Biodefense: Principles and Pathogens Chapter Abstracts
Chapter 1
Introduction
Michael S. Bronze and Ronald A. Greenfield
Abstract
No Abstract available for this chapter, therefore we present the first paragrapf of the introduction instread. Bioterrorism is defined as the deliberate release of a harmful biological agent (either a microorganism or a biological toxin derived from living organisms) to harm or threaten persons and their governments (Annas, 2002a; Ashford et al., 2003). Bioterrorism might also employ biological agents directed at livestock, poultry, or crops (Lutz and Greenfield, 2003). Bioterrorism is considered a criminal act and possibly an act of war (Fidler, 2001b). Deployment of biological weapons for warfare and terrorism is not a new concept; biological weapons have been used for centuries (Noah et al., 2002; Wenzel, 2002). In 1346 AD, Monguls catapulted corpses contaminated with plague bacterium into the city of Kaffa (now Feodossia, Ukraine) initiating plague among the inhabitants and possibly initiating the second plague pandemic (Bellamy and Freedman, 2001; Derbes, 1966; Orent, 2004). The intentional uses of variola virus, the causative agent of smallpox (Bellamy and Freedman, 2001); Salmonellae, the causative agents of typhoid fever and gastroenteritis (Anonymous, 1966; Torok et al., 1997); Ascaris (Phills et al., 1972); Shigella, the causative agent of bacillary dysentery (Kolavic et al., 1997); the plant toxin ricin (Tucker, 1996); and most recently Bacillus anthracis, the causative agent of anthrax (Jernigan et al., 2001), as bioweapons or to commit biocrimes have been reported. The history of bioweapons use and lessons for the future based on this history are presented in chapter 2 of this text.
Chapter 2
History of Biological Weapons Development and Deployment
R. Richard Hamerla
Abstract
This chapter addresses the history of biological weapons development and deployment from the ancient world through today. With Biblical sources as a starting point, the first half of this chapter summarizes the development and deployment of biological weapons from before the Common Era, continuing through the Middle Ages and the modern era. The intensified research and development that characterized the World Wars of the twentieth century are examined, followed by special consideration of the weapons programs of the former Soviet Union and the United States during the Cold War. After noting the impact of the collapse of the USSR on the world's political environment, the second half of this study discusses specific instances when radical groups indigenous to the United States acquired or used biological weapons, after which the likelihood of a sovereign nation using biological agents as offensive weapons is explored. Finally, the possibilities and consequences of these weapons falling into the hands of contemporary terrorist organizations, the particular appeal of biological weapons to modern terrorists, and some of the principal sources of biological weapons proliferation are discussed.
Chapter 3
Public Health Preparedness
R. Gregory Evans and Bruce W. Clements
Abstract
While the state and federal health agencies will play roles in responding to a bioterrorist attack, the initial response must come from local public health agencies because it is crucial that the response be as rapid as possible to minimize loss of life. The first section of this chapter describes the current state of public health in the United States and where applicable, in the United Kingdom and Israel, and outlines steps necessary to upgrade the system so that it can respond to a bioterrorism attack. The second section identifies the planning that must be done by public health agencies in preparation for a potential attack. The third section uses a hypothetical scenario of a bioterrorism attack to illustrate public health's role during and after an attack. The chapter demonstrates that there is much that must be done to prepare the public health community for bioterrorism. The anthrax attacks of October 2001 were only a prelude to the possibilities of bioterrorism. Much progress has been made since those attacks but there is much more that needs to be accomplished in the coming months and years
Chapter 4
Public Policy and Legal Issues Surrounding Terrorism and Preparedness in the United States
Kenneth J. Levit and Peter P. Budetti
Abstract
The events of September 11, 2001 and the intentional release of anthrax in the United States (US) Postal Service later that year have changed the paradigm for the planning and response to terrorist acts. At the very core of the debate over preparedness and response is the ability to maintain the equilibrium between law and order and civil liberties. This chapter defines terrorism and its forms and provides examples of current terrorist organizations, reviews the changing policy context of terrorism and describes recent legal responses in the US to the threat of terrorism. The US Patriot Act, amendments to the US Foreign Intelligence Surveillance Ac and the US Model State Emergency Health Powers Act are discussed.
Chapter 5
Hospital Preparedness and Infection Control
A. Rekha K. Murthy and Matthew Bidwell Goetz
Abstract
Hospitals will inevitably bear the brunt of caring for victims of a bioterrorism event or emerging infectious disease threat. After much debate regarding the possibility and plausibility of such an occurrence, the recent episodes of anthrax and severe acute respiratory syndrome (SARS) have demonstrated the unfortunate reality of such challenges. While it is widely accepted that a catastrophic event would overwhelm any healthcare system, it is certain that some level of disaster preparedness is required to address emerging infectious disease threats, whether intentionally inflicted or naturally occurring. The ability to respond effectively to a bioterrorism threat will depend on the preparedness and awareness at the individual practitioner's level as well as at staff, departmental and institutional levels. Strong institutional support, policy development, education, and resource commitment are necessary to ensure adequate preparation. Once established, such systems also require thoughtful updating and careful maintenance.
Chapter 6
Surveillance and Detection for Bioterrorism: Traditional and Evolving Methods
Kristy K. Bradley, Kenneth D. Clinkenbeard, J. Michael Crutcher, and Rebecca J. Morton
Abstract
Control of infectious diseases has an effective surveillance program as its foundation. The core desirable qualities for a disease surveillance system are efficiency, reliability, and sensitivity. A valuable surveillance program must also be representative of the population at risk and achieve a high positive predictive value. Public health authorities chiefly rely on a passive surveillance system that receives and investigates legally mandated reports of notifiable diseases. In the new realm of bioterrorism preparedness, public health agencies have been galvanized to improve traditional disease surveillance systems, primarily by harnessing electronic communication channels to more rapidly receive surveillance data and disseminate health alerts. The pressing priority for prompt detection of bioterrorism has also spawned a number of innovative methods. These nontraditional surveillance concepts range from electronic real time volume data based systems categorized as "syndromic surveillance" to point detection sensors that could conceivably identify a bioterrorism event at the time and location of the agent release. Although the practical efficacy of these new methods remains to be tested, there is promise that these new surveillance directions will complement core surveillance structure. Ultimately, early identification of a bioterrorism attack will be crucial to expedite public health interventions to lessen morbidity and mortality.
Chapter 7
Psychosocial Issues in Bioterrorism
Betty Pfefferbaum, Carol S. North, and Rose L. Pfefferbaum
Abstract
Much of what is known about the acute and enduring psychosocial consequences of bioterrorism is based on experience with natural disasters, technological accidents, conventional weapons, and epidemics. Potential effects include distress, psychiatric morbidity, and changed attitudes and behavior. Psychiatric morbidity, including but not limited to posttraumatic stress disorder, is generally confined to those most directly affected or endangered by an incident or those with close ties to victims and survivors. Less severe outcomes may be pervasive. Determinants of emotional outcome include predisposing individual characteristics, characteristics of the disaster and exposure, and aspects of the recovery environment. Unique characteristics of bioterrorism, including the novelty of the agents and the public's lack of familiarity with them, the potential for contagion and delayed recognition of exposure and onset of symptoms, and inadequate preparedness of the health care delivery system may exacerbate emotional reactions to actual and threatened attacks.
Chapter 8
Anthrax
Ronald A. Greenfield, Hélène Carabin, Douglas A. Drevets, and Michael S. Gilmore
Abstract
Anthrax, infection with Bacillus anthracis, has been known since antiquity, but human infection had largely disappeared from the developed world until recent intentional dispersion of the organism. It remains a naturally-occurring zoonosis in much of the developing world. During the past few years, the genome of B. anthracis has been presented, and the molecular pathophysiology is being determined. Human clinical disease occurs in cutaneous, gastrointestinal, and inhalational forms; the latter is the most dreaded in the bioterrorism setting. Treatment recommendations focus on therapy with ciprofloxacin or doxycycline, with additional agents used for severe forms of disease. Human anthrax vaccines are available and effective, but difficult to administer due to intense vaccination schedules. Multiple approaches are underway toward discovering improved treatment and prevention strategies.
Chapter 9
Botulism
Ronald A. Greenfield, Leonard N. Slater, and Michael S. Bronze
Abstract
Botulism is the clinical manifestation of intoxication with botulinum neurotoxin (BoNT) produced by Clostridium botulinum and rarely other Clostridium species. Worldwide, most naturally occurring disease results from ingestion of pre-formed BoNT in food sources, typically those that may be low in acidity or improperly preserved. Naturally occurring botulism also may result from BoNT production in the gut or in inadequately débrided wounds. The typical clinical manifestations of cranial nerve palsies followed by descending flaccid paralysis are due to irreversible BoNT - mediated neurotransmitter blockade at the neuromuscular junction. Symptoms usually begin within 12 - 72 hours of exposure. Antitoxins can prevent progression of paralysis, but cannot reverse that which has already developed. Thus, the key to successful treatment is clinical suspicion leading to early diagnosis, followed by antitoxin administration and supportive therapy as required. Aerosolization would be the most likely means of dispersion of BoNT for bioterrorism. Depending upon dose inhaled, onset of effect might be shorter than or comparable to that of ingestion. As the most potent biologic toxin known, very small quantities released into the air could have a devastating effect upon a large number of people.
Chapter 10
Plague
Douglas A. Drevets
Abstract
Yersinia pestis, the causative agent of plague, is a Gram negative bacterium that is a recently emerged clone of Yersinia pseudotuberculosis. Unlike its enteric predecessor, Y. pestis acquired the genes necessary for evolving into a zoonotic pathogen associated with rodents and usually is transmitted between mammalian hosts by fleas. It has been responsible for three pandemics, the first of which began approximately in AD 541 (Justinian's plague), the second in 1347 (the Black Death), and the third in 1855. Molecular analysis shows that Y. pestis possesses a number of virulence genes that enable it to survive and replicate in the disparate biological niches of the flea mid-gut, and as an intracellular and extracellular pathogen of mammals. The three most common forms of human infection caused by Y. pestis are bubonic, septicemic, and pneumonic plague. As a biowarfare or bioterrorism threat agent, it can be aerosolized or spread by respiratory droplets resulting in primary pneumonic plague, a rapidly fatal disease that is highly contagious and can be transmitted person-to-person. Successful treatment of established infections requires rapid diagnosis, supportive care, and antimicrobial therapy with effective antibiotics including streptomycin, gentamicin, or ciprofloxacin. Preventative therapy with ciprofloxacin or doxycycline is indicated for close contacts. An effective vaccine is not yet available.
Chapter 11
Smallpox
Steven H. Nazarian, Grant McFadden, and Mark M. Huycke
Abstract
Smallpox is a highly contagious viral disease that only infects humans. Nearly all non-immune individuals develop severe illness that can lead to death. The successful global eradication of smallpox several decades ago resulted in an increasingly susceptible population that would suffer dramatically should smallpox be re-introduced through bioterrorism. It has been difficult to assess whether live stocks of variola virus exist outside of publicly declared repositories. Recent efforts, however, have begun to prepare us for potential re-appearance of smallpox should covert stocks be used in a bioterrorist attack. This chapter reviews the biology of orthopoxviruses including variola virus, clinical syndromes of smallpox, established and newer methods for diagnosis, current and investigational vaccines, adverse effects from vaccination, potential antiviral agents, evolving policies for vaccine indications, and outbreak modeling. In addition, the effects of immunodeficiency on vaccination and disease transmission are considered.
Chapter 12
Tularemia
Linda J. Machado, Hélène Carabin, and Darrin R. Akins
Abstract
Tularemia is a zoonotic disease caused by the Gram-negative bacterium Francisella tularensis. F. tularensis is further subdivided into at least three different subspecies all of which cause human disease. The three different subspecies have been designated tularensis, holarctica, and mediaasiatica. Among these, subspecies tularensis is the most virulent to humans, with an infectious dose < 10 organisms. While tularemia has been a public health problem since it was first identified in 1911, there has recently been a renewed interest in this disease. The resurgence in tularemia research is a direct result of the fear that this organism may be used as a biological weapon of mass casualty by a terrorist group and has been sharply focused on the identification of new diagnostics, therapeutics, and vaccines.
Chapter 13
Viral Hemorrhagic Fevers
Michael S. Bronze, Hélène Carabin, and Siddhartha Mahanty
Abstract
Viruses that cause hemorrhagic fever belong to four distinct families of viruses. Clinically, they produce a systemic febrile illness associated with hemorrhagic diathesis. As a group, these viruses share common features including lipid encapsulation, genomes containing single stranded RNA, and narrowly defined geographic distribution. Many cause significant infections in animals. They are usually transmitted to humans by animals, although aerosols can transmit some. They are considered to be Category A bioterrorism agents by the Centers for Disease Control and Prevention since they are highly infectious and there are limited strategies either to prevent or treat these infections. It is the intent of this chapter to review the epidemiology and clinical manifestations of infections due to these viruses in humans and animals, discuss the pathogenesis of infection, and to review strategies designed to either prevent infection or to treat it once established.
Chapter 14
Other Biological and Microbiological Toxins: Staphylococcal Enterotoxin B, Epsilon Toxin of Clostridium perfringens, Ricin, and Mycotoxins
Malak Kotb and Michael S. Bronze
Abstract
In this chapter, microbiological and biological toxins with bioterrorism potential are discussed. These agents include staphylococcal enterotoxin B, epsilon toxin of Clostridium perfringens, ricin (derived from castor beans), and T-2 mycotoxins. These agents may cause disease following ingestion, inhalation or for some, following dermal exposure. Depending on the specific toxin, exposure results in gastrointestinal, pulmonary and nervous system toxicity and death occurs due to cardiovascular collapse from multi-organ failure. Some, like the mycotoxins, cause dermal disease and thus have characteristics similar to chemical agents. Unlike microbial pathogens, these agents induce toxicity rapidly. For intoxication due to many of these agents, treatment is largely supportive. Vaccines exist for some of these toxins, but their use is limited to preventing illness in animals.
Chapter 15
Diseases Due to other Category B Bacterial Pathogens I: Brucellosis, Glanders, and Melioidosis
Gene W. Voskuhl, Ronald A. Greenfield, and Michael S. Bronze
Abstract
Brucella spp., Burkholderia mallei, and Burkholderia pseudomallei, the causative agents of brucellosis, glanders, and melioidosis, respectively, have been identified as category B agents for public health preparedness. Brucellosis is one of the world's most important zoonotic diseases. Brucellosis is most common in the Mediterranean basin, the Arabian cap, the Indian subcontinent, and in parts of Mexico and Central and South America. It is a major cause of abortion in domesticated animals. In humans, brucellosis causes a wide spectrum of disease, with acute, subacute, and chronic forms which may present with a variety of local complications. Glanders is a zoonosis infecting solipeds, and man is accidentally infected. Naturally occurring disease has nearly disappeared worldwide. Natural disease includes chronic ulcerative subcutaneous and intramuscular abscesses of the extremities, but the bioterrorism concern involves inhalational exposure. Melioidosis is a tropical disease most common in Southeast Asia and Northern Australia. B. pseudomallei is an environmental pathogen that causes a spectrum of disease from asymptomatic infection to overwhelming septicemia.
Chapter 16
Diseases Due to Other Category B Bacterial Pathogens II: Psittacosis, Q Fever, and Typhus
Karen A. Wendel
Abstract
Although the focus of most bioterrorism prevention efforts is directed at category A biological agents for public health preparedness, this chapter summarizes data on three category B agents which could present a significant health threat after aerosol exposure. These agents include Chlamydia psittaci, Coxiella burnetii, and Rickettsia prowazekii. C. psittaci and C. burnetii are considered zoonoses. Without a history of animal exposure, they may not be suspected by clinicians in the setting of an intentional aerosol release. R. prowazekii is primarily associated with louse-borne human epidemics or exposure to flying squirrels. Confirmatory diagnosis of these agents relies predominantly on serologic testing of acute and convalescent phase sera. Therefore, doxycycline therapy must often be initiated empirically for these infections and can be lifesaving. Unlike most category A biological agents, C. burnetii and R. prowazekii have the ability to cause chronic disease if inappropriately treated. This chapter will summarize the history, microbiology, pathogenesis, clinical manifestations, diagnostics, and treatment regimens for these pathogens.
Chapter 17
Bioterrorism and Threats to Food Safety: Campylobacter, Salmonella, Shigella, diarrheagenic Escherichia coli, and Listeria
James M. Fleckenstein and Seema K. Patel
Abstract
The safety of the global food supply is of paramount importance. Each year foodborne pathogens account for a large number of illnesses worldwide, resulting in significant morbidity and mortality. In developing countries, diarrheal illness is a principal cause of death among children less than five years of age. In industrialized regions the distributed nature of food production makes it vulnerable to intentional contamination as an act of bioterrorism. In fact, the deliberate contamination of food has already been reported. This chapter reviews the major bacterial causes of foodborne illness which pose potential threats as agents of bioterrorism, discusses the pathophysiology of disease, and outlines strategies for surveillance, treatment, and prevention of these infections.
Chapter 18
Bioterrorism and Threats to Water Safety: Cholera and Cryptosporidiosis
Daniel T. Boatright and Ronald A. Greenfield
Abstract
In the developed world, routine availability of safe drinking water is largely taken for granted. Nonetheless, naturally occurring outbreaks of disease due to waterborne pathogens continue to occur. Furthermore, intentional contamination or interruption of the drinking water supply remains a potential means of bioterrorism. In the developing world, availability of safe drinking water remains one of the largest public health challenges. In this chapter, processes of water purification are reviewed, a listing of potential waterborne pathogens is discussed briefly, and then cholera (as an example of a waterborne pathogen naturally occurring in the developing world) and cryptosporidiosis (as an example of a waterborne pathogen naturally occurring in the developed world) are discussed in detail.
Chapter 19
Encephalitis Viruses as Potential Agents of Bioterrorism
Michael S. Bronze, John D. Morrey, Pand Aaron Olsen, DVM
Abstract
The list of causative agents of infectious encephalitis includes viruses belonging to four families collectively referred to as arboviruses due to their transmission to humans by arthropod vectors. As a group, they are single stranded RNA viruses usually producing disease in avian and equine populations. Some of these viruses have been identified as possible agents of bioterrorism because they produce illnesses with significant morbidity and mortality and there are limited strategies to either treat or prevent infection. Members of the Togaviridae family (eastern equine encephalitis, western equine encephalitis and Venezuelan equine encephalitis viruses) are considered the most likely bioterrorism threat agents because of the ease of producing them in culture and the ability to disseminate Venezuelan equine encephalitis virus as an aerosol. However, their true potential as bioweapons is unknown. In this chapter we discuss the epidemiology and clinical manifestations of infection by these viruses. In addition, we discuss potential strategies to treat and prevent infections caused by these viruses.
Chapter 20
Emerging Infectious Diseases
Shu-Hua Wang, Fred A. Lopez and Charles V. Sanders
Abstract
In the last decade a number of microorganisms have emerged that may have bioterrorism potential. The United States (US) Centers for Disease Control and Prevention (CDC) and the US National Institute of Allergy and Infectious Disease (NIAID) have identified several of these organisms as Category A, B, or C pathogens, depending on their characteristics and potential for weaponization. This chapter will focus on several Category C pathogens from the CDC and NIAID lists that have not been addressed elsewhere in this book and some emerging pathogens: multi-drug resistant Mycobacterium tuberculosis, rabies virus, severe acute respiratory syndrome coronavirus, Nipah virus, and human metapneumovirus. Although the bioterrorism potential of these agents is unknown, certain characteristics of each generate concern about their use.
Chapter 21
Miscellaneous Threats: Highly Pathogenic Avian Influenza and Novel Bio-engineered Organisms
Daniel R. Perez, Steven H. Nazarian, Grant McFadden and Michael S. Gilmore
Abstract
Influenza virus type A is considered the prototype of emerging diseases. Influenza viruses have been responsible for devastating, deadly pandemics and constant epidemics in humans. Pandemic influenza has been the result of the introduction into the human population of novel influenza viruses from the natural reservoir, waterfowl. In addition, repeated and serious outbreaks of avian influenza in poultry and occasional avian influenza outbreaks in several mammalian species, including humans, suggest that influenza is a non-eradicable disease. Due to the vast diversity of influenza virus strains, the flexibility of their genomes to mix among them, and the wide range of susceptible hosts, the emergence of a novel strain with pandemic potential is just a matter of time. In recent years, and in addition to the enormous economic implications for the poultry industry, outbreaks of highly pathogenic avian influenza have resulted in strains with the ability to cross from birds to humans, with subsequent fatalities. Such incidents have brought a sense of urgency on the need to fully understand the molecular mechanisms that lead to the interspecies transmission and pathogenesis of influenza viruses. The prospect of intentionally generating novel bacterial and viral strains with pandemic potential is also a concern. There is evidence that research directed toward engineering of bioweapons with improved lethality was conducted in the past, demonstrating that the threat is not simply hypothetical. As journal editorial boards wrestle with the ethical implications of publishing data that could lead to the genesis of more lethal agents of infection, the subject of engineered bioweapons has become highly controversial.
Chapter 22
Animal Diseases as a Possible Consequence of Biological Attack
Hélène Carabin, Daniel Perez, Johnnie Lee Gilpen and Ronald A. Greenfield
Abstract
This chapter presents a discussion of the diseases that could potentially be used in a bioterrorism attack against livestock and poultry. The economic and social consequences of such an attack could be devastating, as analysis of a natural outbreak of a highly contagious animal pathogen, foot and mouth disease, will be used to illustrate. A classification of the animal pathogens whose impact is the greatest has been presented by the Office International des Épizooties of the United Nations. List A diseases discussed in this chapter are foot and mouth disease, swine vesicular disease, vesicular stomatitis, rinderpest, contagious bovine pleuropneumonia, sheep pox and goat pox, African swine fever, peste des petits ruminants, lumpy skin disease, bluetongue, African horse sickness, classical swine fever, and Newcastle disease; Rift Valley fever and highly pathogenic avian influenza are discussed elsewhere in this text. Additionally, bovine spongiform encephalopathy (a List B disease) and associated new variant Creutzfeldt Jakob disease is discussed in detail because of recent international attention. The remaining List B diseases are presented in tabular form.
Chapter 23
Plant Diseases as a Possible Consequence of Biological Attack
Forrest W. Nutter and Lawrence V. Madden
Abstract
Agricultural production systems are likely targets of bioterrorism because they offer a number of strategic and tactical advantages to bioterrorist groups. Potential strategic advantages for targeting crops include: (i) introduction of plant pathogens as weapons to destroy or reduce an enemy's food supply, (ii) use of plant pathogens to compromise international markets due to phytosanitary regulations that prohibit the importation of a commodity from a country that is known to have a quarantinable plant disease, (iii) the introduction of a plant pathogen to reduce a nation's competitiveness in the global marketplace due to the increased production costs that result from the deployment of disease management tactics, (iv) introduction of a pathogen to undermine consumer confidence in a nation's ability to produce a safe and affordable food supply, and (v) the introduction of a plant or human pathogen during crop development to adversely affect human health. Although efforts to deter and prevent the introduction of exotic agricultural pathogens and pests across United States (US) borders have significantly improved following September 11, the potential for biological attack on US agriculture remains an Achilles heel that greatly threatens agricultural biosecurity. In addition to ease of entry, agricultural crops are considered "soft targets" because continuous crop surveillance over extensive acreages is nearly impossible. Many US crop varieties have been bred to have some level of resistance to endemic pathogens, but have little or no resistance to exotic pathogens and therefore, many crops are highly vulnerable to biological attack. A vast array of plant pathogens are already highly infectious and possess extremely high reproductive rates that facilitate doubling times (for disease intensity) to be just a day or two when environmental conditions are favorable for epidemic development. Furthermore, plant pathogens are not harmful to the perpetrators and pathogen inoculum can be easily collected throughout the world, transported, cultured, stored, increased (on live plants or media) and delivered to the target crop. Epidemiological theory, as it pertains to the weaponization of plant pathogens, can be used to understand the probability of a successful biological attack against crops.
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