Biological Weapons Agents Research Articles

Theoretical research of toxic gases adsorbed by Mo-doped two-dimensional VS<sub>2</sub> structure

As is well known, the leakage of four toxic gases, NO<sub>2</sub>, NH<sub>3</sub>, mustard gas and sarin greatly threaten the environment and human health. Among of them, mustard gas and sarin are two serious chemical and biological weapons agents, and exposure to a small amount can cause skin burns and immediate death. NO<sub>2</sub> and NH<sub>3</sub> are two common toxic pollutants produced by automobile exhaust, coal combustion and petrochemical industry. The presence of trace amounts of NO<sub>2</sub> and NH<sub>3</sub> gas in human tissues can cause serious respiratory diseases and damage human brain and other systems. Thus, it is very important to realize the rapid detection of NO<sub>2</sub>, NH<sub>3</sub>, mustard gas and sarin in academia and industry. In this study, we use density functional theory to investigate the ability of a transition metal Mo doped two-dimensional VS<sub>2</sub> structure to detect the four representative toxic gases. The results reveal that Mo atom doping has a significant effect on the stability and gas-sensitivity of the VS<sub>2</sub> structure. The Mo atom can be successfully doped on the S-vacancy in the two-dimensional VS<sub>2</sub> structure. Compared with the undoped structure VS<sub>2</sub>, the doped structure Mo-VS<sub>2</sub> has strong interaction with NO<sub>2</sub>, NH<sub>3</sub>, sarin, and mustard gas, realizing effective adsorption of them. The presence of Mo atom in the VS<sub>2</sub> lattice changes the electronic structure of VS<sub>2</sub>, also modifies its band gap and density of states. The interaction between the Mo-VS<sub>2</sub> structure and the target analytes depends strongly on the nature of the gas molecule. The binding energy values for NO<sub>2</sub>, NH<sub>3</sub>, mustard gas, and sarin on the Mo-VS<sub>2</sub> are significantly higher than those on the pristine VS<sub>2</sub>, indicating stronger interaction between the Mo-VS<sub>2</sub> structure and these gases. Our calculations show that the Mo atom in VS<sub>2</sub> changes its electrical resistance after being exposed to the gases, which can be used to distinguish different gases. Moreover, differences in charge redistribution within the Mo-VS<sub>2</sub> structure upon being exposed to different gases can be used to explain their differential gas-sensitivity. Our results can provide sufficient theoretical basis for experimental researchers to design and optimize the performances of sensors in practical applications.

Pathogenic Bacilli as an Emerging Biothreat?

Bacillus anthracis, present as a very durable endospore in soil, causes zoonotic illness which is mainly associated with herbivores and domestic animals. Human cases are scarce and often involve populations close to infected livestock. If anthrax is no longer of public health concern in developed countries, B. anthracis is one of the top-tier biological weapon agents. It is classified by the CDC as a category A agent. Since 1994, emerging strains of Bacillus cereus have been associated with anthrax-like disease in mammals. Some clinical strains of B. cereus harbor anthrax-like plasmid genes (pXO1 and pXO2) associated with non-human primate and human infections, with the same clinical presentation of inhalation anthrax and mortality rates. Although currently restricted to certain limited areas of circulation, the emergence of these new strains of B. cereus extends the list of potential agents possibly usable for bioterrorism or as a biological weapon. It is therefore important to improve our knowledge of the phylogeny within the B. cereus sensu lato group to better understand the origin of these strains. We can then more efficiently monitor the emergence of new strains to better control the risk of infection and limit potentially malicious uses.

Bioterrorism Preparedness and Response in Poland: Prevention, Surveillance, and Mitigation Planning.

Biological weapons are one of the oldest weapons of mass destruction used by man. Their use has not only determined the outcome of battles, but also influenced the fate of entire civilizations. Although the use of biological weapons agents in a terrorist attack is currently unlikely, all services responsible for the surveillance and removal of epidemiological threats must have clear guidelines and emergency response plans. In the face of the numerous threats appearing in the world, it has become necessary to put the main emphasis on modernizing, securing, and maintaining structures in the field of medicine which are prepared for unforeseen crises and situations related to the use of biological agents. This article presents Poland's current preparation to take action in the event of a bioterrorist threat. The study presents both the military aspect and procedures for dealing with contamination. In Poland, as in other European Union countries fighting terrorism, preparations should be made to defend against biological attacks, improve the flow of information on the European security system, strengthen research centers, train staff, create observation units and vaccination centers, as well as prepare hospitals for the hospitalization of patients-potential victims of bioterrorist attacks.

FRANCISELLA TULARENSIS– REVIEW

Abstract In the early twentieth century, Francisella tularensis was identified as a pathogenic agent of tularaemia, one of the most dangerous zoonoses. Based on its biochemical properties, infective dose and geographical location, four subspecies have been distinguished within the species F. tularensis: the highly infectious F. tularensis subsp. tularensis (type A) occurring mainly in the United States of America, F. tularensis subsp. holarctica (type B) mainly in Europe, F. tularensis subsp. mediasiatica isolated mostly in Asia and F. tularensis subsp. novicida, non-pathogenic to humans. Due to its ability to infect and variable forms of the disease, the etiological agent of tularaemia is classified by the CDC (Centers for Disease Control and Prevention, USA) as a biological warfare agent with a high danger potential (group A). The majority of data describing incidence of tularaemia in Poland is based on serological tests. However, real-time PCR method and MST analysis of F. tularensis highly variable intergenic regions may be also applicable to detection, differentiation and determination of genetic variation among F. tularensis strains. In addition, the above methods could be successfully used in molecular characterization of tularaemia strains from humans and animals isolated in screening research, and during epizootic and epidemic outbreaks. 1. Historical overview. 2. Characteristics and taxonomy of F. tularensis. 3. Morphology. 4. Culture media and conditions. 5. Biochemical properties. 6. Survivability and persistence of F. tularensis. 7. F. tularensis as a biological weapon agent. 8. Tularaemia vaccines. 9. Pathogenicity of F. tularensis. 10. Tularaemia treatment. 11. Laboratory diagnostics of F. tularensis. 12. Summary

The use of Anthrax and orthopox therapeutic antibodies from human origin in biodefense

The use of Anthrax and orthopox therapeutic antibodies from human origin in biodefense

Point-of-care diagnostics for ricin exposure.

A long-sought milestone in the defense against bioterrorism is the development of rapid, simple, and near-patient assays for diagnostic and theranostic purposes. Here, we present a powerful test based on a host response to a biological weapon agent, namely the ricin toxin. A signature for exposure to ricin was extracted and characterized in mice and then integrated into a plastic microfluidic cartridge. This enabled early diagnosis of exposure to ricin in mice using a drop of whole blood in less than 1 h and 30 min. The cartridge stores the reagents and implements all of the steps of the analysis, including mRNA extraction from a drop of blood, followed by tens of parallel RT-qPCR reactions. The simple and low-cost microfluidic cartridge developed here may find other applications in point-of-care diagnostics.

The Soviet Biological Warfare Program and Its Uncertain Legacy

On 22 March 2012, Russian president-elect Vladimir Putin promised to develop new weapons based on advanced technologies, including genetics. Having just completed a history of the Soviet biological warfare (BW) program with Milton Leitenberg, I found Putin's promise exceedingly threatening. It could signal a new Russian military effort to develop third-generation biological weapons agents, building on the first- and second-generation BW programs of the former Soviet Union.

Analysis of Introduced Species as a Form of Biological Weapon: Part 1-Theory and Approaches

The hypothesis of this paper is that introduced species (aka non-indigenous species) could be used as a form of biological weapon (BW). The first step of this paper is a brief review of biological weapon concepts, and a review ofthe definition of an introduced species, as well as a brief survey of historical examples of introduced species. Previous evidence of the use of invasive species as a form of biological weapon is also discussed.The methods to predict a successful invasive species candidate is discussed, and examples of various theories and computer software models to analyze introduced species invasions are reviewed. The use of GARP (Genetic Algorithm for Rule-set Prediction) has found promise in predicting the range and effective invasiveness of an organism, prior to the actual invasion. This research discusses the approaches of invasive species by hostile actors (aggressor nation, crime syndicate,bioterrorists, or lone individual), as well as the various BW targets (public health, ecosystems, agricultural commodities,biofuel feed stocks). The vulnerability of nations to invasive species introduction, as well as the risk factors favoring invasive species BW would also be examined. Some of these risk factors favoring a BW attack using invasive speciesinclude poor communication between local population and government scientists and decision makers; monocultureof agricultural fields; disturbed or damaged ecosystems, and presence of favored niches in the targeted areas. Thestrategies to introduce BW invasive species are discussed, and range from human smuggling and delivery by vectors to biocruise-the technique of using cruise missile technology (aka unmanned aerial vehicles), to deliver and disperse BW agents (e.g. virus, fungal spores, bacteria, even insects), at precise targeted sites. Two models are presented to describe the process of invasive species BW by hostile actors-one, using a single invasive species and one leading to invasion meltdown of the targeted area. Four examples of potential BW using introduced species are discussed, with supportive evidence for their effectiveness and invasive potential on targets (Nipah virus, Striga plant parasite, Heartwater-Ehrlichia ruminantium, and Wheat Stem Rust-Puccinia graminis f. st.tritici). Finally, the data supports the hypothesis that introduced species could be used as a form of biological weapon.

The public health implications of melioidosis

Melioidosis, which is caused by the bacterium Burkholderia pseudomallei, is a potentially fatal tropical infection, little known outside its main endemic zone of Southeast Asia and northern Australia. Though it has received more attention in recent years on account of its claimed suitability as a biological weapon agent, the principal threat from melioidosis is a result of naturally occurring events. Occasional case clusters, sporadic cases outside the known endemic zone and infections in unusual demographic groups highlight a changing epidemiology. As melioidosis is the result of an environmental encounter and not person-to-person transmission, subtle changes in its epidemiology indicate a role environmental factors, such as man-made disturbances of soil and surface water. These have implications for travel, occupational and tropical medicine and in particular for risk assessment and prevention. Practical problems with definitive laboratory diagnosis, antibiotic treatment and the current lack of a vaccine underline the need for prevention through exposure avoidance and other environmental health measures. It is likely that the increasing population burden of the tropical zone and extraction of resources from the humid tropics will increase the prevalence of melioidosis. Climate change-driven extreme weather events will both increase the prevalence of infection and gradually extend its main endemic zone.

High throughput detection of Coxiella burnetii by real-time PCR with internal control system and automated DNA preparation

BackgroundCoxiella burnetii is the causative agent of Q-fever, a widespread zoonosis. Due to its high environmental stability and infectivity it is regarded as a category B biological weapon agent. In domestic animals infection remains either asymptomatic or presents as infertility or abortion. Clinical presentation in humans can range from mild flu-like illness to acute pneumonia and hepatitis. Endocarditis represents the most common form of chronic Q-fever. In humans serology is the gold standard for diagnosis but is inadequate for early case detection. In order to serve as a diagnostic tool in an eventual biological weapon attack or in local epidemics we developed a real-time 5'nuclease based PCR assay with an internal control system. To facilitate high-throughput an automated extraction procedure was evaluated.ResultsTo determine the minimum number of copies that are detectable at 95% chance probit analysis was used. Limit of detection in blood was 2,881 copies/ml [95%CI, 2,188–4,745 copies/ml] with a manual extraction procedure and 4,235 copies/ml [95%CI, 3,143–7,428 copies/ml] with a fully automated extraction procedure, respectively. To demonstrate clinical application a total of 72 specimens of animal origin were compared with respect to manual and automated extraction. A strong correlation between both methods was observed rendering both methods suitable. Testing of 247 follow up specimens of animal origin from a local Q-fever epidemic rendered real-time PCR more sensitive than conventional PCR.ConclusionA sensitive and thoroughly evaluated real-time PCR was established. Its high-throughput mode may show a useful approach to rapidly screen samples in local outbreaks for other organisms relevant for humans or animals. Compared to a conventional PCR assay sensitivity of real-time PCR was higher after testing samples from a local Q-fever outbreak.

Degradation of Biological Weapons Agents in the Environment: Implications for Terrorism Response

We investigate the impact on effective terrorism response of the viability degradation of biological weapons agents in the environment. We briefly review the scientific understanding and modeling of agent environmental viability degradation. In general, agent susceptibility to viability loss is greatest for vegetative bacteria, intermediate for viruses, and least for bacterial spores. Survival is greatest in soil and progressively decreases in the following environments: textiles, water, hard surfaces, and air. There is little detailed understanding of loss mechanisms. We analyze the time behavior and sensitivity of four mathematical models that are used to represent environmental viability degradation (the exponential, probability, and first- and second-order catastrophic decay models). The models behave similarly at short times (<30 min for our example case) but diverge to significantly different values at intermediate to long times. Hence, for a release event in which the majority of atmospheric exposure or deposition occurs oververy short times, the current response models likely provide a good representation of the hazard. For longer time phenomena, including decontamination, the current model capabilities are likely insufficient. Finally, we implement each model in a simple numerical integration of anthrax dispersion, viability degradation, and dose response. Decay models spanning the current knowledge of airborne degradation result in vastly different predicted hazard areas. This confounds attempts to determine necessary medical and decontamination measures. Hence,the current level of understanding and representation of environmental viability degradation in response models is inadequate to inform appropriate emergency response measures.

Weapons of Mass Destruction and the United Nations

What Happened in Iraq? The Success Story of UN Inspections This is an extraordinarily important moment for the United Nations. Before attention is lost in the controversies over the war itself and in the challenges of its aftermath, the UN must capture, clarify, and publicize the record of international inspections in Iraq: for itself, for member governments, and for the public. Was the process encompassing the UN Special Commission (UNSCOM), the International Atomic Energy Agency (IAEA), and the UN Monitoring, Verification and Inspection Commission (UNMOVIC) from 1991 to 2003 a success? Or was it the bumbling embarrassment, the sham, portrayed by top U.S. officials and still understood that way by the American public--and perhaps by the public elsewhere? The bottom line is that it was in fact a rather striking international success that stands out in the record of recent decades. However, it is a success studded with weaknesses that need to be understood and corrected and one that, because it is not yet recognized, is not fully real. Without a concerted analytical effort, the record of what actually happened, and its very real promise for the future, could easily be lost. In the surging controversy over British and U.S. intelligence failures in Iraq, a critical fact is still largely unnoticed: while the national intelligence services were getting it wrong, UN inspectors were getting the picture largely right. In 1991-1998, UNSCOM and the IAEA--while facing unrelenting Iraqi opposition and obstruction--successfully discovered and eliminated most, if not all, of Iraq's unconventional weapons and production facilities and destroyed or monitored the destruction of most of its chemical and biological weapons agents. Iraq's most secret program--its biological weapons program--was discovered through painstaking detective work and was reported to the Security Council four months before the defection of Saddam Hussein's son-in-law Hussein Kamel. UNSCOM also uncovered covert transactions between Iraq and more than five hundred companies from more than forty countries--a body of work that assumes fresh significance in the light of recent disclosures of the nuclear sales network of Pakistan's A. Q. Khan. Also, inspectors put in place a mechanism to track and block banned exports and imports. In the months immediately preceding the war, UN inspectors' assessments of Iraq's programs were remarkably close to what has since been found--and far more accurate than U.S. or British prewar beliefs. UNMOVIC was permitted to operate for less than four months, and only for a matter of weeks at full strength. But to the best of present knowledge, the inspectors were in fact in the process of finding and beginning to dismantle what was there. This record suggests a number of lessons--positive and negative. First, it appears that a package of international restraints--sanctions, the procurement investigations, and the export/import controls combined with core inspections--worked together in a way that is not yet understood, and that this package was considerably more effective than has been appreciated then or since. Second, even though UNSCOM and the early IAEA inspections operated under a degree of Iraqi obstruction that the Security Council never should have tolerated, the UN inspections' greatest area of weakness lay in New York, not in Iraq. Iraq played a highly effective game of divide and conquer in the Security Council, setting the permanent members against each other until political support was so undermined that inspections were forced to a halt in 1998. The lesson is clear. Political unity in backing inspections is as important as technology and expertise on the ground, and the Security Council is not now set up to provide it. Inspections should not again be launched without more settled political support behind them. And the Security Council should never again allow rules of the game that tilt the playing field so steeply in favor of the miscreant and against its own agents. …

Rapid diagnostic assays in the genomic biology era: detection and identification of infectious disease and biological weapon agents.

In this special section of BioTechniques, we examine the role of rapid molecular technologies in the detection and identification of agents of infectious disease (ID) and biological weapons (BWs). Besides the threat posed by the global proliferation of BW technologies, there are numerous emerging and reemerging ID agents with significant public health consequences. Further compounding this already complicated situation are the estimated 600 million international tourists annually, many with the potential to the spread disease globally in a matter of hours. While clinical laboratories have key roles in the detection and identification of potential ID/BW agents, most staff are unfamiliar with these agents because of their rarity and the often laborious conventional methodologies needed to identify them. To meet this challenge, a vast array of rapid assay strategies has been developed for use in clinical diagnostics and environmental detection. Technologies have been developed or adapted to the challenges posed by these agents, permitting detection and identification in several minutes to hours. In particular, the development of improved reagents and detection systems has led to dramatic improvements in the sensitivity and specificity of immunological and nucleic acid-based systems, allowing an ever-increasing range of analytes to be identified and quantitated. In the accompanying articles, we have brought together experts from the many overlapping aspects of this arena in order to present a comprehensive and critical analysis of these technologies.

Which bio‐weapons might be used by terrorists against the United Kingdom?*

The properties of potential biological weapon agents for bioterrorism include a consistent effect at low dosage and short incubation period in a population of low immunity, being difficult to treat, able to be produced in bulk, stable in storage and readily disseminated. Possible agents include smallpox, haemorrhagic fever viruses, anthrax, tularaemia and plague. The example of Severe Acute Respiratory Syndrome (SARS) demonstrates the possible consequences of an act of bioterrorism, but also the necessary global response. There is scepticism about the practicability of surveillance schemes and the global elimination of biological weapons though the Biological and Toxin Weapons Convention remains urgent.

Immunological methods for detection and identification of infectious disease and biological warfare agents.

BW agents.The release of a biological weapon (BW) agent by a terrorist group or military force would likely be silent and undetectable or nearly so. As shown by anthrax attack during the fall of 2001 in the eastern United States, patients would begin appearing at hospitals and clinics within several

Modeling Immune Building Systems for Bioterrorism Defense

This paper presents the results of research on the performance of air-cleaning and air-disinfection systems used for protecting buildings against intentional releases of biological agents. The air-cleaning technologies addressed include dilution ventilation, filtration, and ultraviolet germicidal irradiation. A 40-story commercial office building is modeled using typical occupancy levels and leakage rates for doors, walls, and floors. A steady-state single-zone model is used to predict steady-state conditions resulting from the use of various levels of air cleaning. A transient single-zone model is used to predict transient indoor concentrations from which inhaled doses and estimated casualties are predicted. A transient multizone model is used to evaluate contaminant dispersion and estimate potential casual- ties. Three design-basis attack scenarios are simulated using various biological weapon agents. Predicted casualties are estimated using an epidemiological model of the dose response curves for each of the agents. The effect of increasing levels of air cleaning is examined under the attack scenarios to evaluate their effectiveness. Results indicate that high levels of protection are possible for building occupants with moderate and affordable levels of air cleaning when filtration is combined with ultraviolet germicidal irradiation. Results also suggest that diminishing returns occur when increased levels of air cleaning are applied. It is hypothesized that the maximum useful size of any air-cleaning system is defined and limited by building physical characteristics alone.

Investigating disease outbreaks under a protocol to the biological and toxin weapons convention.

The Biological and Toxin Weapons Convention prohibits the development, production, and stockpiling of biological weapons agents or delivery devices for anything other than peaceful purposes. A protocol currently in the final stages of negotiation adds verification measures to the convention. One of these measures will be international investigation of disease outbreaks that suggest a violation of the convention, i.e., outbreaks that may be caused by use of biological weapons or release of harmful agents from a facility conducting prohibited work. Adding verification measures to the current Biological and Toxin Weapons Convention will affect the international public health and epidemiology communities; therefore, active involvement of these communities in planning the implementation details of the protocol will be important.

Domestic terrorism with chemical or biological agents: psychiatric aspects.

This article highlights the mental health consequences of a domestic terrorist incident involving chemical or biological weapons. The author reviews the literature on the neuropsychiatric effects of selected chemical and biological weapon agents, on the psychological sequelae of mass disasters, and on approaches to crisis intervention. Disturbances of behavior, affect, and cognition can result directly from the pharmacological actions of some chemical and biological weapon agents. In addition, an incident involving these agents can have considerable psychological effects on individuals and the community. In either case, some disorders are acute and others are prolonged or delayed in onset. Effective therapeutic intervention involves a broad range of clinical, social, and administrative actions. Psychiatrists have an important role in the management of a chemical or biological terrorist incident and, along with their other medical colleagues, should train and prepare for it.

Do US Emergency Medicine Residency Programs Provide Adequate Training for Bioterrorism?

Currently, there is no standardized curriculum for training of emergency physicians about the health hazards related to weapons of mass destruction. Opportunities for the widespread teaching of this material have remained limited, and the range of knowledge regarding even general disaster medical care is also variable among most residency training programs in the United States. We developed a survey to ascertain whether any formal training in biological weapons is conducted in emergency medicine programs; to determine the overall subjective ability of program directors or residency directors to recognize and clinically manage casualties of biological weapons agents; and to identify which resources might be used by emergency physicians to identify and treat biological warfare casualties. We also document a baseline of current practices regarding biological weapons training in emergency medicine residency programs. [Pesik N, Keim M, Sampson TR: Do US emergency medicine residency programs provide adequate training for bioterrorism? Ann Emerg Med August 1999;34:173-176.]

Production and Use of Biological Weapons: Need for International Sanctions?

To the Editor. —Offical US government assessments indicate that from 1972 through 1975, when the Biological and Toxin Weapons Convention (BWC) was signed and came into force, 4 countries in the world had biological weapons (BW) development programs. In the 1990s, that number is around 10 and includes China, Egypt, Iran, Iraq, Libya, North Korea, Syria, and Taiwan, with the status of the BW programs that existed in the past in Russia and South Africa ambiguous at present. 1-6 It is not clear exactly how many of these nations are currently producing or stockpiling BW agents, but apparently 2 or 3 (possibly China, Iran, and Iraq) may be. 1-6 Of particular significance is the fact that several of these 10 nations are signatories of the BWC, which prohibits both the development and production of BW. There was no serious international response to the use of chemical weapons by Iraq against