Transcript Surveillance & Epidemiology

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]
Health Santé
Canada Canada
alPHa Teleclass, September 21, 2004
Outline
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Highlights from the 2003-2004 season in
Canada and worldwide
Avian influenza
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H5N1 in Asia
H7N3 in British Columbia
NACI recommendations for 2004-2005
Canadian Pandemic Influenza Plan update
2003-2004 Influenza
Season in Canada
Health
Canada
Santé
Canada
2003-2004 Season Highlights
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Worldwide Influenza A(H3N2) predominated with cocirculations of A(H1) and B viruses
In Canada
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Early start
Relatively severe
A(H3N2) predominated
Four reports of deaths in children with lab confirmed
influenza (7-14 years)
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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
BC
*
**
AB & SK *
**
MB
*
**
ON
*
**
QC
*
Atlantic
*
January
2004
February
2004
**
**
* 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
% Positive
2003
Report w eek ending
Number of tests
% Positive
2004
ILI Rate
7/31
7/3
6/5
5/8
4/10
3/13
2/14
1/17
12/20
11/22
10/25
80
70
60
50
40
30
20
10
0
9/27
8/30
Number of tests
4500
4000
3500
3000
2500
2000
1500
1000
500
0
ILI Reporting Rates, Canada, by
week 2003-2004
Rate per 1,000
patient visits
Influenza-like illness (ILI) reporting rates, Canada, by report week, 2003-2004 compared to
1996/97 through 2002/2003 seasons
100
75
50
25
0
35 37 39 41 43 45 47 49 51 1
2003
2003/2004 ILI Rate
3
5
7
9 11 13 15 17 19 21 23 25 27 29 31 33
Report week
2004
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 2039, 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)
Number of regions
30
25
20
2003
Report week ending
Localized activity
2004
Widespread activity
8/14
7/31
7/17
7/3
6/19
6/5
5/22
5/8
4/24
4/10
3/27
3/13
2/28
2/14
1/31
1/17
1/3
12/20
12/6
11/22
11/8
10/25
10/11
9/27
9/13
8/30
15
10
5
0
Influenza Strain Identification
H1N2
[1]
B/Hong
Kong/330/01-like
[7]
B/Sichuan/379/99like [33]
A/Panama/2007/99
(H3N2)-like
[25]
A/Fujian/411/02like (H3N2) [776]
A/New
Caledonia/20/99like (H1N1)
[3]
Influenza Hospitalizations in
Children- Pilot
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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
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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
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H5N1 - severe
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H9N2 - mild
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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)
1999 Hong Kong: 2 cases (mild)
2003 Hong Kong: 1 case (mild)
H7N7 - mild
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2003 Netherlands: 89 cases;1 death
2004 Canada: 2 cases
Avian H5N1 in Asia
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Continuing presence in Asia since 1996
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Documented direct avian to human transmission, Hong
Kong,1997
Enzootic and epizootic of unprecedented size and
complexity
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9 countries with ongoing outbreaks (most recently in Malaysia)
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Ongoing human cases with high case fatality, mostly in
healthy children and young adults
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Ongoing evolution of the virus’ antigenic, genetic and
functional properties
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No sustained human to human transmission to date
Why are We Concerned?
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Increasing countries/areas with avian influenza
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Ongoing human infection with avian H5N1
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Limited implementation of protective measures
Co-Circulating human influenza viruses
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Uncertainties on progress of control
Risk of genetic reassortment leading to pandemic strain
Majority of human population would have no
immunity
Influenza H5N1: expanded
host range?
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Domestic poultry
Wild birds
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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?
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Hong Kong accomplished this in 1997
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2004 H5N1 situation much more challenging
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Large areas affected in a large number of countries
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Slow and incomplete reporting of H5N1 findings
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Poor public health infrastructure
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Complex political and economic situations
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International action required: support for antivirals
PPE and compensation may help
Highly Pathogenic Avian Influenza
(HPAI) H7N3, BC, 2004
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42 commercial and 11 backyard premises
infected
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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
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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 Outbreak
Human Health Issues
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2 cases of lab confirmed human H7 infections in
cullers
Surveillance of exposed persons
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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
Canada
Santé
Canada
What’s new in the NACI
Statement?
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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
Vaccine composition for 20042005
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Trivalent vaccines to be used in Canada will
contain the following antigens:
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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)
Recommendation for children
6-23 months
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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:
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Vaccine effectiveness
Immunologic response to future encounters with
wild virus
Adverse events e.g. ORS in first time vaccinees
Oseltamivir
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Licensed for treatment and prophylaxis
Any concerns with resistance?
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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
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1988 - 1st draft plan
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1997 - lessons learnt from Hong Kong “Bird flu”
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1998 to 2002
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F/P/T Working Agreement (Mar 2001) : roles and responsibilities
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pandemic vaccine contract signed (Sep 2001)
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Pandemic Influenza Committee (PIC) established (Mar 2002)
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Pandemic Plan consultations – 43 organizations (Sep 2002)
2003
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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)
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Based on the nationally agreed upon goal
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Organized into “components” (framework for national
working group activities)
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Uses WHO Pandemic Phases
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Roles and responsibilities of F/P/T orders of
government identified as per Working Agreement
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Model for P/T contingency plans
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Contains checklists and technical annexes
Key Strategies and Planning
Components
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Rapid detection, monitor spread and assess impact
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Reduce spread and impact
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Surveillance and lab testing protocols
Border measures
Public health measures and infection control
Vaccines
Antivirals
Maintaining health services
Emergency and social services
Maintain public awareness
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Risk communication
The Plan: Current activities
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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 Nations
 Public Health Measures
 Surveillance
The Plan: Current activities - II
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Completion of antiviral drug strategy (2004)
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Testing domestic vaccine production
infrastructure, regulatory processes and clinical
trial protocols (2004-2005, pending funding)
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Influenza research agenda (2004)
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Further “exercising” of the Plan
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Completing the Recovery Section
Public Health and Border
Measures
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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
Droplet>>airborne
Droplet>airborne
Harder?
Age
distribution
Adults
Children/
Unknown
Unclear
Attack rate
Low (variable)
High
Harder
Transmission
Public Health Measures – Scope I
Decrease contact
Isolate cases
Quarantine contacts
Restrict travel
Restrict mixing
Hospital
Advisory
School closure
Home
Screening:
exit / entry
Ban mass
gatherings
Ban
Avoid crowded
places
Conveyances
Public Health Measures – Scope II
Decrease effective contact
Case hygiene
Contact hygiene
Environment
hygiene
Wear mask
Wear mask
Disinfection
Wash hands
Wash hands
Ventilation
Respiratory
hygiene
Antivirals
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Two main types
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Neuraminidase inhibitors (e.g. oseltamivir, zanamivir)
Amantadine
Why use antivirals?
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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
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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
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Options for use and stockpiling
•
•
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Guidelines on use of antivirals in short
supply
•
•
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Neuraminidase inhibitors for treatment and
prophylaxis
Amantadine for prophylaxis (currently not for
stockpiling)
Goal oriented
For planning purposes
Clinical guidelines
Current Thinking: Principles
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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:
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neuraminidase inhibitors for treatment or prophylaxis
amantadine for prophylaxis if strain susceptible
Current Thinking: Policy
Considerations
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Security of supply for antiviral drugs should
be addressed in the pre-pandemic period.
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Stockpiling of oseltamivir for nationally agreed upon
priority groups
The F/P/T governments should control the
supply and distribution of available antiinfluenza 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 Priorities
1.
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
Tx = Treatment
Px = Prophylaxis
Need to review definitions and estimates for priority groups
Cumulative Doses by Priority
Groups
TX hospitalized
Tx HCW and ESW
Px frontline HCW
Tx HR community
Px Remaining HCW
Institutionalized
Px ESW
HR hospitalized
Px of HR in Community
0
50
100
150
200
250
Doses (Millions)
NOTE: THESE PRELIMINARY ESTIMATES HAVE NOT GONE THROUGH SCIENTIFIC OR GOVERNMENT POLICY
CHALLENGE.
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
Approximately equal to
 Px Remaining HCW
14 million doses of
 Tx Institutionalized (Px?)
oseltamivir
 Px ESW (post-exposure)
 Px HR hospitalized
 Px HR community
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
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)
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Oseltamivir for duration of exposure plus 5 days (6 weeks max,
2 weeks between courses) – off-label use
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Post exposure prophylaxis (PEP) for 5 days following significant
exposure for those not on continuous prophylaxis
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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
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Complete priority group definitions and estimates
Funding for stockpile(s) (F/P/T)
Implementation issues:
•
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Evaluation issues:
•
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strategies for delivery, administration, monitoring of
distribution, uptake, wastage
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
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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