Post on 03-Jan-2016
description
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