The Pandemic Potential of the Avian Influenza H5N1 Virus

1
The Pandemic Potential of the Avian Influenza
H5N1 Virus

• Jill Taylor, Ph.D.
• Deputy Director, Wadsworth Center, NYSDOH

2
Presentation Agenda

• Influenza Facts
• Seasonal influenza
• Avian Influenza
• Pandemic Influenza
• Pandemic Preparedness

3
What is Influenza?

• Acute, febrile respiratory illness affecting
  upper and lower respiratory tract
• Epidemics caused by influenza viruses A and B
  (not C)

4
How You Get the Flu?

• Typical incubation 2 days Range 1-4 days
• Viral shedding
• Can begin 1 day before symptom onset
• Peak shedding first 3 days of illness
• Correlates with temperature
• Subsides after 5 days in adults, can be 10 days
  in children
• Transmission is predominately droplet spread

5
The Burden of Influenza

• Seasonal Influenza
• Globally 250,000 to 500,000 deaths each year
• In the United States each year
• 36,000 deaths
• gt200,000 hospitalizations
• 37.5 billion in economic costs from influenza
  and pneumonia
• Avian Influenza
• 256 human cases (including 151 deaths) in 10
  countries (as of October 16 2006)
• Pandemic Influenza
• An ever-present threat

6
If a Pandemic Happens What to Expect

• At the peak of a moderately severe pandemic
  influenza outbreak (i.e. 35 attack rate, 6 week
  duration), New York State (excluding New York
  City) can expect
• 14,916 influenza-related hospital admissions per
  week
• 3,728 influenza-related deaths per week
• 2,609 deaths in the hospital

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Seasonal influenza
http//www.cdc.gov/flu/weekly/
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Influenza Pandemics 20th Century
1918 Spanish Flu
1957 Asian Flu
1968 Hong Kong Flu
A(H1N1)
A(H2N2)
A(H3N2)
20-40 m deaths 675,000 US deaths
1-4 m deaths 70,000 US deaths
1-4 m deaths 34,000 US deaths
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Influenza A Virus

• 16 Antigenically distinct HAs
• (H1-H16)
• 9 Antigenically distinct NAs
• (N1-N9)
• Nomenclature
• A/NY/5/04 (H3N2)
• A/Chicken/HK/122/04 (H5N1)

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Natural Distribution of HA and NA
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Roles of Influenza HA and NA

• HA (Agglutinates RBCs)
• Surface Antigen
• Trimer
• Type I
• Binds SA
• Promotes Entry
• Fusion
• Cleaved
• pH 5

• NA (Dissociates agglutinated RBCs)
• Surface Antigen
• Tetramer
• Type II
• Cleaves SA from Galactose
• Promotes Release
• Removes SA
• E.R., Cell Surface, Virus

Also very important in pathogenesis !
12
How Influenza Viruses Change

• Antigenic Drift
• Small changes in virus over time
• New strains appear and replace older strains
• May not be recognized by antibodies to older
  strains
• Antigenic Shift
• Abrupt, major change (reassortment)
• Results in novel strain or new subtype
• Can cause pandemic influenza

13
Influenza A Virus Evolution Drift
Antigenic Drift
Gradual antigenic (genetic) change without a
change in subtype

• Point mutations
• HA and NA
• Immune pressure
• 36,000 deaths per year in US
• Continuous process

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Antigenic Shift
Complete antigenic (genetic) change due to HA
and/or NA subtype substitution
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Reassortment of RNA Segments from Different
Viruses
256 Possible Combinations
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Interspecies Transmission of Influenza A Virus
17
Pigs Are Mixing Vessels for Influenza A
Viruses
255 otherpossibilities
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Pandemic Strain Emergence Direct Infection
Avian virus
Avian Reservoir
19
Timeline of Emergence of Influenza A Viruses in
Humans
20
Antigenic Shift and Human Pandemics
1918 H1N1
1957 H2N2
1968 H3N2
SCIENCE VOL 306 15 OCTOBER 2004

• Direct interspecies transmission
• Reassortment between 2 co-infecting strains
• Reappearance of a previous strain

21
Avian influenza (H5N1)

• Hong Kong 1997
• First direct avian-to-human infection and serious
  disease
• 18 confirmed cases, 6 deaths
• Risk factor live poultry markets
• Hong Kong 2003
• HK residents returning from S. China
• 2 confirmed cases, one death
• Source of infection unclear

22
Avian influenza
23
Avian Influenza A (H5N1) Outbreak
151 fatal human H5N1 Cases (1-04 to
11-06) (Updated November 3, 2006) Azerbaijan (5)
Cambodia (6) China (14) Djibouti (0) Egypt
(6) Indonesia (55) Iraq (2) Thailand (17) Turkey
(4) Vietnam (42)
httpwww.who.int/csr/disease/avian_influenza/count
ry/cases_table_2006_10_16/en/index.html
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Evolution of H5N1 Viruses
SCIENCE306, 2004
K. S. Li, Y. Guan, Nature 430 (6996)209-213,
2004.
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Pathogenicity of avian influenza strains in
domestic birds

• Low pathogenicity
• Invades only respiratory and digestive tract
  tissues
• Causes mild illness
• May mutate to high pathogenicity
• High pathogenicity
• Invades many tissues
• Causes severe illness and mortality
• H5 and H7

26
Avian influenza virus

• Outbreaks not uncommon in domestic poultry
• 28 outbreaks globally since 1959
• 7 in US
• 4 involved LP to HP transition
• Frequently found in wild birds 10 isolations in
  US since 8/06 - all low-path

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AVIAN INFLUENZA
Surveillance Consortium which will Track Avian
Influenza along major flyways
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Contact between wild and domestic birds
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Proximity of birds and humans
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Economic losses
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Will it happen here?

• H5 outbreaks have already occurred
• Very efficient surveillance network
• Very different husbandry practices
• But..remember SARS in 2003

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Spread from Hotel M, Hong Kong February 2003
Guangdong Province, China
A
A
Hotel MHong Kong
A
Hong Kong SAR 95 HCW
H,J
H,J
gt100 close contacts
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(No Transcript)
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R0 basic case reproduction number On
average, for each primary case, to how many
secondary cases will that infected person
transmit disease? (if that person is not
isolated) For SARS, R0 3 gtgt possible to
control by isolation and quarantine
procedures For influenza, R0 10
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What is our strategy?
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How do we diagnose influenza?

• Multiple levels of testing to determine
• Virus - Influenza A
• Subtype H3N2
• Strain A/NY/1452/06

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Antigen detection assays rapid tests

• More sensitive for pediatric than adult
• Fast but sample dependent
• Expensive
• A positive result is meaningful
• A negative result may only mean not enough virus
  to enable detection

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Conventional virus culture
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Evaluation of virus growth
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Evaluation of virus growth
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PCR molecular amplification
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Conventional RT-PCR assay for sub-typing
influenza virus

• Amplification of HA and NA genes
• Requires gel analysis
• Amplicon can sequenced for strain identification
• TAT about 12 hours

Controls
Specimens
HA1 HA3 Infl B
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Real-time PCR
44
Influenza A real-time RT-PCR assay
97 Efficiency Y-intercept 35.4 R2 .995
Slide courtesy of Dr. Amy Dean
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Control methods

• Vaccination
• Anti-virals

46
Control of Seasonal Influenza Vaccination

• Much of morbidity/mortality can be prevented by
  annual vaccination
• In young adults, vaccine 70-90 effective
• In elderly and immunocompromised, vaccine less
  effective in preventing influenza infection but
  very effective in reducing illness severity,
  complications (70) and death (85)
• In nursing homes, 50 decrease in
  hospitalizations, 80 decrease in death

47
Pandemic Vaccine Supply

• Assumptions
• No vaccine currently available production will
  need to be specific for pandemic strain
• 4-8 months until first vaccine doses available
• At least two doses will be needed for protection
  
• U.S. manufacturing capacity
• Estimated production 5 million doses/week
• Implication less than 2 of the population may
  be protected per week

48
Antiviral Medications

• Treatment target M and N proteins
• Can decrease duration of illness (by 1-3 days)
  and severity of uncomplicated seasonal influenza
• Some strains of flu no longer respond to the most
  common antivirals (Amantadine, Rimantadine)
• Newest generation of antivirals (Tamiflu,
  Relenza) remain in limited supply
• Should be initiated within 48 hours of symptom
  onset
• Treatment after 48 hours may have no benefit

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Pandemic Antiviral Supply

• Antivirals in the Strategic National Stockpile
• Oseltamivir (Tamiflu)
• Federal plan increase stockpile, in
  collaboration with the States, to treat 25 of
  US population (at least 81 million treatment
  courses)
• Oseltamivir production
• Limited worldwide and U.S. production capacity
• U.S. supply chain being established
• Expected production capacity 1.25 million
  courses per month

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Pandemic Influenza Doctrine Saving Lives - 1

• Prevent or at least delay introduction into the
  United States
• May involve travel advisories, exit or entry
  screening
• For first cases, may involve isolation short-term
  quarantine of arriving passengers

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Pandemic Influenza Doctrine Saving Lives - 2

• Slow spread, decrease illness and death, buy time
• Antiviral treatment and isolation for people with
  illness
• Quarantine for exposed
• Social distancing
• Vaccine when available
• Local decisions

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Individual Infection Control Strategies

• Respiratory hygiene/cough etiquette and hand
  hygiene are effective strategies to stop the
  spread of germs.
• We should make good hygiene a habit.
• Our health is in your hands!
  

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Individual and Family Preparedness is Crucial!

• We might have to take care of ourselves and those
  around us
• Would you be ready?

54
Public Health PreparednessA Shared
Responsibility!

• Local - state - federal
• Domestic international
• Public private
• Multi-sector
• Animal human
• Health protection homeland security economic
  protection

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In a severe pandemic... actions of individuals,
businesses, and community organizations,as much
as those of government, will greatly determine
the outcome!
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Will Avian Flu Cause the Next Pandemic?

• No one knows!
• The H5N1 virus could change to spread more easily
  among humansbut it might not
• It could swap genes with another animal virus,
  or with a human flu virus
• Death rate may or may not be lower than with
  current human H5N1 cases
• What about other subtypes?

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Avian flu comes to Florida
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More information..

• http//www.pandemicflu.gov
  
• http//www.nyhealth.gov
• http//www.who.int/csr/disease/avian_influenza/en/
  
• http//www.cdc.gov/flu/avian/
• http/www.usda.gov/birdflu
• http//www.cidrap.umn.edu/cidrap/content/influenza
  /avianflu/
• My e-mail jxt07_at_health.state.ny.us

A number of slides in this presentation were
graciously provided by Lora Santilli and Drs.
David Wentworth, Kirsten St. George and David
Spiro