Additional Information
Book Details
Abstract
Aerobiology is the study of airborne organic particulates in the environment, such as bacteria or fungal spores. These can be either naturally occurring or artificially introduced into the air. Some of the toxicological, pharmacological, and physiological effects of bioaerosols include infections, allergies, and cancer. Research efforts in aerobiology range from remediating household mould to combating bioterrorism.
This book focusses on the toxicological aspects of aerobiology, considering the adverse health effects associated with the inhalation of specific bioaerosols, such as anthrax and ricin. Additionally, chapters cover techniques for generating, sampling and characterizing airborne biological materials as well as methods for establishing standards of exposure. Moreover, mitigation of exposure and protection against exposure are described.
Bringing together the contemporary status of information in the area, this book will be a valuable reference book for pulmonary specialists, general practitioners of medicine, public health and public safety officers, first responders, military personnel, and students studying toxicology and related disciplines.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Cover | Cover | ||
| Aerobiology The Toxicology of Airborne Pathogens and Toxins | i | ||
| Preface | vii | ||
| Dedication | xii | ||
| Acknowledgements | xiii | ||
| Contents | xv | ||
| Chapter 1 - The Atmosphere: Its Developmental History and Contributions to Microbial Evolution and Habitat† | 1 | ||
| 1.1 Introduction | 1 | ||
| 1.2 The Origin and Evolution of the Earth’s Atmosphere | 3 | ||
| 1.2.1 The Primary Atmosphere of the Earth | 3 | ||
| 1.2.2 The Secondary Atmosphere of the Earth | 4 | ||
| 1.2.3 Evolution of an O2-Rich Atmosphere | 5 | ||
| 1.2.4 Present-Day Composition and Structure of the Atmosphere | 6 | ||
| 1.2.5 The Atmosphere As Habitat | 10 | ||
| 1.3 Evolutionary History of the Atmosphere | 12 | ||
| 1.3.1 Aquatic Microbial Life of the Early Precambrian | 12 | ||
| 1.3.2 Middle Precambrian Migration of Microbial Life from Aquatic Habitats | 14 | ||
| 1.3.3 Diversification of Microbial Life During the Late Precambrian | 16 | ||
| 1.3.4 Evolutionary History of Airborne Microorganisms from the Cambrian Explosion | 17 | ||
| 1.3.5 Atmospheric Contributions to Microbial Evolution | 17 | ||
| 1.4 Microbial Life in the Atmosphere | 19 | ||
| 1.4.1 Metabolic Activity of Microorganisms in the Atmosphere | 19 | ||
| 1.4.2 Microorganism Residence Times and Reproduction in the Atmosphere | 21 | ||
| 1.4.3 The Movement of Microorganisms Through the Atmosphere | 23 | ||
| 1.4.4 Biogeography and the Atmosphere | 28 | ||
| 1.5 Conclusion | 29 | ||
| Acknowledgements | 32 | ||
| References | 32 | ||
| Chapter 2 - Orthopoxviruses and Animal Models for Pathogenesis, Vaccine and Drug Studies† | 42 | ||
| 2.1 Introduction | 42 | ||
| 2.2 The Poxviruses | 43 | ||
| 2.2.1 Taxonomy and Morphology | 43 | ||
| 2.2.2 Genomes and Genetic Relationships | 44 | ||
| 2.2.3 Transmission and Routes of Infection | 46 | ||
| 2.3 Clinical Aspects of Poxvirus Infections | 46 | ||
| 2.3.1 Smallpox | 46 | ||
| 2.3.2 Monkeypox | 47 | ||
| 2.3.3 Other Poxvirus Infections | 47 | ||
| 2.4 Animal Models and Aerosol Studies | 48 | ||
| 2.4.1 Pathogenesis | 49 | ||
| 2.4.1.1 Smallpox Model | 52 | ||
| 2.4.1.2 Monkeypox Model | 53 | ||
| 2.4.1.3 Rabbitpox Model | 54 | ||
| 2.4.1.4 Mousepox Model | 55 | ||
| 2.4.1.5 Other Models | 56 | ||
| 2.4.2 Vaccines | 56 | ||
| 2.4.3 Therapeutics | 58 | ||
| 2.5 Conclusion | 59 | ||
| References | 60 | ||
| Chapter 3 - Inhalational Anthrax – Issues in Dose–Response and Hazard Evaluation | 72 | ||
| 3.1 Introduction | 72 | ||
| 3.2 Problem Characterization | 74 | ||
| 3.2.1 Exposure Scenarios | 75 | ||
| 3.2.2 Issues in Host–Pathogen Relationships – Dose–Response and Incubation Period | 77 | ||
| 3.2.3 Microbial Risk Assessment and Regulation, with Reference to Inhalational Anthrax | 78 | ||
| 3.3 Inhalational Anthrax – Pathogenesis and Treatment | 80 | ||
| 3.3.1 The Pathogen | 80 | ||
| 3.3.2 Mechanism of Infection Establishment and Disease Progression | 81 | ||
| 3.3.3 Virulence Factors | 81 | ||
| 3.3.4 Clinical Course, Pathology and Treatment | 82 | ||
| 3.3.5 Medical Treatment | 83 | ||
| 3.4 Physical and Biological Factors Affecting Inhalational Risk | 83 | ||
| 3.4.1 Pulmonary Deposition of Inhaled B. anthracis Spores | 84 | ||
| 3.4.2 In vivo Fate of Inhaled B. anthracis Spores | 86 | ||
| 3.5 Overview of Dose–Response Regression Models | 87 | ||
| 3.5.1 The Log-Normal and Log-Probit Models | 88 | ||
| 3.5.2 Independent Action/“Single Hit” Stochastic Models: The Exponential and Beta–Poisson Models | 89 | ||
| 3.5.3 Biological Evidence in Support of Independent Action/“Single Hit” Hypothesis | 90 | ||
| 3.6 Dose–Response Studies and Modeling in Animals | 91 | ||
| 3.6.1 Guinea Pig Studies | 91 | ||
| 3.6.2 Nonhuman Primate Studies | 93 | ||
| 3.6.3 Dose–Response Modeling | 98 | ||
| 3.6.4 Exposure Dose and Delivered or Deposited Dose | 100 | ||
| 3.6.5 Competing Risks Model | 104 | ||
| 3.6.6 Dynamic Modeling of Cumulative Repeated Exposures | 105 | ||
| 3.6.7 Benchmark Dose Analysis of Nonhuman Primate Studies | 109 | ||
| 3.6.8 Benchmark Dose Analysis of Rabbit Exposure Studies | 110 | ||
| 3.7 The Sverdlovsk Accidental Release and Incubation Period Modeling | 112 | ||
| 3.7.1 The Sverdlovsk Accidental Release and Initial Modeling | 112 | ||
| 3.7.2 Re-Evaluation of Human Inhalational Anthrax on the Basis of the Sverdlovsk Release | 114 | ||
| 3.7.3 Wilkening’s Evaluation of Dose–Response Relationships | 114 | ||
| 3.7.4 Modeling of the Incubation Period | 116 | ||
| 3.7.5 Log-Normal and Log-Linear Models | 116 | ||
| 3.7.6 Brookmeyer’s Competing Risks Model | 117 | ||
| 3.7.7 Wilkening’s Modification of Brookmeyer et al.’s Model | 118 | ||
| 3.7.8 The Exposure–Infection–Symptomatic Illness–Death Model | 123 | ||
| 3.8 The 1957 Goat Hair Mill Outbreak and Its Implications – “From Mills to Mail” | 127 | ||
| 3.8.1 Main Epidemiological Findings | 127 | ||
| 3.8.2 Exposure and Risk Assessment Studies in American Goat Hair Mills | 128 | ||
| 3.8.3 Anthrax Risk in a Present-Day Belgian Hair and Wool Processing Plant | 129 | ||
| 3.8.4 Risk Threshold for Human Inhalational Anthrax | 130 | ||
| 3.8.5 Modeling Indoor Risk from Airborne Anthrax Spores | 131 | ||
| 3.8.6 Experimental Testing of Spore Emission from Spore-Laden Letters and Mail-Sorting Machines | 132 | ||
| 3.8.7 Modeling of the Spore Release at the Brentwood Postal Facility in 2001 | 134 | ||
| 3.9 Evaluation, Conclusions and Future Directions | 135 | ||
| 3.9.1 Applicability of Data Sets for Dose–Response Modeling | 135 | ||
| 3.9.2 Comparison of the Nonhuman Primate and Human Dose–Response Models | 137 | ||
| 3.9.3 Single High-Dose (Bolus) and Multiple Low-Dose Exposure Patterns | 139 | ||
| 3.9.4 Modeling of the Incubation Period | 140 | ||
| 3.9.5 Animal-to-Human Extrapolation of Infectious Doses | 142 | ||
| 3.9.6 Application of the EPA Methodology of Animal-to-Human Extrapolation in Inhalational Anthrax | 143 | ||
| 3.9.7 Retrospective Risk Assessment from Epidemiological and Environmental Studies in Biological Attack Scenarios | 145 | ||
| 3.10 Summary | 150 | ||
| References | 153 | ||
| Chapter 4 - Toxicity of Botulinum Neurotoxin by Inhalation: Implications in Bioterrorism† | 167 | ||
| 4.1 Introduction | 167 | ||
| 4.2 BoNT As a Biowarfare and Bioterrorist Threat | 169 | ||
| 4.3 Potency of BoNT by Inhalation | 170 | ||
| 4.4 Mechanism of Entry of Aerosolized BoNT | 172 | ||
| 4.5 Human Case Reports of Inhalation Botulism | 173 | ||
| 4.5.1 Laboratory Exposure | 173 | ||
| 4.5.2 Inhalation of BoNT-Contaminated Cocaine | 174 | ||
| 4.6 Histopathological Alterations Following BoNT Exposure | 174 | ||
| 4.7 Detection and Diagnosis | 175 | ||
| 4.8 Medical Countermeasures for Inhalation Botulism | 177 | ||
| 4.8.1 Efficacy of Vaccines in Inhalation Botulism | 177 | ||
| 4.8.1.1 Protection by Traditional Pentavalent Vaccine | 177 | ||
| 4.8.1.2 Protection by Recombinant Subunit Vaccine Against Aerosol Exposure of BoNT/A | 178 | ||
| 4.8.1.3 Protection by Recombinant Subunit Vaccine Against Aerosol Exposure of BoNT/B | 178 | ||
| 4.8.2 Efficacy of Botulinum Antitoxins in Inhalation Botulism | 179 | ||
| 4.8.2.1 Efficacy of Human and Equine Antitoxins in Rhesus Monkeys Against Aerosol Challenge by BoNT/A: Prophylactic and Presympto... | 179 | ||
| 4.8.2.2 Efficacy of Equine F(ab′)2 Antitoxin in Rhesus Monkeys Against Aerosol Challenge by BoNT/A: Infusion Delayed Until First ... | 179 | ||
| 4.8.2.3 Efficacy of Human Hyperimmune Globulin Antitoxins in Guinea Pigs Challenged by BoNT/A Aerosol: Fixed Schedule | 180 | ||
| 4.9 Summary and Conclusions | 181 | ||
| Abbreviations | 181 | ||
| Acknowledgements | 182 | ||
| References | 182 | ||
| Chapter 5 - The Structural Biology and Biochemistry of the Ricin Toxin and the Military Use and Inhalation Toxicology of Ricin Aerosols† | 186 | ||
| 5.1 Introduction | 186 | ||
| 5.2 Structural Biology and Biochemistry of the Ricin Ribosome Inactivating Protein | 188 | ||
| 5.2.1 Crystal Structure of the Ricin Toxin | 189 | ||
| 5.2.2 Cultivars and Isotoxins of Ricin | 193 | ||
| 5.2.3 Cellular Internalization of Ricin | 193 | ||
| 5.2.4 N-Glycosidase Activity of Ricin | 194 | ||
| 5.3 Weaponization of the Ricin Toxin | 197 | ||
| 5.3.1 Brief History of Ricin Weaponization | 197 | ||
| 5.3.2 Aerosolization of Ricin | 198 | ||
| 5.3.3 Polydispersity of Ricin Aerosols | 199 | ||
| 5.4 Inhalation of Aerosolized Ricin | 200 | ||
| 5.4.1 The Aerodynamics of Inhaled Ricin Particles | 200 | ||
| 5.4.2 The Fate of Aerosolized Ricin in the Respiratory Tract | 202 | ||
| 5.4.3 Deposition of Aerosol Particles in the Respiratory Tract | 204 | ||
| 5.4.4 Clearance of Inhaled Particles from the Respiratory Tract | 205 | ||
| 5.5 Signs, Symptoms and Toxicity of Ricin Exposure | 205 | ||
| 5.5.1 Inhalation of Ricin | 206 | ||
| 5.5.2 Ingestion and Injection of Ricin | 208 | ||
| 5.6 Conclusions | 208 | ||
| Acknowledgements | 209 | ||
| References | 209 | ||
| Chapter 6 - Bioaerosols in the Environment: Populations, Measurement and Processes | 219 | ||
| 6.1 Introduction | 219 | ||
| 6.2 Ambient Bioaerosol Measurement | 220 | ||
| 6.2.1 Characterization of Collected Particles | 220 | ||
| 6.2.1.1 Collection Techniques | 220 | ||
| 6.2.1.2 Analysis of Collected Bioaerosols | 224 | ||
| 6.2.2 In situ Measurement of Bioaerosols | 226 | ||
| 6.3 Bioaerosol Populations and Sources | 228 | ||
| 6.4 Factors Affecting Bioaerosol Measurement | 233 | ||
| 6.5 Future Directions | 237 | ||
| References | 238 | ||
| Chapter 7 - Bacillus anthracis: An Aerobiological Threat† | 248 | ||
| 7.1 Introduction | 248 | ||
| 7.2 Historical Aspects | 249 | ||
| 7.3 Bacillus anthracis | 251 | ||
| 7.3.1 Bacillus anthracis Spores | 252 | ||
| 7.3.2 Ecology of Bacillus anthracis | 253 | ||
| 7.3.3 B. anthracis Virulence Factors | 255 | ||
| 7.4 Clinical Forms of Anthrax | 256 | ||
| 7.4.1 Cutaneous Anthrax | 256 | ||
| 7.4.2 Gastrointestinal Anthrax | 257 | ||
| 7.4.3 Inhalational Anthrax | 257 | ||
| 7.4.4 Injectional Anthrax | 258 | ||
| 7.5 Aerobiology and Inhalation Exposure to B. anthracis Spores | 258 | ||
| 7.5.1 Particle Size | 258 | ||
| 7.5.2 Crossing the Respiratory Epithelium | 262 | ||
| 7.5.3 Hematogenous Dissemination | 262 | ||
| 7.6 Laboratory Diagnosis | 262 | ||
| 7.7 Prevention and Treatment | 263 | ||
| 7.7.1 Prevention and Treatment in Animals | 263 | ||
| 7.7.2 Prevention and Treatment in Humans | 264 | ||
| 7.8 Anthrax as a Biological Weapon | 270 | ||
| 7.9 Amerithrax | 271 | ||
| 7.10 Detection of B. anthracis Spores in Environmental Samples | 272 | ||
| 7.11 Decontamination | 273 | ||
| Acknowledgements | 278 | ||
| References | 279 | ||
| Chapter 8 - Detection of Airborne Pathogens and Toxins | 300 | ||
| 8.1 Introduction | 300 | ||
| 8.2 Sample Collection | 301 | ||
| 8.3 Sample Preparation | 306 | ||
| 8.4 Identification Based on Macroscopic Methods | 307 | ||
| 8.5 Identification Based on Microscopic Methods | 309 | ||
| 8.6 Identification Based on GC-FAME | 309 | ||
| 8.7 Identification Based on Spectrochemical Methods | 311 | ||
| 8.8 Identification Based on Chemical/Biochemical Methods | 315 | ||
| 8.9 Identification Based on Immunoassays | 316 | ||
| 8.10 Identification Based on Nucleic Acids | 319 | ||
| 8.11 Conclusion | 322 | ||
| References | 324 | ||
| Chapter 9 - Aerobiological Aspects of Biological Warfare† | 330 | ||
| 9.1 Introduction | 330 | ||
| 9.2 Biological Agents As Infectious Aerosols | 333 | ||
| 9.3 Anthrax Spores (Bacillus anthracis) | 334 | ||
| 9.4 Vegetative Bacteria (Francisella tularensis) | 336 | ||
| 9.5 Filoviruses (Marburg and Ebola Viruses) | 338 | ||
| 9.6 Toxins (Ricin) | 338 | ||
| 9.7 Fungal Spores (Wheat Cover Smut – Tilletia sp.) | 339 | ||
| 9.8 Future Prospects for Biological Warfare | 340 | ||
| References | 341 | ||
| Chapter 10 - Aerosol Physics for Bioaerosols† | 345 | ||
| 10.1 Introduction | 345 | ||
| 10.2 Definition of Aerosols | 346 | ||
| 10.3 Bioaerosols | 347 | ||
| 10.4 Particle Size | 347 | ||
| 10.4.1 Diameter | 347 | ||
| 10.4.2 Knudsen Number (Kn) | 349 | ||
| 10.5 Particle Size Distribution | 349 | ||
| 10.6 Particle Shape | 351 | ||
| 10.7 Particle Density | 352 | ||
| 10.8 Particle Surface Area and Mass | 353 | ||
| 10.9 Aerosol Concentration | 353 | ||
| 10.10 Settling Velocity | 354 | ||
| 10.10.1 Reynolds Number (Re) | 354 | ||
| 10.10.2 Drag Force | 355 | ||
| 10.10.3 Terminal Settling Velocity | 356 | ||
| 10.10.4 Nonspherical Particles | 356 | ||
| 10.10.5 Cunningham and Slip Correction Factors | 357 | ||
| 10.11 Aerodynamic Diameter (da) | 359 | ||
| 10.12 Relaxation Time | 360 | ||
| 10.13 Brownian Motion and Diffusion | 360 | ||
| 10.14 Coagulation | 361 | ||
| 10.15 Electrical Properties | 362 | ||
| 10.16 Adhesion and Resuspension of Particles | 363 | ||
| 10.17 Aerosol Sampling and Samplers | 364 | ||
| 10.18 Conclusion | 367 | ||
| Nomenclature | 367 | ||
| References | 368 | ||
| Chapter 11 - Respiratory Protection Against Some Pathogens and Toxins | 371 | ||
| 11.1 Introduction | 371 | ||
| 11.2 Pathogens | 372 | ||
| 11.2.1 The MMAD | 372 | ||
| 11.3 Toxins | 378 | ||
| 11.4 Air Filtration | 378 | ||
| 11.4.1 Mechanisms of Air Filtration | 381 | ||
| 11.4.1.1 Inertial Impaction | 381 | ||
| 11.4.1.2 Interception | 382 | ||
| 11.4.1.3 Diffusion | 382 | ||
| 11.5 Some Comparisons and Applications | 382 | ||
| 11.5.1 Comparisons | 382 | ||
| 11.5.2 Applications | 389 | ||
| 11.6 Conclusion | 395 | ||
| References | 395 | ||
| Chapter 12 - An Improved Model of Human Response to Bioaerosol Exposure | 400 | ||
| 12.1 Introduction | 400 | ||
| 12.1.1 Dry Agent Model for Tularemia | 403 | ||
| 12.1.2 Ricin | 405 | ||
| 12.2 Implementation of a Particle Deposition Model for the Respiratory Tract | 408 | ||
| 12.2.1 Selection of a Model of Inhalation Mechanics | 408 | ||
| 12.2.1.1 Background | 408 | ||
| 12.2.1.2 Investigative Discussions | 409 | ||
| 12.2.1.3 Decision to Use MPPD | 411 | ||
| 12.2.2 Dosimetry Assessment of Inhaled Materials in the Lungs: MPPD Modeling | 411 | ||
| 12.2.2.1 Whole-Lung Modeling/Regional and Total Dosimetry Calculations | 412 | ||
| 12.2.2.2 MPPD Software Development | 414 | ||
| 12.2.3 Inhalability | 415 | ||
| 12.2.4 MPPD as Implemented in the DARRT Model | 415 | ||
| 12.2.5 Agent-Containing Particle Calculation | 419 | ||
| 12.2.5.1 Discussion | 420 | ||
| 12.2.5.2 ACP Model | 422 | ||
| 12.2.5.3 ACP Model Summary | 422 | ||
| 12.3 Development of a Human Response Model Accounting for Aerosol Size – Prototype Agent Francisella tularensis | 423 | ||
| 12.3.1 Development of a Human Response Model | 424 | ||
| 12.3.1.1 ET Infection Calculation | 425 | ||
| 12.3.1.2 Pulmonary Infection Calculation | 429 | ||
| 12.3.2 Summary | 430 | ||
| 12.4 Development of a Model for Particle Size-Dependent Health Effects of Ricin Exposure | 430 | ||
| 12.4.1 Background | 431 | ||
| 12.4.2 Calculations | 432 | ||
| 12.4.3 Summary for Ricin Model | 433 | ||
| 12.5 Parameters for the Inhalation Mechanics of Aerosol Hazards | 434 | ||
| 12.5.1 Parameter Definitions | 434 | ||
| 12.5.2 Definitions Applied to Dissemination of Dry Preparations | 435 | ||
| 12.5.3 Definitions Applied to Dissemination of Wet Preparations | 436 | ||
| 12.5.4 Applications to Inhalation Modeling | 437 | ||
| 12.5.4.1 Inhalability | 437 | ||
| 12.5.4.2 Hygroscopicity | 437 | ||
| 12.5.4.3 Active Agent | 438 | ||
| 12.6 Discussion | 438 | ||
| 12.7 Recommendations | 440 | ||
| Acknowledgements | 441 | ||
| References | 441 | ||
| Chapter 13 - Aerosol Exposure to Pathogenic Bacteria and Virus Particles: Standard Operating Procedure | 445 | ||
| 13.1 Introduction | 445 | ||
| 13.2 Exposure System Considerations | 447 | ||
| 13.3 Exposure | 452 | ||
| 13.4 Outline of System Start-up | 454 | ||
| 13.5 System Operation with Pathogens | 455 | ||
| 13.6 Conclusion | 457 | ||
| References | 458 | ||
| Chapter 14 - Programming an Agent-Based Model for Disease Dynamics with Multiple Sources of Infection† | 460 | ||
| 14.1 Introduction | 460 | ||
| 14.1.1 The Compartmental Susceptible, Infective, Resistant (SIR) Models | 461 | ||
| 14.1.2 The Compartmental Susceptible, Exposed, Infective, Resistant (SEIR) Models | 461 | ||
| 14.1.3 The Compartmental Susceptible, Infective, Susceptible (SIS) Models | 462 | ||
| 14.1.4 Host-to-Host Transmission and Environmental Contamination | 464 | ||
| 14.1.5 Density Dependence and Contact Probabilities | 464 | ||
| 14.1.6 Double Counting and Multiple Routes of Exposure | 465 | ||
| 14.1.7 Net Transformation Probability | 466 | ||
| 14.2 Modeling Building with R | 468 | ||
| 14.2.1 Building a Model with an Example Data Set | 469 | ||
| 14.2.2 Perform the Transition | 471 | ||
| 14.2.2.1 Example 1 | 475 | ||
| 14.2.2.2 Example 2: Performing 100 Time Steps and Recording Values | 475 | ||
| 14.2.2.2.1 Plotting the Results. | 476 | ||
| 14.2.2.3 Example 3: Multiple Interactions and Confidence Levels | 478 | ||
| 14.2.2.3.1 Plot with Expected Values and Confidence Intervals. | 479 | ||
| 14.3 Results | 482 | ||
| 14.4 Discussion | 483 | ||
| 14.4.1 Utility of Models | 483 | ||
| 14.4.2 Heterogeneous Transformation Probabilities | 484 | ||
| 14.5 R Program Code | 484 | ||
| References | 486 | ||
| Subject Index | 487 |