Pandemics: Developing a Coordinated Response

Allen S. Craig, MD, FAAFP

Deputy Director National Center for Immunization and Respiratory Diseases

Centers for Disease Control and Prevention

http://www.hhs.gov/

Influenza Virus Transmission

• Influenza viruses infect respiratory tract cells

• Viruses in respiratory secretions • Transmission of influenza viruses

– Person-to-person transmission through close contact

– Primarily through contact with large respiratory droplets and aerosol

– Transmission from objects (fomites) possible

2

U.S. Centers for Disease Control and Prevention

http://www.hhs.gov/

Influenza

Human infection with influenza viruses 2 common Influenza virus types Types A, B Type A viruses cause greatest illness and death in

humans • Type A viruses are subtyped • (H3N2), (H1N1) are current circulating human

subtypes • 2009 pandemic influenza A (H1N1) virus

3

http://www.hhs.gov/

Individuals at Increased Risk of Complications from Influenza

• Age >65 years

• Young children and especially those age < 2 years

• Persons with chronic medical conditions • Heart or lung disease, including asthma • Metabolic disease, including diabetes • HIV/AIDs, other immunosuppression

http://www.hhs.gov/

Laboratory-Confirmed Influenza Hospitalizations Preliminary cumulative rates as of April 1, 2017

All age groups through Week 13

Cumulative rate for the season of 57.2 hospitalizations per 100,000 population

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http://www.hhs.gov/

Individuals at Increased Risk of Complications from Influenza

• Pregnant women

• Nursing home residents

• Morbidly obese

• Children on long-term aspirin therapy • Alaska Native and Native Americans

PresenterPresentation Notes.

http://www.hhs.gov/

Estimated Annual Burden of Seasonal Influenza Influenza in the United States

Deaths: 3,000 – 49,000 Hospitalizations: 54,000 – 430,000

Cases: 15 – 60 million

Direct Medical Costs: $10.4 billion

http://www.hhs.gov/

Surface proteins (major antigens)

• Hemagglutinin (HA) (18 types)

• Responsible for attachment to host cells during early stages of infection

• Antibody to HA is protective

• Neuraminadase (NA) (11 types)

• Involved in release of virions from infected cells

• Antibody to NA can help modify disease severity

Influenza Viruses: Surface Proteins

http://www.hhs.gov/

H1 H2 H3 H4 H5 H6 H7 H8 H9 H10 H11 H12 H13 H14 H15 H16 H17 H18

N1 N2 N3 N4 N5 N6 N7 N8 N9 N10 N11

Influenza A HA and NA Virus Subtypes

Other Animals

Other Animals

Other Animals

Other Animals

Other Animals

Other Animals

Novel Influenza www.cdc.gov/flu

http://www.hhs.gov/

Influenza Terms Defined • Seasonal (or common) flu (Influenza A and B):

• Most have some immunity • Up to 500,000 deaths globally/year • ~50,000 - 400,000 hospitalizations/year in US • Vaccine is available every flu season to match circulating

strains • Avian (or bird) and swine flu (Influenza A):

• Disease primarily of animals—not readily transmitted from birds/swine to humans

• May cause various levels of illness in birds, poultry and swine

• No human immunity • Limited if any, human vaccine available

http://www.hhs.gov/

Influenza Terms Defined • Pandemic flu (Novel influenza A):

• New virus emerges without warning

• Humans have limited or no natural immunity • Spread easily around the world–causes illness and death

• No/very limited vaccine available at start of pandemic • May be mild, moderate, or severe

http://www.hhs.gov/

Influenza is Particularly Unpredictable – and Novel Strains are Always Emerging and Spreading

Seasonal influenza infects ~20% of the population each year

An influenza pandemic has unparalleled potential to cause widespread illness, death, and economic dislocation

Emerging/novel strains could be highly transmissible and highly lethal

http://www.hhs.gov/

http://www.hhs.gov/

Laboratory – Zoonotic Influenza March 28- April 3, 2017

HPAI H5 outbreaks animals - Reported to OIE and/or FAO; data is from OIE and FAO open sources that are available online

Wild bird

Domestic Poultry

Captive Birds

H5N6 H5N8

H5N1 H5N2 H5N5

H5NX R

S

B

V H5N8 (1)

Taiwan H5N2 (8)

Ni

Vietnam H5N1 (2)

Sl Fr

It

H5N8 Romania(9) Slovakia(1)

H5N1 Nigeria(2) Cameroon(2)

Ca

H5N8 Belgium(1) Italy(3) Slovenia(3) Bosnia&Herzegovina(1)

France H5N1 (1) H5N8(26)

Malaysia H5N1 (10)

http://www.hhs.gov/

H7N9 Avian Influenza in China (2013-Present)

Total Human Cases • 1,329 cases / 412 deaths* • 85% poultry exposure • 68% admitted to an ICU • 40% death*

5th Wave Cases (current) • 531 cases / 89 deaths*

Influenza Risk Assessment remains highest of evaluated novel viruses

Human cases higher in current wave

No sustained human-to-human transmission

Genetic changes indicate need for new CVVs

http://www.hhs.gov/

Geographic Distribution of 5th Wave Epidemic (Oct 2016-Mar 2017) Human A(H7N9) Infections Reported by Date of Onset (N=566)

Unclassified//FOUO

Liaoning 2

Beijing 2

Shandong 6

Henan 14

Jiangsu 136

Shanghai 6

Zhejiang 83

Anhui 55

Hubei 26

Jiangxi 37

Fujian 30

Guangdong 61

Guangxi 24

Hunan 47 Guizhou

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Sichuan 11

Yunnan 2

Chongqing 2

Taiwan 1

Hong Kong 5

Macao 2

Heilongjiang

Jilin Inner Mongolia

Gansu 1 Shaanxi

Tibet 1

Qinghai

Ningxia Shanxi

Hebei Tianjin

Xinjiang

0 140

Mongolia

North Korea

South Korea

Japan

Russia

Vietnam

Laos

Myanmar

Thailand

India

India

Bhutan

Nepal

Bangladesh

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http://www.hhs.gov/

Virologic Update

• Current Chinese viruses – Eastern/Yangtze River Delta viruses reacted with antisera raised

to 2013 candidate vaccine viruses at titers that were 4-16 fold reduced compared to homologous virus titers

– Southern/Pearl River Delta viruses remain antigenically similar to 2013 candidate vaccine viruses

• Antiviral drug susceptibility – Neuraminidase gene sequence data are available for 75 of the

5th epidemic cases • 7 out of 75 viruses (9.3%) have markers in the

neuraminidase gene indicating reduced susceptibility to one or more neuraminidase inhibitors

• Viruses recovered with resistance markers were collected from patients treated with antivirals

http://www.hhs.gov/

Antigen 12M doses (7.5 µg dose) of egg-based H7N9 (as bulk

antigen) Excellent stability in storage 28M dose shortfall to meet 40M dose preparedness goal

Adjuvant ASO3: 24M doses in bulk AS03: 4M doses in Final Container 12M dose shortfall to meet 40M dose preparedness goal

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Current H7N9 U.S. Vaccine Inventory

http://www.hhs.gov/

5th H7N9 wave: October 1, 2016 to present

Influenza Risk Assessment Tool or IRAT

What elements are included in the influenza risk assessment algorithm? Identified 3 categories of consideration - Properties of the virus - Attributes of the population - Ecology & epidemiology

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http://www.hhs.gov/

5th H7N9 wave: October 1, 2016 to present

Influenza Risk Assessment Tool or IRAT

Situation/Question 1 (Emergence): What is the risk that a novel* virus has the potential for sustained human-to-human transmission.

Situation/Question 2 (Impact): If the virus were to achieve sustained human-to-human transmission, what is the risk that a novel virus has the potential for significant impact on public health? *novel = a virus that is not currently circulating in humans

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http://www.hhs.gov/

5th H7N9 wave: October 1, 2016 to present

IRAT preliminary scoring of a 5th wave virus

Virus: H7N9 [A/Hong Kong/125/2017] Score change Antigenic Relatedness Antivirals & Treatment Options Genomic Variation

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http://www.hhs.gov/

IRAT Impact & Emergence Average Risk Scores H5 & H7 Viruses

1.0

2.0

3.0

4.0

5.0

6.0

7.0

8.0

9.0

10.0

1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0

Impa

ct

Emergence

H1N1 Duck

H5N1H3N2 Canine

H5N2H5N8

H10N H7N7H9N2

H3N2v

H7N9H5N1-VNH5N6 Asia

http://www.hhs.gov/Chart6

H7N9 [A/Shanghai/02/2013]6.47.2 H3N2 variant [A/Indiana/08/2011]64.5 H9N2 G1 lineage [A/Bangladesh/0994/2011]5.65.4 H5N1 Clade 1 [A/Vietnam/1203/2004]5.26.6 H5N6 [A/Yunnan/14564/2015] – like56.6 H7N7 [A/Netherlands/2019/2003]4.59999999999999965.8 H10N8 [A/Jiangxi-Donghu/346/2013]4.36 H5N8 [A/gyrfalcon/Washington/41088/2014]4.24.5999999999999996 H5N2 [A/Northern pintail/Washington/40964/2014]3.84.0999999999999996 H3N2v [A/canine/IL/12191/2015] 3.73.7 H5N1 [A/American green-winged teal/Washington/1957050/2014] 3.64.0999999999999996 H1N1 [A/duck/New York/1996]2.29999999999999982.4

Emergence

Impact

Sheet1

VirusEmergence ScoreImpact Score

● A H7N9 [A/Shanghai/02/2013]6.47.2

● B H3N2 variant [A/Indiana/08/2011]6.04.5

● C H9N2 G1 lineage [A/Bangladesh/0994/2011]5.65.4

● D H5N1 Clade 1 [A/Vietnam/1203/2004]5.26.6

● E H5N6 [A/Yunnan/14564/2015] – like5.06.6

● F H7N7 [A/Netherlands/2019/2003]4.65.8

● G H10N8 [A/Jiangxi-Donghu/346/2013]4.36.0

● H H5N8 [A/gyrfalcon/Washington/41088/2014]4.24.6

● I H5N2 [A/Northern pintail/Washington/40964/2014]3.84.1

● J H3N2v [A/canine/IL/12191/2015] 3.73.7

● K H5N1 [A/American green-winged teal/Washington/1957050/2014] 3.64.1

● L H1N1 [A/duck/New York/1996]2.32.4

IRAT Emergence and Impact - Average Risk Scores

H7N9 [A/Shanghai/02/2013]6.47.2 H3N2 variant [A/Indiana/08/2011]64.5 H9N2 G1 lineage [A/Bangladesh/0994/2011]5.65.4 H5N1 Clade 1 [A/Vietnam/1203/2004]5.26.6 H5N6 [A/Yunnan/14564/2015] – like56.6 H7N7 [A/Netherlands/2019/2003]4.59999999999999965.8 H10N8 [A/Jiangxi-Donghu/346/2013]4.36 H5N8 [A/gyrfalcon/Washington/41088/2014]4.24.5999999999999996 H5N2 [A/Northern pintail/Washington/40964/2014]3.84.0999999999999996 H3N2v [A/canine/IL/12191/2015] 3.73.7 H5N1 [A/American green-winged teal/Washington/1957050/2014] 3.64.0999999999999996 H1N1 [A/duck/New York/1996]2.29999999999999982.4

Emergence

Impact

What is a Pandemic?

A new influenza A virus appears or “emerges” in the human population, and It causes serious illness in humans, and It spreads easily from person to person worldwide

Pandemic severity can be mild, moderate, or severe

http://www.hhs.gov/

WHO Phases

http://www.hhs.gov/

Preparedness and Response Framework for Novel Influenza A Virus Pandemics: CDC Intervals

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http://www.hhs.gov/

CDC’s Pandemic Severity Framework • Published in 2013 • Tool that takes into

account both disease transmission and clinical severity

• Allows comparison of characteristics of an emerging influenza virus and the disease it causes

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http://www.hhs.gov/

Initial Assessment of the Potential Effects of an Influenza Pandemic

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http://www.hhs.gov/

2006-07

2007-08

2009 pandemic

1957 pandemic

1968 pandemic

A C

B D

Modern pandemic range

Seasonal range

Pandemic Severity Assessment Framework

1918 pandemic

Adapted from: Reed C, Biggerstaff M, Finelli L, Koonin LM, et al. Novel framework for assessing epidemiologic effect of influenza epidemics and pandemics. Emerg Infect Dis 2013;19(1):85–91.

http://www.hhs.gov/

Influenza Pandemics Are Different from Other Threats • Infectious disease that can spread

rapidly • Severity is greater than seasonal flu • Unannounced • Can last 12-18 months • No physical damage, but human toll:

– Can affect 30-40% of population • Impact on healthcare facilities • Increase in community anxiety and

mental health concerns • Likelihood of societal disruption

– From social distancing measures – From fear and loss

http://www.hhs.gov/

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Timeline of Pandemics and New Influenza A Subtype Infections in Humans

H1

H3 H2

1918 Spanish

Influenza H1N1

1957 Asian

Influenza H2N2

1968 Hong Kong

Influenza H3N2

1915 1925 1935 1945 1955 1965 1975 1985 1995 2005 2010 2015

H7 H5

Avian Influenza

H9

H1

H1

2009 pH1N1

http://www.hhs.gov/

1918-19 Global Influenza Pandemic

50-100 million people killed worldwide (3-5% of global population)

– Life expectancy temporarily declined by 12 years

Massive global economic disruption lasting months

Killed more people in 24 weeks than AIDS killed in 24 years; more in a year than plague killed in a century

– Most killed were previously healthy young adults

– Health care systems overwhelmed worldwide

US Army soldiers in hospital ward ill with influenza

http://www.hhs.gov/

1918

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http://www.hhs.gov/

2009 H1N1: Not the Pandemic We Planned For!

• New type of flu • Location of first cases • Type of flu (expected H5N1) • Pandemic declaration • Severity

– Early in outbreak, very difficult to assess

– Mild – moderate • Heterogeneity in outbreak • Some had partial immunity

Late Feb – Early March First cases in Mexico

April 15 Recognition of a Novel Influenza Swine-Origin Virus

April 27 CDC posts 40 gene sequences on GenBank

May 1 Diagnostic Kits Shipped to State Labs

May 2 Diagnostic Kits Shipped to WHO Network

May 27-28 Vaccine Strain Shipped to Manufacturers

Novel H1N1 Influenza, 2009: Rapid Detection, Identification & Response

Characteristics of 2009 H1N1 Influenza April 15, 2009 to April 10, 2010

Cases 61,000,000

Hospitalizations 274,000

Deaths 12,470

0-4

5-24

25-4

9

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4

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http://www.hhs.gov/

Learning from the 2009 Pandemic Achievements

Rapidly identified novel virus Developed and distributed

diagnostic reagents quickly Vaccinated ~80m US residents Increased use of antiviral

drugs for severely ill Lessons

Preparation paid dividends Vaccine production

expectations Flexibility is critical Importance of communication

PresenterPresentation Notes

http://www.hhs.gov/

Mild-Moderate Severity Pandemic in 2009

• The risk of a future severe pandemic remains

• Emergence of novel influenza strains

• Continued spread of H5N1 and other viruses in wild birds throughout the world

• FLU IS UNPREDICTABLE!

• So planning is needed

Economic Impact of a Pandemic on the U.S.

• 89,000 to 207,000 deaths

• 314,000 to 734,000 hospitalizations

• 18 to 42 million outpatient visits

• 20 to 47 million additional illnesses

• Patients at high risk (15% of the population) would account for

approximately 84% of all deaths.

• Estimated economic impact would be US$71.3 to $166.5 billion

Melzer, M et al. The Economic Impact of Pandemic Influenza in the United States: Priorities for Intervention. Emerg Infect J 1999;5:5

What Can Be Done to Minimize the Risk to Human Health Caused by a Pandemic? Plan!

http://www.hhs.gov/

U. S. Pandemic Planning Assumptions

Moderate (1957-like)

Severe (1918-like)

Illness 90 million (30%) 90 million (30%)

Outpatient medical care 45 million (50%) 45 million (50%)

Hospitalization 865,000 9,900,000

ICU care 128,750 1,485,000

Mechanical ventilation 64,875 745,500

Deaths 209,000 1,903,000

http://www.hhs.gov/

Pandemic Response: Potential Tools in Our Toolbox

• Pandemic Vaccine

• Antiviral Medications

• Infection control measures

• Social Distancing (keeping sick people and well people apart)

http://en.wikipedia.org/wiki/Image:Tamiflu.JPG

TM

Social Distancing

Key Pandemic Social Distancing Strategies • Sick people stay home • Schools close or dismiss students and prevent re-

congregating in the community • Cancellation of mass gatherings • Postpone non-essential travel • Teleworking • Increase space between people in the workplace • Ask all members of a household with a sick person to

stay home

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http://www.hhs.gov/

Why Plan Now? • Pandemic – it will happen again • Pandemic response is not like other short-term

threats – it is disruptive for prolonged period of time • Advance planning is necessary as little or no notice

will be given when a pandemic begins • Maintaining critical infrastructure is vital

http://www.hhs.gov/

Why Plan Now? (continued) • Health care facilities will have a key role in

treating patients and protecting the health of employees and the community

• Planning takes time, partnerships, and resources • Some mitigation strategies (social distancing) can

be disruptive • Planning for a pandemic can strengthen overall

continuity planning for other types of emergencies and disease threats

http://www.hhs.gov/

Key Areas Of Pandemic Influenza Planning for Health Care Facilities

• Plan for the impact on organizations and operations • Plan to protect clinical, administrative staff, patients

and visitors • Write an infection control plan – personal protective

equipment • Communicate to and educate people • Test and exercise your plans • Coordinate plans, response, and recovery

46

http://www.hhs.gov/

HR Policies Can be Critical Employee Protection Policies during a Pandemic

• Plan for emergency policies – CDC guidance - “Sick persons should stay home” – Develop just in case ”emergency sick leave and

other leave policies“ – Set and model the expectation that sick

employees must stay home – Expect that some employees at highest risk may

ask for flexible work arrangements

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http://www.hhs.gov/

Important to Establish Local Partnerships - Now

• Response will be led by local and state public health officials and will be based on local conditions

• Antivirals will be distributed by Strategic National Stockpile to state health departments and targeted for treatment (not prophylaxis)

• Pandemic vaccine will be distributed to state health departments – Who is vaccinated first? – Availability of occupational health resources – Role of pharmacists

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http://www.hhs.gov/

Vaccine Tiers and Target Groups for a Severe Pandemic

http://www.hhs.gov/

Summary

• A future influenza pandemic is inevitable

• Avian flu virus strains continue to evolve and pose risks

• Steps can be taken to mitigate impact - these steps require plans and action before a pandemic

• Health care workers and facilities are critical infrastructure

• Seasonal influenza responses permit some degree of practice for an influenza pandemic

• Tools and guidance exist from CDC and others

http://www.hhs.gov/

We can and should take action now to

prepare for a future pandemic and protect the health of our workforce and

our health care facilities.

http://www.hhs.gov/

THANK YOU!

acraig@cdc.gov

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http://www.hhs.gov/

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http://www.hhs.gov/

Slide Number 1Influenza Virus TransmissionInfluenzaIndividuals at Increased Risk of Complications from InfluenzaLaboratory-Confirmed Influenza Hospitalizations�Preliminary cumulative rates as of April 1, 2017Individuals at Increased Risk of Complications from InfluenzaSlide Number 7Slide Number 8Influenza A HA and NA Virus SubtypesInfluenza Terms Defined�Influenza Terms Defined�Influenza is Particularly Unpredictable – and Novel Strains are Always Emerging and SpreadingSlide Number 13Laboratory – Zoonotic Influenza �March 28- April 3, 2017H7N9 Avian Influenza in China (2013-Present)�Geographic Distribution of 5th Wave Epidemic (Oct 2016-Mar 2017)�Human A(H7N9) Infections Reported by Date of Onset (N=566) Virologic UpdateCurrent H7N9 U.S. Vaccine InventorySlide Number 19Slide Number 20Slide Number 21IRAT Impact & Emergence Average Risk Scores�H5 & H7 VirusesSlide Number 23WHO PhasesPreparedness and Response Framework for Novel Influenza A Virus Pandemics: CDC Intervals CDC’s Pandemic Severity FrameworkInitial Assessment of the Potential Effects of an Influenza PandemicSlide Number 28Influenza Pandemics Are Different from Other ThreatsSlide Number 301918-19 Global Influenza Pandemic19182009 H1N1: �Not the Pandemic We Planned For!Novel H1N1 Influenza, 2009:�Rapid Detection, Identification & ResponseCharacteristics of 2009 H1N1 Influenza�April 15, 2009 to April 10, 2010Slide Number 36Mild-Moderate Severity Pandemic in 2009Economic Impact of a Pandemic on the U.S. What Can Be Done to Minimize the Risk to Human Health Caused by a Pandemic? Plan!Slide Number 40Pandemic Response: Potential Tools in Our ToolboxSlide Number 42Key Pandemic Social Distancing StrategiesWhy Plan Now?Why Plan Now? (continued)Key Areas Of Pandemic Influenza Planning for Health Care FacilitiesHR Policies Can be Critical Employee Protection Policies during a Pandemic�Important to Establish Local Partnerships - NowVaccine Tiers and Target Groups for a Severe PandemicSummarySlide Number 51THANK YOU!��acraig@cdc.govSlide Number 53