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

Preface 6
Acknowledgments 7
Contents 8
Contributing Authors 16
1 Emerging Infections and Children: Influenza and Acute Necrotizing Encephalopathy 29
1. Introduction 29
2. Epidemiology of Influenza 30
3. Mortality from Influenza 31
4. Influenza-Associated Acute Necrotizing Encephalopathy 32
4.1. An Illustrative Case 32
4.2. History of Emergence of Acute Necrotizing Encephalopathy 33
4.3. Clinical Manifestations of ANE 34
4.4. Pathogenesis of ANE 35
4.5. Suggestions 36
References 36
2 Chickenpox Party or Varicella Vaccine? 38
1. Introduction 38
2. VZV Disease in Unvaccinated Populations 38
3. Varicella Vaccine 40
3.1. Safety, Immunogenicity, and Efficacy 40
3.2. The US Varicella Vaccination Program: Design and Coverage 41
3.3. Impact of the US Varicella Vaccination Program 42
4. Issues of Concern in the Varicella Vaccine Era 44
4.1. Identification and Vaccination of Varicella-Susceptibles 45
4.2. Breakthrough Varicella 45
4.3. Herpes Zoster 46
5. Summary 47
References 48
3 The ABC of Epstein-Barr Virus Infections 52
1. Introduction 52
2. Epidemiology and Model of Human Infection 53
2.1. Epidemiology 53
2.2. Model of Human Infection 54
3. EBV-Related Syndromes 54
3.1. Infectious Mononucleosis 55
3.2. X-Linked Lymphoproliferative Syndrome 57
3.3. B-Cell Lymphoproliferative Disorders 57
3.4. Chronic Active EBV Infection 57
4. Diagnostic Tests 57
4.1. Serologic Tests 57
4.2. Nucleic Acid Detection 58
5. EBV and the Immune System 58
5.1. EBV-Encoded Genes in Different States of EBV Infection 58
5.2. Evasion of Immune System 60
5.3. Acquired Disturbances in Immune Surveillance for EBV 60
6. Post-Transplant Lymphoproliferative Disorders 61
6.1. Clinical Manifestations and Diagnosis 61
6.2. PTLD Burden and Associated Risk Factors 62
6.3. Detecting EBV Lymphoproliferation 62
6.4. EBV Viral Load as a Marker of EBV Lymphoproliferation 62
6.5. Treatment of PTLD 63
7. Summary 64
References 64
4 The Immune Response to Viral Lower Respiratory Tract Infection 67
1. Introduction 67
2. Epidemiology and Clinical Aspects 67
2.1. Respiratory Syncytial Virus 68
2.2. Influenza 69
2.3. Adenovirus 70
2.4. Parainfluenza Virus 70
2.5. Rhinovirus 71
2.6. Human Metapneumovirus 71
2.7. SARS Coronavirus 72
3. Immunology of Viral Lower Respiratory Tract Infections 73
3.1. Innate Immunity 73
3.2. Adaptive Immune Response 76
3.3. Immature Immune Response 77
3.4. Genetic Background 77
4. Virus Infection in the Immunocompromised Host 78
4.1. Immunocompromised Patients 78
4.2. Impaired Innate Immune System 79
5. Respiratory Viruses and Asthma 79
5.1. Virus Infections and Asthma Exacerbations 79
5.2. Viral Respiratory Tract Infections and the Inception of Asthma 80
6. Viral Evasion of the Immune System 82
6.1. Viral Entry 82
6.2. The Interferon Antiviral Response 83
6.3. Evasion of Apoptosis 84
6.4. Immune Evasion Techniques by Adenoviruses 84
References 86
5 Chronic Granulomatous Disease: From Genetic Defect to Clinical Presentation 92
1. Introduction 92
2. Biochemistry and Genetics of the NADPH-oxidase and its Deficiency 93
3. Animal Models of CGD 95
4. Roles of ROS in Health and Disease 96
4.1. Microbial Killing 96
4.2. Cell Death Processes 99
4.3. Regulation of Inflammatory Genes 100
4.4. Other Effects of ROS with Possible Implications for the Development and Resolution of Inflammation 101
5. Clinical Characterization of CGD and Current Therapies 102
5.1. Infections 102
5.2. Inflammatory Complications 104
5.3. Current Therapy 105
5.4. Newer Therapies 106
References 107
6 Novel Primary Immunodeficiencies 113
1. Introduction 113
2. Mendelian Susceptibility to Mycobacterial Disease 113
2.1. Complete Interferon- Receptor 1 Deficiency 114
2.2. Complete Interferon- Receptor 2 Deficiency 114
2.3. Partial Recessive IFN R1 and IFN R2 Deficiencies 115
2.4. Partial Dominant IFN R1 Deficiency 115
2.5. IL-12R 1 Deficiency 116
2.6. IL-12 p40 Deficiency 116
2.7. Partial STAT1 Deficiency 117
2.8. Complete STAT1 Deficiency 117
3. Inherited Disorders of the NF- B Signaling Pathway 117
3.1. NEMO Deficiency 118
3.2. I B Deficiency 118
3.3. Interleukin-1 Receptor-Associated Kinase-4 Deficiency 119
4. Conclusion 119
Acknowledgments 120
References 120
7 Periodic Fever 124
1. A Case 124
2. Approach to the Child with Recurring Fevers 125
2.1. History of Episodes and Intervening Periods 125
2.2. Physical Examination 125
2.3. Laboratory Evaluations and Imaging Studies 126
3. Differential Diagnosis of Periodic Fever 126
3.1. Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenopathy 127
3.2. Cyclic Neutropenia 129
3.3. Familial Mediterranean Fever 131
3.4. Hyper-Immunoglobulinemia D and Periodic Fever Syndrome 133
3.5. Tumor Necrosis Factor Receptor-Associated Periodic Syndrome 134
4. Case Denouement and Summary 136
References 136
8 BCG Vaccine 139
1. History of BCG 139
2. Phylogeny of BCG 139
2.1. How BCG Differs from M. bovis 139
3. The Immunological Response to BCG 140
3.1. Host Response to M. tuberculosis 140
3.2. Host Response to BCG 140
4. Efficacy of BCG 142
4.1. Early Studies of BCG Efficacy 142
4.2. BCG Trials 142
4.3. Meta-analyses of BCG Efficacy 144
4.4. Duration of Efficacy of BCG 147
4.5. Explanations for Variability in Observed BCG Efficacy in Trials 147
5. Complications of BCG 150
5.1. Classification of Complications 150
5.2. Frequency of Complications 150
5.3. Specific Complications 151
6. BCG Vaccination Policies 151
6.1. World Health Organization Policy 151
6.2. Policy in the United States 152
6.3. Variations Within Europe 152
6.4. Policy in the United Kingdom 152
7. The Future 154
8. Conclusion 154
References 154
9 Helminth Infections of Children: Prospects for Control 157
1. Introduction 157
2. Global Disease Burden of Helminth Infections 158
3. Anthelminthic Drugs in the Control of Childhood Helminth Infections 161
4. Downstream Alternatives to School-Based De-worming: Rationale and Promise for Developing Anthelminthic Vaccines 162
4.1. Anti-hookworm Vaccines 162
4.2. Anti-schistosomiasis Vaccines 163
5. Conclusions 163
Acknowledgments 164
References 164
10 Rabies on the Doorstep 167
1. Introduction 167
2. Implications of Having Enzootic EBLV in Britain 168
2.1. How prevalent is EBLV among British bats? 168
2.2. Can EBLV be transmitted to other mammals? 168
2.3. How effective are standard rabies vaccines and rabies immune globulin against EBLV? 168
2.4. To whom should pre- and post-exposure prophylaxis be given in the United Kingdom? 169
3. Other Rabies-Related Viruses 169