Global Health: Factors Contributing to Low Vaccination Rates in
Developing Countries (Letter Report, 10/15/1999, GAO/NSIAD-00-4).

Pursuant to a congressional request, GAO examined some of the key issues
involving vaccine availability for children in developing countries,
focusing on the: (1) locations where shortfalls in immunization coverage
are most prevalent; and (2) factors that impede vaccine availability in
these locations.

GAO noted that: (1) while global immunization coverage for six diseases
originally targeted by the World Health Organization (WHO) has improved
significantly since the mid-1970s, coverage rates are low for children
living in the poorest countries, particularly in urban slums and remote
rural areas; (2) WHO data indicate that the poorest countries of the
world have vaccination rates that are about 26 percent below the global
average of 82 percent; (3) in fact, immunization coverage in some
countries in sub-Saharan Africa has declined over the last decade; (4)
some countries in this region reported in 1997 that they immunized less
than a third of their children against the six diseases targeted by WHO;
(5) many of the children who are not immunized live in countries that
have experienced internal conflict in recent years; (6) although the
level of coverage varies, few children in developing countries have
access to the newer vaccines that have been added more recently to WHO's
list of recommended vaccines; (7) several interrelated factors that poor
countries have difficulty overcoming have limited the availability of
vaccines for children in the developing world, including: (a) inadequate
health infrastructure; (b) the relatively higher cost of vaccines
recently recommended by WHO; (c) insufficient information on disease
burden and vaccine efficacy; and (d) changing priorities of
international donors; and (8) in the 1990s, the United Nations
Children's Fund and the U.S. Agency for International Development have
begun to reduce their level of support for immunization.

--------------------------- Indexing Terms -----------------------------

 REPORTNUM:  NSIAD-00-4
     TITLE:  Global Health: Factors Contributing to Low Vaccination
	     Rates in Developing Countries
      DATE:  10/15/1999
   SUBJECT:  International organizations
	     Children
	     Immunization services
	     Immunization programs
	     Infectious diseases
	     Developing countries
IDENTIFIER:  UN Expanded Program on Immunization
	     AID Children's Vaccine Initiative

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ns00004 A Report to Congressional Requesters

October 1999 GLOBAL HEALTH Factors Contributing to Low Vaccination
Rates in Developing Countries

GAO/NSIAD-00-4

  GAO/NSIAD-00-4

Letter 3 Appendixes Appendix I: Objectives, Scope, and Methodology
22

Appendix II: Comments From the Centers for Disease Control and
Prevention 24 Appendix III: Comments From the U. S. Agency for
International Development 26 Appendix IV: GAO Contact and Staff
Acknowledgments 31 Figures Figure 1: Overall Immunization Coverage
Rates for Countries,

Grouped by Region, 1991- 97 7 Figure 2: Immunization Coverage
Rates in the Poorest Countries,

With and Without Conflict, 1991- 97 9 Figure 3: Immunization
Coverage Rates for Measles and

Tuberculosis in Sub- Saharan Africa, 1991- 97 13 Figure 4: UNICEF
Expenditures on Immunization, 1990- 98 19

Abbreviations

DPT Diphtheria, pertussis, and tetanus vaccine Hib Haemophilus
influenzae type b PAHO Pan American Health Organization TB
Tuberculosis UNICEF United Nations Children's Fund USAID U. S.
Agency for International Development WHO World Health Organization

National Security and International Affairs Division

Let ter

B-283270 October 15, 1999 The Honorable Mitch McConnell Chairman
The Honorable Patrick Leahy

Ranking Minority Member Subcommittee on Foreign Operations
Committee on Appropriations United States Senate

Over 11 million children under age 5 die each year in developing
countries, and nearly three- quarters of these deaths result from
infectious diseases. The World Health Organization estimates that
the deaths of at least 4 million of these children are linked to
their lack of access to vaccines. While long- term international
initiatives have significantly increased global immunization
rates, millions of children in the developing world, for various
reasons, lack access to vaccines.

Recognizing the significance of children in the developing world
not having access to vaccines, representatives from the
international public health community, including the World Health
Organization, the United Nations Children's Fund, the United
Nations Development Program, the World Bank, the Rockefeller
Foundation, and the Bill and Melinda Gates Children's Vaccine
Program, along with the U. S. Agency for International

Development and several other bilateral donors, have begun to
explore options for improving immunization coverage in developing
countries. They are seeking close collaboration with vaccine
manufacturers and the

governments of developing countries to devise strategies to meet
current vaccine needs and to improve access to new vaccines as
they are introduced. In anticipation of the United States being
asked to fund and provide other support for the renewed
international effort to promote childhood immunization, you asked
us to examine some of the key issues involving vaccine
availability. As agreed with your offices, this report provides

information and analyses on (1) the locations where shortfalls in
immunization coverage are most prevalent and (2) the factors that
impede vaccine availability in these locations. Our scope and
methodology for this report are outlined in appendix I. We will
report separately on our work

aimed at identifying the implications of various courses of action
that Congress may want to pursue to increase vaccine availability.
Results in Brief While global immunization coverage for six
diseases 1 originally targeted by the World Health Organization
has improved significantly since the mid- 1970s, coverage rates
are low for children living in the poorest countries, particularly
in urban slums and remote rural areas. World Health Organization
data indicate that the poorest countries of the world have
vaccination rates that are about 26 percent below the global
average of 82 percent. 2 In fact, immunization coverage in some
countries in sub- Saharan Africa has declined over the last
decade. Some countries in this region reported in 1997 that they
immunized less than a third of their

children against the six diseases targeted by the World Health
Organization. Many of the children who are not immunized live in
countries that have experienced internal conflict in recent years.
Although the level of coverage varies, few children in developing
countries have access to the newer vaccines that have been added
more recently to the World Health Organization's list of
recommended vaccines. Several interrelated factors that poor
countries have difficulty overcoming have limited the availability
of vaccines for children in the developing world, including (1)
inadequate health infrastructure, (2) the relatively higher cost
of vaccines recently recommended by the World Health Organization,
(3) insufficient information on disease burden 3 and vaccine
efficacy, and (4) changing priorities of international donors. In
the 1990s, the U. N. Children's Fund and the U. S. Agency for
International Development have begun to reduce their level of
support for immunization.

1 Diphtheria, measles, pertussis, polio, tetanus, and
tuberculosis. 2 United Nations Children's Fund officials estimate
that actual coverage rates are about 10 percent lower because of
reporting errors by countries. 3 Disease burden refers to the
level of mortality and reduced quality of life associated with
disease.

Background The international public health community has played an
important role in helping countries to improve immunization
coverage. In 1974, the World Health Organization (WHO), which
typically sets the global public health agenda, created the
Expanded Program on Immunization to increase immunization of the
world's children against six diseases diphtheria, measles,
pertussis, polio, tetanus, and tuberculosis. In 1980, the United
Nations Children's Fund (UNICEF) established a goal of immunizing
80 percent of the world's children against these diseases by 1990
and called upon donors to contribute to this effort. The worldwide
effort that was mobilized by the Expanded Program on Immunization
helped countries increase immunization rates for these diseases
from less than 5 percent of all children when it was established
in 1974 to the current rate of 82 percent worldwide. 4 In 1990,
the international public health community created the Children's
Vaccine Initiative as a forum for coordinating global efforts to
further improve immunization and to promote research and
introduction of new vaccines. More recently, WHO recommended that
countries include several additional vaccines in their
immunization schedules, namely

hepatitis B, yellow fever for endemic countries, and Haemophilus
influenzae type b (Hib). 5 National governments are responsible
for developing and managing their immunization programs, including
sustaining vaccine delivery systems and determining which vaccines
will be included in their immunization schedules. Immunization
programs must compete with other important priorities such as
education and nutrition. In the 1990s, donors and international
organizations have encouraged developing countries to pay an
increasing share of the cost of procuring vaccines. However,
almost all developing countries still rely to some extent on the
technical and financial assistance provided by international
organizations and bilateral donor organizations like the U. S.
Agency for International Development (USAID) to maintain their
immunization programs. 4 This is the average coverage for the
vaccines used to prevent the six diseases originally targeted by
WHO as reported by national governments to WHO in 1997.

5 A vaccine against the Hib bacterium, which causes meningitis and
pneumonia, was recommended by WHO for countries that have
sufficient disease burden and infrastructure capability to warrant
introduction.

Immunization Rates Immunization rates for the six WHO- targeted
diseases in many of the Are Lower Than the

poorest countries of the world are substantially lower than the
global average of 82 percent. In some countries, coverage has
declined in recent Global Average in years. Moreover, few
developing countries have included vaccines recently

Many Poor Countries recommended by WHO for inclusion in national
immunization programs.

Shortfalls in Coverage for Although five countries 6 in other
regions have coverage rates among the Older Vaccines

lowest in the world, most countries with immunization coverage
below 60 percent are in sub- Saharan Africa (see fig. 1). In 1997,
governments in this region reported immunizing only about 60
percent of their children

against the original six targeted diseases. Chad, Sierra Leone,
and the Democratic Republic of the Congo have the lowest rates in
the region, providing vaccines to less than 31 percent of their
children.

6 Afghanistan, Djbouti, the Lao People's Democratic Republic,
Papua New Guinea, and Yemen.

Figure 1: Overall Immunization Coverage Rates for Countries,
Grouped by Region, 1991- 97

100 Overall percent of coverage 90

80 70 60 50 40 30 20 10

0 1991 1992 1993 1994 1995 1996 1997

CEE EA LA ME SA SSA

Legend: CEE = Central and Eastern Europe EA = East Asia LA = Latin
America ME = Middle East SA = South Asia SSA = Sub Saharan Africa

Note: Immunization coverage for diphtheria, measles, pertussis,
tetanus, tetanus, tuberculosis, and polio.

Source: GAO analysis based on data published by WHO in September
1998.

In addition, country studies conducted by donor organizations and
national governments show that immunization coverage often varies
markedly within countries, with substantially lower coverage rates
in urban slums and remote rural areas. One USAID- funded survey,
for example, found that in 1997, 65 percent of all children in
Dhaka, Bangladesh, were immunized

against measles, but only 46 percent of children in Dhaka's
poorest neighborhoods had received the vaccine. Similarly, a 1998
study of measles coverage in Cambodia, prepared by the Cambodian
Ministry of Health, showed that coverage rates ranged from over 75
percent in the capital region to below 30 percent in more remote
regions. Other evidence includes a 1999 study by the Ugandan
Ministry of Health that found that children in rural areas in
Uganda were not immunized at all. While the common characteristic
of countries with low coverage is low per

capita income and a corresponding low per capita spending on
health, 7 countries that have experienced civil conflict tend to
have the lowest immunization rates. Of the 25 poorest countries in
the world, 11 countries had recently experienced or were
experiencing unrest. 8 For the period 1991- 1997, these 11
countries had immunization coverage levels that were on average
about 19 percent below the countries with comparable per capita
income that have not experienced conflict. (See fig. 2.)

7 The World Bank estimates that the poorest countries of the world
spend $22 per capita on health each year, rising to $209 for the
wealthier developing countries. 8 Afghanistan, Angola, Burundi,
Cambodia, Chad, Ethiopia, Mozambique, Myanmar, Nigeria, Rwanda,
and Sierra Leone.

Figure 2: Immunization Coverage Rates in the Poorest Countries,
With and Without Conflict, 1991- 97

70 Overall percent of coverage

60 50 40 30 20 10

0 1991 1992 1993 1994 1995 1996 1997

Non- conflict Conflict

Note: Immunization coverage for diphtheria, measles, pertussis,
tetanus, tuberculosis, and polio. Source: GAO analysis based on
data published by WHO in September 1998 and on data compiled by
Ruthann Leger Sivard, World Military and Social Expenditures
(1998).

Coverage for New Vaccines Efforts by WHO to encourage countries to
incorporate additional vaccines Is Limited

in national immunization programs hepatitis B, yellow fever, and
Hib and to introduce tetanus coverage for pregnant women to
protect babies at birth have not resulted in high coverage rates.
In 1998, WHO reported in its

summary of global vaccine coverage that few of the poorest
developing countries had incorporated the hepatitis B vaccine 9
into their immunization schedules despite the estimated 1 million
deaths that this disease causes each year. 10 Of the 48 countries
that fit UNICEF's category of least developed (less than $785 per
capita income yearly), only 6 countries reported any coverage as
of 1997. 11 In the six poor countries that have adopted the
hepatitis B vaccine, immunization rates average only about 50
percent. Coverage rates for high- income countries that have
adopted the vaccine average about 70 percent. According to WHO, in
1997 only 12 of the 34 African countries at highest

risk for yellow fever had included a yellow fever vaccine in their
national immunization programs. 12 Only two countries in Africa
Cte d'Ivoire and the Gambia-reported coverage levels over 50
percent in 1997. Deaths associated with outbreaks in particular
regions of countries can be significant. For example, in several
remote mountain villages of Cameroon, WHO estimated that one
epidemic in 1990 killed up to 1,000 villagers in

11 villages. 9 In 1991, WHO recommended that all countries include
the hepatitis B vaccine in their national immunization programs by
1997. 10 Most of these deaths are among adults who were infected
as children. Hepatitis B is the primary cause of liver cancer,
which is the leading cause of cancer death in men in

sub- Saharan Africa and much of Asia. It is also an important
cause of cancer deaths in women.

11 Bhutan, Gambia, Kiribati, Maldives, Tuvalu, and Vanuatu. 12 In
1988, WHO recommended that countries at risk for yellow fever
outbreaks should adopt the vaccine into their national
immunization programs. Yellow fever is endemic in 42 African and
South American countries and several Caribbean islands.

WHO estimates that more than 277,000 children die each year from
neonatal tetanus (tetanus developed within the first 4 weeks after
birth). Because infants are infected by neonatal tetanus as a
result of unclean delivery practices and equipment, without
improvements in delivery conditions, the only way to protect
newborns from the disease is to vaccinate expectant mothers. WHO
reported in 1997 that 48 percent of

pregnant women in developing countries do not pass on protective
immunity to their babies against tetanus because they have not
received the neonatal tetanus vaccine. 13

WHO reports that 39 countries have added the Hib vaccine to their
immunization schedules primarily countries in the developed world.
These 39 countries include only 12 percent of the world's
children. However, a WHO official noted that 500,000 children die
each year from this disease, mostly in developing countries. Some
higher income developing countries have successfully introduced
Hib into their immunization programs, particularly in South
America and the Caribbean. As of December 1999, the Pan American
Health Organization (PAHO)

reported that 75 percent of all newborns in the region 14 lived in
countries that had adopted the Hib vaccine. However, in sub-
Saharan Africa, where the risk of Hib is considered high by
experts, only one country, the Gambia, has introduced the Hib
vaccine. Several Factors Four principal factors have limited
vaccine availability in developing Impede Vaccine

countries: (1) inadequate health infrastructure, (2) the
relatively higher cost of vaccines recommended recently by WHO,
(3) insufficient Availability in information on disease burden and
vaccine efficacy, and (4) changing Developing Countries

priorities of international donors. The extent to which these
factors impede vaccine availability varies by country, although
some patterns exist across countries. 13 Tetanus immunization is
part of the three- dose diphtheria, pertussis, and tetanus (DPT3)
vaccine that WHO recommended as part of the original six vaccines.
To decrease deaths due

to tetanus that occurred soon after birth, in 1989 WHO recommended
the tetanus toxoid vaccine for pregnant women.

14 There are 46 countries/ territories in PAHO, spanning Canada,
Central America and the Caribbean, South America, and the United
States.

Inadequate Infrastructure Countries must have systems that can
safely and effectively deliver Impedes Immunization vaccines. WHO
uses several indirect measures to assess countries' Efforts

capability to implement vaccine immunization programs. These
measures, which include countries' ability to administer vaccines
at several intervals during the first year of life, to avoid
vaccine waste, and to ensure vaccine quality, show that many
developing countries have weak infrastructure. Inadequate
infrastructure is most apparent in the poorest countries,
resulting in low coverage rates, even when vaccines are donated.
Typical problems include outdated or insufficient vaccine
refrigeration and a lack of delivery trucks and trained health
workers.

One indicator WHO uses to determine the ability of countries to
effectively deliver vaccines is the percentage of children who
have received the third dose of the combination vaccine for
diphtheria, pertussis, and tetanus. Because three doses are
required, this measure provides an indication of a

country's capability to immunize children at several intervals
during the first year of life. The results of this indicator show
that the poorest countries, particularly in sub- Saharan Africa,
are not sustaining the delivery of all three doses. For example,
in 1997 Chad had coverage for the third dose of the combined DPT3
vaccine of 24 percent, while overall coverage for the six original
vaccines was 31 percent. WHO believes the data reflect weaknesses
in health delivery capabilities.

A second indicator of a country's capability to deliver vaccines
is the percentage of children vaccinated against tuberculosis (TB)
at birth and the percentage of all children receiving the measles
vaccine at about

9 months of age. While some difference occurs in most countries, a
greater difference indicates a less effective delivery system
because it is often easier to reach a child at birth to administer
a vaccine than at 9 months of age. On average, the percentage of
children immunized against measles was about 10 percent lower than
the immunization rate for tuberculosis. The poorest countries had
the largest difference in coverage rates for

tuberculosis and measles, with sub- Saharan African countries
reporting a 12 to 15 percent difference in immunization rates for
tuberculosis and measles (see fig. 3).

Figure 3: Immunization Coverage Rates for Measles and Tuberculosis
in Sub- Saharan Africa, 1991- 97

90 Percent of coverage

80 70 60 50 40 30 20 10

0 1991 1992 1993 1994 1995 1996 1997

TB Measles

Source: GAO analysis based on data published by WHO in September
1998.

Another indicator of the status of a country's health
infrastructure is the amount of vaccine that is purchased but not
administered to children. The difference is considered waste by
WHO and is used to indicate governments' ability to accurately
estimate demand and to effectively deliver the vaccines. In 1997,
WHO officials estimated that, on average, 43 percent of vaccines
delivered to developing countries were not administered to
children. Some of the loss occurs because many vaccines

are heat sensitive and are left unrefrigerated for too long,
resulting in a decrease in potency, so they must be discarded. In
addition, vaccines have a limited shelf- life and must be disposed
of if not used within that period. Finally, health care providers
may decide to open a multidose vial to vaccinate one child even
though the other doses are wasted, so as not to miss the
opportunity to vaccinate the child. WHO estimates that much of the
unused vaccine in developing countries resulted from poor planning
regarding the amount of vaccine needed and the procurement of
vaccine in large, multidose vials (10 to 20 doses). While
multidose vials are the least expensive way to purchase vaccines,
such factors as poor forecasting of

vaccine needs at delivery sites and inadequate training of health
workers regarding the ability to use leftover vaccines led to
unnecessarily high rates of vaccine waste. For example, in 1998,
the difference between vaccines procured and vaccines used in
Bangladesh ranged from 61 percent for DPT to 29 percent for
measles. WHO has made efforts to reduce the amount of vaccine
wasted by encouraging the use of a vaccine vial monitor that
tracks time and temperature exposure of the polio vaccine to
estimate its potency, and the procurement of vaccines in smaller
vials. A WHO official told us that in order to avoid waste,
countries are urged to use smaller vials for the

more expensive hepatitis B and Hib vaccines. UNICEF reports that
by the year 2000 it will require monitors on all heat- sensitive
vaccines in an effort to increase confidence in vaccine potency
and reduce waste. Case studies of particular countries illustrate
the problems that occur due to inadequate infrastructure. A 1998
special report by the United Nations Children's Fund on the
immunization programs of eight countries in

sub- Saharan Africa 15 found that poor organization and management
in vaccine distribution, maintenance of refrigeration, and
immunization scheduling had resulted in an inefficient program.
The study also found a shortage of properly trained staff. As a
result, immunization coverage ranged between 30 and 35 percent in
three of these countries Chad, Mali, and Niger. Studies of Zambia
and Bangladesh also pointed out excessive vaccine waste due to
poor vaccine management practices. Health workers in both
countries often did not know how to check DPT vaccine to ensure
that it had not frozen (and consequently reduced its potency). A
1999 study prepared by the Uganda Ministry of Health found that
health workers were inadequately trained to manage the
immunization services and that these services were provided on an
irregular basis due to the lack of transport.

Higher Prices for Newer Another factor inhibiting the availability
of newer vaccines in developing Vaccines Limit Their countries is
their relatively high price. While the price of vaccines declines
Availability over time as more suppliers enter the market, it has
generally taken a decade after vaccines were first licensed before
developing countries have begun to purchase them. Even as the
prices have declined, they remain high relative to the cost of the
older vaccines, and the poorest countries 15 Vaccine Independence
Initiative Implementation in 1997 and 1998, UNICEF (New York: Oct.
1998) Countries covered were Burkina Faso, Cape Verde, the Gambia,
Mali, Mauritania, Niger, Senegal, and Chad.

have not included them in their immunization schedules. Moreover,
donors have not generally funded purchases of the newer vaccines.
Vaccine companies cite the cost of research and development of
vaccines as the primary reason for the higher prices of newer
vaccines. According to vaccine company officials, the cost of
developing a new product and bringing it to market is substantial,
costing between $100 million and $300 million to license a vaccine
in the United States. Royalty costs the amount vaccine companies
must pay to use production technologies that are patented by
others, such as biotechnology companies can also be

high for new vaccines. In the case of hepatitis B, for example,
WHO estimates that royalty costs are 13 to 15 percent of the sales
price. Experience with the introduction of hepatitis B and Hib
shows that price was a factor inhibiting procurement by developing
countries for almost a decade after the vaccines were first
licensed and then they were only purchased by some higher income
developing countries. For example, hepatitis B was introduced in
the United States in the early 1980s at over

$30 per dose, with only two manufacturers supplying the vaccine.
UNICEF and PAHO did not begin to purchase the vaccine until 1993
and 1994, 16 respectively, after several competitive products had
been introduced to the

market and prices had dropped to less than a dollar per dose. 17
The first Hib vaccines that were effective on infants were
licensed in the United States in late 1987 and sold for about $14
per dose. PAHO did not purchase this vaccine until 1998, when it
was able to negotiate a price of $2.18 per dose. However, very few
of the poorest countries have purchased Hib or hepatitis B
vaccines. According to WHO officials, price continues to be an
impediment in these countries, in part because donors have
generally not

funded the purchase of these vaccines. Insufficient Information
Governments and donors need accurate information that can serve as
a Impedes Investment in basis for deciding how much to invest in
immunization programs. Vaccines and Immunization Surveillance data
are crucial in assessing the impact of individual diseases,
Programs

determining whether existing disease reduction targets are being
met, and deciding where resources should be targeted for maximum
impact. In 16 UNICEF only purchased the vaccine for countries that
reimbursed the agency. PAHO purchases the vaccines with money in
its revolving fund but requires countries to pay for the vaccines.
17 This is the price negotiated by PAHO for hepatitis B vaccine in
1998.

addition, information is necessary for citizens to help generate
demand for vaccines. Even in developed countries that have
sophisticated diagnostic equipment, disease burden data can be
difficult to obtain. In much of the developing world, however,
relevant data are inaccurate, inadequate, or are simply not
collected. For example, Bolivia had refrained from making
additional investments in its immunization system because
government officials had accepted reports from the immunization
program office

claiming that immunization coverage was about 80 percent. Bolivian
officials changed their position when a World Bank/ PAHO team
presented survey data indicating that the immunization coverage
was closer to 40 percent. Moreover, in 1996 WHO reported that a
28- country study uncovered wide- ranging problems in data
gathering on disease prevalence. Many of the data that were
collected were irrelevant, and health officials in developing
countries did not have the necessary skills to analyze the data
that were obtained. Disease burden data are very difficult to
obtain because records indicating cause of death and illness are
often inaccurate

or incomplete. Without the use of sophisticated diagnostic
methods, it is hard for health workers to determine the cause of
death, particularly when malnutrition and other contributing
factors are present. 18 For example, WHO officials estimate that
the incidence of yellow fever is up to 500 times greater than
reported because of difficulty in diagnosing the disease and
insufficiency of local health facilities in endemic countries.

Clinical vaccine trials are used to determine the efficacy of
vaccines in particular countries and groups of countries. In
wealthier countries where markets are assured for successful
products, vaccine companies fund trials that are required for
licensing. In developing countries, donor countries and
multilateral organizations have had a more important role in
funding clinical and disease burden studies. However, there has
been limited clinical testing of vaccines in developing countries,
and when they have

been conducted, they were begun several years after vaccines were
licensed in the developed world. For example, the first clinical
tests for the Hib vaccine effective in infants were initiated by
vaccine companies in the United States in 1984 and Finland in
1985, resulting in a U. S. license in 1987. It was 8 years after
clinical trials began in the United States before trials 18 UNICEF
reported that malnutrition alone accounts for just 3 percent of
deaths for children

under age 5, but it plays a contributing role in more than half of
all child deaths in developing countries.

began in a developing country. Clinical trials supported by donor
countries and vaccine companies began in Chile in 1992 and a year
later in the Gambia. In 1998, a Hib disease burden study,
supported by USAID and WHO, was initiated in Indonesia. As a
result of the time lag before clinical trials were conducted in
poorer countries, governments in developing countries have not had
information regarding the efficacy of new vaccines until several
years after licensing in the developed world. According to a WHO
official, the choice of a site to conduct clinical tests on a new
vaccine is typically determined by the existence of an
infrastructure capable of sustaining a large trial. The challenge,
according to the WHO

official, is that in some cases the highest risk populations live
in areas where the infrastructure is insufficient to support these
trials. While smaller scale demonstration and pilot studies could
be conducted to determine disease burden and vaccine efficacy in
countries where infrastructure is weak, generally these have also
not been conducted until several years after licensing in
developed countries. Information on disease burden and vaccine
efficacy is critical for

governments that must make vaccine investment decisions. For
example, a vaccine that is expected to be licensed soon,
pneumoccocal conjugate, could be more effective in lessening the
overall burden of pneumonia than the existing Hib vaccine. While
the Hib vaccine immunizes against 20 percent of the disease
strains that cause pneumonia, candidate

pneumoccocal conjugate vaccines may prevent up to 70 percent of
the disease strains that cause pneumonia. Information from
clinical trials could provide a better understanding of the burden
of this disease in developing countries and the effectiveness of
various vaccines so that governments have the information they
need to make decisions regarding the purchase of additional
vaccines. These data limitations have prevented experts from
conducting cost- effectiveness studies that could assist
governments in determining the value of investing in additional
vaccines. The Children's Vaccine Initiative, for example, found
that of 190 published vaccination cost- effectiveness studies they
identified, only about 10 percent pertained to developing
countries-and most of those were of poor quality. The Children's
Vaccine

Initiative has recently developed analytical models to estimate
the cost- effectiveness of introducing several additional vaccines
into the immunization programs of developing countries, including
hepatitis B and Hib.

Shifting Priorities of In the 1970s and 1980s, after WHO created
the Expanded Program on International Donors Immunization, the
international donor community provided significant support to
efforts to improve the availability of vaccines in developing
countries. However, during the 1990s, overall commitments by
bilateral

donors for efforts to control infectious diseases, including
immunization, have fluctuated significantly each year. The U. S.
bilateral commitment through USAID declined slightly as a
percentage of funding in the category of child survival 19 over
the 1990s. UNICEF spending for immunization decreased in dollar
value and as a percentage of total health expenditures over the
period. Within the pool of funds committed to control of
infectious diseases, the global effort to eradicate polio received
priority attention. 20 According to USAID and UNICEF officials,
this has resulted in less money

being available to support routine immunization programs. The
priority placed by bilateral donors on infectious diseases, which
includes support for routine immunization and polio eradication as
well as control of other diseases such as malaria and diarrheal
diseases, shifted yearly throughout the 1990s. Annual spending
commitments fluctuated by at least 39 percent per year and up to
330 percent. On average, however, infectious disease commitments
slightly increased from 10.5 to 11.4

percent of total health commitments from the early to the later
1990s. An increasing percentage of infectious disease commitments
was directed to support polio eradication, which increased from
about 14 percent of infectious disease funding in 1995 to about 52
percent in 1997. While USAID funding for overall child survival
programs rose by more than 50 percent since 1990, 21 from about
$223 million to about $341 million in 1998, support for
immunization programs declined as a percentage of funding for
child survival programs. On average, immunization funding

declined from about $53 million (19 percent of child survival
funding) between 1990 and 1993 to about $51 million (17 percent of
child survival funding) from 1994 to 1997. In 1998, immunization
was only about $47 million or 14 percent of the total obligated
for child survival. Since

19 These are programs designed to deal directly with the special
health needs of children and mothers, including those aimed at
improving immunization, nutrition, and sanitation. 20 Polio
eradication is an effort targeted specifically at ensuring that
the incidence of polio is reduced to zero, thus obviating the need
for further control measures. 21 All USAID figures are fiscal year
obligations.

polio eradication began in 1996, on average, about half of USAID's
spending for immunization was directed toward this effort. While
UNICEF expenditures for health programs declined slightly from the
early to the later 1990s, UNICEF funding for immunization declined
more significantly both in terms of dollar value and also as a
percentage of overall UNICEF expenditures (see fig. 4 for an
illustration of UNICEF

spending). Immunization funding decreased from about $182 million
(57 percent of health expenditures) in 1990 to about $51.5 million
(25 percent of health expenditures) in 1998. In addition, a
growing percentage of immunization funds was spent on vaccine
procurement, particularly to support the polio eradication effort,
with vaccine procurement increasing

from 25 percent of the total in 1990 to 83 percent of the total in
1998. As a result, support for other immunization services, such
as maintaining national vaccine delivery systems, has declined.
Figure 4: UNICEF Expenditures on Immunization, 1990- 98

200 Dollars in millions

180 160 140 120 100

80 60 40 20

0 1990 1991 1992 1993 1994 1995 1996 1997 1998

Immunization funding Of which, vaccine procurement

Note: Expenditures are in constant 1997 dollars (in millions).
UNICEF officials note that recent data coding changes may slightly
increase the spending totals for 1997 and 1998.

Source: GAO analysis based on 1999 UNICEF data.

Almost no donor funding has been available to purchase more
recently recommended vaccines. UNICEF, citing a lack of resources,
has not purchased vaccine to prevent Hib for any country and only
purchases

hepatitis B vaccine on a very limited basis-for countries that
reimburse UNICEF. 22 A senior UNICEF official noted that the
agency issued a formal policy in 1998 encouraging their country-
level offices to take a leading role in introducing Hib and
hepatitis B in their countries. However, these offices did not
receive additional funds and have chosen not to use their existing
funds to purchase the newer vaccines. PAHO has a revolving fund
that procures hepatitis B and Hib vaccines but is reimbursed by
countries that place the orders. These countries benefit from the
lower prices that can be

negotiated with larger procurements by UNICEF and PAHO and are
allowed to reimburse the agencies with local currency, rather than
in dollars, which must be used to purchase the vaccines. In
addition, the

Asian Development Bank is considering providing financial support
for purchasing hepatitis B and Hib for its borrowing member
countries. Agency Comments The Centers for Disease Control and
Prevention and USAID provided written comments on a draft of this
report that are reprinted in appendixes II and III. The Centers
for Disease Control and Prevention stated that it generally agrees
with the overall message, noting that the report provides an
excellent introduction to the status of vaccination in developing
countries and the barriers that exist to expanding coverage and
implementing new vaccines. The Centers stated that one of the most
valuable observations made in the report was that developing
countries

were facing different barriers in their attempt to increase
vaccination rates. However, the Centers noted that we did not
mention an important barrier the lack of advocacy for vaccination
from the medical community and the public. We regard advocacy as a
potential option to address immunization shortfalls rather than a
barrier and therefore we did not discuss this matter

in the report. The Centers also provided technical comments that
we incorporated as appropriate. USAID stated that the report
presented the issue clearly, concisely, and fairly. USAID noted
the importance of making investments in immunization programs
within the context of broader health and developmental priorities
and emphasized the need for USAID and national governments to 22
The European Union Initiative, which purchases vaccines for
several countries in western Africa, does not provide support for
the purchase of more recently recommended vaccines.

balance health investments to address all priorities. While
agreeing with our observation that overall coverage rates in
African immunization programs were low, USAID pointed out that
some countries in Africa have developed strong national programs
that indicate the potential for program improvement in other
countries in the region. USAID also noted that vaccine costs are a
small percentage of the total cost associated with

immunization programs and that its implementation strategy assumes
a certain amount of waste. All of USAID's points are valid, but
they do not affect our primary message. Thus, we did not modify
the report.

As agreed with your offices, unless you publicly announce the
contents earlier, we plan no further distribution of this report
until 3 days after its issue date. At that time, we will send
copies of this report to appropriate

congressional committees; the Honorable Madeleine K. Albright,
Secretary of State; the Honorable Donna Shalala, Secretary of
Health and Human Services; the Honorable J. Brady Anderson,
Administrator of USAID; and other interested parties. We will also
make copies available to others on request. Please contact me on
(202) 512- 4128 if you or your staff have any questions concerning
this report. Other GAO contacts and staff acknowledgments are

listed in appendix IV. Benjamin F. Nelson, Director International
Relations and Trade Issues

Appendi I x Objectives, Scope, and Methodology At the joint
request of the Chairman and the Ranking Minority Member of the
Senate Committee on Appropriations, Subcommittee on Foreign
Operations, we identified the (1) locations where shortfalls in
immunization coverage are most prevalent and (2) factors that
impede vaccine availability in these locations. To identify
locations of shortfalls in immunization coverage, we reviewed
pertinent documents and analyzed data collected from the United
Nations Children's Fund (UNICEF), the World Health Organization
(WHO), and the World Bank for the years 1991 to 1997. UNICEF and
WHO collect information on immunization coverage from each country
for the six originally targeted diseases (that is, diphtheria,
measles, pertussis, polio, tetanus, and tuberculosis). WHO also
collects coverage information on hepatitis B, Haemophilus
influenzae type b (Hib), neonatal tetanus, and yellow fever. While
some experts maintain that immunization coverage rates provided by
country officials are overstated, WHO and UNICEF

conduct country- specific surveys to verify accuracy and make
adjustments where necessary. We used reported immunization
coverage from WHO to calculate the global coverage rate for the
six original vaccines for 1997, the most recent year for which
data are available. Data for 1998 will be available in September
1999, but WHO officials said that they did not expect any
significant changes in the trends we identified.

We examined patterns of immunization across regions of the world
and by selected countries. To obtain a better understanding of the
immunization shortfalls that we identified, we reviewed reports on
the immunization programs of specific countries. We used national
economic data from the World Bank to identify the relationship
between immunization rates and per capita income. We also reviewed
the 1998 report, World Military and Social Expenditures, on the
existence of conflict and civil unrest in developing countries to
identify their correlation with immunization coverage. Finally, we
attended two international vaccine conferences in Geneva,
Switzerland, and New York to interview and collect information
from national immunization program officials about the factors
that impeded immunization coverage for older vaccines and the
adoption of new vaccines in their programs. We primarily relied on
reports and unpublished papers from WHO and UNICEF to describe the
burden of disease for vaccines that have been recommended by WHO
for inclusion in national immunization programs. As much of the
disease burden information for developing countries is lacking,
WHO develops models to estimate disease burden. We spoke with

officials from the five global vaccine manufacturers and the
National Institutes of Health to ascertain the status of candidate
vaccines in the research pipeline. We relied on a WHO report on
the anticipated licensing of new vaccines for data on the expected
mortality from diseases that would be prevented through the
widespread availability of these vaccines. To examine the factors
that impede vaccine availability in the developing

world, we interviewed officials from multilateral organizations,
pertinent federal agencies, vaccine manufacturers, key
foundations, and vaccine experts in academia. We also collected
and reviewed documents such as WHO and UNICEF annual reports on
immunization coverage, special publications on vaccines, and
professional papers obtained from these sources. We interviewed
officials responsible for vaccine issues at the Pan American
Health Organization (PAHO), WHO, the World Bank, UNICEF, and the
United Nations Development Program. We also interviewed pertinent
program officials at the Centers for Disease Control and
Prevention, the Commerce Department, the Food and Drug
Administration, the National Institutes of Health, the State
Department, and the U. S. Agency for International Development
(USAID). We interviewed representatives of the Rockefeller and
Gates Foundations and the vaccine

divisions of Chiron; Merck & Co. Inc.; Pasteur Merieux Connaught;
SmithKline Beecham; and Wyeth Vaccines and Nutrition. Finally, we
interviewed a number of academic experts in the vaccine field who
have been particularly active at the international level. We
questioned these officials about their perceptions of the barriers
that have impeded greater availability and use of vaccines by
developing countries. In addition, we collected and reviewed
relevant reports, journal articles, and other publications that
discussed key impediments to vaccine availability. Finally, we
obtained vaccine price data from the Centers for Disease Control
and Prevention, PAHO, and UNICEF. We interviewed officials at
these organizations and vaccine companies to obtain insights into
why prices changed over time. We did not independently verify the

statistical data that were obtained from various sources. We
performed our review from July 1998 through August 1999 in
accordance with generally accepted government auditing standards.

Comments From the Centers for Disease

Appendi I I x Control and Prevention

Comments From the U. S. Agency for

Appendi x I I I International Development

Appendi x V I GAO Contact and Staff Acknowledgments GAO Contact
Lynne Holloway, (202) 512- 4612 Acknowledgments In addition to Ms.
Holloway, Claude Adrien, Maria Durant, Bruce Kutnick, Thomas
Laetz, Mike McAtee, Rona Mendelsohn, and Raymond Wyrsch made key
contributions to this report.

(711365) Let t er

GAO United States General Accounting Office

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Appendix I

Appendix I Objectives, Scope, and Methodology

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Appendix II

Appendix II Comments From the Centers for Disease Control and
Prevention

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Page 26 GAO/NSIAD-00-4 Vaccine Availability

Appendix III

Appendix III Comments From the U. S. Agency for International
Development

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Appendix III Comments From the U. S. Agency for International
Development

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Appendix III Comments From the U. S. Agency for International
Development

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Appendix III Comments From the U. S. Agency for International
Development

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Appendix IV

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