The deliberate use of microorganisms and toxins as weapons has been attempted throughout history. Biological warfare has evolved from the crude use of cadavers to contaminate water supplies to the development of specialized munitions for battlefield and covert use. The modern development of biological agents as weapons has paralleled advances in basic and applied microbiology. These include the identification of virulent pathogens suitable for aerosol delivery and industrial-scale fermentation processes to produce large quantities of pathogens and toxins. The history of biological warfare is difficult to assess because of a number of confounding factors. These include difficulties in verification of alleged or attempted biological attacks, the use of allegations of biological attacks for propaganda purposes, the paucity of pertinent microbiological or epidemiologic data, and the incidence of naturally occurring endemic or epidemic diseases during hostilities. Biological warfare has been renounced by 140 nations, primarily for strategic and other pragmatic reasons. International diplomatic efforts, including the 1972 Biological Weapons Convention, have not been entirely effective in preventing the enhancement and proliferation of offensive biological warfare programs. The threats posed by biological weapons are likely to continue into the future.

Concerns regarding botulinum neurotoxins (BoNTs) as biowarfare and bioterrorist agents have generated interest in developing medical countermeasures for protection against the neurotoxins. Efforts have focused on improvements in the available vaccines and antisera and de novo discovery of pharmacological inhibitors of toxin action. This chapter reviews the various approaches taken to develop next-generation vaccines, antitoxins and pharmacological treatments against intoxication by the BoNTs. The historical progression, current status and future trends are described.

When the agent used in a biological attack is known, response to such an attack is considerably simplified. The first eight chapters of this text deal with agent-specific concerns and strategies for dealing with infections due to the intentional release of these agents. A larger problem arises when the identity of an agent is not known. In fact, in some cases, an attack may be threatened or suspected, but it may remain unclear as to whether such an attack has actually occurred. Moreover, it may be unclear whether casualties are due to a biological agent, a chemical agent, or even a naturally occurring infectious disease process or toxic exposure. Recent experience with West Nile Virus (Fine and Layton, 2001), Severe Acute Respiratory Syndrome (SARS) (Lampton, 2003), and monkeypox highlight this dilemma. In each of these cases, the possibility of bioterrorism was raised, and rightly so, although each outbreak ultimately proved to have a natural origin. This chapter provides a framework for dealing with outbreaks of unknown origin and etiology. Furthermore, it addresses several related concerns and topics not covered elsewhere in this text.

Three well-documented plague pandemics have occurred in the past two millennia, resulting in more than 200 million deaths and great social and economic chaos (Perry and Fetherston, 1997; Pollitzer, 1954). The Justinian pandemic arose in northern Africa in the mid-6th century, and by the 7th century had spread throughout the Mediterranean and near-eastern regions—severely impacting both the Roman and Byzantine empires. The second pandemic, the Black Death or great pestilence, originated in Central Asia, was carried to Sicily in 1347 via ships from the Crimea, and rapidly swept through medieval Europe. By 1352, it had killed 30% or more of afflicted populations, slowly playing itself out in successive epidemics, including the Great Plague of London in 1665 (Perry and Fetherston, 1997). The third (Modern) pandemic began in southwestern China in the mid-19th, struck Hong Kong in 1894, and was soon carried by rat-infested steamships to port cities on all inhabited continents, including several in the United States (US) (Link, 1955; Pollitzer, 1954). By 1930, the third pandemic had caused more than 26 million cases and 12 million deaths. Plague in these three pandemics was predominantly the bubonic form, emanating from Yersinia pestis-infected rats and fleas, although terrifying outbreaks of the more virulent person-to-person spreading pneumonic form were recorded during the course of each. The explosive contagiousness and severity of pneumonic plague was most completely documented in Manchurian epidemics in the early 20th century, which involved tens of thousands of cases, virtually all of them fatal (Wu, 1926).

Many vaccines for bioterrorism agents are investigational and therefore not available (outside of research protocol use) to all at-risk laboratory workers who have begun working with these agents as a result of increased interest in biodefense research. Illness surveillance data archived from the U.S. offensive biological warfare program (from 1943 to 1969) were reviewed to assess the impact of safety measures on disease prevention (including biosafety cabinets [BSCs]) before and after vaccine availability. Most laboratory-acquired infections from agents with higher infective doses (e.g., anthrax, glanders, and plague) were prevented with personal protective measures and safety training alone. Safety measures (including BSCs) without vaccination failed to sufficiently prevent illness from agents with lower infective doses in this high-risk research setting. Infections continued with tularemia (average 15/year), Venezuelan equine encephalitis (1.9/year), and Q fever (3.4/year) but decreased dramatically once vaccinations became available (average of 1, 0.6, and 0 infections per year, respectively). While laboratory-acquired infections are not expected to occur frequently in the current lower-risk biodefense research setting because of further improvements in biosafety equipment and changes in biosafety policies, the data help to define the inherent risks of working with the specific agents of bioterrorism. The data support the idea that research with these agents should be restricted to laboratories with experience in handling highly hazardous agents and where appropriate safety training and precautions can be implemented.

To develop consensus-based recommendations for measures to be taken by medical and public health professionals if hemorrhagic fever viruses (HFVs) are used as biological weapons against a civilian population.The Working Group on Civilian Biodefense included 26 representatives from academic medical centers, public health, military services, governmental agencies, and other emergency management institutions.MEDLINE was searched from January 1966 to January 2002. Retrieved references, relevant material published prior to 1966, and additional sources identified by participants were reviewed.Three formal drafts of the statement that synthesized information obtained in the evidence-gathering process were reviewed by the working group. Each draft incorporated comments and judgments of the members. All members approved the final draft.Weapons disseminating a number of HFVs could cause an outbreak of an undifferentiated febrile illness 2 to 21 days later, associated with clinical manifestations that could include rash, hemorrhagic diathesis, and shock. The mode of transmission and clinical course would vary depending on the specific pathogen. Diagnosis may be delayed given clinicians' unfamiliarity with these diseases, heterogeneous clinical presentation within an infected cohort, and lack of widely available diagnostic tests. Initiation of ribavirin therapy in the early phases of illness may be useful in treatment of some of these viruses, although extensive experience is lacking. There are no licensed vaccines to treat the diseases caused by HFVs.

OBJECTIVE To review and update consensus-based recommendations for medical and public health professionals following a Bacillus anthracis attack against a civilian population. PARTICIPANTS The working group included 23 experts from academic medical centers, research organizations, and governmental, military, public health, and emergency management institutions and agencies. EVIDENCE MEDLINE databases were searched from January 1966 to January 2002, using the Medical Subject Headings anthrax, Bacillus anthracis, biological weapon, biological terrorism, biological warfare, and biowarfare. Reference review identified work published before 1966. Participants identified unpublished sources. CONSENSUS PROCESS The first draft synthesized the gathered information. Written comments were incorporated into subsequent drafts. The final statement incorporated all relevant evidence from the search along with consensus recommendations. CONCLUSIONS Specific recommendations include diagnosis of anthrax infection, indications for vaccination, therapy, postexposure prophylaxis, decontamination of the environment, and suggested research. This revised consensus statement presents new information based on the analysis of the anthrax attacks of 2001, including developments in the investigation of the anthrax attacks of 2001; important symptoms, signs, and laboratory studies; new diagnostic clues that may help future recognition of this disease; current anthrax vaccine information; updated antibiotic therapeutic considerations; and judgments about environmental surveillance and decontamination.

| FULL TEXT | PDF | MEDLINE 4. Biological and chemical terrorism: strategic plan for preparedness and response: recommendations of the CDC Strategic Planning Workgroup. MMWR Morb Mortal Wkly Rep 2000;49(RR-4):1-14. 5. Franz DR, Jahrling PB, Friedlander AM, et al. Clinical recognition and management of patients exposed to biological warfare agents. JAMA. 1997;278:399-411. MEDLINE 6. Gill MD. Bacterial toxins: a table of lethal amounts. Microbiol Rev. 1982;46:86-94. MEDLINE 7. National Institute of Occupational Safety and Health. Registry of Toxic Effects of Chemical Substances (R-TECS). Cincinnati, Ohio: National Institute of Occupational Safety and Health; 1996. 8. Montecucco C, ed. Clostridial neurotoxins: the molecular pathogenesis of tetanus and botulism. Curr Top Microbiol Immunol.

The Working Group on Civilian Biodefense has developed consensus-based recommendations for measures to be taken by medical and public health professionals if tularemia is used as a biological weapon against a civilian population.The working group included 25 representatives from academic medical centers, civilian and military governmental agencies, and other public health and emergency management institutions and agencies.MEDLINE databases were searched from January 1966 to October 2000, using the Medical Subject Headings Francisella tularensis, Pasteurella tularensis, biological weapon, biological terrorism, bioterrorism, biological warfare, and biowarfare. Review of these references led to identification of relevant materials published prior to 1966. In addition, participants identified other references and sources.Three formal drafts of the statement that synthesized information obtained in the formal evidence-gathering process were reviewed by members of the working group. Consensus was achieved on the final draft.A weapon using airborne tularemia would likely result 3 to 5 days later in an outbreak of acute, undifferentiated febrile illness with incipient pneumonia, pleuritis, and hilar lymphadenopathy. Specific epidemiological, clinical, and microbiological findings should lead to early suspicion of intentional tularemia in an alert health system; laboratory confirmation of agent could be delayed. Without treatment, the clinical course could progress to respiratory failure, shock, and death. Prompt treatment with streptomycin, gentamicin, doxycycline, or ciprofloxacin is recommended. Prophylactic use of doxycycline or ciprofloxacin may be useful in the early postexposure period.