Preface p. xiii
Principles and Approaches p. 1
Introduction p. 1
Definitions p. 2
Differentiating Molecular Epidemiology from Taxonomy and Phylogeny p. 4
Epidemiologic Problems Addressed by Molecular Strain-Typing Techniques p. 5
Determining dynamics of disease transmission in geographically widespread areas p. 5
Identifying risk and quantitating attributable risk fractions in sporadic occurrence of infectious diseases p. 7
Stratifying data and refining epidemiologic study designs p. 8
Distinguishing pathovars from nonpathovars p. 9
Addressing hospital and institutional infectious disease problems p. 9
Identifying genetic determinants of disease transmission p. 10
Application to Epidemiology of Molecular Strain-Typing Methods p. 11
When to use molecular strain-typing methods p. 11
How to select molecular strain-typing methods to apply to epidemiologic investigations p. 14
Validating new molecular strain-typing methods p. 15
Concluding Remarks p. 25
References p. 25
Laboratory Methods Used for Strain Typing of Pathogens: Conventional and Molecular Techniques p. 29
Introduction p. 29
Phenotypic Strain-Typing Methods p. 30
Typing by growth and morphologic characteristics p. 30
Typing based on biochemical characteristics p. 31
Typing by serologic characteristics p. 32
Typing by functional or physiologic characteristics p. 33
Genotypic Strain-Typing Methods p. 39
Nucleic acid extraction: overview p. 39
Analysis of extrachromosomal DNA elements p. 43
Genome-based typing methods p. 45
Concluding Remarks p. 55
References p. 55
Laboratory Methods Used for Strain Typing of Pathogens: PCR-Based Strain Typing Methods p. 63
Introduction p. 63
Overview of PCR procedure p. 63
Epidemiologic Application of PCR-Based Strain-Typing Methods p. 65
Simplicity p. 66
High throughput p. 67
Cost p. 67
Appropriateness p. 67
Limitations of PCR tests p. 68
Strain-Typing Methods Based on PCR Assays p. 69
PCR strain-typing methods based on random sequences p. 69
PCR strain-typing methods based on heterogeneity within restriction endonuclease sites p. 71
PCR strain-typing methods based on interspersed DNA repetitive elements p. 76
Concluding Remarks p. 83
References p. 83
Analysis of Similarity and Relatedness in Molecular Epidemiology p. 91
Introduction p. 91
Methods of Classification p. 92
Cladistic models to infer relationships p. 94
Phenetic methods to infer relationships p. 100
Assessing Validity and Reliability of Relationship Measures p. 115
Computer-Assisted Analyses of Pathogen Relationships p. 119
Concluding Remarks p. 121
References p. 122
Distinguishing Epidemic and Endemic Occurrence of Infectious Diseases p. 125
Introduction p. 125
Endemic versus Epidemic Occurrences of Infectious Disease p. 126
Epidemiology of Antimicrobial Drug-Resistant Pathogens p. 127
Sources of drug-resistant strains of Salmonella p. 127
Spatial transmission patterns of drug-resistant infectious diseases p. 135
Epidemiology of Drug-Susceptible Infectious Diseases p. 140
Concluding Remarks p. 142
References p. 143
Stratification and Refinement of Data in Epidemiologic Investigations p. 149
Introduction p. 149
Characterizing Dynamics of Infectious Disease Transmission in Community Settings p. 150
Drug-resistant salmonellosis in Brazil p. 151
Multidrug-resistant (MDR) tuberculosis in New York City p. 153
Determining Attributable Risks in Community- or Institution-Acquired Infections p. 157
Salmonellosis traced to precooked roast beef in New Jersey and Pennsylvania p. 158
Food-borne disease surveillance in Minnesota p. 160
Nosocomial infections with vancomycin-resistant Enterococcus faecium p. 160
Refining Analytical Epidemiologic Study Designs p. 162
Drug-susceptible tuberculosis in New York City p. 163
Making new inferences from rare events revealed by strain typing p. 165
Creating opportunities to identify new intervention strategies p. 167
Concluding Remarks p. 168
References p. 169
Distinguishing Pathovars from Nonpathovars: Escherichia coli p. 175
Introduction p. 175
E. coli Classifications p. 176
E. coli Associated with Intestinal Diseases p. 178
Conventional techniques used to differentiate E. coli strains that cause diarrhea p. 178
Molecular biology techniques used to differentiate E. coli strains that cause diarrhea p. 184
Differentiation of diarrheagenic E. coli pathotypes in epidemiologic investigations p. 189
Extraintestinal E. coli Infections p. 190
Clinical spectrum of ExPEC infections p. 190
Approaches used to differentiate ExPEC p. 191
Molecular epidemiologic approach to discriminate ExPEC p. 193
Concluding Remarks p. 197
References p. 198
Distinguishing Pathovars from Nonpathovars: Streptococcus pneumoniae p. 209
Introduction p. 209
S. pneumoniae (the Pneumococcus) p. 211
Clinical spectrum of pneumococcal disease p. 211
Conventional strain-typing methods for pneumococci p. 212
Genotyping methods for S. pneumoniae p. 213
Application of Strain-Typing Methods to Epidemiologic Investigation of Pneumococcal Infections p. 214
Penicillin-resistant pneumococcal infections p. 214
Pneumococcal colonization and infection p. 216
Comparison of strain types between invasive disease and NP isolates p. 217
Comparison of strain types from outbreaks p. 219
Comparison of pathogenicity of strain types in the mouse model p. 220
Genotype-specific risk factors for sporadic pneumococcal invasive diseases p. 221
Concluding Remarks p. 221
References p. 222
Distinguishing Pathovars from Nonpathovars: Helicobacter pylori p. 229
Introduction p. 229
H. pylori p. 230
Clinical spectrum of H. pylori diseases p. 230
Conventional strain-typing methods for H. pylori p. 230
Genotyping methods for H. pylori p. 230
Whole-genome analysis of H. pylori p. 231
Application of Strain-Typing Methods to Epidemiologic Investigation of H. pylori Infections p. 233
Genotypic differences in H. pylori strains isolated from stomachs with disease versus asymptomatic colonization p. 233
Colonization and population structure of H. pylori strains in the stomach p. 237
Demonstrating clustering of disease and colonization p. 239
Concluding Remarks p. 241
References p. 242
Hospital Infections: Staphylococcus aureus p. 249
Introduction p. 249
Overview of Clinical and Epidemiologic Issues Related to Bacterial Nosocomial Infections p. 250
Staphylococcal Nosocomial Infections p. 252
Clinical spectrum of staphylococcal diseases p. 252
Drug-resistant infections p. 253
Strain-Typing Methods for S. aureus p. 255
Conventional strain-typing methods for S. aureus p. 255
Genotyping methods for S. aureus p. 256
Application of Strain-Typing Methods to Epidemiologic Investigation of Nosocomial S. aureus Infections p. 258
S. aureus colonization versus infection p. 259
Determining clonal distribution of S. aureus isolates p. 262
Comparative genomics approach to differentiate S. aureus strains p. 266
Endemic versus epidemic occurrence of S. aureus hospital infections p. 268
Concluding Remarks p. 270
References p. 271
Hospital Infections: Gram-Negative Bacteria p. 281
Introduction p. 281
Clinical Spectrum and Epidemiology of Infections Caused by Gram-Negative Bacteria p. 282
Antimicrobial Drug Resistance in Gram-Negative Bacilli p. 284
Strain-Typing Methods for Gram-Negative Bacterial Organisms p. 289
Conventional strain-typing methods for gram-negative organisms p. 289
Genotyping methods for gram-negative organisms p. 290
Application of Strain-Typing Methods to Epidemiologic Investigation of Nosocomial Infections Caused by Gram-Negative Bacteria p. 291
Monoclonal versus polyclonal infections p. 291
Reinfection versus relapse infections p. 291
Colonization, environmental contamination, and infection with gram-negative bacteria p. 292
Endemic versus epidemic occurrence of nosocomial infections caused by gram-negative bacteria p. 294
Concluding Remarks p. 298
References p. 299
Identifying a Pathogen's Biologic Determinants of Disease Transmission p. 307
Introduction p. 307
Modes of Disease Transmission p. 308
Identifying Genetic Determinants of Disease Transmission p. 309
Tuberculosis: identifying phenotypic and genetic factors of M. tuberculosis associated with rapid progression to disease p. 309
UTI caused by E. coli: the comparative genomics approach to identify new genes associated with transmission p. 313
Salmonellosis: identifying bacterial factors that allow the organism to establish a reservoir that becomes a risk factor for human transmission p. 315
Concluding Remarks p. 317
References p. 318
Glossary p. 323
Annotated Websites of Databases Useful for Molecular Epidemiologic Investigations p. 333
Index p. 339