Hot Topics in Infection and Immunity in Children VII (eBook)

Preface 4
Acknowledgments 5
Contents 6
Contributors 8
The Value of Vaccination 12
1 Population Health and Economic Well-Being 12
2 A New Paradigm for the Value of Vaccination 16
3 Applications of the New Approach 17
4 Two Calls to Action 18
References 19
Recent Trends in Global Immunisation 20
1 Introduction 20
2 Official Development Assistance at the Global Level 20
3 Health Progress is Possible 21
4 The GAVI Alliance, Formerly the Global Alliance for Vaccines and Immunisation 22
5 Polio Eradication Still Somewhat Problematic 23
6 Recent Developments in Malaria 23
7 HIV/AIDS Vaccine A Long Way to Go 24
8 Measles Remains a Threat 25
9 Anti-Vaccine Activists are a Real Danger 25
10 Conclusion 26
References 27
New Advances in Typhoid Fever Vaccination Strategies 28
1 Introduction 28
2 Typhoid Fever Epidemiology 29
3 Typhoid Fever: Clinical Presentation and Outcome 30
3.1 Diagnosis 31
3.2 Management 32
4 Control Strategies 32
4.1 Antimicrobial Resistance 33
4.2 Vaccination 34
4.2.1 Ty21a 36
4.2.2 Vi Capsular Polysaccharide 38
4.2.3 New Vaccines in Pipeline 38
4.3 Perceived Risk of Disease and Vaccination Acceptance 40
4.4 The Market (Vaccine Demand and Supply) 40
4.4.1 Vaccination Strategies 41
4.4.2 Determining Endemicity 42
5 Population Impact 42
5.1 Guangxi Province, China 42
5.2 National Immunization Program, Vietnam 43
5.3 Delhi State, India 44
5.4 Disease of Most Impoverished (DOMI) Studies in South and SouthEast Asia 44
6 Conclusion 46
References 46
Prevention of Vertical Transmission of HIVin Resource-Limited Countries 51
1 Introduction Global Status of Efforts to Prevent Vertical Transmission of HIV 51
2 Program Experience 52
2.1 Thailand and Botswana National Programs 52
2.1.1 Thailand 52
2.1.2 Botswana 53
2.2 Elizabeth Glaser Pediatric AIDS Foundation Program and Experience 53
3 Lessons Learned 56
3.1 Counseling 56
3.2 Testing 56
3.3 ARV Prophylaxis 56
3.4 Uptake of Maternal and Infant Prophylaxis 57
3.5 HIV Testing in Labor and Delivery 58
4 Modeling Service Coverage 58
4.1 2000--2002 60
4.2 2003--2005 60
4.3 2006--2008 61
5 Effectiveness of Prevention of Vertical Transmission Programs: The PEARL Study 61
6 Importance of Identifying Pregnant Women Eligible for ART 62
7 Prevention of Vertical Transmission During Breastfeeding 63
8 Conclusion 65
References 65
Pneumonia in Children in Developing Countries 68
1 Introduction 68
2 Aetiology 68
3 Standard Management 69
4 Which Children Need an Antibiotic 70
5 Which Children Need Admission 71
6 Which Children Have Very Severe Pneumonia 71
7 Which Antibiotic for Outpatients With Non-severe Pneumonia 72
8 Which Antibiotics for Severe Pneumonia 73
9 Which Antibiotics for Very Severe Pneumonia 74
10 Oxygen Therapy 75
11 Fluid Therapy 75
12 Fever 75
13 Neonates, Malnutrition and HIV 76
14 Overall Effect of Case Management 76
15 Immunisation 76
16 Conclusion 77
References 80
Darwin, Microbes and Evolution by Natural Selection 85
1 Darwin, Microbes and Evolution by Natural Selection 85
Box 1 92
References 93
Human Herpesvirus 6 95
References 98
Advances in the Diagnosis and Management of Central Venous Access Device Infections in Children 99
1 Introduction 99
2 Types of Devices Used in Children for Central Venous Access 100
2.1 Temporary CVAD 100
2.2 Permanent, Tunnelled CVAD 100
3 Pathogenesis 101
3.1 Common Organisms 101
4 Epidemiology 102
5 Diagnosis 103
6 Prevention 104
7 Management 105
7.1 Antimicrobial Therapy 105
7.2 New Strategies 106
8 Antimicrobial Lock Therapy (ALT) 106
9 Ethanol Locks 107
10 Hydrochloric Acid Locks 107
11 Taurolidine Citrate Locks (TauroLock) 109
12 Urokinase Locks and Infusions 109
13 Conclusions 109
References 110
Moraxella catarrhalis -- Pathogen or Commensal? 115
1 Introduction 116
2 Phylogenetic Evidence for Virulence 116
3 Expression of Virulence Factors 117
3.1 Complement Resistance 117
3.2 Adherence to Human Epithelial Cells 117
3.3 Colonization and Immune Response 118
3.4 Biofilm Formation 119
3.5 Cellular Invasion 120
3.6 Proinflammatory Activity of Moraxella catarrhalis 120
4 Cold Shock Response of Moraxella catarrhalis 120
5 Summary 122
References 122
Anaerobic Infections in Children 125
1 Introduction 125
2 Microbiology 126
2.1 Gram-Positive Spore-Forming Bacilli 126
2.2 Gram-Positive Non-Spore-Forming Bacilli 128
2.3 Gram-Negative Bacilli 129
2.4 Gram-Positive Cocci 130
2.5 Gram-Negative Cocci 130
3 Pathogenicity and Virulence 130
3.1 Anaerobes as Normal Flora 130
3.2 Conditions Predisposing to Anaerobic Infection 132
3.3 Virulence Factors 134
4 Diagnostic Microbiology 134
4.1 Collection of Specimens for Anaerobic Bacteria 134
4.2 Transportation of Specimens 136
4.3 Laboratory Diagnosis 136
4.4 Antimicrobial Susceptibility Testing 137
5 Prevention 137
6 Clinical Infections 138
6.1 Central Nervous System Infections 138
6.2 Head and Neck Infections 139
6.2.1 Sinusitis 141
6.2.2 Parotitis 141
6.2.3 Cervical Lymphadenitis 141
6.2.4 Thyroiditis 142
6.2.5 Infected Cysts 142
6.2.6 Wound Infection After Head and Neck Surgery 142
6.2.7 Tonsillitis 142
6.3 Pleuropulmonary Infections 143
6.4 Intra-Abdominal Infections 145
6.5 Female Genital Tract Infection 146
6.6 Skin and Soft Tissue Infections 146
6.7 Osteomyelitis and Septic Arthritis 147
6.8 Bacteremia 148
6.9 Neonatal Infection 148
7 Management 149
7.1 Hyperbaric Oxygen 149
7.2 Surgical Therapy 149
7.3 Antimicrobial Therapy 150
7.4 Antimicrobial Agents 153
7.4.1 Penicillins 153
7.4.2 Cephalosporins 154
7.4.3 Carbapenem (imipenem, meropenem) 154
7.4.4 Chloramphenicol 155
7.4.5 Clindamycin and Lincomycin 155
7.4.6 Metronidazole 155
7.4.7 Macrolids (Erythromycin, Azithromycin, Clarithromycin) 155
7.4.8 Glycopeptides (Vancomycin, Teicoplanin) 155
7.4.9 Tetracyclines 156
7.4.10 Quinolones 156
7.5 Choice of Antimicrobial Agents 156
References 157
Encephalitis Diagnosis and Management in the Real World 161
1 Approach to Focusing Possible Etiologies 161
1.1 Pathogenesis 161
1.2 Prioritizing Treatable Etiologies 163
1.3 Etiologically Focussed Prevention of Acute Encephalitis 165
1.4 Season, Geography, and Epidemiology of Viral Encephalitis 166
1.5 Studies of Causes of Acute Encephalitis 169
1.6 Additional Noteworthy Diagnoses 172
1.6.1 Acute Disseminated Encephalomyelitis (ADEM) 172
1.6.2 Acute Necrotizing Encephalopathy (ANE) 174
1.7 Additional Noteworthy Pathogens 175
1.7.1 B. burgdorferi 175
1.7.2 Parvovirus B19 175
1.7.3 Balamuthia mandrillaris 176
1.8 Specific Clinical Neurologic Syndromes 176
2 Approach to Empiric Management 176
References 179
Toxic Shock Syndrome -- Evolution of an Emerging Disease 182
1 Introduction 182
2 Epidemiology 182
3 Pathogenesis 182
4 Clinical Findings 183
5 Management 184
6 Prognosis 185
References 186
Dissection of B-Cell Development to Unravel Defectsin Patients with a Primary Antibody Deficiency 189
1 Introduction 189
2 Generation of Nave Mature B Cells by Stepwise Differentiation in Bone Marrow 189
3 Antigen-Dependent B-Cell Maturation in Secondary Lymphoid Organs 191
4 Dynamics in the Peripheral B-Cell Compartment During Early Childhood 194
5 Antibody Deficiencies 194
5.1 Agammaglobulinemia 195
5.2 B-Cell Antigen Receptor Signaling Deficiency 198
5.3 IgCSR Deficiency 198
5.4 Common Variable Immunodeficiencies (CVID) 199
6 Conclusion 200
References 200
Mumps is Back: Why is Mumps EradicationNot Working? 203
1 Introduction 203
2 Mumps: The Clinical Presentation 204
3 Mumps: The Virus 205
4 Mumps: The Pathogenesis and Transmission 207
5 Mumps: The Diagnosis 207
5.1 Mumps: Laboratory Diagnosis for Mumps Infection 208
5.1.1 Specimen Collection 208
5.1.2 Tissue Culture 208
5.1.3 Molecular Testing 209
5.1.4 IgM Serology 209
5.1.5 IgG Serology 210
6 Mumps: The Epidemiology 211
7 Mumps: The Vaccines 212
8 Mumps: Recent Resurgence 213
8.1 Vaccine Program: Refusal to Accept Immunization: 2007--2008 Outbreak in the Netherlands 214
8.2 Vaccine Program: Failure to Immunize an Age Group: --Lost Cohort--: 2004--2006 Outbreak in United Kingdom 214
8.3 Vaccine Program: Single Dose: Forgotten Cohort 2004--2007 Outbreaks in Canada, 2005--2007 in Australia 217
8.4 Vaccine Failure: Primary Vaccine Failure: Ineffective Vaccine -- Rubini 218
8.5 Vaccine Failure: Two-dose Vaccine Failure: Waning Immunity: 2006 Outbreaks in the United States 219
9 Mumps Elimination in Finland 219
10 Mumps: Public Health Control Strategies in Outbreaks 220
11 Mumps Outbreaks: Lessons Learned 220
12 Mumps Control: Unanswered Questions 221
13 Summary 222
References 222
Neonatal Herpes Simplex Virus Infections: Where Are We Now 227
1 Background 227
2 Epidemiology of Neonatal HSV 228
3 Clinical Manifestations of Neonatal HSV 228
4 Mortality and Morbidity 228
5 Antiviral Therapy 229
6 Determining Dosage and Duration of Treatment 230
7 Polymerase Chain Reaction (PCR)-Guided Therapy 230
8 Oral Suppression Therapy 233
9 Antiviral Resistance 234
10 Conclusion 235
References 235
Rational Approach to Pediatric Antifungal Therapy 237
1 Introduction 237
2 Treatment of Pediatric Invasive Aspergillosis 238
2.1 Voriconazole Dosing in Children 240
2.2 Combination Therapy for Invasive Aspergillosis 242
3 Treatment of Pediatric Invasive Candidiasis 243
4 Conclusion 246
References 246
Antiviral Therapy of CMV Disease in Children 249
1 Spectrum of Clinical Disease 249
1.1 Congenital CMV 249
1.1.1 Clinical Features 250
1.1.2 Predicting Long-Term Neurological Impairment 251
1.2 PostNatal CMV 252
1.2.1 Clinical Features 252
1.3 CMV Disease in Older Children 252
2 Ganciclovir and Valganciclovir Use in Children 253
2.1 Pharmacokinetics 253
2.1.1 Ganciclovir 253
2.1.2 Valganciclovir 254
2.1.3 CSF and CNS Penetration 255
2.2 Pharmacodynamics 255
2.3 Resistance 256
2.4 Drug Levels 257
2.5 Safety 257
3 Clinical Studies of GCV in Childhood CMV Infection 258
3.1 Congenital CMV 258
3.2 Clinical Use of GCV in Postnatal CMV Infection 262
3.3 CMV Disease and GCV Treatment in Older Immunocompromised Children 262
4 Summary 263
References 263
Infectious Hazards from Pets and Domestic Animals 267
1 Introduction 267
2 Global Trends in Emerging Infectious Diseases (EID) 268
3 Pets and Domestic Animals as Reservoirs of Antimicrobial Resistance (AMR) 270
4 Staphylococcus intermedius in Pets 271
5 MRSA in Pets and Domestic Animals 273
6 A Call for an Action 274
7 Pets and Immunocompromised Hosts 275
8 Conclusion 275
References 276
Novel Technology to Study Co-Evolution of Humans StaphylococcusINTtie aureus: Consequences for Interpreting theINTtie
1 Introduction 279
2 The Microorganism 280
2.1 Detection and Identification 280
2.2 Habitat and Genome Complexity 280
3 The Host 281
3.1 Human Niches 281
3.2 Patterns of and Susceptibility to Carriage 282
4 Artificial Colonisation Studies 282
4.1 Setting Up a Nasal Colonisation Study 283
4.2 Examples of Previous Colonisation Studies 284
4.3 Ongoing Experiments and Ideas for Future Colonisation Studies 285
5 Example Of A Cohort Study 286
5.1 Relevance of Cohort Studies 286
5.2 Microbiology in Generation R 286
5.3 Preliminary Results 287
6 Humoral Immunity and S. aureus Carriage and Infection 288
6.1 Technical Aspects of Multiplex Anti-staphylococcal Antibody Measurements 288
6.2 Application of the Luminex Technology and Microbiological Implications 288
7 Conclusion 290
References 290
A Practical Approach to Eosinophilia in a Child Arriving orINTtie Returning From the Tropics
1 Introduction 295
2 Why it is Often Difficult to Determine the Parasite Causing Eosinophilia 295
2.1 Patients with Helminthic Infection may be Asymptomatic 295
2.2 Patients with Eosinophilia may have a Helminthic Infection that is too Early to Diagnose 296
2.3 It is Difficult to Distinguish Between Different Helminthic Infections by Either Degree or Persistence of Eosinophilia 296
2.4 Whether a Child is an Immigrant or Returned Traveller does not help to Distinguish Between Different Helminthic Infections 297
2.5 Serum IgE Level does not help to Distinguish Between Different Helminthic Infections or Exclude a Non-Parasitic Cause for Eosinophilia 298
2.6 Patients with Helminthic Infection may not have Eosinophilia 298
2.7 The Degree of Eosinophilia does not Necessarily Relate to the Burden of Infection 299
2.8 Negative Investigations for Parasites do not Exclude Helminthic Infection 299
2.9 Eosinophilia may Worsen Despite Appropriate Treatment 300
2.10 Patients from a Tropical Country may have an Alternative Explanation Other than Helminthic Infection for Their Eosinophilia 300
3 An Approach to Diagnosing and Treating Parasitic Infections in Children with Eosinophilia Returning From Tropical Countries 300
3.1 History 301
3.2 Investigations 302
3.3 Treatment 304
References 304
Subject Index 306