The 12 year anniversary of the Chemical and Biological Medical Treatment Symposia (CBMTS)
The Sixth Plenary
Spiez Laboratory Switzerland
Spiez , Switzerland
30 April - 05 May 2006
The 13th meeting in the Chemical and Biological Medical Treatment Symposia (CBMTS) series, and the sixth international meeting to be held at the birthplace of the series, the SPIEZ LABORATORY, was another very, very successful gathering of the CBMTS professionals. Outstanding presentations from the podium and poster, an international mix of the very best professionals in science and medicine, produced a symposium with dynamic and far reaching results, a trademark of the CBMTS series.
Dr. Marc Cadisch, Director SPIEZ LABORATORY and Director CBMTS VI, provided the welcome and opening of the CBMTS VI. He introduced a series of internationally well known and recognized speakers who were able to provide our members an insight, an appreciation and an overview of current events that would directly shape the efforts of all CBMTS professionals in attendance at this 13th meeting. These opening speakers included the Swiss Federal Councillor Samuel Schmid, Head of the Federal Department of Defence, Civil Protection and Sports and the person responsible for the support of the CBMTS series in Switzerland; Ambassador Rogelio Pfirter, the Director General of the Organization for the Prohibition of Chemical Weapons (OPCW) and the person responsible for the broad worldwide reception for the CBMTS series; and David Poythress, the Adjutant General for the US State of Georgia who has long been a supporter and direct participant in the CBMTS series. Col. Richard Price, CBMTS VI Co-Director, closed the Opening Ceremony by recognizing the contributions of the CBMTS distinguished members and guests and especially Federal Councillor Samuel Schmid for his support of the CBMTS series through the CBMTS Host and Sponsor The SPIEZ LABORATORY.
This Opening was following by a fascinating first Session which included Dr. Brian Davey, Head Health and Safety OPCW with a description of the OPCW’s planning for a possible pandemic; Dr. David Robinson, Senior CBMTS member from Battelle Memorial Institute and his report on Influenza: An Enduring Pathogen; Dr. Erna Tresnaningsih, the Head of Indonesia’s Centers for Disease Control and her most current report on the Spread of the H5N1 Infection amongst Humans in Indonesia; and, Dr. Sergey Netesov, Deputy Director for VECTOR in Novosibirsk and his report on The Epizooty of Avian Influenza in 2005 in Russia. These exceptionally current and dynamic presentations set the stage for an unprecedented series of reports from our professionals that would last until the closing ceremony on Friday 05 May 2006. Below are excerpts from the follow-on sectors and sessions.
Excerpts from the Sector Chair summaries
SECTOR 1: CHEMICAL ASPECTS
CHAIR: David Moore, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland USA
CO-CHAIR: Weng Keong Loke, Defence Medical and Environmental Research
Institute, DSO National Laboratories
Presented by: David Moore
The chemical sector was comprised of 9 lectures and 6 posters delivered by scientists from 8 countries. The prevalent theme of the contributions was the development of improved medical countermeasures to chemical warfare nerve agents. Specifically, studies of one class of nerve agent countermeasure, oximes, comprised the majority of the contributions. In general, it was clear that the decades-long debates as to 1. the selection of the most efficacious oxime enzyme reactivator and 2. the selection of the best experimental model for extrapolation of oxime efficacy data to the human condition continues to persist. To complicate matters, criteria for the best oxime reactivator for use by various military forces may not be the most appropriate for use by civilian populations. In addition to the therapeutic index and the safety profile for the oxime, planners must consider the availability of other countermeasures and the risks of the agents most likely to be encountered by the different populations. From the presentations, it was again evident that in some laboratories and experimental conditions the oxime HI-6 is clearly the most effective AChE reactivator. However, in other laboratories and in different experimental model systems the advantages and the broad spectrum efficacy of HI-6 are less apparent when compared to current and potential replacement reactivators. Going forward, this continuing debate is expected to generate much less emphasis, as most countries represented in the CBMTS have made firm decisions as to their next generation oxime antidote and these drugs are now in the regulatory cycle prior to licensure. An interesting new contribution to CBMTS was the report of the clinical application of Diethyxime as an antidote for acute poisoning of people and animals with OP pesticides. This compound, with low toxicity, is reported to provide reactivation of OP-inhibited AChE in the central nervous system.
One of the most important advances in medical chemical defense in the past two decades is the recognition of the neurological squeala of nerve agent-induced seizures and the resultant development and clinical application of effective anticonvulsants as post-exposure therapy. Several contributions to this sector described efforts to improve this therapy by providing more rapid onset of action and a longer period of therapeutic efficacy of anticonvulsants while at the same time providing measurable improvements in neuronal protection. It is hoped that by utilizing drugs currently approved for other indications, and by meeting the new regulatory requirements for animal testing, that these improvement in efficacy will be available in the near-term.
The development effort of a broad-spectrum OP bioscavenger has made remarkable progress since it was first described as a concept at CBMTS II. By now having this protien produced in significant quantities and under GMP conditions and by having a strong industry-government partnership, this program should continue to advance.
Other important areas of medical chemical defense were addressed in this sector. The development of pharmaceutical countermeasures to botulinum toxin is one of three research strategies to counter this threat. Along with vaccines and anti-toxin, drugs can make a significant impact in mitigating the effects of the toxin if a safe and effective drug can be delivered to the intra-cellular site of action of the toxin. In the case of sulfur mustard, modern molecular techniques such as proteomics is being used to provide better resolution to our understanding of the mechanism of the toxic insult to living tissue. This line of research will also make specific antidotal and therapeutic drug discovery more efficient.
Finally in this sector we were introduced to the serious potential toxic inhalation hazard of certain classes of obscurant smokes and made aware of new sensitive analytical techniques for measuring chemical agents in biological fluids. We were also educated as to the genetic basis of human susceptibility to toxic chemicals a phenomenon now recognized as an area of enormous interest to the pharmaceutical industry.
In conclusion, I would like to thank the session chairs and co-chairs and all of the presenters for their valuable contributions to this sector. I also thank all of the congress participants for their attention and interactions during the proceedings.
SECTOR 2: BIOLOGICAL ASPECTS
CHAIR: David Robinson, Battelle Memorial Institute, Columbus, Ohio USA
CO-CHAIR: Sergey Netesov, SRC Virology and Biotechnology, Vector, Novosibirsk, Russia
Presented by: Sergey Netesov
Avian influenza became the #1 infectious threat for poultry during 2003-2006 and could soon become the same for humans. And therefore many international organizations put their attention to the development of measures for its control. The opening lecture was devoted to the possible OPCW role in the struggle with the possible coming pandemy. An excellent overview report on the history of influenza outbreaks followed and pointed out that decision-makers must determine the financial investment necessary to mitigate the effects of a rare event (i.e. pandemic influenza) that will produce disastrous effects on the economics and life on the world’s human population.
We were very fortunate to have first hand data and detailed data presented on the H5N1 cases among humans in Indonesia (totally, 37 cases with 74% mortality). The CBMTS was presented very interesting data on the usage of modified horse RBC HI test for fast diagnostics. It was shown that 13 H5N1 viruses associated with human cases were determined to be genetically distinct indigenous Indonesia viruses of avian origin and the remaining cases were phylogenetically similar to the Chinese strain. The source of infection was likely due to human exposure to infected poultry, or environmental contamination (i.e. poultry manure as fertilizer), with limited person-to-person transmission.
Biological aspects I (Part 2)
An SRC VB Vector, Russia author gave the description of H5N1 epizooty in Russia in 2005. He reported that there were no human cases of H5N1. He indicated that Siberian residents were advised to avoid close contacts with ill or dead birds, that poultry on positive private premises were culled and sanitary measures were implemented at poultry plants. The hunting of wild fowl was also later prohibited. He expects migratory birds to continue to transport avian influenza into Siberia in 2006 from Europe and South-east Asia.
A CBMTS representative from Brazil presented a list of possible bioterroristic threats to agriculture in South America especially engaged with ethanol mass production from sugar cane. The results of a simulation of the effects of agro-terrorism attack on the sugarcane business in Brazil was presented and revealed that a 15% fall in sugarcane production would force over 1 million people in the region below the poverty line. Another study conducted by Dr Santana, et al., described the reasons why agro-terrorism might be attractive to terrorists groups and pointed to a series of vulnerabilities in the region, specially, with regards to the Brazilian reality. The presentation discussed the current FMD outbreak and its effects on the Brazilian economy: at the time of writing the report, 57 countries had banned the imports of meat products from Brazil.
The International Programme on Chemical Safety (IPCS), World Health Organization (WHO) reprersentative gave a presentation on the WHO Chemical Incidents Alert and Response system based on an analysis of more than 3000 events of which about 100 were considered to be of international importance. The system was established in 2002 and serves as the chemical safety arm of the WHO, providing public health and medical management, early detection, and verification and alert systems. The Global Public Health Information Network strongly relies on partners and it has been very successful. The Network identified 78 chemical incidents of international public health concern in 2004-05, with the majority detected within two days. He emphasized that the WHO can provide technical assistance, analytical lab support, deployment of experts and materials (antidotes), and participants in field missions in response to chemical incidents as requested.
From SRC VB Vector, Russia the CBMTS was presented a report on the major role of viruses as pathogens of humans, gave the main sources of emerging viral pathogens and suggested the ways of controlling them in the future which should include tight international collaboration.
Vector also reported the results of the study of morphological parameters of different orthopoxvirus infections in chick embryos and showed that the virus replication is accompanied with production of specific structures which can be used for differential diagnostics of poxviruses.
From the Military Medical Academy, Bulgaria we were presented detailed data on the tularemia outbreaks in Bulgaria (250 cases during 1997-2004) and main identification procedures (PCR and genotyping) used for detection and recognition of this infection. Three different species of this pathogen were identified.
A Serbia and Montenegro member gave a review on hemorrhagic fevers occurrence in her country. In 1992 isolation of the new genotype of hantavirus – Belgrade – was reported. The largest HFRS epidemics was registered in 1995 during the civilian war. HFRS and CCHF occur sporadically in southern part of Kosovo, Serbia, Montenegro and Macedonia. The existence of active CCHF natural foci in the territory of former Yugoslavia was confirmed.
From the University of Zambia, Zambia was presented the detailed data of Cryptosporidum infection with its main symptoms and treatment methods and warned about its potential as bioterroristic agent, especially in poor resource settings. Massive cryptosporidial water contamination would lead to very serious consequences because of difficulties in diagnostics and high cost of treatment.
A Croatian participant presented data to prove the usefulness of the development and introduction of informal Codes of Conduct for researchers working in the dual-use areas of chemical, biological and radiological sciences. It would increase the level of safety and security of these investigations and diminish possible hostile use of life sciences.
A report was given on the Polish Biological Identification and Alert System. It consists of Biological Response Teams (collection of samples, primary identification of pathogen, delivery of pathogen to lab and primary decon procedures), a few regional Military Centers of Preventive Medicine, Epidemiological Reaction Center of Polish Armed Forces (BSL-3+) , and additional independent (MOH) network of Sanitary Epidemiological Stations.
The US EPA reported on the first stage of development by the US EPA of the tools and technologies for microbial risk assessment which consists of collection and assessment of data pertaining to the transport, fate and decontamination of biological agents.
Biological aspects : Poster Session
A report from the Pedagogical University, Bishkek, Kyrgyzstan provided interesting historical data regarding human exposure to viruses in Central Asia and how this “data base” increases our knowledge and lessons learned about the current avian epidemic.
A Serbia and Montenegro presenter described the therapeutic efficacy of different zeolite formulations in treatment of acute T-2 toxicosis.
Two Chinese contributions demonstrated the incredible power of molecular biology in identifying and understanding the genetics of all pathogens. One report described the work on a proteomic analysis of Shigella. An important discovery was an antigen (YaeT) strongly immunogenic to Shigella serum and a potential vaccine candidate.
A second report from China described screening the inhibitor of staphylococcal enterotoxin B (SEB) from phage peptide libraries. The most interesting screened peptide may serve as a potential anti-SEB drug in the future.
Conclusions: Biological Aspects
Avian influenza became #1 infectious threat for poultry during 2003-2006 and may soon become the same for humans. And therefore a lot of countries and international organizations are developing measures for its control. The Symposium speakers agreed that the more tight international cooperation and data exchange are needed to struggle with emerging and re-emerging infections.
A few interesting reports added to our knowledge of the need to continue to develop new, fast, effective and accurate diagnostic methods for detection and identification of infectious agents.
The monitoring of infectious pathogens in natural reservoirs and foci is becoming of high importance for early warning about new and emerging infections for animals and humans.
The possible agro-terrorism and another cases of deliberate use of pathogens with terroristic purposes should be also a point of attention .
The need of search and screening of new antimicrobial and antiviral preparations has been demonstrated by scientists of different countries.
International cooperation is also needed for the further development of ethical codes for investigators in the field of life sciences and, especially, in the field of infectious diseases and for their more active participation in different existing networks.
SECTOR 3: MEDICAL/RADIOLOGICAL ASPECTS
CHAIR: Slavko Bokan, Ministry of Defence, Policy & Planning, Zagreb, Croatia
CO-CHAIR: Steven Bice, Battelle Life Sciences Division, Atlanta, Georgia USA
Presented by: Slavko Bokan
The Medical and Radiological Aspects Sector of CBMTS VI consisted of 11 oral presentations and 6 poster presentations delivered by scientists from 13 counties.
The emphasis was primarily in one of two areas:
1. The Medical Aspects of chemical and biological warfare agents, medical treatment and prophylactic measures, and
2. Issues related to radiological threat today.
Session 5 Radiological Aspects was dedicated to the radiological threat in connection with the prevention of nuclear and radiological terrorism, including preparedness for these events.
A very interesting lecture regarding the interactions of infection with radiation injury was presented. Also, a presenter provided data pointing to the limitations in antibiotic therapy and vaccine efficacy after radiation injury.
Next we listened to an interesting presentation regarding to radiation accidents and the medical consequences as a model for radiological and nuclear terrorism.
The presentation regarding the new method for detection of radioactive materials as border security technology and one presentation which described a different model for estimating radiation contamination associated with a 137-Cs dirty bomb event also was presented.
In Session 6 Medical Aspects I authors presented 4 interesting lectures regarding medical treatment and prophylactic measures. This session included presentations regarding forty years experiences with blood cholinesterase monitoring of workers with nerve agents and medical treatment of intermediate syndrome of organophosphate poisoning. The always interesting lectures regarding the Iranian experiences of management of late complications of sulfur mustard poisoning and prevalence of long term cutaneous effects of mustard gas in CW victims were presented.
Session 13 Medical Aspects II contained 3 presentations. We heard interesting lectures regarding to antidotal therapy and choosing the right oxime in treatment of nerve agent poisoning and pre-hospital use of hydroxocobalamin in case of children exposed to fire smoke. Additional presentation concentrated on the epidemiological consideration and impact on prophylactic measures under field conditions that may increase the microbial resistance and made more difficult the treatment of common infections.
The sub-session on medical aspects which was incorporated in poster session, authors of 6 countries presented 6 posters addressing long-term consequences from the accidental exposure to pesticides, comparison of antidotal effects in dermal toxicity induced by T2 toxin, defense R&D initiatives in Canada, medical monitoring in sanitary zones of CW storages, medical decontamination procedures and life cycle assessment of sulfur mustard in aquatic environment.
Finally, I would like to thank all of the presenters and Session Chairs and Co-chairs in the Medical and Radiological Aspects Sector for their contributions to this productive meeting. Also, I would like to thank the symposium attendees for their interest in the subjects covered in this Sector.
SECTOR 4: CRISIS MANAGEMENT
CHAIR: Florin Paul, Ministry of National Defence, Bucharest, Romania
CO-CHAIR: Murray Hamilton, Rocky Mountain Center for Homeland Defense, Denver, Colorado USA
Presented by: Murray Hamilton
This sector is newly added to the CBMTS areas of concern and addresses a fundamental concern: that of integrating the civilian and defense related research in a coordinated effort to counter terrorism. The dominant theme of all 3 sessions was the significant complexity, real or potential, of a disaster caused crisis. The era of responding ad hoc to natural or terrorist produced disasters is no longer acceptable.
Several presentations dealt with actual crisis situations ranging from contamination of government buildings with the deadly toxin ricin to the accidental release of chlorine (a toxic industrial chemical, TIC) during a train derailment in South Carolina to the intrinsic danger(s) in TICs and the vulnerability of legitimate industrial chemical plants. It is noteworthy that fatalities occurred from the chlorine release but not the ricin “attack”. These examples underscored the need for proper and systematic planning for disasters, most successfully using computer-aided models, coupled with a system for rapid identification of a chemical or biological event and a risk and vulnerability response plan. The difficulties in achieving these goals require coordination and cooperation: the need for partnerships, useful and accessible databases for chemical identification and toxicology and protection of critical infrastructure such as agriculture and food supply was emphasized. Programs that support these objectives, such as Project Bioshield in the USA were reviewed. The need for continuing observation was highlighted by the information available on procuring or making toxic substances from the internet.
A “whole of government” approach to counter-terrorism was presented and, if inter-agency cooperation could be achieved, would reduce “stove-piping” and promote sharing of data. Finally the use of medical surveillance of ambulance dispatch data to suggest a possible terrorist event or biological outbreak was also discussed. To quote one of our senior participants: “The only thing more difficult than planning for a crisis is explaining why you didn’t!”
SECTOR 5: DETECTION/DECONTAMINATION
CHAIR: Douglas Eaton, Special Associated Services, Niagra on the Lake, Ontario, Canada
CO-CHAIR: Cynthia Sonich-Mullin, National Homeland Security Research, Center, US EPA, Cincinnati, Ohio USA
Presented by: Cynthia Sonich-Mullin
This report provides a summary of the presentations and discussions related to Detection and Decontamination at CBMTS VI. Three sessions provided the forum for presentations by representatives from nine countries covering a range of issues and research related to this important area of research. This report summarizes the main issues covered in the presentations and discussions amongst the symposium participants. Main topics covered were: detection/identification and decontamination methods; however, some general information, case studies and safety issues were also highlighted. This report provides an overview of the presentations and highlights the salient points. The annex to this report contains summaries of each individual presentation.
The detection or identification of agents and potential exposures is a critical step toward successful remediation/decontamination of any contamination event. There is a growing need and demand for fast, sensitive, selective and reliable detectors for CBR agents. Speakers at CBMTS provided interesting information and research related to this important area, covering a range of agents.
“Smart testing” of chemical detectors was presented focusing on 9 characteristics identified as key. Of particular note was the effect of humidity in reducing the performance of the detectors, specifically in the detection of sarin and HD. The use of mass spectrometry (MS) to rapidly identify ricin was presented highlighting the limitations of various MS methods and those likely to yield future success as well as the detection questions relating to identifying the whole molecule versus segments of the molecule, as would be needed for forensic analysis.
An interesting overview was provided of current screening methods for several biological agents, including demonstration of how field usable methods would not apply to the laboratory and vice versa. The key point was that several test methods need to be employed to assure accurate detection (and increase the level of confidence in results). However, a complementary presentation made a very clear case that several of the commercial biological agent detection tickets had limitations that need to be known by users as they could provide consistent false positive and false negative readings. Several additional tests were developed to represent real-world interference problems that ticket users might find in the field. The study demonstrated which materials could adversely impact the use of the BW agent tickets.
The clear message emanating from these presentations was the importance of and need to fully test chemical detectors before their acceptance and use both in the laboratory and in the field for specific situations. This includes not only knowledge of the specificity of the method relating to the agent of concern, but also consideration of characteristics or environmental conditions that might impact the results. The need for the use of multiple screening/identification methods is important to ensure accuracy and increase confidence in results.
Rapid decontamination following an incident is critical for reentry as well as for the prevention of additional exposures. Decontamination is the reduction or removal of the agent of concern. Personal decontamination of workers is also important. Presentations on this topic provided insight into new methods of decontamination.
The use of photosensitizers for killing of bacteria and potentially, chemical agents was discussed. Singlet oxygen causes oxidation of the outer membranes or microorganisms. They also may have the capacity to break the sulfur bonds on chemical agents. These sensitizers (porphyrins) are activated by light and produce singlet oxygen which is key to the destruction of the target organism/substance. Chemical binding of sylsens to polymer surfaces was also presented. Following the completion of various challenge studies on select bacteria including spores, it was concluded that the system has the potential to be incorporated within protective clothing, air filters, bandages and other platforms.
A study on the utilization of the accelerated electrons for decontamination of select items was presented. Flat items (such as mail, paper money, floppy disc) where contaminated with Bacillus thuringensis and vaccinia virus. Aerosol generation was demonstrated by opening of a standard letter. There was also significant bacterial residue (150 million spores) on the hands after opening the letters. The objects and samples were irradiated with a pulse linear electron accelerator. This research demonstrated that this system effectively decontaminated the tested items.
One aspect of decontamination is the chemical neutralization or detoxification of the contaminant as opposed to cleanup. An update was presented on the successful employment of CASCAD decontamination foam in fighting the spread of Avian Flu. CASCAD could be used to minimize the possible re-aerosolization and spread of the virus. It was shown that CASCAD is able to rapidly destroy the virus on surfaces and in the environment.
Poster presentations provided excellent data on current research in this area. One such poster demonstrated the decontamination of a wide range of biological agents as well as information on chemical and radiological agents. Discussions with the author revealed that in general, biological decontamination could be achieved in ~5 minutes (lab tests) chemical decontamination in ~10 minutes, and radiological decontamination in ~20 minutes. A decontamination process using a rotary kiln was demonstrated through a separate poster. While the kiln is very similar to units used in other countries, the difference between most of those and the process presented is the size of the kiln and the recovery of usable materials from the process. In an example provided, arsenic was recovered and sold, thereby off-setting the operating costs of the process. Discussions with the presenter revealed that effluents from the decontamination process are well-controlled.
A final poster related to decontamination, provided results of the use of Finnish Emulsion (FE) to decontaminate biological material and further, compared the FE with commercial materials. This comparison demonstrated that there is little benefit from using the FE; in some cases it takes as long as 60 minutes to achieve adequate decontamination. Sodium hypochlorite was identified as being much more effective.
Two additional presentations focused on human decontamination and the protection of responders. Trends in the decontamination of human skin was presented. This research focused on various techniques/systems for the immediate decontamination of skin in the Czech armed forces. Two key detoxificants where discussed: Alkaline Peroxide and Amino Alcohol. Alkaline Peroxide used with detergents were effective against VX, whereas amino alcohol, alkaline alcoholate used with aprotic solvent was effective against all main types of CW agents. Given these results, it was concluded that Amino Alcohol is preferred. The second presentation focused on personal protection against CBR agents of nanoparticle dimensions. Nanometer-diameter particles are more toxic than larger particles on a mass basis, however, protective equipment may not be protective against these small particles. In this regard, the necessity to re-examine the conventional approach to establishing criteria for efficiency PPE was highlighted. This presentation analyzed the results of measuring protection factors (PF) for several types of respirators in NaCl and ambient air test atmosphere. Further actions were proposed to develop methods of measuring fractional PF of filters, respirators and protective clothing taking in account nanodiameter particles. It was shown that there are gaps in testing PPE in the range of nanoparticles particularly taking in face seal leakage.
Finally, within the United States, the Environmental Protection Agency is mandated through various legislation, to protect the environment and human health and specifically, to cleanup environments following a spill or intentional contamination. Since the events of September 11, and the promulgation of additional legislation, the USEPA founded the National Decontamination Team (NDT) to address an identified void in response and decontamination needs. An overview of the new team’s roles and responsibilities was presented and highlighted through the specific example of a recent response to a confirmed case of Anthrax contamination in NYC. The cleanup of three contaminated sites was reviewed, highlighting issues such as time, cost and personal considerations. Lessons learned include the need for multi-disciplined teams to address the problem in an integrated fashion and the importance of interagency cooperation in the time of crisis.
The papers presented were extremely relevant to today and will hopefully lead to cooperation and future reports to CMBTS of additional findings. The results presented from several research presentations were of immediate use and supportive of the needs of first responders and decontamination experts worldwide, as well as to military personnel.
The information summarized and highlighted through these presentations offered a starting point for additional discussions and potential collaborations. An overwhelming observation was the fact that we all face similar issues within our countries or organizations. The need for cooperation and collaboration to facilitate continual improvement of our collective knowledge base and to aid in our responses was recognized and valued. The role of CMBTS in this effort was overwhelming applauded.
to the ASA CBMTS webpage Issue no. 114