The CBMTS VII "Seventh International Plenary" begins 13 April 2008 at the home of the CBMTS series, the Swiss National Laboratory, the SPIEZ LABORATORY. We would like to provide our readers with a selected group of Abstracts which demonstrate the breath and depth of this 15th CBMTS meeting.
Innovative Radiological Countermeasure Strategies for Public Health, Emergency Response, and Medical Systems
Steven A. Adams (CDC, Strategic National Stockpile)
Robert C. Whitcomb, Jr. (CDC, Radiation Studies Branch)
Radiation emergencies pose unique challenges to public health and medical systems. One such challenge is the identification, selection, and administration of radiological countermeasures for treatment of Acute Radiation Syndrome and/or decorporation of internalized radioactive material. Public health, emergency response, and medical systems are well practiced in administering countermeasures for biological and toxicological threats, but few in the US have similar proficiency or experience with the use of radiological countermeasures.
Furthermore, treatment efficacy for some radiological countermeasures is heavily time dependent and therefore treatment outcome is significantly improved where there is timely identification, clinical assessment, and administration of the appropriate radiological countermeasures. The U.S. Centers for Disease Control and Prevention (CDC) is proactively developing innovative strategies to decrease the time needed to provide radiological countermeasures and associated health guidance to public health, emergency response, and medical systems. This presentation will provide an update on these strategies and how CDC is working with state and local public health, emergency response, and medical authorities to develop operational approaches and guidance to maximize the impact of investments in Strategic National Stockpile materiel.
Preparedness in France Towards the Cyanide Risk
Frédéric J Baud, Medical and Toxicological Critical Care Department. Assistance Publique Hôpitaux de Paris; University Paris 7; INSERM U705. Lariboisire Hospital, 2, rue Ambroise Paré. 75010 Paris. France
No more than 10 terrorist attempts involving NRBC weapons happened in France between 1970 and 2000 (1). However, there is a major concern regarding preparedness towards these risks. Accordingly, national plans have been prepared. Since 1988, a general plan, the "red plan" has existed aiming at facing any incident involving a large number of victims. In addition, a plan specific for hospitals, the "white plan", has existed since 2002. Specialized plans have been implemented to face specific risks (2). The plan devoted to chemicals, "Piratox", was elaborated in 1970, initially aiming at controlling the production and use of selected chemicals. Thereafter, Piratox was extended to the care of individuals exposed to chemicals. Piratox includes the preparedness in France towards the cyanide risk. Preparedness in France towards the cyanide risk mainly consist in considering that cyanide should be considered in any large-scale chemical incident as well as stockpiling antidotes to cyanide including hydroxocobalamin. However, a number of gaps do exist, precluding any prediction regarding the efficiency of these sophisticated plans. Our capability of emergency diagnosis of cyanide poisoning is still speculative. Stocks of antidotes exist. Supply chain of these antidotes to the right place should be reinforced to maximize the benefit of such strategic stockpiling. In contrast, the availability of hydroxocobalamin on board of medically-staffed ambulance to treat smoke inhalation-induced cyanide poisoning provides the certainty of its immediate availability for other conditions of cyanide poisoning. It is our experience that this large availability has improved the management of cyanide poisoning, mostly resulting from suicidal attempt in selected professions.
DU-ammunition: A Threat to Civilian Population?
Emmanuel Egger, Mario Burger, Ernst Schmid, Stefan Röllin, Christoph Wirz, Markus Astner, Ruth Holzer, Hans Sahli, Alfred Jakob, SPIEZ LABORATORY, Austrasse, CH-3700 Spiez,
Depleted uranium (DU) ammunition is a recent advancement in military weapons use. Due to its effectiveness against armor, DU ammunition has gained its role in the battle fields as an offensive weapon among NATO and other armies. Large amounts of DU ammunitions were used in the Balkan and the second Iraq wars. In regions affected by DU impact, papers were published pretending that the incidence of malignant cancers (such as high leukemia rates), heart problems, and bizarre malformations among new-born had increased.
SPIEZ LABORATORY was one of the institutions charged by UNEP (the United Nations Environment Programme) to analyze the situation in those areas and to elaborate adequate measures to protect their inhabitants in accordance with international radiation protection recommendations. The results of this work are presented on the basis of the mission in Bosnia and Herzegovina. Based on these measurements and a review of the literature published on the subject, we estimate that an increased incidence of malignant cancers and bizarre malformations among new-born can not be caused by DU-ammunition alone. Other possible factors are discussed.
Nevertheless, this kind of ammunition leaves behind a long-lasting local contamination on the battlefields, which - at and close around the impact point - is above civil radiation protection limit values. This argument holds independently whether or not - objectively - there is a danger to man and the environment. However, the contamination itself can be eliminated and its further spread prevented by simply removing the DU penetrators and DU fragments as has been recommended.
A Comparison of the Therapeutic and Reactivating Efficacy of Newly Developed Bispyridinium Compounds (K206, K269) with Currently Available Oximes Against Tabun in Rats and Mice
Jiri Kassa1, Jana Karasova1, Jiri Bajgar1, Kamil Kuca1,2, Kamil Musilek1
1Department of Toxicology and 2Center of Advanced Studies, Faculty of Military Health Sciences, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic
The potency of newly developed bispyridinium compounds (K206, K269) in reactivating tabun-inhibited acetylcholinesterase and eliminating tabun-induced lethal toxic effects was compared with commonly used oximes (obidoxime, trimedoxime, the oxime HI-6) using in vivo methods. Studies determined percentage of reactivation of tabun-inhibited blood and tissue AChE in poisoned rats showed that the reactivating efficacy of both newly developed oximes is comparable with obidoxime and trimedoxime in blood but lower than the reactivating potency of trimedoxime and obidoxime in diaphragm and brain. Nevertheless, the differences in reactivating efficacy of obidoxime, trimedoxime and K206 are not significant while the potency of K269 to reactivate tabun-inhibited acetylcholinesterase is significantly lower. Both newly developed oximes were also found to be relatively efficacious in the elimination of lethal toxic effects in tabun-poisoned mice. Their therapeutic efficacy corresponds to the therapeutic potency of obidoxime. The oxime HI-6 did not seem to be effective oxime in reactivation of tabun-inhibited AChE and to counteract lethal effects of tabun. Both newly developed oximes (K206, K269) are significantly more efficacious to reactivate tabun-inhibited AChE in rats and to eliminate lethal toxic effects of tabun in mice than the oxime HI-6 but their reactivating and therapeutic potency does not prevail the effectiveness of currently available obidoxime and trimedoxime and, therefore, they are not suitable for the replacement of commonly used oximes by them for the treatment of acute tabun poisoning.
Disposable Integrated Microfluidic Microarray Tests for Simple to Use, Low Cost Identification of Infectious Agents
Charles Daitch, Akonni Biosystems Inc., Frederick, Maryland; Dr. Rich Karalus, CUBRC Inc., Buffalo, New York.
An array-based approach to respiratory disease diagnosis is recommended because of the difficulty in distinguishing between viral and bacterial infections based on clinical signs or radiographic evidence of infections, and because single-antibody tests are unreliable and only available for a small number of pathogens. The CUBRC-Akonni technical solution to these challenges is to combine the attributes of patented three-dimensional gel element microarrays and injection-molded fluidics to integrate nucleic acid and antibody-based arrays into disposable test cartridges. Data will be presented for clinical surveillance and diagnosis of common and emerging respiratory infections including influenza A (including avian), influenza B, parainfluenza (types 1-3), human respiratory syncitial virus (RSV), adenovirus (types A-f), SARS coronavirus, group A Streptococcus, multi-drug resistant Mycobacterium tuberculosis, Yersinia pestis, and Staphylococcus pneumoniae. The TruArrayTM technology includes a portable controller instrument and plastic disposable tests onto which a clinical sample may be placed. The technology incorporates state of the art microfluidic processing with microarray detection for fully automated amplification and multiplexed identification. The technology will offer healthcare professionals the opportunity to assess clinical samples for hundreds of genetic or protein signatures in one, rapid, simple to use, low cost test.
Development of Generic Scenarios for Release of Chemicals by Terrorist as a Tool for Crisis Management Teams and Public Health
Gudrun Cassel1, Jan Burman1, Åsa Andersson-Scott1, Rune Berglind1, Håkan Eriksson1, SÅ Persson1 and Jonas Holst2.
1 FOI CBRN Defence and Security, 90182 Umeå, Sweden and 2National Board of Health and Welfare, 10630 Stockholm, Sweden.
The principle objective of this project was to support the development of National health preparedness in case of a terrorist attack with a chemical substance as a weapon. The development of generic scenarios for chemical agents needs therefore a map of grouped chemicals. The threat spectrum from the viewpoint of the actors, agents, means of delivery and targets is very wide and as a result the number of thinkable realistic scenarios is extremely large. Therefore a risk prioritisation matrix has been utilised as a reference for assessing the risks from chemicals of concern in this context, with the chemicals of concern subsequently was analysed in a multivariate model. Five groups of chemicals in two different source strengths and four different environments were established. The outcome of the scenarios and a battery of questions as well as information regarding needs for handling the terrorist attack were established as tools for crisis management teams and Public Health.
Use of the Animal Rule by the U.S Department of Defense to Achieve Food and Drug Administration Approval of New Drugs and Biologics
Dr. Ronald Clawson, Chemical Biological Medical Systems, 64 Thomas Johnson Drive, Frederick, Maryland
In 2002, the U.S. Food and Drug Administration (FDA) published the Animal Rule to allow for the approval of drugs and biologics used to prevent or treat the effects of chemical, biological, radiological, or nuclear threats based on evidence of effectiveness in animals. The Animal Rule amended the new drug and biological product regulations to identify the information needed to provide substantial evidence of efficacy in animals, when human efficacy studies are not ethical, and field trials are not feasible. To date, the FDA's Center for Drug and Evaluation Research has approved only two products under the Animal Rule, whereas the Center for Biological Research and Evaluation has not approved any. The first drug approved was Pyridostigmine Bromide (PB), sponsored by the Department of the Army, for use as a pretreatment against the nerve agent Soman (GD). The original New Drug Application for PB was submitted to the Food and Drug Administration in 1994, however, it was not approved until February 2003, 10 months after the advent of the Animal Rule. This presentation will discuss how the Animal Rule provided the mechanism for approval for PB as well as strategies for seeking licensure for biological warfare defense vaccines.
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