oversight

Global Health: Factors Contributing to Low Vaccination Rates in Developing Countries

Published by the Government Accountability Office on 1999-10-15.

Below is a raw (and likely hideous) rendition of the original report. (PDF)

                 United States General Accounting Office

GAO              Report to Congressional Requesters




October 1999
                 GLOBAL HEALTH

                 Factors Contributing
                 to Low Vaccination
                 Rates in Developing
                 Countries




GAO/NSIAD-00-4
Contents



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




             Page 1                                    GAO/NSIAD-00-4 Vaccine Availability
Page 2   GAO/NSIAD-00-4 Vaccine Availability
United States General Accounting Office                                                 National Security and
Washington, D.C. 20548                                                           International Affairs Division



                                    B-283270                                                                       Leter




                                    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




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                   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 diseases1 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.




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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.




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Immunization Rates           Immunization rates for the six WHO-targeted diseases in many of the
                             poorest countries of the world are substantially lower than the global
Are Lower Than the           average of 82 percent. In some countries, coverage has declined in recent
Global Average in            years. Moreover, few developing countries have included vaccines recently
                             recommended by WHO for inclusion in national immunization programs.
Many Poor Countries

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.




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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



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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.




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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).




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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 vaccine9 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—Côte 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.




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                       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 region14 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
                       countries: (1) inadequate health infrastructure, (2) the relatively higher
Impede Vaccine         cost of vaccines recommended recently by WHO, (3) insufficient
Availability in        information on disease burden and vaccine efficacy, and (4) changing
                       priorities of international donors. The extent to which these factors impede
Developing Countries   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.




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Inadequate Infrastructure   Countries must have systems that can safely and effectively deliver
Impedes Immunization        vaccines. WHO uses several indirect measures to assess countries’
                            capability to implement vaccine immunization programs. These measures,
Efforts                     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).




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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



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                          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 Africa15 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
                          over time as more suppliers enter the market, it has generally taken a
Availability              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.




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                            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.
                            Surveillance data are crucial in assessing the impact of individual diseases,
Vaccines and Immunization
                            determining whether existing disease reduction targets are being met, and
Programs                    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.




                            Page 15                                                GAO/NSIAD-00-4 Vaccine Availability
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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.




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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.




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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.




                         Page 18                                                  GAO/NSIAD-00-4 Vaccine Availability
B-283270




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.




Page 19                                                      GAO/NSIAD-00-4 Vaccine Availability
                  B-283270




                  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.




                  Page 20                                             GAO/NSIAD-00-4 Vaccine Availability
B-283270




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




Page 21                                       GAO/NSIAD-00-4 Vaccine Availability
Appendix I

Objectives, Scope, and Methodology                                                            Appendx
                                                                                                    Ii




              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



              Page 22                                       GAO/NSIAD-00-4 Vaccine Availability
Appendix I
Objectives, Scope, and Methodology




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.




Page 23                                      GAO/NSIAD-00-4 Vaccine Availability
Appendix II

Comments From the Centers for Disease
Control and Prevention                                          Appendx
                                                                      Ii




              Page 24         GAO/NSIAD-00-4 Vaccine Availability
Appendix II
Comments From the Centers for Disease
Control and Prevention




Page 25                                 GAO/NSIAD-00-4 Vaccine Availability
Appendix III

Comments From the U.S. Agency for
International Development                                       AppendxIi




               Page 26        GAO/NSIAD-00-4 Vaccine Availability
Appendix III
Comments From the U.S. Agency for
International Development




Page 27                             GAO/NSIAD-00-4 Vaccine Availability
Appendix III
Comments From the U.S. Agency for
International Development




Page 28                             GAO/NSIAD-00-4 Vaccine Availability
Appendix III
Comments From the U.S. Agency for
International Development




Page 29                             GAO/NSIAD-00-4 Vaccine Availability
Appendix III
Comments From the U.S. Agency for
International Development




Page 30                             GAO/NSIAD-00-4 Vaccine Availability
Appendix IV

GAO Contact and Staff Acknowledgments                                                              Appendx
                                                                                                         iIV




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)      Leter   Page 31                                    GAO/NSIAD-00-4 Vaccine Availability
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