Introduction Model Outcome Measures Results Conclusions

Optimizing Influenza Vaccine Distribution

Jan Medlock

Clemson University
Department of Mathematical Sciences

03 August 2009
 2005/WHO_POLIO_05.03.pdf).
Introduction Model
2. Funding update (www.polioeradication.org/fundingback-
ground.asp).
3. F. Fenner, D. A. Henderson, I. Arita, Z. Jezek, I. D. Ladnyi,
Smallpox and Its Eradication (WHO, Geneva, 1988).
4. R. B. Aylward, R. W. Sutter, D. L. Heymann, Science 310,
625 (2005).
5. O. M. Kew, R. W. Sutter, E. M. de Gourville, W. R. Dowdle,
M. A. Pallansch, Annu. Rev. Microbiol. 59, 587 (2005).
6. A. Nomoto, I. Arita, Nat. Immunol. 3, 205 (2002).
PUBLIC HEALTH
Who Should Get Influenza Vaccine
When Not All Can?
Ezekiel J. Emanuel* and Alan Wertheimer
T
he potential threat of pandemic influenza
is staggering: 1.9 million deaths, 90 mil-
lion people sick, and nearly 10 million
people hospitalized, with almost 1.5 million
requiring intensive-care units (ICUs) in the
United States (1). The National Vaccine Advisory
Committee (NVAC) and the Advisory Com-
mittee on Immunization Policy (ACIP) have
jointly recommended a prioritization scheme that
places vaccine workers, health-care providers,
and the ill elderly at the top, and healthy people
• Should value people “on the basis of the amount the person
aged 2 to 64 at the very bottom, even under
embalmers (1) (see table on page 855). The pri-
mary goal informing the recommendation was to
invested in his or her life balanced by the amount left to live.”
“decrease health impacts including severe mor-
bidity and death”; a secondary goal was minimiz-
ing societal and economic impacts (1). As the
• Then vaccinate the most-valued people!
NVAC and ACIP acknowledge, such important
policy decisions require broad national discus-
sion. In this spirit, we believe an alternative ethi-
• Misses epidemiology: Transmission, Case mortality, Vaccine
cal framework should be considered.
The Inescapability of Rationing
efficacy
Because of current uncertainty of its value, only
“a limited amount of avian influenza A (H5N1)
vaccine is being stockpiled” (1). Furthermore, it
will take at least 4 months from identification of
a candidate vaccine strain until production of
the very first vaccine (1). At present, there are
few production facilities worldwide that make
influenza vaccine, and only one completely in
the USA. Global capacity for influenza vaccine
news/releases/2005/pr49/en/index.html).
Outcome Measures
10. “Can infectious diseases be eradicated? A report on the
International Conference on the Eradication of Infectious
Diseases,” Rev. Infect. Dis. 4 (5), 916 (1982).
11. I. Arita, in The Eradication of Infectious Diseases, W. R.
Dowdle, D. R. Hopkins, Eds. (Wiley, New York, 1998),
chap. 15.
12. The World Bank, World Development Indicators 2004
(World Bank, Washington DC, 2004).
13. “Finance and economics: Recasting the case for aid.”
production is just 425 million doses per annum,
if all available factories would run at full capac-
ity after a vaccine was developed. Under cur-
rently existing capabilities for manufacturing
vaccine, it is likely that more than 90% of the
Science 2006
U.S. population will not be vaccinated in the
first year (1). Distributing the limited supply
will require determining priority groups.
Who will be at highest risk? Our experience
with three influenza pandemics presents a com-
plex picture. The mortality profile of a future
pandemic could be U-shaped, as it was in the
mild-to-moderate pandemics of 1957 and 1968
and interpandemic influenza seasons, in which
the very young and the old are at highest risk.
Or, the mortality profile could be an attenuated
W shape, as it was during the devastating 1918
pandemic, in which the highest risk occurred
among people between 20 and 40 years of age,
while the elderly were not at high excess risk
(2, 3). Even during pandemics, the elderly
appear to be at no higher risk than during inter-
pandemic influenza seasons (4).
Clear ethical justification for vaccine prior-
ities is essential to the acceptability of the pri-
ority ranking and any modifications during the
pandemic. With limited vaccine supply, uncer-
tainty over who will be at highest risk of infec-
tion and complications, and questions about
which historic pandemic experience is most
applicable, society faces a fundamental ethical
dilemma: Who should get the vaccine first?
699 (2005).
Results
16. WHO, UNICEF, “GIVS global immunization vision and Conclusions
strategy 2006–2015” (WHO/VB/05.05, WHO UNICEF, IVB
Document Centre, Geneva, 2005; (www.who.int/
vaccines/GIVS/english/english.htm).
17. We are grateful for the advice from D. A. Henderson,
T. Miyamura, and T. Nakano.
10.1126/science.1124959
Rather than thinking only about saving the
most lives when considering vaccine rationing
strategies, a better approach would be to
maximize individuals’ life span and
opportunity to reach life goals.
beds despite the presentation of another patient
who is equally or even more sick; “Save the
most quality life years” is central to cost-effec-
tiveness rationing. “Save the worst-off ”
plays a role in allocating organs for transplan-
tation. “Reciprocity”—giving priority to people
willing to donate their own organs—has been
proposed. “Save those most likely to fully
recover” guided priorities for giving penicillin
to soldiers with syphilis in World War II. Save
those “instrumental in making society flourish”
through economic productivity or by “con-
tributing to the well-being of others” has been
proposed by Murray and others (5, 6).
The save-the-most-lives principle was
invoked by NVAC and ACIP. It justifies giving
top priority to workers engaged in vaccine pro-
duction and distribution and health-care work-
ers. They get higher priority not because they
are intrinsically more valuable people or of
greater “social worth,” but because giving them
first priority ensures that maximal life-saving
vaccine is produced and so that health care is
provided to the sick (7). Consequently, it values
all human life equally, giving every person
equal consideration in who gets priority regard-
less of age, disability, social class, or employ-
ment (7). After these groups, the save-the-most-
lives principle justifies priority for those pre-
dicted to be at highest risk of hospitalization and
dying. We disagree with this prioritization.
 2005/WHO_POLIO_05.03.pdf).
Introduction Model
2. Funding update (www.polioeradication.org/fundingback-
ground.asp).
3. F. Fenner, D. A. Henderson, I. Arita, Z. Jezek, I. D. Ladnyi,
Smallpox and Its Eradication (WHO, Geneva, 1988).
4. R. B. Aylward, R. W. Sutter, D. L. Heymann, Science 310,
625 (2005).
5. O. M. Kew, R. W. Sutter, E. M. de Gourville, W. R. Dowdle,
M. A. Pallansch, Annu. Rev. Microbiol. 59, 587 (2005).
6. A. Nomoto, I. Arita, Nat. Immunol. 3, 205 (2002).
PUBLIC HEALTH
Who Should Get Influenza Vaccine
When Not All Can?
Ezekiel J. Emanuel* and Alan Wertheimer
T
he potential threat of pandemic influenza
is staggering: 1.9 million deaths, 90 mil-
lion people sick, and nearly 10 million
people hospitalized, with almost 1.5 million
requiring intensive-care units (ICUs) in the
United States (1). The National Vaccine Advisory
Committee (NVAC) and the Advisory Com-
mittee on Immunization Policy (ACIP) have
jointly recommended a prioritization scheme that
places vaccine workers, health-care providers,
and the ill elderly at the top, and healthy people
• Should value people “on the basis of the amount the person
aged 2 to 64 at the very bottom, even under
embalmers (1) (see table on page 855). The pri-
mary goal informing the recommendation was to
invested in his or her life balanced by the amount left to live.”
“decrease health impacts including severe mor-
bidity and death”; a secondary goal was minimiz-
ing societal and economic impacts (1). As the
• Then vaccinate the most-valued people!
NVAC and ACIP acknowledge, such important
policy decisions require broad national discus-
sion. In this spirit, we believe an alternative ethi-
• Misses epidemiology: Transmission, Case mortality, Vaccine
cal framework should be considered.
The Inescapability of Rationing
efficacy
Because of current uncertainty of its value, only
“a limited amount of avian influenza A (H5N1)
vaccine is being stockpiled” (1). Furthermore, it
will take at least 4 months from identification of
a candidate vaccine strain until production of
the very first vaccine (1). At present, there are
few production facilities worldwide that make
influenza vaccine, and only one completely in
the USA. Global capacity for influenza vaccine
news/releases/2005/pr49/en/index.html).
Outcome Measures
10. “Can infectious diseases be eradicated? A report on the
International Conference on the Eradication of Infectious
Diseases,” Rev. Infect. Dis. 4 (5), 916 (1982).
11. I. Arita, in The Eradication of Infectious Diseases, W. R.
Dowdle, D. R. Hopkins, Eds. (Wiley, New York, 1998),
chap. 15.
12. The World Bank, World Development Indicators 2004
(World Bank, Washington DC, 2004).
13. “Finance and economics: Recasting the case for aid.”
production is just 425 million doses per annum,
if all available factories would run at full capac-
ity after a vaccine was developed. Under cur-
rently existing capabilities for manufacturing
vaccine, it is likely that more than 90% of the
Science 2006
U.S. population will not be vaccinated in the
first year (1). Distributing the limited supply
will require determining priority groups.
Who will be at highest risk? Our experience
with three influenza pandemics presents a com-
plex picture. The mortality profile of a future
pandemic could be U-shaped, as it was in the
mild-to-moderate pandemics of 1957 and 1968
and interpandemic influenza seasons, in which
the very young and the old are at highest risk.
Or, the mortality profile could be an attenuated
W shape, as it was during the devastating 1918
pandemic, in which the highest risk occurred
among people between 20 and 40 years of age,
while the elderly were not at high excess risk
(2, 3). Even during pandemics, the elderly
appear to be at no higher risk than during inter-
pandemic influenza seasons (4).
Clear ethical justification for vaccine prior-
ities is essential to the acceptability of the pri-
ority ranking and any modifications during the
pandemic. With limited vaccine supply, uncer-
tainty over who will be at highest risk of infec-
tion and complications, and questions about
which historic pandemic experience is most
applicable, society faces a fundamental ethical
dilemma: Who should get the vaccine first?
699 (2005).
Results
16. WHO, UNICEF, “GIVS global immunization vision and Conclusions
strategy 2006–2015” (WHO/VB/05.05, WHO UNICEF, IVB
Document Centre, Geneva, 2005; (www.who.int/
vaccines/GIVS/english/english.htm).
17. We are grateful for the advice from D. A. Henderson,
T. Miyamura, and T. Nakano.
10.1126/science.1124959
Rather than thinking only about saving the
most lives when considering vaccine rationing
strategies, a better approach would be to
maximize individuals’ life span and
opportunity to reach life goals.
beds despite the presentation of another patient
who is equally or even more sick; “Save the
most quality life years” is central to cost-effec-
tiveness rationing. “Save the worst-off ”
plays a role in allocating organs for transplan-
tation. “Reciprocity”—giving priority to people
willing to donate their own organs—has been
proposed. “Save those most likely to fully
recover” guided priorities for giving penicillin
to soldiers with syphilis in World War II. Save
those “instrumental in making society flourish”
through economic productivity or by “con-
tributing to the well-being of others” has been
proposed by Murray and others (5, 6).
The save-the-most-lives principle was
invoked by NVAC and ACIP. It justifies giving
top priority to workers engaged in vaccine pro-
duction and distribution and health-care work-
ers. They get higher priority not because they
are intrinsically more valuable people or of
greater “social worth,” but because giving them
first priority ensures that maximal life-saving
vaccine is produced and so that health care is
provided to the sick (7). Consequently, it values
all human life equally, giving every person
equal consideration in who gets priority regard-
less of age, disability, social class, or employ-
ment (7). After these groups, the save-the-most-
lives principle justifies priority for those pre-
dicted to be at highest risk of hospitalization and
dying. We disagree with this prioritization.
 2005/WHO_POLIO_05.03.pdf).
Introduction Model
2. Funding update (www.polioeradication.org/fundingback-
ground.asp).
3. F. Fenner, D. A. Henderson, I. Arita, Z. Jezek, I. D. Ladnyi,
Smallpox and Its Eradication (WHO, Geneva, 1988).
4. R. B. Aylward, R. W. Sutter, D. L. Heymann, Science 310,
625 (2005).
5. O. M. Kew, R. W. Sutter, E. M. de Gourville, W. R. Dowdle,
M. A. Pallansch, Annu. Rev. Microbiol. 59, 587 (2005).
6. A. Nomoto, I. Arita, Nat. Immunol. 3, 205 (2002).
PUBLIC HEALTH
Who Should Get Influenza Vaccine
When Not All Can?
Ezekiel J. Emanuel* and Alan Wertheimer
T
he potential threat of pandemic influenza
is staggering: 1.9 million deaths, 90 mil-
lion people sick, and nearly 10 million
people hospitalized, with almost 1.5 million
requiring intensive-care units (ICUs) in the
United States (1). The National Vaccine Advisory
Committee (NVAC) and the Advisory Com-
mittee on Immunization Policy (ACIP) have
jointly recommended a prioritization scheme that
places vaccine workers, health-care providers,
and the ill elderly at the top, and healthy people
• Should value people “on the basis of the amount the person
aged 2 to 64 at the very bottom, even under
embalmers (1) (see table on page 855). The pri-
mary goal informing the recommendation was to
invested in his or her life balanced by the amount left to live.”
“decrease health impacts including severe mor-
bidity and death”; a secondary goal was minimiz-
ing societal and economic impacts (1). As the
• Then vaccinate the most-valued people!
NVAC and ACIP acknowledge, such important
policy decisions require broad national discus-
sion. In this spirit, we believe an alternative ethi-
• Misses epidemiology: Transmission, Case mortality, Vaccine
cal framework should be considered.
The Inescapability of Rationing
efficacy
Because of current uncertainty of its value, only
“a limited amount of avian influenza A (H5N1)
vaccine is being stockpiled” (1). Furthermore, it
will take at least 4 months from identification of
a candidate vaccine strain until production of
the very first vaccine (1). At present, there are
few production facilities worldwide that make
influenza vaccine, and only one completely in
the USA. Global capacity for influenza vaccine
news/releases/2005/pr49/en/index.html).
Outcome Measures
10. “Can infectious diseases be eradicated? A report on the
International Conference on the Eradication of Infectious
Diseases,” Rev. Infect. Dis. 4 (5), 916 (1982).
11. I. Arita, in The Eradication of Infectious Diseases, W. R.
Dowdle, D. R. Hopkins, Eds. (Wiley, New York, 1998),
chap. 15.
12. The World Bank, World Development Indicators 2004
(World Bank, Washington DC, 2004).
13. “Finance and economics: Recasting the case for aid.”
production is just 425 million doses per annum,
if all available factories would run at full capac-
ity after a vaccine was developed. Under cur-
rently existing capabilities for manufacturing
vaccine, it is likely that more than 90% of the
Science 2006
U.S. population will not be vaccinated in the
first year (1). Distributing the limited supply
will require determining priority groups.
Who will be at highest risk? Our experience
with three influenza pandemics presents a com-
plex picture. The mortality profile of a future
pandemic could be U-shaped, as it was in the
mild-to-moderate pandemics of 1957 and 1968
and interpandemic influenza seasons, in which
the very young and the old are at highest risk.
Or, the mortality profile could be an attenuated
W shape, as it was during the devastating 1918
pandemic, in which the highest risk occurred
among people between 20 and 40 years of age,
while the elderly were not at high excess risk
(2, 3). Even during pandemics, the elderly
appear to be at no higher risk than during inter-
pandemic influenza seasons (4).
Clear ethical justification for vaccine prior-
ities is essential to the acceptability of the pri-
ority ranking and any modifications during the
pandemic. With limited vaccine supply, uncer-
tainty over who will be at highest risk of infec-
tion and complications, and questions about
which historic pandemic experience is most
applicable, society faces a fundamental ethical
dilemma: Who should get the vaccine first?
699 (2005).
Results
16. WHO, UNICEF, “GIVS global immunization vision and Conclusions
strategy 2006–2015” (WHO/VB/05.05, WHO UNICEF, IVB
Document Centre, Geneva, 2005; (www.who.int/
vaccines/GIVS/english/english.htm).
17. We are grateful for the advice from D. A. Henderson,
T. Miyamura, and T. Nakano.
10.1126/science.1124959
Rather than thinking only about saving the
most lives when considering vaccine rationing
strategies, a better approach would be to
maximize individuals’ life span and
opportunity to reach life goals.
beds despite the presentation of another patient
who is equally or even more sick; “Save the
most quality life years” is central to cost-effec-
tiveness rationing. “Save the worst-off ”
plays a role in allocating organs for transplan-
tation. “Reciprocity”—giving priority to people
willing to donate their own organs—has been
proposed. “Save those most likely to fully
recover” guided priorities for giving penicillin
to soldiers with syphilis in World War II. Save
those “instrumental in making society flourish”
through economic productivity or by “con-
tributing to the well-being of others” has been
proposed by Murray and others (5, 6).
The save-the-most-lives principle was
invoked by NVAC and ACIP. It justifies giving
top priority to workers engaged in vaccine pro-
duction and distribution and health-care work-
ers. They get higher priority not because they
are intrinsically more valuable people or of
greater “social worth,” but because giving them
first priority ensures that maximal life-saving
vaccine is produced and so that health care is
provided to the sick (7). Consequently, it values
all human life equally, giving every person
equal consideration in who gets priority regard-
less of age, disability, social class, or employ-
ment (7). After these groups, the save-the-most-
lives principle justifies priority for those pre-
dicted to be at highest risk of hospitalization and
dying. We disagree with this prioritization.
Introduction Model Outcome Measures Results Conclusions

Problem Setup

• For influenza
• Age structure but not risk or occupation
• Given an outcome measure
• How to distribute limited vaccine doses?
• Nonlinear constrained optimization
Introduction Model Outcome Measures Results Conclusions

Model

νU
λ τ γ
US UE UI UR

(1 − )λ τ γ
VS VE VI VR

νV

Age structured (0, 1–4, 5–9, 10–14, 15–19, . . . , 70–74, 75+)

No birth or natural death
Introduction Model Outcome Measures Results Conclusions

2007 US Population Age Structure

5M

4M

3M
Number

2M

1M

0M
0 20 40 60 80 100
Age (years)
Introduction Model Outcome Measures Results Conclusions

Parameters

Parameter Ages Value Ref

Latent period, 1/τ all 1.2 d [1]

Infectious period, 1/γ all 4.1 d [1]

Vaccine efficacy 0–64 0.80 [2, 3]

against infection, a 65+ 0.60

Vaccine efficacy 0–19 0.75
against death 20–64 0.70 [4, 2]

65+ 0.60
[1] Longini et al, Science, 2005; [2] Galvani, Reluga, & Chapman, PNAS, 2007;
[3] CDC, ACIP, 2007; [4] Meltzer, Cox, & Fukuda, Emerg Infect Dis, 1999.
Introduction Model Outcome Measures Results Conclusions

Death Rate

0.010
1957, unvaccinated
Influenza death rate (per day)

1957, vaccinated
0.008 1918, unvaccinated
1918, vaccinated
0.006

0.004

0.002

0.000
0 20 40 60 80
Age (years)
Sources: Serfling, Sherman, & Houseworth, Am J Epidemiol, 1967; Luk, Gross, & Thompson, Clin Infect Dis, 2001;
Glezen, Epidemiol Rev, 1996.
Introduction Model Outcome Measures Results Conclusions

Contacts

PLoS MEDICINE

Social Contacts and Mixing Patterns Relevant to

the Spread of Infectious Diseases
Joël Mossong1,2*, Niel Hens3, Mark Jit4, Philippe Beutels5, Kari Auranen6, Rafael Mikolajczyk7, Marco Massari8,
Stefania Salmaso8, Gianpaolo Scalia Tomba9, Jacco Wallinga10, Janneke Heijne10, Malgorzata Sadkowska-Todys11,
Magdalena Rosinska11, W. John Edmunds4
1 Microbiology Unit, Laboratoire National de Santé, Luxembourg, Luxembourg, 2 Centre de Recherche Public Santé, Luxembourg, Luxembourg, 3 Center for Statistics,

PLoS Med 2008

Hasselt University, Diepenbeek, Belgium, 4 Modelling and Economics Unit, Health Protection Agency Centre for Infections, London, United Kingdom, 5 Unit Health Economic
and Modeling Infectious Diseases, Center for the Evaluation of Vaccination, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium, 6 Department of
Vaccines, National Public Health Institute KTL, Helsinki, Finland, 7 School of Public Health, University of Bielefeld, Bielefeld, Germany, 8 Istituto Superiore di Sanità, Rome,
Italy, 9 Department of Mathematics, University of Rome Tor Vergata, Rome, Italy, 10 Centre for Infectious Disease Control Netherlands, National Institute for Public Health
and the Environment, Bilthoven, The Netherlands, 11 National Institute of Hygiene, Warsaw, Poland

Funding: This study formed part of

POLYMOD, a European Commission ABSTRACT
project funded within the Sixth
Framework Programme, Contract
number: SSP22-CT-2004–502084. Background
Surveyedroute
7,290
The funders had no role in study
Europeans
Mathematical modelling
design, data collection and analysis,
decision to publish, or preparation
for transmitted
of infectious diseases daily bycontacts
the respiratory or close-contact
(e.g., pandemic influenza) is increasingly being used to determine the impact of possible
of the manuscript.
interventions. Although mixing patterns are known to be crucial determinants for model
Competing Interests: The authors outcome, researchers often rely on a priori contact assumptions with little or no empirical basis.
have declared that no competing We conducted a population-based prospective survey of mixing patterns in eight European
interests exist.
countries using a common paper-diary methodology.
Academic Editor: Steven Riley,
Hong Kong University, Hong Kong
Methods and Findings
Citation: Mossong J, Hens N, Jit M,
Beutels P, Auranen K, et al. (2008) 7,290 participants recorded characteristics of 97,904 contacts with different individuals
Introduction Model Outcome Measures Results Conclusions

Contacts
70+

Contact rate (per person per day)

65–69 100
60–64
55–59
50–54
45–49
Age (years)

40–44
35–39
30–34
25–29
20–24
15–19 10
10–14
5–9
0–4
10–14
15–19
20–24
25–29
30–34
35–39
40–44
45–49
50–54
55–59
60–64
65–69
70+
0–4
5–9

Age (years)
Introduction Model Outcome Measures Results Conclusions

R0

• R0 = 1.4 for Swine Flu (Fraser et al, Science, 2009)

• R0 = 2.0 for 1918 Pandemic (Mills et al, Nature, 2004)

• We considered R0 = 1.4 and also R0 = 1.2, 1.6, 1.8, 2.0

Introduction Model Outcome Measures Results Conclusions

Outcome Measures

Map outcome (number infected, dead, etc) to objective

• Total Infections
• Total Deaths
• Years of Life Lost: Using expectation of life (NCHS, US Life Tables, 2003)

• Contingent Valuation: Indirect assessment of value of lives of

different ages
• Total Cost: Converts deaths, infections, etc into dollars
Introduction Model Outcome Measures Results Conclusions

Contingent Valuation

• Survey asked about

20, 30, 40, 60 year 1.0

Relative disutility of death

olds and fit
0.8

va = a ω−1
exp (−ψa ) ω
0.6

(Cropper et al, J Risk Uncertain,

0.4
1994) 0.2
• Alternative:
0.0
wage–risk market 0 20 40 60 80
data, but only for Age (years)
working-aged adults
Introduction Model Outcome Measures Results Conclusions

Total Cost

• Monetary cost of
1.5
illness

Future lifetime earnings

(Meltzer, Cox, &

Fukuda, Emerg Infect Dis, 1999)

• Monetary cost of 1.0

death
• Future lifetime 0.5
earnings (Haddix et
al, 1996)
0.0
• Alternatives:
0 20 40 60 80
Include value of
Age (years)
non-work time
Introduction Model Outcome Measures Results Conclusions

Outcome Measures

1.0
Total Deaths
Years of Life Lost
0.8 Contingent Valuation
Relative disutility of death

Total Cost

0.6

0.4

0.2

0.0
0 20 40 60 80
Age (years)
Introduction Model Outcome Measures Results Conclusions

No Vaccination

10M
1957
1918
8M
Number infected

6M

4M

2M

0M
0 60 120 180 240 300 360
Time (days)
Introduction Model Outcome Measures Results Conclusions

Current Vaccination

CDC estimate 60%

Vaccine coverage
• 84M doses used in
2007 40%

• 100M+ doses
20%
annually
• 600M doses for Swine
0%
Flu 0 20 40 60 80
Age (years)

Sources: CDC, ACIP, 2008; NHIS, 2007.

Introduction Model Outcome Measures Results Conclusions

Eradication

150
1957
1918
125
Eradication doses

100

75

50

25

0
1 1.2 1.4 1.6 1.8 2
R0
Introduction Model Outcome Measures Results Conclusions

1957-like Mortality
20M Doses 40M Doses 60M Doses
60M
Number of doses

40M

20M

0M
In
D cts
YL ths
CV
Co

In
D cts
YL ths
CV
Co

In
D cts
YL ths
CV
Co
ea

ea

ea
fe

fe

fe
st

st

st
L

L
5–9 20–24 45–49
10–14 30–34 65–69
15–19 35–39 75+
Introduction Model Outcome Measures Results Conclusions

1918-like Mortality
20M Doses 40M Doses 60M Doses
60M
Number of doses

40M

20M

0M
In
D cts
YL ths
CV
Co

In
D cts
YL ths
CV
Co

In
D cts
YL ths
CV
Co
ea

ea

ea
fe

fe

fe
st

st

st
L

L
5–9 20–24 45–49
10–14 30–34 65–69
15–19 35–39 75+
Introduction Model Outcome Measures Results Conclusions

1957-like Mortality
1.0 1.0
Infections

Deaths
0.5 0.5

0.0 0.0
1.0 1.0
YLL

0.5 0.5

CV
0.0 0.0
1.0 0M 20M 40M 60M
5–9 35–39
10–14 45–49
Cost

0.5
15–19 65–69
20–24 70–74
0.0 25–29 75+
0M 20M 40M 60M 30–34
Vaccine doses
Introduction Model Outcome Measures Results Conclusions

1918-like Mortality
1.0 1.0
Infections

Deaths
0.5 0.5

0.0 0.0
1.0 1.0
YLL

0.5 0.5

CV
0.0 0.0
1.0 0M 20M 40M 60M
Vaccine doses
Cost

0.5
5–9 20–24
0.0 10–14 30–34
0M 20M 40M 60M 15–19 35–39
Vaccine doses
Introduction Model Outcome Measures Results Conclusions

R0 = 2.0, 1957-like Mortality

1.0 1.0
Infections

Deaths
0.5 0.5

0.0 0.0
1.0 1.0
YLL

0.5 0.5

CV
0.0 0.0
1.0 0M 50M 100M
Vaccine doses
Cost

0.5

0.0
0M 50M 100M
Vaccine doses
Introduction Model Outcome Measures Results Conclusions

R0 = 2.0, 1918-like Mortality

1.0 1.0
Infections

Deaths
0.5 0.5

0.0 0.0
1.0 1.0
YLL

0.5 0.5

CV
0.0 0.0
1.0 0M 50M 100M

0 25–29
Cost

0.5
5–9 30–34
10–14 35–39
0.0 15–19 40–44
0M 50M 100M 20–24
Vaccine doses
Introduction Model Outcome Measures Results Conclusions

Sensitivity Analysis

• Reduced vaccine efficacy against infection

Shifts to protecting at risk
• Reduced vaccine efficacy against death
Reduced susceptibility in elderly
Reduced infectious period for vaccinees
Reduced infectiousness for vaccinees
Little change for 50% reduction
Introduction Model Outcome Measures Results Conclusions

1957-like Mortality, 40M Doses

60%
Reduction

40%

20%

0%
In

YL

CV

Co
ea
fe

st
L
ct

t
hs
s

Optimal Former CDC Ages 5–19

Current Seasonal
Uniform Pandemic
Introduction Model Outcome Measures Results Conclusions

1918-like Mortality, 40M Doses

60%
Reduction

40%

20%

0%
In

YL

CV

Co
ea
fe

st
L
ct

t
hs
s

Optimal Former CDC Ages 5–19

Current Seasonal
Uniform Pandemic
Introduction Model Outcome Measures Results Conclusions

Conclusions

• 65M doses prevents an R0 = 1.4 epidemic

• 135M doses prevents an R0 = 2.0 epidemic
• Can improve vaccination policies
• Infections: Vaccinate transmitters, children (5–19) & parents
(30–39)
• Deaths, YLL, Contingent, & Cost:
• When vaccine limited, vaccinate those at risk of death
• When vaccine plentiful, vaccinate transmitters
• Transition varies between outcome measures
• Deaths averted transitions last
• Joint work with Alison Galvani
Funded by NSF grant SBE-0624117