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Smallpox vaccination and bioterrorism with pox viruses.

Bioterrorist attacks occupy a special place amongst the innumerable potential types of terrorist attack, with the intentional release of pox viruses being especially feared in this connection. Apart from the variola virus, the agent responsible for smallpox in humans, the monkeypox virus and numerous other animal pox viruses pose potential risks for humans and animals. This risk scenario also includes recombinations between the various pox viruses, changes in hosts and genetically engineered manipulations of pox viruses. For over 200 years, the method of choice for combatting smallpox was via vaccination with a reproductive, original vaccinia virus. Worldwide eradication of smallpox at the end of the 1970s and the discontinuation of routine smallpox vaccination in 1980 can be credited to such vaccination. Unfortunately, these vaccinations were associated with a large number of postvaccinal impairments, sometimes resulting in death (e.g. postvaccinal encephalitis). The only way to restrict such postvaccinal complications was to carry out initial vaccination within the first 2 postnatal years. Initial vaccination at a later age led to such a sharp increase in the number of vaccines with complications that vaccination had to be discouraged. The dilemma of the smallpox vaccine stocks stems from the fact that a large portion of these stocks are produced with the same vaccinia strains as before. This is irresponsible, especially as the percentage of immune-suppressed persons in the population, for whom vaccination-related complications pose an especial threat, is increasing. One solution to the dilemma of the smallpox vaccine stocks is the MVA strain. It is harmless, protects humans and animals equally well against smallpox and can be applied parenterally.

Animals↗

Smallpox: a potential agent of bioterrorism.

The events of 11 September 2001, in New York City, and subsequent identification of anthrax in the United States Postal System, have generated a new sense of awareness for the potential of biological terrorism, if not warfare. Among those agents identified by the Centers for Disease Control and Prevention as 'Class A Bioterrorist Threats', smallpox is among the most dangerous. The ease of transmission of this agent, the lack of immunity in the population at large to this agent, and rapidity of its spread, if released, all generate significant concern for its deployment. A vaccine directed against smallpox is available but it is also associated with significant adverse events-some of which are life-threatening. Further, no antiviral drug has proven efficacious for therapy of human disease, although one licensed drug, cidofovir, does have in vitro activity. Regardless, heightened awareness should lead to the development of a vaccine without significant adverse events and safe and efficacious antiviral drugs. The availability of a vaccine and antiviral drugs that are safe would significantly remove any major threat of smallpox deployment by a terrorist.

Biological Warfare↗

The potential use of influenza virus as an agent for bioterrorism.

Influenza A virus has been responsible for widespread human epidemics because it is readily transmitted from humans to humans by aerosol. Recent events have highlighted the potential of influenza A virus as a bioterrorist weapon: the high virulence of the influenza A virus that infected people in Hong Kong in 1997; and the development of laboratory methods to generate influenza A viruses by transfection of DNAs without a helper virus. Antiviral drugs that are directed at functions shared by all influenza A viruses constitute the best line of defense against a bioterrorist attack. Consequently, new antiviral drugs need to be developed, and the few currently available antiviral drugs should be stockpiled.

Antiviral Agents↗

Overview: cause and prevention in biowarfare and bioterrorism.

Bioweaponry is rooted in the ancient past. It became a science in the early 20th century following the breakthrough discoveries in microbiology and immunology of the late 1800s. The 20th century, with its major and minor wars, saw the research and development of biological weapons capable of immense destruction of life, which were used both by nations in preparation for military warfare and by individuals who engage in asymmetric warfare. Treaties, international agreements, and political pursuits have not been able either to control or to rid the world of bioweapons. The tools for specific defense against bioweapons consist of vaccines against both viruses and bacteria, and of antibiotics and drugs against bacteria. Vaccines and antimicrobials are of limited usefulness because of the large number of possible microbes that can be used for weapons, because of antimicrobial resistance to drugs and antibiotics, and because of limitations in technical feasibility for developing vaccines and antibacterials against certain of the agents. Induction of non-specific innate immunity by immunostimulatory vaccines (at one time licensed) needs to be explored for possible immunoprophylactic-therapeutic activity when administered immediately following exposure to bioweapon pathogens. The ideal solution to the bioweapons problem lies in measures to end their development and application throughout the world. Emphasis was made at the recent World Economic Forum of the need to end poverty and hunger in the world as a means to reduce the incentive to engage in warfare. Added to this is betterment of health, focused mainly on preventable diseases. A further solution to the problem may lie in the development of modern robotic systems for rapid forensic detection of development and production of bioweapons by "rogue" nations and even by individuals. This review deals with the specifics of the development of bioweapons and their control by vaccines, by therapy with antibacterials, by non-specific immunostimulants, by advanced systems for detection of development and deployment of biological agents of destruction, and by political and health-giving initiatives.

Adjuvants, Immunologic↗

Threats in bioterrorism. II: CDC category B and C agents.

A variety of agents have potential for use as weapons of biological terrorism. Knowledge of the likely organisms may be useful in preparations to mitigate the effects of a BT event. Recognition of the clinical presentation of these organisms could help physicians identify them quickly, allowing more appropriate management and possible prophylaxis of others who may have been exposed. Although many of these agents do not have specific treatments, it is important to recognize those that do. It is also important to know which infections require isolation because of potential for person-to-person spread. Table 3 summarizes important features of the CDC category B and C agents. The list of agents discussed in this article is by no means exhaustive. It is always possible that some "mad scientist" could modify an existing organism or engineer some new agent for use in biological terrorism. The possibilities are limited only by the ingenuity and depravity of those individuals who would take part in such an attack.

Bacterial Infections↗

Bioterrorism preparedness. II: The community and emergency medical services systems.

Disaster planning is an arduous task. Perhaps no form of disaster is more difficult to prepare for than one resulting from the intentional, covert release of a biological pathogen or toxin. The complexities of response operations and the perils of inadequate preparation cannot be overemphasized. Even with detailed planning, deviations from anticipated emergency operations plans are likely to occur. Several federal programs have been initiated to assist communities in enhancing their preparedness for events involving biological and other agents of mass destruction. Many of these, such as the Metropolitan Medical Response Systems (MMRS) Program [37,38], will be discussed elsewhere. Community preparedness will be enhanced by: 1. Implementing a real-time public health disease surveillance program linking local healthcare, emergency care, EMS, the CDC, local law enforcement, and the FBI 2. Improved real-time regional patient and healthcare capacity status management 3. Development of affordable, accurate biological agent detection systems 4. Incorporation of standardized education and training curricula (appropriate for audience) on terrorism and biological agents into healthcare training programs 5. Expansion of federal and state programs to assist communities in system development 6. Increased public awareness and education programs.

Bioterrorism↗

Bioterrorism and critical care.

A bioterrorist attack of any kind has the potential to overwhelm a community and, indeed, in the case of smallpox, an entire nation. During such an attack the number of patients requiring hospitalization and specifically critical care is likely to be enormous. Intensivists will be at the forefront of this war and will play an important role in dealing with mass casualties in an attempt to heal the community. A high degree of suspicion and prompt recognition of an event will be required to contain it. Specific knowledge of the possible agents that can be used will be key in managing patients and in estimating the needs of a health care facility and community to deal with the future course of events. Intensivists play various roles aside from the delivery of critical care to the patient in the ICU. These roles include making triage decisions regarding the appropriate use of critical care beds (which automatically dictates how other non-ICU beds are used and managed) and serving as a team member of ethics committees (on such issues as dying, futility, and withdrawal of care). Indeed, intensivists are no strangers to disaster management and have served on the forefront of many. A biologic weapons attack, however, is likely to push this multidimensional nature of the intensivist to the maximum, because such an attack is likely to result in a more homogeneous critically ill population where the number of critical care staff and supplies to treat the victims may be limited. One hopes that such an event will not occur. Sadly, however the events of September 11, 2001, have only heightened the awareness of such a possibility.

Anthrax↗

[Bioterrorism with brucellosis].

A CONTAMINATING SPRAY: Brucellosis is a zoonosis due to a bacteria of the Brucella. B. melitensis species and is the principle agent of human brucellosis. The interest of Brucella as a biological weapon resides in the fact that transmission through a spray is possible, as has been reported with human contamination during abortion of infected animals or bacterial spraying in laboratories. The bacteria is highly contagious. It is suggested that 10 to 100 bacteria would be sufficient to produce a contaminating spray for humans. THE MENACE: In 1954, B. suis was the first infectious agent used as a biological weapon in the United States. Several other countries have been suspected of studying the agent as a biological weapon, but to date, no use of Brucella in a bioterrorist attack has been reported. THE EXTENT OF RISK: Brucella, and notably B. melitensis and B. suis, are considered as agents unlikely to be used as biological weapons: their incubation is long, the majority of infections are asymptomatic and mortality is low. However, the morbidity of this agent should not be underrated since it leads to chronic and disabling pathologies.

Bioterrorism↗

[Bioterrorism and health security in the European Union].

A PROGRAM OF ACTION AND COOPERATION: Since 2001, a series of measures have been taken by the Member States, the European Union and the International authorities to reinforce the preparation and response to biological and chemical terrorist acts. It is essential that the Member States can mutually consult and coordinate their preparation and response as widely as possible. THE ROLE OF THE HEALTH SECURITY COMMITTEE: Together with the health security committee, the European Union has setup a mechanism of consultation and coordination that can be recommend and guide joint action in an emergency, and guarantee the coherence of the counter-actions throughout the Union. This is a committee also constitutes the framework within which the emergency strategies and model-simulations are exchange, and in which assistance in the form of expertise and other resources can be obtained among the Member States. IN THE YEARS TO COME: The future European Centre for the prevention and control of disease, the implantation and functioning of which will start in Sweden in 2005, will play a fundamental part in the harmonisation of the European response to any eventual terrorist acts, whether biological or chemical.

Bioterrorism↗

[Risk of smallpox, vaccination, bioterrorism].

The use of the smallpox virus as a biological weapon is very old. Confronted with a high probability of a current bioterrorist menace, counteracting strategies have been developed. One of the principle aims relies on the vaccination of teams dedicated to the management of persons infected and the stocking of vaccine for the whole population of a country. Following worldwide eradication of the disease, preventive vaccination was topped in 1978 in France for the primo-vaccination, and in 1984 for repeat vaccinations. The various strains used in the first generation vaccinations are weakened living vaccine, the natural host and origin of which is unknown. Second and third generations vaccines are under study; the principle objective is to obtain efficacy with a minimum of side effects. There are two types of adverse events, generally observed with the first generation vaccines: the first, extremely rare, can be life-threatening; the others, more frequent (10 to 15% of patients) are benign. In emergency situations, in the presence of smallpox, there should be no absolute contraindications to vaccination. In the bioterrorist context, massive vaccination campaigns of the population are unadvisable (because of the considerable risk of death and severe adverse events) in the absence of any real permit, in each case, definition of the vaccinal strategy to be adopted.

Bioterrorism↗