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Bioregulators as instruments of terror.

Bioregulators are naturally occurring organic compounds that regulate diverse cellular processes. Unlike traditional disease-causing biowarfare agents that take hours or days to act, many bioregulators act within minutes of administration. If exploited for the purpose of bioterrorism, they could potentially cause profound physiologic effects. Other effects may be more subtle. The main groups of bioregulators discussed are cytokines; eicosanoids, neurotransmitters, hormones, and proteolytic enzymes. Because advances continually are being made in their development, bioregulators should be considered as weapons with increasing bioterrorism potential.

Biological Factors↗

We are all in this together. Terrorism and the physician executive.

The threat of bioterrorism striking America is no longer a threat. It's real. Take a look at how the anthrax-laced letters and future acts of terrorism impact physician executives. Also consider some ways to prepare your physicians for a bioterrorism emergency.

Anthrax↗

Anthrax attack at the United States Capitol. Front line thoughts.

One great fear was realized on October 15, 2001 when United States citizens witnessed firsthand the unprecedented release of anthrax into a community. Although the office of the Attending Physician to Congress had been preparing for such an unthinkable act, lessons were learned as the events unfolded. The following is a summary of the findings: Preparation, planning, and frequent review of bioterrorism response procedures are essential. Effective communication remains the key to successful team performance. Briefings conducted daily and on an as needed basis shape the progress and performance of the team members. Electronic mail may not necessarily be the most effective way to disseminate critical information because not everyone can access the Internet outside of the work environment. Setting up a call center for answering client's questions is crucial. Clients potentially exposed to anthrax should be evacuated from the immediate area. Testing is not indicated for everyone, only those in the immediate areas. Allow health care personnel to decide whom should be tested. Such health care decisions must not be made based on anxiety or expediency. A data collection template should be set up in advance. This template should include, at least, the following: name, date of birth, social security number, the physical location of where the client might have been exposed, antibiotics administered and dosage, test results, and home and work phone number. This should be networked so a group can access and update data in real time. If the occupational health clinic has its own pharmacy, have a pill counter available to help with antibiotic distribution. The team should meet several times daily to ensure dissemination of a reliable and consistent message to the clients. Team members should be prepared to review the medical aspects of anthrax with clients on a frequent basis. A website with updated information might prove helpful for those with Internet access. This experience provided a unique opportunity for the Office of the Attending Physician to Congress to put its bioterrorism plan into action. Nothing substitutes for preparedness. Communication was the most important tool because it kept the team informed and focused on the mission at hand. It behooves all occupational health nurses to begin preparing for future acts as extraordinary as the anthrax attack that occurred on October 15, 2001.

Allied Health Personnel↗

Preparation for an outbreak of smallpox in Israel.

Because of its high case-fatality rate, its very high transmission potential, and the worldwide shortage of effective vaccine, smallpox tops international lists of over a dozen possible bioterror and biologic warfare agents. In a scenario involving aerosol variola virus release, tens to hundreds of first-generation cases would ensue, as would hundreds to thousands of subsequent cases resulting from person-to-person transmission. A smallpox outbreak in Israel must not be regarded as a doomsday event: the methods of smallpox outbreak control are known and will be implemented. The rapidity with which organized outbreak control measures are competently executed will determine how many generations of cases occur before the outbreak is brought under control. Planning, vaccine stockpiling, laboratory expansion, professional training and public education, all carried out well in advance of an epidemic, will minimize the number of casualties. The reinstitution of routine smallpox vaccination in Israel, as in other countries, must be given serious consideration, since it has the potential for eliminating the threat of smallpox as a bioterror agent.

Bioterrorism↗

Smallpox.

With recent events, the threat of bioterrorism has become a reality. In late 2001, multiple cases of cutaneous and inhalation anthrax were spread through the US mail. On the front line were dermatologists who diagnosed the first cases of cutaneous anthrax in New York City. Since then, physicians who are unsure if they are facing a new form of bioterrorism frequently have consulted dermatologists to evaluate rashes. Because most biological weapons (anthrax, tularemia, plague, smallpox) can have cutaneous manifestations, dermatologists will continue to have an important role in evaluating these potential threats.

Bioterrorism↗

Anthrax 2001--lessons learned: clinical laboratory and beyond.

OBJECTIVE: Re-visit the 2001 anthrax outbreak to assess the ideas and concepts learned from the event as they relate to the illness and to bioterrorism preparedness. DATA SOURCES: Current literature. CONCLUSION: A multitude of lessons have been brought to light. The future of bioterrorism preparedness depends on whether those lessons are acknowledged and acted upon.

Anthrax↗

Public health law in the new century.

Public health law is a broad and sometimes nebulous field which has undergone extensive reform and rethinking over the past decade. This article provides a survey of current issues in public health law, highlighting these reforms and the potential for public health legislation to deal with upcoming threats, notably bioterrorism. While recognising the anxieties bioterrorism brings, public health responses must be grounded in a coherent philosophy of risk management. Its administrators must also be aware that large-scale threats to public health are not unprecedented and that past experience can provide an important guide for future strategies.

Acquired Immunodeficiency Syndrome↗

Emerging technologies for bioweapons defense.

The Global War on Terrorism (GWOT) has changed the way we think about national security. The tragic events of Sept.11 have shown us that world of the 21(st) century is clearly a dangerous place. Terrorism, more than ever, affects the very lives of each and every citizens of our country. Al Qaida has proven that it is able to use simple rudimentary methods to invoke strategic economic losses to our society with our own domestic resources as its weapons. The dawn of the new century has brought forth a new kind of asymmetric war where guerilla fighters are armed not with rifles but with technology at the touch of a keyboard. Warfare as we know it has changed and just as the military has its "transformation", medicine so too must have its own transformation in order to protect our citizen against the ever changing threat of bioterrorism. Virtual Reality and its applications can play a vital role in developing new countermeasures to minimize the catastrophic effects of a potential bioterror attack.

Bioterrorism↗

Vaccination strategies for the last stages of global polio eradication.

Launched in 1988, the Global Poliomyelitis Eradication Initiative has enjoyed remarkable success. The WHO anticipates isolation of the last wild polio virus during late 2004/early 2005, paving the way for certification of a world free of polio in 2008. However, the ultimate objective of this campaign, discontinuation of polio vaccination, has been jeopardised by two recent developments: the characterisation of vaccine-derived polio viruses (VDPV), and renewed concerns over the risk of bioterrorism. The threat posed by VDPV has led the WHO to recommend discontinuation of OPV usage as soon as possible after eradication certification. Cessation of vaccination with OPV needs to be carefully designed to avoid creating conditions where VDPV will develop. For the longer term, strategies must be designed to guard against the risk of polio reemergence due to long-term VDPV excretors, accidental release of wild viruses or bioterrorism. The main strategies under consideration are a surveillance and response approach or a continuation of vaccination with IPV. Choosing between these strategies will pose a major dilemma for India and for many other countries.

Bioterrorism↗

Forensic dentistry in a terrorist world.

While body identification by dental means has not changed substantially since 9/11, or even since the bombing of the Murrah Federal Building in Oklahoma City in 1995, the conditions and potential risks of a bioterrorism action to the dental personnel is new. The purpose of this article is to review general forensic dentistry disaster responses and to address the impact a bioterrorism action might have on primary, secondary and tertiary dental responders. It will also examine the triage role that dental offices might play in the event of such a disaster.

Bacillus anthracis↗

[Botulinum and ricin toxins].

Due to their acute toxicity, accessibility and history of use, ricin and botulinum toxins are at the present time the most relevant bioterror toxins. We give a brief review of their toxicity and possible uses in bioterror attacks and describe two cases in Denmark in which immunochemical, PCR and mass spectrometric assays developed in-house were used to confirm a foodborne botulinum toxin E case and to identify bovine serum albumin as the powder enclosed in a letter sent to the U.S. Embassy in Copenhagen.

Animals↗

Prediction of smallpox outbreak and evaluation of control-measure policy in Japan, using a mathematical model.

Since the September 1 terrorist attacks and moreover, since the anthrax exposure events in 2001 in the United States, bioterrorism attacks seem to be a real threat. Of course, the public health authorities in Japan have started to prepare control measures for such events. We report here our attempts, using a mathematical model, to estimate outbreak size and to examine the most effective measures; comparing ring vaccination (contact tracing, isolation, and vaccination among contacts) and mass vaccination of the susceptible population in the area. The basic framework of the mathematical model follows a model used in previous research. The initial susceptible population is assumed to be 30 million persons. Concerning the important parameters, such as the number of initial-exposure cases, R0 (infectious power, or natural history) and, the starting day of intervention after the initial exposure, we checked the robustness of our conclusions by sensitivity analysis. We found that mass vaccination is preferable to ring vaccination when the values for the initial-exposure cases and R0 are high and when the start of intervention by public health authorities is delayed. In the base-case situation, the mass vaccination strategy needs almost 30 million vaccine doses. On the other hand, though ring vaccination needs fewer doses, it needs fewer than 50,000 doses in the worst-case scenario, that with larger first exposure, higher R0, or later start of public health authority intervention. This mathematical model can measure the prevalence of an infectious disease and can evaluate control measures for it before an outbreak. Especially, it is useful for the planning of the outbreaks of emerging diseases such as severe acute respiratory syndrome (SARS) or for bioterrorism attacks involving such diseases as smallpox. In further research, we will have to take into account the population people vaccinated of for smallpox, who account for about 70% of the total population in Japan.

Disease Outbreaks↗

Protective efficacy of a recombinant plague vaccine when co-administered with another sub-unit or live attenuated vaccine.

Vaccines against bioterrorism agents offer the prospect of providing high levels of protection against airborne pathogens. However, the diversity of the bioterrorism threat means that it may be necessary to use several vaccines simultaneously. In this study we have investigated whether there are changes to the protective immune response to a recombinant sub-unit plague vaccine when it is co-administered with other sub-unit or live attenuated vaccines. Our results indicate that the co-administration of these vaccines did not influence the protection afforded by the plague vaccine. However, the co-administration of the plague sub-unit vaccine with a live vaccine resulted in markedly increased levels of IgG2a subclass antibodies, and markedly reduced levels of IgG1 subclass antibodies, to the plague sub-unit vaccine. This finding might have implications when considering the co-administration of other vaccine combinations.

Animals↗

Cloning, expression, and purification of Brucella suis outer membrane proteins.

Brucella, an aerobic, nonsporeforming, nonmotile Gram-negative coccobacillus, is a NIH/CDC category B bioterror threat agent that causes incapacitating human illness. Medical defense against the bioterror threat posed by Brucella would be strengthened by development of a human vaccine and improved diagnostic tests. Central to advancement of these goals is discovery of bacterial constituents that are immunogenic or antigenic for humans. Outer membrane proteins (OMPs) are particularly attractive for this purpose. In this study, we cloned, expressed, and purified seven predicted OMPs of Brucella suis. The recombinant proteins were fused with 6-His and V5 epitope tags at their C termini to facilitate detection and purification. The B. suis surface genes were PCR synthesized based on their ORF sequences and directly cloned into an entry vector. The recombinant entry constructs were propagated in TOP 10 cells, recombined into a destination vector, pET-DEST42, then transformed into Escherichia coli BL21 cells for IPTG-induced protein expression. The expressed recombinant proteins were confirmed with Western blot analysis using anti-6-His antibody conjugated with alkaline phosphatase. These B. suis OMPs were captured and purified using a HisGrab plate. The purified recombinant proteins were examined for their binding activity with antiserum. Serum derived from a rabbit immunized intramuscularly with dialyzed cell lysate of Brucella rough mutant WRR51. The OMPs were screened using the rabbit antiserum and purified IgG. The results suggested that recombinant B. suis OMPs were successfully cloned, expressed and purified. Some of the expressed OMPs showed high binding activity with immunized rabbit antiserum.

Animals↗

Passive immunotherapy for anthrax toxin mediated by an adenovirus expressing an anti-protective antigen single-chain antibody.

In the 2001 U.S. bioterror attacks, 33,000 individuals required postexposure prophylaxis, 18 subjects contracted anthrax (11 inhalation, 7 cutaneous), and despite optimal medical therapy, 5 deaths resulted. Rapid protection against anthrax is required in a bioterrorism scenario; this study describes an in vivo gene transfer-based therapy that uses a human adenovirus (Ad)-based vector (AdalphaPAscAb) encoding a single-chain antibody directed against protective antigen (PA), a critical component of Bacillus anthracis lethal toxin. Following AdalphaPAscAb administration to mice, anti-PA single-chain antibody and anti-PA neutralizing activity were detected in serum over a 2-week period. Substantial survival advantage from anthrax lethal toxin was conferred by AdalphaPAscAb following administration from 1 to 14 days prior to toxin challenge, compared to no survival associated with an Ad vector expressing a control single-chain antibody. Passive immunotherapy with an Ad-based vector may be a rapid, convenient approach for protecting a susceptible population against anthrax, including use as an adjunct to antibiotic therapy.

Adenoviridae↗

Lack of hospital preparedness for chemical terrorism in a major US city: 1996-2000.

INTRODUCTION: The [US] Nunn-Lugar-Domenici Defense Against Weapons of Mass Destruction (WMD) Act (the WMD Act of 1996) heralded a new wave of spending by the federal government on counter-terrorism efforts. Between 1996 and 2000, the United States of America (US) federal government allocated large sums of funding to the States for bioterrorism preparedness. Distribution of these funds between institutions involved in first-responder care (e.g., fire and safety departments) and hospitals was uneven. It is unknown whether these additional funds had an impact on the level of hospital preparedness for managing mass casualties involving hazardous materials at the local level, including potential terrorist attacks with chemical agents. OBJECTIVES: (1) To compare 1996 and 2000 measures of preparedness among hospitals of a major US metropolitan area for dealing with hazardous material casualties, including terrorism that involved the use of weapons of mass destruction; and (2) To provide guidance for the improvement of emergency preparedness and response in US hospitals. METHODS: In July 1996 and again in July 2000,21 hospitals in one major US city were surveyed by questionnaire. A survey was used to assess the amounts of antidote stocks held available for treatment of casualties caused by toxic chemical agents and institutional response capabilities including the number of showers for decontaminating patients, the level of worker protection, and the number of staff trained to decontaminate patients. RESULTS: Hospital preparedness for treating and decontaminating patients exposed to toxic chemical agents was inadequate in 1996 and in 2000. From 1996 to 2000, there was no statistically significant change in the lack of hospital preparedness for stocking of nerve agent and cyanide antidotes. Capacity for decontamination of patients, which included appropriate hazardous material infrastructure and trained staff, generally was unimproved from 1996 to 2000 with the exception of an increase of nearly 30% in hospitals with at least one decontamination shower facility. CONCLUSION: Hospitals surveyed in this study were poorly prepared to manage chemical emergency incidents, including terrorism. This lack of hospital preparedness did not change significantly between 1996 and 2000 despite increased funds allocated to bioterrorism preparedness at the local level.

Disaster Planning↗

Social, psychological, and psychiatric interventions following terrorist attacks: recommendations for practice and research.

The terrorist attacks of September 11, 2001, and the constant threat of imminent terrorist activity have brought into the forefront the urgent need to prepare for the consequences of such attacks. Such preparation entails utilization of existing knowledge, identification of crucial gaps in our scientific knowledge, and taking steps to acquire this knowledge. At present, there is little empirical knowledge about interventions following terrorism and absolutely no available empirical knowledge about interventions following bioterrorism. Therefore, this paper reviews knowledge about (1) reactions following the September 11 terrorist attacks in New York City and other places, (2) the practical experiences accumulated in recent years in countries (eg, Israel) that have had to cope with the threat of bioterrorism and the reality of terrorism, and (3) interventions for acute and chronic stress reactions following other types of traumatic events (eg, rape, war, accidents). Our review found several treatments efficacious in treating individuals for acute and chronic post-traumatic stress disorder (PTSD) related to other traumatic events that will likely be efficacious in treating PTSD related to terrorist attacks. However, there were significant gaps in our knowledge about how to prepare populations and individuals for the possibility of a terrorist attack and what interventions to apply in the immediate aftermath of such an attack. Accordingly, we conclude the paper with several questions designed to guide future research.

Health Planning Guidelines↗

The impact of terrorism on brain, and behavior: what we know and what we need to know.

Following the recent US experience with terrorism, including bioterrorism, significant biomedical research resources have been appropriately focused on bioterror weapons. Far less research attention has been focused on the behavioral and psychobiological effects of terrorism. Yet, the psychological responses to terrorism exert significant effects on mental and physical health and on society. We present a research agenda, based on a comprehensive review of the literature, to address the troubling gaps in our knowledge about the long-term effects of terrorism on brain, behavior, and physical health, the risk factors for predicting who will be most affected by terrorism, and interventions that might promote resilience at an individual and population level.

Behavior↗