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                                                     Vaccine Research Center

                       Rollins School of Public Health, Emory University

                                                    Atlanta, GA

VRC joins war against anthrax, bioterrorism

By Poul Olson                                                                                     

From: Emory Report

April 15, 2002

The Vaccine Research Center has begun a five-year study of Anthrax Vaccine Adsorbed (AVA), the only human vaccine approved for the bacterium, Bacillus anthracis. Sponsored by a $4.2 million grant from the Centers for Disease Control and Prevention (CDC) and under the direction of Robert Mittler, assistant professor of surgery and a VRC researcher, the program will assess and compare the efficacy of three different vaccine regimens in rhesus macaque monkeys starting in June. Researchers also hope to determine the strength of protective immunity against anthrax after inoculation. No live anthrax bacteria will be used in the Yerkes study; Mittler and his team instead will use harmless proteins derived from anthrax toxins to assess the immune response promoted by AVA. The study will involve 33 rhesus macaques equally divided among three groups. One group will receive a course of three AVA shots at full concentration. A second group will be vaccinated with three shots diluted to 10 percent strength, and the third group of monkeys will be inoculated with three shots at 5 percent of the full concentration. A single monkey in each group will serve as a control and will receive a placebo shot. When inhaled, anthrax spores enter specialized immune cells called macrophages, where they germinate into vegetative cells that produce two deadly toxins that kill cells. Death can result as quickly as two days after these toxins enter the circulatory system. AVA produces antibodies against a component of the toxin called protective antigen (PA). By blocking the activity of PA, these antibodies prevent the toxins from entering and subsequently killing cells.

The threat of anthrax as a bioterrorism agent became a public reality last fall following a series of mailings of anthrax spores and the deaths of five people. In the wake of these attacks, federal funding for research on anthrax, smallpox, and other potential bioterrorism agents has increased substantially.

                                                                                      

                                     IndianaUniversity, Pardue University

                                           Department of Public Health

                                                    Indianapolis, IN

 

Bioterrorism Preparedness Facts

Top bioterrorism agents - Government experts dealing with bioterrorism have come up with a list of the most likely candidates that might be used in possible future attacks. This list includes:
1) Bacillus anthracis,the cause of anthrax
2) Brucellaspecies, the cause of undulant fever
3) Francisella tularensis,the cause of tularemia or rabbit fever
4) Yersinia pestis,the cause of plague or black death
5) Variola virus, the cause of small pox
6) Vaccinia virus chimeras (mythical monsters composed of several animal parts), the cause of small pox and/or serious toxic diseases derived from other infectious agents.

Why anthrax? Out of all of the potential biowarfare agents, B. anthracis is the easiest to grow and is the most environmentally stable. The other agents range from mildly difficult to grow to very difficult to grow. Moreover, once taken out of their protective container they are readily destroyed by moisture and atmospheric oxygen over a period of hours to a few days. On the other hand, when B. anthracisis used as a tactical weapon the land becomes uninhabitable for centuries even possibly millennia because of the longevity of the spores in the soil. When used as a bioterrorist agent the question of conquest is usually not an issue.

All of the above agents except the small pox virus can be obtained from natural sources if terrorists are knowledgeable and determined. Furthermore, agents as lethal or worse than the above are also endemic or naturalized in this country. Certain limitations of potential bioterrorists will usually protect us from these microbes. Knowledge of how to isolate them from nature and grow them takes considerable sophistication and training if the terrorist is not to be his own first victim. More over, knowledge of how to weaponize various agents is in most countries a closely guarded secret, if in fact the procedure has already been worked out. There are several procedures we must consider in order to weaponize or to turn an infectious agent into a tactical weapon. Each agent will have its own procedures. One of the most simplistic examples is anthrax. Here is a microbe with a big reputation, but because of its growth properties in culture it is considered by trained microbiologists as a fairly safe organism to work with, comparatively speaking. The spores stick together in culture and must be separated from each other in order to be small enough to enter the alveoli or air sacs of the lungs. Next the spores are electrically charged and tend to stick to surfaces that are oppositely charged, much like the attraction of opposite poles of a magnet. This characteristic prevents them in an other way from reaching their pulmonary target. To keep the spores on target they are electrically neutralized with a chemical. To further weaponize this agent traits such as antibiotic resistance may be engineered as well. The end product is a preparation of spores that float in the breeze and will easily penetrate dust masks. And when they have finally come to rest in dust or dirt, over and over again they can be re-born in air currents to cause pulmonary anthrax. Fortunately, there are a defined number of spores that it takes on an average to cause disease. This average is called the ID50 or infectious dose. For weaponized agents the LD50 or average lethal dose is often very close to the ID50. Still, as one moves away from the primary source of the agent the number of propagules, in this case, spores, decrease in number exponentially. What may be an LD50 at ground zero moves to a noninfectious dose for most people even 10 feet away(in still air).

Contrary to the anthrax bacillus which is not normally infectious or spread to others, the non-spore forming biowarfare agents, which are more delicate, depend on both primary and secondary sources of inoculation. In heavily populated areas the rate of secondary spread from primary infected individuals can be horrifying. However, as is the case with most biological agents, secondary spread is via an aerosol of respiratory droplets. These droplets can be filtered out in large part by ordinary dust masks. Another note on the upside is that the vaccines for some of the non-spore forming agents can act soon enough to prevent death after exposure.

                                                                       

                                               UCLA Department of  Epidemiology

                                        UCLA School of Public Health

                                                  Los Angeles, CA

Epidemiologists are often called "disease detectives," using many of the same methods as regular detectives to determine the cause of disease outbreaks, epidemics (i.e., larger excess in disease cases), or even pandemics (i.e., worldwide excess in disease cases).  The anthrax outbreak in the United States which occurred during the latter part of 2001 has many of the same characteristics as a typical outbreak.  What is different, however, is that there was no transmission from infected to susceptible persons that linked one case with another.  Instead, all of the cases were generated by a terrorist or group of terrorists who sent letters containing anthrax spores through the postal system.  These spores -- very small in size -- typically entered the skin or lungs or victim when the envelop was handled or opened, when coming in contact with an environment where envelopes had previously been handled or opened, or when passing through small holes in unopened envelops. While police detectives and disease detectives employ similar methods of investigation, the use of their findings is far different.  Police detectives typically keep information secret or under wraps, allowing them to build a legal case against the alleged criminal.  Eventually the information becomes public, but only when presented in a court of law.  Their intent in the American legal system is to convict and then punish the criminal, with hope that such actions will prevent future crimes. Disease detectives typically have a different goal, although related.  They usually try to figure out what went wrong in a social or physical environment, identifying factors that allow a disease agent to generating an outbreak or epidemic. The goal of the disease detective is first to contain the outbreak and then to educate people on how to prevent similar outbreaks in the future.  By necessity, these containment and education efforts  involve the general public.  Thus disease detectives work closely with the news media who as effective speakers and writers are best able to transmit educational messages.  Thus disease detectives tend to be more open and collaborative then police detectives.   When faced with a bioterrorist, however, police detectives and disease detectives share a goal, namely to find and stop the responsible terrorist or group of terrorists. The nature and occasional difficulties of such collaboration are described in the Anthrax media section of the UCLA Bioterrorism website. 

                                                                      

                                      

                                 Center for Infectious Diseases

               Tulane University School of Public Health and Tropical Medicine

                                            New Orleans, LA

OVERVIEW/ PERSPECTIVE ON BIOTERRORISM. 

Since September 11th, we have entered into a new era, which includes not only conventional terrorist events (World Trade Center, Pentagon), but the use of biological agents against a civilian population in a way that has not occurred previously in our lifetimes.  However, despite the powerful psychological impact that anthrax has produced, the actual numbers of deaths and serious illnesses has remained much smaller. This paradox preserves one of the central dichotomies in bioterrorism:  the contrast between its efficacy in producing a psychological impact in large numbers of individuals and the relatively small numbers of individuals who have died or become seriously ill. 

As we have struggled to come to grips with these rapidly evolving events, one of our first conclusions was that one of the important ways in which a university can contribute is to make information available.  The information provided here is the first step in that process.  We sincerely hope that it will be useful, and encourage comments from those who have the time to do so.  Questions and comments on this WEB Site and its contents, as well as suggestions, should be directed to the Center for Infectious Diseases (center.infecdis@tulane.edu). 

Questions about this WEB Site and its contents should be directed to Dr. Don Krogstad (krogstad@tulane.edu  Questions about the basic biology of anthrax should be directed to Dr. John Clements (jclemen@tulane.edu).  Questions about the municipal water supply and the safety of the food supply should be directed to Dr. William Hartley (hartley@tulane.edu), and questions about air-borne spread should be directed to Roy Rando (rando@tulane.edu).  Questions about interactions between the community and the city and state health departments should be directed to Dr. Rebecca Meriwether (rmeriwe@tulane.edu), whereas clinical questions should be directed to Dr. Susan McLellan (smclell@tulane.edu).   

                                                                      

                                             BioMedical Security Institute (BMSI)

                        Carnegie Mellon University & University of Pittsburgh

                                                                      Pittsburgh, PA          

"Airborne Defense"

By Jason Togyer

From: Pitt Magazine June 2002

" With Specter's support, Carnegie Mellon University and the University of Pittsburgh formed the BioMedical Security Institute (BMSI) two years ago to coordinate research by the universities into ways to prevent, detect, and respond to both terrorist activity and natural outbreaks of disease.  Computers are the backbone of a BMSI-affiliated research project. Like Web-crawling search engines that comb Internet data to find documents, RODS filters hospital admissions records to locate where people become ill, how old they are, and what symptoms they have. Using data that indicate where patients are from and which hospitals they are in, RODS pinpoints where people are ill. The information is plotted onto maps. A spike in hospital admissions from a neighborhood, or a message that something is "strange" by RODS standards, could merely indicate that there's a flu bug going around. Or it could mean that a chemical or biological weapon has been released"

                                                                   

                                                                     

 

                               Center for Study of Bioterrorism and Emerging Infections

                              School of Public Health, Saint Louis University

                                                      St. Louis, MO

What we need to know about bioterrorism preparedness: Results from focus groups

conducted at APIC 2000

"Infection control practitioners (ICPs) are important partners in enhancing the US Public health infrastructure, both as essential recipients of continuing education and as instructors responsible for providing this education. Focus groups were conducted at APIC 2000, the annual meeting for the Association for Professionals in Infection Control and Epidemiology, Inc. to determine the ICPs priorities for educational opportunities in bioterrorism preparedness and the preferred methods of education delivery. Focus group participants affirmed the need to provide education in sessions of less than 60 minutes, with use of a variety of technologies and methods of presentation such as video, Internet, and paper-based self-learning texts. The participants' comments suggested a lack of awareness by employees in health care institutions about the potential threat of bioterrorism in the United States and a deficiency in knowledge about the potential consequences of an attack. The focus group participants believed this lack of awareness also leads to unwillingness by their administrators to allocate funds for planning and education. Since it appears that ICP's will be looking for direction and expertise from the local health departments and their communities, the first subset of professionals to target for bioterrorism education and preparedness should probably be the public health professionals". (Am J Infect Control 2001;29;347;-51)

Brooke N. Shadel, Ph.D., MPH

Bruce Clements, MPH

Brenda Arndt, MPH

Terri Rebmann, RN, MSM, CIC

R. Gregory Evans, PhD, MPH

St Louis, Missouri

                                                                  

Note from HSF: It seems that the most effective ways to avoid high number of casualties in bio/chemical attacks are: 1) having " vigilant" Public Health Systems and  2) providing the communities with knowledge, guidelines and tools of how to protect themselves.  Public Health Schools and Public Health Departments have the responsibility to train public health professionals (medical  students, nurses, health practitioners, etc. ) in bioterrorism preparedness. These professionals are responsible in making the Public Health System work effectively, to train individuals in the community and to keep the community safe. Parents, school's teachers, school's administrators, business owners and nursing home administrators should be among those individuals to receive the training in the communities. These individuals should be able to teach those under their care. Contributions from the government and private sectors should go to strengthen the capacity in training and research of Public Health Schools and Public Health Departments nation wide. All of the above represent the main purposes of the 20CitiesProject.                                              

 

Please, send to us your opinions, suggestions and most recent publications (including an abstract) about bioterrorism. Your opinions, suggestions and publication's abstract should be no longer of 200 words and could be sent either by mail or e-mail:

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