Vaccine 21 (2003) 4105–4117
Discussion
The value of vaccination: a global perspective
Jenifer Ehreth∗
Tulane University and Medtronic Europe, SARL, 48, rue Sainte Croix de la Bretonnerie, 75004 Paris, France
Received 5 February 2002; received in revised form 30 April 2003; accepted 3 May 2003
1. Introduction
Let us assume that we agree that vaccination is one of
the most significant public health interventions in the past
century, sparing millions of people from infectious diseases.
How do we explain that each year when 130 million chil-
dren are born, about 30 million of these children have no
access to vaccinations? Since the establishment of the Ex-
panded Programmed on Immunisation (EPI) by the World
Health Assembly in 1974, much progress has been made
to bring vaccination into the global limelight but a big gap
remains. This study combines economic studies of specific
vaccines together to show the broader impact of vaccination
as a strategy for better health and economic development.
The purpose is to help those making resource allocation de-
cisions have a more accurate picture of return on investing
in vaccination.
World-wide, immunisation programs have had a tremen-
dous impact on the prevalence of many life-threatening dis-
eases. Each year vaccines prevent up to three million deaths
and 750,000 children are saved from disability [1]. The ma-
jor success stories: eradication of smallpox, elimination of
wild poliovirus from the western hemisphere and most of
the eastern hemisphere, the elimination of Haemophilus in-
fluenzae type b (Hib) within a few years of introduction of
conjugate Hib vaccines in USA, Canada, UK, Scandinavia,
France, Germany, Chile, etc. and control of measles in North
America—are the tip of the iceberg in terms of the impact
of vaccines on our society. Not only have the achievements
of vaccination prevented much suffering world-wide, vacci-
nation is a more cost-effective health investment available
to healthcare providers than most commonly paid for treat-
ments. The eradication of smallpox alone has resulted in
global savings of over US$ 2 billion each year.
While most agree that vaccination is one of the most ac-
cepted and cost-effective public health practices world-wide,
∗ Tel.: +33-1-42-78-00-92; mobile: +41-79-616-01-44;
fax: +33-1-42-78-00-92.
E-mail address: jeniferehreth@wanadoo.fr (J. Ehreth).
0264-410X/$ – see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0264-410X(03)00377-3
vaccines continue to be under-used and under-valued,
and vaccine-preventable diseases remain a threat to world
health. That is to say that, assuming governments and in-
surers intend to allocate resources efficiently and to use
these resources to improve the lives of the people they
are accountable to, vaccination should have been dissemi-
nated to the point that additional resources would be more
effectively spent elsewhere. If payers see only a part of
the benefits of vaccination and all of the costs, they are
likely to under-invest in vaccination. If doctors do not see
the cases prevented of vaccine-preventable disease but do
experience the time and effort to provide and monitor vac-
cination programs, they will not emphasis the importance in
their practice. If parents don’t see children with polio and
diphtheria; if they read articles about the dangers of vacci-
nation; and have to take the initiative to bring their healthy
children into a clinic for vaccination, they are not as likely
to be compliant as if they fully understood the value that
vaccination provides. Perhaps one reason there remains this
gap is that decision-making on logistic and budgetary issues
generally is made on a limited vaccine-by-vaccine basis.
There has been less attention to the importance and value
of vaccination as a health care strategy. As vaccination is
more than vaccines, it implies a process of delivery and
monitoring. This process is seldom considered including all
vaccine series and over the lifetimes of the individuals.
In hopes of more clearly identifying the overall value
of vaccination, this paper reviews the global value of vac-
cination for those making resource allocation decisions,
the effectiveness of vaccination initiatives, and the steps
necessary to sustain progress and overcome the effects of
under-valuation of vaccination on a global scale.
2. Methods
Estimates of vaccine-preventable cases world-wide, vac-
cine coverage levels, disease incidence, vaccine costs and
cost-effectiveness were obtained through in a four-stage
process. First, an electronic document search using Medline,
4106 J. Ehreth / Vaccine 21 (2003) 4105–4117
PubMed, the National Library of Medicine, HEED, HSTAT,
the Scientific Citation Index, and disease websites, was
conducted to obtain online references and statistics from
public agencies and academic centres in the United States
(Centres for Disease Control, GAVI, National Institutes of
Allergy and Infectious Diseases, United Nations/UNICEF,
World Bank), the UK (Public Health Laboratory Service),
France (INSERM), Australia (Australian Department of
Health and Aged Care) and Switzerland (World Health
Organisation). Second, government documents and aca-
demic publications were reviewed using the following
search terms: vaccination, vaccine, immunisation, per-
tussis, diphtheria, DTaP/DTP, measles, mumps, rubella,
MMR, polio/poliomyelitis, influenza, HiB/Hib, hepatitis,
meningitis, meningococcal disease, pneumoccocal disease,
tetanus, cost-effectiveness, QALY and DALY. Third, aca-
demic and government experts in vaccine cost-effectiveness
were contacted to obtain several estimates. Fourth, the epi-
demiological and economic data obtained from the first
two stages were converted to the following common units:
US$, life-years saved, deaths prevented, quality-adjusted
life-years, and disability-adjusted life-years, to allow for
further economic analyses of the value of vaccination.
The compiled data from the first three stages of the analy-
sis described above were adapted for comparative purposes
in accordance with the following economic rationale. Two
types of cost-effectiveness studies: the cost-effectiveness
of developing and disseminating new vaccines and the
cost-effectiveness of immunising populations with existing
vaccines are possible. This paper focuses on the latter but
briefly discusses the former for completeness.
As data were taken from studies in different years, where
possible, monetary data were carried forward to 2002 US$
using the Consumer Price Index in the United States. Where
these data were reported in other monetary units, they were
converted to US$ using current exchange rates. The dura-
tion of protection for most vaccines in this report is longer
than 1 year. Therefore, offsetting savings in health care re-
sources could occur for a number of years subsequent to the
vaccination. This savings were not discounted for the fol-
lowing two reasons. First, the economic nature of preventive
care such as that provided by vaccines differs significantly
from treatment of disease. In treatment, the intervention is
for amelioration of a disease that the patient is known to
have. There is no significant uncertainty about whether or
not the patient has the disease. The benefits may last for a
number of years. As a result, there can be a disassociation
between the time of the treatment and the time of the bene-
fit. When this disassociation occurs, discounting can be used
to compare monetary value in terms of a common year.
The economic aspects of preventive services resemble
those of insurance. That is, healthy people decide to be vac-
cinated to reduce the risk of contracting disease. The benefit
of this risk reduction is realised as soon as the vaccine starts
working. Therefore, there is no disassociation between the
vaccination and its benefits if one views the benefits as risk
reduction. The reduced probability of incurring health care
costs associated with becoming ill starts with vaccination.
The accommodation for risk is taken into account in the as-
signment of costs to the proportion of the population that is
at risk of disease and the vaccine effectiveness. For example,
while the primary goals of hepatitis B infection are to pre-
vent deaths and morbidity from hepatitis B-related chronic
liver disease and primary hepatocellular carcinoma which
occur many years after infection, the risk of these future
events is reduced from the time of vaccination.
2.1. Cost-effectiveness calculation
Most of the cost-effectiveness studies reviewed evaluated
the provision of existing vaccines in terms of cost per unit
of output or cost per unit of outcome as compared to an-
other intervention [2]. Costs in the cost-effectiveness analy-
ses typically included direct and indirect costs. Direct costs
were all costs associated with the provision and support for
patient care, including provider time, administrative time,
capital inputs and overhead [3]. Indirect costs referred to the
costs of illness associated with income loss due to missed
workdays, death, travel and waiting time and caregiver time.
The incremental cost-effectiveness ratio used in this study
was:
(direct costs + indirect costs)treatment
−(direct costs + indirect costs)control
effectivenesstreatment − effectivenesscontrol
Effectiveness in this ratio has been defined in one of three
ways:
(1) the number of potential life-years saved due to the in-
tervention (e.g. vaccination),
(2) the number of quality-adjusted life-years (QALYs)
saved, or
(3) the number of disability-adjusted life-years (DALYs)
saved.
QALYs and DALYs are complementary concepts that in-
corporate morbidity (or quality of life) and mortality effects
into a single metric and are considered preferable measures
of effectiveness for this reason.1
Several tables below present estimates of life-years
saved and DALYs due to vaccination for different vaccine-
preventable diseases in different countries and regions of
the world. Life-years saved estimates indicate historical
health gains that have been made by immunising people
against a vaccine-preventable disease, while DALYs repre-
sent the additional health gains that have yet to be made by
1 There are economic and accounting definitions for direct and indirect
costs, but the economic definitions are the ones discussed. For complete-
ness, the accounting definition of direct costs includes costs directly related
to patient care, such as provider time and capital inputs. The accounting
definition of indirect costs includes costs that support patient care, such
as administrative time, janitorial services, linen services and overhead.
The economic definition of direct costs subsumes both accounting terms.
 J. Ehreth / Vaccine 21 (2003) 4105–4117
introducing vaccination in some countries and regions or
eradicating vaccine-preventable diseases altogether.
Historical life-years-saved estimates have not been made
directly in many cases, so extrapolation has been required.
These estimates were generated by multiplying published
estimates of deaths prevented by certain vaccines and an
estimated life expectancy for infants. In most cases, the life
expectancy was assumed to be 65 years, which may be an
upper bound but is consistent with the DALY approach to
identifying an optimal life expectancy.
Estimates for DALYs for the United States were obtained
from two sources. Dr. Matthew McKenna from the Centres
for Disease Control and Prevention provided provisional es-
timates of DALYs for the United States for Table 4 for the
diseases listed in the Global Burden of Disease and Illness
Study. The additional DALY estimates for diphtheria in the
United States were extrapolated from the tetanus estimate,
under the assumption that the case-fatality rates were com-
parable. However, a much larger proportion of survivors of
diphtheria have long-term sequelae, thus the DALY is some-
what understated. Similarly, the DALY estimates for mumps
and rubella in the United States were extrapolated from the
measles estimate, again under the assumption that these dis-
eases had similar morbidity and mortality profiles knowing
that neither mumps nor rubella have the same impact as
measles. Given the small number of incident cases in 1999,
violations of this assumption will not significantly change
the overall estimate of illness burden of vaccine-preventable
diseases in the United States.
3. The global status of vaccination
3.1. Under-valuation and under-utilisation of vaccines
Prevention is ultimately the most efficient and humane
means toward improved world health. Today we have at least
26 diseases that can be prevented or the incidence lowered
by vaccination [4]. Yet vaccines are not being used to their
full potential [5,6].
Using EPI program data (DTP, OPV, measles, and BCG
series) as a proxy, world-wide average vaccination cov-
erage of children under the age of five fell from 80% in
1990 to 74% in 1999 [7]. One in four children in the world
remains without immunisation against the six diseases ini-
tially covered by EPI (measles, polio, pertussis, diphtheria,
tetanus and tuberculosis) [8]. Moreover if vaccination is
under-valued, there may be a lack of adequate investment
in research and development for new vaccines to combat
the diseases that are prevalent in developing countries:
diarrhoeal diseases, malaria, tuberculosis, pneumonia and
HIV/AIDS [1].
3.1.1. Situation in industrialised countries
The under-utilisation of vaccines in industrialised coun-
tries is caused in part by underestimating the seriousness
4107
of vaccine-preventable diseases [9,11], underestimating the
benefits of vaccination, and concerns regarding the side ef-
fects of vaccines [5]. Immunisation has reduced the occur-
rence of diseases such as, in the United States, diphtheria
declined from over 175,000 pre-vaccination cases each year
to 1 case in 1998; pertussis declined from 140,000 to 7000
in 1998 and tetanus declined from 1300 to 40 cases in 1998
[10].
Anti-vaccine groups have reinforced the under-valuation
of vaccination by spreading false allegations of vaccine risk
thus leading to increased infections at times. For example,
in the late 1970s in the UK and the 1990s in Russia, per-
tussis outbreaks occurred following anti-vaccine campaigns
[12].
3.1.2. Situation in developing countries
There is great disparity throughout the world with regard
to severity of disease, availability of vaccines, and the qual-
ity of vaccination programs. A child in a developing coun-
try has more than a 10-fold greater chance of dying of a
vaccine-preventable disease than a child in an industrialised
country. In some countries in sub-Saharan Africa, up to 70%
of children do not receive the full set of vaccines. In Africa
as a whole, over 40% of children are not immunised against
measles, a major cause of infant mortality that kills one child
every minute. A child in an industrialised country receives
11 vaccines on an average, while a child from a developing
country is lucky to receive half that number [1].
In developing countries, the under-utilisation of vaccina-
tion results from a lack of resources, inadequate budget for
primary care and focus on other budget priorities (targeted
on military spending during times of war), ineffective pub-
lic health policies and lack of basic infrastructure, sanitation
and health education [13,53]. In countries where the services
and funding are inadequate the focus tends to be on thera-
peutic intervention to avert crises rather than on prevention
and early treatment.
4. The beneficiaries of vaccination—individuals,
communities and nations
Vaccination is a collective activity in the sense that the act
of immunising one person can, for some diseases, lead to the
protection of people they would come in contact with. As re-
cently seen with the SARS outbreak, infectious diseases can
cross boundaries between countries and continents resulting
in a global impact. High vaccination rates benefit all as the
spread of infection declines [14]. High rates in one genera-
tion can benefit the next generation where disease eradica-
tion is achieved [15]. For a few diseases where vaccination
that can create herd immunity, once a high percentage of vac-
cinated individuals is attained, the risk to the unvaccinated
members of the group of contracting the disease dramatically
decreases [16] The increase in mobility and population den-
sity has enabled communicable diseases to spread rapidly
4108 J. Ehreth / Vaccine 21 (2003) 4105–4117

between and among different regions and throughout the Table 1

world. Epidemics such as meningococcal disease or cholera Vaccination coverage rates (%) among children aged 19–35 months, by
selected vaccines—National Immunization Survey, United States, 1995–
that have occurred in recent years can easily become pan-
1999 [60]
demic. HIV already has taken hold world-wide. Ultimately
the aim of vaccination programs must be a local and a Vaccine/dose 1995a 1996b 1997c 1998d 1999e
global effort to limit the transmission of vaccine-preventable DTPf
disease. Three doses 94.7 95.0 95.5 95.6 95.9
Four doses 78.5 81.1 81.5 83.9 83.3
Poliovirus
5. Vaccine effectiveness Three doses 87. 9 91.1 90.8 90.8 89.6
Hibg
The effectiveness of vaccination has been demonstrated Three doses 91.7 91.7 92.7 93.4 93.5
in industrialised countries where, following routine vaccina- MMRh
tions, several infectious diseases have been controlled and in Three doses 87.8 90.7 90.5 92.0 91.5
some cases, eradicated. As shown in Table 1 for the United Hepatitis B
States, vaccination coverage for the vaccine-preventable Three doses 68.0 81.8 83.7 87.0 88.1
childhood diseases has been high for the older vaccines Varicellai
such as DTP, polio, and MMR and increasing for the One dose NA NA 25.9 43.2 59.4
newer vaccines such as Hep B (going from 68% in 1995 Combined series:
to 88.1% in 1999) and varicella (starting at 25.9% in 1997 4 DTP/3 polio/1 76.2 78.4 77.9 80.6 79.9
to 59.4% by 1999). Combined series coverage rates have MCVj
stayed stable over the 5 years. As a result of the high level 4 DTP/3 polio/1 74.2 76.5 76.2 79.2 78.4
of immunisation, the reported incidence of many of these MCV/3 Hibk
a Children in this survey period were born during February 1992–May
childhood diseases have declined dramatically as shown in
1994.
Table 2. Another way too look at the benefits of vaccination b Children in this survey period were born during February 1993–May
is to compare the consequences of the prevented disease 1995.
to side-effects of vaccines. Nearly all of the vaccines’ side c Children in this survey period were born during February 1994–May

effects are limited to brief soreness around the injection, 1996.

occasional rash, and infrequent fever. The consequences
of the diseases are much higher in frequency and have
life-altering effects. One could imagine a world in which
you take the peak incidence in column 2 and the conse-
d Children in this survey period were born during February 1995–May
1997.
e Children in this survey period were born during February 1996–May
1998.
f Includes diphtheria–tetanus–pertussis (DTP) vaccine, diphtheria–

quences in column 4 as compared to 1999 in column 3
and column 5 of Table 2. At the peak incidence, thousands
fold more people had encephalitis from varicella, deaf-
ness from mumps, death from tetanus. Moving from the
United States, Table 3 shows the estimated annual impact
of vaccination just on deaths world-wide. Nearly 3 million
mostly young people’s lives are cut short each year be-
cause they are not vaccinated. The perceived value of some
vaccines clearly has led to under-vaccination. For example,
measles, which is perceived in the developed world as an
innocuous childhood disease, is killing over 800,000 people
annually.
Going back to the United States where data are more avail-
able, Table 4 calculates the economic impact of vaccination
against childhood diseases in terms of the cost per life-year
saved, QALY and DALY. All vaccination except pneumo-
coccal is cost saving in terms of QALY and less than US$
25 per DALY. From an economic point of view, this indi-
cates that rational governments should be vaccinating every-
one. Allocating budgets to nearly anything else before their
population is fully vaccinated is a poor use of funds. Even
where the vaccines cost something per life-year-saved, due
to the morbidity effects, they should vaccinate before other
uses of their budget.
tetanus toxoids DT, and diphtheria and tetanus toxoids and acellular per-
tusssis vaccine.
g H. influenzae type b (Hib) vaccine.
h Previous reports of vaccination coverage were for measles-containing
vaccine (MCV); the above reflects coverage with measles–mumps–rubella
(MMR) vaccine.
i Data not available in this reporting period. Data collection for vari-
cella vaccine began July 1996.
j Four doses of DTP/DT, three doses of poliovirus vaccine, and one
dose of MCV.
k Four doses of DTP/DT, three doses of poliovirus vaccine, one dose
of MCV, and three doses of Hib.
In France, over the past 50 years, morbidity and mortality
from vaccine-preventable diseases has also decreased sig-
nificantly as shown in Table 5. There are major differences
between developed countries, however, in perceptions about
disease. For example, France routinely uses the BCG tuber-
culosis (TB) vaccine and cases of TB are reportable whereas
the United States does not have a childhood BCG program.
The reasons for this difference are not clear and may rest in
the differences in the impact of TB historically with France
having many more centuries to draw upon. Today the inci-
dence of TB is growing in particularly at-risk populations in
both countries. Conversely, measles and measles vaccination
 J. Ehreth / Vaccine 21 (2003) 4105–4117 4109

Table 2
Impact of vaccination on annual disease in the United States (1999) [61]
Vaccine (year introduced) Peak disease 1999 disease Consequence of natural disease Known vaccine side effectsa
incidence incidence
Varicella (1995) 4 × 106 46016 Encephalitis (2/10000 cases), bacterial Mild rash (1/20 doses), rare: seizure,
(under-estimate) skin infections, shingles (300000 per pneumonia
year)
DTaP See below See below See below Soreness, rare: fever ≥105 ◦ F, vomiting
Diphtheria (1921) 206939 1 Death (5/10000 cases), muscle Soreness, rare: fever ≥105 ◦ F, vomiting
paralysis
Tetanus (1927) 1314 40 Death (30/100 cases), fractured bones, Soreness, fever, rare: peripheral neuritis
pneumonia vomiting, Guillain–Barré syndrome
Pertussis (1934 whole 265269 7288 Death (2/1000 cases), pneumonia Soreness, rare: high fever, brain disease
cell) (1991 acellular) (10/100 cases), seizures (1–2/100 cases) (0–10/1 million doses—whole-cell
vaccine only)
H. influenza type b 20000b 363 Death (2–3/100 cases), meningitis, Soreness, rare: headaches, fever
(childhood) (1984) pneumonia, blood poisoning, ≥101 ◦ F, Guillain–Barré syndrome
inflammation of epiglottis, skin or
bone infections
Hepatitis B (1981) 300000b 136 Death from cirrhosis or liver cancer Soreness, rare: difficulty breathing or
(4000–5500 per year) swallowing; hives; itching, joint pain,
fever, rash; dizziness
MMR See below See below See below Rare: fever ≥103 ◦ F (5–15/100 doses),
joint pain
Measles (1941) 894134 62 Encephalitis (1/1000 cases), pneumonia Rare: fever ≥103 ◦ F (5–15/100 doses),
(6/100 cases), death (1–2/1000 cases), rash
seizure (6–7/1000 cases)
Mumps (1968) 152209 221 Deafness (1/20000 cases), inflamed Rare: rash, fever
testicles (20–50/100 post-pubertal
males)
Rubella (1969) 57686 35 Blindness, deafness, heart defects Rare: temporary joint pain (25/100
and/or retardation in 85% of children adult doses in women), rash, fever
born to mothers infected in early
pregnancy
Pneumococcalc 93000b 19118d Meningitis (800 cases per year), Rare: fever ≥100.3 ◦ F (22/100 doses)
(childhood) (2000) pneumonia (77000 cases), blood
poisoning (15000 cases)
Polio (paralytic) (1955) 21269 0 Death (2–5/100 cases in children), Rare: vaccine-induced polio with oral
respiratory failure, paralysis, vaccine only (1/2.4 million doses)
post-polio syndrome
a Mild side effects such as pain, injection site redness and/or swelling, mild fever may occur after any vaccine.
b Estimated.
c Journal of the America Medical Association, 15 March 2000.
d Projection based on 1999 ABCs report on Streptococcus pneumoniae from CDC.

receive more attention in the United States than in
France.
The UK has had great success with a short, intensive vac-
cination campaign to decrease morbidity of meningococcal
C disease (Table 6). In 1998/1999, an estimated 1530 cases
of meningococcal C infection were reported, resulting in
150 deaths. In the UK, meningococcal disease is the leading
cause of death in infants from 1 to 5 years, and the leading
cause of death from an infection up to the age of 20 years,
killing 1 in 10 people infected. In 1998, approximately 40%
of cases were due to group C diseases. It has been sug-
gested that the higher incidence of the disease may be re-
lated to the emergence of a new clone of group C infection
that has spread through England and Wales, as well as other
areas of Europe [17]. These results were achieved in only 1
year, and other than the impact of conjugate Hib vaccination
on invasive Hib disease, [18] represent the greatest reduc-
tion in morbidity and mortality from a potentially deadly
illness since the polio vaccine was introduced in the 1950s
[23].
5.1. Smallpox eradication
The smallpox virus was a good candidate for eradi-
cation and WHO made an enormous effort and invested
more than US$ 300 million over 11 years in the Intensified
Smallpox Eradication Program. This cost has been repaid
many times in saving human lives and in the elimination
of costs for vaccines, treatment and international surveil-
lance activities [19,20]. To date, eradication has spared
4110 J. Ehreth / Vaccine 21 (2003) 4105–4117

Table 3 5.2. Polio eradication

Global impact of increased vaccine coverage on vaccine-preventable dis-
eases [62]
Vaccination has resulted in the elimination of wild po-
Disease Annual number of deaths liovirus from the Western Hemisphere. The goal of the World
from vaccine-preventable
Health Assembly to eradicate poliomyelitis by the end of
disease: world-widea,b
the year 2000 was adopted in 1988. Since then, many suc-
Hepatitis B 900000
Measles 888000
cesses have been accomplished. Of the three types of wild
H. influenzae type b (Hib) 400000 polioviruses, type 2 was last seen in 1999 and appears to have
Pertussis (whooping cough) 346000 been eradicated. More than 190 countries and territories are
Neonatal tetanus 215000 polio-free and the disease now exists in only about 20 coun-
Tetanus 195000 tries, all in the regions of Southeast Asia and Sub-Sahara
Yellow fever 30000
Diphtheria 5000
Africa. Since 1988, the number of cases reported to WHO
Poliomyelitis 720 has declined by 99%. In the year 2000, fewer than 3000
cases world-wide were reported compared with 35,000 cases
Total 2979720
reported in 1988 [22,23].
a GAVI and WHO Department of Vaccines and Biologicals. The four strategies of the poliomyelitis eradication ini-
http://www.vaccinealliance.org/press/press disease.html. Accessed June
tiative have been: strong routine immunisation programs,
2001.
b By permission from WHO World Health Report 1999 and WHO national immunisation days, surveillance for acute flaccid
Department of Vaccines and Biologicals. paralysis, and house-to-house “catch-up and mop-up” op-
erations. A new WHO strategic plan 2001–2005, improv-
the global community of some 350 million new small- ing the previous strategies, has been elaborated in order to
pox victims and some 40 million deaths from the disease achieve polio eradication and the certification of eradication
[21]. The annual savings as a result of vaccination being in 2005 [24]. Every child must be vaccinated; every part of
stopped and hospitals being able to be converted to other the globe must be declared polio-free. WHO estimates that
uses is estimated to be in excess of US$ 2 billion each the final eradication push will cost US$ 1 billion with a cur-
year [9]. rent funding gap of US$ 0.4 billion [25].

Table 4
Impact of vaccination on economic outcomes in the United States (1999)
Vaccine (year introduced) Peak incidence 1999 incidence Cost per life-year Cost per QALY Cost per DALY
saved (US$) (US$) (US$)
Varicella (1995) 4 × 106 46016 under-estimate 3163–9027a <0 (cost-savingb ) –
DTaP See below See below <0 (cost-savingc ) <0 (cost-savingb ) <25/DALYd
Diphtheria (1921) 206939 1 – <0 (cost-savingb ) <25/DALYd
Tetanus (1927) 1314 40 143138e <0 (cost-savingb ) <25/DALYd
Pertussis (1934 whole 265269 7288 25000 (acellular) <0 (cost-savingb ) <25/DALYd
cell) (1991 acellular)
H. influenza type b 20000f 363 1635g <0 (cost-savingb ) –
(childhood) (1984)
Hepatitis B (1981) 300000f 136 21–29h <0 (cost-savingb ) <25/DALYd
MMR See below See below <0 (cost-savingc ) <0 (cost-savingb ) See below
Measles (1941) 894134 62 <0 (cost-savingc ) <0 (cost-savingb ) 5–17i
Mumps (1968) 152209 221 <0 (cost-savingc ) <0 (cost-savingb ) –
Rubella (1969) 57686 35 <0 (cost-savingc ) <0 (cost-savingb ) –
Pneumococcal (childhood) 93000j 19118 – 3795 25–75/DALYd
(2000)
Polio (paralytic) (1955) 21269 0 <0 (cost-savingc ) <0 (cost-savingb ) <25/DALYd
Source: http://www.skyaid.org/Skyaid%20Org/Medical/international health.htm.
a [63].
b [64].
c [65].
d [11].
e [66].
f Estimated.
g [67].
h [68].
i [69].
j Journal of the America Medical Association, 15 March 2000.
 J. Ehreth / Vaccine 21 (2003) 4105–4117 4111

Table 5
Morbidity and mortality of vaccine-preventable diseases in France
Before 1950 1990 After 1990
Annual morbidity Annual mortality Percent vaccination Annual morbidity Annual mortality Annual life-years
(per million) (per million) coverage in childrena (per million) (per million) savedb
Diphtheria 100–1000 50–100 90 0 0 199875
Tetanus >30c 20–50 90 1–2 0.25–0.50 91788
Pertussis 2000–10000 20–50 88 <50d ≈0.10 92879
Tuberculosis 1000c 300–1000 83 100–150c 13 25857
Poliomyelitis 100 5–10 88 0 0 308
Source: INSERM: vaccination, actualities and perspectives. Collective expertise. INSERM Editions, Paris 1999, vol. 1, 344 pp. (pp. 7–8).
http://dicdoc.kb.inserm.fr:2010/basisrepp/vaccination.html; 1950 data—Vallin and Mesle, 1988; after 1990—RNSP, 1997.
a [70].
b Estimates of annual life-years saved based upon the following assumptions (1940 population of 41 million and 1998 population of 61 million) and

the formula: LYS = mortality pre-1950; 1940 population − mortality after 1990; 1998 population.
c Important under-reporting.
d Estimate based on the number of children hospitalized with whooping cough. Impact of vaccination on morbidity and mortality of infectious

diseases—French data.

5.3. Control of diseases in childhood
The EPI program was established in 1974 when fewer
than 5% of the world’s children were immunised against the
six most common vaccine preventable childhood diseases
(diphtheria, tetanus, pertussis, measles, polio and TB). Its
impact can be best understood by reviewing the diseases
individually.
5.3.1. Measles
Measles is one of the most contagious diseases known to
man and yet several regions of the world are in the process of
eliminating it. This is dramatic when considering that as late
as 1999 almost a million children died from measles in 1 year
in developing countries and measles was the leading cause
of death for children under the age of five [17]. The disease
is still rampant in other parts of the world. Approximately
25% of the global birth cohort gets measles resulting in
28 million cases and 691,000 deaths. Eighty-four percent
(578,000) of the global deaths occur in the World Health
Organisation’s African and Southeast Asian regions. Twenty
countries account for 82% of deaths attributable to measles.
In nine countries, over 2% of the birth-cohort each year is
estimated to die from measles [26].
Table 6
One-year meningococcal program in the UK (1999–2000)
Age group Cost of 1-year Reduction in Cases
(years) program (£) morbidity over prevented
1 year (%)
Under 1 20 × 106 82 60a
15–17 90 63a
Source: [17].
a Based on 1999–2000 change in number of reported meningococ-
cal cases in http://www.phls.co.uk/publications/CDR%20Weekly/archive/
news0201.html#impact.
b Cost per life-year saved based upon United States figure of US$
80,000 converted on 30 June 1999 at rate of US$ 1 = £0.63492.
To eradicate measles from the western hemisphere, the
Pan American Health Organization (PAHO) developed an
enhanced measles vaccination strategy with three compo-
nents: a catch-up campaign, maintenance of high vaccina-
tion coverage (keep-up), and periodic follow-up campaigns
[27]. North America and Europe have two-dose campaign
strategies and then EPI has a one-dose at 9 months focusing
on infant mortality rather than measles transmission [28].
Three World Health Organisation (WHO) regions have tar-
geted measles elimination [29]. Between 1997 and 1998,
the American region had 1.6 cases per 100,000 persons, a
75% decline, Europe had a 59% decrease but the Eastern
Mediterranean reported an increase of 58% largely where
implementation had not occurred [28].
5.3.2. Tetanus
Today, WHO stands poised to eliminate tetanus as a
public health problem through a global vaccine campaign
[19]. Elimination is defined as the reduction of case trans-
mission to a predetermined very low level. Tetanus is the
only vaccine-preventable disease that is not communicable.
Neonatal tetanus (NT) is a major cause of mortality in devel-
oping countries, with over 400,000 deaths estimated to oc-
cur annually [30]. In view of the significant disease burden,
the elimination of neonatal tetanus as a public health prob-
lem by the year 2005 (defined as a rate of neonatal tetanus
below 1/1000 live births at district level) has been agreed
to by all member states of WHO, UNICEF and UNFP [31]
Cost per This requires assurance that all doses meet WHO produc-
life-years tion and quality requirements and that the field effectiveness
saved (£) of the vaccine is monitored to assess vaccine coverage.
50794b The benefits of smallpox and polio eradication and
50794b
measles and tetanus control through immunisation, in terms
of annual life-years saved (LYS) and disability-adjusted
life-years (DALYs) saved in the United States, Africa and
globally, is shown in Table 7. In terms of life-years-saved
or DALYs, measles vaccination is the most important in all
regions. Clearly there are differences across regions with
4112 J. Ehreth / Vaccine 21 (2003) 4105–4117

Table 7
Benefits of disease eradication and control by vaccination, in terms of annual life-years saved (LYS) and disability-adjusted life-years (DALYs) saveda
Disease United States Africa Global
LYS DALYs LYS DALYs LYS DALYs

Smallpoxb 1685740 NA 933065 NA 5000000 NA

Polioc 212690 NA 484230 279000 35750000 1725000
Measlesd 5811852 26 2125500 17463000 71500000 29838000
Tetanuse 42705 9 2801500 3039000 56030000 12020000
NA: not available.
a [62].
b Note that the estimate of life-years saved in the United States is based upon 48,164 average deaths between 1900 and 1904 multiplied by 35-year

life expectancy [71]. Estimate of life-years saved in Africa based upon 26,659 deaths reported in 1971 multiplied by 35-year life expectancy [72].
c Dr. Matthew McKenna at CDC; Murray and Lopez, Global Burden of Disease, 1999; Children’s Vaccine Initiative, World Health Organization,

1995. Note: Estimate of United States life-years saved is based on 21,269 average number of paralytic polio cases times an assumed 50% mortality rate
between 1951 and 1954 times an assumed 20-year life expectancy (Source: [71]). Estimate of African life-years saved is based on difference between
1999 polio cases (http://www.polioeradication.org/pdfs/Polio news no7.pdf, p. 3) and 1988 cases (http://www.ifrc.org/what/health/archi/fact/fpolerad.htm)
of 35,000–2718 times assumed 15-year life expectancy.
d World Health Organization, 2000. Estimate of United States life-years saved based on 894,131 times a mortality rate at peak incidence of

10% times 65-year life expectancy. Estimate of African life-years saved based upon estimate of 32,700 deaths prevented between 1998 and 2000
(http://www.whoafr.org/ddc/vpd/2000tfi/measlescontrol/acceleratedmeaslescontrol.pdf) times assumed 65-year life expectancy.
e [73]. Estimate of tetanus life-years saved in the United States is based on assumed 657 deaths prevented from peak incidence of 1314 and 50%

mortality rate times 65-year life expectancy. Estimate of tetanus life-years saved in Africa in 1993 based on estimate that 5% of world-wide tetanus
deaths and deaths prevented occurred in Africa times 65-year life expectancy.

tetanus and polio being more important in Africa than in
the United States. Cost data were not available globally to
calculate the cost per DALY.
5.3.3. Examples of other success stories
Congenital rubella syndrome (CRS) is an under-recognised
public health problem in many developing countries. As of
1997, less than one-third of developing countries included
rubella vaccine in their national immunisation programs.
In developed countries such as Canada, Finland, Sweden,
and UK, the two-dose MMR program targeting CRS in
unvaccinated immigrant mothers has been quite successful
with no case of CRS since 1986 in Sweden and Finland
[32].
Pneumococcal disease causes morbidity and mortality in
infants and young children world-wide. The efficacy of a
seven-valent conjugate vaccine was 97.4% against invasive
pneumococcal disease, and 57% against otitis media, caused
by the vaccine serotypes. Evidence also shows that the vac-
cine has the potential to prevent pneumonia. Widespread
use of a pneumococcal conjugate vaccine could control the
global spread of antibiotic resistance in pneumococci as it
has been shown to reduce nasal carriage [38].
H. influenzae type b (Hib) invasive disease was the lead-
ing cause of childhood meningitis and was associated with
high death rates and sequelae [5]. Before a Hib vaccine was
available, an estimated 445,000 cases of invasive Hib dis-
ease occurred globally, each year, in children under 5 years
of age, 115,000 of which resulted in death [33]. The advent
of an available vaccine has led to a tremendous drop in the
incidence of this disease. The incidence of Hib meningitis
in Europe has been reduced by over 90% in less than 10
years because of vaccination [34]. A study involving six Eu-
ropean countries showed that 12–54/100000 children who
are under 5 years old had Hib invasive infection prior to the
introduction of a vaccine. After the Hib vaccination was in-
corporated into routine childhood immunisation schedules
(all countries except Spain), the incidence rate in this age
group fell to 0.00–2.24 per 100,000 by 1997 [35]. In the
United States Hib cases dropped more than 99% in children
under 5 years since the introduction of the vaccine in 1990
[22]. In France, after the introduction of Haemophilus vac-
cine in 1992, the incidence of meningitis due to H. influen-
zae per 100,000 decreased from 0.91 in 1992 to 0.10 in 1997
[36].
The primary goal of hepatitis B vaccination is to reduce
future liver disease rather than to reduce Hep B infection
and transmission. However, vaccination has decreased car-
rier rates in highly endemic countries in Asia and Africa
from over 8% to less than 2% [37]. Due to hepatitis B vac-
cination campaigns in Taiwan, liver cancer morbidity per
100,000 has decreased from about 0.8 in 1982 to 0.3 in 1994
with a similar decrease in mortality rates [43].
6. Ancillary benefits of vaccination
Vaccination not only provides disease specific benefits to
individuals but also ancillary benefits that are often difficult
to assess monetarily. The vaccination activities can estab-
lish a basis for other health care activities where these are
lacking [5,38,39]. It provides an opportunity to focus on pre-
vention of disease [40]. In areas with malnutrition, the pro-
grams can be opportunities for Vitamin A supplementation
[38,41,42,43]. There can be social benefits such as reduced
fertility rates as child mortality rates reduce [39].
 J. Ehreth / Vaccine 21 (2003) 4105–4117 4113

7. Economic burden of vaccine preventable diseases
and vaccine cost-effectiveness
If a disease cannot be controlled by other cost-effective
means, or if control is not feasible, the importance of devel-
oping a vaccine against the disease increases. For example,
incidence of rotavirus diarrhoea is similar world-wide even
in developed nations that have adequate sewage disposal sys-
tems, clean water supplies, and adequate housing. In choos-
ing control strategies the added value of immunisation is
compared to treatment after infection. While chemothera-
peutic agents are currently available, they are not considered
the most cost-effective strategy in the developing world [44].
The rationale for investing in immunisation programs in
developing countries is clear. These programs represent a
low risk investment in human capital development with a
proven impact. They are highly cost effective, have signifi-
cant economies of scale, and can be financially sustained by
developing countries [45]. The World Bank considers that a
health care intervention is cost-effective if it buys a year of
healthy life for less than the per-capita gross national prod-
uct (GNP) of the country. Most of the low income countries
(GNP of US$ 765 or less) participate in the WHO’s EPI,
whose vaccines cost no more than US$ 20 per year of healthy
life gained in these countries [46]. Newer vaccines such as
hepatitis B and H. influenzae type b have not been added to
EPI programs in most low-income countries because of their
“crude” cost even though these diseases are highly preva-
lent in these countries. While vaccine prices may still be a
powerful influence on deciding which vaccines to introduce,
it may be better decision-making to justify expenditures on
vaccines that demonstrate their cost-effectiveness [46]. Most
immunisations cost less than US$ 50 per healthy life-year
saved. This is compared to the cost of treating a disease such
as hypertension, which is estimated in the United States to
be between US$ 4340 and 87,940 per healthy life-year saved
[47]. When infectious diseases are not controlled they can
place a tremendous burden on the economy of communities
and regions. A few assessments from the literature are as
shown in Table 8. For example, cholera cost US$ 770 mil-
lion in lost seafood export in Peru in 1991. For every dollar
spent on DTP vaccine, 24 are saved in treatment.

Table 8
Direct and indirect savings from vaccinationa
Comparative savings Direct or indirect savings (US$)
Disease
Smallpoxb,c NA 300 million in direct costs per year
Polioc,d NA 13.6 billion in total savings world-wide by 2040d
700 million in United States between 1991 and 2000e
Measlesf One case of measles is 23 times the cost of 10 per disability-adjusted life-year (DALY)
vaccinating one child against measlesc
Cholerag NA 770 million lost in seafood export Peru, 1991
Malariag NA 100 billion GDP lost annually in sub-Sahara Africa because of
malariah
MMRi For every US$ 1 spent on MMR vaccine, more 100 million in direct medical costs from 1989 to 1991 measles
than US$ 21 is saved in direct medical care costs outbreakj
DTaPi For every US$ 1 spent on DTaP vaccine, US$ 23.6 billion in direct and indirect costs without DTP vaccinesk
24 is saved
Hibi For every US$ 1 spent on Hib vaccine, more 5 billion in direct costs and 12 billion in indirect costs incurred
than US$ 2 is saved in United Statesl
Other public health problemsm
Plague NA 1.7 billion lost tourist income and trade
AIDS NA 14 billion annual treatment cost in the United States
Drug resistance NA 4 billion annual treatment cost in the United States
NA: not available, MMR: measles–mumps–rubella, DTaP: diphtheria–tetanus–acellular pertussis, Hib: H. influenzae type b.
a [62].
b Based on eradication of smallpox in 1977.
c CDC, Immunization Services Division, Health Services Research and Evaluation Branch, 1999.
d Based on eradication of polio by 2005 [74].
e http://clinton1.nara.gov/White House/EOP/OSTP/CISET/html/iintro.html.
f Canadian Institute for Health Information. http://www.cihi.com/Programme%20Information/Crosscutting%20Programmes/imm96p.pdf.
g [1].
h http://www.who.int/inf-pr-2000/en/pr2000-28.html.
i Basic principles of immunization cited in: why is immunization important today? Module 1: basic principles of immunization. http://healthsoftonline.

com/tip/matem1l1.htm. Accessed 23 June 2001.

j [75].
k [76].
l http://www.ostp.gov/CISET/html/iintro.html#table1, United States Government Accounting Office, Immunization: HHS could do more to increase

vaccination among older adults (Washington, DC, June 1995), p. 11.

m WHO 1999. WHO infectious diseases report: removing obstacles to healthy development. http://www.who.int/infectious-disease-report/pages/

graph24.html.
4114 J. Ehreth / Vaccine 21 (2003) 4105–4117

The ability to reduce global disease burden with vaccines Table 10

continues to expand, as new vaccines are developed to pre- Comparison of public health related interventionsa
vent new diseases. Policy makers must decide where re- Intervention Cost per life-year
sources can be most effectively allocated. Factors such as saved (US$)
safety, efficacy, feasibility, cost-effectiveness, indications for Mandatory seat-belt-use law 69
use, social and ethical aspects must all be considered in or- Influenza vaccination for all citizens 140
Sickle-cell screening for black newborns 240
der to objectively justify introducing a new vaccine or vac-
Federal law requiring smoke detectors in homes 920
cination program [12]. Mandatory motorcycle-helmet laws 2000
Vaccination is one of the few preventive public health Pneumonia vaccination for seniors 2200
measures that directly save money. American Journal of Chlorination of drinking water 3100
Public Health study documented a 14:1 return on invest- Smoking-cessation advice for smokers (one or 9800
more packs per day)
ment for the MMR vaccine. For every dollar spent, US$
Alcohol-safety programs for drunk drivers 21000
3.94–4.91 was saved; not including reduced absenteeism or AZT for people with AIDS 26000
improved productivity [54]. Immunisation reduces the social Smoke detectors in aeroplane lavatories 30000
and financial costs of treating diseases, offering opportuni- Child-resistant cigarette lighters 42000
ties for poverty reduction and greater social and economic Ban asbestos in pipeline wrap 65000
Child-restraint systems in cars 73000
development.
Promote voluntary helmet use for all-terrain 44000
In the developing world, the annual cost of immunising vehicles
millions of children against six infectious diseases is equiva- National 55 mph speed limit 89000
lent to the cost of a single day of health care in United States. Community health-care services for women and 100000
For less than US$ 20 in vaccine and administration costs, infants
Widen lanes on rural roads from 9 to 11 ft 150000
a child can be immunised against polio, diphtheria, pertus-
Redesign chain saws to reduce rotational 230000
sis, measles and tetanus. Additional “life-saving” vaccines kickback injuries
could be added for approximately US$ 10 per vaccine. If it Ban pesticide amitraz on pears 350000
costs around US$ 30 to immunise one child, that is equal to Ozone-control program for southern coast of 610000
about US$ 3–4 billion a year to immunise 100–120 million California
Warning letters sent to problem drivers 720000
children [55]. At a cost of US$ 2.9 billion, measles vacci-
Ejection system for the Air Force B-58 bomber 1200000
nation coverage could be increased to 95% in low income Triple the wind-resistance capabilities of new 2600000
countries, resulting in an estimate of 579,000 child deaths buildings
averted per year [56]. Seat belts for school-bus passengers 2800000
It is becoming increasingly clear that relatively modest Ban asbestos in packing 5700000
Strengthen buildings in earthquake-prone areas 18000000
spending on immunisation can bring significant gains that
a Source: [65]. Reported by J. McCarthy in http://www.psych.upenn.
benefit households and national economies. The cost esti-
mates in Table 9 take into account the local disease bur- edu/∼baron/900/risk.htm#s3. Life-saving interventions were defined as
any behavioural and/or technological strategy that reduces the probability
den, the total costs of the vaccine and its administration
of premature death among a specified target population. Cost-effectiveness
and the efficacy of the vaccine. In the literature, the cost was defined as the net resource costs of an intervention per year of life
per-life-year-saved ranges between US$ 8–11, for Hep B in saved. To improve the comparability of cost-effectiveness ratios arrived
high prevalence areas, to US$ 42–59 in low prevalence ar- at with diverse methods, the authors established fixed definitional goals
and revised published estimates, when necessary and feasible, to meet
Table 9 these goals.
Vaccine cost per life-year saved
Immunization Cost per life-year eas. To put this into the perspective of the government or
saved (US$) insurer making resource allocation decisions, Table 10 com-
Measlesa <11.7 (2–15) pares other funded health care interventions. Clearly, vacci-
EPI cluster: polio, DTP, BCG, measles: 14–20 nation is highly cost-effective but this value is not adequately
low-incomea
translated into coverage rates in many parts of the world.
EPI cluster: polio, DTP, BCG, measles: 29–41
mid-incomea
Hepatitis B—low-income countries, 42–59
prevalence <2%b 8. Strategies to address the under-valuation of
Hepatitis B—low-income countries, 8–11 vaccination
prevalence >8%b
Hib, Africab 21–22
Hib, low-income Asiac 55 From 1985 to 1990 significant progress was made in im-
proving global vaccination programs. However, immunisa-
Source: [46]. http://www.vaccinealliance.org/text/reference/vacc cost.html.
a [77]. tion rates and infrastructure have since deteriorated and new
b [68]. vaccines have not been available to the developing countries
c [78]. [48,49]. Current international incentives for new vaccine
 J. Ehreth / Vaccine 21 (2003) 4105–4117
utilisation are inadequate and imbalanced. A rich child in
a rich country receives a new vaccine 10–15 years before
a poor child in a poor country receives the same vaccine.
In order to accelerate the introduction of new vaccines into
developing countries, new means must be employed to im-
prove understanding of the value of vaccination in the eyes
of policy makers world-wide.
A major barrier to the appropriate valuation of vac-
cines is adequate knowledge of disease burden and vaccine
cost-effectiveness based on a larger picture of the true cost
and benefits of a healthy society. Access to information
about the cost-effectiveness of the vaccines, as opposed
to their price is the key to making informed decisions re-
garding health care budgeting. Data on the magnitude of
the disease burden particular to a region and population,
information about the local costs of treating the disease
and of administering the vaccine should be available at
national and regional level, so that each nation can make
its own assessment. Although crude cost of a vaccine may
be used to decide which new vaccines to introduce, it may
be easier to justify expanding a national program if there
are data such as these to demonstrate that specific vaccines
are cost-effective [46]. Table 12 summarises this study’s
findings regarding the valuation of vaccination.
The Children’s Vaccine Initiative worked with UNICEF,
WHO and manufacturers to develop a universal methodol-
ogy to evaluate vaccination [50] to make comparisons of
the costs and efficiencies of vaccine interventions and thus
enable them to objectively assess the value of vaccination.
When reviewing the burden of disease, other issues partic-
ular to a specific disease may increase its importance to soci-
ety. For example, meningococcal meningitis, dengue fever,
and cholera in developing countries, because of the rapid
morbidity and mortality, can often cause significant disrup-
tions in the provision of health care services and impact
heavily on health care resources [44].
9. Strategies to address the under-utilisation
of vaccines
There are additional ways to increase vaccination besides
better resource allocation. One could reduce the number
of immunisation visits and improve delivery technology.
The reduction of wastage by better managing expiration
dates; streamlined logistics for storage and supply; and
reducing the number of injections needed would all lead
to better coverage. Reduced dosing has been success-
ful with the Hib conjugate vaccine. Combination vac-
cines reduce non-compliance and costs [51]. A number
of innovative funding mechanisms with international and
inter-government co-operation are being discussed for direct
aid, loans, [5] and multi-lateral agreements [52] in addition
to tiered pricing [52]. Building infrastructure is another op-
tion [54–58] And finally, increased vaccine research could
improve both vaccines and delivery [59].
4115
10. Conclusion
Vaccines are unquestionably one of the most cost-effective
public health measures available, yet they are under-valued
and under-utilised throughout the world. It is important for
international agencies, governments, and health policy mak-
ers to keep this preventive measure in the spotlight. It is
important to remind parents, the general population, and
health care providers world-wide to take advantage of this
life-saving measure so that no one will suffer diseases that
can so easily be prevented.
Strategies such as combining vaccines to reduce cost and
the number of injections, innovative funding strategies in
developing countries, and multi-lateral agreements in coun-
tries at war will improve access to vaccines. Developing and
improving infrastructure to ensure adequate vaccine delivery
and stepping up vaccine research will also lead to improved
vaccine access. Ultimately, it is the global society and future
generations that benefit when all countries make the effort to
protect their populations from vaccine-preventable diseases.
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