also prevent exploitation of ventilation systems by terrorists. Such research might have non-counterterrorism application as well; it could provide knowledge about the use of filters for reducing the current epidemic of asthma in U.S. cities, particularly among children. Recommendation 10: Improve environmental and personal protective equipment. Agencies such as EPA, NIOSH, CDC, DOD, and DOE should perform and support research on new technologies that increase the protection factors of such equipment, and ensure uniform testing oversight to certify efficacy. APPROACHES TO PREPARING THE HEALTH CARE SYSTEM FOR RESPONSE AND RECOVERY: THE NEED FOR SURGE CAPACITY The U.S. health care system has focused on efficiency in the past decade. Redundancies have been eliminated through hospital closures, decreases in the
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Countering Bioterrorism: The Role of Science and Technology numbers of physicians in many specialty practices, and consolidation of traditional public health activities within health care delivery organizations. Furthermore, the budgets of many agencies that could deal with significant epidemics have been curtailed because no such incidents have occurred in the United States in recent years. Efficient systems use resources to deal with predictable health problems, but almost by definition they lack the resilience (in the form of excess capacity) to deal with unusual episodes of disease, particularly large-scale outbreaks or those that may result from an act of bioterrorism. The challenge is to devise a system that would create capacity on demand to cope with sporadic and potentially very large demands on the health care infrastructure without destroying the efficient use of resources that characterizes the current situation. It is probable that the given medical capacity in any community can respond immediately to a terrorist attack, providing the following two conditions are met: The attack does not destroy the hospitals and emergency departments in that community. A chemical attack might destroy multiple hospital emergency departments or contaminate them so completely that they could no longer be used; a biological attack could quickly spread to medical personnel, thereby effectively destroying their capacity to respond. The attack is short-lived and can be handled within a short time frame (less than 24 hours). For example, during the attack with sarin on the Tokyo subway in 1995, there were few fatalities and a small number of serious cases. Yet the total number of patients (of all types) created an overwhelming workload for the emergency departments of Tokyo hospitals, though only for a short period of time. Had the attacks continued on a daily basis (as in the case of a biological agent that would spread over time, such as the plague bacterium or smallpox virus), there would have been a need to divert some capacity to care for the usual daily workload—thereby reducing the number of staff medical professionals for handling the bioterrorism-related workload. In most urban communities of the United States, a bioterrorism attack could pose major problems for the hospital emergency departments, which are already close to their maximum utilization capacities. Some capabilities do exist for reducing the usual workload under such circumstances: patients with marginal cases of illness or minor injuries could be quickly discharged from specialty-care units; elective cases of treatment or surgery could be delayed; and incoming emergency patients could be triaged. However, a large number of patients would continue to need care so that they did not deteriorate into a more serious state. Numerous off-duty medical personnel could be pressed into longer hours of service in a crisis, but the amount of time during which they could respond without relief is still finite. Thus, although the prehospital care agencies might be able to gear up quickly into a disaster mode and accommodate a sudden influx of
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Countering Bioterrorism: The Role of Science and Technology patients with illnesses related to an acute attack, there is not high confidence that emergency departments in most cities could do the same. The initial symptoms of the illnesses caused by virtually all infective agents, be they bacterial, viral, or fungal in nature, are very similar. In fact, in everyday clinical practice it is common to confuse a serious bacterial infection with a trivial viral infection, with a loss of opportunity for effective intervention and curative treatment. If individuals or government agencies outside the medical community have knowledge about a pending attack with a specific agent, they may still not be able to dispel such confusion; no mechanism currently exists for the transmission of that information to the medical community so that it can recognize infected individuals and respond to their needs more quickly. The federal government already has systems in place for responding to disasters. HHS coordinates Disaster Medical Assistance Teams, Disaster Mortuary Operational Response Teams, Veterinary Medical Assistance Teams, and other medical specialty teams located throughout the country. These units can be deployed immediately in the event of natural disasters. In addition, HHS coordinates the National Medical Response Teams for Weapons of Mass Destruction— weapons of mass destruction include chemical, biological, radiological, nuclear, or explosive (CBRNE) agents—to deal with the medical consequences of such incidents, and it is helping metropolitan areas across the nation prepare to deal with such incidents through the Metropolitan Medical Response System. The Metropolitan Medical Response System emphasizes enhancement of local planning and response capabilities, as well as that of local hospital capacities, tailored to each jurisdiction so that it can best apply local resources to care for victims of a terrorist incident involving a weapon of mass destruction. The resulting systems are characterized by a concept of operations; specially trained responders; a special stockpile of pharmaceuticals; equipment for the detection of biological, chemical, and nuclear agents along with personal protective equipment; decontamination capabilities; communications equipment, medical equipment, and other supplies; and enhanced emergency-medical-transport and emergency-room capabilities. The program focuses on responses to a biological attack, including early warning and surveillance, mass-casualty care, and plans for the management of mass fatalities. The concept of operations also includes the local jurisdiction’s plan for augmentation of health and medical assistance by the federal, state, and neighboring governments, including the movement of patients (when local health-care systems become overloaded) via the National Disaster Medical System (NDMS). Each major medical center in cities across the nation must have response plans in place. These should include designated hospital areas that can be converted into isolation zones and decontamination areas, triage plans, and ongoing training sessions for disaster response teams among the medical personnel. The Office of Emergency Preparedness leads the NDMS, a partnership of four federal agencies (HHS, DOD, the VA, and FEMA) and the private sector.
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Countering Bioterrorism: The Role of Science and Technology The system has three components: direct medical care, patient evacuation, and nonfederal hospital care. NDMS also includes more than 7,000 private sector medical and support personnel organized into 80 disaster-assistance teams. These teams provide immediate medical attention to sick and injured individuals during disasters, as well as mortuary and veterinary care when local emergency-response systems become overwhelmed. All of these systems (e.g., NDMS and the Metropolitan Medical Response System) should be supplemented with additional local capacities for responding to attacks on humans, animals, and plants. A national, regional, and local planning process should identify human and other resources that could be brought out of reserve during such times. In addition, public health laboratories need to build surge capacities as well as expertise in containment. Microbiology laboratories are the first lines of defense for the detection of new cases of antibiotic resistance, outbreaks of food-borne infection, and a possible bioterrorism event. Maintaining high-quality clinical microbiology laboratories on site or near the institutions and communities that they serve is the best approach at present for managing infectious diseases and detecting resistance to antimicrobial agents. However, a public health reserve system, consisting of certified laboratory personnel with the ability to provide expertise when the health care system becomes overloaded, needs to be created. In addition, before a crisis occurs, it is critical to have in place agreements between public health and emergency response agencies across jurisdictions. Drills using both threats and scenario models can test the full range of capabilities and assure the availability within a short distance of Level 4 public health laboratory capability. Recommendation 11: Create a public health reserve system and develop surge capacity. As part of a broader planning process, create a health reserve system of health care professionals (modeled on the military reserve system), and prepare local and regional laboratories for deploying surge capacity to supplement and enhance disaster-response capabilities. APPROACHES TO PREPARING THE FOOD AND AGRICULTURE SYSTEM FOR RESPONSE AND RECOVERY The U.S. food and agriculture system has undergone profound changes since World War II that have increased the vulnerability to plant and livestock diseases and to widespread human illnesses caused by food-borne pathogens. Food processing and distribution have become increasingly concentrated. For example, four companies now slaughter and process 85 percent of the domestically produced meat, livestock is raised in large, centralized feeding operations, and vast amounts of land are devoted to one or two crops, such as corn and soybeans. Meanwhile, government support for agricultural research has remained flat (in constant dollars) for nearly 25 years. The private sector supports more agri-
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Countering Bioterrorism: The Role of Science and Technology culture research than the state and federal governments combined, but most of these industry initiatives are in the development of biotechnology products, pesticides, and other inputs to agricultural production. A USDA-state system of laboratories that investigates outbreaks of livestock diseases does exist, but it varies somewhat in structure from state to state, with some relying on state laboratories and others on colleges of veterinary medicine or agriculture, usually located at land-grant universities. Within USDA, the Animal and Plant Health Inspection Service (APHIS) leads efforts to prepare for and respond to outbreaks of crop and livestock diseases, both indigenous and exotic. APHIS develops the basic emergency-response plans, while state agriculture departments extend the plans to apply to the conditions and administrative structures within their domains. Recommendation 12: Create an agricultural health reserve system and develop surge capacity. As part of a broader planning process, create a reserve system of veterinarians and plant pathologists (modeled on the military reserve system), and prepare local and regional laboratories for deploying surge capacity to supplement and enhance disaster-response capabilities. COMMUNICATING RISKS AND RESPONSES TO THE PUBLIC In 2000, a workshop cosponsored by the Defense Threat Reduction Agency (DTRA), the FBI, and the U.S. Joint Forces Command was held on the communication of risk resulting from a weapons of mass destruction (WMD) attack. A report published in March 2001 describes the results of the workshop and recounts lessons learned from past experiences, addresses unresolved issues that were identified by the expert participants, and presents prioritized recommendations for future research, analysis, and other activities (DTRA, 2001). A disaster response program should include many elements if it is to be successful in dealing with the effects of a WMD attack and restoring public order. In the United States, several agencies at the federal, state, and local levels have been assigned to handle contingencies such as natural disasters, chemical spills, and nuclear mishaps. The Federal Response Plan, a signed agreement among 27 federal departments and agencies, and including the American Red Cross, provides a mechanism for coordinating delivery of federal assistance and resources to augment state and local efforts in major disasters or emergencies. This plan, however, does not describe an integrated, comprehensive blueprint for crisis/risk communications in the event of a large-scale disaster such as a WMD attack. It should be noted that in the 1918 pandemic of influenza, there was a severe lack of mortuary services and facilities, which must also be provided for by the plan. To help fill the gap, research and analysis on communication and awareness campaigns, and training and preparation, are needed. However, it is essential that all federal agencies involved in response develop, through a panel of outside
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Countering Bioterrorism: The Role of Science and Technology experts, a plan for analyzing data, developing a response, coordinating the response with other agencies and the Office of Homeland Security, and communicating with the public. DEVELOPMENT OF TREATMENT PROTOCOLS In most cases, there is insufficient research and information on which to base a sound public health protocol and medical response in the event of a biological attack. We cannot, for example, answer the following questions with confidence: How long should individuals continue antibiotic treatment after exposure to biological agents? How long after exposure will vaccination be effective? What other types of interventions will increase survival rates and decrease spread of the disease? Sound protocols are a necessary prerequisite for communicating information about appropriate postattack responses to the public, physicians, and public health officers. The anthrax attacks of 2001 illustrated the lack of preparedness in this area. Recommendation 13: Develop protocols for public health responses to bioterrorist attack. OHS should develop a plan for achieving this objective, and HHS, through its various agencies, should support the necessary research. DEVELOPMENT OF DECONTAMINATION PROTOCOLS At present there are few data on which to base decontamination procedures, particularly for biological agents. A review of the literature shows that dose-response information is often lacking or controversial, and that regulatory limits or other industrial health guidelines (which could be used to help establish the maximum concentrations of such agents for declaring a “decontaminated” environment) are generally unavailable or not applicable to public settings (Raber et al., 2001). Moreover, the correct means for identifying the presence of many biological agents are not known, nor is the significance of the presence of biological agents in the natural environment (e.g., anthrax spores are found in the soil in some parts of the United States). Research is therefore needed to determine what level of cleanup will be required to meet public health needs in the aftermath of a bioterrorist attack. Although the lack of dose information, cleanup criteria, and decontamination protocols presents challenges to effective planning, several decontamination approaches are available. Such approaches should be combined with risk-informed decision making to establish reasonable cleanup goals for the protection of health, property, and resources. Efforts in risk assessment should determine what constitutes a safety hazard and whether decontamination is necessary. Modeling exercises are needed that take into consideration the characteristics of a particular
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Countering Bioterrorism: The Role of Science and Technology pathogen, public perceptions of the risk that the pathogen poses to their health, the level of public acceptance of recommendations based on scientific criteria, levels of political support, time constraints in responding to the threat posed by a pathogen, and economic concerns (Raber et al., 2001). Specialized robots may have to be developed and used in highly contaminated or extremely hazardous situations. Agricultural Decontamination For agricultural biological threats, critical components of the response include quarantines, disposal of contaminated plant or animal material, and decontamination of products, facilities, equipment, and, in some cases, soil (especially for agents that are persistent and can survive in the environment) (NRC, 2002). The disposal or decontamination procedures used, as well as their effectiveness and acceptability, are highly specific to each biological agent: They depend on the nature of the agent, the commodity affected, and the extent of disease or infestation. For example, foot-and-mouth disease (FMD) is so highly contagious that large numbers of infected and potentially exposed animals may need to be slaughtered and disposed of at the farm of origin. Mass burial and burning are the major alternative means for disposal. Both methods are expensive, repugnant to many people, and raise environmental concerns. Novel methods for carcass disposal, for inactivation of FMD virus in and on carcasses, and alternatives to mass slaughter during FMD outbreaks are urgently needed. Decontamination of products, equipment, or facilities is less of a problem because FMD virus is inactivated by heat, irradiation, or treatment with chemicals at high or low pH. Similar issues apply to plant pests and pathogens. In general, decontamination of seeds and combines, trucks, or other field or handling equipment is possible by fumigation with appropriate chemicals, but this is costly, from both an economic and environmental perspective. Eradication, especially of soil-borne spores of plant pathogens, is virtually impossible. Methyl bromide, one of the few standard chemicals used for fumigation of soil and containers, will be banned after 2005 in developed countries and 2010 in developing countries as the result of an international agreement made in response to evidence that the chemical depletes the ozone layer. Live steam can be used to clean up facilities and handling equipment, but its cost and damage to the equipment can make this method unappealing. Alternative methods for decontamination and eradication of biological threats to plants are needed (NRC, 2002). Recommendation 14: Develop methods and standards for decontamination. Develop standards for levels of decontamination and certification of products to ensure safety. Research is needed on chemical fumigation and irradiation as methods for decontamination of buildings and mail; development and evaluation of novel
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Countering Bioterrorism: The Role of Science and Technology decontaminants; disposal of crops and livestock carcasses; and decontamination of trucks, railroad cars, container ships, and warehouses used to transport and store contaminated crops, livestock, food, and feed. This effort will require collaboration among all agencies with expertise and a mission in this area, including HHS, EPA, USDA, the Coast Guard, and DOD. Because cross-agency collaboration is often challenging, the Office of Homeland Security should designate a lead agency on these issues and ensure that collaborating agencies provide the necessary resources to identify and support research efforts in this area.
Representative terms from entire chapter: