PRB

(June 2001) Massive resources are dedicated to immunizing the children of developing countries against an array of vaccine-preventable diseases. Donors include governments, intergovernmental consortiums — such as the United Nations Children’s Fund (UNICEF), World Health Organization (WHO) and the Global Alliance for Vaccines and Immunization (GAVI) — and private foundations and service clubs (such as the Bill and Melinda Gates Foundation and Rotary International). Why is this money so important, and what are the challenges involved in the global drive to save lives?

Competing Priorities, Global Commitment, and Long-Term Attention

Public health leaders must choose among competing health priorities. There is much discussion regarding priorities for the dollars allocated to immunizations. For example, some scientists question the commitment to polio eradication, given the far greater toll taken by measles (approximately 1 million deaths each year) and hepatitis B. The long-term pay off (freeing money to go after other diseases) must be weighed against other strategies.

According to a 1999 United States General Accounting Office report on vaccine availability, the global effort to eradicate polio received priority attention within the pool of funds committed to control of infectious diseases. Polio’s percentage increased from about 14 percent in 1995 to about 52 percent in 1997, as a result of a drop in total funding for all diseases. According to USAID and UNICEF officials, this has resulted in less money to support routine immunizations for other infectious diseases.

For optimal efficacy, immunization programs require a steady long-term commitment. Government funding levels tend to fluctuate, and disease outbreaks often follow a lessening of commitment. The Global Fund for Children’s Vaccines was created by GAVI to increase resources and commitment to immunizing children in poorer countries.

Affordability

While UNICEF has obtained conventional vaccines at discount of more than 90 percent of prices in the industrialized world, the combined cost of vaccinating a child against diphtheria, tuberculosis, pertussis, measles, tetanus, and polio, estimated by GAVI at US$20 per child, leaves full coverage beyond the reach of many. The Global Fund for Children’s Vaccines was created by GAVI to fill this gap. The Gates Foundation has pledged US$750 million (883.9 million euros), and the governments of Norway, the United Kingdom, the United States and The Netherlands have all come on board, raising total commitments to above US$1 billion. GAVI and the Global Fund have targeted 74 of the world’s poorest countries, each with per capita GNP below US$1000, to receive the hepatitis B, pneumococcus, and Hib (haemophilus influenza type B) vaccines in addition to the “conventional” vaccines against polio, diphtheria, pertussis, tetanus, tuberculosis, and measles.

In addition, the alliance has developed a new vaccine procurement system that gives manufacturers long-term purchasing commitments, allowing them to respond to the needs of the poorest people. In fact, the prices for the most in-demand vaccine formulations have been drastically reduced through this process.

Logistics

While the developing world is increasingly urbanized, many people still live in settlements with no roads, running water, electricity, or telephones. To contact potential recipients and then deliver vaccines requires an immense effort. A mass immunization campaign against polio held December 6, 1998, required, in India alone, coordination of 2.6 million health care workers and volunteers, who traveled by bus, camel, and on foot, following dirt roads and dry riverbeds.

The capacity to keep certain vaccines in the proper temperature range is key to a successful program. There is a systematic effort to keep polio vaccine below 40 degrees F throughout the manufacturing, transport and delivery processes. In 1997, thousands of children near New Delhi, India were given oral polio vaccine thought to have been warmed and thus rendered biologically inactive. These children were not adequately protected from the poliovirus.

Social Stability

In war-torn countries such as the Congo and Democratic Republic of Congo (Zaire), and many other countries experiencing political discord, civil unrest makes organization of vaccine programs and actual delivery of vaccines almost impossible. Dr. Gro Harlem Brundtland, director general of WHO/Africa, said that Africa would never be able to come anywhere close to health for all when there are wars and armed conflict on the continent. Armed conflicts and civil unrests afflict about 20 of the 46 member states of WHO in Africa. According to Dr. Ebrahim M. Samba, WHO regional director for Africa, “Africa has more than nine million refugees and more than 40 million internally displaced persons. These are the highest numbers in the world — and they are increasing.” For example, in 1998 WHO reported that national immunization days planned for the Democratic Republic of Congo, Sierra Leone, and Liberia were cancelled or reduced for reasons of political instability and/or civil war.

Safety

Safe immunizations remain a challenge and a priority for all nations. There are three major elements of immunization safety. Health care providers must be concerned with the safety of vaccines themselves (their composition), administration of the vaccination (handling, scheduling, and injections), and surveillance and evaluation of the immunization program, including documentation of efficacy and adverse events. There are additional concerns regarding safe waste disposal.

Of these elements, injections entail the most significant health risks in the developing world. WHO estimates that 12 billion injections are given each year in the developing world, and of these, 1 billion are given as part of immunization programs. A recent review of injection safety in the developing world found that unsafe injections occur routinely, providing opportunity for transmission of blood-borne pathogens. Unsafe injections currently account for a significant proportion of new hepatitis B and C infections and a smaller proportion of HIV infections. While these statistics apply to all injections (both curative and preventive), they have significant import for immunizations by injection.

Credibility

Fears regarding safety and credibility can be almost impossible obstacles to overcome and must be addressed head-on. Widespread reports of forced sterilization in the 1970s in India caused many to distrust the anti-polio campaign in that country. To address this problem, health care workers invited villagers to look in the UNICEF vehicle, to prove that it carried only vaccine.

Sufficient Markets

The markets needed to research, develop, and distribute experimental vaccines are often too small to galvanize vaccine makers. While the need is there, the money often is not. Vaccine executives are hoping that GAVI’s financial clout will change this situation, and this seems to be happening, with the creation of the Global Fund for Children’s Vaccines. According to GAVI, the alliance which created the fund has “created a viable market in poor countries for sophisticated vaccines that combine new and old antigens, such as hepatitis combined with DTP (diphtheria, tetanus and pertussis), a market that vaccine manufacturers are now striving to fulfill.”

In addition, the alliance has agreed to increase resources to bring to market three vaccines against viral diarrhoea, pneumonia, and meningitis, diseases that together cause approximately two million child deaths each year. Without a concerted effort, these vaccines would not be available in developing countries for many years.

Resources to Handle Complexity

Many vaccines require multiple doses over time. For convenience and efficiency, some vaccines are combined in a single injection (for example, MMR and DTP). Thus, the infrastructure of each vaccine delivery system must be capable of successfully implementing an increasingly complex vaccination schedule. In the U.S., according to the United States Centers for Disease Control and Prevention (CDC), each child requires 15-19 doses of vaccine by age 18 months to be protected against 11 childhood diseases. Every vaccine added increases the complexity. For the developing world, the difficulty is multiplied by faster population growth, lack of infrastructure to provide the appropriate schedule for each particular vaccine being administered, and dependence upon donated vaccines (which may require differing schedules from dose to dose).

Another problem, according to an American Academy of Pediatrics policy statement, is that chemical incompatibility or immunologic interference when different antigens are combined into one vaccine can be difficult to overcome. In addition, vaccine combinations that require different schedules might cause confusion and uncertainty when multiple vaccine providers use different products treat children.

Evolving Organisms

Immunizations will always be important because — in most cases — we can’t get rid of microbial pathogens. Vaccines are targeted to specific organisms. The organisms continue to evolve, and this can result in a mismatch of vaccine strain and the strain circulating in a population. An example of this situation occurred in 1996 with a re-emergence of pertussis in the highly vaccinated population of the Netherlands. It could not be explained by a change in vaccine quality, interference with the introduction of vaccination against Haemophilus influenzae type b in 1993, or a fall in vaccination coverage (96 percent at the age of 12 months). The largest increase was observed among vaccinated children aged 1 to 9 years. This shift towards older, vaccinated cases was reflected in a decrease in vaccine. The re-emergence of pertussis was found to be associated with an upsurge in strains that were antigenically distinct from those used in the whole cell vaccine used in the Netherlands. This suggested a causative role for a mismatch between vaccine strains and circulating strains.

A recent outbreak of an oral polio vaccine-derived polio virus in Dominican Republic and Haiti has also reminded the world of the speed and ease of viral mutations, the need for vigilant surveillance, and the importance of high vaccination rates even where a country or region is declared disease free. The outbreak, reported December 8, 2000, on the Pan American Health Organization’s website, was caused by an unusual derivative of the Sabin type 1 oral polio vaccine.

According to Dr. D.A. Henderson, chair of PAHO’s Technical Advisory Group, the virus is “derived from a vaccine strain that made a transition two years ago” and “occurred in an area where vaccinations levels were low….” The strain is unusual, according to PAHO, because it is derived from an OPV and appears to have assumed the characteristics of wild poliovirus type 1, both in terms of neurovirulence and transmissibility.

“The lesson is clear. We must keep vaccination coverage high until we get to the zero point of stopping polio transmission….”

Surveillance

While the surveillance needed for a safe and effective immunization program is a drain on resources devoted to immunization; these data are essential for studies of vaccine safety, efficacy and coverage. Surveillance requires accurate record keeping regarding whom is given what vaccine at what time(s), and who gets which disease. Surveillance programs are needed to spot any outbreaks so the high-risk population in the effected area can be safeguarded. Setting up reliable programs, and paying for them, are major challenges.

Record keeping is critical. Major studies have detected substantial rates of missing and erroneous data (>=10%) in the recording of vaccine type and brand or lot number in the medical records of vaccine recipients. Health care providers require training and incentives to ensure accurate and complete records.

Ann Moss Joyner is a researcher with McMillan & Moss Research.

References

American Academy of Pediatrics, Policy Statement, “Combination Vaccines for Childhood Immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP), the American Academy of Pediatrics (AAP), and the American Academy of Family Physicians (AAFP)” Pediatrics 103, no. 5 (May 1999): 1064-1077, www.aap.org.

CDC, “Impact of Vaccines Universally Recommended for Children – United States, 1990-1999,” Morbidity and Mortality Weekly Report 48, no. 12 (April 2, 1999): 243-248, www.cdc.gov.

CDC, “Poliomyelitis Prevention in the U.S. Updated Recommendations of the Advisory Committee on Immunization Practices (ACIP),” Morbidity and Mortality Weekly Report 49, no. RR-5 (May 19, 2000), ftp://ftp.cdc.gov/

pub/Publications/mmwr/rr/rr4905.pdf.

Global Alliance for Vaccines and Immunization (GAVI), www.vaccinealliance.org/.

H.E. de Melker et al., “Re-Emergence of Pertussis in the Highly Vaccinated Population of the Netherlands: Observations of Surveillance Data,” Emerging Infectious Diseases 6, no. 4 (July-August 2000).

S.E. Neppelenbroek et al., “The Incidence of Pertussis in the Netherlands Has Remained High Since an Outbreak Occurred in 1996,” Eurosurveillance 4, no. 12 (December 1999): 133-4.

PAHO, “Pan American Health Organization Working With Countries to Investigate and Control Outbreak of Polio Derived from Sabin Vaccine Virus in Dominican Republic and Haiti” (December 8, 2000), www.paho.org/

english/dpi/press_001208.htm.

Polio: Death of a Disease,” The Philadelphia Inquirer, February 1999, www.philly.com.

United States General Accounting Office, “Factors Contributing to Low Vaccination Rates in Developing Countries, Vaccine Availability” Global Health Report GAO/NSIAD-00-4 (October 1999).

L. Simonsen et al., “Unsafe Injections in the Developing World and Transmission of Bloodborne Pathogens: A Review” Bulletin of the World Health Organization 77, no. 10 (1999).

Wall Street Journal Europe (Nov. 20, 2000) (abstract).

World Health Organization/Africa www.afro.who.int.