UPDATES ON AGING
Update on Vaccination Guidelines for Older Adults Mark Alexander Pilkinton, MD, PhD and H. Keipp Talbot, MD, MPH
Vaccination is a vital component of routine preventative health. Older adults can potentially benefit most from vaccines because they have greater susceptibility to disease and associated complications. The number of infections covered and the types of vaccines available has grown significantly in recent years. Although this represents tremendous progress, it can also result in confusion and missed opportunities to provided recommended vaccinations. This review summarizes the current guidelines for vaccination of older adults and highlights the latest innovations. J Am Geriatr Soc 2015.
Key words: vaccination; immunizations; influenza; Pneumococcus; shingles
to determine quickly within the time constraints of a routine clinic visit which vaccines, if any, to administer. The Advisory Committee on Immunization Practice (ACIP) is a body of medical and public health experts responsible for developing the guidelines that inform medical practice and public health decisions on vaccines. They meet periodically to discuss the latest data related to vaccine effectiveness and safety and publish detailed guidelines for individual vaccine-preventable disease. Frequent updates to the guidelines combined with a complicated population can lead to missed opportunities to prevent infections.3 This review will summarize the current recommendations for vaccination of older adults and highlight the most recent changes in ACIP guidelines.
INFLUENZA
V
accination is the most effective way to combat the morbidity and mortality associated with infectious disease.1 Current gains in understanding of vaccines have opened a wave of innovations. This knowledge, combined with a changing epidemiology of infectious agents, has led to a rapid cycle of updates to the guidelines to keep clinical practice current with scientific progress. Generalizing vaccine guidelines for adults and implementing them in practice is more complicated than for childhood vaccines. A range of comorbidities may affect vaccine recommendations; for instance, there are no agespecific recommendations for Haemophilus influenzae or meningococcus vaccination, although they are recommended in all asplenic adults.2 There is the practical hurdle of understanding payer responsibility and reimbursement, and there is the challenge of understanding the potential benefits and limitations of a vaccine. These factors make it more demanding than ever for a provider From the Department of Medicine, School of Medicine, Vanderbilt University, Nashville, Tennessee. Address correspondence to Helen Keipp Talbot, Department of Medicine, Division of Infectious Diseases, Vanderbilt University School of Medicine, A2200 MCN, 1161 21st Avenue South, Nashville, TN 37232. E-mail: [email protected]
Influenza affects older adults disproportionately. On average, there are 23,000 influenza-related deaths in the United States annually, 90% of which occur in individuals aged 65 and older.4,5 Acute respiratory failure attributed to influenza is 10 to 30 times as likely to affect older as younger adults.6 Universal vaccination for adults aged 65 and older has been a mainstay of ACIP influenza vaccine recommendations, but the last few years have shown tremendous growth in the types of influenza vaccines and the methods for administering them. The high burden of disease has led to development of new influenza vaccine products and more-nuanced guidelines.7 Currently licensed influenza vaccine products are classified as inactivated influenza vaccine (IIV), live attenuated influenza vaccine, and recombinant influenza vaccine. The only vaccine class currently approved for use in individuals aged 65 and older is the IIV, which includes different vaccine types or formulations that are described below. IIV is conventionally given as an intramuscular injection. There is a version that can be administered intradermally, but this is approved only for adults aged 18 to 64 and requires a specially designed microinjection system. Historically, three different strains of the hemagglutinin antigen have been included (trivalent influenza vaccine or IIV3). Two strains of influenza A (such as H1N1 and H3N2) and one strain of B are included. IIV3 is recommended for everyone aged 6 months and older. Choosing one of two possible influenza B strains can lead to a significant gap in vaccine coverage. Therefore, a vaccine was
DOI: 10.1111/jgs.13375
JAGS 2015 © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society
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developed that included B strains in addition to the two influenza A strains. In 2013, the quadrivalent influenza vaccine (IIV4) was licensed and approved for everyone aged 6 months and older. There is now a high-dose formulation of IIV3 approved only for adults aged 65 and older.7 It includes four times the amount of hemagglutinin for each strain. Better hemagglutinin inhibitory antibody titers and greater rates of seroconversion are found in response to high-dose influenza vaccine than with the standard dose.8–10 It has a tendency to elicit more injection site reactivity, but that is well tolerated.8 A recently published clinical efficacy study of more than 30,000 participants demonstrated 24% greater efficacy of high-dose IIV than of the standard dose, reducing the breakthrough incidence of laboratoryconfirmed influenza from 1.9% to 1.5%.11 The virus used for inactivated influenza vaccines is grown in eggs, which can lead to residual egg protein in the formulation. Although reactions are rare, an individual’s allergic response to egg products must be considered when administering the IIV. If the reaction is only hives, then administering IIV is appropriate, although the vaccine recipient should be observed for at least 30 minutes after each vaccine dose. For a history of more-serious reactions to egg, such as angioedema or respiratory distress, an allergist should be consulted. There has been an effort to circumvent the need for eggs. A recombinant influenza vaccine bypasses the need for eggs and is the only vaccine approved for administration to someone with a severe egg allergy, but the recombinant influenza vaccine is recommended only for individuals aged 18 to 49. An inactivated influenza virus propagated in cell culture has been developed (ccIIV3) and approved for individuals aged 18 and older, but because the initial virus was from stock propagated in egg, it is technically not free from egg protein, containing an estimated 10 14 g of protein per dose (vs 10 6 g/dose of IIV) and therefore did not meet strict criteria for administration to individuals with egg anaphylaxis. Vaccinating all adults for influenza is a long-standing preventative health measure. In individuals aged 65 and older, the inactivated influenza virus is still the approved mainstay, but in addition to standard-dose IIV3, this now includes quadrivalent vaccine (IIV4), high-dose trivalent vaccine, and cell culture trivalent vaccine. The current ACIP recommendation states that immunization should occur with any of these vaccines, without a preferential recommendation for any of them. Expanded understanding of vaccine responses has paved the way for new products, and ongoing updates are expected as knowledge continues to grow.
PNEUMOCOCCUS Streptococcus pneumoniae has historically been associated with an enormous disease burden. It remains the most common bacterial cause of community-acquired pneumonia and can cause invasive infections with significant morbidity and mortality.12 Invasive pneumococcal disease (IPD) includes meningitis and pneumococcal pneumonia with concomitant bacteremia or seeding of other sterile sites. It strikes with a bimodal peak, affecting young children and older adults most commonly.12 The overall
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incidence of IPD is approximately 43,500 cases annually, with 5,000 deaths, the majority of which occur in older adults.12 Routine pneumococcus vaccination is recommended for all adults at age 65 to prevent invasive pneumococcus, but coverage in this population is estimated at only 60%.3 There are two types of vaccines for S. pneumoniae: the pneumococcal polysaccharide vaccine (PPSV) and the pneumococcal conjugate vaccine (PCV). Antibodies conveying protection from invasive disease are type specific, and the numbering at the end of the vaccine indicates how many capsular subtypes are in the vaccine. The vaccine derived directly from the polysaccharide capsule was the initial design and in 1983 was released as pneumococcal polysaccharide vaccine 23 (PPSV-23). This vaccine has an estimated efficacy of 74% for preventing IPD but no known efficacy for the prevention of pneumococcal pneumonia.13,14 In 2000, a pneumococcal vaccine with the polysaccharides conjugated to a protein was introduced for vaccinating children younger than 2 years (PCV-7). In 2010, the conjugate vaccine was updated to PCV-13. The serotypes covered in PCV-13 account for 44% of disease in individuals aged 65 and older, although PPSV-23 covers 66% of the serotypes of invasive disease in this population.13 Full implementation of the PCV-7 in children has had a major effect on the epidemiology of IPD in all age groups.15 When children were vaccinated, all age groups demonstrated an 87 to 92% reduction in pneumococcal disease caused by serotypes in PCV-7. The overall incidence rate of invasive pneumococcal disease in all ages was reduced by 45%, and the incidence of IPD in adults 65 and older was reduced by 37%.13 Determining the effect on pneumococcal disease since the introduction of PCV-13 in infants is widely anticipated. The ACIP recently changed its recommendation for routine pneumococcal vaccination in adults aged 65 and older.16 As a result of the Community-Acquired Pneumonia Immunization Trial in Adults, a large study in the Netherlands involving 85,000 vaccine-naive individuals aged 65 and older who received PCV-13 or placebo, these new recommendations now incorporate PCV-13 universally in all individuals aged 65 and older. Preliminary data released this year showed 75% fewer cases of vaccine type–specific IPD and 45% fewer cases of type-specific community-acquired pneumonia, including nonbacteremic, noninvasive disease. This follows an earlier change in the guidelines from 2012 that recommend PCV-13 to adults under certain immunocompromising or high-risk conditions, including asplenia or having a cerebrospinal fluid leak or cochlear implant.17 PCV-13 is now recommended to all vaccine-naive adults when they turn 65, followed by PPSV-23 6 to 12 months later.16 For those who have already received their age-appropriate dose of PPSV-23 according to the prior guidelines, they can be given PCV-13 at least 1 year later to complete their pneumococcus vaccine series. If one has received PPSV-23 before turning 65, there should be a 1-year interval before PCV-13 is administered, and the follow-up PPSV-23 should be administered no sooner than 5 years after the previous PSPV-23 dose (Figure 1). These intervals are designed to maximize immunogenicity using
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UPDATE ON VACCINATION GUIDELINES FOR OLDER ADULTS
Contraindicated immunosuppressive conditions include active hematological malignancy, chronic high-dose steroids (e.g., >20 mg/d of prednisone for >2 weeks), or the use of tumor necrosis factor alpha inhibitors. Zoster vaccine uptake is very low (6–20%) despite the greater risk of zoster in adults aged 60 and older and a vaccine efficacy of 50%.3 The barrier that stands out most consistently is cost and reimbursement.20 Medicare Part D covers the zoster vaccine as a prescription benefit, which is different than for influenza or pneumococcus. Depending on plans, the direct cost and when that cost is incurred can vary. Also, the availability of the vaccine at a physician’s office varies. In many cases, an individual will need to take a prescription for the zoster vaccine to a pharmacy and return to have it injected or have a qualified pharmacist inject it.
PCV-13 Schedule for All Adults Aged 65 Scenario 1: Pneumococcal vaccine naive PCV-13
PPSV-23 6-12 months later
PPSV-23
Scenario 2: PPSV given since turning 65 1 year since e PPSV-23 PCV-13
Scenario 3: Prior PPSV but not given since turning 65 1 year since e PPSV-23 PCV-13
PPSV-23 6-12 months later but no sooner than 5 years from last PPSV-23
3
PPSV-23
Figure 1. Pneumococcal conjugate vaccine (PCV)-13 schedule for individuals aged 65 and older. The scenarios illustrate the timing for administering PCV-13 based on history of pneumococcal polysaccharide vaccine (PPSV)-23 vaccine.
the different vaccine formulations. Outside of these recommendations, further PPSV-23 doses after age 65 are not recommended.
SHINGLES Varicella zoster virus (VZV) latently resides in the nerve roots and manifests as shingles with an increasing incidence with age.18 Vesicles and excruciating pain occur along the dermatome that the virus spreads. Even after the vesicular manifestations run their course, the pain of postherpetic neuralgia can be prolonged and severe, leading to a significant effect on quality of life. The effectiveness of the shingles vaccine was demonstrated in a large, randomized, double-blind placebo trial that included 38,546 adults aged 60 and older with 3 years of follow up.18 The VZV vaccine reduces the incidence of shingles by 50%. Secondary benefits include a reduction in the incidence of postherpetic neuralgia by 60% in vaccinees who still develop shingles. Although vaccine efficacy for preventing shingles decreases with age, the efficacy at preventing postherpetic neuralgia was maintained across all ages studied. The shingles vaccine has proven very safe. Although there was greater likelihood of reaction site rash than with placebo, there was no greater likelihood of serious adverse events and no evidence of more episodes of shingles after vaccination.18 The ACIP published the current guidelines for the shingles vaccine in 2008.19 Routine immunization of individuals aged 60 and older is recommended. Individuals who have already had an episode of shingles should still be vaccinated because repeat episodes can occur. Information about a previous history of chickenpox or serological testing for VZV antibodies is not necessary to determine eligibility for the vaccine. The shingles vaccine is a live attenuated virus, so immunosuppression status needs to be considered before administering the vaccine.
TETANUS, DIPHTHERIA, AND PERTUSSIS The routine use of vaccinations for tetanus, diphtheria, and pertussis helped usher in the current era of vaccinations. Rates of tetanus have declined by 95% since the introduction of the vaccine.1 There were only 55 cumulative diphtheria cases, once a common childhood infection, from 1980 to 2010. A childhood series using the diphtheria, tetanus, and pertussis (DTaP) vaccine has been the mainstay of continued control, but a rising incidence of Bordetella pertussis infection has prompted recent updates in the vaccine recommendations.21,22 In the early 20th century, there were routinely 100,000 to 200,000 cases of pertussis reportedly annually. This dropped to approximately 5,000, on average, in the 1990s, but since the beginning of the 21st century, rates have been rising, to a peak of 48,000 reported cases in 2012. These are only the reported cases and probably underestimate the true incidence of B. pertussis infection in the community.21 The reason for the resurgence in pertussis is multifactorial. A decline in childhood vaccine rates is one culprit. It also coincides with the change from using whole-cell pertussis, which had the risk of greater reactogenicity and high fevers, to exclusively using acellular pertussis. The duration of protection that the acellular pertussis vaccine offers is shorter than that of the whole-cell pertussis vaccine. Additionally, the rate of asymptomatic shedding is higher with the acellular pertussis vaccine.23 Increasing the number of acellular pertussis doses can help improve duration of protection.24 This prompted changes in vaccination recommendations that now include a tetanus, diphtheria, and pertussis (Tdap) booster for adolescents and adults.22 The vaccine recommended for adults is different from the vaccine for children, containing less diphtheria and acellular pertussis immunogen (as denoted by the lowercase letters). Since 2012, the ACIP has recommended a one-time Tdap booster that includes all adults aged 18 and older, with no upper age limit. The benefit of these recommendations is to not only prevent disease in the adult population but also to prevent spread of disease to vulnerable children who are most susceptible to severe manifestations. For individuals aged 65 and older who have yet to receive a one-time Tdap booster, the Tdap vaccine should be given at the soonest opportunity, regardless of when
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their last tetanus and diphtheria (Td) vaccine was. A onetime Tdap booster is sufficient to meet current guidelines, with resumption of routine Td every 10 years. A role for additional Tdap doses is being investigated.
HEPATITIS A AND B Hepatitis A and B vaccines are routinely recommend in all children, but there is no age-specific recommendation in adults.2 Risk factors, including comorbidities such as liver failure, renal failure, and diabetes mellitus; international travel; and high-risk populations such as men who have sex with men and intravenous drug users, drive vaccine indication. Diabetes mellitus, renal failure, and liver failure are increasingly prevalent in an aging population, and individuals with these conditions have a greater risk of acquiring hepatitis infection or having a more-fulminant course.25,26 Because adults with diabetes mellitus younger than 60 have twice the risk of acquiring hepatitis B virus (HBV) as those without diabetes mellitus, the ACIP recommends that they be vaccinated.27 The evidence is not as strong for adults aged 60 and older, and the decision can be individualized. Individuals with chronic renal insufficiency should be vaccinated for HBV, ideally before the initiation of dialysis. Chronic liver disease is an indication for vaccination against HBV and HAV. Older adults are increasingly undertaking international travel for work and pleasure. Hepatitis A and B remain highly prevalent throughout much of the world.25,27 The risk of acquiring hepatitis A from international travel to endemic countries is significant. Vaccination with two doses of inactivated HAV provides essentially 100% immunogenicity. Older adults tend to have the same rate of response to HAV, although with lower antibody titers. The rate of natural infection with hepatitis A in individuals aged 60 and older is nearly 60%, so it is cost effective to screen for preexisting HAV immunity before
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vaccinating.28 Hepatitis B infection is also associated with travel and would warrant vaccination, with prevaccine screening based on risk factors independent of age.26 Primary care providers would be responsible for these vaccinations in travelers, whereas recommendations for destination-specific vaccinations can be sought at a travel clinic.
MEASLES Measles transmission within the United States was declared eliminated in 2000. In the first decade after elimination, there were, on average, 60 reports of measles in the United States annually, with nearly all proven to be importation related.29 Twenty-seven percent of these cases were adults. Nearly all were unvaccinated, inadequately vaccinated based on current guidelines (received only one dose of measles, mumps, rubella vaccine), or had unknown vaccination status. In contrast, more than 600 cases were reported to the Centers for Disease Control and Prevention in 2014. Adults born before 1957 are considered to be immune to measles, mumps, and rubella, but there is no age-specific contraindication to administering the MMR vaccine.30 Adults born after 1957 should have received at least one dose of MMR or have evidence of immunity. International travelers are at greater risk for measles transmission, because measles remains endemic in most of the world, with more than 20 million cases annually. Presumptive immunity in individuals born before 1957 is still acceptable for international travelers. Alternatively, a provider can document serological immunity and, if needed, provide two doses of MMR 28 days apart, assuming there are no contraindications to a live attenuated vaccine.30
CONCLUSION Treating infectious diseases is a costly endeavor associated with greater likelihood of complications in older adults.
Table 1. Vaccine Recommendations for Older Adults Vaccine
General Recommendations
Influenza
All adults
Pneumococcal conjugate vaccine Zoster vaccine
All adults aged ≥65
Tetanus, diphtheria, acellular pertussisa Hepatitis A Hepatitis B
Measles or MMR
All adults aged ≥60 Give once to all adults No age-specific recommendation; give based on risk factors Give based on risk factors
Adults born before 1957 considered immune; if born after 1957, documentation of ≥1 dose of MMR
Notes
For adults aged ≥65 intramuscular only; standard or high dose Pneumococcal polysaccharide vaccine 6–12 months later Live vaccine, avoid if immunocompromised No upper age limit
Payment
Medicare Part B Medicare Part B Medicare Part D Medicare Part Da Medicare Part D
Recommended for /=65 years: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2014;63:822–825. 17. CDC. Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2012;61:816– 819. 18. 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;352:2271–2284. 19. Harpaz R, Ortega-Sanchez IR, Seward JF, Advisory Committee on Immunization Practices, Centers for Disease Control and Prevention. Prevention of herpes zoster: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2008;57:1–30 quiz CE32–34. 20. Hurley LP, Lindley MC, Harpaz R et al. Barriers to the use of herpes zoster vaccine. Ann Intern Med 2010;152:555–560. 21. Cherry JD, Grimprel E, Guiso N et al. Defining pertussis epidemiology: Clinical, microbiologic and serologic perspectives. Pediatr Infect Dis J 2005;24:S25–S34. 22. CDC. Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine in adults aged 65 years and older—Advisory Committee on Immunization Practices (ACIP), 2012. MMWR Morb Mortal Wkly Rep 2012;61:468–470. 23. Smallridge WE, Rolin OY, Jacobs NT et al. Different effects of whole-cell and acellular vaccines on Bordetella transmission. J Infect Dis 2014;209:1981–1988. 24. Witt MA, Arias L, Katz PH et al. Reduced risk of pertussis among persons ever vaccinated with whole cell pertussis vaccine compared to recipients of acellular pertussis vaccines in a large US cohort. Clin Infect Dis 2013;56:1248–1254. 25. Advisory Committee on Immunization Practices, Fiore AE, Wasley A, Bell BP. Prevention of hepatitis A through active or passive immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2006;55:1–23. 26. Mast EE, Weinbaum CM, Fiore AE et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: Recommendations of the Advisory Committee on Immunization Practices (ACIP) Part II: Immunization of adults. MMWR Recomm Rep 2006;55:1–33 quiz CE31–34. 27. CDC. Use of hepatitis B vaccination for adults with diabetes mellitus: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2011;60:1709–1711. 28. Bell BP, Kruszon-Moran D, Shapiro CN et al. Hepatitis A virus infection in the United States: Serologic results from the third national health and nutrition examination survey. Vaccine 2005;23:5798–5806. 29. CDC. Measles – United States, January 1-August 24, 2013. MMWR Morb Mortal Wkly Rep 2013;62:741–743. 30. McLean HQ, Fiebelkorn AP, Temte JL et al. Centers for Disease Control and Prevention. Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013: Summary recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2013;62:1–34.
Update on Vaccination Guidelines for Older Adults Mark Alexander Pilkinton, MD, PhD and H. Keipp Talbot, MD, MPH
Vaccination is a vital component of routine preventative health. Older adults can potentially benefit most from vaccines because they have greater susceptibility to disease and associated complications. The number of infections covered and the types of vaccines available has grown significantly in recent years. Although this represents tremendous progress, it can also result in confusion and missed opportunities to provided recommended vaccinations. This review summarizes the current guidelines for vaccination of older adults and highlights the latest innovations. J Am Geriatr Soc 2015.
Key words: vaccination; immunizations; influenza; Pneumococcus; shingles
to determine quickly within the time constraints of a routine clinic visit which vaccines, if any, to administer. The Advisory Committee on Immunization Practice (ACIP) is a body of medical and public health experts responsible for developing the guidelines that inform medical practice and public health decisions on vaccines. They meet periodically to discuss the latest data related to vaccine effectiveness and safety and publish detailed guidelines for individual vaccine-preventable disease. Frequent updates to the guidelines combined with a complicated population can lead to missed opportunities to prevent infections.3 This review will summarize the current recommendations for vaccination of older adults and highlight the most recent changes in ACIP guidelines.
INFLUENZA
V
accination is the most effective way to combat the morbidity and mortality associated with infectious disease.1 Current gains in understanding of vaccines have opened a wave of innovations. This knowledge, combined with a changing epidemiology of infectious agents, has led to a rapid cycle of updates to the guidelines to keep clinical practice current with scientific progress. Generalizing vaccine guidelines for adults and implementing them in practice is more complicated than for childhood vaccines. A range of comorbidities may affect vaccine recommendations; for instance, there are no agespecific recommendations for Haemophilus influenzae or meningococcus vaccination, although they are recommended in all asplenic adults.2 There is the practical hurdle of understanding payer responsibility and reimbursement, and there is the challenge of understanding the potential benefits and limitations of a vaccine. These factors make it more demanding than ever for a provider From the Department of Medicine, School of Medicine, Vanderbilt University, Nashville, Tennessee. Address correspondence to Helen Keipp Talbot, Department of Medicine, Division of Infectious Diseases, Vanderbilt University School of Medicine, A2200 MCN, 1161 21st Avenue South, Nashville, TN 37232. E-mail: [email protected]
Influenza affects older adults disproportionately. On average, there are 23,000 influenza-related deaths in the United States annually, 90% of which occur in individuals aged 65 and older.4,5 Acute respiratory failure attributed to influenza is 10 to 30 times as likely to affect older as younger adults.6 Universal vaccination for adults aged 65 and older has been a mainstay of ACIP influenza vaccine recommendations, but the last few years have shown tremendous growth in the types of influenza vaccines and the methods for administering them. The high burden of disease has led to development of new influenza vaccine products and more-nuanced guidelines.7 Currently licensed influenza vaccine products are classified as inactivated influenza vaccine (IIV), live attenuated influenza vaccine, and recombinant influenza vaccine. The only vaccine class currently approved for use in individuals aged 65 and older is the IIV, which includes different vaccine types or formulations that are described below. IIV is conventionally given as an intramuscular injection. There is a version that can be administered intradermally, but this is approved only for adults aged 18 to 64 and requires a specially designed microinjection system. Historically, three different strains of the hemagglutinin antigen have been included (trivalent influenza vaccine or IIV3). Two strains of influenza A (such as H1N1 and H3N2) and one strain of B are included. IIV3 is recommended for everyone aged 6 months and older. Choosing one of two possible influenza B strains can lead to a significant gap in vaccine coverage. Therefore, a vaccine was
DOI: 10.1111/jgs.13375
JAGS 2015 © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society
0002-8614/15/$15.00
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developed that included B strains in addition to the two influenza A strains. In 2013, the quadrivalent influenza vaccine (IIV4) was licensed and approved for everyone aged 6 months and older. There is now a high-dose formulation of IIV3 approved only for adults aged 65 and older.7 It includes four times the amount of hemagglutinin for each strain. Better hemagglutinin inhibitory antibody titers and greater rates of seroconversion are found in response to high-dose influenza vaccine than with the standard dose.8–10 It has a tendency to elicit more injection site reactivity, but that is well tolerated.8 A recently published clinical efficacy study of more than 30,000 participants demonstrated 24% greater efficacy of high-dose IIV than of the standard dose, reducing the breakthrough incidence of laboratoryconfirmed influenza from 1.9% to 1.5%.11 The virus used for inactivated influenza vaccines is grown in eggs, which can lead to residual egg protein in the formulation. Although reactions are rare, an individual’s allergic response to egg products must be considered when administering the IIV. If the reaction is only hives, then administering IIV is appropriate, although the vaccine recipient should be observed for at least 30 minutes after each vaccine dose. For a history of more-serious reactions to egg, such as angioedema or respiratory distress, an allergist should be consulted. There has been an effort to circumvent the need for eggs. A recombinant influenza vaccine bypasses the need for eggs and is the only vaccine approved for administration to someone with a severe egg allergy, but the recombinant influenza vaccine is recommended only for individuals aged 18 to 49. An inactivated influenza virus propagated in cell culture has been developed (ccIIV3) and approved for individuals aged 18 and older, but because the initial virus was from stock propagated in egg, it is technically not free from egg protein, containing an estimated 10 14 g of protein per dose (vs 10 6 g/dose of IIV) and therefore did not meet strict criteria for administration to individuals with egg anaphylaxis. Vaccinating all adults for influenza is a long-standing preventative health measure. In individuals aged 65 and older, the inactivated influenza virus is still the approved mainstay, but in addition to standard-dose IIV3, this now includes quadrivalent vaccine (IIV4), high-dose trivalent vaccine, and cell culture trivalent vaccine. The current ACIP recommendation states that immunization should occur with any of these vaccines, without a preferential recommendation for any of them. Expanded understanding of vaccine responses has paved the way for new products, and ongoing updates are expected as knowledge continues to grow.
PNEUMOCOCCUS Streptococcus pneumoniae has historically been associated with an enormous disease burden. It remains the most common bacterial cause of community-acquired pneumonia and can cause invasive infections with significant morbidity and mortality.12 Invasive pneumococcal disease (IPD) includes meningitis and pneumococcal pneumonia with concomitant bacteremia or seeding of other sterile sites. It strikes with a bimodal peak, affecting young children and older adults most commonly.12 The overall
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incidence of IPD is approximately 43,500 cases annually, with 5,000 deaths, the majority of which occur in older adults.12 Routine pneumococcus vaccination is recommended for all adults at age 65 to prevent invasive pneumococcus, but coverage in this population is estimated at only 60%.3 There are two types of vaccines for S. pneumoniae: the pneumococcal polysaccharide vaccine (PPSV) and the pneumococcal conjugate vaccine (PCV). Antibodies conveying protection from invasive disease are type specific, and the numbering at the end of the vaccine indicates how many capsular subtypes are in the vaccine. The vaccine derived directly from the polysaccharide capsule was the initial design and in 1983 was released as pneumococcal polysaccharide vaccine 23 (PPSV-23). This vaccine has an estimated efficacy of 74% for preventing IPD but no known efficacy for the prevention of pneumococcal pneumonia.13,14 In 2000, a pneumococcal vaccine with the polysaccharides conjugated to a protein was introduced for vaccinating children younger than 2 years (PCV-7). In 2010, the conjugate vaccine was updated to PCV-13. The serotypes covered in PCV-13 account for 44% of disease in individuals aged 65 and older, although PPSV-23 covers 66% of the serotypes of invasive disease in this population.13 Full implementation of the PCV-7 in children has had a major effect on the epidemiology of IPD in all age groups.15 When children were vaccinated, all age groups demonstrated an 87 to 92% reduction in pneumococcal disease caused by serotypes in PCV-7. The overall incidence rate of invasive pneumococcal disease in all ages was reduced by 45%, and the incidence of IPD in adults 65 and older was reduced by 37%.13 Determining the effect on pneumococcal disease since the introduction of PCV-13 in infants is widely anticipated. The ACIP recently changed its recommendation for routine pneumococcal vaccination in adults aged 65 and older.16 As a result of the Community-Acquired Pneumonia Immunization Trial in Adults, a large study in the Netherlands involving 85,000 vaccine-naive individuals aged 65 and older who received PCV-13 or placebo, these new recommendations now incorporate PCV-13 universally in all individuals aged 65 and older. Preliminary data released this year showed 75% fewer cases of vaccine type–specific IPD and 45% fewer cases of type-specific community-acquired pneumonia, including nonbacteremic, noninvasive disease. This follows an earlier change in the guidelines from 2012 that recommend PCV-13 to adults under certain immunocompromising or high-risk conditions, including asplenia or having a cerebrospinal fluid leak or cochlear implant.17 PCV-13 is now recommended to all vaccine-naive adults when they turn 65, followed by PPSV-23 6 to 12 months later.16 For those who have already received their age-appropriate dose of PPSV-23 according to the prior guidelines, they can be given PCV-13 at least 1 year later to complete their pneumococcus vaccine series. If one has received PPSV-23 before turning 65, there should be a 1-year interval before PCV-13 is administered, and the follow-up PPSV-23 should be administered no sooner than 5 years after the previous PSPV-23 dose (Figure 1). These intervals are designed to maximize immunogenicity using
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UPDATE ON VACCINATION GUIDELINES FOR OLDER ADULTS
Contraindicated immunosuppressive conditions include active hematological malignancy, chronic high-dose steroids (e.g., >20 mg/d of prednisone for >2 weeks), or the use of tumor necrosis factor alpha inhibitors. Zoster vaccine uptake is very low (6–20%) despite the greater risk of zoster in adults aged 60 and older and a vaccine efficacy of 50%.3 The barrier that stands out most consistently is cost and reimbursement.20 Medicare Part D covers the zoster vaccine as a prescription benefit, which is different than for influenza or pneumococcus. Depending on plans, the direct cost and when that cost is incurred can vary. Also, the availability of the vaccine at a physician’s office varies. In many cases, an individual will need to take a prescription for the zoster vaccine to a pharmacy and return to have it injected or have a qualified pharmacist inject it.
PCV-13 Schedule for All Adults Aged 65 Scenario 1: Pneumococcal vaccine naive PCV-13
PPSV-23 6-12 months later
PPSV-23
Scenario 2: PPSV given since turning 65 1 year since e PPSV-23 PCV-13
Scenario 3: Prior PPSV but not given since turning 65 1 year since e PPSV-23 PCV-13
PPSV-23 6-12 months later but no sooner than 5 years from last PPSV-23
3
PPSV-23
Figure 1. Pneumococcal conjugate vaccine (PCV)-13 schedule for individuals aged 65 and older. The scenarios illustrate the timing for administering PCV-13 based on history of pneumococcal polysaccharide vaccine (PPSV)-23 vaccine.
the different vaccine formulations. Outside of these recommendations, further PPSV-23 doses after age 65 are not recommended.
SHINGLES Varicella zoster virus (VZV) latently resides in the nerve roots and manifests as shingles with an increasing incidence with age.18 Vesicles and excruciating pain occur along the dermatome that the virus spreads. Even after the vesicular manifestations run their course, the pain of postherpetic neuralgia can be prolonged and severe, leading to a significant effect on quality of life. The effectiveness of the shingles vaccine was demonstrated in a large, randomized, double-blind placebo trial that included 38,546 adults aged 60 and older with 3 years of follow up.18 The VZV vaccine reduces the incidence of shingles by 50%. Secondary benefits include a reduction in the incidence of postherpetic neuralgia by 60% in vaccinees who still develop shingles. Although vaccine efficacy for preventing shingles decreases with age, the efficacy at preventing postherpetic neuralgia was maintained across all ages studied. The shingles vaccine has proven very safe. Although there was greater likelihood of reaction site rash than with placebo, there was no greater likelihood of serious adverse events and no evidence of more episodes of shingles after vaccination.18 The ACIP published the current guidelines for the shingles vaccine in 2008.19 Routine immunization of individuals aged 60 and older is recommended. Individuals who have already had an episode of shingles should still be vaccinated because repeat episodes can occur. Information about a previous history of chickenpox or serological testing for VZV antibodies is not necessary to determine eligibility for the vaccine. The shingles vaccine is a live attenuated virus, so immunosuppression status needs to be considered before administering the vaccine.
TETANUS, DIPHTHERIA, AND PERTUSSIS The routine use of vaccinations for tetanus, diphtheria, and pertussis helped usher in the current era of vaccinations. Rates of tetanus have declined by 95% since the introduction of the vaccine.1 There were only 55 cumulative diphtheria cases, once a common childhood infection, from 1980 to 2010. A childhood series using the diphtheria, tetanus, and pertussis (DTaP) vaccine has been the mainstay of continued control, but a rising incidence of Bordetella pertussis infection has prompted recent updates in the vaccine recommendations.21,22 In the early 20th century, there were routinely 100,000 to 200,000 cases of pertussis reportedly annually. This dropped to approximately 5,000, on average, in the 1990s, but since the beginning of the 21st century, rates have been rising, to a peak of 48,000 reported cases in 2012. These are only the reported cases and probably underestimate the true incidence of B. pertussis infection in the community.21 The reason for the resurgence in pertussis is multifactorial. A decline in childhood vaccine rates is one culprit. It also coincides with the change from using whole-cell pertussis, which had the risk of greater reactogenicity and high fevers, to exclusively using acellular pertussis. The duration of protection that the acellular pertussis vaccine offers is shorter than that of the whole-cell pertussis vaccine. Additionally, the rate of asymptomatic shedding is higher with the acellular pertussis vaccine.23 Increasing the number of acellular pertussis doses can help improve duration of protection.24 This prompted changes in vaccination recommendations that now include a tetanus, diphtheria, and pertussis (Tdap) booster for adolescents and adults.22 The vaccine recommended for adults is different from the vaccine for children, containing less diphtheria and acellular pertussis immunogen (as denoted by the lowercase letters). Since 2012, the ACIP has recommended a one-time Tdap booster that includes all adults aged 18 and older, with no upper age limit. The benefit of these recommendations is to not only prevent disease in the adult population but also to prevent spread of disease to vulnerable children who are most susceptible to severe manifestations. For individuals aged 65 and older who have yet to receive a one-time Tdap booster, the Tdap vaccine should be given at the soonest opportunity, regardless of when
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their last tetanus and diphtheria (Td) vaccine was. A onetime Tdap booster is sufficient to meet current guidelines, with resumption of routine Td every 10 years. A role for additional Tdap doses is being investigated.
HEPATITIS A AND B Hepatitis A and B vaccines are routinely recommend in all children, but there is no age-specific recommendation in adults.2 Risk factors, including comorbidities such as liver failure, renal failure, and diabetes mellitus; international travel; and high-risk populations such as men who have sex with men and intravenous drug users, drive vaccine indication. Diabetes mellitus, renal failure, and liver failure are increasingly prevalent in an aging population, and individuals with these conditions have a greater risk of acquiring hepatitis infection or having a more-fulminant course.25,26 Because adults with diabetes mellitus younger than 60 have twice the risk of acquiring hepatitis B virus (HBV) as those without diabetes mellitus, the ACIP recommends that they be vaccinated.27 The evidence is not as strong for adults aged 60 and older, and the decision can be individualized. Individuals with chronic renal insufficiency should be vaccinated for HBV, ideally before the initiation of dialysis. Chronic liver disease is an indication for vaccination against HBV and HAV. Older adults are increasingly undertaking international travel for work and pleasure. Hepatitis A and B remain highly prevalent throughout much of the world.25,27 The risk of acquiring hepatitis A from international travel to endemic countries is significant. Vaccination with two doses of inactivated HAV provides essentially 100% immunogenicity. Older adults tend to have the same rate of response to HAV, although with lower antibody titers. The rate of natural infection with hepatitis A in individuals aged 60 and older is nearly 60%, so it is cost effective to screen for preexisting HAV immunity before
JAGS
vaccinating.28 Hepatitis B infection is also associated with travel and would warrant vaccination, with prevaccine screening based on risk factors independent of age.26 Primary care providers would be responsible for these vaccinations in travelers, whereas recommendations for destination-specific vaccinations can be sought at a travel clinic.
MEASLES Measles transmission within the United States was declared eliminated in 2000. In the first decade after elimination, there were, on average, 60 reports of measles in the United States annually, with nearly all proven to be importation related.29 Twenty-seven percent of these cases were adults. Nearly all were unvaccinated, inadequately vaccinated based on current guidelines (received only one dose of measles, mumps, rubella vaccine), or had unknown vaccination status. In contrast, more than 600 cases were reported to the Centers for Disease Control and Prevention in 2014. Adults born before 1957 are considered to be immune to measles, mumps, and rubella, but there is no age-specific contraindication to administering the MMR vaccine.30 Adults born after 1957 should have received at least one dose of MMR or have evidence of immunity. International travelers are at greater risk for measles transmission, because measles remains endemic in most of the world, with more than 20 million cases annually. Presumptive immunity in individuals born before 1957 is still acceptable for international travelers. Alternatively, a provider can document serological immunity and, if needed, provide two doses of MMR 28 days apart, assuming there are no contraindications to a live attenuated vaccine.30
CONCLUSION Treating infectious diseases is a costly endeavor associated with greater likelihood of complications in older adults.
Table 1. Vaccine Recommendations for Older Adults Vaccine
General Recommendations
Influenza
All adults
Pneumococcal conjugate vaccine Zoster vaccine
All adults aged ≥65
Tetanus, diphtheria, acellular pertussisa Hepatitis A Hepatitis B
Measles or MMR
All adults aged ≥60 Give once to all adults No age-specific recommendation; give based on risk factors Give based on risk factors
Adults born before 1957 considered immune; if born after 1957, documentation of ≥1 dose of MMR
Notes
For adults aged ≥65 intramuscular only; standard or high dose Pneumococcal polysaccharide vaccine 6–12 months later Live vaccine, avoid if immunocompromised No upper age limit
Payment
Medicare Part B Medicare Part B Medicare Part D Medicare Part Da Medicare Part D
Recommended for /=65 years: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2014;63:822–825. 17. CDC. Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2012;61:816– 819. 18. 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;352:2271–2284. 19. Harpaz R, Ortega-Sanchez IR, Seward JF, Advisory Committee on Immunization Practices, Centers for Disease Control and Prevention. Prevention of herpes zoster: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2008;57:1–30 quiz CE32–34. 20. Hurley LP, Lindley MC, Harpaz R et al. Barriers to the use of herpes zoster vaccine. Ann Intern Med 2010;152:555–560. 21. Cherry JD, Grimprel E, Guiso N et al. Defining pertussis epidemiology: Clinical, microbiologic and serologic perspectives. Pediatr Infect Dis J 2005;24:S25–S34. 22. CDC. Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine in adults aged 65 years and older—Advisory Committee on Immunization Practices (ACIP), 2012. MMWR Morb Mortal Wkly Rep 2012;61:468–470. 23. Smallridge WE, Rolin OY, Jacobs NT et al. Different effects of whole-cell and acellular vaccines on Bordetella transmission. J Infect Dis 2014;209:1981–1988. 24. Witt MA, Arias L, Katz PH et al. Reduced risk of pertussis among persons ever vaccinated with whole cell pertussis vaccine compared to recipients of acellular pertussis vaccines in a large US cohort. Clin Infect Dis 2013;56:1248–1254. 25. Advisory Committee on Immunization Practices, Fiore AE, Wasley A, Bell BP. Prevention of hepatitis A through active or passive immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2006;55:1–23. 26. Mast EE, Weinbaum CM, Fiore AE et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: Recommendations of the Advisory Committee on Immunization Practices (ACIP) Part II: Immunization of adults. MMWR Recomm Rep 2006;55:1–33 quiz CE31–34. 27. CDC. Use of hepatitis B vaccination for adults with diabetes mellitus: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2011;60:1709–1711. 28. Bell BP, Kruszon-Moran D, Shapiro CN et al. Hepatitis A virus infection in the United States: Serologic results from the third national health and nutrition examination survey. Vaccine 2005;23:5798–5806. 29. CDC. Measles – United States, January 1-August 24, 2013. MMWR Morb Mortal Wkly Rep 2013;62:741–743. 30. McLean HQ, Fiebelkorn AP, Temte JL et al. Centers for Disease Control and Prevention. Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013: Summary recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2013;62:1–34.
