Avian Influenza: The Threatening Pandemic

Table of Contents for Avian Influenza: The Threatening Pandemic

Table of Contents:

1. Overview 6
1.1 Statement of Report 6
1.2 Scope of Report 6
1.3 Objectives 7
1.4 Methodology 7
1.5 Executive Summary 8
2. The Basics of Human Influenza 12
2.1 Influenza, the Disease 12
2.1.1 Symptoms 12
2.1.2 Transmission 12
2.1.3 Public Health Factors 13
2.1.4 Influenza Diagnosis 13
2.2 Influenza Viruses 15
2.2.1 Types, Subtypes, and Strains 15
2.2.1.1 Influenza Type A and Its Subtypes 15
2.2.1.2 Highly Pathogenic versus Lowly Pathogenic Avian Influenza A Viruses 16
2.2.1.3 Human Influenza Viruses and Avian Influenza A Viruses 16
2.2.1.3.1 Influenza A H5 17
2.2.1.3.2 Influenza A H7 17
2.2.1.3.3 Influenza A H9 17
2.2.1.4 Influenza Type B 17
2.2.1.5 Influenza Type C 17
2.2.2 How Influenza Viruses Change: Drift and Shift 18
2.2.3 Seasons and Human Influenza 19
2.2.4 Risk Factors and Human Influenza 20
2.2.5 Human Influenza Complications, Comorbidities and Dangers 20
2.2.5.1 Flu complications in children and teenagers 21
2.2.6 Human Influenza Prognosis 21
2.3 Pandemic Influenza 22
2.4 How Influenza Viruses Change 22
3. The Basics of Avian Influenza 24
3.1 Avian Influenza versus Human Influenza 24
3.2 Avian Influenza in Birds 24
3.2.1 Avian Influenza Outbreaks in Poultry 26
3.2.2 More information about avian influenza viruses 26
3.3 Transmission of Influenza A Viruses between Animals and People 26
3.4 Avian Influenza Infection in Humans 27
3.4.1 Instances of Avian Influenza Infections in Humans 28
3.4.2 Symptoms of Avian Influenza in Humans 29
3.4.3 Antiviral Agents for Influenza 29
3.5 Avian Influenza (H5N1) 29
3.6 Avian Influenza (H5N1) Outbreaks 29
3.7 All Types of Avian Influenza (Not Just H5N1) Worldwide Outside of Asia 31
3.7.1 Canada 31
3.7.2 Netherlands 32
3.7.3 United States 33
3.7.3.1 Delaware 33
3.7.3.2 Texas 33
3.7.3.3 Maryland 33
3.7.3.4 International Response 34
3.7.3.5 Available options 34
4. Epidemiology of Avian Influenza 35
4.1 Worldwide Avian Influenza 37
4.2 H5N1 avian influenza: timeline 41
4.3 U.S. Avian Influenza 48
5. Influenza Diagnosis & Laboratory Issues 49
5.1 "Classic" Methods for Influenza Diagnosis 49
5.2 Example Lab: Yale New Haven Hospital (YNHH) 51
5.3 Conventional PCR Assay for Sub-typing Influenza Virus 52
5.3.1 Gel Analysis 52
5.4 Real Time TaqMan PCR 55
5.4.1 From PacMan to TaqMan - a computer game revisited 55
5.4.2 The advantages of real-time TaqMan PCR over conventional quantitative PCR 58
5.5 Example Strategy for Avian Influenza 59
5.6 Laboratory safety issues for H5N1 viruses 59
5.6.1 Biosafety Level 3 59
5.6.2 Biosafety Level 3 -Ag 63
5.6.3 CDC Criteria for testing 64
5.6.4 What samples are needed? 65
6. Preparedness 66
6.1 Education 66
6.2 Ethical and Legal Issues 68
6.3 Worldwide 71
6.3.1 Overarching goals, objectives and actions for WHO and national authorities, by phase 71
6.3.1.1 Interpandemic period, phase 1 - Overarching goal 72
6.3.1.2 Interpandemic period, phase 2 - Overarching goal 74
6.3.1.3 Pandemic alert period, phase 3 - Overarching goal 77
6.3.1.4 Pandemic alert period, phase 4 - Overarching goal 79
6.3.1.5 Pandemic alert period, phase 5 - Overarching goal 82
6.3.1.6 Pandemic period, phase 6 - Overarching goal 84
6.3.2 Recommendations for non-pharmaceutical public health interventions 88
6.4 U.S. 92
6.4.1 U.S. National Plan 92
6.4.2 U.S. Locally 101
6.4.2.1 Community Preparedness Leadership and Networking 101
6.4.2.2 Surveillance 102
6.4.2.3 Public Health and Clinical Laboratories 102
6.4.2.4 Healthcare and Public Health Partners 103
6.4.2.5 Infection Control and Clinical Guidelines 103
6.4.2.6 Vaccine Distribution and Use 104
6.4.2.7 Antiviral Drug Distribution and Use 104
6.4.2.8 Community Disease Control and Prevention 104
6.4.2.9 Public Health Communications 105
6.4.2.10 Workforce Support: Psychosocial Considerations and Information Needs 105
6.4.2.11 State Plans 106
6.5 The Hospital Response 106
6.5.1 Introduction 106
6.5.2 Key Assumptions 106
6.5.3 Arrival 106
6.5.4 Triage 108
6.5.5 Isolation 109
6.5.6 Patient Movement 110
6.5.7 Communication 110
6.5.8 Medical Evaluation 111
6.5.9 Diagnosis 111
6.5.10 Treatment 112
6.5.11 Potential for Surge 112
6.6 Business Preparedness 113
6.7 School Preparedness 115
6.8 Individual Preparedness 118
7. Economics of Avian Influenza 122
7.1 Impact on Governments 122
7.1.1 Worldwide Economic Impact of Avian Flu 122
7.1.2 U.S. Nationally 126
7.2 Impact of a Pandemic 138
7.2.1 Supply Side Effect 138
7.2.2 Demand Side Effect 139
8. Fighting the Flu 141
8.1 The Worldwide Pharmaceutical Industry 141
8.1.1 FDA Approved Vaccines: Tamiflu and Relenza 141
8.1.2 Stockpiling 141
8.1.3 Total Avian Influenza Drug Market Size and Growth 142
8.2 Funding 142
8.3 Antiviral Agents for Influenza: Background Information 142
8.3.1 Introduction 142
8.3.1.1 2005-06 Antiviral Usage Recommendation 142
8.3.2 Neuraminidase Inhibitors (Zanamivir, Oseltamivir) 142
8.3.3 How do the neuraminidase inhibitor drugs work? 143
8.3.4 How effective are the neuraminidase inhibitor drugs? 143
8.3.4.1.1 Treatment 143
8.3.4.1.2 Chemoprophylaxis 143
8.3.4.2 Side effects of the neuraminidase inhibitor drugs: 143
8.3.4.3 Antiviral resistance to the neuraminidase inhibitor drugs: 143
8.3.5 Adamantane Derivatives (Amantadine, Rimantadine) 144
8.3.5.1 Antiviral activity: How do the adamantane drugs work? 144
8.3.5.2 How effective are the adamantane drugs? 144
8.3.5.2.1 Treatment 144
8.3.5.2.2 Chemoprophylaxis 144
8.3.5.3 Side effects of the adamantane drugs: 144
8.3.5.4 Antiviral resistance: 145
8.3.6 Adamantanes Compared with Neuraminidase Inhibitors 145
8.3.7 Anti-Avian Influenza Drugs, Generics and Patents 146
8.3.7.1 Taiwan 147
8.3.7.2 India 147
8.3.7.3 Other countries 148
8.3.8 Regulatory Issues 149
8.3.9 New Anti-Avian Influenza Therapy 149
8.3.10 Pharmaceutical Business Perspective 150
8.3.10.1 A market dominated by GSK and Roche 150
8.3.10.2 Generic presence 150
8.3.10.3 Challenging Tamiflu 151
8.4 Other Treatment Requirements 151
8.5 Business Opportunities 152
LIST OF TABLES
Table 1: Probability of Influenza Diagnosis Using Office-Based Testing 14
Table 2: Prescribing Guidelines for Treating Influenza 15
Table 3: Influenza Virus Types 15
Table 4: H5N1 Cases and Deaths, Dec. 26, 2003, to June 8, 2005 19
Table 5: Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO 37
Table 6: Early (pre Wave I) events in Asia 41
Table 7: Wave I 42
Table 8: Wave II 42
Table 9: Wave III 43
Table 10: Methods for Influenza Diagnosis 49
Table 11: Summary of Current Clinical Virology Laboratory Tests for Influenza 51
Table 12: Interpandemic period, phase 1 - Planning and coordination 72
Table 13: Interpandemic period, phase 1 - Prevention and containment 72
Table 14: Interpandemic period, phase 1 - Health system response 73
Table 15: Interpandemic period, phase 1 - Communications 73
Table 16: Interpandemic period, phase 2 - Planning and coordination 74
Table 17: Interpandemic period, phase 2 - Situation monitoring and assessment 75
Table 18: Interpandemic period, phase 2 -Prevention and containment 75
Table 19: Interpandemic period, phase 2 - Health system response 76
Table 20: Interpandemic period, phase 2 - Communications 76
Table 21: Pandemic alert period, phase 3 - Planning and coordination 77
Table 22: Pandemic alert period, phase 3 - Situation monitoring and assessment 77
Table 23: Pandemic alert period, phase 3 -Prevention and containment 78
Table 24: Pandemic alert period, phase 3 - Health system response 78
Table 25: Pandemic alert period, phase 3 - Communications 79
Table 26: Pandemic alert period, phase 4 - Planning and coordination 79
Table 27: Pandemic alert period, phase 4 - Situation monitoring and assessment 80
Table 28: Pandemic alert period, phase 4 -Prevention and containment 80
Table 29: Pandemic alert period, phase 4 - Health system response 81
Table 30: Pandemic alert period, phase 4 - Communications 81
Table 31: Pandemic alert period, phase 5 - Planning and coordination 82
Table 32: Pandemic alert period, phase 5 - Situation monitoring and assessment 82
Table 33: Pandemic alert period, phase 5 -Prevention and containment 83
Table 34: Pandemic alert period, phase 5 - Health system response 83
Table 35: Pandemic alert period, phase 5 - Communications 84
Table 36: Pandemic period, phase 6 - Planning and coordination 85
Table 37: Pandemic period, phase 6 - Situation monitoring and assessment 85
Table 38: Pandemic period, phase 6 -Prevention and containment 86
Table 39: Pandemic period, phase 6 - Health system response 87
Table 40: Pandemic period, phase 6 - Communications 88
Table 41: National Measures (living or traveling within an affected country) 88
Table 42: International Measures (for entering or exiting a country) 90
Table 43: State & Local Planning Checklist - Community Preparedness Leadership and Networking 101
Table 44: State & Local Planning Checklist - Surveillance 102
Table 45: State & Local Planning Checklist - Public Health and Clinical Laboratories 102
Table 46: State & Local Planning Checklist - Healthcare and Public Health Partners 103
Table 47: State & Local Planning Checklist - Healthcare and Public Health Partners 103
Table 48: State & Local Planning Checklist - Vaccine Distribution and Use 104
Table 49: State & Local Planning Checklist - Antiviral Drug Distribution and Use 104
Table 50: State & Local Planning Checklist - Community Disease Control and Prevention 104
Table 51: State & Local Planning Checklist - Public Health Communications 105
Table 52: State & Local Planning Checklist - Workforce Support: Psychosocial Considerations and Information Needs 105
Table 53: Arrival 107
Table 54: Triage 108
Table 55: Isolation 109
Table 56: Patient Movement 110
Table 57: Communication 110
Table 58: Medical Evaluation 111
Table 59: Diagnosis 112
Table 60: Treatment 112
Table 61: Surge 112
Table 62: Plan for the impact of a pandemic on your business 113
Table 63: Plan for the impact of a pandemic on your employees and customers: 114
Table 64: Establish policies to be implemented during a pandemic 114
Table 65: Allocate resources to protect your employees and customers during a pandemic 115
Table 66: Communicate to and educate your employees: 115
Table 67: Coordinate with external organizations and help your community 115
Table 68: Planning and Coordination: 116
Table 69: Continuity of Student Learning and Core Operations: 116
Table 70: Infection Control Policies and Procedures: 117
Table 71: Communications Planning: 117
Table 72: Items to have on hand for an extended stay at home 120
Table 73: Immunizations FAQ 120
Table 74: WHO Global Plan for Pandemic Preparedness: 123
Table 75: Assumptions Underlying Estimates of the Supply-Side Impact of an Avian Flu Pandemic 139
Table 76: Assumed Declines in Demand, by Industry, in the Event of an Avian Flu Pandemic 139
Table 77: Top 30 pharmaceutical and biotech companies ranked by healthcare revenue ("Big Pharma") 141
Table 78: Recommended Daily Dosage of Influenza Antiviral Medications for Treatment and Prophylaxis 146
Table 79: Examples of Preparedness Supplies 151
LIST OF FIGURES
Figure 1: Influenza Subtypes 16
Figure 2: Timeline of Emergence of Influenza A Viruses in Humans 18
Figure 3: Model of the Emergence of a Pandemic Virus 23
Figure 4: Map of H5N1 Instances and Asian Migratory Bird Zones 31
Figure 5: Map of H7N3 in British Columbia 32
Figure 6: Phase 3 is the Current WHO Phase of Alert 36
Figure 7: Nations with Confirmed Cases of H5N1 Avian Influenza (as of May 19, 2006) 37
Figure 8: World: Affected areas with confirmed cases of H5N1 avian influenza since 2003 (as of May 30, 2006) 38
Figure 9: World: Affected areas with confirmed cases of H5N1 avian influenza since January 2006 (as of May 30, 2006) 39
Figure 10: World: Areas reporting confirmed occurrence of H5N1 avian influenza in poultry and wild birds since January 2006 (as of June 9, 2006) 40
Figure 11: World: Areas reporting confirmed occurrence of H5N1 avian influenza in poultry and wild birds since 2003 (as of June 9, 2006) 41
Figure 12: Waterfowl Flyways of North America 48
Figure 13: FDA-approved Kit Based Test 49
Figure 14: Immunofluorescence-based detection 50
Figure 15: Uninfected and Infected Tissue Cultures 50
Figure 16: TEM of Negatively Stained Influenza Virions (from Cultures) 51
Figure 17: PCR Assay Graphic 53
Figure 18: PCR assay 54
Figure 19: "Amplicon" Generation 54
Figure 20: the TaqMan 5'-3' Nuclease Assay 56
Figure 21: TaqMan Amplification Plot 57
Figure 22: TaqMan Fluorescent Reaction Components 57
Figure 23: Biosafety Level 3 -Ag- Full Tyvek body suit 64
Figure 24: Signage: Informing Staff 107
Figure 25: Signage: Informing Patients 108
Figure 26: Respiratory Etiquette Kit 109
Figure 27: Isolation 110
Figure 28: Communication Scheme 111
Figure 29: Surge 113

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