This statement on adult immunization is a supplement to the "General Recommendations on Immunization" of the Immunization Practices Advisory Committee (ACIP) (1) and updates the previous supplement published in September 1984. This statement presents an overview on immunization for adults and makes specific immunization recommendations. The statement provides information on vaccine-preventable diseases; indications for use of vaccines, toxoids, and immune globulins recommended for adults; and specific side effects, adverse reactions, precautions, and contraindi- cations associated with use of these immunobiologics. It also gives immunization recommendations for adults in specific age groups and for those who have special immunization requirements because of occupation, life-style, travel, environmental situations, and health status.

This statement is a compendium of ACIP recommendations and will not be updated regularly. The ACIP periodically reviews individual immunization statements that are published in the MMWR. The reader must use the detailed, up-to-date individual statements in conjunction with this compendium to keep abreast of current information. A list of the current ACIP recommendations for specific diseases and vaccines can be found in Appendix 1.

INTRODUCTION

General Considerations

Immunization policies have primarily been directed towards vaccinating infants, children, and adolescents. Although vaccination is routine in pediatric practice, it is not commonplace in the practice of physicians who treat adults.

The widespread implementation of childhood vaccination programs has substantially reduced the occurrence of many vaccine-preventable diseases. However, successful childhood vaccination alone will not eliminate specific disease problems. A substantial proportion of the remaining morbidity and mortality from vaccine-preventable diseases presently occurs among older adolescents and adults. Persons who escaped natural infection or were not vaccinated with toxoids or vaccines against diphtheria, tetanus, measles, mumps, rubella, and poliomyelitis may be at risk of these diseases and their complications. Many factors have influenced the use of vaccines among adults, including lack of awareness of safe vaccines and vaccine- preventable health burdens, unfounded concerns about adverse reactions, and missed opportunities by health-care providers to vaccinate adults during office, clinic, or hospital visits. To improve adult immunization levels, the National Coalition for Adult Immunization (NCAI) was formed in 1988. The coalition consists of professional, private, public, and voluntary organizations with the common goal of improving vaccine use among adults by educating health-care providers and patients. A listing of member organizations is provided in Appendix 2.

To reduce further the unnecessary occurrence of these vaccine- preventable diseases, health-care providers for older adolescents and adults should provide vaccinations as a routine part of their practice. In addition, the epidemiology of other vaccine-preventable diseases (e.g., hepatitis B, rabies, influenza, and pneumococcal disease) indicates that persons in certain age, occupational, environmental, and life-style groups and those with special health problems are at increased risk of these illnesses and should be vaccinated. Travelers to some countries may also be at increased risk of exposure to vaccine-preventable illnesses. Finally, foreign students, immigrants, and refugees may be susceptible to these diseases.

A systematic approach to vaccination is necessary to ensure that every adult is appropriately protected against vaccine-preventable diseases. Every visit by an adult to a health-care provider should be an opportunity to provide this protection. However, several factors need to be considered before any patient is vaccinated. These include the susceptibility of the patient, the risk of exposure to the disease, the risk from the disease, and the benefits and risks of the immunizing agent.

Physicians should maintain detailed records containing information about each person's previous vaccinations. The National Childhood Vaccine Injury Act of 1986 (NCVIA) requires physicians and other health-care providers who administer vaccines to maintain permanent vaccination records and to report occurrences of certain adverse events specified in the Act for all vaccines containing measles, mumps, rubella, poliomyelitis, diphtheria, tetanus, and pertussis antigens for all patients, adults as well as children (Table_1). Ideally, information for all vaccines and toxoids should be recorded. Information should also include the person's history of vaccine-preventable illnesses, occupation, and life-style. Vaccines and toxoids administered at appropriate ages and intervals should be documented in writing.

Attention to factors such as military service and age may help to determine whether vaccines or toxoids are advisable for an individual. Persons who have served in the military can be considered to have been vaccinated against measles, rubella, tetanus, diphtheria, and polio. However, the practitioner should be aware that policies of the different branches of the military have varied over time and among the branches. After being administered any immunobiologic, the patient should be given written documentation of its receipt and information about which vaccines or toxoids will be needed in the future. For this purpose, a vaccination record such as the suggested form found in Appendix 3 should be used routinely.

The patient or responsible person (e.g., guardian) should be given information on the risks of immunobiologics as well as their major benefits in preventing disease, both among individuals and in the community. No formal, legally acceptable statement has been universally adopted for the private medical sector. The NCVIA requires development and use of materials providing vaccine information for all covered vaccines. All physicians must give those materials, when available, to prospective vaccinees. However, CDC has developed "Important Information Statements" for use with vaccines purchased through federal contracts. (Many of these will be replaced by "Vaccine Information Pamphlets" in April 1992.) Practitioners may wish to consider these or similar materials for patients. Examples of Important Information Statements can be obtained from state and many local health departments. Forms are not available for all vaccines, however, especially those of limited use. Regardless, the ACIP recommends that health-care providers allow ample opportunity for questions before each vaccination.

Modern immunobiologics are extremely safe and effective, but not completely so. Adverse events have been reported after administration of all immunobiologics. These adverse events range from frequent, minor, local reactions to extremely rare, severe systemic illness, such as paralysis associated with oral poliovirus vaccine, live, trivalent (OPV). Cause-and- effect relationships frequently cannot be established when adverse events occur after vaccination, because temporal association alone does not necessarily indicate causation. All temporally associated events severe enough to require the recipient to seek medical attention should be evaluated and reported in detail to the Vaccine Adverse Event Reporting System (VAERS) in order to improve knowledge about adverse reactions. (See "Requirements for Permanent Vaccination Records and Reporting of Adverse Events" section.)

General vaccination considerations and recommendations are found in the ACIP statement "General Recommendations on Immunization" (1). The following recommendations apply to persons in the indicated groups. For more detailed information on immunobiologics -- including indications, side effects, adverse reactions, precautions, contraindications, dosages, and routes of administration -- providers should refer to the tables and appendices at the back of this supplement. Also, package inserts for the individual products should be consulted as necessary. Appendix 4 provides a list of vaccines, toxoids, and immune globulins available in the United States as of March 1, 1991.

Reference can also be made to the Guide for Adult Immunization (2), published by the American College of Physicians, and to the recommendations of the U.S. Preventive Services Task Force (3).

Age Groups

The following text and Table_2 summarize the vaccines and toxoids recommended for most adults, by specific age groups. Table_3 summarizes the vaccines and toxoids recommended for normal infants and children. Refer to the section "Vaccine-Preventable Diseases and Their Immunobiologics" for other essential information.

Adults 18-24 Years Old

All young adults should complete a primary series of diphtheria and tetanus toxoids if they have not done so during childhood. A primary series for adults is three doses of preparations containing diphtheria and tetanus toxoids; the first two doses should be given at least 4 weeks apart and the third dose, 6-12 months after the second. Those who have completed a primary series should receive a booster dose every 10 years. Doses need not be repeated when the series schedule is delayed. The combined tetanus and diphtheria toxoids, adsorbed (for adult use) (Td), should be used. Persons with unknown or uncertain histories of receiving diphtheria or tetanus toxoids should be considered unvaccinated and should receive a full three- dose primary series of Td.

Young adults should be immune to measles, rubella, and mumps. In 1989, as a result of outbreaks of measles in school and college settings, new recommendations were made to implement a routine two-dose schedule for measles-mumps-rubella vaccine, live (MMR). The schedule will usually be implemented gradually, one age group at a time, beginning with entry into kindergarten or first grade. Some areas of the country may implement the second dose of MMR at an older age (e.g., entry into middle school or junior high school). Young adults who are attending college (or other post- high school educational institutions) or who are newly employed in situations that place them at high risk of measles transmission (e.g., health-care facilities) should have documentation of having received two doses of live MMR on or after their first birthday or other evidence of immunity. Persons born after 1956 who are traveling to areas endemic with measles should be given two doses of live MMR. All other young adults in this age group should have documentation of a single dose of live MMR on or after their first birthday, documentation of physician-diagnosed disease, or laboratory evidence of immunity. Eventually, all persons in this age group will require two doses of measles vaccine. However, until the new recommendations are fully implemented, a single dose on or after the first birthday will be sufficient evidence of immunity for most persons.

During outbreaks of measles, all persons at risk should have evidence of immunity to measles. Acceptable evidence of measles immunity consists of documentation of two doses of a live measles vaccine (preferably MMR), given at least 1 month apart after the first birthday; documentation of physician-diagnosed measles; or laboratory evidence of immunity to measles. During outbreaks of mumps and rubella, all persons at risk should have evidence of immunity to mumps and rubella. Acceptable evidence of mumps/rubella immunity consists of documentation of at least one dose of live mumps- and/or rubella-containing vaccine (preferably MMR), laboratory evidence of immunity, or physician-diagnosed mumps. Physician diagnosis is not adequate evidence of immunity against rubella.

Persons vaccinated with killed-measles-virus vaccine (available in the United States from 1963 until 1967) or with a measles vaccine of unknown type should receive two doses of live-measles-virus vaccine at least 1 month apart to prevent measles disease or atypical measles syndrome -- if exposed to wild measles virus. Persons are considered immune to rubella only if they have a record of vaccination with rubella vaccine on or after their first birthday or laboratory evidence of immunity. MMR is the vaccine of choice if recipients are likely to be susceptible to more than one of the three diseases. Persons lacking adequate documentation should be vaccinated.

Adults 25-64 Years Old

All adults 25-64 years of age should have completed a primary series of diphtheria and tetanus toxoids. If needed, a primary series for adults is three doses of preparations containing diphtheria and tetanus toxoids -- the first two doses given at least 4 weeks apart and the third dose given 6-12 months after the second. Those who have completed a primary series should receive a booster dose every 10 years. To enhance protection against both diseases, Td should be used. Persons with unknown or uncertain histories of receiving diphtheria or tetanus toxoids should be considered unvaccinated and should receive a full three-dose primary series of Td.

All adults born in 1957 or later who do not have a medical contraindi- cation should receive one dose of measles vaccine unless they have a dated record of vaccination with at least one dose of live measles vaccine on or after their first birthday, documentation of physician-diagnosed disease, or laboratory evidence of immunity. Serologic studies of hospital workers indicate that up to 9.3% of persons born before 1957 were not immune to measles (4,5). In addition, of all measles cases reported to the CDC from 1985 through 1990, 3.7% occurred among persons born before 1957. These data suggest that most persons born before 1957 can be considered immune to measles and do not need to be vaccinated. However, 97 (29%) of 341 health- care workers who had measles in the period 1985-1989 were born before 1957 (6). Therefore, because health-care workers are at particularly high risk of measles and a small proportion born before 1957 will be susceptible, vaccine should be offered to such persons if there is reason to believe that they may be susceptible.

Some adults, such as college students, persons working in health-care facilities, and international travelers, are at increased risk of measles. Such persons should have evidence of two doses of live measles vaccine or other evidence of measles immunity, if born in 1957 or later.

Although most adults are likely to have been infected naturally with mumps, mumps vaccine should be given to adults who are considered susceptible. Persons born in 1957 or later can be considered immune if they have evidence of one dose of live mumps vaccine or other evidence of mumps immunity.

Unless proof of vaccination with rubella vaccine or laboratory evidence of immunity is available, rubella vaccine is recommended for adults, especially women of childbearing age. The vaccine of choice is MMR if recipients are likely to be susceptible to more than one of these three diseases.

Adults Greater Than or Equal To 65 Years Old

All older adults should have completed a primary series of diphtheria and tetanus toxoids. If needed, a primary series for adults is three doses of preparations containing diphtheria and tetanus toxoids; the first two doses should be given at least 4 weeks apart and the third dose 6-12 months after the second. Those who have completed a primary series should receive a booster dose every 10 years. Td should be used to provide protection against both diseases. Persons with unknown or uncertain histories of receiving diphtheria or tetanus toxoids should be considered unvaccinated and should receive a full three-dose primary series of Td.

All older adults should receive influenza vaccine annually. They should also receive a single dose of pneumococcal polysaccharide vaccine. Revaccination should be strongly considered greater than or equal to 6 years after the first dose for those at highest risk of a) fatal pneumococcal disease (such as asplenic patients) or b) rapid decline in antibody levels (e.g., transplant recipients or those with chronic renal failure or nephrotic syndrome).

Special Occupations

Persons in specific occupations may be at increased risk of exposure to certain vaccine-preventable illnesses. Such persons may need selected vaccines and toxoids in addition to those routinely recommended for their age group. Table_4 provides a summary of immunobiologics recommended for various special occupational groups. The reader is referred to the section on "Vaccine-Preventable Diseases and Their Immunobiologics" for other essential information.

Health- and Public-Safety-Related Occupations

Because of their contact with patients or infectious material from patients, many health-care workers (e.g., physicians, nurses, dental professionals, medical and nursing students, laboratory technicians, and administrative staff) and public-safety workers (e.g., police, emergency medical personnel, firefighters) are at risk for exposure to and possible transmission of vaccine-preventable diseases. Optimal use of immunizing agents will not only safeguard the health of workers but also will protect patients from becoming infected. A consistent program of vaccinations could eliminate the problem of having susceptible health-care workers in hospitals and health departments (with the attendant risks to other workers and patients). The CDC publication "Immunization Recommendations for Health-Care Workers" (7) and the section below discuss this subject in detail.

Hepatitis B virus (HBV) infection is a major occupational hazard for health-care and public-safety workers. The risk of acquiring HBV infection from occupational exposures depends on the frequency of percutaneous and permucosal exposures to blood or blood products. Any health-care or public- safety worker may be at risk for HBV exposure, depending on the tasks that he or she performs. If those tasks involve contact with blood or blood- contaminated body fluids, workers should be vaccinated. Vaccination should be considered for other workers, depending on their exposure to blood and/or bodily fluids. Selected staff of institutions for the develop- mentally disabled may be at increased risk of HBV infection because of exposure to human bites and contact with skin lesions, saliva, and other potentially infected secretions in addition to blood. The Occupational Safety and Health Administration, Department of Labor, is developing regulations that will require employers who have employees at risk of occupational exposure to hepatitis B to offer these employees hepatitis B (HB) vaccine at the employer's expense. These regulations are expected to accelerate and broaden the use of HB vaccine among health-care workers and to assure efforts to prevent this occupational disease.

Among health-care personnel with frequent exposure to blood, the prevalence of serologic evidence of HBV infection ranges between approximately 15% and 30%. In contrast, the prevalence in the general population averages 5%. The cost-effectiveness of serologic screening to detect susceptible individuals among health-care personnel depends on the prevalence of infection and the costs of testing and of the HB vaccine. Each institution must decide whether serologic screening is cost effective. Vaccination of persons who already have antibodies to HBV has not been shown to cause adverse effects. HB vaccine provides protection against HBV for greater than or equal to 7 years after vaccination; booster doses are not recommended during this interval. The need for later booster doses will be assessed as additional information becomes available.

Influenza vaccination is recommended yearly for physicians, nurses, and other personnel in hospital, chronic-care, and outpatient-care settings who have contact with high-risk patients in all age groups. Those who provide essential community services (e.g., public-safety workers) may consider receiving the vaccine also. Vaccination should reduce the possibility of transmitting influenza from health-care workers to patients and reduce health-care workers' risk of illness and absenteeism due to influenza.

Transmission of rubella in health facilities (e.g., hospitals, physicians' or dentists' offices, and clinics) can disrupt hospital or office routines and cause considerable expense. Although no cases of congenital rubella syndrome (CRS) have been reported in association with rubella transmission in health facilities, therapeutic abortions have been sought by pregnant staff members after rubella infection (8). To prevent such situations, all medical, dental, laboratory, and other support health personnel, both male and female, who might be at risk of exposure to patients infected with rubella or who might have contact with pregnant patients should be vaccinated. Rubella vaccine is recommended for all such personnel unless they have either proof of vaccination with rubella vaccine on or after their first birthday or laboratory evidence of immunity. The vaccine of choice is MMR if recipients are likely to be susceptible to measles and/or mumps as well as to rubella.

Measles and mumps transmission in health facilities can also be disruptive and costly. To prevent such situations, all new employees in health-care facilities who were born in 1957 or later who may have direct patient contact should be vaccinated. Such persons can be considered immune only if they have documentation of having received two doses of live measles vaccine and at least one dose of live mumps vaccine on or after their first birthday, a record of physician-diagnosed measles or mumps, or laboratory evidence of immunity. Institutions may wish to extend this requirement to all employees, not only beginning ones. If recipients are likely to be susceptible to rubella as well as to measles and mumps, MMR is the vaccine of choice. Adults born before 1957 can be considered immune to both measles and mumps because these infections were virtually universal before the availability of measles and mumps vaccines. However, because serologic studies of hospital workers indicate that up to 9.3% of those born before 1957 were not immune to measles (4,5) and because 97 (29%) of 341 health-care workers who had measles in the period 1985-1989 in medical facilities were born before 1957 (6), health facilities should consider requiring at least one dose of measles vaccine for older employees who are at risk of occupational exposure to measles and do not have proof of immunity to this disease.

Poliovirus vaccine is not routinely recommended for persons older than high-school age (greater than or equal to 18 years old). However, hospital personnel who have close contact with patients who may be excreting wild polioviruses and laboratory personnel who handle specimens that may contain wild polioviruses should have completed a primary series of poliovirus vaccine. For personnel who do not have proof of having completed a primary series, completion with enhanced potency inactivated poliovirus vaccine (eIPV)is recommended. This vaccine is preferred because adults have a slightly increased risk of vaccine-associated paralysis after receiving OPV. In addition, because vaccine polioviruses may be excreted by OPV recipients for greater than or equal to 30 days, the use of OPV increases the risk of acquiring vaccine-associated paralytic poliomyelitis among susceptible immunocompromised OPV recipients and/or their close contacts.

Smallpox (vaccinia) vaccination is indicated only for laboratory workers involved with orthopox viruses and certain health-care workers involved in clinical trials of vaccinia recombinant vaccines. When indicated, smallpox (vaccinia) vaccination should be given at least every 10 years.

Plague vaccine is indicated for laboratory personnel working with Yersinia pestis possibly resistant to antimicrobial agents and for persons performing aerosol experiments with Y. pestis.

Anthrax vaccine is indicated for laboratory personnel working with Bacillus anthracis.

Preexposure rabies vaccination is indicated for laboratory workers directly involved with testing or isolating rabies virus.

Veterinarians and Animal Handlers

Veterinarians and animal handlers are at risk of rabies exposure because of occupational contact with domestic and wild animals. They should receive preexposure prophylaxis with human diploid cell rabies vaccine (HDCV). Preexposure vaccination against rabies does NOT eliminate the need for additional therapy after exposure to rabies. Preexposure vaccination does, however, simplify postexposure therapy by eliminating the need for human rabies immune globulin (HRIG) and by decreasing the number of postexposure doses of vaccine needed. Persons at continued risk of frequent exposure should receive a booster dose of HDCV every 2 years or have their serum tested for rabies antibody every 2 years; if the titer is inadequate (<5 by the rapid fluorescent-focus inhibition test), they should receive a booster dose.

Plague vaccine should be considered in the western United States for veterinarians and their assistants who may be exposed to bubonic or pneumonic infection in animals, particularly domestic cats.

Selected Field Personnel

Plague vaccine is indicated for field personnel who cannot avoid regular exposure to potentially plague-infected wild rodents and rabbits and their fleas.

Preexposure rabies vaccine prophylaxis should be considered for field personnel who are likely to have contact with potentially rabid dogs, cats, skunks, raccoons, bats, or other wildlife species.

Selected Occupations

Anthrax vaccine is indicated for individuals who come in contact in the workplace with imported animal hides, furs, bonemeal, wool, animal hair (especially goat hair), and bristles.

Sewage workers, as all other adults, should be adequately vaccinated against diphtheria and tetanus. Sewage workers are not at increased risk of polio, typhoid fever, or hepatitis A; poliovirus and typhoid vaccines and immune globulin (IG) are not routinely recommended for them.

Life-Styles

Various life-styles may increase the risk of exposure to certain vaccine-preventable illnesses. Persons with these life-styles may require vaccines in addition to those routinely recommended for their age group. Table_4 provides a summary of the vaccines recommended.

Homosexually Active Males

Homosexually active males are at high risk of HBV as well as human immunodeficiency virus (HIV) infection. Between 35% and 80% have serologic evidence of HBV infection. Susceptible homosexual males should be vaccinated with HB vaccine as early as possible after they begin homosexual activity because 10%-20% can be expected to acquire HBV infection each year. Because of the high prevalence of infection, serologic screening of homosexual males before vaccination may be cost effective regardless of age or length of homosexual activity. Homosexual men known to have HIV infection should be tested for antibody to hepatitis B surface antigen (HBsAg) 1-6 months after completing the vaccine series (HB vaccine is less effective among HIV-infected persons than among similar persons without HIV infection). Revaccination with one or more doses should be considered if the level of antibody to HBsAg (anti-HBs) is <10 milli-international units {mIU}/milliliter (mL).

Injecting Drug Users

Injecting drug users are at high risk of HBV as well as HIV infection. Serologic evidence of HBV infection has been found in 60%-80% of these individuals. Efforts should be made to vaccinate susceptible users with HB vaccine as early as possible after their drug use begins, because 10%-20% can be expected to acquire HBV infection each year. Because of the high prevalence of infection, serologic screening of injecting drug users before vaccination to avoid unnecessary vaccination is cost effective. Injecting drug users with known HIV infection should be tested for antibody to HBsAg 1-6 months after completion of the vaccine series; revaccination with one or more doses should be considered if their anti-HBs level is <10 mIU/mL.

Drug users are also at increased risk of tetanus; their tetanus vaccination status should therefore be kept up to date with Td.

Heterosexually Active Persons

Heterosexually active persons with multiple sex partners are at increased risk of HBV infection. Vaccination is recommended for persons who are diagnosed to have other sexually transmitted diseases, for male or female prostitutes, and for persons who have had sexual activity with multiple partners during the previous 6 months.

Environmental Situations

Certain environments may place an individual at increased risk of vaccine-preventable diseases. Table_4 summarizes additional vaccines recommended for persons in selected environments. The section on "Vaccine- Preventable Diseases and Their Immunobiologics" contains other essential information.

Inmates of Long-Term Correctional Facilities

Serologic evidence of HBV infection has been found among 10%-80% of male prisoners. Although the frequency of transmission during imprisonment has not been clearly documented, the environment of long-term correctional facilities may be associated with a high risk of transmission of HBV infection because of the likelihood of homosexual behavior and of injecting drug use. In selected long-term institutional settings, prison officials may elect to undertake serologic HBV screening and vaccination programs.

Measles and rubella outbreaks have been documented in long-term correctional facilities. All inmates of such facilities should be vaccinated against measles and rubella. If recipients are likely to be susceptible to mumps as well as to measles and rubella, MMR is the vaccine of choice.

All inmates of such facilities greater than or equal to 65 years of age and those with high-risk conditions, including HIV infection, should receive yearly influenza vaccination. Pneumococcal vaccination within the past 6 years should also be documented.

Residents of Institutions for the Developmentally Disabled

Institutions for the developmentally disabled provide a setting conducive to the transmission of HBV infection through human bites and contact with residents' blood, skin lesions, saliva, and other potentially infectious secretions. Serologic evidence of HBV infection has been found among 35%-80% of residents of such institutions. Persons newly admitted to these institutions should be vaccinated as soon as possible. For current residents, screening and vaccination of susceptible residents is recommended. Because of the high prevalence of infection, serologic screening before vaccination of those already institutionalized may be cost effective; however, screening of new admissions very likely will not be. Residents of group homes, foster homes, and similar settings who have household contact with an HBV carrier should also be vaccinated.

Many of the residents of these institutions have chronic medical conditions that put them at risk for complications from influenza illness; therefore, all residents should receive influenza vaccine yearly.

Household Contacts of HBV Carriers

Household contacts of HBV carriers are at high risk of infection. When HBV carriers are identified through routine screening of donated blood, prenatal screening, or other screening programs, the carriers should be notified of their status. All household contacts should be tested and susceptible contacts vaccinated.

Homeless Persons

There are limited data on vaccine-preventable diseases among the homeless. However, such persons will need completed vaccinations for tetanus, diphtheria, measles, mumps, rubella, influenza, and pneumococcal disease. Also, some will be at risk for HBV infection and some will require tuberculin skin testing. The vaccination status of homeless persons should be assessed whenever they are seen in any medical setting.

Travel

The risk of acquiring illness during international travel depends on the areas to be visited and the extent to which the traveler is likely to be exposed to diseases. When considering travel, people often seek advice regarding vaccination from health-care personnel. This provides a good opportunity to review the person's vaccination status and to administer primary series or booster doses, if needed.

In most countries, measles, mumps, and rubella remain uncontrolled. Therefore, the risk of acquiring these diseases while traveling outside the United States is greater than the risk incurred within the United States. Approximately 61% of imported measles cases reported for 1985-1989 occurred among citizens returning to the United States (CDC, unpublished data). To minimize diseases imported by U.S. citizens, all persons traveling abroad should be immune to measles. Consideration should be given to providing a dose of measles vaccine to persons born in or after 1957 who travel abroad, who have not previously received two doses of measles vaccine, and who do not have other evidence of measles immunity (e.g., physician-diagnosed measles or laboratory evidence of measles immunity). If recipients are likely to be susceptible to mumps or rubella in addition to measles, MMR is the vaccine of choice. Travelers, particularly women of childbearing ages, should be immune to rubella before leaving the United States.

In developed countries such as Japan, Canada, Australia, New Zealand, and European countries, the risk of acquiring other vaccine-preventable diseases such as poliomyelitis, diphtheria, and tetanus is usually no greater than the risk incurred while traveling in the United States. In contrast, travelers to developing countries are at increased risk of exposure to many infections, including wild polioviruses and diphtheria. Accordingly, such travelers should be immune to poliomyelitis and diphtheria in particular.

For protection against poliomyelitis, unvaccinated adults should receive at least two doses of eIPV 1 month apart, preferably a complete primary series, before traveling to a developing country or any country with endemic polio; eIPV is preferred because the risk of vaccine- associated paralysis is slightly higher for adults than for children. If travel plans do not permit this interval, a single dose of either OPV or eIPV is recommended. For adults previously incompletely vaccinated with OPV or inactivated poliovirus vaccine (IPV), the remaining doses of either vaccine required for completion of the primary series should be given, regardless of the interval since the last dose or the type of vaccine previously received. Travelers to developing countries who have previously completed a primary series of OPV should receive a single supplementary dose of OPV. Those who have previously received a primary series of IPV should receive a single supplementary dose of either OPV or eIPV. The need for further doses of either vaccine has not been established.

Persons whose age or health status places them at increased risk of complications from influenza illness and who are planning travel to the tropics at any time of year or the southern hemisphere during April through September should review their influenza vaccination history. If not vaccinated during the previous fall or winter, such persons should consider influenza vaccination before travel. Persons in the high-risk categories should be especially encouraged to receive the most currently available vaccine. Persons at high risk given the previous season's vaccine in preparation for travel should be revaccinated in the fall or winter with the current vaccine and therefore may receive two doses of influenza vaccine within 1 year.

Selective vaccination of travelers with vaccines against yellow fever, cholera, typhoid, plague, meningococcal disease, rabies, or HBV infection, or administration of IG to prevent hepatitis A, is recommended on the basis of known or perceived disease-specific risks in the country or countries to be visited and the type and duration of travel within a country. For cholera and yellow fever, vaccination requirements may have been established by the country to be visited. Countries currently reporting yellow fever, cholera, and plague are identified biweekly in the "Summary of Health Information for International Travel." * Information on known or possibly infected areas is published annually in "Health Information for International Travel," * which also lists specific requirements for cholera and yellow fever vaccinations for each country. All state health departments and many county and city health departments receive both publications. They may also be obtained by calling CDC Information Services at 404-639-1819. For entry into countries requiring yellow fever or cholera vaccination, travelers must have an International Certificate of Vaccination validated by an appropriate authority. State or local health departments can provide the addresses of persons or centers able to validate certificates.

Additional information on specific vaccine-preventable illnesses that a traveler might encounter is provided in the sections describing specific vaccines.

Foreign Students, Immigrants, and Refugees

In many countries, children and adolescents are not routinely vaccinated against diphtheria, tetanus, measles, mumps, rubella, and poliomyelitis. As a result, persons entering the United States as college or postgraduate students, immigrants, or refugees may be susceptible to one or more of these diseases.

Refugees from areas of high HBV endemicity (e.g., Southeast Asia) should be screened for HBsAg and anti-HBs. Susceptible household and sexual contacts of HBsAg carriers should receive HB vaccine.

Unless foreign students, immigrants, and refugees can provide a vaccination record documenting the receipt of recommended vaccines or toxoids at appropriate ages and intervals or laboratory evidence of immunity, they should receive the appropriate vaccines for their age, as noted in the "Age Groups" section and in Table_2.

Special Health Status

Some vaccines may be contraindicated for persons with certain health problems; other vaccines may be indicated because of an underlying health condition. Table_5 provides a summary of immunobiologics indicated or contraindicated for persons with selected health problems.

Pregnancy

When any vaccine or toxoid is to be given during pregnancy, delaying until the second or third trimester, when possible, is a reasonable precaution to minimize concern about possible teratogenicity.

Pregnant women not vaccinated previously against tetanus and diphtheria should receive two doses of Td, properly spaced. Those who have previously received one or two doses of tetanus or diphtheria toxoid should complete their primary series during pregnancy. A primary series is three doses of preparations containing diphtheria and tetanus toxoids, with the first two doses given at least 4 weeks apart and the third dose given 6-12 months after the second. Pregnant women who have completed a primary series should receive a booster dose of Td if greater than or equal to 10 years have elapsed since their last dose.

Because of a theoretical risk to the developing fetus, live-virus vaccines usually should not be given to pregnant women or to those likely to become pregnant within 3 months. If, however, immediate protection against poliomyelitis or yellow fever is needed because of imminent exposure, OPV or yellow fever vaccine may be given. If the only reason to vaccinate a pregnant woman with yellow fever vaccine is an international travel requirement, efforts should be made to obtain a waiver letter. The ACIP strongly recommends that rubella vaccine be administered in the postpartum period to women not known to be immune, preferably before discharge from the hospital.

Data are not available on the safety of HB vaccines for the developing fetus. Because the vaccines contain only noninfectious HBsAg particles, the fetus should not be at risk. In contrast, HBV infection in a pregnant woman may result in severe disease for the mother and chronic infection of the newborn. Therefore, pregnancy or lactation should not be considered a contraindication to the use of this vaccine for persons who are otherwise eligible. Prenatal screening of all pregnant women for HBsAg is recommended. Such screening identifies those who are HBsAg positive and allows treatment of their newborns with hepatitis B immune globulin (HBIG) and HB vaccine, a regimen that is 85%-95% effective in preventing the development of chronic carriage of the HBV.

Pregnant women who have other medical conditions that increase their risks for complications from influenza should be vaccinated; the vaccine is considered safe for pregnant women. Administering the vaccine after the first trimester is a reasonable precaution to minimize any concern over the theoretical risk of teratogenicity. However, it is undesirable to delay vaccinating pregnant women who have high-risk conditions and who will still be in the first trimester of pregnancy when the influenza season begins.

The safety of pneumococcal vaccine for pregnant women has not been evaluated. Ideally, women at high risk of pneumococcal disease should be vaccinated before pregnancy.

Information about immunobiologics and vaccine-preventable diseases during pregnancy is summarized in Appendix 5.

Conditions that Compromise the Immune System

Persons receiving immunosuppressive therapies or with conditions that compromise their immune responses (e.g., leukemia, lymphoma, generalized malignancy, and HIV infection) should receive annual influenza vaccinations with the currently formulated vaccine. Persons with these conditions have been associated with increased risk of pneumococcal disease or its complications and should receive a single dose of pneumococcal polysaccharide vaccine; revaccination should be considered 6 years after the first dose. Haemophilus influenzae type b (Hib) conjugate vaccine (HbCV) is of unproven benefit in immunocompromised persons but may be considered for those with anatomic or functional asplenia or HIV infection. The effectiveness of these vaccines among such persons may be limited, but the risk of disease is substantial and adverse reactions are minimal.

Bacille Calmette-Guerin (BCG), oral typhoid vaccine, or live-virus vaccines should not be given to persons who are immunocompromised as a result of immune deficiency diseases, leukemia, lymphoma, or generalized malignancy or who are immunosuppressed as a result of therapy with cortico- steroids, alkylating drugs, antimetabolites, or radiation. However, susceptible patients with leukemia in remission who have not had chemotherapy for at least 3 months may receive live-virus vaccines. The exact interval between discontinuing immunosuppressives and regaining the ability to respond to individual vaccines is not known. Estimates of experts vary from 3 months to 1 year (9). In addition, persons with asymptomatic HIV infection should be vaccinated against measles, mumps, and rubella. Such vaccination should be considered for persons with symptomatic HIV infection because of the danger of serious or fatal measles and the accumulating evidence of the safety of administering MMR to these patients (Table_6).

Short-term (<2-week) corticosteroid therapy, topical steroid therapy (e.g., nasal or skin), and intra-articular, bursal, or tendon injections with corticosteroids should not be immunosuppressive and do not contra- indicate vaccination with live-virus vaccines. Vaccination should be avoided if systemic immunosuppressive levels are achieved by topical application.

Vaccines given to immunocompromised patients cannot be assumed to be as effective as when given to normal individuals. When available, postvaccin- ation antibody titrations can be done, but, in the absence of specific antibody information, appropriate immune globulins should be considered for exposures to vaccine-preventable diseases, as discussed in the "Immune Globulins" section.

Hemodialysis and Transplantation

Persons receiving hemodialysis have been at high risk of infection with HBV, although environmental control measures have reduced this risk during the past decade. Nationwide, an estimated 15% of hemodialysis patients have serologic evidence of HBV infection, and routine serologic screening of hemodialysis patients is currently recommended. Susceptible patients who will soon require or are currently receiving long-term hemodialysis should receive three doses of HB vaccine as soon as possible. Larger doses (two to four times those for healthy adults) and/or increased numbers of doses are recommended for these patients because of lower vaccine immunogenicity. The individual manufacturer's vaccine package inserts should be inspected to learn the proper dosages of each vaccine. Postvaccination screening to demonstrate antibody to HBsAg is recommended in this group. Approximately 60% of hemodialysis patients who receive recommended doses of HB vaccine develop protective antibodies against HBV. Revaccination with one or more additional doses should be considered for persons who do not respond to vaccination. In hemodialysis patients, protection lasts only as long as anti-HBs levels remain >10 mIU/mL. Such patients should be tested for anti- HBs annually and revaccinated when anti-HBs declines below this level.

Because renal transplant recipients and persons with chronic renal disease are at increased risk of adverse consequences (including transplant rejection) from infections of the lower respiratory tract, these persons should receive annual influenza vaccination with the current formulated vaccine. Because these patients are also at increased risk of developing pneumococcal infection and experiencing more severe pneumococcal disease, they should receive pneumococcal polysaccharide vaccine.

Splenic Dysfunction or Anatomic Asplenia

Persons with splenic dysfunction or anatomic asplenia are at increased risk of contracting fatal pneumococcal bacteremia and should receive pneumococcal polysaccharide vaccine. They are also at risk for meningococcal bacteremia and should receive meningococcal polysaccharide vaccine. The theoretical increased risk for invasive Hib disease suggests that such persons may be considered for HbCV. Persons scheduled for elective splenectomy should receive both pneumococcal and meningococcal polysaccharide vaccines at least 2 weeks before the operation.

Factor VIII and IX Deficiencies

Patients with clotting disorders who receive factor VIII or IX concentrates have an increased risk of HBV infection. Such patients without serologic markers for hepatitis B should be vaccinated against hepatitis B before receiving any blood products. To avoid hemorrhagic complications, vaccination should be given subcutaneously (SC), rather than intramus- cularly (IM) as in the nonhemophilic patient. Prevaccination serologic screening for HBV markers is recommended for patients who have already received multiple infusions of these products.

Chronic Alcoholism

Persons with chronic alcoholism may be at increased risk of contracting a pneumococcal infection or having a more severe pneumococcal illness. Such persons, especially those with cirrhosis, should receive pneumococcal polysaccharide vaccine.

High-Risk Diseases

Persons with disease conditions that increase the risk of adverse consequences from lower-respiratory-tract infections should receive annual influenza vaccination with the current formulated vaccine. These conditions include the following: acquired or congenital heart disease with actual or potentially altered circulatory dynamics; any chronic disorder or condition that compromises pulmonary function; diabetes mellitus or other metabolic diseases that increase the likelihood that infections will be more severe; chronic renal disease with azotemia or nephrotic syndrome; and chronic hemoglobinopathies, such as sickle cell disease.

Some chronic illnesses (e.g., chronic pulmonary disease, congestive heart failure, diabetes mellitus) predispose individuals to an increased risk of pneumococcal illness or its complications. Such persons should receive pneumococcal polysaccharide vaccine.

REQUIREMENTS FOR PERMANENT VACCINATION RECORDS AND REPORTING ADVERSE EVENTS

NCVIA requires physicians and other health-care providers who administer vaccines to maintain permanent vaccination records and to report occurrences of certain adverse events specified in the Act (Table_1). The vaccines and toxoids to which these requirements apply are measles, mumps, and rubella single-antigen vaccines and combination vaccines (MMR, measles, rubella vaccine, live {MR}); diphtheria and tetanus toxoids, adsorbed (pediatric) (DT); Td; tetanus toxoid, adsorbed (T); OPV; IPV; diphtheria and tetanus toxoids and pertussis vaccine, adsorbed (pediatric) (DTP); and pertussis vaccine (P).

Requirements for Recording

All health-care providers who administer one or more of these vaccines or toxoids are required to ensure that the recipient's permanent medical record (or a permanent office log or file) states the date the vaccine was administered, the vaccine manufacturer, the vaccine lot number, the name, the address, and the title of the person administering the vaccine. The term health-care provider is defined as any licensed health-care professional, organization, or institution, whether private or public (including federal, state, and local departments and agencies), under whose authority a specified vaccine is administered.

Requirements for Reporting Adverse Events

Health-care providers are required to report selected events occurring after vaccination to the Vaccine Adverse Events Reporting System (VAERS).

Reportable adverse events are shown in Table_1 and include events described in the vaccine manufacturer's package insert as contraindications to receiving additional doses of vaccine.

Adverse events other than those listed on Table_1 or occurring after administration of other vaccines, especially events that are serious or unusual, can also be reported to VAERS. VAERS forms and instructions are available in the "FDA Drug Bulletin" (Food and Drug Administration) and the "Physicians' Desk Reference" or by calling VAERS at 1-800-822-7967.

Vaccine Injury Compensation

The National Vaccine Injury Compensation Program is a system under which compensation can be paid on behalf of an individual who died or was injured as a result of being given a vaccine. The program is intended as an alternative to civil litigation under the traditional torts system in that negligence need not be proven. The program was created by NCVIA and became effective on October 1, 1988.

The law established a vaccine injury table (Table_1), which lists the vaccines covered by the program as well as the injuries, disabilities, illnesses, and conditions (including death) for which compensation may be paid. The program also sets out the period of time during which the first symptom or significant aggravation of the injury must appear. This period often differs from that required for reporting. Persons may be compensated for an injury listed in Table_1 or one that can be demonstrated to result from administration of a listed vaccine. Additional information about the program is available from:

Administrator National Vaccine Injury Compensation Program Health Resources and Services Administration 6001 Montrose Road, Room 702 Rockville, MD 20852 Telephone: (301) 443-6593

Persons wishing to file a claim for a vaccine injury should call or write to:

U.S. Claims Court 717 Madison Place, N.W. Washington, D.C. 20005 Telephone: (202) 633-7257

VACCINE-PREVENTABLE DISEASES AND THEIR IMMUNOBIOLOGICS

Vaccines, toxoids, and immune globulins are available for use in preventing many diseases. These diseases and their specific immunobiologics are presented in this section. For each immunobiologic, the dosage, route of delivery, indications for use, side effects, adverse reactions, precautions, and contraindications are described here. These are also summarized in Table_7.

Toxoids

Diphtheria

The occurrence of diphtheria has decreased dramatically in the United States, largely because of the widespread use of diphtheria toxoid. Only 11 cases of respiratory diphtheria were reported in the period 1985-1989. Seven of these 11 cases occurred among adults greater than or equal to 20 years of age, and three among adults greater than or equal to 60 years of age. Diphtheria occurs primarily among unvaccinated or inadequately vaccinated individuals. Limited serosurveys done since 1977 indicate that 22%-62% of adults 18-39 years of age and 41%-84% of those greater than or equal to 60 years of age lack protective levels of circulating antitoxin against diphtheria (10-13).

Diphtheria toxoid. Complete and appropriately timed vaccination is at least 85% effective in preventing diphtheria. The combined preparation Td is recommended for use among adults because a large proportion of them lack protective levels of circulating antibody against tetanus (10-13). Further- more, Td contains much less diphtheria toxoid than other diphtheria toxoid- containing products, and, as a result, reactions to the diphtheria component are less likely. Vaccination with any diphtheria toxoid does not, however, prevent or eliminate carriage of Corynebacterium diphtheriae.

Toxoid indications. All adults lacking a completed primary series of diphtheria and tetanus toxoids should complete the series with Td. A primary series for adults is three doses of preparations containing diphtheria and tetanus toxoids, with the first two doses given at least 4 weeks apart and the third dose given 6-12 months after the second. All adults for whom greater than or equal to 10 years have elapsed since completion of their primary series or since their last booster dose should receive a dose of Td. Thereafter, a booster dose of Td should be administered every 10 years. There is no need to repeat doses if the schedule for the primary series or booster doses is delayed.

Tetanus

The occurrence of tetanus has decreased dramatically, largely because of the widespread use of tetanus toxoid. Nevertheless, the number of cases remained relatively constant from 1986 through 1989, during which 48-64 cases were reported annually. Tetanus occurs almost exclusively among unvaccinated or inadequately vaccinated persons. Immune pregnant women transfer temporary protection against tetanus to their infants through transplacental maternal antibody.

In the period 1982-1989, persons greater than or equal to 20 years of age accounted for 95% of the 513 reported tetanus cases for which patient ages were known; persons greater than or equal to 60 years of age accounted for 59%. The age distribution of persons who died from tetanus was similar. Serosurveys done since 1977 indicate that 6%-11% of adults 18-39 years of age and 49%-66% of those greater than or equal to 60 years of age lack protective levels of circulating antitoxin against tetanus (10-13). Although surveys of emergency rooms suggest that only 1%-6% of all persons who receive medical care for injuries that can lead to tetanus receive inadequate prophylaxis (14), in 1987-1988, 81% of the people who developed tetanus after an acute injury and sought medical care did not receive adequate prophylaxis as recommended by the ACIP (14).

Tetanus toxoid. Complete and appropriately timed vaccination is nearly 100% effective in preventing tetanus. Td is the preferred preparation for active tetanus immunization of adults because a large proportion of them also lack protective levels of circulating antitoxin against diphtheria (10-13).

Toxoid indications. All adults lacking a complete primary series of diphtheria and tetanus toxoids should complete the series with Td. A primary series for adults is three doses of preparations containing tetanus and diphtheria toxoids, with the first two doses given at least 4 weeks apart and the third dose given 6-12 months after the second. Persons who have served in the military can be considered to have received a primary series of diphtheria and tetanus toxoids. The practitioner should be aware that policies of the different branches of the military have varied among themselves and over time. All adults for whom greater than or equal to 10 years have elapsed since completion of their primary series or since their last booster dose should receive a booster dose of Td. Thereafter, a booster dose of Td should be administered every 10 years. Doses need not be repeated if the primary schedule for the series or booster doses is delayed.

The recommended pediatric schedule for DTP includes a booster dose at age 4-6 years. The first Td booster is recommended at age 14-16 years (10 years after the dose at age 4-6 years). One means of ensuring that persons continue to receive boosters every 10 years is to vaccinate persons routinely at mid-decade ages (e.g., 25 years of age, 35 years of age).

For wound management, the need for active immunization, with or without passive immunization, depends on the condition of the wound and the patient's vaccination history. A summary of the indications for active and passive immunization is provided in Table_8. Only rarely have cases of tetanus occurred among persons with a documented primary series of toxoid injections.

Evidence indicates that complete primary vaccination with tetanus toxoid provides long-lasting protection (greater than or equal to 10 years among most recipients). Consequently, after complete primary tetanus vaccination, boosters are recommended at 10-year intervals. For clean and minor wounds occurring during the 10-year interval, no additional booster is recommended. For other wounds, a booster is appropriate if the patient has not received tetanus toxoid within the preceding 5 years. Antitoxin antibodies develop rapidly in persons who have previously received at least two doses of tetanus toxoid.

Persons who have not completed a full primary series of injections or whose vaccination status is unknown or uncertain may require tetanus toxoid and passive immunization at the time of wound cleaning and debridement. Ascertaining the interval since the most recent toxoid dose is not sufficient. A careful attempt should be made to determine whether a patient has previously completed primary vaccination and, if not, how many doses have been given. Persons with unknown or uncertain previous vaccination histories should be considered to have had no previous tetanus toxoid doses.

In managing the wounds of adults, Td is the preferred preparation for active tetanus immunization. This toxoid preparation is also used to enhance protection against diphtheria, because a large proportion of adults are susceptible. Thus, if advantage is taken of visits for care of acute health problems, such as for wound management, some patients who otherwise would remain susceptible can be protected against both diseases. Primary vaccination should ultimately be completed for persons documented to have received fewer than the recommended number of doses, including doses given as part of wound management.

If passive immunization is needed, human tetanus immune globulin (TIG) is the product of choice. The currently recommended prophylactic dose of TIG for wounds of average severity is 250 units IM. When T or Td and TIG are given concurrently, separate syringes and separate sites should be used. Most experts consider the use of adsorbed toxoid mandatory in this situation.

Toxoid Side Effects and Adverse Reactions

Local reactions (usually erythema and induration, with or without tenderness) can occur after Td is administered. Fever and other systemic symptoms are less common.

Arthus-type hypersensitivity reactions, characterized by severe local reactions starting 2-8 hours after an injection and often associated with fever and malaise, may occur, particularly among persons who have received multiple boosters of tetanus toxoid, adsorbed (T).

Rarely, severe systemic reactions, such as generalized urticaria, anaphylaxis, or neurologic complications, have been reported after administration of tetanus and diphtheria toxoids. Peripheral neuropathy has been reported rarely after administration of T, although a causal relationship has not been established.

Toxoid Precautions and Contraindications

Although no evidence suggests that diphtheria and tetanus toxoids are teratogenic, waiting until the second trimester of pregnancy to administer Td is a reasonable precaution.

A history of a neurologic reaction or a severe hypersensitivity reaction (e.g., generalized urticaria or anaphylaxis) after a previous dose is a contraindication to diphtheria and tetanus toxoids. Local side effects alone do not preclude continued use. If a prior systemic reaction suggests allergic hypersensitivity, appropriate skin testing to document immediate hypersensitivity may be useful before T vaccination is discontinued. Protocols exist for using both Td and single-antigen tetanus toxoids for skin testing (15). Mild, nonspecific skin-test reactivity to T toxoid is common. Most vaccinees develop a delayed but inconsequential cutaneous hypersensitivity to the toxoid.

Persons experiencing severe Arthus-type hypersensitivity reactions to a dose of T usually have very high serum tetanus antitoxin levels and should not be given even emergency booster doses of Td more frequently than every 10 years.

If a contraindication to using preparations containing T exists in a person who has not completed a primary immunizing course of T and other than a clean minor wound is sustained, only passive immunization should be given using TIG.

Although a minor illness, such as a mild upper respiratory infection, should not be cause for postponing vaccination, a severe febrile illness is reason to defer routine vaccination.

Live-Virus Vaccines

Measles

Before the introduction of measles vaccine in 1963, approximately 500,000 cases of measles and 500 measles-associated deaths were reported annually in the United States. Because of the widespread use of measles vaccine, the number of reported measles cases decreased to an all-time low of 1,497 in 1983. From 1984 through 1988, the annual number of reported measles cases averaged 3,600, which represents <1% of the cases reported annually in the prevaccine era. In 1989 and 1990, a substantial increase in cases was reported, primarily because of a large number of outbreaks among unvaccinated preschool-age children and vaccinated high-school and college- age students. The 27,786 cases provisionally reported in 1990 represent the largest number of cases reported in any year since 1978. Measles cases were reported from 49 states and the District of Columbia. Adults greater than or equal to 20 years of age accounted for 22% of cases, of which 67% were not appropriately vaccinated (unvaccinated with vaccine indicated). Twenty- five percent of these adults with measles required greater than or equal to 1 day of hospitalization. A provisional total of 130 measles-associated deaths was reported in 1989 and 1990; 36 (28%) of these were persons greater than or equal to 20 years of age. At least 267 measles outbreaks were reported; 17 (6%) occurred on college campuses. Two percent of reported cases were among college students or were epidemiologically linked to campus outbreaks.

Encephalitis or death follows measles disease in approximately one case per 1,000. Aside from infants, the risk of encephalitis is greatest among adult patients.

Measles illness during pregnancy increases rates of spontaneous abortion, premature labor, and low birth weight for infants. Although cases of congenital malformation after measles infection during pregnancy have been reported, no specific syndrome has been demonstrated.

Measles vaccine. Measles vaccine produces a mild or inapparent noncommunicable infection. A single subcutaneously administered dose of live measles vaccine provides durable protection against measles illness for greater than or equal to 95% of susceptible children vaccinated at greater than or equal to 15 months, extending probably for their lifetime. The vaccine of choice is MMR.

Vaccine indications. All adults born in 1957 or later who do not have a medical contraindication should receive one dose of measles vaccine unless they have a dated record of vaccination with at least one dose of live measles vaccine on or after their first birthday, documentation of physician-diagnosed disease, or laboratory evidence of immunity. Most persons born before 1957 can be considered immune and do not need vaccination. Of all measles cases reported to CDC from 1985 through 1990, 96.3% occurred among persons born in 1957 or later. However, because a small proportion will be susceptible, vaccine should be offered to such individuals, particularly health-care workers, if there is reason to believe that they may be susceptible. Serologic studies of hospital workers indicate that up to 9.3% of persons born before 1957 were not immune to measles (4,5). Ninety-seven (29%) of 341 health-care workers who developed measles in the period 1985-1989 were born before 1957 (6).

As noted above, a single dose of live measles vaccine given on or after the first birthday can be expected to provide long-lasting immunity to measles in at least 95% of recipients. In most situations, a high rate of vaccination resulting in 95% of the population being immune is sufficient to prevent transmission of measles. However, in some circumstances, 5% susceptibility provides enough nonimmune persons to sustain transmission of measles. This situation occurs most commonly in school and college settings, where large numbers of young adults congregate. Other circum- stances in which transmission may occur despite high levels of immunity are in hospitals and other health-care facilities and among persons traveling in places where measles is endemic. In these situations, assuring high levels of immunity to measles among vaccinees by providing a second dose of measles vaccine is desirable. The two-dose schedule is expected to provide protection to most persons who do not respond to their initial vaccination.

Entrants into colleges, universities, and other institutions of post- high school education as well as employees in health-care facilities who do not have evidence of immunity to measles (documented physician-diagnosed measles or laboratory evidence of immunity) should be required to provide documentation of two doses of measles vaccine on or after their first birthday. Use of MMR is preferred for both vaccine doses to assure immunity to all three viruses. Individuals who have no documentation of ever having received any doses of measles vaccine and who do not have other evidence of measles immunity should be given one dose of measles vaccine on entry into college or when beginning employment; they should be revaccinated with a second dose not less than 1 month later. If feasible, colleges and health- care facilities may wish to extend this requirement to all students and employees.

During outbreaks of measles in schools, colleges, or health-care facilities, all persons born in 1957 or later who cannot provide evidence of receiving two doses of measles vaccine or other evidence of measles immunity should receive one dose of measles-containing vaccine. Those persons should receive their second dose of vaccine not less than 1 month later. Because some medical personnel who have acquired measles in medical facilities were born before 1957, vaccination of older employees who may have occupational exposure to measles should also be considered during outbreaks.

An estimated 600,000-900,000 persons in the United States received killed measles vaccine in the period 1963-1967. Individuals who received killed measles vaccine, killed measles vaccine followed within 3 months by live measles vaccine, measles vaccine of unknown type in the period 1963-1967, or vaccine before their first birthday should be considered unvaccinated and should receive at least one dose of live measles vaccine. If these persons are beginning college or other post-high school education or beginning employment in a medical setting, they should receive two doses of measles vaccine at least 1 month apart, as described above.

Because the risk of acquiring measles outside the United States is greater than the risk incurred in the United States, travelers should be immune to measles before leaving the United States. Consideration should be given to providing a dose of measles vaccine to persons born during or after 1957 who travel abroad, who have not previously received two doses of measles vaccine, and who do not have other evidence of measles immunity.

Young adults who are exposed to measles and who have no or uncertain documentation of live measles vaccination on or after their first birthday, no record of physician-diagnosed measles, and no laboratory evidence of immunity should be vaccinated within 72 hours after exposure; vaccination is most likely to be protective during that time. If the exposure did not result in infection, the vaccine should induce protection against subsequent measles infection. An acceptable alternative is to use immune globulin (IG), which can prevent or modify infection if administered within 6 days after exposure. This alternative is principally indicated when measles vaccine is contraindicated. IG should not be used in an attempt to control measles outbreaks. The recommended dose of IG is 0.25 mL/kg IM, not to exceed 15 mL. Live measles vaccine should be given 3 months after IG is administered, by which time the passive measles antibodies should have disappeared. Because postexposure vaccination or administration of IG is not completely effective, medical personnel should be removed from patient contact 5-21 days after exposure.

Vaccine side effects and adverse reactions. A temperature of greater than or equal to 103 F (39.4 C) may develop among approximately 5%-15% of vaccinees, usually beginning between the fifth and twelfth days after vaccination; fever usually lasts 1-2 days and, rarely, up to 5 days.

Rashes have been reported among approximately 5% of vaccinees. Encephalitis after measles vaccination is extremely rare, and its incidence cannot be discerned from the background incidence rate of encephalitis of an unknown etiology. The incidence of postvaccination encephalitis is much lower than the incidence after natural measles.

Reactions after live measles vaccination occur among 4%-55% of prior recipients of killed measles vaccine. The reactions are generally mild, consisting of a local reaction with or without a low-grade fever of 1-2 days duration. Such reactions can be fairly severe but are milder than atypical measles syndrome, an illness that may affect prior recipients of killed measles vaccine who are exposed to natural measles.

No evidence suggests increased risk from live measles vaccination among persons who are already immune to measles as a result of either previous vaccination or natural disease.

Vaccine precautions and contraindications. Vaccination should not be postponed because of a minor illness, such as a mild upper-respiratory infection. However, vaccination of persons with severe febrile illnesses should be postponed until recovery. Vaccine should be given 14 days before -- or deferred for at least 6 weeks and preferably 3 months after -- a person has received IG, whole blood, or other blood products containing antibody.

Because of a theoretical risk to the developing fetus, measles vaccine should not be given to pregnant women.

Measles vaccine also should not be given to persons who are immunocom- promised as a result of immune deficiency diseases, leukemia, lymphoma, or generalized malignancy or who are immunosuppressed as a result of therapy with corticosteroids, alkylating drugs, antimetabolites, or radiation. However, persons with leukemia who are in remission and have not received chemotherapy for at least 3 months and HIV-infected persons should be vaccinated against measles, if considered susceptible. (See "Conditions that Compromise the Immune System" and Table_5 and Table_6.)

No evidence suggests that live measles vaccine exacerbates tuberculosis. If tuberculin skin testing is needed, the testing should be done on the day of vaccination and read 48-72 hours later. A recent vaccinee should wait 4-6 weeks after receiving measles vaccine before a tuberculin skin test is administered, because measles vaccination may temporarily suppress tuberculin reactivity.

Persons with a history of any sign or symptom of an anaphylactic reaction (e.g., hives, swelling of the mouth and throat, difficulty breathing, hypotension, or shock) after ingestion of eggs or receipt of neomycin should be given measles vaccine only with extreme caution. Protocols have been developed for vaccinating such persons (16). Persons with reactions that are not anaphylactic are not at increased risk and can be vaccinated.

Mumps

The reported occurrence of mumps cases in the United States has decreased steadily since the introduction of live mumps vaccine. In 1985, a record low of 2,982 cases was reported; this number represented a 98% decline from the 185,691 cases reported in 1967, the year live mumps vaccine was licensed. However, reported cases increased to 7,790 in 1986, followed by 12,848 cases in 1987. In 1988, 1989, and 1990, totals of 4,866, 5,712, and 5,075 cases, respectively, were reported. Largely because of expense, mumps vaccine was not recommended by the ACIP for routine use until 1977, which led to the development of a relatively underimmunized cohort of teenagers and young adults (17). Data from the U.S. Immunization Survey suggest that only approximately 50% of persons of college age in 1986 had received mumps vaccine. In 1989, 38% of reported mumps cases for whom age was known occurred among persons greater than or equal to 15 years of age, compared with 12% in 1977.

Although mumps disease is generally self limiting, meningeal signs may appear in up to 15% of cases, and orchitis in 20%-30% of clinical cases among postpubertal males. Sterility is a rare sequela of mumps orchitis among males. Unilateral sensorineural deafness occurs at a rate of one case per 20,000 cases of mumps.

Mumps vaccine. Live mumps vaccine has been available since 1967. A single dose of live mumps vaccine administered SC provides protective and long-lasting levels of antibody in >90% of recipients. Clinical vaccine efficacy reports range between 75% and 95%. If recipients are likely to be susceptible to measles and/or rubella as well as to mumps, MMR is the vaccine of choice.

Vaccine indications. Mumps vaccine is indicated for all adults believed to be susceptible. Persons should be considered susceptible to mumps unless they have documentation of physician-diagnosed mumps, adequate immunization with live mumps vaccine on or after their first birthday, or laboratory evidence of immunity. Most adults born before 1957 are likely to have been infected naturally and can be considered immune, even if they did not have clinically recognizable mumps disease. Killed mumps vaccine was available from 1950 until 1978. Persons who received killed mumps vaccine might benefit from vaccination with live mumps vaccine. Revaccination with MMR is recommended under certain circumstances for measles (see "Measles" section) and may also be important for mumps because recent studies have shown that mumps can occur in highly vaccinated populations. Persons who are unsure of their mumps disease/vaccination history should be vaccinated.

Vaccine side effects and adverse reactions. Parotitis and fever after vaccination have been reported rarely. Allergic reactions including rash, pruritus, and purpura have been associated temporally with mumps vaccination but are uncommon, usually mild, and of brief duration. The frequency of reported central nervous system (CNS) dysfunction after mumps vaccination is not greater than the observed background incidence rate in the general population.

Because of the recommendation to use MMR for revaccination against measles, many persons will receive two doses of live mumps vaccine. No evidence suggests an increased risk from live mumps vaccination among persons who are already immune to mumps as a result of either previous vaccination or natural disease.

Vaccine precautions and contraindications. Vaccine should be given at least 14 days before, or deferred for at least 6 weeks -- and preferably 3 months -- after a person has received IG, whole blood, or other blood products containing antibody.

Because of the theoretical risk of fetal harm after administration of a live-virus vaccine to a pregnant woman, avoiding administering mumps vaccine to pregnant women is prudent.

Mumps vaccine should not be given to persons who are immunocompromised as a result of immune deficiency diseases, leukemia, lymphoma, or generalized malignancy or to persons who are immunosuppressed as a result of therapy with corticosteroids, alkylating drugs, antimetabolites, or radiation. Mumps vaccine should be given to asymptomatic HIV-infected individuals and may be considered for those who are symptomatic. (See "Conditions that Compromise the Immune System" and Table_5 and Table_6.) Persons with a history of any sign or symptom of an anaphylactic reaction (e.g., hives, swelling of the mouth and throat, difficulty breathing, hypotension, or shock) after ingestion of eggs or receipt of neomycin should be vaccinated only with extreme caution. Protocols have been developed for vaccinating persons with severe egg allergy (16). Persons with reactions that are not anaphylactic are not at increased risk and can be vaccinated.

Rubella

Preventing fetal infection and consequent CRS are the objectives of rubella immunization. Fetal infection occurring during the first trimester of pregnancy can lead to CRS in up to 80% of fetuses. Also, fetal death because of miscarriage or therapeutic abortion after maternal rubella disease or exposure during the first trimester continues to occur frequently.

The number of reported rubella cases has decreased steadily from >56,000 cases in 1969, the year rubella vaccine was licensed, to 225 cases in 1988. Until the mid-1970s, the strategy was to vaccinate all children; this strategy dramatically reduced the incidence of rubella but had less impact on older age groups, resulting in an increased proportion of cases in adolescents and adults. During the period 1976-1979, >70% of the reported rubella cases occurred among persons greater than or equal to 15 years of age. During 1980 to 1990, this percentage varied widely, reaching a low of 38% in 1988. However, a fivefold increase in rubella incidence occurred between 1988 and 1990. Provisional data indicate that incidence rose sharply among persons greater than or equal to 15 years of age to approximately 57% of 931 cases (with known age) in 1990. A cluster of at least 11 CRS cases among infants born in 1990 was reported to the National CRS Registry. Increased efforts to increase delivery of vaccine to college- age and older persons have led to the current decline in the incidence rates for these age groups. However, an estimated 6%-11% of young adults remain susceptible to rubella, and limited outbreaks continue to be reported in universities, colleges, and places of employment -- notably hospitals.

Vaccination of young children has prevented widespread epidemics of rubella and of CRS and eventually will lead to the elimination of CRS as vaccinated cohorts enter the childbearing age. However, increased efforts to ensure that all adults, particularly women of childbearing age, are vaccinated will hasten the elimination of rubella and CRS in the United States. Additional aids to eliminate rubella and CRS include achieving and maintaining high vaccination levels, maintaining vigorous surveillance, and practicing aggressive outbreak control.

Rubella vaccine. A single SC-administered dose of live, attenuated rubella vaccine provides long-term (probably lifetime) immunity among approximately 95% of vaccinees. Moreover, there has been no identified transmission of vaccine virus in studies of >1,200 susceptible household contacts of vaccinees and in >20 years of experience with live rubella vaccine. If recipients are likely to be susceptible to measles and/or mumps as well as to rubella, MMR is the vaccine of choice.

Vaccine indications. Rubella vaccine is recommended for adults, particularly females, unless proof of immunity is available (i.e., documented rubella vaccination on or after the first birthday or positive results from a serologic test) or unless the vaccine is specifically contraindicated. In particular, nonpregnant susceptible women of childbearing age should be provided rubella vaccination a) during routine internal medicine and gynecologic outpatient care, b) during routine care in a family planning clinic, c) after premarital screening, d) before discharge from a hospital for any reason, and e) after childbirth or abortion. Ideally, any contact with the health-care system should be used as an opportunity to vaccinate susceptible women. Also, evidence of rubella immunity should be required for all persons in colleges and universities. Health-care programs in workplaces and in other places where women of childbearing age congregate should ensure that the vaccination status of every employee is evaluated and that rubella vaccination is made available. All hospital personnel (male and female) who might be at risk of exposure to patients infected with rubella or who might have contact with pregnant patients or personnel should be immune to rubella. Consideration should be given to making rubella immunity a condition for employment. Finally, since the risk of acquiring rubella while traveling outside the United States is greater than the risk incurred within the United States, all women travelers, particularly those of childbearing age, should be immune before leaving the United States.

Vaccine side effects and adverse reactions. Up to 25% of susceptible postpubertal female vaccinees in large-scale field trials have had arthralgia after vaccination; arthritis signs and symptoms occur transiently among 10% of recipients. Arthralgia and transient arthritis occur more frequently and tend to be more severe among susceptible women than among seropositive women and children. When joint symptoms or other types of pain and paresthesias do occur, they usually begin 1-3 weeks after vaccination, persist from 1 day to 3 weeks, and rarely recur. Adults with joint problems usually have not had to disrupt work activities. Sporadic cases of persistent joint symptoms among susceptible vaccinees, primarily adult women, have been reported. Although one group of investigators has reported the frequency of chronic joint symptoms and signs among adult women to be as high as 5%-11% (18,19), other data from the United States and experience from other countries that use the RA 27/3 strain suggest that such phenomena are rare. In comparative studies, the frequency of chronic joint complaints is substantially higher after natural infection than after vaccination (19). Complaints of transient peripheral neuritis, such as paresthesias and pain in the arms and legs, have occurred very rarely and only among susceptible vaccinees; these symptoms rarely persist.

Because a two-dose schedule of MMR is being implemented in the United States, some persons will receive two doses of rubella vaccine. There is no conclusive evidence of any increased risk of the reactions described above for persons who are already immune when vaccinated.

Vaccine precautions and contraindications. Rubella vaccine should be given at least 14 days before administration of IG or deferred for at least 6 weeks -- and preferably 3 months -- after administration. On the other hand, previous administration of whole blood or other blood products containing antibody (e.g., human anti-Rho {D} IG) does not interfere with an immune response and is not a contraindication to postpartum vaccination. However, in this situation, serologic testing should be done 6-8 weeks after vaccination to assure that seroconversion has occurred.

Rubella vaccine should not be given to pregnant women or to those likely to become pregnant within 3 months after receiving the vaccine. Through 1988, CDC monitored prospectively 305 susceptible pregnant women who had received rubella vaccine within 3 months before or after conception and carried their pregnancies to term. Ninety-four received Cendehill or HPV-77, 210 received RA 27/3, and one received an unknown strain of vaccine. None of the infants had malformations compatible with CRS. The ACIP believes that the risk of vaccine-associated malformation is so small as to be negligible. Although a final decision must rest with the individual patient and her physician, the ACIP believes that rubella vaccination during pregnancy should not ordinarily be a reason to recommend interruption of pregnancy.

Because of the theoretical risk to the fetus, reasonable precautions should be taken before women of childbearing age are vaccinated. These precautions include a) asking women if they are pregnant, b) excluding those who say they are, and c) explaining the theoretical risks of the vaccine to the others and counseling them not to become pregnant for 3 months after vaccination. If a pregnant woman is vaccinated or if a woman becomes pregnant within 3 months after vaccination, she should be counseled on the theoretical risks to the fetus.

Rubella vaccine should not be given to persons who are immunocom- promised as a result of immune deficiency diseases, leukemia, lymphoma, or generalized malignancy or who are immunosuppressed as a result of therapy with corticosteroids, alkylating drugs, antimetabolites, or radiation. HIV infection is an exception; rubella vaccine should be given to asymptomatic HIV-infected persons and may be considered for those who are symptomatic. (See "Conditions that Compromise the Immune System" and Table_5 and Table_6.)

Rubella vaccine is prepared in human diploid cell cultures and has rarely been reported to be associated with allergic reactions. The vaccine does contain trace amounts of neomycin to which patients may be allergic. Persons with a history of any sign or symptom of an anaphylactic reaction (e.g., hives, swelling of the mouth and throat, difficulty breathing, hypotension, or shock) after receipt of neomycin should not receive rubella vaccine. Persons with reactions to neomycin that are not anaphylactic are not at increased risk and can be vaccinated. Rubella vaccine does not contain penicillin.

Smallpox (Vaccinia)

In May 1980, the World Health Organization (WHO) declared the world free of smallpox (vaccinia). A smallpox vaccination certificate is not required by any country as a condition of entry for international travelers. In May 1983, the distribution of vaccine for civilian use in the United States was discontinued.

Vaccine indications. Only laboratory personnel working with orthopox viruses and certain health-care workers involved in clinical trials of vaccinia recombinant vaccines may need to be given smallpox vaccine. Otherwise, there are no indications for its use in civilian populations.

No evidence suggests that smallpox vaccination has therapeutic value in the treatment of recurrent herpes simplex infection, warts, or any other disease. Smallpox vaccine should never be used therapeutically for these or any other conditions.

When indicated, smallpox vaccination should be given every 10 years. For advice on vaccine administration and contraindications, contact the CDC Drug Service, Building 1, Room 1259, CDC, Atlanta, GA 30333, telephone: 404-639-3356, or the Division of Immunization, CDC Mailstop (E05), Atlanta, GA 30333, telephone: 404-639-1870.

Varicella Zoster

Most adults (85%-95%) with negative or unknown histories of varicella (chickenpox) are likely to be immune. Primary varicella can be more severe among adults than it is among normal (immunocompetent) children; however, the risk of serious complications among normal adults is substantially less than it is among those who are immunocompromised. Live, attenuated varicella-zoster vaccine may be licensed for use in normal children in the near future. Its potential use among adults, particularly health-care workers, has not been defined.

Yellow Fever

Cases of yellow fever are reported only from Africa and South America. Two forms of yellow fever -- urban and jungle -- are distinguishable epidemiologically. Clinically and etiologically, the two forms are identical.

Urban yellow fever is an epidemic viral disease transmitted from infected to susceptible persons by the Aedes aegypti mosquito. In areas where the Ae. aegypti mosquito has been eliminated or suppressed, urban yellow fever has disappeared. However, periodic reinfestations of some countries in Central and South America have occurred in recent years, and other countries remain infested. In West Africa, an Ae. aegypti-transmitted epidemic involving an urban population occurred as recently as 1987.

Jungle yellow fever is an enzootic viral disease transmitted among nonhuman hosts by a variety of mosquito vectors. Only in forested areas of South America and forest-savannah zones of tropical Africa has it been observed, but it occasionally extends into Central America and the island of Trinidad. In South America, 100-300 cases are recognized annually, mainly among persons with occupational exposure in forested areas; the disease is, however, believed to be greatly underreported. In Africa, sporadic endemic cases and epidemics that affect thousands of persons are spread by forest mosquito vectors. The cycle of jungle yellow fever may be active but unrecognized in forested areas of countries within the endemic yellow fever zone (Figure_1).

Yellow fever vaccine. The yellow fever vaccine available in the United States is an attenuated, live-virus vaccine prepared from the 17D strain of virus grown in chick embryos. Immunity is induced by a single SC injection of 0.5 mL of reconstituted vaccine and persists for >10 years.

Yellow fever vaccines must be approved by WHO and administered at an approved Yellow Fever Vaccination Center. Centers can be identified by contacting state and local health departments. Vaccinees should have an International Certificate of Vaccination filled out, dated, signed, and validated with the stamp of the center where the vaccine is given. Vaccine must be received 10 days to 10 years before travel for the certificate to be valid.

Vaccine indications. Vaccination is recommended for persons traveling or living in areas in which yellow fever infection occurs -- currently parts of Africa and Central and South America. Information on known or probably infected areas is published annually in "Health Information for International Travel". Countries currently reporting yellow fever are noted biweekly in "Summary of Health Information for International Travel" (see page 11). All state health departments and many county and city health departments receive these publications. The actual areas of yellow fever activity far exceed the zones officially reported to be infected. Vaccination is also recommended for laboratory personnel who might be exposed to virulent yellow fever virus.

Booster doses are needed at 10-year intervals. Some countries, especially in Africa, require evidence of vaccination from all entering travelers. Other countries may waive the requirements for travelers coming from noninfected areas and staying <2 weeks. Some countries require a traveler, even if only in transit, to have a valid certificate if the traveler has visited any country thought to harbor yellow fever virus. Requirements of individual countries may change, and the most current information is published biweekly in "Summary of Health Information for International Travel" and summarized annually in "Health Information for International Travel" (see page 11).

Vaccine side effects and adverse reactions. Reactions to 17D yellow fever vaccine are generally mild. From 2% to 5% of vaccinees have mild headache, myalgia, low-grade fever, or other minor symptoms 5-10 days after vaccination. Fewer than 0.2% curtail regular activities. Immediate hyper- sensitivity reactions, characterized by rash, urticaria, and/or asthma, are extremely uncommon and occur principally among persons with a history of egg allergy. Although >34 million doses of vaccines have been distributed, only two cases of encephalitis temporally associated with vaccinations have been reported in the United States; in one fatal case, 17D virus was isolated from the brain.

Vaccine precautions and contraindications. Yellow fever vaccine should not be given to persons who are immunocompromised as a result of immune deficiency diseases (including symptomatic HIV infection), leukemia, lymphoma, or generalized malignancy, or to persons who are immunosuppressed as a result of therapy with corticosteroids, alkylating drugs, antimeta- bolites, or radiation. (See "Conditions that Compromise the Immune System.") Persons who have asymptomatic HIV infection and who cannot avoid potential exposure to yellow fever virus should be offered the choice of vaccination.

Although specific information is not available on adverse effects of yellow fever vaccine on the developing fetus, avoiding vaccination of pregnant women and advising that they postpone travel to areas where yellow fever occurs until after delivery seems prudent. Pregnant women who must travel to areas in which the risk of yellow fever is high should be vaccinated. The risk of yellow fever infection far outweighs the small theoretical risk to mother and fetus from vaccination in such circumstances. However, if international travel regulations constitute the only reason to vaccinate a pregnant woman or a patient hypersensitive to eggs, efforts should be made to obtain a letter of waiver from a physician clearly stating the contraindication to vaccination. Ideally, this letter should be written on letterhead stationery and bear the stamp used by health departments and official immunization centers to validate the International Certificates of Vaccination. Under these conditions, travelers should obtain specific, authoritative advice from the country or countries they plan to visit. The countries' embassies or consulates may be contacted and a letter substantiating the waiver of requirements should be obtained.

Because live yellow fever vaccine is produced in chick embryos, persons with a history of any signs or symptoms of an anaphylactic reaction (e.g., hives, swelling of the mouth and throat, difficulty breathing, hypotension, or shock) after eating eggs should not receive yellow fever vaccine. If vaccination of an individual with a questionable history of egg hyper- sensitivity is considered essential because of a high risk of exposure, an intradermal (ID) test dose may be administered under close medical supervision. Specific directions for skin testing are found in the package insert.

Some data have indicated that persons given yellow fever and cholera vaccines simultaneously or 1-3 weeks apart had lower than normal antibody responses to both vaccines. Unless there are time constraints, cholera and yellow fever vaccines should be administered at a minimum interval of 3 weeks. If the vaccines cannot be administered at least 3 weeks apart, they can be administered simultaneously or at any time within the 3-week interval.

Yellow fever vaccine may be given simultaneously with measles, BCG, or hepatitis B vaccines, as well as with IG.

Both Live-Virus and Inactivated-Virus Vaccines

Poliomyelitis

The risk of poliomyelitis is very small in the United States; however, epidemics could occur if the high immunity level of the general population is not maintained by vaccinating children routinely or if wild poliovirus is introduced into susceptible populations in communities with low immunization levels. In the United States, inapparent infection with wild poliovirus strains no longer contributes significantly to establishing or maintaining immunity. Most adults are already immune.

Poliovirus vaccines. Two types of poliovirus vaccines are currently licensed in the United States: OPV and eIPV. A primary vaccination series with either vaccine produces immunity to all three types of poliovirus in >95% of recipients. The primary series of OPV consists of three doses: two doses given 6-8 weeks apart and a third dose given at least 6 weeks and customarily 12 months after the second. The primary series for eIPV consists of three doses: two doses each given 4-8 weeks apart and a third dose given 6-12 months after the second. A primary vaccine series need not be given to adults living in the United States who have not had a primary series as children. However, for adults who have not had a primary series and who are at greater risk of exposure than the general population to wild polioviruses because of foreign travel or health occupation, eIPV is preferred because the risk of OPV-associated paralysis is slightly higher among adults than among children. Poliovirus vaccine is not routinely recommended for persons older than high school age (greater than or equal to 18 years old).

Vaccine indications. Travelers to areas where wild poliovirus is epidemic or endemic should have completed a primary series of poliovirus vaccine. For previously unvaccinated adults, eIPV is indicated. However, if <4 weeks is available before protection is needed, a single dose of OPV or eIPV is recommended. Travelers who have previously received less than a full primary course of OPV or IPV should be given the remaining required doses of either vaccine, regardless of the interval since the last dose and the type of vaccine previously received. Travelers to developing countries who have previously completed a primary series of OPV should receive a single dose of OPV. Those who have previously received a primary series of IPV should receive a dose of either OPV or eIPV. The need for further doses of either vaccine has not been established.

Health-care personnel in close contact with patients who may be excreting wild polioviruses and laboratory personnel handling specimens that may contain wild polioviruses should have completed a primary series of poliovirus vaccine. Because of the slightly increased risk to adults of vaccine-associated paralysis after OPV administration, eIPV is indicated; also, virus may be shed after receipt of OPV vaccine and may inadvertently expose susceptible immunocompromised contacts to live vaccine virus.

Vaccine adverse reactions

Inactivated poliovirus vaccine. No serious side effects of currently available eIPV have been documented. Because eIPV contains trace amounts of streptomycin and neomycin, hypersensitivity reactions are possible among persons sensitive to these antibiotics. Persons with signs and symptoms of an anaphylactic reaction (e.g., hives, swelling of mouth and throat, difficulty breathing, hypotension, or shock) after receipt of streptomycin or neomycin should not receive eIPV. Persons with reactions that are not anaphylactic are not at increased risk and may be vaccinated.

Oral poliovirus vaccine. In rare instances, administration of OPV has been associated with paralysis among healthy recipients and their contacts. Although the risk of vaccine-associated paralytic poliomyelitis is extremely small for immunologically normal vaccinees (approximately one case per 1.4 million first doses distributed and one case per 41.5 million subsequent doses) and for their susceptible immunologically normal household contacts (approximately one case per 1.9 million first doses distributed and one case per 13.8 million subsequent doses), vaccinees should be informed of this risk (20).

Vaccine precautions and contraindications

Inactivated poliovirus vaccine. No convincing evidence of adverse effects of eIPV for the pregnant woman or developing fetus exists; regardless, theoretically vaccination of pregnant women should be avoided. However, if immediate protection against poliomyelitis is needed, OPV, not eIPV, is recommended.

Oral poliovirus vaccine. Unlike other live-virus vaccines that are administered parenterally, OPV is administered orally. IG and other antibody-containing blood products do not appear to interfere with the immune response to OPV.

OPV should not be administered to persons who are or may be immuno- compromised as a result of immune deficiency diseases, HIV infection, leukemia, lymphoma, or generalized malignancy or to persons who are or may be immunosuppressed as a result of therapy with corticosteroids, alkylating drugs, antimetabolites, or radiation. (See "Conditions that Compromise the Immune System.")If polio vaccination is indicated for immunosuppressed patients, their household members, or other close contacts, these persons should be given eIPV rather than OPV. Although OPV has not been harmful when administered to asymptomatic HIV-infected children, eIPV is the vaccine of choice if the patient is known or suspected to be infected. The use of eIPV not only eliminates any theoretical risk to the vaccinee but also prevents the possibility of vaccine virus spread to immunocompromised close contacts. Although a protective immune response cannot be assured in the immunocompromised patient, some protection may be provided.

OPV should not be used for vaccinating household contacts of patients immunocompromised as a result of immune deficiency disease, HIV infection, leukemia, lymphoma, or generalized malignancy or for vaccinating patients immunosuppressed as a result of therapy with corticosteroids, alkylating drugs, antimetabolites, or radiation. If protection is indicated, eIPV should be used for vaccinating household contacts of such patients. OPV should not be given to anyone in a family with a known family history of immunodeficiency until the immune status of all family members is documented.

When children in the household receive OPV, adults who are not adequately vaccinated against poliomyelitis are at a very small risk of contracting OPV-associated paralytic poliomyelitis. Because of the overriding importance of ensuring prompt and complete vaccination of the child and the extreme rarity of OPV-associated disease in contacts of vaccinees, the ACIP recommends the administration of OPV to a child, regardless of the poliovirus-vaccine status of adult household contacts. This is the standard practice in the United States. The responsible adult should be informed of the small risk involved and of the precautions to be taken, such as hand washing after changing a diaper. An acceptable alternative, if there is strong assurance that ultimate, full vaccination of the child will not be jeopardized or unduly delayed, is to vaccinate adults with eIPV or OPV, as appropriate to their immunity status, before giving OPV to the child.

Inactivated-Virus Vaccines

Hepatitis B Virus Infection

The estimated lifetime risk of acquiring HBV infection in the United States is approximately 5% for the population as a whole but may approach 100% for the highest risk groups. Annually, an estimated 300,000 HBV infections occur in the United States, leading to approximately 10,000 hospitalizations and 250 deaths due to fulminant hepatitis B.

In 1988, 89% of HBV cases for which the patient's age was known occurred among persons greater than or equal to 20 years of age. Between 6% and 10% of adults with HBV infection become carriers. The United States currently has 750,000-1,000,000 carriers. Chronic active hepatitis occurs among an estimated 25% of carriers. Each year in the United States, approximately 4,000 persons die of HBV-related cirrhosis and 800 of HBV- related liver cancer.

Hepatitis B vaccine. Two types of HB vaccines are currently licensed in the United States. Plasma-derived HB vaccine consists of a suspension of inactivated, alum-adsorbed 22-nm HBsAg particles that have been purified from human plasma. Although still available, plasma-derived vaccine is no longer being produced in the United States. Currently licensed recombinant HB vaccines are produced by Saccharomyces cerevisiae (common baker's yeast), into which a plasmid containing the gene for the HBsAg has been inserted. These vaccines contain >95% HBsAg protein.

Dosages of vaccines vary with manufacturer and age of the recipient. Package inserts should be consulted for proper dosages. Both types of vaccines are given as three-dose series, with the first two doses given 1 month apart, and the third dose 5 months after the second. An alternative schedule for one vaccine, with three doses 1 month apart followed by a fourth dose 12 months after the first, has been approved for postexposure prophylaxis or for more rapid induction of immunity. However, no clear evidence that this regimen offers greater protection than the standard schedule exists. Duration of protection from HB vaccines is at least 7 years among healthy adults; the possible need for booster doses will be assessed as further information becomes available.

Because the prevalence of HBV infection varies widely among various population groups, serologic screening to detect susceptible individuals before vaccination may or may not be cost effective. Cost-effectiveness depends on the known or expected prevalence of immune individuals in the target population, the cost of screening, and the cost of HB vaccine. Postvaccination testing for immunity is not recommended routinely but is advised for persons whose subsequent management depends on knowing their immune status (dialysis patients and staff) and for those in whom suboptimal response is anticipated (persons with HIV infection and those who have received vaccine in the buttock). When indicated, such testing should be done within 1-6 months after completing vaccination. Postvac- cination testing should also be considered for health-care workers at risk of needlestick exposures. If such testing demonstrates an antibody level <10 mIU/mL, revaccination with one or more doses should be considered.

Vaccine indications. Vaccination is recommended for adults at increased risk of occupational, social, family, environmental, or illness- related exposure to HBV. These include homosexual males, injecting drug users, heterosexual persons with multiple partners or other sexually transmitted diseases, household and sexual contacts of HBV carriers, workers in health-related and public-safety occupations requiring frequent exposure to blood, residents and staff of institutions for the develop- mentally disabled, hemodialysis patients, recipients of factor VIII or IX concentrates, and morticians and their assistants. Inmates in some long- term correctional facilities may also be candidates for vaccination.

Vaccination should also be considered for persons who plan to reside for >6 months in areas with high levels of endemic HBV and who will have close contact with the local population and for travelers intending a short stay who are likely to have contact with blood from or sexual contact with residents of areas with high levels of endemic disease (particularly areas of eastern Asia and sub-Saharan Africa). Such persons should allow 6 months before travel to complete the HB vaccine primary series. The alternative four-dose schedule may offer better protection if three doses can be given before travel.

HB vaccine is intended primarily for preexposure prophylaxis; however, it has been recommended for postexposure use in certain situations, particularly for nonimmune persons who belong to a high-risk group for whom preexposure administration of vaccine is recommended (21). HB vaccine, in combination with HBIG, provides sustained protective levels of antibody and obviates the need for a second dose of HBIG in such exposures. Therefore, a normal series of HB vaccine, combined with a single dose (0.06 mL/kg or 5 mL for adults) of HBIG given at a different site, is recommended for postexposure prophylaxis of nonimmune (and previously unvaccinated) health workers after accidental percutaneous or mucous-membrane exposure to blood containing HBsAg, and after all sexual exposure to HBsAg-positive persons if the first dose of vaccine can be administered within 14 days of sexual exposure or if sexual contact with the infected person will continue.

Vaccine side effects and adverse reactions. The most common side effect observed after vaccination with each of the available vaccines has been soreness at the injection site. Postvaccination surveillance for 3 years after licensure of the plasma-derived vaccine showed an association of borderline significance between Guillain-Barre syndrome (GBS) and receipt of the first vaccine dose (22). The rate of this occurrence was very low (0.5/100,000 vaccinees), and, even if a true side effect, was more than compensated for by disease prevented by the vaccine. Such postvac- cination surveillance information is not available for the recombinant HB vaccines. Early concerns about safety of plasma-derived vaccine, particularly the concern that infectious agents such as HIV present in the donor plasma pools might contaminate the final product, have proved to be unfounded.

Vaccine precautions and contraindications. Pregnancy should not be considered a contraindication to vaccinating women who are otherwise candidates for receiving HB vaccine. Although data are not available on the safety of the vaccine for the developing fetus, HB vaccine contains only noninfectious HBsAg particles and should pose no risk to the fetus. In contrast, HBV infection in a pregnant woman may result in a severe disease for the mother and chronic infection for the newborn.

Influenza

Influenza viruses have continually demonstrated the ability to cause major epidemics of respiratory disease. High attack rates of acute illness and the frequent occurrence of lower respiratory tract complications usually result in dramatic rises in visits to physicians' offices and hospital emergency rooms. Furthermore, influenza frequently infects individuals who, because of their age or underlying health status, are poorly able to cope with the disease and often require medical attention, including hospitalization. Such persons are considered, medically, to be at "high risk" in epidemics. In one recent study, for example, rates of hospitalization for adults with high-risk medical conditions increased during major epidemics by approximately twofold to fivefold in different age groups, reaching a maximum rate of about 800/100,000 population.

Influenza epidemics cause excess mortality that is attributable not only to influenza pneumonia but also to cardiopulmonary disease. Nineteen times in the period 1957-1986 epidemics have been associated with greater than or equal to 10,000 excess deaths. Approximately 80%-90% of the excess deaths attributed to pneumonia and influenza were among persons greater than or equal to 65 years of age during major epidemics.

Influenza has its greatest impact when new strains appear against which most of the population lacks immunity. In these circumstances (e.g., 1957 and 1968), pandemics occur. During pandemics, one-fourth or more of the U.S. population has been affected over a period of 2-3 months.

Because the proportion of elderly persons in the United States is increasing and because age and its associated chronic diseases are risk factors for severe influenza illness, the toll of influenza may also increase unless control measures are used more vigorously than in the past.

Influenza vaccine. Influenza A viruses are classified into subtypes on the basis of two antigens: hemagglutinin (H) and neuraminidase (N). Three subtypes of hemagglutinin (H1, H2, H3) and two subtypes of neuraminidases (N1, N2) are recognized among influenza A viruses that have caused widespread human disease. Immunity to these antigens, especially hemagglutinin, reduces the likelihood of infection and the severity of disease if a person does become infected. However, sufficient antigenic variation (antigenic drift) within the same subtype over time may exist, so that infection or vaccination with one strain may not induce immunity to distantly related strains of the same subtype. Although influenza B viruses have shown much more antigenic stability than influenza A viruses, antigenic variation does occur. As a consequence, the antigenic characteristics of current strains provide the basis for selecting virus strains to be included in the vaccine for a given year.

The potency of present vaccines is such that nearly all vaccinated young adults develop hemagglutination-inhibition antibody titers that usually protect them against infection by strains like those in the vaccine, and often by related variants that emerge. The elderly, the very young, and patients with certain chronic diseases may develop lower antibody titers after vaccination than do young adults. Under these circumstances, influenza vaccine may be more effective in preventing lower- respiratory-tract involvement or other complications of influenza than in preventing upper-respiratory-tract involvement. Influenza vaccine will not prevent primary illnesses caused by other respiratory pathogens.

Vaccine indications. Use of inactivated influenza vaccine is the single most important measure in preventing and attenuating influenza infection. Since 1963, annual vaccination against influenza has been recommended for individuals at high risk of lower-respiratory-tract complications and death after influenza infection (i.e., the elderly and persons with chronic disorders of the cardiovascular, pulmonary, and/or renal systems; metabolic diseases; severe anemia; and/or compromised immune function, including HIV infection). These groups have been identified primarily by review of death certificate data, supported by hospital-based or population-based studies. Within each broadly defined high-risk category, however, some persons are more likely than others to suffer severe complications from influenza infection.

Among nursing-home residents, chronic diseases and other debilitating conditions are common, and influenza can often be spread explosively, with attack rates as high as 60% and case-fatality ratios greater than or equal to 30%.

Medical personnel, while working, may transmit influenza infections to their high-risk patients while they themselves are incubating an infection, undergoing a subclinical infection, or having mild symptoms. Nosocomial outbreaks of influenza have been reported. The potential for introducing influenza to a high-risk group, such as patients with severely compromised cardiopulmonary or immune systems or infants in neonatal intensive care units, should be reduced by targeted vaccination programs of medical personnel.

On the basis of these observations, the previous, broadly defined high- risk adult groups have been assigned further priority for receiving vaccine so that special efforts can be directed at providing vaccine to those who may derive the greatest benefit.

Groups at increased risk for influenza-related complications. To maximize protection of high-risk persons, both the persons at risk and their close contacts should be targeted for organized vaccination programs. These include the following:

1. Persons greater than or equal to 65 years of age.

2. Residents of nursing homes and other chronic-care facilities housing patients of any age with chronic medical conditions.

3. Adults and children with chronic disorders of the pulmonary or cardiovascular systems, including children with asthma.

4. Adults and children who have required regular medical follow-up or hospitalization during the preceding year because of chronic metabolic diseases (including diabetes mellitus), renal dysfunction, hemoglobinopathies, or immunosuppression (including immunosupp- ression caused by medications).

5. Children and teenagers (ages 6 months-18 years) who are receiving long-term aspirin therapy and therefore may be at risk of developing Reye syndrome after an inf