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Medical Microbiology E-Book

Medical Microbiology E-Book

Michael R. Barer | Will L Irving

(2018)

Additional Information

Abstract

Medical microbiology concerns the nature, distribution and activities of microbes and their impact on health and wellbeing. In spite of the introduction of many antimicrobial agents and immunisations, we continue to face major challenges in combatting infection, not least the gathering crisis in antimicrobial resistance.

Now in a fully revised and updated 19th edition, Medical Microbiology provides comprehensive coverage of infection from the microbial perspective, combining a clear introduction to key principles with a focus explicitly geared to modern clinical practice. It provides ideal coverage for medical and biomedical students – with ‘Key Points’ boxes throughout to highlight the essentials – and sufficient detail to also inform specialists in training.

Building on the success of previous editions, updates in Medical Microbiology 19e include:

  • New and expanded coverage of hot topics and emerging areas important to clinical practice, including:

    • Genomics
    • The Human Microbiome
    • Direct acting antiviral agents for the treatment of HCV infection
    • Molecular methods in diagnostic microbiology
    • Antibiotic Stewardship

  • A new and improved downloadable eBook (from studentconsult) for anytime access to the complete contents plus BONUS interactive learning materials:

    • Clinical cases - to introduce how patients with infections present and help relate key principles to practice
    • MCQs for each chapter - to check understanding and aid exam preparation

Table of Contents

Section Title Page Action Price
Front Cover cover
Inside Front Cover ifc1
Medical Microbiology i
Copyright Page iv
Preface v
Acknowledgements vi
Contributors vii
Table Of Contents xiii
1 Microbial biology 1
1 Microbiology and medicine 2
Key points 2
An outline history of microbiology and infection 3
Microorganisms and infection 3
Hygiene, treatment and prevention of infection 5
Sources and spread of infection 6
Recommended reading 7
Websites 7
MCQs 7.e1
Microbiology and medicine 7.e1
2 Morphology and nature of microorganisms 8
Key points 8
Prokaryotic and eukaryotic cells 9
Anatomy of the bacterial cell 10
Bacterial nucleoid 11
Ribosomes 12
Cytoplasmic membrane 12
Cell wall 12
Extracellular polysaccharides: capsules, microcapsules and loose slime 16
S-layers 16
Flagella and motility 16
Fimbriae and pili 17
Importance of microbial surface structures in infection 18
The bacterial ‘life cycle’ 18
Bacterial spores 18
Conidia (exospores) 19
Pleomorphism and involution 19
Spheroplasts, protoplasts and L-forms 19
The nature and composition of viruses 20
Structure 20
Viral nucleic acid 21
Virion enzymes 21
Viral proteins 21
Viroids, defective viruses and prions 21
Recommended reading 21
Websites 21
MCQs 21.e1
3 Classification, identification, typing and diversity of bacteria 22
Key points 22
Taxonomy 23
Methods of classification 23
Polyphasic approaches 24
DNA composition 24
DNA homology (DNA:DNA hybridisation) 24
Sequencing of genes encoding 16S ribosomal RNA and other housekeeping genes 25
Whole genome sequencing (WGS) 25
Classification in clinical practice 25
Actinobacteria 26
Firmicutes 27
Proteobacteria 27
Bacteroidetes 27
Spirochaetes 27
Chlamydiae 27
Identification of bacteria 27
Microscopy 28
Cultural characteristics 28
Biochemical reactions 28
Matrix-assisted laser desorption ionisation-time of flight mass spectrometry (MALDI-TOF MS) 28
Nucleotide sequence-based identification 29
Antigenic characterisation 29
Typing of bacteria 29
Restriction endonuclease typing 30
Gene probe typing 31
Polymerase chain reaction-based methods 31
Multilocus sequence typing 31
Variable number tandem repeat analysis 31
Whole genome–based typing 32
Recommended reading 32
Websites 32
MCQs 32.e1
4 Bacterial growth, physiology and death 33
Key points 33
Bacterial growth 34
Types of growth 34
Growth phases in broth culture 34
Media for bacterial growth 36
Media used for isolation and identification of pathogens 36
Selective and indicator media 36
Media for laboratory studies 36
Bacterial physiology 37
Nutritional types 37
Physical conditions required for growth 37
Growth atmosphere 38
Growth temperature 38
Extremophiles 39
Bacterial metabolism 39
Adaptive responses in bacteria 39
Bacterial defence against antibiotics and other noxious chemicals 41
Bacterial viability 41
Bacterial death 42
Sterilisation and disinfection 42
Key definitions 42
Sterilisation 42
Disinfection 42
Antisepsis 43
Methods used in sterilisation and disinfection 43
Heat 43
Ionising radiation 43
Filtration 43
Gaseous chemical agents 43
Liquid chemical agents 43
Incorporation of agents into solids for surface antisepsis 43
Choice of method 43
Measurement of microbial inactivation 44
D value 44
Resistance to sterilisation and disinfection 44
Sterilisation by moist heat 45
Sterilisation by dry heat 45
Disinfection by chemicals 45
Recommended reading 46
Websites 46
MCQs 46.e1
5 Antimicrobial agents 47
Key points 47
Antibacterial agents 47
Sites of action and mechanisms of resistance 47
Inhibitors of bacterial cell wall synthesis 48
β-lactam agents 48
Penicillins 48
Cephalosporins 49
Other β-lactam agents 51
Glycopeptides 51
Other inhibitors of bacterial cell wall synthesis 51
Inhibitors of bacterial protein synthesis 51
Tetracyclines 51
Chloramphenicol 51
Aminoglycosides 51
Macrolides 52
Lincosamides 52
Fusidic acid 52
Linezolid 52
Streptogramins 53
Mupirocin 53
Inhibitors of nucleic acid synthesis 53
Sulphonamides and diaminopyrimidines 53
Quinolones 53
Nitroimidazoles 54
Nitrofurans 54
Rifamycins 54
Disruption of cell membranes 54
Polymyxins 54
Daptomycin 54
Antimycobacterial agents 54
Antifungal agents 54
Antiviral agents 55
Treatment of herpesvirus infections 56
Nucleoside analogues 56
Nonnucleoside antiherpes agents 57
Treatment of influenza 57
Neuraminidase inhibitors 57
Agents that block viral uncoating 58
Treatment of chronic hepatitis B virus infection 58
Interferons 58
HBV DNA polymerase inhibitors 58
Treatment of chronic hepatitis C virus infection 58
Other antiviral drugs—ribavirin 58
Antiretroviral agents 58
Nucleoside and nucleotide reverse transcriptase inhibitors 58
Nonnucleoside reverse transcriptase inhibitors 59
HIV protease inhibitors 59
HIV fusion inhibitors 59
HIV entry inhibitors 59
HIV integrase inhibitors 59
Recommended reading 59
Websites 59
MCQs 59.e1
6 Bacterial genetics 60
Key points 60
Genetic organisation and regulation of the bacterial cell 60
Processes leading to protein synthesis 61
Gene regulation 61
Mutation 62
Phenotypic variation 63
Types of mutations 64
Horizontal gene transfer 64
Transformation 64
Conjugation 65
Mobilisation of chromosomal genes by conjugation 65
Transduction and bacteriophages 65
Lysogenic conversion 66
Plasmids 66
Properties encoded by plasmids 66
Plasmid classification 66
Plasmid epidemiology and distribution 66
Transposons, integrons and genomic islands 66
Genetic basis of antibiotic resistance 67
Intrinsic resistance 67
Acquired resistance 67
Chromosomal mutations 67
Transferable antibiotic resistance 68
Control of antibiotic resistance 68
The bacterial species and molecular typing of microorganisms 69
Microbial genomes and genomics 70
Recommended Reading 73
MCQs 73.e1
7 Virus–cell interactions 74
Key points 74
The cytolytic or cytocidal growth cycle 74
Attachment (adsorption) 75
Entry (penetration) 75
Uncoating 76
Synthesis of viral components 76
Class 1: Double-stranded DNA viruses 76
Class 2: Single-stranded DNA viruses 77
Class 3: Double-stranded RNA viruses 77
Class 4: + single-stranded RNA viruses 77
Class 5: − single-stranded RNA viruses 77
Class 6: Retroviruses 78
Class 7: Partial double-stranded DNA viruses 78
Assembly and release 78
Microscopy of infected cells 79
Chronic/persistent infections 80
Latency 80
Transformation 81
Recommended reading 82
MCQs 82.e1
2 Infection and immunity 83
8 Innate and adaptive immunity 84
Key points 84
Innate and adaptive immunity 84
The immune system 84
Lymphoid cells 84
Myeloid cells 85
Mononuclear phagocytes 85
Granulocytes 85
Innate immunity 85
Features of innate immunity 86
Mechanisms of innate immunity 86
Mechanical barriers and surface secretions 86
Humoral defence mechanisms 87
Lysozyme 87
Basic polypeptides 87
Acute-phase proteins 87
Interferon 87
Complement 87
Regulation 88
Membrane attack complex (MAC) 89
Functions 89
Innate immune cells 89
Phagocytes 89
Phagocytosis 90
Natural killer (NK) cells 90
Eosinophils 90
Inflammation 91
Adaptive immunity 91
Antibodies 92
IgG 93
IgA 93
IgM 93
IgD 93
IgE 93
Antibody diversity 93
Antibody function 93
T cell receptor 93
Tissues involved in adaptive immune reactions 94
Development of the immune system 94
Lymphocyte trafficking 95
Initiation of adaptive responses 95
Thymus-independent antigens 95
Thymus–dependent antigens 95
Antigen processing and presentation 96
T cell activation 96
Humoral immunity – synthesis of antibody 96
Cell-mediated immunity 97
Regulatory T cells 98
Recommended reading 98
Websites 98
MCQs 98.e1
9 Immunity in infection 99
Key points 99
Immunity in infection 99
Immunopathology 99
The response to viral infections 99
Interferons 99
Acquired immunity 101
Humoral immunity 102
Cell-mediated immunity 103
Induction of an immune response 103
Immunopathology 103
Persistence of virus 104
Vaccines 105
Immunity in bacterial infection 105
Host defences 105
Inflammation 105
Humoral immunity 106
Cell-mediated immunity 106
Evasion 107
Intracellular bacteria 107
Immunopathology 107
Effects of endotoxin 107
Mycobacterial disease 108
Parasitic infections: pathogenesis and immunity 108
Pathogenic mechanisms 108
Mechanical tissue damage 108
Physiological effects 108
Tissue damage 109
Immune defence mechanisms 109
Innate defences 109
Macrophages 109
Granulocytes 110
Mast cells 110
Acquired immunity 110
Antibody 110
T cells 110
Evasion mechanisms 111
Seclusion 111
Evasion 111
Immunosuppression 111
Immunopathology 112
Vaccination 112
Recommended reading 112
Websites 112
MCQs 112.e1
10 Bacterial pathogenicity 113
Key points 113
Types of bacterial pathogens 113
Opportunistic pathogens 113
Primary pathogens 114
Zoonoses and nonzoonotic pathogens 114
Virulence determinants 114
Expression and analysis of virulence determinants 114
Establishment of infection 115
Colonisation 115
Adhesion 115
Fimbrial adhesins 116
Nonfimbrial adhesins 116
Binding to connective tissue proteins 117
Consequences of adhesion 117
Invasion 117
Uptake into host cells 117
Role of cell receptors 118
Survival and multiplication 118
Avoidance of host defence mechanisms 118
Capsules 118
Streptococcal M protein 119
Meningococcal Factor H–binding protein 119
Resistance to killing by phagocytic cells 119
Antigenic variation 119
Immunoglobulin A proteases 120
Serum resistance 120
Iron acquisition 120
Damage or dysfunction 121
Toxins 121
Endotoxin 121
Exotoxins 121
Systemic effects of toxins 123
Other extracellular aggressin 123
Recommended reading 124
MCQs 124.e1
11 The natural history of infection and the human microbiome 125
Key points 125
Meetings between human beings and microorganisms 125
Obligate pathogens 126
Accidental or incidental pathogens 126
Pathogens in the environment 126
Stages of infection 126
Pathological patterns associated with infection 127
Toxin-mediated bacterial infections 127
Acute pyogenic bacterial infections 128
Subacute bacterial infections 129
Chronic granulomatous bacterial infections 129
Timing of key events in infection 129
Virulence and infectivity 129
The human microbiome in health and disease 130
Microbiomic methods and analyses 131
Examples of disordered physiology and diseases associated with microbiomic imbalances (dysbioses) 131
Recommended reading 132
Website 132
MCQs 132.e1
3 Bacterial pathogens and associated diseases 133
12 Staphylococcus 134
Key points 134
Staphylococcus aureus 134
Description 134
Pathogenesis 135
Virulence factors 135
Staphylococcal toxins 135
Enterotoxins 135
Toxic shock syndrome toxin (TSST) 136
Epidermolytic toxins 136
Panton-Valentine leukocidin (PVL) 136
Epidemiology 136
Sources and acquisition of infection 136
Infected lesions 136
Healthy carriers 136
Animals 136
Environment 137
Meticillin-resistant Staph. aureus (MRSA) 137
Laboratory investigation 137
Typing 137
Treatment 138
Susceptibility to antibiotics 138
Choice of antibiotic for therapy 138
Coagulase-negative staphylococci 138
Description 139
Pathogenesis 139
Treatment 139
Recommended reading 140
Websites 140
MCQs 140.e1
Clinical scenario 140.e2
Staphylococcal infection 140.e2
13 Streptococcus and Enterococcus 141
Key points 141
Classification 141
Haemolytic activity 142
Lancefield grouping 142
Streptococcus pyogenes 142
Pathogenesis 143
Virulence factors 143
Adhesion 143
M proteins 143
Capsule 144
C5a peptidase 144
Streptolysins 144
Pyrogenic exotoxins 144
Hyaluronidase 145
Streptokinase 145
Deoxyribonucleases (DNAases) 145
Clinical features 145
Noninvasive streptococcal disease 145
Pharyngitis 145
Scarlet fever 145
Skin infections 146
Invasive soft tissue infections 146
Necrotising fasciitis 147
Streptococcal toxic shock syndrome 147
Other suppurative infections 147
Bacteraemia 147
Nonsuppurative sequelae 147
Rheumatic fever 148
Acute poststreptococcal glomerulonephritis 148
Streptococcus agalactiae 148
Pathogenesis 148
Virulence factors 148
Clinical features 149
Infection in the neonate 149
Early-onset disease 149
Late-onset disease 149
Infections in the adult 149
Other pyogenic streptococci 150
Streptococcus pneumoniae 150
Pathogenesis 150
Virulence factors 150
Capsule 150
IgA1 protease 150
Pneumolysin 150
Autolysin 150
Clinical features 150
Predisposing factors 150
Pneumonia 151
Otitis media and sinusitis 151
Meningitis 151
Conjunctivitis 151
Commensal streptococci 152
Viridans streptococci 152
Mitis group 152
Mutans group 152
Anginosus group 152
Bovis group 152
Enterococcus species 152
Laboratory investigation 153
Collection of specimens 153
Cultivation and identification 153
Antigen detection 153
Antibody detection 154
Typing of streptococci 154
Treatment 154
Prevention and control 155
Hygienic measures 155
Chemoprophylaxis 155
Vaccines 155
Pyogenic streptococci 155
Pneumococci 156
Recommended reading 156
Websites 156
MCQs 156.e1
Clinical scenario 156.e2
A case of necrotising fasciitis 156.e2
14 Coryneform bacteria, Listeria and Erysipelothrix 157
Key points 157
Coryneform bacteria 157
Corynebacterium diphtheriae and C. ulcerans 157
Description 157
Pathogenesis 158
Clinical features 158
Diagnosis 159
Treatment 160
Epidemiology 160
Control 161
Other medically important corynebacteria 161
Corynebacterium pseudotuberculosis 161
Corynebacterium jeikeium 161
Treatment 162
Corynebacterium urealyticum 162
Corynebacterium amycolatum 162
Corynebacterium glucuronolyticum 163
Corynebacterium minutissimum 163
Corynebacterium striatum 163
Corynebacterium pseudodiphtheriticum 163
Corynebacterium kroppenstedtii 163
Arcanobacterium haemolyticum 163
Rhodococcus equi 163
Other Corynebacterium species and coryneform bacteria 164
Listeria 164
Listeria monocytogenes 164
Description 164
Pathogenesis 164
Clinical aspects of infection 165
Infection in pregnancy and the neonate 165
Adult and juvenile infection 165
Meningitis 166
Bacteraemia 166
Gastroenteritis 166
Other infections 166
Epidemiology 166
Incidence 166
Transmission 167
Diagnosis and treatment 167
Prognosis 168
Erysipelothrix 168
Recommended reading 168
Websites 168
MCQs 168.e1
Listeria monocytogenes and Corynebacterium diphtheriae 168.e1
Clinical scenario 168.e2
15 Bacillus 169
Key points 169
Bacillus anthracis 169
Description 169
Pathogenesis 170
Virulence factors 170
Clinical features 170
Cutaneous anthrax 171
Inhalational anthrax 171
Gastrointestinal anthrax 172
Injectional anthrax 172
Meningitis 172
Naturally occurring infections of animals 172
Human infections in the United Kingdom (since the 1980s) 173
Animal models of disease 173
Laboratory investigation 173
Clinical specimens 173
Environmental samples 174
Treatment 174
Epidemiology and control 174
Immunisation 175
Bacillus cereus 175
Description 175
Pathogenesis 175
Food poisoning 176
Laboratory investigation 176
Treatment 176
Control 176
Other bacillus species 176
Sterilisation test bacilli 176
Recommended reading 177
Websites 177
MCQs 177.e1
Clinical scenario 177.e2
16 Escherichia coli and Shigella 178
Key points 178
Classification 178
Laboratory investigation 179
Typing 179
Clinical syndromes associated with extraintestinal E. coli 181
Pathogenesis 181
Gastrointestinal disease 182
Enteropathogenic E. coli (EPEC) 182
Enterotoxigenic E. coli (ETEC) 182
Enteroaggregative E. coli (EAEC) 183
Shiga toxin–producing E. coli (STEC) 183
Enteroinvasive E. coli (EIEC) 184
Shigella 184
Treatment 185
Control 186
Vaccination 186
Recommended reading 186
Websites 187
MCQs 187.e1
Clinical scenario 187.e2
E. coli 0157 haemolytic uraemic syndrome (HUS) 187.e2
17 Salmonella 188
Key points 188
Description 188
Host range 188
Pathogenesis 188
Clinical syndromes 189
Enteric fever 189
Onset 190
Progression 190
Relapse 190
Morbidity and mortality 190
Gastroenteritis and food poisoning 190
Bacteraemia and metastatic disease 190
The prolonged carrier state 191
Infective dose 191
Laboratory investigation 191
Enteric fever 191
Blood culture 191
Stool and urine culture 191
Serological tests 192
Serotyping and phage typing 192
Molecular typing 192
Treatment 193
Enteric fever 193
Gastroenteritis 193
Salmonella bacteraemia 194
Chronic asymptomatic carriers 194
Epidemiology 194
Incidence of enteric fever 194
Gastroenteritis and Salmonella food poisoning 194
Source attribution 195
Outbreaks 195
Surveillance 196
Prevention and control 196
Enteric fever 196
Nontyphoidal Salmonella 196
Vaccination 196
Recommended reading 197
Websites 197
MCQs 197.e1
Clinical scenario 197.e2
Typhoid 197.e2
18 Klebsiella, Enterobacter, Proteus and other enterobacteria 198
Key points 198
Klebsiella 198
Classification 198
Description 198
Pathogenesis 199
Pathogenic mechanisms 200
Treatment 200
Enterobacter 200
Description 200
Pathogenesis 200
4 Viral pathogens and associated diseases 361
37 Adenoviruses 362
Key points 362
Description 362
Classification 363
Replication 364
Clinical features 364
Respiratory diseases 364
Eye infections 365
Gut infections 365
Other diseases of immunocompetent patients 366
Disease in immunosuppressed transplant recipients 366
Pathogenesis 366
Laboratory Investigation 366
Direct demonstration of virus 366
Detection of viral DNA 366
Virus antigen 367
Electron microscopy 367
Culture 367
Serology 367
Treatment 367
Epidemiology 367
Control 367
Adenovirus-associated viruses 368
Recommended reading 368
MCQs 368.e1
Clinical scenario 368.e2
Disseminated adenovirus disease 368.e2
38 Herpesviruses 369
Key points 369
Latent infection 369
Reactivation 369
Recurrence or recrudescence 369
Description 370
Biological classification 370
Replication 370
Herpes simplex virus 371
Description 371
HSV glycoproteins 371
Pathogenesis 371
Primary infection 371
Latent infection 372
Reactivation 372
Clinical features 372
Primary infection 372
Recurrent infection 372
Oral infection 373
Skin infection 373
Herpetic whitlow 373
Eczema herpeticum 373
Eye infection 373
Central nervous system (CNS) infection 373
HSV encephalitis 374
HSV meningitis 374
Genital tract infection 375
Recurrent genital herpes 375
Neonatal herpes 375
Laboratory investigation 376
Diagnosis of HSV 376
Antibody tests for HSV 377
Treatment 377
Epidemiology 377
Control 378
Varicella–zoster virus (VZV) 378
Description 378
Pathogenesis 378
Varicella 378
Zoster 379
Clinical features 379
Varicella 379
Pneumonitis 380
Central nervous system 380
Varicella in pregnancy 380
Zoster 380
Postherpetic neuralgia 381
Ophthalmic zoster 381
Recurrent and chronic VZV 381
Laboratory Investigation 381
Virus detection 381
Serological diagnosis 381
Treatment 381
Epidemiology 382
Control 382
Passive immunization 382
Varicella vaccine 383
Epstein–Barr virus 383
Description 383
Replication 383
Pathogenesis 384
Clinical features 385
Infectious mononucleosis/glandular fever 385
Complications of infectious mononucleosis/glandular fever 385
Other EBV-associated disease, tumours and immunosuppression 385
Laboratory Investigation 385
Treatment 386
Epidemiology 386
Control 386
Cytomegalovirus 387
Description 387
Replication 388
Pathogenesis 388
Intrauterine infection 388
Perinatal infection 388
Postnatal infection 388
Host responses 389
Clinical features 389
Congenital CMV infection 389
Infection in children and adults 389
Infection in immunocompromised patients 389
Laboratory Investigation 389
Virus detection 390
Serology for CMV 390
Treatment 390
Epidemiology 390
Control 391
Human herpesviruses 6 and 7 391
Description 391
Pathogenesis and clinical features 391
Exanthem subitum (roseola infantum) 391
Neurological disease 392
Other associations 392
Laboratory Investigation 392
Treatment 392
Epidemiology 392
Human herpesvirus 8 (Kaposi’s sarcoma–associated herpesvirus) 392
Kaposi’s sarcoma 393
Body cavity–associated B lymphoma/primary effusion lymphoma/multicentric Castleman’s disease 393
Laboratory Investigation 393
Epidemiology 393
Treatment and control 394
Cercopithecine herpesvirus 1 (herpesvirus B; B virus; herpesvirus simiae) 394
Description 394
Diagnosis and treatment 394
Prevention of B virus infection 394
Recommended reading 395
Websites 395
MCQs 395.e1
Clinical scenario 395.e2
Key points 395.e2
39 Poxviruses 396
Key points 396
Description 396
Classification 396
The virion 397
The genome 398
Replication 398
Clinical features 398
Control of smallpox 398
Before vaccination 398
Vaccination 398
The eradication campaign 398
Smallpox and bioterrorism 399
Other human poxvirus infections 399
Molluscum contagiosum 399
Monkeypox 400
Parapoxvirus infections 400
Vaccinia 400
Vaccinia virus as a vaccine vector 400
Myxomatosis: an evolving disease 400
Recommended reading 401
MCQs 401.e1
Clinical scenario 401.e2
Smallpox, London, 1973. A case report 401.e2
40 Papillomaviruses 402
Key points 402
Description 402
Introduction including classification and major features 402
Classification 402
Genome organisation 402
Epidemiology 403
Major patterns including reservoir and transmission 403
Replication 404
Life cycle 404
Transformation 405
Clinical features and pathogenesis 406
HPV infections 406
Cutaneous warts 406
Anogenital warts 406
Orolaryngeal warts 407
Recurrent respiratory papillomatosis (RRP) 407
Oral papillomatosis 408
HPV and cancer 408
Cervical cancer (CC) 408
Anal and penile cancer (AC) 408
Vulvar and vaginal cancer 409
Squamous cancers of the head and neck 409
Diagnosis 409
Clinical and morphological identification 409
Serology 409
Molecular detection 409
Treatment and control 409
Vaccines 410
Acknowledgment 410
Recommended reading 410
MCQs 410.e1
Clinical scenario 410.e2
HPV 410.e2
Comments 410.e2
41 Polyomaviruses 411
Key points 411
Introduction 411
Replication and transformation 411
Clinical features and pathogenesis 411
Haemorrhagic cystitis (HC) 412
Polyomavirus-associated nephropathy (PVAN) 412
Progressive multifocal leuco-encephalopathy (PML) 412
Laboratory Investigation 413
Transmission and epidemiology 413
Treatment 413
Recommended reading 414
MCQs 414.e1
Clinical scenario 414.e2
42 Hepadnaviruses 415
Key points 415
Hepatitis B virus 415
Structure 415
Genetic variation 416
Stability 416
Replication 417
Acute infection 417
Pathology of acute infection 417
Chronic infection 417
Pathology and pathogenesis of chronic infection 419
Hepatocellular carcinoma (HCC) 419
HBV variants 419
HBsAg variants 420
HBcAg variants 420
Polymerase variants 420
Laboratory Investigation 420
Acute infection 420
Chronic infection 421
Treatment 421
Epidemiology 422
Control 423
Passive immunization 423
Active immunisation 423
Who should be immunised? 423
The delta agent (hepatitis D virus, HDV) 424
Clinical features and pathogenesis 424
Diagnosis 424
Epidemiology 424
Treatment and control 425
Recommended reading 425
Websites 425
MCQs 425.e1
Clinical Scenario 425.e2
43 Parvoviruses 426
Key points 426
Description 426
Epidemiology 426
Replication 427
Pathogenesis 427
Clinical features 429
Minor illness or subclinical infection 429
Rash illness 429
Joint disease 429
Transient aplastic crisis (TAC) 430
Persistent infection in the immunocompromised 431
B19V in pregnancy 431
Other 431
Diagnosis (Table 43.2) 431
Clinical 431
Cultivation 431
Molecular 431
Immunological 432
Investigations during pregnancy and infection in the foetus 432
Treatment (Table 43.2) 433
Control 433
Acknowledgment 433
Recommended reading 434
Website 434
MCQs 434.e1
Clinical Scenario 434.e2
44 Picornaviruses 435
Key points 435
Enteroviruses 435
Description and classification 435
Composition 436
Properties of enteroviruses 436
Replication 437
Clinical features 437
Paralytic poliomyelitis 437
Viral meningitis 438
Encephalitis 438
Neonatal infections 438
Epidemic pleurodynia 438
Myocarditis, pericarditis and dilated cardiomyopathy 438
Herpangina 439
Maculopapular rash 439
Hand, foot and mouth disease 439
Respiratory infections 439
Conjunctivitis 440
Pathogenesis 440
Epidemiology and transmission 440
Prevention and control 440
Immunisation 440
Inactivated polio vaccine (Salk vaccine) 441
Live-attenuated oral polio vaccine (Sabin vaccine) 442
Global eradication 442
Prospects for the future 443
Rhinoviruses 443
Properties 443
Classification 444
Stability 444
Replication 444
Clinical features and pathogenesis 444
Immunity 445
Epidemiology and transmission 445
Parechoviruses 445
Properties 445
Clinical features 445
Epidemiology 446
Laboratory Investigation of enterovirus, rhinovirus and parechovirus infections 446
Culture 446
Molecular methods 446
Serological tests 447
Treatment and control of enterovirus, rhinovirus and parechovirus infections 447
Hepatoviruses 447
Hepatitis a virus 447
Clinical features 448
Pathogenesis 448
Laboratory investigation 448
Epidemiology 448
Prevention and control 448
Recommended Reading 449
Websites 449
MCQs 449.e1
Clinical scenario 449.e3
45 Orthomyxoviruses 450
Key points 450
Influenza A, B and C host range 450
Nomenclature 451
Physical characteristics 451
The viruses 451
Virus variability 453
Epidemic and pandemic influenza 453
Cross-species influenza a infection 454
Zoonotic transmission to humans 455
Human seasonal influenza A, B and C infections 456
Clinical features in human seasonal influenza A infection 457
Complications of human seasonal influenza 457
Clinical features in zoonotic influenza A infections 457
Clinical features in human seasonal influenza B infection 458
Influenza C 458
Seasonal influenza a epidemics 458
Pathogenesis 458
Immunity 459
Laboratory investigation 459
Serology 459
Treatment 459
Control measures 461
Infection control 461
Immunisation 461
Global surveillance 462
Recommended reading 463
Websites 463
Clinical scenario 463.e1
Influenza 463.e1
Learning points 463.e1
MCQs 463.e2
46 Paramyxoviruses and Pneumoviruses 464
Key points 464
Structure and replication 464
Structure 464
Replication 466
The paramyxoviridae 466
Parainfluenza viruses 466
Classification 466
Clinical features and pathogenesis 467
Laboratory investigation 467
Epidemiology and transmission 467
Mumps virus 467
Description 467
Clinical features and pathogenesis 468
Laboratory investigation 468
Detection and isolation 468
Serology 468
Epidemiology 468
Control 469
Measles virus 469
Description 469
Clinical features and pathogenesis 469
Laboratory investigation 470
Epidemiology 470
Control 470
Nipah and hendra viruses 471
The pneumoviridae 471
Human respiratory syncytial virus 471
Description 471
Clinical features 471
Laboratory investigation 472
Detection and isolation 472
Serology 472
Treatment 472
Epidemiology 472
Control 473
Human metapneumovirus 473
Description 473
Clinical features 473
Laboratory investigation 473
Epidemiology 473
Treatment and control 474
Acknowledgment 474
Recommended reading 474
MCQs 474.e1
Clinical scenario 474.e2
47 Arboviruses: alphaviruses, flaviviruses and bunyaviruses 475
Key points 475
Description 475
Classification 475
Properties 476
Replication 477
Alphaviruses 477
Flaviviruses 478
Bunyaviruses 478
Pathogenesis 478
Clinical features 479
Encephalitis 479
Yellow fever 479
Dengue 479
Dengue haemorrhagic fever 480
Miscellaneous tropical fevers 481
Undifferentiated fever 481
Hantavirus pulmonary syndrome 481
Congenital Zika Syndrome 481
Laboratory Investigation 481
Virus isolation 481
Arbovirus-specific RNA detection 481
Serology 482
Treatment 482
Epidemiology 482
Natural cycles 482
Alphaviruses 482
Western equine encephalitis virus 482
Eastern equine encephalitis virus 483
Venezuelan equine encephalitis virus 483
Ross River virus 484
Chikungunya virus 485
O’nyong-nyong virus 485
Flaviviruses: mosquito-borne 485
St. Louis encephalitis virus 485
Japanese encephalitis virus 485
West Nile virus 485
Usutu virus 486
Murray Valley encephalitis virus 486
Yellow fever virus 486
Dengue viruses 486
Zika virus 487
Flaviviruses: tick-borne 487
Powassan virus 487
Tick-borne encephalitis viruses 487
Bunyaviruses: Bunyavirus genus 488
California (CAL) serogroup 488
Oropouche (ORO) 488
Garissa virus 488
Bunyaviruses: Phlebovirus genus 488
Rift Valley fever virus 488
Severe fever with thrombocytopenia syndrome virus 489
Sandfly fever group 489
Toscana virus 489
Bunyaviruses: Nairovirus genus 489
Crimean–Congo haemorrhagic fever virus 489
Bunyaviruses: Hantavirus genus 489
Hantaan and Puumala viruses 489
Sin Nombre virus 489
Control 490
Vector control 490
Vaccines 490
Alphaviruses 490
Flaviviruses 490
Bunyaviruses 491
Recommended reading 491
MCQs 491.e1
Clinical scenario 491.e2
Yellow fever case history 491.e2
Examination 491.e2
Laboratory tests 491.e2
Management 491.e2
Comments 491.e2
48 Hepatitis C virus 492
Key points 492
Properties 492
Structure 492
Replication 492
Classification 494
Virus stability 494
Diagnosis 494
Serological diagnosis 494
Direct detection methods 495
Genetic variation 496
Epidemiology 496
Clinical features 496
Acute hepatitis 497
Chronic hepatitis 497
Extrahepatic manifestations 497
Treatment and control 497
Treatment 497
Prevention 499
Immunisation 500
Recommended reading 500
MCQs 500.e1
Clinical Scenario 500.e2
Learning points 500.e2
49 Hepeviruses 501
Key points 501
Description 501
Epidemiology 501
Developing world 501
Developed world 503
Replication 503
Clinical features 504
Acute HEV infection 504
Chronic HEV infection 504
Extrahepatic manifestations 504
Diagnosis 504
Treatment 505
Control 506
Immunisation 506
Reducing exposure 506
Transfusion-transmitted HEV 506
Recommended reading 506
MCQs 506.e1
Clinical scenario 506.e2
50 Arenaviruses and filoviruses 507
Key points 507
Arenaviruses 507
Introduction 507
Properties 508
Replication 508
Clinical features and pathogenesis 510
Lymphocytic choriomeningitis virus 510
Lassa fever 510
South American haemorrhagic fever 511
Diagnosis 512
Genome detection 512
Antigen detection 512
Serology 512
Virus isolation 512
Treatment 512
Epidemiology and transmission 513
Control 513
Filoviruses 513
Introduction 513
Properties 513
Replication 514
Clinical features and pathogenesis 515
Diagnosis 516
Genome detection 516
Antigen detection 516
Serology 516
Virus isolation 516
Treatment 516
Epidemiology and transmission 517
Control 517
Recommended reading 519
MCQs 519.e1
Clinical scenario 519.e2
Ebola Virus Disease 519.e2
51 Reoviruses 520
Key points 520
Rotaviruses 520
Epidemiology 520
Morphology 521
Genome and gene-coding assignments 522
Antigenic and genetic diversity 523
Replication 524
Pathogenesis and immunity 525
Clinical features 525
Laboratory investigation 526
Treatment 526
Control 526
Recommended reading 526
MCQs 526.e1
Clinical scenario 526.e2
History 526.e2
Examination 526.e2
Investigations 526.e2
Management 526.e2
Progress 526.e2
Comment 526.e2
52 Retroviruses 527
Key points 527
Description 527
Classification 527
Genome and gene coding assignment 529
Replication 530
HIV infection 530
Epidemiology of HIV 530
Transmission 531
Sexual intercourse 531
Mother to child 531
Blood and blood products 531
Clinical features 531
Pathogenesis of HIV infection and AIDS 533
Disease progression 534
Paediatric infection 534
Laboratory investigation 534
Tests for anti-HIV 534
Combination assays 535
PCR 535
Treatment 535
Monitoring progress 536
Prevention and control 536
Sexual transmission 536
Mother to child transmission 536
Exposure to blood 537
Vaccines 537
HTLV-I and -II infection 538
Epidemiology and transmission 538
Pathogenesis 538
Clinical features 538
Laboratory investigation 539
Treatment 539
Control 539
Recommended reading 539
Websites 539
MCQs 539.e1
Clinical scenario 539.e3
53 Caliciviruses and astroviruses 540
Key points 540
Description 540
Morphology and classification 540
Caliciviridae 540
Norovirus 540
Sapovirus 541
Astroviridae 541
Major features 541
Norovirus genome organisation 541
Sapovirus genome organisation 542
Astrovirus genome organisation 542
Norovirus structure 542
Sapovirus structure 543
Astrovirus structure 543
Epidemiology 543
Replication 544
Clinical features 544
Diagnosis 545
Clinical 545
Cultivation 545
Antigen detection assays 545
Genome detection assays 545
Treatment 546
Control 546
Recommended reading 546
Websites 547
MCQs 547.e1
Clinical scenario 547.e2
54 Coronaviruses 548
Key points 548
TAXONOMY 548
Properties 549
Morphology and structure 549
Replication 550
Pathogenesis 550
Transmission 551
Epidemiology 551
SARS and MERS coronavirus 551
Clinical features 552
SARS and MERS coronaviruses 552
Gastrointestinal disease caused by coronaviruses and toroviruses 552
Laboratory investigation 552
Case study of the discovery of a new human pathogen, SARS coronavirus 553
Control 554
Treatment 554
Prevention 554
Recommended reading 554
Clinical scenario 554.e1
55 Rhabdoviruses 555
Key points 555
Virus structure and life cycle 555
Virion morphology 555
Virus genome structure 555
Viral life cycle 556
Virus transmission, pathogenesis and treatment 557
Clinical features 558
Epidemiology 558
Laboratory Investigation 559
Diagnostic methods 560
Rabies virus antigen detection techniques 560
Rabies virus isolation 560
Histopathological examination 560
Serological assays 560
Molecular methods for the detection of rabies viral RNA 560
Prevention 561
Vaccination 561
Preexposure prophylaxis 561
Postexposure prophylaxis (PEP) 561
Control 562
Recommended reading 562
Websites 562
MCQs 562.e1
Clinical scenario 562.e3
Human case of rabies-encephalitis 562.e3
Learning points 562.e4
56 Togaviruses 563
Key points 563
Description 563
Epidemiology 563
Replication (virology) 563
Clinical features 564
Postnatal primary rubella 564
Rubella reinfection 564
Congenital rubella 564
Pathogenesis 565
5 Fungal pathogens, parasitic infections and medical entomology 577
58 Fungi 578
Key points 578
Fungal diseases of humans 579
Fungal pathogens 579
Epidemiology 579
Types of infection 579
Superficial mycoses 579
Subcutaneous mycoses 579
Systemic mycoses 579
Incidence 580
Diagnosis 580
Clinical features 580
Laboratory investigation 580
Types of specimen 580
Direct microscopy 580
Histology 581
Culture 581
Serology 581
Polymerase chain reaction 581
Treatment 581
Superficial infections 582
Dermatophytosis 582
Epidemiology 582
Clinical features 583
Laboratory investigation 584
Collection of samples 584
Wood’s lamp 584
Hairbrush sampling 584
Processing of specimens 584
Direct microscopy 585
Culture 585
Treatment and prevention 585
Superficial candidosis 585
Epidemiology 585
Clinical features 586
Mucosal infection 586
Skin and nail infection 586
Chronic mucocutaneous candidosis 586
Laboratory investigation 586
Treatment and prevention 587
Pityriasis versicolor 587
Epidemiology 587
Clinical features 587
Laboratory investigation 587
Treatment 587
Other superficial infections 588
Skin and nail 588
Otomycosis 588
Mycotic keratitis 588
Subcutaneous infections 588
Mycetoma 588
Epidemiology 588
Clinical features 589
6 Diagnosis, treatment and control of infection 639
62 Infective syndromes 640
Key points 640
Specific syndromes 640
Upper respiratory tract 640
Pharyngitis 640
Sinusitis and otitis media 642
Lower respiratory tract 642
Epiglottitis 642
Pneumonia 643
Gastrointestinal infection 644
Acute diarrhoea 644
Intraabdominal sepsis, peritonitis, biliary sepsis and pancreatitis 644
Urinary tract infections 644
Infections of the central nervous system 645
Meningitis 645
Cerebral infections 646
Cardiovascular infections 646
Infective endocarditis 646
Infections associated with intravascular lines 647
Skin and soft tissue infections 647
Genital tract infections 648
Eye infections 648
Infection of bone and joints 649
Infective arthritis 649
Acute osteomyelitis 649
General syndromes 649
Fever of unknown origin 649
Sepsis 650
Travel-associated infections 650
Recommended reading 651
MCQs 651.e1
63 Laboratory investigations 652
Key points 652
Collection of specimens 653
Transport 655
Reception 655
Specimen processing in the laboratory 656
Microscopy 656
Nonculture methods 656
Antigen detection 656
Nucleic acid–based tests 657
Detection of host immunological response to microorganisms 657
Laboratory culture of microorganisms 657
Identification 658
Point-of-care testing 659
Antimicrobial susceptibility testing 659
Communication of results of laboratory investigations 659
Notification of infectious diseases 660
Recommended reading 660
MCQs 660.e1
64 Molecular methods in diagnostic microbiology 661
Key points 661
Introduction 661
Molecular diagnostics—the historical perspective 661
Molecular techniques—the gold standards 662
Global trends in molecular techniques 662
Molecular techniques: polymerase chain reaction (PCR) 662
Molecular characterisation 664
Selective fragment amplification typing methods 664
Developments in selective fragment amplification typing methods 664
Gel-based characterisation methods 664
Pulsed-field gel electrophoresis 665
Restriction fragment length polymorphism 665
Multiple-locus enzyme electrophoresis 665
Amplified fragment length polymorphism 665
Single-stranded conformational polymorphism analysis 666
Sequence-based detection and typing methods 666
Multilocus sequence typing 666
Matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) analysis 668
Pyrosequencing 668
Microarrays 669
Whole genome sequencing 669
Key challenges for the future 669
Recommended reading 670
MCQs 670.e1
65 Management of antimicrobial chemotherapy 671
Key points 671
Principles of antimicrobial therapy 671
Principles of in vitro susceptibility testing and the different methods 672
Empiric and directed therapy 675
Selecting the right agent 676
Pharmacodynamics 677
Principles of using antimicrobials agents in prophylaxis 678
Antimicrobial stewardship 678
Recommended Reading 680
Websites 680
MCQs 680.e1
66 Epidemiology and control of community infections 681
Key points 681
Introduction 681
Epidemiological principles 682
Definitions 682
The microorganism 682
The host 683
Herd immunity 683
The environment 683
Socioeconomic development and infection 683
Climate change 683
The spread of infection 683
Efficacy of transmission 683
Spread of infections 684
Infection spread directly from one person to another 684
Infection in which healthy carriers are involved 684
Infection in which persons harbour the organism before the onset of clinical illness 684
Infection derived from animal sources 684
Infections derived from environmental sources 684
Outbreaks of infection 685
Nomenclature of outbreaks 685
Types of outbreaks 685
Point source outbreak 685
Continuous common-source outbreak 685
Intermittent common-source outbreak 686
Propagated outbreak 686
Mixed outbreak 686
Analysis of outbreaks 686
Investigation of outbreaks 687
The application of new technologies to outbreak investigations 688
Control of outbreaks 688
Sources of infection 688
Route of transmission 689
Persons at risk 690
Mathematical models 690
Association and causation of infection 690
Conclusion 691
Acknowledgments 691
Recommended reading 691
Websites 692
MCQs 692.e1
67 Healthcare–associated infections 693
Key points 693
Definition and classification 693
Epidemiology 694
Sources 694
Patients and staff as a source of infection 695
Inanimate reservoirs of infection 695
Role of antibiotic treatment 695
Common infections 695
Common organisms 695
Routes of transmission 696
Airborne transmission 696
Contact spread 696
Foodborne spread 697
Bloodborne spread 697
Prevention and control 697
Exclusion of sources of microorganisms from health-care settings 697
Interrupting spread of microorganisms from source to susceptible hosts 698
Enhancing the host’s ability to resist infection 699
Infection control policy 699
Surveillance and the role of the laboratory 699
Efficacy of infection control 699
Recommended reading 700
Websites 700
MCQs 700.e1
68 Immunisation 701
Key points 701
Rationale of immunisation 701
Passive immunization 701
Pooled immunoglobulins 702
Specific immunoglobulins 702
Active immunisation 702
Types of vaccines 702
Toxoids 702
Inactivated killed vaccines 702
Attenuated live vaccines 702
Special procedures 702
Immune response 702
Duration of immunity 703
Age of commencement of active immunisation 703
Controlled studies of vaccines 703
Contraindications to the use of vaccines 703
Hazards of immunisation 704
Site of injection 704
Herd immunity 705
Immunisation programmes 705
Immunisation schedules 705
Notes on common vaccines in use 705
Adsorbed tetanus and diphtheria toxoid 705
Pertussis vaccine 705
Poliomyelitis vaccines 707
Haemophilus influenzae type B (Hib) vaccine 707
Meningococcal vaccines (MenC, Men B, MenACWY) 707
Pneumococcal vaccines 707
Measles, mumps and rubella (MMR) vaccine 708
Rotavirus 708
Human papillomavirus vaccine types 6, 11, 16 and 18 (HPV) 708
Hepatitis B vaccine 708
BCG 709
Other vaccines 709
Protecting the traveller 709
Unresolved problems 709
Recommended reading 710
Websites 710
MCQs 710.e1
Index 711
A 711
B 713
C 715
D 719
E 720
F 721
G 722
H 723
I 725
J 727
K 727
L 727
M 728
N 731
O 732
P 732
Q 735
R 735
S 736
T 739
U 741
V 741
W 742
X 743
Y 743
Z 743
Inside Back Cover ibc1