influenza a pre-season update
DESCRIPTION
Influenza A Pre-Season Update. Dr. Theresa Tam Immunization and Respiratory Infections Division Centre for Infectious Disease Prevention and Control Hosted by Paul Webber [email protected]. alPHa Teleclass, September 21, 2004. HealthSanté CanadaCanada. Outline. - PowerPoint PPT PresentationTRANSCRIPT
Health SantéCanada Canada
alPHa Teleclass, September 21, 2004alPHa Teleclass, September 21, 2004
InfluenzaA Pre-Season Update
Dr. Theresa Tam
Immunization and Respiratory Infections DivisionCentre for Infectious Disease Prevention and Control
Hosted by Paul Webber [email protected]
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
2003-2004 Influenza Season in Canada
Health SantéCanada Canada
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 < 18 years (40 states)
Influenza Season
Province October 2003
November 2003
December 2003
January 2004
February2004
BC * **
AB & SK * **
MB * **
ON * **
QC * **
Atlantic * **
* Beginning of laboratory-confirmed influenza
** Peak of influenza activity
Influenza tests by week
Influenza tests reported and percentage of tests positive, Canada, by report week, 2003-2004
0500
10001500200025003000350040004500
8/30
9/27
10/2
5
11/2
2
12/2
0
1/17
2/14
3/13
4/10 5/
8
6/5
7/3
7/31
2003 Report week ending 2004
Number of tests
01020304050607080
% Positive
Number of tests % Positive ILI Rate
ILI Reporting Rates, Canada, by week 2003-2004
Influenza-like illness (ILI) reporting rates, Canada, by report week, 2003-2004 compared to 1996/97 through 2002/2003 seasons
0
25
50
75
100
35 37 39 41 43 45 47 49 51 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 332003 Report week 2004
Rate per 1,000 patient visits
2003/2004 ILI Rate Mean Rate | 95% Interval (1996/97 - 2002/03)
Note: No data available for mean rate in previous years for w eeks 21 to 39 (1996-1997 through 2002-2003 seasons). During w eeks 20-39, 2002-2003/ 2003-2004 seasons, ILI is reported once every tw o w eeks, on even w eeks only
Number of Influenza regions reporting widespread of localized activity
Number of influenza surveillance regions† reporting widespread or localized influenza activity, Canada, by report week, 2003-2004 (N=52)
0
5
10
15
20
25
30
8/30
9/13
9/27
10/1
1
10/2
5
11/8
11/2
2
12/6
12/2
0 1/3
1/17
1/31
2/14
2/28
3/13
3/27
4/10
4/24 5/
8
5/22 6/
5
6/19 7/
3
7/17
7/31
8/14
2003 Report week ending 2004
Number of regions
Localized activity Widespread activity
Influenza Strain Identification
B/ Sichuan/ 379/ 99-like [33]
H1N2[1]
A/ Panama/ 2007/ 99 (H3N2)-like
[25]
A/ Fujian/ 411/ 02-like (H3N2) [776]
A/ New Caledonia/ 20/ 99-
like (H1N1) [3]
B/ Hong Kong/ 330/ 01-like
[7]
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
Avian Influenza
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 cases;1 death 2004 Canada: 2 cases
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
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
Influenza H5N1: expanded host range?
Domestic poultry Wild birds
infected reservoir
Humans Swine (China) Cats? (Netherlands)
The natural hosts of the influenza A virus
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
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?
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.
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”
NACI Recommendations
June 15, 2004
Health SantéCanada Canada
What’s 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
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)
Vaccine composition for 2004-2005
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 (<1000), 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
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
Canadian Pandemic Influenza Plan -
Update.
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
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
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
The Plan: Current activities
Using pandemic influenza structures and processes to define Canada’s 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 NationsPublic Health MeasuresSurveillance
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
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
Comparison with SARS
SARS Influenza Control
Incubation period
Average 5 days Average 2 days Harder
Infectious period
Peaks day 10 Peaks day 2 Harder
Transmission Droplet>>airborne Droplet>airborne Harder?
Age distribution
AdultsChildren/ Unknown
Unclear
Attack rate Low (variable) High Harder
Public Health Measures – Scope I
Decrease contact
Isolate cases Quarantine contacts
Restrict travel Restrict mixing
Hospital Advisory School closure
HomeScreening: exit / entry
Ban mass gatherings
Conveyances BanAvoid crowded
places
Public Health Measures – Scope II
Decrease effective contact
Case hygiene Contact hygieneEnvironment
hygiene
Wear mask Wear mask Disinfection
Wash hands Wash hands Ventilation
Respiratory hygiene
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
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
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
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
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.
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.
Current Thinking: National Priorities1. Tx of persons hospitalized for influenza
2. Tx of ill HCW and ESW
3. Px of “front line” HCW and key health decision makers
4. Tx of high-risk in the community
5. Px of remaining HCW
6. Control outbreaks in high-risk residents of institutions
7. Px of ESW
8. Px of high-risk persons hospitalized for illnesses other than influenza
9. Px of high-risk in the community
Need to review definitions and estimates for priority groupsTx = Treatment Px = Prophylaxis
Cumulative Doses by Priority Groups
0 50 100 150 200 250
Px of HR in Community
HR hospitalized
Px ESW
Institutionalized
Px Remaining HCW
Tx HR community
Px frontline HCW
Tx HCW and ESW
TX hospitalized
Doses (Millions)
NOTE: THESE PRELIMINARY ESTIMATES HAVE NOT GONE THROUGH SCIENTIFIC OR GOVERNMENT POLICY CHALLENGE.
Current 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
PIC Priority Groups for pandemic planning compared to those currently being considered in policy discussions:
Approximately equal to 14 million doses of
oseltamivir
Antiviral Use in Phase 0WHO 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
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
Antiviral Use During Domestic Avian Flu Outbreaks: Treatment
Persons (>= 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 )
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
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 CommitteeWashington DC, June 1-2, 2004