Prophylaxis of influenza in the eldery. Is there any alternative?
Keywords:
influenza, flu-related illness, flu vaccine, elderly, vitamin D3, extraskeletal effects.Abstract
The benefits of influenza vaccination in the elderly individuals are the subject of serious discussion. Evidence-based medicine can not boast of a large number of randomized clinical trials of the anti-influenza vaccine effectiveness in the elderly due to ethical issues. Over the past 20 years, the only large randomized clinical trial was to investigate an inactivated anti-influenza vaccine in adults aged ≥60 years, which was performed during one season and limited to healthy subjects. This trial demonstrated a 58% reduction in the risk of serologically verified uncomplicated influenza infection in the patients aged 60-69, but no conclusive findings were made for the individuals aged ≥70 years, because the capacity of this study was insufficient to investigate the vaccination efficiency in this age group. Moreover, an evidence of efficacy in healthy subjects aged 60-69 can not be related to the elderly at the age of 70, since elderly age and concomitant diseases are associated with an increased risk of complications and the immune system weakening. With respect to the lack of an evidence, based on randomized clinical trials, we use the results of observational, usually retrospective cohort trials that may be biased. We analyzed the results of randomized multicenter vaccine trials including Fluzone High-Dose Vaccine, meta-analysis data, and concluded that evidence for protection in adults aged 65 years or older is lacking. As an alternative, the results of clinical trials and a meta-analysis of the effectiveness of vitamin D3 for the prevention of influenza / influenza-like illnesses are considered. The extraskeletal effects of vitamin D are analyzed. The interest in vitamin D extraskeletal effects has rapidly grown over the last thirty years due to the identification of Vitamin D receptors (VDRs) in different systems, organs, and cell types. The effects of 1.25 (OH) 2D3 on regulation of both inherent and adaptive immune systems are string and their evaluation has been just started. VDR was detected in activated CD4+ and CD8 + T cells, B cells, neutrophils, monocytes, macrophages, and dendritic cells. The results of the meta-analysis twenty five randomized controlled trials (11,321 participants aged from 0 to 95 years) published by Adrian R. Martineau et al. were presented. The meta-analysis has found that adding vitamin D reduced the risk of acute respiratory infections among all the participants (0.88 corrected odds ratio, 95% 0.81-0.96 confidence interval, P for heterogeneity <0.001). Vitamin D did not affect a part of participants who experience at least one serious adverse event (corrected odds ratio of 0.98, 0.80-1.20, P=0.83). It was finally concluded that the vitamin D supplement was safe and generally protected against acute respiratory infections. A conclusion was drawn on the need for a large clinical trial comparing the efficacy and safety of a flu vaccine and vitamin D3.
References
Fireman B., Lee J., Lewis N. et al. Influenza vaccination and mortality: differentiating vaccine effects from bias // Am J Epidemiol. 2009. Vol. 170(5). P. 650-656.
Jackson L. A., Nelson J. C., Benson P. et al. Functional status is a confounder of the association of influenza vaccine and risk of all cause mortality in seniors // Int J Epidemiol. 2006. Vol. 35(2). P. 345-352.
Jackson M. L., Nelson J. C., Weiss N. S., Influenza vaccination and risk of community-acquired pneumonia in immunocompetent elderly people: a population-based, nested case-control study // Lancet. 2008. Vol. 372(9636). P. 398-405.
Jefferson T. Influenza vaccination: policy versus evidence // BMJ. 2006. Vol. 333(7574). P. 912-915.
Simonsen L., Taylor R. J., Viboud C. et al. Mortality benefits of influenza vaccination in elderly people: an ongoing controversy // Lancet Infect Dis. 2007. Vol. 7(10). P. 658-666.
Vaccines against influenza WHO position paper – November 2012 // Wkly Epidemiol Rec. 2012. Vol. 87(47). P. 461-476.
Schanzer D. L., Sevenhuysen C., Winchester B. et al. Estimating Influenza Deaths in Canada, 1992–2009 // Plos. 2013. https://doi.org/10.1371/journal.pone.0080481.
Thompson W. W., Shay D. K., Weintraub E. et al. Influenza-associated hospitalizations in the United States // JAMA. 2004. Vol. 292(11). P. 1333-1340.
Smith K. J., Raviotta J. M., DePasse J. V. et al. Cost Effectiveness of Influenza Vaccine Choices in Children Aged 2–8 Years in the U.S. // Am J Prev Med. 2016. Vol. 50(5). P. 600–608.
Valenciano M., Ciancio B. C. I-MOVE: a European network to measure the effectiveness of influenza vaccines // Euro Surveill. 2012. Vol. 17(39). pii=20281. https://doi.org/10.2807/ese.17.39.20281-en.
Jefferson T., Rivetti D., Rivetti A. et al. Efficacy and effectiveness of influenza vaccines in elderly people: a systematic review // Lancet. 2005. Vol. 366(9492). P. 1165-1174.
Nelson M., Spiro D., Wentworth D. et al. The early diversification of influenza A/H1N1pdm // PLoS Curr. 2009. Vol. 1. P. RRN1126.
Govaert T. M., Thijs C. T., Masurel N. et al. The efficacy of influenza vaccination in elderly individuals. A randomized double-blind placebo-controlled trial // JAMA. 1994. Vol. 272(21). P. 1661-1665.
Hovden A.-O., Cox R. J., Haaheim L. R. et al. Influenza: the virus and prophylaxis with inactivated influenza vaccine in “at risk” groups, including COPD patients // Int J Chron Obstruct Pulmon Dis. 2007. Vol. 2(3). P. 229–240.
Deng Y., Jing Y., Campbell A.E. et al. Age-related impaired type 1 T cell responses to influenza: reduced activation ex vivo, decreased expansion in CTL culture in vitro, and blunted response to influenza vaccination in vivo in the elderly // J Immunol. 2004. Vol. 172. P. 3437–3446.
Ershler W. B., Moore A. L., Socinski M. A. Influenza and aging: age-related changes and the effects of thymosin on the antibody response to influenza vaccine // J Clin Immunol. 1984. Vol. 4(6). P. 445-454.
Goodwin K., Viboud C., Simonsen L. Antibody response to influenza vaccination in the elderly: a quantitative review // Vaccine. 2006. Vol. 24. P. 1159–1169.
Kang I., Hong M. S., Nolasco H. et al. Age-Associated Change in the Frequency of Memory CD4 + T Cells Impairs Long Term CD4 + T Cell Responses to Influenza Vaccine // J Immunol. 2004. Vol. 173. P. 673-681.
Ruf B. R., Colberg K., Frick M. et al. Open, Randomized Study to Compare the Immunogenicity and Reactogenicity of an Influenza Split Vaccine with an MF59-Adjuvanted Subunit Vaccine and a Virosome-Based Subunit Vaccine in Elderly // Infection. 2004. Vol. 32(4). P. 191-198.
Simons R. J., Reynolds H. Y. Altered immune status in the elderly // Semin Respir Infect. 1990. Vol. 5(4). P. 251-259.
Nelson J. C., Papakostas G. I. et al. Atypical antipsychotic augmentation in major depressive disorder: a meta-analysis of placebo-controlled randomized trials // Am J Psychiatry. 2009. Vol. 166(9). P. 980-991.
Ridenhour B. J., Campitelli M. A., Kwong J. C. et al. Effectiveness of inactivated influenza vaccines in preventing influenza-associated deaths and hospitalizations among Ontario residents aged ≥ 65 years: estimates with generalized linear models accounting for healthy vaccinee effects // PLoS One. 2013. Vol. 8(10). P. e76318.
Voordouw B. C. G., van der Linden P. D., Simonian S. et al. Influenza Vaccination in Community-Dwelling ElderlyImpact on Mortality and Influenza-Associated Morbidity // Arch Intern Med. 2003. Vol. 163(9). P. 1089-1094.
Fedson D. S., Wajda A., Nicol J. P. et al. Clinical effectiveness of influenza vaccination in Manitoba // JAMA. 1993. Vol. 270(16). P. 1956–1961.
Foster D. A., Talsma A., Furumoto-Dawson A. et al. Influenza vaccine effectiveness in preventing hospitalization for pneumonia in the elderly // Am J Epidemiol. 1992. Vol. 136. P. 296–307.
Hak E., Buskens E., van Essen G. A. et al. Clinical Effectiveness of Influenza Vaccination in Persons Younger Than 65 Years With High-Risk Medical Conditions The PRISMA Study // Arch Intern Med. 2005. Vol. 165(3). P. 274–280.
Mullooly J. P., Bennett M. D., Hornbrook M. C. et al. Influenza Vaccination Programs for Elderly Persons: Cost-Effectiveness in a Health Maintenance Organization // Ann Intern Med. 1994. Vol. 121. P. 947–952.
Fireman B., Lee J., Lewis N. et al. A cohort study of the effectiveness of influenza vaccine in older people, performed using the United Kingdom general practice research database // J Infect Dis. 2004. Vol. 190(1). P. 1-10.
Nichol K. L., Wuorenma J., von Sternberg T. Benefits of influenza vaccination for low-, intermediate-, and high-risk senior citizens // Arch Intern Med. 1998. Vol. 158(16). P. 1769-1776.
Nichol K. L., Baken L., Nelson A. Relation between influenza vaccination and outpatient visits, hospitalization, and mortality in elderly persons with chronic lung disease // Ann Intern Med. 1999. Vol. 130(5). P. 397-403.
Nichol K. L. The efficacy, effectiveness and cost-effectiveness of inactivated influenza virus vaccines // Vaccine. 2003. Vol. 21(16). P. 1769-1775.
Nichol K. L., Nordin J. D., Nelson D. B. et al. Effectiveness of influenza vaccine in the community-dwelling elderly // N Engl J Med. 2007. Vol. 357(14). P. 1373-1381.
Nichol K. L., Margolis K. L., Wuorenma J. et al. The efficacy and cost effectiveness of vaccination against influenza among elderly persons living in the community // N Engl J Med. 1994. Vol. 331(12). P. 778-784.
Nordin J., Mullooly J., Poblete S. et al. Influenza vaccine effectiveness in preventing hospitalizations and deaths in persons 65 years or older in Minnesota, New York, and Oregon: data from 3 health plans // J Infect Dis. 2001. Vol. 184(6). P. 665-670.
Monto A. S., Ohmit S. E., Margulies J. R. et al. Medical practice-based influenza surveillance: viral prevalence and assessment of morbidity // Am J Epidemiol. 1995. Vol. 141(6). P. 502-506.
Puig-Barbera J., Márquez-Calderon S., Masoliver-Fores A. et al. Reduction in hospital admissions for pneumonia in non-institutionalised elderly people as a result of influenza vaccination: a case-control study in Spain // J Epidemiol Community Health. 1997. Vol. 51. P. 526–530.
Puig-Barbera J., Diez-Domingo J., Perez Hoyos S. et al Effectiveness of the MF59-adjuvanted influenza vaccine in preventing emergency admissions for pneumonia in the elderly over 64 years of age // Vaccine. 2004. Vol. 23. P. 283–289.
Wang S. T., Lee L. T., Chen L. S. et al. Economic evaluation of vaccination against influenza in the elderly: an experience from a population-based influenza vaccination program in Taiwan // Vaccine. 2005. Vol. 23(16). P. 1973-1980.
Couch R.B. An overview of serum antibody responses to influenza virus antigens // Dev Biol (Basel). 2003. Vol. 115. P. 25-30.
Harper S. A., Fukuda K., Uyeki T. M. et al. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP) // MMWR Recomm Rep. 2004. Vol. 53(RR-6). P. 1-40.
Gross P. A., Hermogenes A. W., Sacks H. S. et al. The efficacy of influenza vaccine in elderly persons. A meta-analysis and review of the literature // Ann Intern Med. 1995. Vol. 123(7). P. 518-527.
Poland G. A., Murray D., Bonilla-Guerrero R. New vaccine development // BMJ : British Medical Journal. 2002. Vol. 324(7349). P. 1315-1319.
Sande M. A., Ronald A. R. Update in infectious diseases // Ann Intern Med. 2004. Vol. 140. P. 290–295.
Simonsen L., Reichert T. A., Viboud C. et al. Impact of influenza vaccination on seasonal mortality in the US elderly population // Arch Intern Med. 2005. Vol. 165(3). P. 265-272.
De Villiers P. J., Steele A. D., Hiemstra L. A. et al. Efficacy and safety of a live attenuated influenza vaccine in adults 60 years of age and older // Vaccine. 2009. Vol. 28(1). P. 228-234.
Jefferson T., Di Pietrantonj C., Al-Ansary L. A. et al. Vaccines for preventing influenza in the elderly // Cochrane Database Syst Rev. 2010. Vol. 2. P. CD004876.
Osterholm M. T., Kelley N. S., Sommer A. et al. Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis // Lancet Infect Dis. 2012. Vol. 12(1). P. 36-44.
Vu T., Farish S., Jenkins M. et al. A meta-analysis of effectiveness of influenza vaccine in persons aged 65 years and over living in the community // Vaccine. 2002. Vol. 20(13-14). P. 1831-1836.
Trucchi C., Paganino C., Orsi A. et al. Influenza vaccination in the elderly: why are the overall benefits still hotly debated? // J Prev Med Hyg. 2015. Vol. 56(1). P. E37–E43.
Belongia E. A., Kieke B. A., Donahue J. G. et al Effectiveness of Inactivated Influenza Vaccines Varied Substantially with Antigenic Match from the 2004–2005 Season to the 2006–2007 Season // The Journal of Infectious Diseases. 2009. Vol. 199(2). P. 159–167.
Centers for Diseases Control and Prevention / [Electronic resourse] / Access mode: http://www.cdc.gov/
Dean A. S., Moffatt C. R., Rosewell A. et al. Incompletely matched influenza vaccine still provides protection in frail elderly // Vaccine. 2010. Vol. 28. P. 864–867.
Talbot H. K., Zhu Y., Chen Q. et al. Effectiveness of influenza vaccine for preventing laboratory-confirmed influenza hospitalizations in adults, 2011-2012 influenza season // Clin Infect Dis. 2013. Vol. 56(12). P. 1774-1777.
Manzoli L., Ioannidis J. P. A., Flacco M. E. et al. Effectiveness and harms of seasonal and pandemic influenza vaccines in children, adults and elderly // Hum Vaccin Immunother. 2012. Vol. 8(7). P. 851–862.
Lang P. O., Mendes A., Socquet J. et al. Effectiveness of influenza vaccine in aging and older adults: comprehensive analysis of the evidence // Clin Interv Aging. 2012. Vol. 7. P. 55-64.
Lang P. O., Aspinall R. Immunosenescence and herd immunity: with an ever-increasing aging population do we need to rethink vaccine schedules? // Expert Rev Vaccines. 2012. Vol. 11(2). P. 167-176.
Nelson J. C., Jackson M. L., Weiss N. S., et al. New strategies are needed to improve the accuracy of influenza vaccine effectiveness estimates among seniors // J Clin Epidemiol. 2009. Vol. 62(7). P. 687–694.
Chiatti C., Barbadoro P., Marigliano A. et al Determinants of influenza vaccination among the adult and older Italian population with chronic obstructive pulmonary disease: a secondary analysis of the multipurpose ISTAT survey on health and health care use // Hum Vaccin. 2011. Vol. 7. P.1021–1025.
Исаенко Е. Ю., Бабич Е. М., Елисеева И. В. et al. Адъюванты в современной вакцинологии // Annals of Mechnikov Institute. 2013. N 4. P. 5-21.
NVIC.org. A Guide to Reforming Vaccine Policy and Low, 2016.
Uitterlinden A. G., Fang Y., Van Meurs J. B. et al. Genetics and biology of vitamin D receptor polymorphisms // Gene. 2004. Vol. 338(2). P. 143-156.
Wolden-Kirk H., Gysemans C., Verstuyf A. et al. Extraskeletal effects of vitamin D // Endocrinol Metab Clin North Am. 2012. Vol. 41(3). P. 571-594.
Baeke F., Takiishi T., Korf H. et al. Vitamin D: modulator of the immune system // Curr Opin Pharmacol. 2010. Vol. 10(4). P. 482-496.
Hewison M.. Antibacterial effects of vitamin D // Nat Rev Endocrinol. 2011. Vol. 7(6). P. 337-345.
Alvarez-Rodriguez L., Lopez-Hoyos M., Munoz-Cacho P. et al. Aging is associated with circulating cytokine dysregulation // Cell Immunol. 2012. Vol. 273(2). P. 124-132.
Liu P. T., Stenger S., Li H. et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response // Science. 2006. Vol. 311(5768). P. 1770-1773.
Cantorna M. T. Why do T cells express the vitamin D receptor? // Ann N Y Acad Sci. 2011. Vol. 1217. P. 77-82.
Selvaraj P., Harishankar M., Afsal K. Vitamin D: Immuno-modulation and tuberculosis treatment // Can J Physiol Pharmacol. 2015. Vol. 93(5). P. 377-384.
Kong J., Xu F., Qu J. et al. Genetic polymorphisms in the vitamin D pathway in relation to lung cancer risk and survival // Oncotarget. 2015. Vol. 6(4). P. 2573–2582.
Verone-Boyle A. R., Shoemaker S., Attwood K. et al. Diet-derived 25-hydroxyvitamin D3 activates vitamin D receptor target gene expression and suppresses EGFR mutant non-small cell lung cancer growth in vitro and in vivo // Oncotarget. 2016. Vol. 7(1). P. 995-1013.
Miller R. A. The aging immune system: primer and prospectus // Science. 1996. Vol. 273. P. 70–74.
Ginaldi L., Loreto M. F. et al. Immunosenescence and infectious diseases // Microbes Infect. 2001. Vol. 3(10). P. 851–857.
Sambhara S., McElhaney J. E. Immunosenescence and Influenza Vaccine Efficacy // Curr Top Microbiol Immunol. 2009. Vol. 333. P. 413-429.
Reber A. J., Chirkova T., Kim J. H. et al. Immunosenescence and Challenges of Vaccination against Influenza in the Aging Population // Aging Dis. 2012. Vol. 3(1). P. 68-90.
Joshi S. R., Shaw A. C., Quagliarello V. J. Pandemic Influenza H1N1 2009, Innate Immunity, and the Impact of Immunosenescence on Influenza Vaccine // Yale J Biol Med. 2009. Vol. 82(4). P. 143–151.
Taylor A. K., Cao W., Vora K. P. et al. Protein energy malnutrition decreases immunity and increases susceptibility to influenza infection in mice // J Infect Dis. 2013. Vol. 207(3). P. 501-510.
Cao W., Kim J. H., Chirkova T. et al. Improving immunogenicity and effectiveness of influenza vaccine in older adults // Expert Rev Vaccines. 2011. Vol. 10(11). P. 1529-1537.
Coleman L. A., Mishina M., Thompson M. et al. Age, serum 25-hydroxyvitamin D and vitamin D receptor (VDR) expression and function in peripheral blood mononuclear cells // Oncotarget. 2016. Vol. 7(24). P. 35512-35521.
van Duin D., Allore H. G., Mohanty S. et al. Prevaccine determination of the expression of costimulatory B7 molecules in activated monocytes predicts influenza vaccine responses in young and older adults // J Infect Dis. 2007. Vol. 195(11). P. 1590-1597.
Plowden J., Renshaw-Hoelscher M., Engleman C. et al. Innate immunity in aging: impact on macrophage function // Aging Cell. 2004. Vol. 3(4). P. 161-167.
Sambhara S., Kurichh A., Miranda R. et al. Heterosubtypic immunity against human influenza A viruses, including recently emerged avian H5 and H9 viruses, induced by FLU-ISCOM vaccine in mice requires both cytotoxic T-lymphocyte and macrophage function // Cell Immunol. 2001. Vol. 211(2). P. 143-153.
Sambhara S., Kurichh A., Miranda R. et al. Enhanced immune responses and resistance against infection in aged mice conferred by Flu-ISCOMs vaccine correlate with up-regulation of costimulatory molecule CD86 // Vaccine. 1998. Vol. 16(18). P. 1698-1704.
Martineau A. R., Jolliffe D. A., Hooper R. L. et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data // BMJ. 2017. Vol. 356. P. i6583.
Miller D. Avoid flu shots, take vitamin D instead / [Electronic resourse] / Access mode: https://therefusers.com/avoid-flu-%20shots-take-%20vitamin-d-%20instead-by-%20donald-w-%20miller-jr-%20md/
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