Avian Influenza

Table of Contents

1. Overview

• 1.1 Statement of Report
• 1.2 Scope of Report
• 1.3 Objectives
• 1.4 Methodology
• 1.5 Executive Summary

2. The Basics of Human Influenza

• 2.1 Influenza, the Disease
  • 2.1.1 Symptoms
  • 2.1.2 Transmission
  • 2.1.3 Public Health Factors
  • 2.1.4 Influenza Diagnosis
• 2.2 Influenza Viruses
  • 2.2.1 Types, Subtypes and Strains
    • 2.2.1.1 Influenza Type A and its Subtypes
    • 2.2.1.2 Highly Pathogenic versus Lowly Pathogenic Avian Influenza A Viruses
    • 2.2.1.3 Human Influenza Viruses and Avian Influenza A Viruses
      • 2.2.1.3.1 Influenza A H5
      • 2.2.1.3.2 Influenza A H7
      • 2.2.1.3.3 Influenza A H9
    • 2.2.1.4 Influenza Type B
    • 2.2.1.5 Influenza Type C
  • 2.2.2 How Influenza Viruses Change: Drift and Shift
  • 2.2.3 Seasons and Human Influenza
  • 2.2.4 Risk Factors and Human Influenza
  • 2.2.5 Human Influenza Complications, Comorbidities and Dangers
  • 2.2.5.1 Flu complications in children and teenagers
  • 2.2.6 Human Influenza Prognosis
• 2.3 Pandemic Influenza
• 2.4 How Influenza Viruses Change

3. The Basics of Avian Influenza

• 3.1 Avian Influenza in Birds
• 3.1.1 Avian Influenza Outbreaks in Poultry
  • 3.1.2 More Information About Avian Influenza Viruses
• 3.2 Transmission of Influenza A Viruses between Animals and People
• 3.3 Avian Influenza Infection in Humans
  • 3.3.1 Instances of Avian Influenza Infection in Humans
  • 3.3.2 Symptoms of Avian Influenza in Humans
  • 3.3.3 Antiviral Agents for Influenza
• 3.4 Avian Influenza (H5N1)
  • 3.4.1 Avian Influenza (H5N1) Outbreaks
• 3.5 All Types of Avian Influenza Worldwide Outside of Asia
  • 3.5.1 Canada
  • 3.5.2 Netherlands
  • 3.5.3 United States
    • 3.5.3.1 Delaware
    • 3.5.3.2 Texas
    • 3.5.3.3 Maryland
    • 3.5.3.4 International Response
    • 3.5.3.5 Available Options

4. Epidemiology of Avian Influenza

• 4.1 Worldwide Avian Influenza
• 4.2 H5N1 Avian Influenza: Timeline
• 4.3 U.S. Avian Influenza

5. Influenza Diagnosis and Laboratory Issues

• 5.1 "Classic" Methods for Influenza Diagnosis
• 5.2 Example Lab: Yale New Haven Hospital (YNHH)
• 5.3 Conventional PCR Assay for Sub-typing Influenza Virus
  • 5.3.1 Gel Analysis
• 5.4 Real Time TaqMan PCR
  • 5.4.1 From PacMan to TaqMan-A Computer Game Revisited
  • 5.4.2 The Advantages of Real-Time TaqMan PCR Over Conventional Quantitative PCR
• 5.5 Example Strategy for Avian Influenza
• 5.6 Laboratory Safety Issues for H5N1 Viruses
  • 5.6.1 Biosafety Level 3
  • 5.6.2 Biosafety Level 3-Ag
  • 5.6.3 CDC Criteria for Testing
  • 5.6.4 What Samples Are Needed?

6. Preparedness

• 6.1 Education
• 6.2 Ethical and Legal Issues
• 6.3 Worldwide
  • 6.3.1 Overarching Goals, Objectives and Actions for WHO and National Authorities, by Phase
    • 6.3.1.1 Interpandemic Period, Phase 1-Overarching Goal
    • 6.3.1.2 Interpandemic Period, Phase 2-Overarching Goal
    • 6.3.1.3 Pandemic Alert Period, Phase 3-Overarching Goal
    • 6.3.1.4 Pandemic Alert Period, Phase 4-Overarching Goal
    • 6.3.1.5 Pandemic Alert Period, Phase 5-Overarching Goal
    • 6.3.1.6 Pandemic Period, Phase 6-Overarching Goal
  • 6.3.2 Recommendations for Non-Pharmaceutical Public Health Interventions
• 6.4 U.S.
  • 6.4.1 U.S. National Plan
  • 6.4.2 U.S. Locally
    • 6.4.2.1 Community Preparedness Leadership and Networking
    • 6.4.2.2 Surveillance
    • 6.4.2.3 Public Health and Clinical Laboratories
    • 6.4.2.4 Healthcare and Public Health Partners
    • 6.4.2.5 Infection Control and Clinical Guidelines
    • 6.4.2.6 Vaccine Distribution and Use
    • 6.4.2.7 Antiviral Drug Distribution and Use
    • 6.4.2.8 Community Disease Control and Prevention
    • 6.4.2.9 Public Health Communications
    • 6.4.2.10 Workforce Support: Psychosocial Considerations and Information Needs
    • 6.4.2.11 State Plans
• 6.5 The Hospital Response
  • 6.5.1 Introduction
  • 6.5.2 Key Assumptions
  • 6.5.3 Arrival
  • 6.5.4 Triage
  • 6.5.5 Isolation
  • 6.5.6 Patient Movement
  • 6.5.7 Communication
  • 6.5.8 Medical Evaluation
  • 6.5.9 Diagnosis
  • 6.5.10 Treatment
  • 6.5.11 Potential for Surge
• 6.6 Business Preparedness
• 6.7 School Preparedness
• 6.8 Individual Preparedness

7. Economics of Avian Influenza

• 7.1 Impact on Governments
  • 7.1.1 Worldwide Economic Impact of Avian Flu
  • 7.1.2 U.S. Nationally
• 7.2 Impact of a Pandemic
  • 7.2.1 Supply Side Effect
  • 7.2.2 Demand Side Effect

8. Fighting the Flu

• 8.1 The Worldwide Pharmaceutical Industry
  • 8.1.1 FDA Approved Vaccines: Tamiflu and Relenza
  • 8.1.2 Stockpiling
  • 8.1.3 Total Avian Influenza Drug Market Size and Growth
• 8.2 Funding
• 8.3 Antiviral Agents for Influenza: Background Information
  • 8.3.1 Introduction
  • 8.3.1.1 Antiviral Usage Recommendation-2005-06
  • 8.3.2 Neuraminidase Inhibitors (Zanamivir, Oseltamivir)
  • 8.3.3 How do the Neuraminidase Inhibitor Drugs Work?
  • 8.3.4 How Effective are the Neuraminidase Inhibitor Drugs?
    • 8.3.4.1 Treatment
    • 8.3.4.2 Chemoprophylaxis
    • 8.3.4.3 Side Effects of the Neuraminidase Inhibitor Drugs
    • 8.3.4.4 Antiviral Resistance to the Neuraminidase Inhibitor Drugs
  • 8.3.5 Adamantane Derivatives (Amantadine, Rimantadine)
    • 8.3.5.1 Antiviral Activity: How do the Adamantane Drugs Work?
    • 8.3.5.2 How Effective are the Adamantane Drugs?
      • 8.3.5.2.1 Treatment
      • 8.3.5.2.2 Chemoprophylaxis
    • 8.3.5.3 Side Effects of the Adamantane Drugs
    • 8.3.5.4 Antiviral Resistance
  • 8.3.6 Adamantanes Compared with Neuraminidase Inhibitors
  • 8.3.7 Anti-Avian Influenza Drugs, Generics and Patents
    • 8.3.7.1 Taiwan
    • 8.3.7.2 India
    • 8.3.7.3 Other Countries
  • 8.3.8 Regulatory Issues
  • 8.3.9 New Anti-Avian Influenza Therapy
  • 8.3.10 Pharmaceutical Business Perspective
    • 8.3.10.1 A Market Dominated by GSK and Roche
    • 8.3.10.2 Generic Presence
    • 8.3.10.3 Challenging Tamiflu
• 8.4 Other Treatment Requirements
• 8.5 Business Opportunities

INDEX OF FIGURES

• Figure 2.1: Influenza Subtypes
• Figure 2.2: Timeline of Emergence of Influenza A Viruses in Humans
• Figure 2.3: Model of the Emergence of a Pandemic Virus
• Figure 3.1: Map of H5N1 Instances and Asian Migratory Bird Zones
• Figure 3.2: Map of H7N3 in British Columbia
• Figure 4.1: Nations with Confirmed Cases of H5N1 Avian Influenza
• Figure 4.2: World: Affected Areas with Confirmed Cases of H5N1 Avian Influenza Since 2003
• Figure 4.3: World: Affected Areas with Confirmed Cases of H5N1 Avian Influenza Since January 2006
• Figure 4.4: World: Areas Reporting Confirmed Occurrence of H5N1 Avian Influenza in Poultry and Wild Birds Since January 2006
• Figure 4.5: World: Areas Reporting Confirmed Occurrence of H5N1 Avian Influenza in Poultry and Wild Birds Since 2003
• Figure 4.6: Waterfowl Flyways of North America
• Figure 5.1: FDA-approved Kit-based Test
• Figure 5.2: Immunofluorescence-based Detection
• Figure 5.3: Uninfected and Infected Tissue Cultures
• Figure 5.4: TEM of Negatively Stained Influenza Virions (from Cultures)
• Figure 5.5: PCR Assay Graphic
• Figure 5.6: PCR assay
• Figure 5.7: "Amplicon" Generation
• Figure 5.8: The TaqMan 5' -3' Nuclease Assay
• Figure 5.9: TaqMan Amplification Plot
• Figure 5.10: TaqMan Fluorescent Reaction Components
• Figure 5.11: Biosafety Level 3-Ag-Full Tyvek Body Suit
• Figure 6.1: Signage: Informing Staff
• Figure 6.2: Signage: Informing Patients
• Figure 6.3: Respiratory Etiquette Kit
• Figure 6.4: Isolation
• Figure 6.5: Communication Scheme
• Figure 6.6: Surge

INDEX OF TABLES

• Table 2.1: Probability of Influenza Diagnosis Using Office-Based Testing
• Table 2.2: Prescribing Guidelines for Treating Influenza
• Table 2.3: Influenza Virus Types
• Table 2.4: H5N1 Cases and Deaths, 2003-2005
• Table 4.1: Phase 3 is the Current WHO Phase of Alert
• Table 4.2: Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO, 2003-2006
• Table 4.3: Early (Pre Wave I) Events in Asia, 1996, 1997 and 2003
• Table 4.4: Wave I
• Table 4.5: Wave II
• Table 4.6: Wave III
• Table 5.1: Methods for Influenza Diagnosis
• Table 5.2: Summary of Current Clinical Virology Laboratory Tests for Influenza
• Table 6.1: Interpandemic Period, Phase 1-Planning and Coordination
• Table 6.2: Interpandemic Period, Phase 1-Prevention and Containment
• Table 6.3: Interpandemic Period, Phase 1-Health System Response
• Table 6.4: Interpandemic Period, Phase 1-Communications
• Table 6.5: Interpandemic Period, Phase 2-Planning and Coordination
• Table 6.6: Interpandemic Period, Phase 2-Situation Monitoring and Assessment
• Table 6.7: Interpandemic Period, Phase 2-Prevention and Containment
• Table 6.8: Interpandemic Period, Phase 2-Health System Response
• Table 6.9: Interpandemic Period, Phase 2-Communications
• Table 6.10: Pandemic Alert Period, Phase 3-Planning and Coordination
• Table 6.11: Pandemic Alert Period, Phase 3-Situation Monitoring and Assessment
• Table 6.12: Pandemic Alert Period, Phase 3-Prevention and Containment
• Table 6.13: Pandemic Alert Period, Phase 3-Health System Response
• Table 6.14: Pandemic Alert Period, Phase 3-Communications
• Table 6.15: Pandemic Alert Period, Phase 4-Planning and Coordination
• Table 6.16: Pandemic Alert Period, Phase 4-Situation Monitoring and Assessment
• Table 6.17: Pandemic Alert Period, Phase 4-Prevention and Containment
• Table 6.18: Pandemic Alert Period, Phase 4-Health System Response
• Table 6.19: Pandemic Alert Period, Phase 4-Communications
• Table 6.20: Pandemic Alert Period, Phase 5-Planning and Coordination
• Table 6.21: Pandemic Alert Period, Phase 5-Situation Monitoring and Assessment
• Table 6.22: Pandemic Alert Period, Phase 5-Prevention and Containment
• Table 6.23: Pandemic Alert Period, Phase 5-Health System Response
• Table 6.24: Pandemic Alert Period, Phase 5-Communications
• Table 6.25: Pandemic Period, Phase 6-Planning and Coordination
• Table 6.26: Pandemic Period, Phase 6-Situation Monitoring and Assessment
• Table 6.27: Pandemic Period, Phase 6-Prevention and Containment
• Table 6.28: Pandemic Period, Phase 6-Health System Response
• Table 6.29: Pandemic Period, Phase 6-Communications
• Table 6.30: National Measures (Living or Traveling Within an Affected Country)
• Table 6.31: International Measures (for Entering or Exiting a Country)
• Table 6.32: State and Local Planning Checklist-Community Preparedness Leadership and Networking
• Table 6.33: State and Local Planning Checklist-Surveillance
• Table 6.34: State and Local Planning Checklist-Public Health and Clinical Laboratories
• Table 6.35: State and Local Planning Checklist-Healthcare and Public Health Partners
• Table 6.36: State and Local Planning Checklist-Healthcare and Public Health Partners
• Table 6.37: State and Local Planning Checklist-Vaccine Distribution and Use
• Table 6.38: State and Local Planning Checklist-Antiviral Drug Distribution and Use
• Table 6.39: State and Local Planning Checklist-Community Disease Control and Prevention
• Table 6.40: State and Local Planning Checklist-Public Health Communications
• Table 6.41: State and Local Planning Checklist-Workforce Support: Psychosocial Considerations and Information Needs
• Table 6.42: Arrival
• Table 6.43: Triage
• Table 6.44: Isolation
• Table 6.45: Patient Movement
• Table 6.46: Communication
• Table 6.47: Medical Evaluation
• Table 6.48: Diagnosis
• Table 6.49: Treatment
• Table 6.50: Surge
• Table 6.51: Plan for the Impact of a Pandemic on Your Business
• Table 6.52: Plan for the Impact of a Pandemic on Your Employees and Customers
• Table 6.53: Establish Policies to be Implemented During a Pandemic
• Table 6.54: Allocate Resources to Protect Your Employees and Customers During a Pandemic
• Table 6.55: Communicate to and Educate Your Employees
• Table 6.56: Coordinate with External Organizations and Help Your Community
• Table 6.57: Planning and Coordination:
• Table 6.58: Continuity of Student Learning and Core Operations
• Table 6.59: Infection Control Policies and Procedures
• Table 6.60: Communications Planning
• Table 6.61: Items to have on Hand for an Extended Stay at Home
• Table 6.62: Immunizations FAQ
• Table 6.63: WHO Global Plan for Pandemic Preparedness
• Table 7.1: Assumptions Underlying Estimates of the Supply-Side Impact of an Avian Flu Pandemic
• Table 7.2: Assumed Declines in Demand, by Industry, in the Event of an Avian Flu Pandemic
• Table 8.1: Top 30 Pharmaceutical and Biotech Companies Ranked by Healthcare Revenue ("Big Pharma")
• Table 8.2: Recommended Daily Dosage of Influenza Antiviral Medications for Treatment and Prophylaxis
• Table 8.3: Examples of Preparedness Supplies