Currently Viewing:
Supplements A Managed Care Perspective on the Importance of Optimizing Influenza Vaccinations in Older Adults
Currently Reading
Influenza in Older Patients: A Call to Action and Recent Updates for Vaccinations
Miranda Wilhelm, PharmD
Participating Faculty

Influenza in Older Patients: A Call to Action and Recent Updates for Vaccinations

Miranda Wilhelm, PharmD
There is an intradermal, quadrivalent, standard-dose influenza vaccine (Fluzone Intradermal Quadrivalent [IIV4]) that is approved for people aged 18 through 64 years.46 Viral particles are produced in chicken eggs, purified in sucrose gradients, inactivated with formaldehyde, and disrupted with detergents. It contains 9 mcg of each hemagglutinin (36 mcg total) and is injected intradermally. The same level of seroprotection may be obtained with less antigen through intradermal vaccination, compared with vaccination via the intramuscular route, due to the greater concentration of immune cells and a more robust immune response to antigen.47 Greater than trace amounts of formaldehyde and detergents may remain. It is latex-free.

Vaccination in Older Patients with Comorbidities

The population of older patients with comorbidities is at high risk for complications due to influenza. These patients often have pulmonary and cardiac deficits. In this at-risk population, high-dose vaccination appears to be safe and efficacious. Over a 6- to 8-month period after receiving either high- or standard-dose IIV3 influenza vaccination, these vaccine efficacy results against laboratory-confirmed influenza-like illness were noted.48

Age: 19.7% (95% CI, 0.4%-35.4%) for participants 65 to 74 years and 32.4% (95% CI, 8.1%-50.6%) for those 75 years or older

Comorbidities: 22.1% (95% CI, 3.9%-37.0%) for participants with 1 or more high-risk comorbidity and 23.6% (95% CI, –3.2% to 43.6%) for those with 2 or more high-risk comorbidities

Frailty: 27.5% (95% CI, 0.4%-47.4%) for persons with 1 frailty condition, 23.9% (95% CI, –9.0% to 47.2%) for those with 2 frailty conditions, and 16.0% (95% CI, –16.3% to 39.4%) for those with 3 or more frailty conditions. (Included frailty conditions were vision or hearing loss; impaired mobility; difficulty toileting, bathing, dressing, grooming, or going out; skin, urinary, or gastrointestinal problems; resting tremor; changes in sleep; and hypertension.)

Another potentially serious adverse effect of vaccination can occur in persons with egg allergies. Only the recombinant, trivalent, standard-dose influenza vaccine (Flublok [RIV3]); recombinant, quadrivalent, standard-dose, inactivated influenza vaccine (Flublok Quadrivalent [RIV4]); and the recombinant, quadrivalent, standard-dose inactivated influenza vaccine produced in cell culture (Flucelvax Quadrivalent [RIV4]) are manufactured without the use of eggs as incubators. The recombinant, quadrivalent, standard-dose inactivated influenza vaccine produced in cell culture (Flucelvax Quadrivalent) uses starter cultures grown in eggs, meaning there is a theoretical 5x10-8 mcg of total egg protein per 0.5-mL vaccine dose.27

Influenza Vaccination Recommendations for 2017-2018

The position of the ACIP is that any age-appropriate IIV formulation (standard-dose or high-dose, trivalent or quadrivalent, unadjuvanted or adjuvanted) or RIV is acceptable for persons 65 years or older. The ACIP states quite clearly, “No preferential recommendation is made for any specific vaccine product.”27 Instead, ACIP specifies only that all eligible patients should be vaccinated in a timely manner and that patients should not wait to vaccinate if a specific product is not available. The difficulty in recommending one product over another in the 65 years or older group lies in the lack of data: Most data are for the 18- to 64-year age group. Currently, no head-to-head data exist that compare the high-dose with the adjuvanted vaccines in patients 65 years or older. The ACIP recommends27:
  • Persons with a history of egg allergy who have experienced only urticaria (hives) after exposure to egg should receive influenza vaccine. Any licensed and recommended influenza vaccine may be used
  • Persons who report having had reactions to egg involving symptoms other than urticaria (hives), such as angioedema, respiratory distress, lightheadedness, or recurrent emesis, or who required epinephrine or another emergency medical intervention, may receive an influenza vaccination. Any licensed and recommended influenza vaccine may be used. Vaccine administration should be supervised by a healthcare provider who is able to recognize and manage severe allergic conditions
  • A previous severe allergic reaction to influenza vaccine is a contraindication to future receipt of the vaccine, regardless of the component suspected of being responsible for the reaction

Vaccination is a proven tool to reduce the morbidity and mortality associated with seasonal influenza, especially in the elderly population. The ACIP recommends that most people receive the vaccine, but particularly at-risk populations, including elderly persons and those who work with at-risk populations. New vaccine preparations have been introduced to boost vaccine seroprotection in older patients. They contain higher doses of antigen, vaccine adjuvants, or recombinant proteins. Healthcare systems will be challenged to integrate these new agents into full use. Factors affecting use depend heavily on the cost-effectiveness of the vaccines. As we will see in the next article, use of these vaccines by managed care organizations will require superior vaccine effectiveness and improved cost-effectiveness, as compared with currently available trivalent, standard-dose influenza vaccines.

Author affiliation: Department of Pharmacy Practice, Southern Illinois University Edwardsville, Edwardsville, IL.
Funding source: This activity is supported by an educational grant from Sanofi Pasteur U.S.
Author disclosure: Dr Wilhelm reports serving on the speakers’ bureau for Merck Vaccines.
Authorship information: Concept and design, drafting of the manuscript, and critical revision of the manuscript for important intellectual content.
Address correspondence to:
1. About flu. CDC website. Updated October 5, 2017. Accessed October 27, 2017.
2. Saunders-Hastings PR, Krewski D. Reviewing the history of pandemic influenza: understanding patterns of emergence and transmission. Pathogens. 2016;5(4). pii: E66. doi: 10.3390/pathogens5040066.
3. Dawood FS, Iuliano AD, Reed C, et al. Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: a modelling study. Lancet Infect Dis. 2012;12(9):687-695. doi: 10.1016/s1473-3099(12)70121-4.
4. Molinari NA, Ortega-Sanchez IR, Messonnier ML, et al. The annual impact of seasonal influenza in the US: measuring disease burden and costs. Vaccine. 2007;25(27):5086-5096. doi: 10.1016/j.vaccine.2007.03.046.
5. Neuzil KM, O’Connor TZ, Gorse GJ, Nichol KL. Recognizing influenza in older patients with chronic obstructive pulmonary disease who have received influenza vaccine. Clin Infect Dis. 2003;36(2):169-174. doi: 10.1086/345668.
6. Doherty M, Schmidt-Ott R, Santos JI, et al. Vaccination of special populations: protecting the vulnerable. Vaccine. 2016;34(52):6681-6690. doi: 10.1016/j.vaccine.2016.11.015.
7. Horimoto T, Kawaoka Y. Influenza: lessons from past pandemics, warnings from current incidents. Nat Rev Microbiol. 2005;3(8):591-600.
8. Clancy S. Genetics of the influenza virus. Nature Education. 2008;1(1):83.
9. Moghadami M. A narrative review of influenza: a seasonal and pandemic disease. Iran J Med Sci. 2017;42(1):2-13.
10. Garg S, Jain S, Dawood FS, et al. Pneumonia among adults hospitalized with laboratory-confirmed seasonal influenza virus infection—United States, 2005-2008. BMC Infect Dis. 2015;15:369. doi: 10.1186/s12879-015-1004-y.
11. Klein EY, Monteforte B, Gupta A, et al. The frequency of influenza and bacterial coinfection: a systematic review and meta-analysis. Influenza Other Respir Viruses. 2016;10(5):394-403. doi: 10.1111/irv.12398.
12. Sellers SA, Hagan RS, Hayden FG, Fischer WA 2nd. The hidden burden of influenza: a review of the extra-pulmonary complications of influenza infection. Influenza Other Respir Viruses. 2017;11(5):372-393. doi: 10.1111/irv.12470.
13. Kodama M. Influenza myocarditis. Circ J. 2010;74(10):2060-2061.
14. Glaser CA, Winter K, DuBray K, et al. A population-based study of neurologic manifestations of severe influenza A(H1N1)pdm09 in California. Clin Infect Dis. 2012;55(4):514-520. doi: 10.1093/cid/cis454.
15. Jain A, van Hoek AJ, Boccia D, Thomas SL. Lower vaccine uptake amongst older individuals living alone: a systematic review and meta-analysis of social determinants of vaccine uptake. Vaccine. 2017;35(18):2315-2328. doi: 10.1016/j.vaccine.2017.03.013.
16. Blanton L, Alabi N, Mustaquim D, et al. Update: influenza activity in the United States during the 2016-17 season and composition of the 2017-18 influenza vaccine. MMWR Morb Mortality Wkly Rep. 2017;66(25):668-676. doi: 10.15585/mmwr.mm6625a3.
17. Palache A, Oriol-Mathieu V, Fino M, Xydia-Charmanta M; Influenza Vaccine Supply Task Force (IFPMA IVS). Seasonal influenza vaccine dose distribution in 195 countries (2004-2013): little progress in estimated global vaccination coverage. Vaccine. 2015;33(42):5598-5605. doi: 10.1016/j.vaccine.2015.08.082.
18. Schmid P, Rauber D, Betsch C, Lidolt G, Denker ML. Barriers of influenza vaccination intention and behavior—a systematic review of influenza vaccine hesitancy, 2005-2016. PLoS One. 2017;12(1):e0170550. doi: 10.1371/journal.pone.0170550.
19. Arriola C, Garg S, Anderson EJ, et al. Influenza vaccination modifies disease severity among
community-dwelling adults hospitalized with influenza. Clin Infect Dis. 2017;65(8):1289-1297.
doi: 10.1093/cid/cix468.
20. Ferdinands JM, Fry AM, Reynolds S, et al. Intraseason waning of influenza vaccine protection: evidence from the US Influenza Vaccine Effectiveness Network, 2011-12 through 2014-15. Clin Infect Dis. 2017;64(5):544-550. doi: 10.1093/cid/ciw816.
21. Kositanont U, Assantachai P, Wasi C, Puthavathana P, Praditsuwan R. Kinetics of the antibody response to seasonal influenza vaccination among the elderly. Viral Immunol. 2012;25(6):471-476. doi: 10.1089/vim.2012.0024.
22. Skowronski DM, Tweed SA, De Serres G. Rapid decline of influenza vaccine-induced antibody in the elderly: is it real, or is it relevant? J Infect Dis. 2008;197(4):490-502. doi: 10.1086/524146.
23. Song JY, Cheong HJ, Hwang IS, et al. Long-term immunogenicity of influenza vaccine among the elderly: risk factors for poor immune response and persistence. Vaccine. 2010;28(23):3929-3935. doi: 10.1016/j.vaccine.2010.03.067.
24. Available tools for increasing influenza vaccination among health care personnel in long-term settings.  CDC website.  Updated June 8, 2017.  Accessed December 18, 2017.
25. Goodwin K, Viboud C, Simonsen L. Antibody response to influenza vaccination in the elderly: a quantitative review. Vaccine. 2006;24(8):1159-1169. doi: 10.1016/j.vaccine.2005.08.105.
26. Talbot HK. Influenza in older adults. Infect Dis Clin North Am. 2017;31(4):757-766. doi: 10.1016/j.idc.2017.07.005.
27. Grohskopf LA, Sokolow LZ, Broder KR, et al. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices–United States, 2017-18 Influenza Season. Am J Transplant. 2017;17(11):2970-2982. doi: 10.1111/ajt.14511.
28. Langmuir AD, Henderson DA, Serfling RE. The epidemiological basis for the control of influenza. Am J Public Health Nations Health. 1964;54:563-571.
29. Afluria [package insert]. Summit, NJ: Seqirus; 2017.
30. Fluvirin [package insert]. Summit, NJ: Seqirus; 2017.
31. Flublok [package insert]. Meriden, CT: Protein Sciences; 2017.
32. Fluzone High-Dose [package insert]. Swiftwater, PA: Sanofi Pasteur; 2017.
33. DiazGranados CA, Dunning AJ, Kimmel M, et al. Efficacy of high-dose versus standard-dose influenza vaccine in older adults. N Engl J Med. 2014;371(7):635-645. doi: 10.1056/NEJMoa1315727.
34. Chit A, Becker DL, DiazGranados CA, Maschio M, Yau E, Drummond M. Cost-effectiveness of high-dose versus standard-dose inactivated influenza vaccine in adults aged 65 years and older: an economic evaluation of data from a randomised controlled trial. Lancet Infect Dis. 2015;15(12):1459-1466. doi: 10.1016/s1473-3099(15)00249-2.
35. Robertson CA, DiazGranados CA, Decker MD, Chit A, Mercer M, Greenberg DP. Fluzone High-Dose influenza vaccine. Expert Rev Vaccines. 2016;15(12):1495-1505. doi: 10.1080/14760584.2016.1254044.
36. Fluad [package insert]. Summit, NJ: Seqirus; 2017.
37. Domnich A, Arata L, Amicizia D, Puig-Barberà J, Gasparini R, Panatto D. Effectiveness of MF59-adjuvanted seasonal influenza vaccine in the elderly: a systematic review and meta-analysis. Vaccine. 2017;35(4):513-520. doi: 10.1016/j.vaccine.2016.12.011.
38. Afluria Quadrivalent [package insert]. Summit, NJ: Seqirus; 2017.
39. Fluzone Quadrivalent [package insert]. Swiftwater, PA: Sanofi Pasteur; 2017.
40. Fluarix Quadrivalent [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2017.
41. Flulaval Quadrivalent [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2017.
42. Flublok Quadrivalent [package insert]. Meriden, CT: Protein Sciences; 2017.
43. Dunkle LM, Izikson R, Patriarca P, et al; PSC12 Study Team. Efficacy of recombinant influenza vaccine in adults 50 years of age or older. N Engl J Med. 2017;376(25):2427-2436. doi: 10.1056/NEJMoa1608862.
44. Vaccines, Blood & Biologics: Flublok. FDA website. Updated October 24, 2017. Accessed October 25, 2017.
45. Flucelvax Quadrivalent [package insert]. Summit, NJ: Seqirus; 2017.
46. Fluzone Intradermal Quadrivalent [package insert]. Swiftwater, PA: Sanofi Pasteur; 2017.
47. Chi RC, Rock MT, Neuzil KM. Immunogenicity and safety of intradermal influenza vaccination in healthy older adults. Clin Infect Dis. 2010;50(10):1331-1338. doi: 10.1086/652144.
48. DiazGranados CA, Dunning AJ, Robertson CA, Talbot HK, Landolfi V, Greenberg DP. Efficacy and immunogenicity of high-dose influenza vaccine in older adults by age, comorbidities, and frailty. Vaccine. 2015;33(36):4565-4571. doi: 10.1016/j.vaccine.2015.07.003.
Copyright AJMC 2006-2020 Clinical Care Targeted Communications Group, LLC. All Rights Reserved.
Welcome the the new and improved, the premier managed market network. Tell us about yourself so that we can serve you better.
Sign Up