| Biotechnology and the Public Health Response to Bioterrorism | p. 1 |
| Introduction | p. 1 |
| US Public Health Service Infrastructure-the Laboratory Response Network | p. 2 |
| Threat Agents by Category | p. 3 |
| Detection, Monitoring, and Identification of BT Agents | p. 5 |
| The Potential for Misuse of Biotechnology | p. 8 |
| Biotechnology, Public Health Interest and the Exchange of Scientific Information | p. 10 |
| Public Perception of Biodefense Research | p. 11 |
| Summary | p. 12 |
| References | p. 12 |
| Historical Perspectives of Microbial Bioterrorism | p. 15 |
| Introduction | p. 15 |
| Definitions | p. 15 |
| Development and Prohibition of Biological Weapons | p. 16 |
| Early use of Biological Agents in Warfare | p. 17 |
| Early Theories of Infectious Disease | p. 17 |
| Selected Incidents from the Fourteenth to the Nineteenth Centuries | p. 18 |
| The Germ Theory and Bioterrorism | p. 20 |
| Selected Confirmed Incidents, 1900-2003 | p. 20 |
| Probable or Possible use of Biological Agents, 1900-2003 | p. 25 |
| Concluding Remarks and Perspectives | p. 27 |
| References | p. 27 |
| The Infectious Disease Physician and Microbial Bioterrorism | p. 31 |
| Introduction | p. 31 |
| The Evolution of the Global Community, Infection, and Bioterrorism | p. 31 |
| The Evolving Practice of Infectious Disease | p. 33 |
| Integrating the Infectious Disease Physician with Public Health Response | p. 33 |
| Prevention, Early Recognition, and the Infectious Disease Physician | p. 34 |
| Education, the Infectious Disease Physician, and Preparedness | p. 36 |
| Summary | p. 37 |
| References | p. 37 |
| Modulation of Innate Immunity to Protect Against Biological Weapon Threat | p. 39 |
| Bioterrorism and Biological Weapons Threat | p. 39 |
| Current Medical Defense Against Biological Weapons | p. 42 |
| Immune System | p. 45 |
| Innate Immunity | p. 47 |
| Pulmonary Innate Immunity | p. 48 |
| Major Components of Pulmonary Innate Immunity | p. 48 |
| Interferons and Other Cytokines | p. 50 |
| Known Pathways of Pathogen Elimination by the Pulmonary Innate Immunity | p. 50 |
| Modulation of Immunity for Protection Against Infection | p. 53 |
| Modulation of Innate Immunity to Protect Against Biological Weapon Threat-a Summary | p. 57 |
| References | p. 58 |
| Smallpox: Pathogenesis and Host Immune Responses Relevant to Vaccine and Therapeutic Strategies | p. 63 |
| Introduction | p. 63 |
| History of Smallpox Infection and its Eradication | p. 64 |
| Clinical and Epidemiological Features | p. 65 |
| Virus Structure and Classification | p. 67 |
| Pathogenesis, Host Defense, and the Immune Response | p. 67 |
| Features of Smallpox Making it a Likely Bioterror Agent | p. 69 |
| History and Potential of Smallpox as a Bioweapon | p. 69 |
| Smallpox Vaccines and Antiviral Therapies | p. 70 |
| Smallpox Vaccine Strategies and Related Issues | p. 71 |
| Smallpox Antiviral Therapies | p. 74 |
| Conclusions | p. 76 |
| References | p. 76 |
| Bacillus anthracis: Agent of Bioterror and Disease | p. 83 |
| Introduction | p. 83 |
| Clinical Presentation of Anthrax | p. 84 |
| B. anthracis and Bioterror | p. 86 |
| Evolution into a Pathogen | p. 87 |
| Spore Structure and Function | p. 88 |
| Sporulation and Germination | p. 88 |
| Spore Coat Proteins and Exosporium | p. 91 |
| Virulence Factors | p. 94 |
| Anthrax Toxins | p. 94 |
| Anthrax Toxin Receptor-Mediated Internalization | p. 96 |
| Toxin Gene Regulation | p. 97 |
| Capsule: Chemistry and Composition | p. 98 |
| Capsule Gene Regulation | p. 100 |
| Capsule Function | p. 100 |
| Accessory Virulence Factors | p. 102 |
| B. anthracis and Macrophage Interactions | p. 103 |
| Vaccine and Therapeutic Approaches | p. 107 |
| References | p. 111 |
| Tularemia Pathogenesis and Immunity | p. 121 |
| Introduction | p. 121 |
| Pathogenesis | p. 123 |
| Human Disease | p. 123 |
| Animal Models | p. 124 |
| Cellular Pathogenesis | p. 125 |
| Molecular Pathogenesis | p. 126 |
| Immunity | p. 128 |
| Natural Infection and Immunity | p. 128 |
| Live Vaccines | p. 129 |
| Subunit Vaccines | p. 131 |
| Mechanisms of Protection in Adaptive Immunity | p. 132 |
| Conclusions | p. 133 |
| References | p. 133 |
| Brucella and Bioterrorism | p. 139 |
| Introduction | p. 139 |
| Brucellosis: a Zoonotic Disease | p. 139 |
| Clinical Symptoms of Human Brucellosis | p. 140 |
| Life Within the Macrophage and Subversion of Host Immune Responses | p. 142 |
| History of the use of Brucella as an Agent of Biological Warfare | p. 143 |
| Impact of an Attack Using Brucella as an Agent of Bioterrorism | p. 144 |
| Diagnosis and Treatment of Brucellosis | p. 145 |
| Vaccine Development: Historical Perspectives and Considerations for the Future | p. 147 |
| Summary | p. 149 |
| Acknowledgments | p. 149 |
| References | p. 150 |
| Pneumonic Plague | p. 155 |
| Introduction | p. 155 |
| Plague in Humans | p. 156 |
| Flea-Borne Plague | p. 156 |
| Aerosol-Transmitted Plague | p. 158 |
| Bacterial Pathogenesis | p. 162 |
| Experimental Models of Pneumonic Plague | p. 162 |
| Y. pestis Virulence Factors | p. 164 |
| Role of Y. pestis Virulence Factors in Pneumonic Plague | p. 166 |
| Bacterial Genetics | p. 168 |
| Epidemiology of Pneumonic Plague | p. 169 |
| Biological and Epidemiological Determinants of Pneumonic Plague Epidemics | p. 170 |
| Management and Control of Pneumonic Plague Outbreaks | p. 171 |
| Lessons from Modern Pneumonic Plague Outbreaks | p. 172 |
| Current and Future Needs | p. 174 |
| References | p. 174 |
| Coxiella burnetii, Q Fever, and Bioterrorism | p. 181 |
| Introduction | p. 181 |
| A Brief History | p. 181 |
| Q Fever | p. 183 |
| Epidemiology | p. 184 |
| Coxiella burnetii Lifecycle Stages | p. 185 |
| Coxiella burnetii Genome | p. 186 |
| Lipopolysaccharide | p. 187 |
| Phase Transition | p. 188 |
| Invasion of Host Cells | p. 190 |
| Environment of Acidified Phagosome | p. 191 |
| Metabolic Pathways | p. 192 |
| Transport | p. 192 |
| Transformation Studies | p. 194 |
| Coxiella burnetii Outbreaks in the Military | p. 194 |
| Coxiella burnetii as a Biological Weapon | p. 195 |
| Sterilization/Disinfection | p. 197 |
| Detection Methods | p. 197 |
| Treatments of Q Fever | p. 199 |
| Vaccine | p. 200 |
| References | p. 200 |
| Genomic and Proteomic Approaches Against Q Fever | p. 209 |
| Introduction | p. 209 |
| Disease and Threat | p. 209 |
| Host-Parasite Interaction | p. 210 |
| Secretion of Virulence Factors | p. 212 |
| Pathogenesis | p. 213 |
| Isolate Diversity and Virulence | p. 214 |
| Acquired Immunity | p. 215 |
| Whole Cell C. burnetii Vaccines | p. 217 |
| New Opportunities with Genomic and Proteomic Approaches | p. 220 |
| Genomic Comparison of Isolate Groups | p. 220 |
| Development of New-Generation Vaccines | p. 220 |
| Acknowledgement | p. 221 |
| References | p. 221 |
| Rickettsia rickettsii and Other Members of the Spotted Fever Group as Potential Bioweapons | p. 227 |
| Introduction | p. 227 |
| SFG Rickettsiae with Bioweapon Potential | p. 228 |
| Feasibility of Obtaining, Propagating, Stablizing, and Weaponizing SFG Rickettsiae | p. 229 |
| Methods of Dispersal | p. 230 |
| Pathogenesis of Aerosol Transmission | p. 231 |
| Available Methods for Diagnosis, Treatment, and Prevention | p. 232 |
| Needed Countermeasures | p. 233 |
| References | p. 234 |
| Index | p. 237 |
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