IMMUNIZATIONS

Immunization is the induction of immunity against an infectious disease by a means other than experiencing the natural infection. The term is usually used interchangeably with vaccination. Active immunization involves administration of an antigenic substance that then induces development of protective antibodies by the person immunized. This protection usually lasts for years, even for life. Passive immunization refers to temporary immunity resulting from antibodies developed by someone else, either through administration of immune globulin (e.g., gamma globulin, rabies immune globulin) or through the natural transfer across the placenta of antibodies developed by the mother, which provide protection to the newborn infant. Passive immunity usually lasts only a few weeks to a few months.

Substances used for active immunization include vaccines and toxoids. Vaccines may contain living, weakened (attenuated) organisms (measles), killed whole organisms (whole cell pertussis, influenza), portions of organisms (subunit influenza), purified components of organisms (acellular pertussis, pneumococcal polysaccharide), or they may be manufactured artificially (hepatitis B produced by recombinant DNA technology). For some diseases, vaccines may be available in more than one form (live attenuated and inactivated [killed] poliovirus vaccines, whole cell and acellular pertussis vaccines). Toxoids are made by preparing the toxins excreted by microorganisms and inactivating them physically or chemically. Diphtheria and tetanus are the most commonly used toxoids. Vaccines and toxoids may also contain adjuvants, substances that enhance the immune response, as well as preservatives.

Some vaccines (particularly live, attenuated vaccines) provide long-term, even lifelong protection following administration of only a single dose. Others (particularly inactivated vaccines and toxoids) may require administration of more than one dose in order to induce long-lasting immunity. Some vaccines (diphtheria, tetanus) require periodic booster doses in order to maintain immunity. Many vaccines may be inactivated by changes in temperature, particularly heat, and must be kept refrigerated or frozen from the time of manufacture until just before being administered. The need for this "cold chain" makes it difficult to carry out immunization programs in developing countries where refrigerators and freezers are not commonplace.

The rate of development of new vaccines has been accelerating as a result of improved knowledge of immunity and improvements in biotechnology. It was nearly one hundred years between Edward Jenner's first use of smallpox vaccine in 1796 and Louis Pasteur's development of the second vaccine (against rabies) in 1885. In the last twenty years of the twentieth century, many new or improved vaccines were developed and introduced, including vaccines directed against Haemophilus influenzae type b (Hib), hepatitis A, hepatitis B, Japanese encephalitis, meningococcal meningitis, pertussis, typhoid, and varicella (chicken pox). Dozens of other vaccines are under development.

Repeated economic analyses have shown that vaccines are among the most cost-effective health interventions available. For most of the vaccines used in infants and young children, the economic benefits of vaccination (avoidance of costs of medical care, hospitals, etc.) far outweigh the costs of vaccination, and the vaccines are truly cost saving. For others, the cost to prevent an illness or death is quite small and is substantially smaller than the cost to treat or cure the condition.

VACCINE RECOMMENDATIONS

In the United States, recommendations for vaccine use are made by the Public Health Service Advisory Committee on Immunization Practices, in conjunction with the American Academy of Pediatrics, American Academy of Family Practice, American College of Physicians (representing adult medicine specialists), and other professional organizations. Some vaccines are recommended for use in all persons (typically infants and young children, since most communicable diseases primarily strike them) and others are recommended for specific persons or groups who are at increased risk of contracting the particular disease. Vaccines currently recommended for use in all infants and children in the United States are DTP/DTaP (diphtheria and tetanus toxoids and pertussis [or acellular pertussis] vaccine), IPV (inactivated poliovirus vaccine), MMR (measles, mumps, and rubella vaccine), Hib vaccine (Haemophilus influenzae type b vaccine), hepatitis B vaccine, and varicella (chicken pox) vaccine. Several of these vaccines require more than one dose. The recommended schedule of immunizations in the year 2000 for infants and young children is shown in Figure 1.

Adolescents and adults also need vaccines, including MMR and hepatitis B if they have not already received them, as well as periodic boosters of tetanus and diphtheria toxoids. In addition, in the United States it is recommended that all persons sixty-five years of age or older receive a single dose of pneumococcal polysaccharide vaccine and annual doses of influenza vaccine because of the increased risk of complication or death if infected. Individuals younger than sixty-five who have chronic illnesses should also receive pneumococcal and influenza vaccines. Some vaccines recommended for persons at increased risk include yellow fever, hepatitis A, typhoid, meningococcal, and Japanese encephalitis vaccines for travelers to certain developing countries; rabies vaccine for veterinarians and persons working with potentially rabid animals; and hepatitis B vaccine for health care workers and others who might come in contact with body fluids.

VACCINE SAFETY

Although modern vaccines are safe and effective, they are neither perfectly effective nor perfectly safe. Some persons who have been vaccinated may still be susceptible to the disease, and some persons who receive the vaccine may suffer an adverse event caused by the vaccine. In developing a vaccine, major efforts are made to maximize effectiveness and minimize the risk of adverse events.

In determining whether to use a vaccine, it is necessary to balance the benefits of the vaccine against the risk of the disease and the risks from the vaccine. This balance may change over time.

Figure 1

For example, oral polio vaccine (OPV, Sabin vaccine) is made from live, attenuated polioviruses. Rarely, the person who receives the vaccine or someone who is in close contact with him or her may develop paralysis. Vaccine-associated paralysis occurs with a frequency of approximately one case for every million doses of OPV administered. By contrast, the inactivated polio vaccine (IPV, Salk vaccine) has no such risk of paralysis. However, OPV has advantages over IPV because it may be spread from the person who receives the vaccine to family members or other persons in contact with the vaccinee, thereby protecting them. Because it provides greater intestinal immunity than IPV, it protects against the spread of wild poliovirus if the vaccinated individual is exposed to wild poliovirus. The relative advantages of OPV have resulted in its being the vaccine chosen by virtually all countries of the world to control and eradicate polio. However, as the risk of wild poliovirus becomes smaller, the rare complications associated with OPV assume greater prominence. In the United States, the marked decline in risk of exposure to wild poliovirus as a result of global polio eradication efforts led in 1999 to a change in policy to favor use of IPV rather than OPV.

Assessment of adverse events associated with vaccines can be quite difficult. Pre-licensure trials typically involve a few thousand individuals and cannot be expected to detect reactions that occur with a frequency as low as (or lower than) one in 100,000. Consequently, it is important to maintain surveillance for adverse events after vaccines are licensed and introduced for widespread use. It may be very difficult to determine whether an event that occurs after vaccination was caused by the vaccine rather than occurring by chance, particularly if the event is known to occur in that age group. For example, sudden infant death syndrome (SIDS) is the leading cause of death in children two to four months of age. Since children typically receive DTP vaccine at two and four months, it is inevitable that on occasion a child will die of SIDS in the twenty-four hours following vaccination (or in the twenty-four hours preceding planned vaccination). The question is whether there is an increased incidence of SIDS following vaccination. Several studies have demonstrated that the incidence of SIDS is not increased following DTP vaccination.

IMPACT OF VACCINES IN THE UNITED STATES

Immunization provides protection both to the individuals immunized and to the community because immunized individuals do not transmit disease. If a high proportion of the population is immunized, the risk of exposure is reduced both for those who have not been immunized and those who have received vaccine but have not been protected. This "herd immunity" has led to the disappearance of disease in defined geographic areas, even though not everyone has received vaccine.

Introduction and widespread use of vaccines has had a dramatic effect on the occurrence of many diseases in the United States. Table 1 demonstrates the maximum number of cases of specified diseases ever reported in the United States, the number of cases reported in 1998, and the proportion reduction in incidence. Declines of greater than 95 percent are the rule. Similar dramatic reductions have been seen from deaths due to these diseases. Smallpox is not shown on this table as smallpox has been eradicated from the world. Most industrialized countries have seen comparable declines in illnesses and deaths due to vaccine-preventable diseases. Most developing countries have not yet experienced the same level of decline because they have not achieved the same level of immunization coverage.

In the United States, immunization levels in young children are at record highs and reported incidence of vaccine-preventable diseases are at record lows. Nonetheless, several factors threaten this continued success, including the birth every day of eleven thousand infants who will all need to be immunized, the changing immunization schedule, the movement of children between health care providers (25% of U.S. 2-year-olds have received vaccines from two or more providers), continued overestimation of coverage by parents and providers, and the absence of disease as a continuing reminder of the need for immunization (even though the causative organisms are still in circulation).

Because of the continuing birth of susceptible infants, unless communicable diseases are eradicated it will be necessary to continue immunizing

Table 1

against them indefinitely. Several examples exist in industrialized countries (including England and Japan) where epidemic resurgence of pertussis (whooping cough) has occurred as a consequence of declining use of pertussis vaccine. In the United States, a resurgence of measles resulted from the diversion of effort from measles vaccination to rubella vaccination following introduction of rubella vaccine in 1969 (at that time it was not combined with measles vaccine).

Several techniques have been demonstrated to be highly effective in improving and maintaining immunization coverage, including improving access to immunization, developing reminder and recall systems to notify parents and providers about needed or overdue immunizations, assessing immunization coverage in individual facilities, and linking immunization services with other services. By providing accurate, up-to-date information to health care providers, immunization registries (confidential, computerized information systems that contain information about immunizations and children) can make it easier to carry out the demonstrably effective immunization strategies. All states are currently in the process of establishing population-based immunization registries containing information on all children within their borders.

In the United States, infants and children may receive immunizations from private providers (typically in conjunction with other well-child services) or from public sector sites such as local health departments (in which case immunizations might be the only services provided) or community health centers. Traditionally, vaccines provided in the public sector have been free, whereas private providers have charged for the vaccines. Consequently, lower-income families typically went to public sector facilities to receive vaccine, even though they might have been using a private physician for other care. Until the middle of the 1990s, it was estimated that approximately one-half of all U.S. children received immunizations from private providers and one-half from the public sector. Enactment of the Vaccines For Children (VFC) program in 1994 made free vaccine available to private providers for use in uninsured or under-insured children and led to a major shift in immunization provision. In 1998, approximately 70 percent of all childhood vaccines were administered in the private sector and 30 percent in the public sector, meaning that more children were receiving immunizations in their "medical home" than had been the case previously.

IMMUNIZATIONS WORLDWIDE

Since 1979, the World Health Organization (WHO) has coordinated an Expanded Program on Immunization (EPI), which seeks to bring vaccines against six diseases—diphtheria, measles, pertussis (whooping cough), poliomyelitis, tetanus, and tuberculosis—to all children in the world. An abbreviated immunization schedule has been developed that calls for a dose of BCG (Bacille Calmette-Guerin) at birth; three doses of DTP (combined diphtheria and tetanus toxoids and pertussis vaccine) and OPV (oral polio vaccine) given at six, ten, and fourteen weeks of age; and a single dose of measles vaccine at nine months of age. BCG protects infants against severe forms of tuberculosis (such as tuberculous meningitis) but does not alter the overall transmission of tuberculosis.

The EPI succeeded in reaching immunization coverage levels of approximately 80 percent in the world's children by 1990 (the year of the Children's Summit), but levels have been relatively stagnant since that time, even decreasing in some areas. Coverage varied markedly among (and within) countries. Some of the reasons for the lack of further progress include: the overall economic situation in many countries, the fragile nature of the countries' health services, lack of political support, and problems in management of immunization programs. In 1991 a recommendation was made to administer hepatitis B vaccine to all children (three doses: at birth, six weeks, and fourteen weeks; or along with the DTP vaccine) but this has not been widely implemented in most developing countries. Introduction of other (newer) vaccines such as Hib is problematic. These vaccines are considerably more expensive than traditional vaccines, there are few manufacturers (sometimes only one, as a result of innovation and patent protection), and purchase of vaccines may require hard currency, which may be difficult for some developing countries to obtain. The development of the Global Alliance for Vaccines and Immunization and the Global Children's Vaccine Fund in early 2000 give hope that mechanisms may be developed to facilitate introduction of important new vaccines in developing countries.

ERADICATION OF VACCINE— PREVENTABLE DISEASES

Global eradication of smallpox in the late 1970s is probably the greatest single achievement in health to date. Although both William Jenner and Thomas Jefferson predicted eventual eradication at the end of the eighteenth century, it took nearly two hundred years to accomplish. The intensive global effort for eradication began in 1967 with the result that the last naturally occurring case of smallpox occurred in 1977. The World Health Assembly certified eradication in 1980. The initial strategy to achieve eradication was mass vaccination of the population, but over time this was refined to a strategy of search and containment— search for cases of smallpox and containment of transmission through vaccinating all persons who might have been exposed in a geographic area.

An effort is currently underway to eradicate polio from the world by the end of 2000. The strategy for eradication involves attaining high levels of coverage with routine vaccination with OPV, special immunization campaigns, and vigorous surveillance to detect and investigate possible cases of polio. The special immunization campaigns typically occur as National Immunization Days, semiannual events in which all children in the country less than five years old are given OPV on a single day, regardless of their previous vaccination status. Significant progress is being made: no locally arising cases of polio have occurred in the Americas since 1991, none in the Western Pacific Region of the World Health Organization (including China) since 1997, and none in the European Region since 1998. At the beginning of 2000, the major problems remaining were in South Asia and sub-Saharan Africa. Whether the target will be met on schedule is not clear. It is clear that eradication is technically feasible—the uncertainties relate to political will and financial support.

Other diseases that are potential candidates for eradication through appropriate use of vaccines include measles, mumps, and rubella. Measles is the most serious of these, still accounting for nearly 900,000 deaths a year (half of them in sub-Saharan Africa), and there is substantial support for consideration for elimination or eradication. The public health impact of rubella and mumps is not as widely recognized and there is not the same degree of enthusiasm for their eradication, although it is estimated that more than 100,000 cases of congenital rubella syndrome occur each year around the world. Although all three conditions could be attacked simultaneously by using MMR (combined measles-mumps-rubella) vaccine, the additional vaccine costs would be substantial.

FUTURE VACCINES

Recent advances in biotechnology and understanding of the immune process make it likely that the pace of vaccine development and introduction will accelerate. Although this will mean that there is greater opportunity for prevention of disease and death, it will have additional consequences, such as increasing complexity of the immunization schedule and the need for additional injections. Development of combination vaccines can help alleviate this problem but, since there is at least a theoretical issue of incompatibility and interference between different vaccines, each combination must be tested thoroughly before it can be approved. Additionally, the prospective availability of combined vaccines from different manufacturers with slightly different components may add further complexity to the schedule and to decision making about what a given individual needs.

The biotechnology revolution has made it possible to explore novel approaches to immunization, such as incorporating into other microorganisms the antigens that elicit protective antibodies (another way of making combination vaccines) or even incorporating antigens into foodstuffs such as potatoes or bananas. Additionally, the prospect of administering vaccines by aerosol or using transdermal patches is being investigated, as is the possibility of using purified DNA from the causative organism as the means to induce immunity. Because of the potential for transmission of infectious diseases (e.g., hepatitis B, HIV/AIDS) through reuse of needles or inadvertent needle-sticks, disposal of needles has become a significant problem and has led to the development of "auto-destruct" syringes and needles that cannot be used more than once. Most designs to date do not prevent inadvertent needlesticks, however. Consequently, needleless approaches to administration are being pursued, including pressure injection of liquid or powder vaccine, aerosol/inhalation, and use of transdermal absorption.

CONCLUSION

Immunizations have been among the most successful public health interventions to date. Through appropriate use of vaccines, smallpox has been eradicated from the earth, poliomyelitis is on the verge of eradication, and there have been dramatic reductions in morbidity and mortality due to with many other diseases. Recent scientific advances give promise that even more diseases can be brought under effective control. A remaining challenge is to ensure that all people of the world benefit from immunizations.

Alan R. Hinman

(see also: Hepatitis A Vaccine; Hepatitis B Vaccine; Influenza; and articles on specific diseases mentioned herein )

Bibliography

Centers for Disease Control and Prevention (1999). "Achievements in Public Health, 1900–2000: Impact of Vaccines Universally Recommended for Children; United States, 1900–1998." Morbidity and Mortality Weekly Report 48(12):243–248.

—— "Recommendations of the Advisory Committee on Immunization Practices." Available online at http://www.cdc.gov/nip/publications/ACIP-list.htm.

Offit, P. A., and Bell, L. M. (1998). What Every Parent Should Know About Vaccines. New York: MacMillan.

Plotkin, S. A., and Orenstein, W. A., eds. (1999). Vaccines, 3rd edition. Philadelphia, PA: W. B. Saunders.

World Health Organization/UNICEF (1996). State of the World's Vaccines and Immunization. Geneva: WHO/UNICEF. Available online at www.who.int/vaccinesdocuments/DocsPDF/www9532.pdf.

IMMUNIZATION

Immunization is recognized as one of the greatest public health achievements of the twentieth century. The widespread use of immunization is responsible for dramatic reductions in, and in some cases the elimination of, specific infectious diseases.

Goals of Immunization

Immunizations can partially or completely prevent illness by a specific microorganism. By preventing illness, immunizations avert the acute effects of disease, complications of disease, and long-term disability related to disease. When immunizations are widely used, the spread of disease within the population can also be prevented. By preventing outbreaks of disease, immunizations reduce health-care expenditures, including the costs of: (1) prescription and over-the-counter medications, (2) health-care provider visits (including office and emergency room visits), (3) hospitalization, and (4) long-term disability or long-term care. Immunizations also save money by reducing the number of days of work loss by employees because of personal illness or illness in a dependent family member.

Immunizations can provide active or passive protection against an infectious disease. In active immunization, entire organisms (e.g., inactivated bacteria; live, weakened virus) or their parts (e.g., bacterial toxoid; inactivated, viral antigen) are administered. The immune system responds to the vaccine by producing a long-lasting, protective immune response in the recipient. Examples of active immunization include all of the vaccines used in the standard childhood immunization schedule (see Table 1). In passive immunization, preformed antibodies against specific microorganisms are administered. Protection lasts only months because of the relatively short half-life of the antibodies. Passive immunization is used before or immediately after an exposure to an infectious agent to prevent infection. Passive immunization is used for a number of infectious agents, including hepatitis B, rabies, respiratory syncitial virus, tetanus, and varicella-zoster. The remainder of this discussion will be directed toward active immunizations used during childhood.

Immunizations can be recommended on either a universal or a selective basis. Universal immunizations are directed at all members of a population. The eventual goal of immunizing all susceptible individuals is the complete eradication of a disease, as in the case of smallpox. Selective immunizations are directed at individuals who are considered at high risk of a disease, or at high risk of complications of a disease.

In the United States, the choice and timing of immunizations are made jointly by three national organizations—the Advisory Committee on Immunization Practices branch of the federal government's Centers for Disease Control and Prevention, the Committee on Infectious Diseases of the American Academy of Pediatrics, and the American Academy of Family Physicians. The complete schedule for universal immunizations is updated and published annually (see Table 1). Alterations to the schedule (e.g., addition of newly approved vaccines and changes in the timing of vaccines) can nevertheless be made throughout the year.

Immunization Success

Immunization against smallpox is an example of the success possible through universal vaccination programs. Accounts of immunization against smallpox were reported as long ago as the 1600s. At that time, uninfected individuals were exposed to material (e.g., pus) from patients suffering from mild disease in the hopes of preventing more serious or fatal disease. In the late 1700s, Edward Jenner, a physician in England, promoted the widespread use of the cowpox virus to prevent smallpox. Two centuries later, on October 26, 1979, the World Health Organization declared that smallpox had been eradicated from the entire world.

The success of other immunization campaigns in the United States is shown in Table 2. The incidence of vaccine-preventable disease has been reduced between 97.6 and 100 percent through the use of universal immunization.

This success could not have been achieved without the combined efforts of researchers, health-care providers, and families. Researchers are responsible for the development of a wide variety of safe, effective vaccines against common childhood diseases. Health-care providers are responsible for ensuring that children receive the appropriate and required immunizations. And families are responsible for bringing their children in for routine child-health supervision visits. At the beginning of the twenty-first century in the United States, record numbers of children were being immunized. This is an essential part of the success of immunizations in this country.

Universal Immunizations

A combination vaccine against diphtheria, tetanus, and pertussis (DTP) was first licensed in the 1940s. The initial vaccine consisted of diphtheria and tetanus toxoids (a weakened form of the toxin that actually does the damage in the infections), and inactivated, whole pertussis bacteria. As seen in Table 2, tremendous reductions have been achieved in all three diseases. Use of the original whole-cell pertussis vaccine was marred in the past by concerns that the vaccine could cause brain injury (specifically, an encephalopathy). While this was largely disproven, the concerns were enough to lead many people to refuse the vaccine in the 1970s. In both Great Britain and Japan, the decline in immunization coverage resulted in epidemics of pertussis. In Great Britain alone, more than 100,000 cases of pertussis occurred between 1977 and 1979. In both countries, vaccination programs were restarted after the consequences of low immunization rates were seen. In the United States, a switch from the whole-cell pertussis vaccine to an acellular preparation with significantly less fever and local reactions was made in 1991.

The first polio vaccine was the injectable, inactivated polio vaccine (IPV) introduced in 1955. The live-attenuated oral polio vaccine (OPV) was licensed in 1960. Since the polio virus attacks the nerve cells that control muscle movement, vaccines against polio are responsible for enormous reductions in paralytic poliomyelitis throughout the world, and for the eradication of natural polio infection from the entire western hemisphere. In the United States, the OPV was used principally from the 1960s until 1997. Since 1997, a transition has been made to the IPV in order to eliminate any chance of vaccine-associated paralytic poliomyelitis caused by OPV. IPV has no risk of causing paralytic poliomyelitis. A complete switch to IPV occurred in the United States in January 2000.

The first live, attenuated measles vaccine was licensed in 1963, followed by mumps and rubella (German measles) vaccines in 1967 and 1969. The combined measles, mumps, and rubella (MMR) vaccine has been available since 1971. In the 1980s, epidemics of measles in the United States demonstrated the importance of immunizing and reimmunizing against measles. Concerns have been expressed over a possible link between autism and the measles vaccine, and this issue is discussed below under "Controversy over Vaccination."

The first hepatitis B vaccine was licensed in 1981. In the United States, an attempt at selective immunization of individuals (e.g., those having contact with blood or blood products, including health-care workers) with the hepatitis B vaccine did not control the number of new cases. Universal immunization of infants against hepatitis B with a vaccine began in 1990.

The Haemophilus influenzae type b (HIB) vaccine was first licensed in 1985. The initial vaccine could only be used in older children because it did not evoke protective immunity in younger infants. Unfortunately, most HIB disease occurs in the first two years of life. Subsequently, a new vaccine was introduced in 1990 that proved extremely effective in early infancy. By 1998, rates of serious bacterial infection due to HIB had declined by 99.7 percent since the introduction of the newer HIB vaccine in 1985.

A chicken pox (varicella) vaccine was licensed in 1995. Before the vaccine was available, an estimated four million cases of chicken pox infection occurred in the United States each year. While most cases of natural infection were uncomplicated, chicken pox was responsible for an estimated eleven thousand hospitalizations and one hundred deaths per year. Once the vaccine was available, chicken pox became the most common vaccine-preventable cause of death in the United States. Universal immunization with the chicken pox vaccine began the same year that the vaccine was licensed.

The pneumococcal-conjugate vaccine was licensed in 2000. Streptococcus pneumoniae (pneumococcus) is a leading cause of serious bacterial infection in childhood, including pneumonia, bacteremia (bacteria in the blood), and meningitis. Pneumococcus is also the most common cause of ear infections in children.

Selected Immunizations

Selected immunizations are directed at high-risk populations. These populations include: (1) individuals with underlying immune system disorders, (2) individuals with chronic underlying medical conditions that make them more susceptible to severe infection, and (3) individuals with increased risk of contracting infection.

Impediments to Vaccination

The success of universal immunization campaigns requires high rates of immunization. Factors that interfere with the delivery of immunizations include: (1) lack of access to health care, (2) lack of knowledge about appropriate immunizations for children, (3) misconceptions about contraindications to vaccination (reasons that vaccination may be inadvisable), and (4) missed opportunities for immunizations.

Controversy over Vaccination

Public fears about the possibility of adverse central nervous system effects of immunizations have followed several routine childhood vaccines. In the 1970s there were concerns over neurologic side effects (primarily, encephalopathy) of pertussis vaccination. In the mid-1990s there were concerns over central nervous system demyelinating disease (e.g., Guillain-Barré syndrome, multiple sclerosis) and the hepatitis B vaccine. While concerns over pertussis and hepatitis B vaccines have largely diminished in the United States, fear increased in the late 1990s over a possible association between autism and the MMR vaccine.

Controversy over the MMR vaccine followed publication of an article in the journal Lancet in early 1998 written by Andrew Wakefield. Based on observations and investigations made in twelve children, the authors suggested a link among the MMR vaccine, chronic intestinal inflammation, and autism.

Two subsequent epidemiologic studies, by B. Taylor and L. Dales, failed to identify an association between the MMR vaccine and autism. The Taylor study, from the United Kingdom, demonstrated increasing rates of autism, but a comparison of rates before and after the MMR vaccine was introduced in the United Kingdom in 1988 failed to uncover a link between the two. The Dales study, from California, demonstrated an almost fourfold relative increase (373%) in autism between 1980 and 1994. Immunization rates, however, increased by only 14 percent during the same period.

Until the cause or causes of autism are better defined, controversy will continue in this area. Currently, there is little, if any, scientific evidence linking the MMR vaccine and autism. Meanwhile, the global eradication of measles is still a possibility through widespread use of measles-containing vaccines. Eradication of measles would eliminate the estimated 880,000 deaths that occur worldwide as a result of measles infection.

The Future

The immunization schedule is constantly evolving. Future changes include vaccines against additional diseases, new vaccine combinations, and novel approaches to immunization. New routes for vaccine administration (e.g., nasal vaccines, vaccines incorporated into foods) are also being evaluated.

See also:BIRTH DEFECTS; RUBELLA

Bibliography

American Academy of Pediatrics. Committee on Infectious Diseases. Red Book, 2000: Report of the Committee on Infectious Diseases, 25th edition. Elk Grove Village, IL: American Academy of Pediatrics, 2000.

American Academy of Pediatrics. Committee on Infectious Diseases. "Recommended Childhood Immunization Schedule: United States, January-December 2001." Pediatrics 107, no. 1 (2001):202-204.

Centers for Disease Control and Prevention. "Achievements inPublic Health, 1900-1999: Impact of Vaccines Universally Recommended for Children—United States, 1990-1998." Morbidity and Mortality Weekly Report 48, no. 12 (1999):243-248.

Centers for Disease Control and Prevention [web site]. Atlanta, GA, 2001. Available from http://www.cdc.gov; INTERNET.

Dales, L., S. J. Hammer, and N. J. Smith. "Time Trends in Autism and in MMR Immunization Coverage in California." Journal of the American Medical Association 285, no. 9 (2000):1183-1185.

Radetsky, Michael. "Smallpox: A History of Its Rise and Fall." Pediatric Infectious Disease Journal 18, no. 2 (1999):85-93.

Taylor, Brent, Elizabeth Miller, C. Paddy Farrington, Maria-Christina Petropoulos, Isabelle Favot-Mayaud, Jun Li, and Pauline A. Waight. "Autism and Measles, Mumps, and Rubella Vaccine: No Epidemiologic Evidence for a Causal Association." Lancet 353 (June 12, 1999):2026-2029.

Wakefield, A.J., S. H. Murch, A. Anthony, J. Linnell, D. M. Casson, M. Malik, M. Berelowitz, A. P. Dhillon, M. A. Thomson, P. Harvey, A. Valentine, S. E. Davies, and J. A. Walker-Smith. "Ileal-Lymphoid-Nodular Hyperplasia, Non-specific Colitis, and Pervasive Developmental Disorder in Children." Lancet 351 (February 28, 1998):637-641.

AlanUba

immunization Immunization is the process of conferring increased resistance (or decreased susceptibility) to infection. The term ‘vaccination’ is also used to describe this kind of protective measure, although, strictly speaking, this term refers only to the protection conferred against smallpox by material taken from a cow infected with vaccinia virus (which causes cowpox). Inoculation also is used synonymously for immunization, but less commonly nowadays.

The history of immunization goes back to early attempts to prevent smallpox by the Chinese; much later, in the eighteenth century, came the classical experiments of Edward Jenner in Gloucestershire, who induced protection in a child by the inoculation of material from a cow infected with cowpox.

Achievements in the history of immunization are summarized in Table 1. Although the early work to control infection was made before microbiological methods were firmly established, rapid progress was made, based on sound scientific principles, once modern bacteriology, and later virology, came on to the scene. For example, the isolation of poliovirus allowed for the development by Jonas Salk, and later by Albert Sabin in the 1950s, of highly effective poliovaccines, which led to a dramatic diminution in poliomyelitis. Before then, there were alarming outbreaks of this paralytic disease: over 8000 cases occurred in the UK in 1950. By the late 1980s, poliovirus capable of producing paralysis was still circulating widely in all continents of the world except Australia. But by 1998 the Americas were polio-free and elsewhere there is substantial progress being made towards the goal of worldwide eradication of this much dreaded disease.

Similarly, with measles the isolation of measles virus in 1954 made it possible to culture a strain which is now the basis of the measles vaccine in use today. Prior to the use of the vaccine, in the UK as many as 800 000 cases were notified annually, but its introduction has resulted in a dramatic decline.

Table 1 Some important dates in the history of immunization

Active immunization

Active immunization is brought about by stimulating the individual's own immunity by introducing either inactivated (killed) or attenuated (live, but enfeebled) agents (Table 2). The protective response by the body is mainly expressed through: (i) specific antibodies, measurable by serological tests, which confer protection against many agents, particularly viruses and toxins. (ii) the cellular immune response, which involves both phagocytes and ‘memory cells’.

Inactivated vaccines

are prepared in three ways (examples in Table 2): (i) from killed whole organisms; (ii) from sub-units of the killed organisms; (iii) from the toxins which the organisms release, inactivated by formaldehyde (toxoids).

When the organisms have been killed there can be no multiplication within the body, and thus these vaccines cannot produce infection similar to the natural disease. On the other hand, local and whole body reactions may result from response to the organism or to foreign protein used in the vaccine. If the person has not previously been immunized, more than one dose is usually required, although some response can be produced by even a single dose. Protection often lasts for many years, although periodic ‘boosts’ by subsequent injections may be required to maintain immunity.

Attenuated vaccines

are prepared from modified strains of the causal organisms or from related organisms. Because of this, some live vaccines may sometimes cause illness resembling the natural disease, but the symptoms are usually milder. In general, however, these vaccines have fewer side-effects than inactivated ones and the immunity usually lasts for many years.

Passive immunization

Passive immunization is obtained by giving pre-formed, antibodies. These are usually injected in the form of human immunoglobulin or, rarely, antisera prepared in animals. Protection is usually rapid, but the immunity derived is often short-lived, being limited to the time taken for the antibodies to be broken down in the body — from a week or so, with animal antisera, to about six months for protection against hepatitis A by human normal immunoglobulin.

Special risk groups

include those persons particularly liable to suffer from complications of infection, for whom protection by appropriate immunization is therefore of particular importance: for example, those with chronic lung disease, asthma, congenital heart disease, Down's syndrome, or Human Immunodeficiency Virus (HIV) infection, and babies who are born prematurely or are ‘small-for-dates’. Immunization of travellers to some countries overseas is often a particular problem, as the risk of certain infections may be especially high and it often has to be given when time is short.

Surveillance of immunization

procedures is necessary. Immunization it is not without its occasional hazard and it is important that those involved should balance the risk of the disease against the possible risk of the vaccine. Surveillance measures should be aimed at assessing not only the application, utilization, and effectiveness of vaccines in the control of infection, but also any side effects, so that rational decisions about whether to vaccinate can be made.

In conclusion, the achievements of successful immunization policies have been spectacular when the ravages caused by vaccine-preventable infections in former years are compared with those of today. Smallpox has now been eradicated, and other greatly feared infections (such as poliomyelitis) are well under control. Because immunization can often be given quite cheaply and quickly to large numbers of people, it is a remarkably cost-effective measure, which has undoubtedly made a major (if not the major) contribution to the overall protection of the world's population against infection.

Table 2 Examples of viral and bacterial vaccines

Daniel Reid

Bibliography

Department of Health, Welsh Office, Scottish Home and Health Department (1996). Immunisation against infectious disease. HMSO London.
Nicholl, A. and Rudd, P. (ed.) (1989). British Paediatric Association Manual on infection and immunizations in children. Oxford University Press, Oxford.
Wiedermann, G. and and Jong, E. C. (1997). Vaccine-preventable diseases: principles and practice. In Textbook of travel medicine. B. C. Decker Inc., Hamilton, Ontario.

IMMUNIZATION AND CHILDREN'S PHYSICAL HEALTH

With the exception of safe water, no other public health intervention has had a greater impact in reducing deaths related to infectious disease than vaccinations. Smallpox was eradicated in 1977; wild-type poliomyelitis was eliminated from the Western hemisphere in 1991. Among children under five, measles and invasive Haemophilus influenzae type b (Hib) have both been reduced to record low numbers. Deaths associated with smallpox, diphtheria, pertussis, tetanus, paralytic poliomyelitis, measles, mumps, rubella, congenital rubella syndrome, and Hib decreased an average of nearly 100 percent during the twentieth century.

Though the United States is reaching record low levels of vaccine-preventable disease, continued immunization is important. Pathogenic viruses and bacteria still circulate in the United States, and with continuing globalization, the threat of disease spread increases. Immunization protects the general population from disease; individuals who are immunized have inherent protection from disease while those who are not immunized are protected by the limited likelihood that they will be exposed to another unimmunized and infected individual. Furthermore, immunization protects a population from disease; vaccinated individuals acquire immunologic protection from pathogens for themselves. As a consequence, immunized individuals are protected secondary to a decreased incidence of disease. This phenomenon of herd immunity, however, will not be achieved unless 80 percent to 95 percent of the population is immunized.

Childhood Immunizations

A detailed childhood immunization schedule is released yearly by the National Immunization Program (NIP), the American Academy of Pediatrics (AAP), and the American Academy of Family Physicians (AAFP). This schedule informs parents and health care providers which vaccines children need to receive and when they should receive them. An updated schedule can be found at the website of the Centers for Disease Control and Prevention.

State governments are responsible for passing and enforcing school immunization laws. Currently all fifty states have immunization requirements for children entering school. The vaccinations required may be different for different states. Additionally, states may also differ in the number and types of philosophical or religious exemptions they allow for children entering school. Vaccination decreases the risk of infection and outbreaks in schools by reducing the number of unprotected people who may be infected that are capable of transmitting the disease within their schools and communities.

Immunizations are available either free of charge or for a reduced cost at local health departments for children whose parents cannot afford to take their children to private physicians for immunization. Furthermore, on August 10, 1993, the Omnibus Budget Reconciliation Act (OBRA) created the Vaccines for Children Program (VFC) program as Section 1928 of the Social Security Act in order to increase access to immunizations. The program began on October 1, 1994; it provides vaccinations at no cost to VFC-eligible children seeing either public or private providers.

Vaccine-Preventable Diseases

The following eleven vaccine-preventable diseases are addressed through standard vaccination programs. A number of these diseases are covered by mandatory school immunization laws.

Diphtheria is a respiratory disease caused by a virus that is spread by coughing and sneezing. Symptoms include sore throat and low-grade fever. Left untreated, diptheria can lead to airway obstruction, coma, and death. Vaccines that contain the diptheria toxoid include the DTP, DtaP, DT, and Td vaccines.

Tetanus (lockjaw) is a disease of the nervous system that is caused by bacteria that enters the body through a break in the skin. Early symptoms include lockjaw, stiffness in the neck and abdomen, and difficulty in swallowing. Later onset symptoms include fever, elevated blood pressure, and severe muscle spasms. Death occurs in one third of all cases, especially among the elderly. Tetanus toxoid is also contained in the DTP, DT, DtaP, and Td vaccines.

Pertussis (whooping cough) is a highly contagious bacterial respiratory disease spread through coughing and sneezing. Symptoms include severe fits of coughing that may interfere with eating, drinking, and breathing. Pertussis may cause pneumonia, encephalitis, and infant death. The pertussis vaccine is contained within the DTP and DtaP vaccines.

Haemophilus influenzae type b is a bacterial infection that predominantly affects infants. It is spread by coughing and sneezing. Symptoms include skin and throat infections, meningitis, pneumonia, sepsis, and arthritis and may be severe for children under the age of one. Risk of disease is reduced after the age of five. A Hib vaccine can prevent the disease.

Hepatitis A is caused by the Hepatitis A virus and is spread most commonly through the fecaloral route when the stool of an infected person is put into another person's mouth. It can also be transmitted by ingesting food or water that contain the virus. The disease affects the liver. Symptoms are unlikely, but if present they may include yellow skin or eyes, fatigue, stomach ache, loss of appetite, and nausea. This disease is prevented using the Hepatitis A vaccine.

Hepatitis B is caused by the Hepatitis B virus and is spread through sexual contact or through contact with the blood of an infected person. As with the initial clinical presentation of Hepatitis A, infection with Hepatitis B may follow an indolent course and manifest no symptoms. The likelihood of developing Hepatitis B increases with age. If present, symptoms are similar to Hepatitis A. The Hepatitis B vaccine prevents the disease.

Mumps is caused by a virus and is spread through coughing and sneezing. It is a disease that affects the lymph nodes. Symptoms include fever, headache, muscle ache and swelling of the lymph nodes close to the jaw. Infection with the mumps virus may also lead to meningitis, inflammation of the testicles or ovaries, inflammation of the pancreas and permanent deafness.

Measles is a highly contagious respiratory disease caused by a virus that is transmitted through coughing or sneezing. Symptoms include rash; high fever; cough; runny nose; and red, watery eyes lasting about a week. The measles may cause diarrhea, ear infections, pneumonia, encephalitis, seizures, and death. The measles vaccine is contained within the MMR, MR and measles vaccines.

Rubella (German measles) is a viral respiratory disease spread through coughing and sneezing. Symptoms may include a mild rash and fever for two to three days in children and young adults. Complications are severe for pregnant women, whose children frequently have congenital birth defects. The rubella vaccine is contained within the MMR, MR, and rubella vaccines.

Polio is a viral disease of the lymphatic and nervous systems. Transmission occurs through contact with an infected person. Symptoms include fever, sore throat, nausea, headaches, stomach aches, and stiffness in the neck, back and legs. OPV and IPV are the vaccines in current use.

Varicella (chickenpox) is a highly contagious disease caused by bacteria and is spread by coughing or sneezing. Symptoms are a skin rash of blister-like lesions on the face, scalp, or trunk. The varicella vaccine prevents this disease.

Immunization Safety

Before vaccines are approved by the Food and Drug Administration, they undergo rigorous scientific testing to ensure that they are safe and effective. However, differences in each individual's response to an antigenic vaccine challenge account for the rare occurrences ranging from vaccine failure to anaphylaxis. The National Childhood Vaccine Injury Act (NCVIA) of 1986 created the National Vaccine Program Office within the Department of Health and Human Services. It requires that all providers who administer vaccines provide a Vaccine Information Statement that explains the disease and the risks and benefits of vaccination to the vaccine recipient, parent, or legal guardian. The NCVIA also created the Vaccine Adverse Event Reporting System, a mandatory reporting system for health care providers. The National Vaccine Injury Compensation Program was also created under the NCVIA as a no-fault system for compensating people injured by vaccination.

See also: Health Education; Health Services, subentry on School.

bibliography

Plotkin, Stanley A., and Orenstein, Walter A. 1999. Vaccines, 3rd edition. Philadelphia: W. B. Saunders Co.

internet resources

Centers for Disease Control and Prevention. 2002. "Immunization Laws." <www.cdc.gov/od/nvpo/law.htm>.

Centers for Disease Control and Prevention. 2002. "Parent's Guide to Childhood Immunizations." <www.cdc.gov/nip/publications/Parents-Guide>.

Centers for Disease Control and Prevention. 2002. "Recommended Childhood Immunization Schedule." <www.cdc.gov/nip/recs/childschedule.htm>.

Angela Huang

Immunization

Immunization is a method of helping the body's natural immune system be able to resist a particular disease. It is usually carried out by giving someone a mild version of the disease. This allows the body to make antibodies that will resist the disease in the future. Active immunization, or vaccination, has proven to be a highly successful method of disease prevention.

Long before modern science discovered the causes of disease, it was folk practice in some parts of the world to give a powder made from the scabs of recovering smallpox patients to healthy children in the belief that it would somehow protect them in the future. If this risky custom, which originated in China, did not kill the child, it often did grant him or her immunity against a full-blown case of smallpox (a highly infectious viral disease). This same idea was at work when the English physician Edward Jenner (1749–1823) decided to try a dangerous experiment. He based his experiment on the fact that people who had suffered a case of the less serious cowpox (a contagious skin disease found in cattle) often did not catch the deadly smallpox. In 1796 Jenner prepared what he called a vaccine (because the cowpox virus name was "vaccinia") and gave it to a young boy. Months later, he injected real smallpox into the boy. Fortunately, the boy did not get the disease.

This marked the modern beginnings of immunization. Jenner, however, made no claims that he understood why immunization worked. It was not until a century later that the French chemist and microbiologist (a person specializing in the study of microorganisms) Louis Pasteur (1822–1895) proved experimentally that disease-causing microorganisms (organisms that can only be seen through a microscope) that were "attenuated," or weakened, would create an immune response in a person without actually causing the disease itself. On the basis of this breakthrough, active immunization began. It is now known that immunization uses the mechanisms of the body's natural immune system to protect the body against future diseases.

IMMUNIZATION AND ANTIBODIES

In the twentieth century, science learned that the body produces substances called antibodies. These fight and kill what the body recognizes as foreign invaders (disease-producing microorganisms). These antibodies are specific to that particular disease and will remain in the body's "memory cells" for a long time, ever ready to fight should the body recognize the disease in the future.

Today, many viral vaccines are made from live, weakened viruses, including those for yellow fever, measles, mumps, rubella, and polio. Using a live form means that the body will react with a very strong immune response to the particular virus, thereby protecting the individual against future infection. Other vaccines, like rabies, flu, and intravenous polio, use dead viruses and do not confer as strong a protection.

PASSIVE IMMUNIZATION

All of the above are considered to be forms of active immunization, but there is also another method called passive immunization. This method is used when a quick response to a disease is required. Passive immunization consists of injecting specific antibodies into a person to fight a specific disease. For example, a person who is bitten by a snake or who has been exposed to hepatitis cannot wait for his own system to build up antibodies against them. Instead, the person is given a direct and immediate dose of the antibodies in order to neutralize the venom or to kill the microorganism. While passive immunization usually works, it is not long-lasting like active immunization and usually will not protect the person in the future.

IMMUNIZATION WORKS

Immunization has proven to be the safest, least expensive, and most effective means of protecting people against contagious diseases. In many ways it is ideal, since it prevents the disease rather than trying to cure it once it has taken hold. Today, immunization in the developed world has nearly eliminated the threat of typical childhood diseases like measles, mumps, rubella, whooping cough, and polio. In 1980 the World Health Organization declared that smallpox was the first disease to be totally eradicated (destroyed) worldwide.

[See alsoAntibody and Antigen; Immune System; Vaccine ]