Health SantéCanada Canada

alPHa Teleclass, September 21, 2004alPHa Teleclass, September 21, 2004

InfluenzaA Pre-Season Update

Dr. Theresa Tam

Immunization and Respiratory Infections Division

Centre for Infectious Disease Prevention and Control

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 groups

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