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Immunization for the Elderly MAZEN S. BADER, MD, MPH ABSTRACT: The morbidity and mortality of vaccinepreventable diseases among older adults are high. Despite the benefits of elderly vaccination, vaccination rates remain low and especially among some minority groups. Specific strategies for improving the rate of vaccination have been developed for medical offices and clinics, hospitals, and other health care institutions. There are vaccines that are recommended routinely for the elderly while other vaccines are recommended in certain circumstances. Knowing the indications, contraindications, and adverse reactions to the recommended vaccines for the elderly is very important to the primary care physicians. KEY INDEXING TERMS: Immunization; Elderly; Influenza; Pneumococcal vaccine; Herpes-zoster vaccine. [Am J Med Sci 2007;334(6):481–486.] I number of older persons is increasing, particularly persons ages ⬎85 years.5 Influenza-related deaths can result from pneumonia and from exacerbations of cardiopulmonary conditions. Influenza and its complications can be prevented with either influenza vaccination or antiviral prophylaxis with neuroaminidase inhibitors. Prevention of influenza with neuroaminidase inhibitors is only supportive to the vaccine because of its lower cost-to-benefit ratio. Immunity to the surface antigens, particularly the hemagglutinin, by inducing specific antibody production reduces the likelihood of infection and severity of disease if infection occurs.6 The effectiveness of inactivated influenza vaccine depends primarily on the age and immunocompetence of the vaccine recipient, and the degree of similarity between the viruses in the vaccine and those in circulation. Older persons might have lower postvaccination antibody titers than healthy young adults and can remain susceptible to influenza virus infection and influenza-related upper respiratory tract illness.7 In the 40% to 60% of elderly patients in whom the influenza vaccine produces the desired immunity, an effective immune response can be mounted within 10 to 14 days of vaccination.8 Prevaccination titers and the number of previous influenza vaccinations have been identified as factors that influence postvaccination titers. Having one or more vaccinations over the previous 4 years confers greater reduction in mortality than first-time immunization.9 Among older persons who reside in nursing homes the vaccine can be 50% to 60% effective in preventing influenza-related hospitalization or pneumonia, 80% effective in preventing influenza-related death, and 30% to 40% effective in preventing influenza illness.10 However, the effectiveness of influenza vaccine in community-dwelling elderly is modest.11 Moreover, economic studies of influenza vaccination in persons older than 65 years conducted in the nfectious diseases, particularly influenza and pneumonia, are the fifth leading cause of death among older adults.1 Immunization is one of the most effective means of preventing disease, disability, and death from infectious diseases. By the time most people reach old age, they have been immunized or exposed to many disorders. Nonetheless, they still need immunizations. Despite the benefits of elderly vaccination, vaccination rates remain low and especially among some minority groups. Influenza vaccination coverage among adults ages ⬎65 years is 65% which remain below the Healthy People 2010 objective of 90% coverage nationwide. Despite increase in the pneumococcal vaccination coverage among adults ages ⱖ65 years from 1997 to 2005, 25% of older adults have reported never having received pneumococcal vaccine.2 Strategies for increasing vaccination rates among older adults are summarized in Table 1.3 In this review we will focus on the routinely recommended vaccinations for elderly individuals (Table 2). Influenza Vaccine Although influenza is a very common, moderate, and self-limited viral infection, it could be seriously complicated in elderly. Approximately 90% of influenza-related deaths occur among adults ages ⱖ65 years.4 In the United States, the number of influenzaassociated deaths has increased in part because the From the Division of Infectious Diseases, Memorial University School of Medicine, St. John’s, Newfoundland, Canada. Submitted May 18, 2007; accepted in revised form July 27, 2007. Correspondence: Dr. Mazen S. Bader, Memorial University of Newfoundland Health Sciences Center, 300 Prince Phillip Drive, 1J426, St. John’s, NL A1B3V6. Canada (E-mail: msbader1@ hotmail.com.). THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES 481 Immunization for the Elderly Table 1. Interventions to Increase Vaccination Rates Among Older Adults* Intervention Comments Patient reminder/recall systems Reminders that vaccinations are due or late through telephone calls, letters, or postcards This can include free vaccination and insurance coverage Reducing distance from setting to patients Expanding access through more convenient hoursProviding vaccination in the inpatient settings Providing a well-publicized day for free influenza vaccination of all employees at the work site (hospital, long-term care facility) This can include both vaccines administration and education Reminders to who administer vaccinations that patients are due or overdue through patient’s chart, computer, and mail This involves assessing the performance of providers in delivering recommended vaccines to their patients and giving this information to the providers This involves administration of vaccines to patients by nonphysician medical personnel through a protocol without physician involvement at clinics, hospitals, and nursing homes Reducing out-of-pocket costs Expanding access in medical or public health clinical settings Home visits Provider reminder Assessment and feedback for vaccination providers Standing orders * References 3. United States have reported overall societal cost savings.5 There are 2 types of licensed influenza vaccines in the United States: inactivated influenza vaccine and live attenuated inhaled influenza vaccine. Live attenuated inhaled influenza vaccine (FluMist) has not been approved in persons ages 50 years and older.5 The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) recommends annual influenza vaccination for all adults ages 50 years and older and for all residents of long-term care facilities.5 Immunization should be administered shortly before the anticipated onset of influenza season. In the United States, this usually corresponds to mid-October through mid-November. However, health-care providers should continue to offer influenza vaccine during December and throughout the influenza season, even after influenza activity has been documented in the community. The committee also recommends vaccination for persons who could transmit influenza to elderly patients, such as healthcare personnel, employees of long-term care facilities, providers of home care to people at high risk, and household contacts (includ482 ing children). Vaccination of healthcare workers has been associated with fewer deaths among nursing home patients.12 Inactivated influenza vaccine is most commonly associated with mild local reactions such tenderness at vaccination site. Systemic symptoms (eg, fever, malaise, myalgia, and headache) are rare among vaccinated older adults. Immediate, presumably allergic, reactions (eg, hives, angioedema, allergic asthma, and systemic anaphylaxis) rarely occur after influenza vaccination. These reactions probably result from hypersensitivity to residual egg protein or thimerosal, which is a mercurial antibacterial agents acting as a preservative. The currently licensed inactivated influenza vaccine has either no or minimal amount of thimerosal mercury, ⬍1.25 h Hg/0.5 mL dose, except the 5.0-mL multidose vial which contains approximately 25 h Hg of mercury as a preservative.5 Persons with a history of severe hypersensitivity, such as anaphylaxis, to eggs should not receive influenza vaccine.5 Evidence for a causal relation of Guillian-Barre syndrome (GBS) with influenza vaccine is unclear. The potential benefits of influenza vaccination in preventing serious illness, hospitalization, and death among older adults substantially outweigh the possible risk for experiencing vaccine-associated GBS.5 Pneumococcal Vaccine Pneumococcal disease is a significant cause of morbidity and mortality in the elderly. The case fatality rate of invasive pneumococcal disease increase from 20% for those ages ⱖ65 years to 40% for those ages ⱖ85 years.13 The currently available pneumococcal polysaccharide vaccine (PPV) includes 23 purified capsular antigens. These serotypes in the vaccine represent 85% to 90% of serotypes that cause invasive pneumococcal disease in the United States.14 Pneumococcal capsular polysaccharide antigens induce typespecific antibodies that enhance opsonization, phagocytosis and killing of pneumococci by leukocytes. The antibodies against pneumococcal antigens remain elevated for at least 5 years in healthy adults.15 The vaccine protects against invasive pneumococcal diseases such as bacteremia, pneumonia with bacteremia, and meningitis. However, it is less effective for preventing pneumonia without bacteremia.16 The vaccine should be regarded as 23 different vaccines, rather than 1. Older persons who fail to respond to one serotype may well be protected against infection by the other 22 serotypes. Pneumococcal vaccination was found to cost-saving among adults ages ⱖ65 years.17 The vaccine is administered intramuscularly, not intradermally which can cause severe local reaction. It can be administered with other vaccines such as influenza vaccine, but at a separate site. ApproxiDecember 2007 Volume 334 Number 6 Bader Table 2. Routinely Recommended Vaccines for the Elderly* Pneumococcal Polysaccharide Vaccine Inactivated Influenza Vaccine Type of vaccine Killed or inactivated virus Indications for vaccination All adults ⱖ50 years of age Contraindication for vaccination Severe hypersensitivity reaction to the vaccine or eggs Revaccination schedule Annually Varicella-Zoster Vaccine Tetanus and Diphtheria Vaccine 23-Valent purified bacterial capsular polysaccharides All adults ⱖ65 years of age Live attenuated virus Bacterial toxoids All adults ⱖ60 years of age Severe allergic reaction to the vaccine All previously unvaccinated adults Patients with contaminated wound if ⬎5 years have elapsed since last dose Severe allergic reactions to the vaccine Immunocompromised adults such as those with leukemia, lymphoma, or generalized malignancy and in patients receiving chemotherapy, radiation, and large doses of corticosteroids. Persons with active, untreated tuberculosis and with anaphylactic reaction to neomycin or gelatin None Every 10 years One-time revaccination after 5 yr for adults ⱖ65 years of age if first dose before age 65 Intramuscular injection Intramuscular injection Subcutaneous injection Route of administration Can be given Yes simultaneously with other vaccines Yes Yes Yes * References 4, 13, 17, 25, and 29. mately one-third of persons who receive pneumococcal vaccine develop mild local side effects such as erythema, pain, or swelling. These local side effects are more common with revaccination with pneumococcal polysaccharide vaccine than with initial vaccination. Systemic reaction such as fever and myalgias are very rare.14 PPV is recommended for all persons 65 years and older. The ACIP does not recommend routine revaccination with the vaccine every 5 years. The ACIP recommends that persons ages 65 years and older who were initially vaccinated before age 65 should receive only one revaccination provided that at least 5 years have elapsed since the initial vaccination. Furthermore, 1-time revaccination after 5 years is recommended for older adults with chronic renal failure or nephritic syndrome, immunosuppressive conditions such as leukemia, lymphoma, generalized malignancy, organ or bone marrow transplantation, and multiple myeloma, or chemotherapy with alkylating agents, antimetabolites, or highdose, long-term corticosteroids.18 The 7-valent conjugate pneumococcal vaccine is not recommended for older adults. However, vaccination of young children with the conjugate pneumococcal vaccine has significantly reduced the inciTHE AMERICAN JOURNAL OF THE MEDICAL SCIENCES dence of pneumonia caused by only the 7 conjugate vaccine serotypes among older adults.19 Herpes Zoster Vaccine Varicella-zoster virus (VZV) causes chickenpox as a primary infection and herpes zoster (HZ) or shingles as a reactivation form of the infection. About 25% of people develop zoster during their lifetime, and there are about 1 million cases of shingles per year. The risk is highest in the elderly, where more that two-thirds of cases occur in people over the age of 50 years.20 Postherpetic neuralgia (PHN) is the most debilitating complication of HZ. Both the incidence and the duration of postherpetic neuralgia are directly related to increasing age.21 This increase in the incidence of zoster among older adults is due to a decline in specific cell-mediated immune responses to (CMI) VZV with advancing age. A single dose of live attenuated zoster vaccine substantially reduced the risk for HZ (by 51%) and PHN (by 67%) by increasing VZV-specific CMI in older adults 60 years of age and older over 5.5 years. The vaccine is not 100% effective in preventing HZ. However, cases of HZ and PHN after vaccination appear to be much milder than in those people who develop HZ in the 483 Immunization for the Elderly absence of vaccination. The vaccine was more efficacious in preventing HZ among persons who were 60 to 69 years of age than among those who were 70 years or older. On the other hand, the vaccine prevented postherpetic neuralgia to a greater extent among adults ages 70 or more years.22 VZV vaccination improved the quality of life among older adults because of prevention of both acute pain associated with HZ and postherpetic neuralgia. The cost-effectiveness of the varicella zoster vaccine varies substantially with patient age and often exceeds $100,000 per quality-adjusted life-year saved.23 The ACIP has recommended people age 60 and older receive zoster vaccine (Zostavax) once regardless of previous history of chickenpox or HZ.24 It is administered subcutaneously as a single 0.65-mL dose. It must be stored in a freezer with an average temperature of –15°C (5°F) and should not be used if a temperature deviation above –5°C (23°F).25,26 If the vaccine is not used with 30 minutes after reconstitution with the supplied diluent, it should be discarded. Although the current recommendation is to vaccinate the elderly once with Zostavax, it is not clear how long the boosted immunity will last and whether an additional booster vaccination will be required. The current vaccine resulted in increased VZV-specific CMI for up to 5 years.27 It is contraindicated in people with active, untreated tuberculosis and in immunocompromised adults such as those with leukemia, lymphoma, or generalized malignancy and in patients receiving chemotherapy, radiation, and large doses of corticosteroids. The vaccine should not be administered to persons with a history of anaphylactic reaction to gelatin, neomycin, or any other vaccine component. In general, adverse reactions associated with Zostavax are limited to injection-site reactions, such as pain, erythema or swelling, itching, and headache. Rarely, zosteriform rash due to preexisting wild-type virus has been reported at the injection site within the first 42 days after vaccination. Cardiac events occurred more often among the vaccine recipients than among the placebo recipients.28 Tetanus Toxoid Tetanus in the United States is most commonly reported in older persons who are less likely to be adequately vaccinated than younger persons. In 2004, 47% of the 34 cases reported were among persons ⬎60 years of age. 94% of persons who contract tetanus in the United States are not up-to-date on tetanus vaccination or have never received the primary series.29 Tetanus toxoid consists of a formaldehyde-treated toxin. There are 2 types of toxoids available, adsorbed toxoid and fluid toxoid and adsorbed toxoid is preferable because of higher and longer standing antitoxin titers. Tetanus toxoid is combined with diphtheria toxoid in the adult vac484 cine, Td, or with both reduced diphtheria toxoid and acellular pertussis, Tdap.18,30 Tdap is not licensed for use among adults ages ⱖ65 years. Routine boosters are recommended every 10 years for all persons, including older adults 65 years and older, because antitoxin titers approach the minimal protective level by 10 years after the last dose. Although Tdap is the recommended booster vaccine for tetanus in adults ages 19 to 64, Td is still the recommended one for adults 65 or older.18 In a small percentage of individuals, antitoxin titers fall below the protective level within 10 years of last booster. Therefore, persons who sustain a wound that is other than clean and minor should receive a tetanus booster if more than 5 years have elapsed since their last booster. For individuals who were never vaccinated against tetanus, a primary series of 3 doses is recommended (0 month, 1 month, 6 to 12 months).18 Local adverse reactions such as erythema and tenderness are common and often self-limited. An extensive local reaction presented 2 to 8 hours after vaccination as extensive painful swelling of injection site is rare. It is more common in adults who have received frequent doses of tetanus toxoid. Brachial neuritis and Guillian-Barre syndrome, although very rare, is associated with Td vaccination. Td is contraindicated in individuals with severe allergic reactions to the vaccine. In these individuals tetanus immune globulin should be considered whenever an injury other than clean minor wound is sustained.18 Other Vaccines The vaccines that are indicated for special circumstances in older adults are summarized in Table 3. Information for travel-related vaccination can be accessed through CDC website at http://www.cdc. gov/travel. Conclusion Vaccination appears to be safe and effective in the elderly. It is routinely recommended for influenza and pneumococcal pneumonia, herpes zoster, and tetanus. Annual influenza vaccination with inactivated vaccine is recommended for all adults 50 years and older. Live attenuated influenza vaccine is not recommended for elderly. PPV is recommended for all persons 65 years and older. Revaccination with PPV every 5 years is not recommended. However, one-time revaccination is recommended if they were vaccinated ⱖ5 years previously and were ages ⬍65 years at the time of primary vaccination. Unless contraindicated, all adults ages 60 and older should receive zoster vaccine (Zostavax) once. For all older adult who were never vaccinated against tetanus, a primary series of 3 doses is recommended; otherwise routine boosters are recommended every 10 years. December 2007 Volume 334 Number 6 Bader Table 3. Vaccines Indicated for Special Circumstances for the Elderly* Vaccine Indication Comments Hepatitis A vaccine Persons with chronic liver disease Persons who receive clotting factors Men who have sex with men Persons who use illegal drugs Persons traveling to or working in endemic countries for hepatitis A Persons with end-stage renal disease, including patients receiving hemodialysis Persons with chronic liver disease Persons who receive clotting factors Household or sexual contacts of hepatitis B carriersHealthcare workers or volunteers who are exposed to blood or other potentially infectious body fluids Persons who have close contact withother individuals who are at high riskfor serious varicella complications P⫹atients who are receiving inhaled corticosteroids for the treatment of pulmonary disease. International travelers A susceptible individual who has had close contact with VZV Complement-deficient and asplenic patients Persons who travel to areas where meningococcal disease is hyperendemic or epidemic and to Mecca for the Hajj It is a killed virus vaccine given IM in 2-dose schedule at either 0 and 6 to 12 months, or 0 and 6 to 18 months If combined hepatitis A and B vaccine is used, 3 doses at 0, 1, and 6 months Hepatitis B vaccine Varicella vaccine Meningococcal vaccine Recombinant hepatitis B surface antigen given IM in the deltoid region in 3 dose-schedule at 0, 1, and 6 months Give serologically negative adultsa 0.5-mL dose of varicella vaccine administered subcutaneously, followed by a second 0.5-mL dose 4 to 8 weeks later It is contraindicated in individuals with diminished cellmediated immunity because it is alive virus vaccine It must be given within 3 to 4 days of exposure to a susceptible individual It is a bacterial polysaccharides from serotypes A, C, W-135, and Y.given once subcutaneously The quadrivalent conjugate meningococcal vaccine is indicated only for persons aged 11 to 55 years * References 17. 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Prevention and Control of Influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2007;56:1–54. 6. Clements ML, Betts RF, Tierney EL, et al. Serum and nasal wash antibodies associated with resistance to experimental challenge with influenza A wild-type virus. J Clin Microbiol 1986;24:157–60. 7. McElhaney JE, Beattie BL, Devine R, et al. Age-related decline in interleukin 2 production in response to influenza vaccine. J Am Geriatr Soc 1990;38:652–8. THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES 8. Palache A, Beyer W, Sprenger M. Antibody response after influenza immunization with various vaccine doses: a doubleblind, placebo-controlled, multi-centre, dose-response study in elderly nursing- home residents and young volunteers. Vaccine 1993;11:3–9. 9. Ahmed AE, Nicholson KG, Nguyen-Van-Tam JS. Reduction in mortality associated with influenza vaccine during 1989 –90 epidemic. Lancet 1995;346:591–5. 10. 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The 23-valent pneumococcal polysaccharide vaccine, part I: efficacy of PPV in the elderly: 485 Immunization for the Elderly 17. 18. 19. 20. 21. 22. a comparison of meta-analyses. Eur J Epidemiol 2004;19: 353–63. Sisk J, Moskowitz A, Whang W. Cost-effectiveness of vaccination against pneumococcal bacteremia among elderly people. JAMA 1997;278:1333–9. Centers for Disease Control and Prevention (CDC). Recommended adult immunization schedule: United States, October 2006-September 2007. MMWR Morb Mortal Wkly Rep 2006;55:Q1–4. Lexau CA, Lynfield R, Danila R, et al. Bacterial Core Surveillance Team: changing epidemiology of invasive pneumococcal disease among older adults in the era of pediatric pneumococcal conjugate vaccine. JAMA 2005;294:2043–51. Dworkin RH, Johnson RW, Breuer J. Recommendations for the management of herpes zoster. Clin Infect Dis 2007; 44:S1–26. Helgason S, Petursson G, Gudmundsson S, et al. Prevalence of postherpetic neuralgia after a first episode of herpes zoster: prospective study with long term follow up. BMJ 2000;321:794–6. Oxman MN, Levin MJ, Johnson GR, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med 2005;352:2271–84. 486 23. Rothberg MB, Virapongse A, Smith KJ. Cost-effectiveness of a vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. Clin Infect Dis 2007;44:1280–8. 24. ACIP provisional recommendations for the use of zoster vaccine. Centers for Disease Control and Prevention, 2006. Available at: http://www.cdc.gov/nip/recs/provisional-recs/ zoster-11-20-06.pdf. 25. Holodniy M. Prevention of shingles by varicella zoster virus vaccination. Expert Rev Vaccines 2006;5:431–43. 26. Herpes zoster vaccine (Zostavax). Med Lett Drugs Ther 2006; 48:73–4. 27. Levine MJ, Murray M, Zerbe GO, et al. Immune responses of elderly persons 4 years after receiving a live attenuated varicella vaccine. J Infect Dis 1994;170:522–6. 28. Kimberlin DW, Whitley RJ. Varicella-zoster vaccine for the prevention of herpes zoster. N Engl J Med 2007;356: 1338–43. 29. Kretsinger K, Broder K, Cortese M, et al. Preventing tetanus, diphtheria, and pertussis among adults: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine. MMWR Morb Mortal Wkly Rep 2006;55:1–33. 30. Tetanus. Available at: http://www.cdc.gov/nip/publication/ pink/tetanus. December 2007 Volume 334 Number 6