Defining Priority Groups for Pandemic Vaccine & Antiviral

Drugs: Risk Groups and Critical

Infrastructure

Ben Schwartz, M.D.National Vaccine Program Office,

U.S. Department of Health and Human Services

NVAC Meeting, July 19, 2005

Background

Pandemic vaccine supply will be limited Expect only U.S.-produced vaccine in a pandemic Estimate ~6 million doses/wk from U.S.

manufacturing Antiviral drug (neuraminidase inhibitor)

supply also will be limited U.S. supply chain for oseltamivir expected in late-

2005 but will produce only ~15 million courses/yr Stockpiled drugs will be major source of pandemic

supply

Background

Given limited supply, priority groups must be defined for receipt of early vaccine & antiviral drugs

Targeting the limited supply of vaccine and antiviral drug to high risk groups and persons providing critical infrastructure will help achieve pandemic response goals of: Decreasing pandemic health impacts Decreasing societal impacts Limiting economic disruption

Presentation Objectives

Present analysis of high risk groups for severe influenza disease and death in a pandemic to facilitate designation of priority groups

Define critical infrastructures and estimate population sizes in these groups

Methodology

Definition of high-risk groups Working group (Pascale Wortley & Ted Eickhoff,

co-chair) analyzed data on risk groups in prior pandemics and interpandemic influenza

Definition of critical infrastructure Working group (Carolyn Bridges, chair) assessed

potential critical infrastructure groups Collaboration with the Department of Homeland

Security Total industry populations were further analyzed

to identify those who provide essential services

Part 1: Risk groups for illness, hospitalization, and death

0

5

10

15

20

25

30

35

40

45

<1 1 to4

5 to9

10 to14

15 to19

20 to24

25 to29

30 to34

35 to39

40 to44

45 to49

50 to54

55 to59

60 to64

65 to69

70 to74

75+

Clinical Influenza Attack Rates, 1918

*approximations based on figure in Frost 1919—household surveys conducted Dec 1918

Hennessey (1964)

Dunn(1959)

Jordan*(1958)

Woodall(1958)

Chin(1960)

Pop. Tecumseh households

5 schools, 1 factoryLA parish

Cleveland families

General practice, London

Family contacts of KC HS students

0-4 26% 31% (pre-school)

43% 31% 32%

5-9 38% 39% (elementary)

58% 49% 33%

10-14 40% 48% (high school)

59% 39%

15-19 34% 47% 25%

(60+ 12%)

38%

20-29 20% 20%(adults)

19% 27%

30-39 16%

40-49 14% 17%

50+ 10%

Clinical Influenza Attack Rates, Fall 1957

*lab-confirmed

Monto (1970)* Davis (1970)

<1 16.5% 40%

1-4 40%

5-9 11.6% 43%

10-14 9.2% 40%

15-19 8.9% 38%

20-24 12.7% 35%

25-29 33%

30-39 8.1% 38%

40-49 8.9% 38%

50-64 35%

65+ 30%

Population Adrian (comparison to Tecumseh)*

Southwest high school families (Kansas City)

Clinical Influenza attack rates, Nov 1968-Jan 1969

*weekly mean averages

0

200

400

600

800

1000

1200

<1 1 to4

5 to9

10to14

15to19

20to24

25to29

30to34

35to39

40to44

45to49

50to54

55to59

60to64

65to69

70to74

75+

per

100

,000

Pneumonia & Influenza (P & I) Mortality Rates, 1918

*Frost 1919, approximations based on figure

0

50

100

150

200

250

300

<1 1 to 24 25 to 44 45 to 64 65+

rate

P&I Mortality Rates (per 105), 108 Cities, Aug-Dec 1957

Age groupDauer 1958

0

200

400

600

800

1000

1200

1400

<1 1 to4

5 to14

15 to24

25 to34

35 to44

45 to54

5 to64

65 to74

75 to84

>84

rate

P&I Mortality Rates (per 105), 1968-69

Age groupLuk, 2001

Proportion of Excess P & I Deaths in Persons <65 y.o. in Influenza Pandemic & Inter-pandemic Seasons, 1918-95

Simonsen et al. JID 1998

Hospitalizations and Deaths Among Persons >65 Yrs. Old, 1996-1998

050

100150200250300350400

Year 1 Year 2

Source: Hak 2002 CID

*Renal disease, immunodeficiency, organ transplants, non-hematologic cancer

Rate

(p

er

10

5)

Hospitalizations and Deaths per 10,000 Persons 15-64, 1973-1992

0

50

100

150

200

250

300

350

400

Neuzil 1999 JAMA

Neuzil 2003 JAIDS*NS

Range 36-76/10,000

*HIV-HAART data: 1995-1999

P & I Deaths by Number of High Risk Conditions - Oregon HMO

Status P&I deaths

Population Rate per 105

15-44 No HR 0 134,000 -

1 HR 0 6,260 -

>1 HR 0 260 -

45-64 No HR 1 43,900 2

1 HR 7 6,900 10

>1 HR 4 1,060 377

>64 No HR 1 11,760 9

1 HR 14 6,460 217

>1 HR 11 1,380 797Barker, Arch Intern Med 1982

Previous Hospitalization as a Risk Factor for Severe Influenza

39 – 46% of the elderly discharged for an influenza-associated respiratory condition had a recent hospitalization

62 – 67% of those who died had a recent hospitalization

6% of elderly persons were hospitalized during the influenza season

Fedson, Annals of Internal Medicine 1992;116:550-5

Adjusted OR

Previous P/I hosp. 8.1 (5.7-11.5)

Outpatient visits 1.5 (1.3-1.8)

Heart disease 1.2 (1.0-1.5)

Pulm disease 1.8 (1.4-2.3)

Dementia, stroke 2.1 (1.6-2.7)

Renal disease 1.5 (1.1-2.1)

Cancer 4.9 (3.4-7.0)

Diabetes ns

Immunodeficiency* ns

Risk Factors for P & I Hospitalization & Death During Influenza Season

* Immunodeficiency and organ transplants Hak 2004 JID

Specific Conditions: Bone Marrow Transplants

Limited studies (Nichols 2004, Whimbey 1994) , but both suggest high rates of complications.

Largest study (Nichols): 18/62 BMT pts with lab confirmed influenza had LRI; 6/62 died (5 of 6 had LRI)

Likely greater benefit from antiviral drugs than vaccine

Risk of Pandemic Influenza Death in Pregnancy

Harris 1919: case series of pregnant women with influenza; 50% had pneumonia, and 50% CFR w/ pneumonia (7-9th months: 60% vs 1-6 m:45-53%).

Woolston 1918: 2154 pts admitted to Cook County Hospital; 50% of pregnant women died compared with 33% of other pts.

Greenberg 1958: NYC mortality data fall 1957; 47 P&I deaths in women 15-49; 22/47 (47%) were pregnant.

Group Number in millions*

Comment

Transplants 0.15 Includes solid organ transplants

Cancer 1.4 Annual incidence—assume equal to immunosuppresed

> 2 high risk conditions

10 Ages 2-64 and 65+

<12 months 4

Pregnant women

0.4

*groups may overlap

Size of Potential Priority Groups for Pandemic Vaccine & Antiviral Drugs

Part 2: Critical Infrastructures for a pandemic response

Critical Infrastructure: Potential Vaccine and Antiviral Target Groups

Definition of infrastructure:

“The framework of interdependent networks and systems comprising identifiable industries, institutions and distribution capabilities that provide a reliable flow of products and services essential to the defense and economic security of the of the US, the smooth functioning of government at all levels, and society as a whole.”

President’s Commission on Critical Infrastructure Protection, Critical Foundations Protecting America’s Infrastructure, October 1997

Approach to Define Critical Infrastructures & Populations

Focus on occupations/industries that contribute to achieving pandemic response goals

Consider critical infrastructure definitions from other sources (White House, Congress, Canadian pandemic plan) and experience from preparedness exercises

Defined population sizes from Bureau of Labor Statistics data

Honed populations based on input from DHS

Key Issues and Limitations

Importance of networks and supply chains E.g., what industries/personnel are required to

assure that medical supplies reach healthcare facilities and food reaches persons in cities?

Estimates of absenteeism during a pandemic What proportion of persons will miss work and

can function be preserved with this work loss? Experience from prior pandemics is not

informative and no comparable health emergencies have occurred

Estimate of Days Lost From Work Due to Illness in Self or Family

Modeled lost work days from illness using FluAid and FluSurge (based on 1957/1968 pandemics) and 2000 Census

Inputs: Days lost from work due to illness Days lost from work due to caring for family member Employment rate, marriage rate, work days per month

Assumed outbreak period 8 weeks and 25% influenza illness rate as base-case

Xinzhi Zhang, MD PhD and Martin I. Meltzer, PhD MS

Model Inputs and Total Lost Work Days

Scenario

Self-care

Outpatient

Hosp. DeathSelf-care

Outpatient

Hosp. Death

A 1 3 7 40 1 3 7 10

B 5 7 12 40 3 5 10 12

Days of work for own illness Days caring for others

Work Days Lost

Scenario A Scenario B

Most Likely

130,672,484

269,845,189

Minimum

110,435,229

249,341,669

Maximum

161,643,371

300,682,747

Scenario B (10%)

Scenario A (4.8%)

Proportion of Work Days Lost Due to Pandemic Influenza

0%

2%

4%

6%

8%

10%

12%

1 8 15 22 29 36 43 50

Days of outbreak

Limitations of Work Loss Model

Wide range of estimates for of work day loss Largely unknown from literature For interpandemic influenza, lost work days per

illnfluenza-like illness average 1 day in US studies Impacts are likely to vary between communities,

industries, and worksites Estimates are based on less severe pandemics Some experts felt that peak would be sharper than

in the model resulting in greater proportion of work loss at the height of the outbreak

Potential Critical Infrastructures to Achieve Pandemic Response Goals

Decrease pandemic health impacts Health care workers Public health workers & other pandemic

responders Health decision makers

Decrease health and societal impacts Transportation (food & medical supplies; people) Utilities (electricity, gas, water) Public safety (police, fire, and corrections) Mortuary Sanitation

Military and government

Health Care Workers: Categories and Populations

Inpatient (5.1 M) Outpatient (7.4 M)

General hospitals (4.7 M) -- Healthcare/technical (3 M) -- Other/support (1.7 M)

Offices (3.25 M) -- Physician (2 M) -- Dentist (750,000) -- Other (500,000)Nursing residential (2.8 MHome health care (700,000)Outpatient care ctrs (400,000)Laboratories (180,000)

Other hospitals (420,000) -- Psychiatric (240,000) -- Specialty (180,000)

Emergency services (820,000)Bureau of Labor Statistics, 2003

Proposed Critical Infrastructure for Pandemic Vaccine & Antiviral Priority

Inpatient and outpatient health care workers Estimate that ~2/3 have direct patient contact

or are essential for quality care N = 8,375,000

Emergency medical services Assume all are essential in a pandemic

(820,000) Total number of HCWs/EMS = 9,195,000

Proposed Critical Infrastructure for Pandemic Vaccine & Antiviral PriorityGroup Number

Vaccine & antiviral mfrs 20,000

Health care decision-makers ?

Public health workers (non HCW)

300,000

Public safety workers 2,987,000

Utility workers 364,000

Transportation 3,800,000

Telecommunications 1,080,000

Mortuary 62,000

Sanitation 321,000

Judiciary 73,000

Financial services 1,000

Total = 9,008,000

Future Work to Be Done

Hone definitions of infrastructure groups and population sizes Further define specific sections of each group

critical for maintenance of function Evaluate ability to absorb some work loss and

surge capacity Identify additional groups along supply chains that

may also need to be prioritized (e.g. critical food groups needed to supply food for transportation)

Consider implementation issues How can persons in target groups be identified for

vaccination and antiviral treatment?

Acknowledgements & Thanks Pascale Wortley, Ted Eickhoff & the

pandemic impact working group Carolyn Bridges & the critical infrastructure

group Dale Brown, Department of Homeland

Security Elizabeth Falcone, NVPO intern Xinzhi Zhang & Martin Meltzer,

CDC/modeling