Influenza A Pre-Season Update

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InfluenzaA Pre-Season Update

• Dr. Theresa Tam
• Immunization and Respiratory Infections Division
• Centre for Infectious Disease Prevention and
  Control
• Hosted by Paul Webber paul_at_webbertraining.com

alPHa Teleclass, September 21, 2004
Health SantéCanada Canada
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Outline

• Highlights from the 2003-2004 season in Canada
  and worldwide
• Avian influenza
• H5N1 in Asia
• H7N3 in British Columbia
• NACI recommendations for 2004-2005
• Canadian Pandemic Influenza Plan update

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2003-2004 Influenza Season in Canada
Health SantéCanada Canada
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2003-2004 Season Highlights

• Worldwide Influenza A(H3N2) predominated with
  co-circulations of A(H1) and B viruses
• In Canada
• Early start
• Relatively severe
• A(H3N2) predominated
• Four reports of deaths in children with lab
  confirmed influenza (7-14 years)
• IMPACT network reported additional 3 deaths
• US reported 152 deaths in persons lt 18 years (40
  states)

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Influenza Season
Beginning of laboratory-confirmed influenza
Peak of influenza activity
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Influenza tests by week
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ILI Reporting Rates, Canada, by week 2003-2004
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Number of Influenza regions reporting widespread
of localized activity
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Influenza Strain Identification
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Influenza Hospitalizations in Children- Pilot

• Over 500 children hospitalized with laboratory
  confirmed influenza in 9 IMPACT centres
• Weekly admissions ranged over the season, with a
  peak occurring at week 52
• Influenza A was identified in 99 of cases
• 86 under age of 6 years
• 57 under 2 years
• one third of cases were in 6-23 month age-group
• One third had underlying medical conditions for
  which annual immunization is recommended

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Avian Influenza
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Human Infections

• H5N1 - severe
• 1997 Hong Kong 18 cases 6 deaths
• 2003 Hong Kong 2 cases 1 death
• 2004 Vietnam and Thailand 40 cases 29 deaths (9
  Sep 2004)
• H9N2 - mild
• 1999 Hong Kong 2 cases (mild)
• 2003 Hong Kong 1 case (mild)
• H7N7 - mild
• 2003 Netherlands 89 cases1 death
• 2004 Canada 2 cases

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Avian H5N1 in Asia

• Continuing presence in Asia since 1996
• Documented direct avian to human transmission,
  Hong Kong,1997
• Enzootic and epizootic of unprecedented size and
  complexity
• 9 countries with ongoing outbreaks (most recently
  in Malaysia)
• Ongoing human cases with high case fatality,
  mostly in healthy children and young adults
• Ongoing evolution of the virus antigenic,
  genetic and functional properties
• No sustained human to human transmission to date

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Why are We Concerned?

• Increasing countries/areas with avian influenza
• Uncertainties on progress of control
• Ongoing human infection with avian H5N1
• Limited implementation of protective measures
• Co-Circulating human influenza viruses
• Risk of genetic reassortment leading to pandemic
  strain
• Majority of human population would have no
  immunity

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Influenza H5N1 expanded host range?

• Domestic poultry
• Wild birds
• infected
• reservoir
• Humans
• Swine (China)
• Cats? (Netherlands)

The natural hosts of the influenza A virus
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Containing an Initial Outbreak of Novel Influenza
Can this be done?

• Hong Kong accomplished this in 1997
• 2004 H5N1 situation much more challenging
• Large areas affected in a large number of
  countries
• Slow and incomplete reporting of H5N1 findings
• Poor public health infrastructure
• Complex political and economic situations
• International action required support for
  antivirals PPE and compensation may help

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Highly Pathogenic Avian Influenza (HPAI) H7N3,
BC, 2004

• 42 commercial and 11 backyard premises infected
• Feb 19 low path Avian influenza (AI) H7 first
  detected in a commercial chicken breeder farm
• March 8 HPAI detected on the same farm
• Mar 11 HPAI on second farm
• Approx 19 million birds depopulated
• Spread likely by movement of people, equipment or
  birds. Airborne transmission through dust and
  feathers?

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Avian H7N3 in BC, 2004

• Movement restrictions
• Susceptible birds within 3km of infected premises
  depopulated
• Active surveillance and testing of flocks birds
  tested negative slaughtered through normal
  commercial channels
• Depopulation activities suspended on June 4 after
  21 days with no new reports.
• Outbreak declared contained on August 18, 21 days
  after last infected premise cleaned and
  disinfected.

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BC Avian H7 OutbreakHuman Health Issues

• 2 cases of lab confirmed human H7 infections in
  cullers
• Surveillance of exposed persons
• Farm family and workers
• Persons involved in depopulation of infected
  poultry
• Immunization with current seasonal flu vaccine
• Personal protective equipment
• Antivirals prophylaxis and treatment
• Pandemic Influenza Committee guidelines on Human
  Health Issues related to Domestic Avian Influenza
  Outbreaks

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NACI Recommendations

• June 15, 2004

Health SantéCanada Canada
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Whats new in the NACI Statement?

• New vaccine strains
• Immunization of healthy children 6-23 months
• Immunization of cullers involved in depopulation
  of poultry infected with avian flu
• Prophylactic use of neuraminidase inhibitors

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Vaccine composition for 2004-2005

• Trivalent vaccines to be used in Canada will
  contain the following antigens
• A/New Caledonia/20/99 (N1H1)-like
• A/Wyoming/3/2003 (H3N2) (an A/Fujian411/2002
  (H3N2)-like strain)
• B/Jiangsu/10/2003 (a B/Shanghai/361/2002-like
  strain)

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Recommendation for children 6-23 months

• Increased risk of morbidity hospitalizations
• Vaccine efficacy, based on a limited total number
  of subjects in this age group (lt1000), is similar
  to estimated for the elderly and those with high
  risk medical conditions.
• Further study required
• Vaccine effectiveness
• Immunologic response to future encounters with
  wild virus
• Adverse events e.g. ORS in first time vaccinees

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Oseltamivir

• Licensed for treatment and prophylaxis
• Any concerns with resistance?
• Resistance strains in 0.33-9 of treated patients
• Children have higher likelihood of developing
  resistant strains. Japanese study (Kiso) of 50
  children showed 18 with resistant genotypes
• Currently little evidence of de novo resistance
• Data needed on clinical significance of resistant
  strains - pathogenicity, viral shedding and
  transmissibility

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Canadian Pandemic Influenza Plan - Update

• .

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Pandemic Preparedness Milestones

• 1988 - 1st draft plan
• 1997 - lessons learnt from Hong Kong Bird flu
• 1998 to 2002
• F/P/T Working Agreement (Mar 2001) roles and
  responsibilities
• pandemic vaccine contract signed (Sep 2001)
• Pandemic Influenza Committee (PIC) established
  (Mar 2002)
• Pandemic Plan consultations 43 organizations
  (Sep 2002)
• 2003
• Plan revised in light of SARS experience and
  approved by Deputy Ministers of Health (Dec 2003)

Public Release of the Plan February 2004
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Canadian Pandemic Influenza Plan (CPIP)

• Based on the nationally agreed upon goal
• Organized into components (framework for
  national working group activities)
• Uses WHO Pandemic Phases
• Roles and responsibilities of F/P/T orders of
  government identified as per Working Agreement
• Model for P/T contingency plans
• Contains checklists and technical annexes

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Key Strategies and Planning Components

• Rapid detection, monitor spread and assess impact
• Surveillance and lab testing protocols
• Reduce spread and impact
• Border measures
• Public health measures and infection control
• Vaccines
• Antivirals
• Maintaining health services
• Emergency and social services
• Maintain public awareness
• Risk communication

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The Plan Current activities

• Using pandemic influenza structures and processes
  to define Canadas response to avian influenza
  (Phase 0, level 2)
• Management of Human Health Issues related to
  Domestic Avian Influenza Outbreaks
• Finalize and post new Annexes (2004)
• First Nations
• Public Health Measures
• Surveillance

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The Plan Current activities - II

• Completion of antiviral drug strategy (2004)
• Testing domestic vaccine production
  infrastructure, regulatory processes and clinical
  trial protocols (2004-2005, pending funding)
• Influenza research agenda (2004)
• Further exercising of the Plan
• Completing the Recovery Section

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Public Health and Border Measures

• To avert a pandemic or appreciably slow the
  spread of a novel virus, prior to the development
  of efficient and sustained human to human
  transmission

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Comparison with SARS
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Public Health Measures Scope I
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Public Health Measures Scope II
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Antivirals

• Two main types
• Neuraminidase inhibitors (e.g. oseltamivir,
  zanamivir)
• Amantadine
• Why use antivirals?
• Minimise risk of emergence of a novel virus with
  pandemic potential, through preventing human
  infection
• Buying time and limiting spread at the start of a
  pandemic until vaccine becomes available
• Minimize health care system disruption and
  mortality

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Antivirals Not A Panacea

• Global production capacity limited high cost
• Ability to use antivirals to limit spread depends
  on rapid case detection and contact tracing
• Need to start treatment early
• Effectiveness on serious illnesses and mortality
  unknown
• Prophylaxis may require ongoing use for 6 weeks
  or longer
• Antiviral resistance and side effects may limit
  use

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Antiviral Strategy Status

• Options for use and stockpiling
• Neuraminidase inhibitors for treatment and
  prophylaxis
• Amantadine for prophylaxis (currently not for
  stockpiling)
• Guidelines on use of antivirals in short supply
• Goal oriented
• For planning purposes
• Clinical guidelines

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Current Thinking Principles

• Antivirals are the only virus-specific
  intervention prior to vaccine becoming available
• Priority groups in times of short supply should
  be determined for planning purposes (but maintain
  flexibility to change based on epidemiology or
  local needs)
• Priority groups should be based on overall goal
• Use of all anti-influenza drugs available
• neuraminidase inhibitors for treatment or
  prophylaxis
• amantadine for prophylaxis if strain susceptible

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Current Thinking Policy Considerations

• Security of supply for antiviral drugs should be
  addressed in the pre-pandemic period.
• Stockpiling of oseltamivir for nationally agreed
  upon priority groups
• The F/P/T governments should control the supply
  and distribution of available anti-influenza
  drugs, to the end user, during a pandemic.

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Overall Goal of Pandemic Preparedness and Response

• First, to minimize serious illness and
  overall deaths, and second to minimize societal
  societal disruption among Canadians as a result
  of an influenza pandemic.

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Current Thinking National Priorities

• Tx of persons hospitalized for influenza
• Tx of ill HCW and ESW
• Px of front line HCW and key health decision
  makers
• Tx of high-risk in the community
• Px of remaining HCW
• Control outbreaks in high-risk residents of
  institutions
• Px of ESW
• Px of high-risk persons hospitalized for
  illnesses other than influenza
• Px of high-risk in the community

Tx Treatment Px Prophylaxis
Need to review definitions and estimates for
priority groups
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Cumulative Doses by Priority Groups
Doses (Millions)
NOTE THESE PRELIMINARY ESTIMATES HAVE NOT GONE
THROUGH SCIENTIFIC OR GOVERNMENT POLICY CHALLENGE.
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Current Policy Discussions
PIC Priority Groups for pandemic planning
compared to those currently being considered in
policy discussions

• Tx Hospitalized
• Tx HCW and ESW
• Px front line HCW, key health decision makers
• Tx HR community
• Px Remaining HCW
• Tx Institutionalized (Px?)
• Px ESW (post-exposure)
• Px HR hospitalized
• Px HR community

Approximately equal to 14 million doses of
oseltamivir
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Antiviral Use in Phase 0

• WHO Discussions
• P0L1 Px of at risk (e.g. cullers), early Tx of
  symptomatic persons
• P0L2-L3 focus on clusters of cases to prevent,
  reduce or delay spread, early Tx and Px of
  contacts including HCW, consideration for
  intense prophylaxis around a limited number of
  small, well defined clusters
• Buying time, slowing spread early in a pandemic??
• International stockpile

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Antiviral Use During Domestic Avian Flu
Outbreaks Prophylaxis

• Persons potentially exposed to avian flu
• Involved in outbreak control culling, disposal,
  cleaning of infected poultry/materials
• Living/working on affected farms with contact to
  infected materials (those without contact offered
  early treatment)
• Oseltamivir for duration of exposure plus 5 days
  (6 weeks max, 2 weeks between courses)
  off-label use
• Post exposure prophylaxis (PEP) for 5 days
  following significant exposure for those not on
  continuous prophylaxis
• PEP should not be routinely given to close
  contacts of human cases of avian flu, but may be
  considered if index case severe or unusual

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Antiviral Use During Domestic Avian Flu
Outbreaks Treatment

• Persons (gt 1 year of age) who develop compatible
  illness following avian exposure
• In light of evidence showing continuing
  replication of avian influenza virus beyond 48
  hours after onset of symptoms, consideration
  should be given to treating individuals
  presenting at any point during their illness
  (i.e. not just during first 48 hours )

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Antiviral Strategy To Do

• Complete priority group definitions and estimates
• Funding for stockpile(s) (F/P/T)
• Implementation issues
• strategies for delivery, administration,
  monitoring of distribution, uptake, wastage
• Evaluation issues
• monitoring for adverse events and resistance
• Modeling of potential impact
• Alone and in combination with other potential
  interventions
• Containing a localized cluster in P0

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Next Steps on Influenza Research

• Development of national research agenda
• Collaborative evaluation of the Ontario's
  Universal Influenza Immunization Program
• Identifying funding for production and clinical
  trials with novel influenza vaccine strains
  (H5N1)
• Vaccine coverage survey
• Vaccine effectiveness studies

Meeting of the National Vaccine Advisory
Committee Washington DC, June 1-2, 2004