Published: August 2010
Morbidity and mortality from vaccine-preventable diseases remain substantial, particularly in adults. In the United States, between 50,000 and 90,000 adult deaths per year are caused by pneumococcal disease, influenza, and hepatitis B, whereas 300 to 500 deaths in children are caused by vaccine-preventable diseases.1 Research on the reasons for vaccine underuse, and strategies to increase levels of vaccination coverage in the adult population, are areas of active endeavor.2-6
Several national organizations and other groups have provided detailed guides to immunization in adults, regarding both specific vaccines and proposed comprehensive vaccination schedules.1, 5-31 The Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) is the source of many monographs containing definitive recommendations for immunization in general,6,14,24 vaccine adverse effects,17 safety and efficacy of specific vaccines,16, 18-20, 22-23, 25, 26 and vaccination in immunocompromised persons15,27,28 and in health care workers.21 The American Academy of Pediatrics,12,24 the American Public Health Association,13 the Infectious Diseases Society of America,9,10 the American College of Physicians—American Society of Internal Medicine,9,11 the American Medical Association,24 and the American Association of Family Physicians24 have all participated in the formulation of guidelines for immunization. The Institute of Medicine (IOM) has convened a panel of experts to review specific vaccine safety issues,29 and the National Coalition for Adult Immunization30 has been formed for the purpose of increasing vaccination coverage and meeting national Healthy People goals.31 The U.S. Preventive Services Task Force has included immunizations among the recommendations for general preventive measures.6 Detailed recommendations for adult immunization have also been issued by the Mayo Vaccine Research Group.1 The March 2001 issue of Infectious Disease Clinics of North America was devoted to “Vaccine Recommendations: Challenges and Controversies.” This compendium of reviews by experts is highly recommended for additional in-depth reading on these topics.7, 8, 32, 33
In 1994, the National Vaccine Advisory Committee (NVAC) reported on the status of adult vaccination in the United States and cited missed opportunities to vaccinate adults during health care visits.5 The American College of Physicians Task Force on Adult Immunization and the Infectious Diseases Society of America (IDSA) recommended linking an assessment of vaccination status with other preventive measures at age 50 years.9 This approach has been endorsed by the ACIP of the CDC, which recommends that all primary care physicians schedule a prevention visit at age 50 years,34 at which time the patient’s vaccination status can be reviewed, tetanus-diphtheria toxoid vaccine can be updated, and it can be determined whether the patient has an indication for the pneumococcal vaccine,22 initiation of annual influenza vaccination, or both. The preventive visit at age 50 is all the more important because new recommendations from the CDC include influenza vaccination annually, beginning at age 50.23
In 1991, the U.S. Public Health Service introduced national goals for health promotion and disease prevention under the heading of Healthy People 2000.31 At the start of this campaign, in the 50- to 64-year-old age group, only 9% and 15% of persons with cardiac or pulmonary high-risk conditions, respectively, had ever received pneumococcal vaccination, and only 21% and 28%, respectively, had received influenza vaccine the previous year,34 although vaccination levels were higher in the over-65 age group.34 The Healthy People 2000 national goals included an increase to 60% vaccination levels for these vaccines. Although many states met this objective with regard to influenza vaccination, pneumococcal vaccine coverage lagged considerably behind. The recently released Healthy People 2010 goals include achievement of 90% pneumococcal vaccination coverage in older adults and high-risk younger individuals.32
Current ACIP recommendations for adult immunization, endorsed by the IDSA and many of the above organizations, are summarized in Table 1.
|Measles-mumps-rubella (MMR)*,†||Two doses for persons born after 1956 who are at high risk of exposure; one dose for persons born after 1956 who are at low risk of exposure.|
|Tetanus-diphtheria* and tetanus-reduced diphtheria-acellular pertussis (Tdap)19||Tetanus-diphtheria primary series consisting of first dose, second dose after 1 mo, and third dose 6-12 mo later, followed by a booster every 10 yr or once at age 50 yr; substitute Tdap for Td booster for adults ages 19-64; health care workers or those in close contact with infants should receive Tdap even if Td received within 10 yr|
|Influenza‡,§||Annual vaccination (see text)|
|Pneumococcal‡,¶¶||One vaccination, with possible revaccination after 6 yr or more (see text)|
|Hepatitis B¶¶,**||First dose, followed by second dose 1-2 mo later, third dose 5 mo later|
|Varicella¶,†† and zoster vaccine38||Varicella vaccine for seronegative, nonimmunocompromised adults-first dose, followed by second dose 1-2 mo later|
|Zoster vaccine for nonimmunocompromised adults age 60 yr and older-single dose|
|Hepatitis A¶¶,‡‡||First dose, followed by second dose 6-12 mo later|
|Human papillomavirus vaccine||Three doses for girls ages 11-12 yr, with catch-up vaccination for girls and women ages 13-26 yr|
Used with permission from Gershon AA, Gardner P, Peter G, et al: Quality standards for immunization. Clin Infect Dis 1997;25:782-786.
Copyrighted 1997, University of Chicago.
¶ For all adults in high-risk groups.
* For all adults lacking immunity.
† Adults born in or before 1956 are considered naturally immune; adults born after 1956 should receive one dose of MMR vaccine; some adults, such as college students, persons working in health care facilities, and international travelers, may need two doses.
‡ For all adults 65 yr of age and older and for persons with chronic illnesses (all adults 50 yr of age and older, as per updated recommendations for influenza).
§ Includes other persons at high risk, such as those with chronic cardiopulmonary disease, chronic metabolic diseases (including diabetes mellitus), chronic renal dysfunction, hemoglobinopathies, and immunosuppression, as well as residents of long-term care facilities, providers of home health care or health care to high-risk persons, and others who wish to avoid influenza.
¶¶ Includes younger individuals with high-risk conditions such as cardiopulmonary disease, diabetes, alcoholism, chronic liver disease, chronic renal failure, or cerebrospinal fluid leaks or immunocompromise because of conditions such as splenic dysfunction or asplenia, Hodgkin's disease, lymphoma, multiple myeloma, nephrotic syndrome, and organ transplantation. Revaccination should be considered for persons at highest risk who have received the 14-valent vaccine or the 23-valent vaccine 6 years or more previously.
** Includes those who are exposed to blood and blood products during their work (e.g., health care workers), clients and staff of institutions for the developmentally disabled, hemodialysis patients, sexually active homosexual or bisexual males, injection drug users, recipients of certain blood products such as factor VIII and IX concentrates, household and sexual contacts of hepatitis B virus (HBV) carriers, sexually active heterosexual individuals with multiple partners or a recent episode of a sexually transmitted disease, inmates of long-term correctional facilities, individuals from high-risk populations (e.g., Pacific Islanders, Alaskan natives, and first-generation immigrants and/or refugees from countries where HBV infection is of high or intermediate endemicity), and international travelers planning prolonged visits to areas with high rates of hepatitis B infection.
†† Includes susceptible persons who may be at increased risk of exposure or who have close contact with persons at high risk for serious complications from varicella infection, including health care workers, susceptible family contacts of immunocompromised individuals, teachers of young children, daycare workers, residents and staff in institutional settings, college students, inmates and staff of correctional institutions, military personnel, nonpregnant women of childbearing age, and international travelers.
‡‡ Includes persons traveling to or working in countries with high rates of hepatitis A virus (HAV) infection, persons who live in communities with high rates of HAV infection (e.g., Native Americans, Alaskan natives, and Pacific Islanders), homosexual and bisexual males, injection drug users, persons with chronic liver disease, and food handlers (optional.)
The complex issues surrounding pneumococcal vaccination have been well summarized by Poland.32 The pneumococcus bacteria is responsible for 500,000 cases of pneumonia, 50,000 cases of sepsis, 3,000 cases of meningitis, 40,000 deaths, and 7 million cases of otitis media annually in the United States. Unfortunately, pneumococcal vaccination is severely underused. The 23-valent pneumococcal polysaccharide vaccine, licensed in 1980, contains the serotypes responsible for 85% to 90% of invasive pneumococcal disease in adults, including the six pneumococcal serotypes, which are most frequently drug resistant.32 The reported efficacy of the pneumococcal polysaccharide vaccine has ranged from 55% to 80% and varies between different risk groups, but its benefits in preventing invasive disease are significant despite less than 100% efficacy.32 A 7-valent conjugated pneumococcal vaccine was licensed in 2000 and has been recommended for young children, for whom it is more immunogenic than the standard vaccine, but data in adults are limited.32
Current ACIP recommendations22 (see Table 1.) state that the pneumococcal vaccine should be administered to all adults age 65 years or older; individuals ages 2 to 64 years with chronic cardiovascular or pulmonary disease, diabetes, alcoholism, chronic liver disease, cerebrospinal fluid (CSF) leaks, functional or anatomic asplenia, who are immunocompromised, and those in high-risk environments, including residents of nursing homes or long-term care facilities, Alaskan natives, and Native American populations (who have high rates of pneumococcal disease). Reimmunization is recommended after 5 years, in patients older than 65, if the patient is immunocompromised, has chronic renal failure or nephrotic syndrome, has had organ or bone marrow transplantation, or had the first dose before age 65. Patients ages 10 to 65 years with splenic dysfunction or who are immunocompromised should receive reimmunization after 5 years.22
One report has highlighted the fact that smoking is a major risk factor for pneumococcal disease.35 Given that approximately one third of adults smoke, and other risk factors are common in the age 50 to 64 group, some experts have anticipated that recommendations for universal pneumococcal vaccination may be extended to the age 50 to 64 group in the future, analogous with influenza vaccination.32 As with influenza vaccine, strategies such as standing orders at hospital discharge and in long-term care facilities have the potential to increase pneumococcal vaccination levels significantly.6
Tetanus and diphtheria are rare diseases in the United States today. However, there has been a recent widespread outbreak of diphtheria in the states of the former Soviet Union, prompting concerns about the possibility of transmission to other populations with waning immunity, such as older adults in the United States. The tetanus-diphtheria toxoid vaccine (Td) is composed of bacterial toxins rendered inactive by chemical treatment. It is safe and efficacious and is currently recommended to be administered as a booster every 10 years, or earlier if a tetanus-prone wound occurs.19 Some experts have questioned the need for a booster every 10 years, instead recommending a single booster dose at midlife for persons who previously received a full primary immunization series.7 For individuals not previously immunized, a three-dose primary series should be administered (see Table 1.).
In recognition of the underreported burden of pertussis in adults, a new vaccine—tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap)—was licensed in 2005 in the United States for those ages 11 to 64 years. In 2006, the ACIP recommended that adults ages 19 to 64 should receive a single dose of Tdap in place of a Td booster if their last dose of Td was 10 years previously or earlier. Tdap can also be given even if the Td dose was more recent if protection against pertussis is desired. This is particularly important for health care workers and those expected to have close contact with an infant younger than 12 months.19
Meningococcal vaccine is a polysaccharide vaccine that covers serogroups A, C, Y, and W-135, but not B. This vaccine is not required for all adults. Recent recommendations from the American College Health Association and the ACIP20 have encouraged physicians to inform incoming college freshmen about the vaccine. The risk for meningococcal disease is higher among college freshmen than in other college students.
Arguments for and against routinely vaccinating college-bound freshmen have been summarized by Gordon36; these include the devastating nature of the illness, safety and efficacy of the vaccine, higher risk among college freshmen, experience with vaccination of military recruits, and the fact that the serogroup distribution in the United States is moving toward those serotypes covered by the vaccine. Arguments against routine vaccination of freshmen include the cost of the vaccine ($54-$88/person) for 2 million incoming freshmen and 500,000 freshmen already living in dormitories, the lack of protection against serogroup B, decline of antibody levels over 2 to 3 years, and only 5% of all cases occurring in college students.36 At present, counseling and offering the vaccine to interested incoming and current freshmen are recommended, but administration of the vaccine is not required.20
There are fewer cost-effective, efficacious medical interventions subject to more mythology than the influenza vaccine. Barriers to immunization include patient concerns about potential adverse effects or induction of illness, or both. Sadly, these concerns are reinforced by some clinicians. In actuality, the trivalent influenza vaccine is extremely safe and effective. It is an inactivated vaccine, not a live vaccine, and therefore cannot transmit infection. Since the swine flu vaccine of 1976, no vaccine preparations have been associated with a significantly increased risk of Guillain-Barré syndrome.33 The trivalent influenza vaccine is composed of two strains of influenza A and one strain of influenza B, which are the strains predicted to be circulating during the upcoming influenza season. Because these strains vary from year to year, annual immunization is recommended. Allergic hypersensitivity to egg proteins is a contraindication.
Influenza accounts for approximately 20,000 deaths and 200,000 hospitalizations each year, and is also responsible for many days of work lost and many visits to health care providers.33 About 10% of adults develop influenza each year.33 The burden of illness is most significant in older adults, in whom mortality can result from postinfluenza bacterial pneumonia and exacerbations of cardiopulmonary conditions.33 The efficacy of influenza vaccine has been estimated to be 70% to 90% in healthy persons23 and, although lower in older adults, it still has significant benefit in the prevention of overall mortality.23 Although past recommendations focused on those 65 years of age and older, and younger individuals with chronic medical conditions, the most recent ACIP recommendations target persons 50 years of age and older, because it has been noted that age-based recommendations result in higher immunization rates than risk-based recommendations. Immunization continues to be recommended for persons younger than 50 years who are residents of nursing homes or other chronic care facilities or who have chronic cardiac or pulmonary conditions or chronic metabolic disease, including diabetes, renal dysfunction, hemoglobinopathies, or immunosuppression. In addition, women who will be in the second or third trimester of pregnancy during the influenza season, and children and adolescents receiving long-term aspirin who are at risk for Reye’s syndrome, are among those for whom vaccination is recommended.23
A live, attenuated, trivalent intranasal vaccine for influenza has also been licensed for healthy individuals ages 5 to 49 years. This vaccine is not recommended for those who are immunocompromised.
Strategies for increasing immunization rates are of paramount importance6 (see later). The importance of immunization of health care workers cannot be overemphasized. Immunosuppressed patients such as transplant recipients may not develop adequate antibody titers after immunization, and are at risk for nosocomial transmission of influenza when hospitalized during the influenza season, as well as for community-acquired infection. Therefore, immunization of health care workers and family members can be an effective means of augmenting the protection of immunocompromised patients.
The varicella vaccine is a live, attenuated vaccine that provides long-lasting immunity. Although most adults are seropositive from prior infection, seronegative adults are susceptible to varicella primary infection, which is often more severe in adults than in healthy children. Current recommendations are to immunize susceptible adults (not immunocompromised adults), with priority given to those at increased risk of exposure or those who could expose persons at risk for serious complications of varicella. These groups include seronegative health care workers, family members of immunocompromised patients, teachers and child care workers, residents and staff of long-term care facilities or prisons, college students, military personnel, nonpregnant women of childbearing age, adolescents and adults in households with children, and international travelers.10,16 Because the varicella vaccine is a live vaccine, it is not administered to immunocompromised patients. Although the fraction of those vaccinated who develop a rash after vaccination could theoretically transmit the vaccine strain of the virus to household contacts, such transmission is considered to be unlikely and the disease would most likely be mild. In addition, the risk of exposing an immunocompromised family member to actual varicella is much more serious, so administration of the varicella vaccine to seronegative household contacts of immunocompromised patients is encouraged rather than contraindicated.12
Postexposure prophylaxis with varicella-zoster immune globulin (VZIg) is not recommended routinely for all susceptible adults exposed to varicella, but is indicated for immunocompromised or pregnant seronegative patients. VZIg should be given within 96 hours for maximum effectiveness.13,16 Some clinicians also administer antiviral therapy to exposed seronegative immunocompromised patients.
Herpes zoster (shingles) is caused by re-activation of the varicella virus. In addition to the pain of the acute zoster episode, post-herpetic neuralgia is a major cause of chronic pain, particularly in older adults. A live attenuated vaccine for shingles prevention has been licensed on the basis of a placebo-controlled trial of over 38,000 adults, in whom zoster vaccine was associated with a reduction in zoster from 11.1 to 5.4 cases per 1000 person-years.37 The ACIP has provisionally recommended a single dose of zoster vaccine for administration to adults 60 years of age and older, whether or not they have had a prior zoster episode.38 The vaccine is contraindicated for immunocompromised and pregnant patients, and those on immunosuppressive medications or with active tuberculosis.
The measles-mumps-rubella (MMR) vaccine is a live vaccine that prevents potentially serious diseases, including congenital rubella syndrome. A measles outbreak between 1989 and 1991 in undervaccinated inner city residents was a reminder that these diseases remain a threat and reinforced the need to maintain high immunization levels in the general population. Persons born before 1956 are considered to have natural immunity to these infections. Traditionally, a single dose of MMR vaccine was given, but more recent childhood recommendations are for two doses, one at 12 to 15 months and the second at 4 to 6 years or 11 to 12 years, because immunity can wane after a single dose. For adults born after 1956 who are not immune, a single dose of MMR should be administered, but high-risk groups such as college students, health care workers, and international travelers should receive two doses.10 Because MMR is a live vaccine, it is not generally administered to immunocompromised patients, with the exception of HIV patients with early disease27and stable bone marrow transplant (BMT) recipients 2 years or more after transplantation without graft-versus-host disease.28
There are currently two formulations of hepatitis A vaccine, which are inactivated, safe, and immunogenic. Administration of a two-dose series is recommended for adults in high-risk groups, which include international travelers, residents of communities with high rates of infection (Native Americans, Alaskan natives, and Pacific Islanders), homosexual and bisexual men, injection drug users, persons with chronic liver disease, and food handlers.10 Persons with chronic liver disease appear to be particularly susceptible to fulminant disease when they develop hepatitis A infection and should be high-priority candidates for vaccination.39
Two formulations of recombinant hepatitis B vaccine are available in the United States. Recently, the ACIP released a comprehensive strategy to prevent transmission of hepatitis B virus (HBV) in the United States.26 A strategy of vaccinating high-risk groups was devised originally, but current recommendations are for universal infant vaccination and catch-up vaccination of nonimmune older children and adolescents. For adults, high-risk groups should be the top priority for vaccination, with a three-dose series. These groups include health care workers and others who may be exposed to blood and blood products, residents and staff of long-term care facilities or prisons, homosexual or bisexual men or heterosexuals with multiple partners, injection drug users, recipients of clotting factor concentrates, household or sexual contacts of HBV carriers, and persons from high-risk populations (Pacific Islanders, Alaskan natives, and immigrants from countries of high endemicity).10 International travelers planning lengthy stays in endemic areas should be vaccinated.
Human papillomavirus (HPV) is the cause of anogenital warts and is associated with cervical cancer in women and other anogenital cancers in men and women. It has been estimated that 6,200,000 new cases of HPV infection occur every year in the United States.40
The HPV vaccine was recently licensed for girls and young women ages 9 to 26 years, with recommended immunization at age 11 to 12 years using a three-dose series, and catch-up vaccination for girls and women 13 to 26 years who have not yet received it. The ideal time to vaccinate is before the onset of sexual activity, but women who have been infected with one type of HPV may benefit from prevention of infection with the other types included in the vaccine. The components are antigenic materials related to HPV types 6, 11, 16, and 18. Types 6 and 11 are responsible for 90% of anogenital warts, whereas types 16 and 18 are associated with cervical cancer. The vaccine is not live and can be given to immunocompromised patients, although its efficacy in those who are immunocompromised is unknown.
With the events of the past few years, attention has been focused on the possibility of deliberately induced larger outbreaks of infectious diseases. Vaccines exist for some of the pathogens mentioned as possible agents of bioterrorism, including anthrax, smallpox, and plague (Yersinia pestis). The Working Group on Civilian Biodefense has published recommendations for the management of anthrax41 and smallpox42 as public health threats, and updated information on all topics related to bioterrorism can be found on the CDC website.43 The anthrax vaccine is a cell-free inactivated vaccine given in a six-dose series, and is currently available in the United States only for military personnel or certain high-risk persons, such as laboratory workers working directly with Bacillus anthracis.13 Currently, efforts to manufacture much larger numbers of doses of vaccine are underway. The safety of the vaccine remains a controversial issue. The CDC website43 has up-to-date information on the indications for and safety of anthrax vaccine.
Smallpox was the first disease for which vaccination was found to be effective. It now has been certified as eradicated, with the last naturally acquired case in the world having occurred in 1977. However, the specter of smallpox has again been raised with the threat of bioterrorism. The current vaccine for smallpox is derived from vaccinia virus, which is a live attenuated viral vaccine, of which supplies are currently limited and not available for the general public.13 During the era when smallpox vaccination was universal, adverse reactions to the vaccine were not uncommon, including neurologic effects, and inadvertent vaccination of immunocompromised patients sometimes resulted in severe progressive or disseminated vaccinia infection.44 Current efforts are focused on dramatically increasing the production of smallpox vaccine and the development of measures to render the vaccine safer.
An inactivated whole cell bacterial vaccine is available for the prevention of bubonic plague, but may not be effective against pneumonic plague.13 It is currently recommended only for persons at high risk, such as laboratory workers working with the organism.
Bacillus Calmette-Guérin (BCG) vaccination is not routinely recommended in the United States for the prevention of tuberculosis, although it is administered to children in many other countries in which the prevalence of tuberculosis is higher. BCG is a live attenuated vaccine that should not be administered to immunocompromised persons, including those with HIV. The efficacy of BCG vaccine for prevention in adults has varied in different studies, and currently is recommended in the United States only for the following: infants and children who live where the likelihood of TB transmission is high; and health care workers highly likely to be exposed to multidrug-resistant TB (MDR-TB) in settings where other TB prevention measures have failed. If the incidence of MDR-TB rises, these indications could be expanded in future.25
There are currently three rabies vaccines licensed in the United States; the human diploid cell vaccine (HDCV) is most commonly used. It is indicated for pre- and postexposure prophylaxis in conjunction with rabies immune globulin (RIg). Persons at high risk because of potential occupational exposure or travel are candidates for pre-exposure prophylaxis.13
Vaccines for international travel are discussed in more detail elsewhere in this section (“Travel Medicine for the Primary Care Physician”).
Given the morbidity and mortality of vaccine-preventable diseases in adults, and the documented underuse of safe and cost-effective vaccines, it is appropriate that significant attention has been drawn to strategies to increase vaccination rates.1-6, 30-34 Many organizations involved in the development of guidelines for immunization have published or endorsed such measures. Standing orders at hospital discharge or in long-term care facilities have the potential to increase opportunities for vaccination. Within the context of individual clinical practices, patient reminder or recall systems have been found to be effective. More educational materials for clinicians and patients and other interventions are actively promoted by organizations such as the National Coalition for Adult Immunization; details can be found on their website.30
Adult immunizations are extremely important. Guidelines for immunization standards from national organizations should be implemented and the preventive visit at age 50 should be used to update vaccination status. Interventions such as standing orders at hospital discharge and in long-term care facilities should be pursued. Educational efforts to reduce barriers to vaccination for clinicians and patients should be actively pursued. Changing guidelines for vaccination can be found in the recommendations of the Advisory Committee on Immunization Practice, which are frequently updated. Further information and recommendations for vaccines against agents of bioterrorism will undoubtedly be forthcoming.