Provides the latest QMRA methodologies to determine infection risk cause by either accidental microbial infections or deliberate infections caused by terrorism
• Reviews the latest methodologies to quantify at every step of the microbial exposure pathways, from the first release of a pathogen to the actual human infection
• Provides techniques on how to gather information, on how each microorganism moves through the environment, how to determine their survival rates on various media, and how people are exposed to the microorganism
• Explains how QMRA can be used as a tool to measure the impact of interventions and identify the best policies and practices to protect public health and safety
• Includes new information on genetic methods
• Techniques use to develop risk models for drinking water, groundwater, recreational water, food and pathogens in the indoor environment

PREFACE xi

CHAPTER 1 MOTIVATION 1

Prevalence of Infectious Disease 1

Prior Approaches 4

Scope of Coverage 4

Potential Objectives of a QMRA 5

      Site-Specific Assessment 5

      Ensemble of Sites 6

Secondary Transmission 7

Outbreaks versus Endemic Cases 7

References 10

CHAPTER 2 MICROBIAL AGENTS AND TRANSMISSION 15

Microbial Taxonomy 15

      Eukaryotes 15

      Prokaryotes 18

      Viruses 20

      Prions 22

Clinical Characterization 24

Microorganisms of Interest 27

      Viruses 27

      Bacteria 37

      Protozoa 42

Transmission Routes 45

      Inhalation 48

      Dermal Exposure 50

      Oral Ingestion 50

References 55

CHAPTER 3 RISK ASSESSMENT PARADIGMS 63

Chemical Risk Assessment: National Academy of Sciences Paradigm 63

Ecological Risk Assessment 67

Approaches for Assessing Microbial Risks 71

      Background 71

      The QMRA Framework 74

      Hazard Identification 74

      Dose–Response Assessment 74

      Exposure Assessment 76

      Risk Characterization 77

      Risk Management 79

Development of the QMRA Framework and Processes 79

      QMRA and the Safety of Water 82

      QMRA, Food Safety, and the HACCP System 84

References 86

CHAPTER 4 CONDUCTING THE HAZARD IDENTIFICATION (HAZ ID) 91

Identifying and Diagnosing Infectious Disease 92

Health Outcomes Associated with Microbial Infections 95

Sensitive Populations 100

Women during Pregnancy, Neonates, and Young Babies 101

Diabetes 102

The Elderly 102

The Immunocompromised 104

Databases for Statistical Assessment of Disease 106

ICD Codes 107

Waterborne and Foodborne Outbreaks 111

Epidemiological Methods for Undertaking HAZ ID 117

Controlled Epidemiological Investigations 118

HAZ ID Data Used in the Risk Assessment Process 119

Recommendations for Updating Quantitative Data for HAZ ID Information 121

References 122

CHAPTER 5 ANALYTICAL METHODS AND THE QMRA FRAMEWORK: DEVELOPING OCCURRENCE AND EXPOSURE DATABASES 129

Introduction 129

Approaches for Developing Occurrence and Exposure Databases 132

Overview of Methodological Issues 134

      Sampling Water 136

      Sampling Surfaces and Food 138

      Sampling Aerosols 138

Specific Techniques for Bacteria, Protozoa, and Viruses 140

      Bacteria 140

      Protozoa 142

      Viruses 143

Molecular Techniques 145

      Probes (FISH) 146

      Typing 146

      Metagenomics 147

      PCR and Quantitative PCR 147

References 151

CHAPTER 6 EXPOSURE ASSESSMENT 159

Conducting the Exposure Assessment 159

Characterizing Concentration/Duration Distributions 160

      Random (Poisson) Distributions of Organisms 160

      Estimation of Poisson Mean in Count Assay (Constant and Variable Volumes) 162

      Count Assay with Upper Limits 163

      Estimation with Quantal Assay 164

      Goodness of Fit to Poisson: Plate Assay 168

      Goodness of Fit: MPN 178

      Confidence Limits: Likelihood 182

      Implications for Risk Assessment 187

Consumption Distributions 214

      Systematic Subpopulation Differences 221

Afterword 223

Appendix 224

      Microsoft Excel 224

      MATLAB 225

      R 227

References 230

CHAPTER 7 PREDICTIVE MICROBIOLOGY 235

Objective 235

Basic First-Order Processes and Deviations 236

      Biological and Physical Bases for Deviations 236

Physical Removal 238

Types of Decay Processes 238

      General Forms of Decay and Reasons for Nonlinearity 238

      Spontaneous/Endogenous 240

      Chemical Agents 241

      Thermally Induced 243

      Ionizing and Nonionizing Radiation 243

      Predation and Antagonism 245

Types of Growth Processes 245

      Mathematical Modeling of Growth Curves 246

      Substrate Dependency 252

      Structured Growth Models 255

      Incorporation of Decay into Growth Models 256

      Systems Biology Approaches 258

      CONTENTS vii

      Dependence of Growth Parameters on Other Environmental Variables 258

      Interacting Populations 258

Data Sources 260

References 263

CHAPTER 8 CONDUCTING THE DOSE–RESPONSE ASSESSMENT 267

Plausible Dose–Response Models 268

Framework for Mechanistic Dose–Response Relationships 269

      Exponential Dose–Response Model 271

      Beta-Poisson Dose–Response Model 272

      Simple Threshold Models 274

      Negative Binomial Dose Distributions 277

      Variable Threshold Models 278

      Other Mixture Models 279

      Biological Arguments for One-Hit Models 281

Empirical Models 282

Fitting Available Data 283

      Types of Data Sets 284

      Potential Impacts of Immune Status 298

Relationship between Dose and Severity (Morbidity and Mortality) 299

      Morbidity Ratio (PD:I) 299

      Mortality Ratio 303

Reality Checking: Validation 304

      Validation: 1993 Milwaukee Outbreak 304

Use of Indicators and Other Proxy Measures in Dose–Response 305

      Indicator Methods 305

      Molecular Methods 307

Advanced Topics in Dose–Response Modeling 308

      Dose–Response–Time Models 308

      Physiological Models 313

Appendix 315

References 317

CHAPTER 9 UNCERTAINTY 323

Point Estimates of Risk 324

Terminology: Types of Uncertainty 326

Sources of Uncertainty 327

Sources of Variability 328

Variability that is Uncertain 329

Approaches to Quantify Parametric Uncertainty 329

      Likelihood 329

      Bootstrap 330

      Other Methods 330

Applications 332

      Exposure Assessment 332

      Dose–Response Assessment 338

Combining Parametric Uncertainty from Multiple Sources 344

      Propagation Methods 344

      Monte Carlo Analyses 347

Overall Risk Characterization Example 365

Second-Order Methods 368

Model Uncertainty and Averaging 370

References 373

CHAPTER 10 POPULATION DISEASE TRANSMISSION 377

Introduction: Models for Population and Community Illnesses 377

      Basic SIR Model 378

      Incubation Period 386

      Duration of Illness 388

      Secondary Cases 389

      Impact of Immunity 392

      Outbreak Detection 393

References 397

CHAPTER 11 RISK CHARACTERIZATION AND DECISION MAKING 399

Introduction 399

Valuing Residual Outcomes 400

      Classical Economics 400

      DALYs and QALYs 404

Decision Making 407

      Cost–Benefit Analysis 408

      Multivariate Approaches 411

Other Aspects Entering into a Decision 412

      Equity and Justice Aspects 412

References 413

INDEX 415

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