• Online Features  This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (216)  • Contact me when this article is cited  Related Content  • Related letters  • Similar articles in this journal  Topic Collections  • Aging/ Geriatrics  • Viral Infections  • Public Health  • Immunization  • Infectious Diseases  • Alert me on articles by topic  Social Bookmarking   What's this?

Lone Simonsen, PhD; Thomas A. Reichert, MD, PhD; Cecile Viboud, PhD; William C. Blackwelder, PhD; Robert J. Taylor, PhD; Mark A. Miller, MD

Arch Intern Med. 2005;165:265-272.

Background  Observational studies report that influenza vaccination reduces winter mortality risk from any cause by 50% among the elderly. Influenza vaccination coverage among elderly persons (65 years) in the United States increased from between 15% and 20% before 1980 to 65% in 2001. Unexpectedly, estimates of influenza-related mortality in this age group also increased during this period. We tried to reconcile these conflicting findings by adjusting excess mortality estimates for aging and increased circulation of influenza A(H3N2) viruses.

Methods  We used a cyclical regression model to generate seasonal estimates of national influenza-related mortality (excess mortality) among the elderly in both pneumonia and influenza and all-cause deaths for the 33 seasons from 1968 to 2001. We stratified the data by 5-year age group and separated seasons dominated by A(H3N2) viruses from other seasons.

Results  For people aged 65 to 74 years, excess mortality rates in A(H3N2)-dominated seasons fell between 1968 and the early 1980s but remained approximately constant thereafter. For persons 85 years or older, the mortality rate remained flat throughout. Excess mortality in A(H1N1) and B seasons did not change. All-cause excess mortality for persons 65 years or older never exceeded 10% of all winter deaths.

Conclusions  We attribute the decline in influenza-related mortality among people aged 65 to 74 years in the decade after the 1968 pandemic to the acquisition of immunity to the emerging A(H3N2) virus. We could not correlate increasing vaccination coverage after 1980 with declining mortality rates in any age group. Because fewer than 10% of all winter deaths were attributable to influenza in any season, we conclude that observational studies substantially overestimate vaccination benefit.

Author Affiliations: National Institute of Allergy and Infectious Diseases (NIAID) (Dr Simonsen) and Fogarty International Center (Drs Viboud and Miller), National Institutes of Health, Bethesda, Md; and Entropy Research Institute, Boston, Mass (Dr Reichert).

CiteULike    Connotea    Delicious    Digg    Facebook    Reddit    Technorati    Twitter     What's this?

RELATED LETTERS

Influenza Vaccination and Mortality in the United States
Heath Kelly, Trang Vu, and David Smith
Arch Intern Med. 2005;165(17):2037-2038.
EXTRACT | FULL TEXT  

Vaccinate Schoolchildren to Reduce Influenza Toll
Gilbert Ross
Arch Intern Med. 2005;165(17):2038.
EXTRACT | FULL TEXT  

Influenza Vaccination Among the Elderly in the United States
William W. Thompson, David K. Shay, Eric Weintraub, Lynnette Brammer, Nancy J. Cox, and Keiji Fukuda
Arch Intern Med. 2005;165(17):2038-2039.
EXTRACT | FULL TEXT  

Influenza Vaccination Among the Elderly in the United States—Reply
Lone Simonsen, Thomas A. Reichert, Cecile Viboud, William C. Blackwelder, Robert J. Taylor, and Mark A. Miller
Arch Intern Med. 2005;165(17):2039-2040.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Influenza emergence in the face of evolutionary constraints
Kucharski and Gog
Proc R Soc B 2012;279:645-652.
ABSTRACT | FULL TEXT  

Statins and Influenza: Can We Move Forward?
Walsh
The Journal of Infectious Disease 2012;205:1-3.
FULL TEXT  

Time series methods for obtaining excess mortality attributable to influenza epidemics
Nunes et al.
Stat Methods Med Res 2011;20:331-345.
ABSTRACT  

Impact of Pneumococcal Conjugate Vaccination of Infants on Pneumonia and Influenza Hospitalization and Mortality in All Age Groups in the United States
Simonsen et al.
mBio 2011;2:e00309-10-e00309-10.
ABSTRACT | FULL TEXT  

Effectiveness of Seasonal Vaccine in Preventing Confirmed Influenza-Associated Hospitalizations in Community Dwelling Older Adults
Talbot et al.
The Journal of Infectious Disease 2011;203:500-508.
ABSTRACT | FULL TEXT  

Elevated Influenza-Related Excess Mortality in South African Elderly Individuals, 1998-2005
Cohen et al.
Clinical Infectious Diseases 2010;51:1362-1369.
ABSTRACT | FULL TEXT  

A Paradigm for the Control of Influenza
Lewin
The Journal of Infectious Disease 2010;202:1619-1622.
FULL TEXT  

Available evidence points to low effectiveness of influenza vaccines for older people
Simonsen
Evid. Based Med. 2010;15:109-110.
FULL TEXT  

The reproduction number of seasonal influenza epidemics in Brazil, 1996-2006
Chowell et al.
Proc R Soc B 2010;277:1857-1866.
ABSTRACT | FULL TEXT  

Influenza Circulation and the Burden of Invasive Pneumococcal Pneumonia during a Non-pandemic Period in the United States
Walter et al.
Clinical Infectious Diseases 2010;50:175-183.
ABSTRACT | FULL TEXT  

mTOR Regulation and Therapeutic Rejuvenation of Aging Hematopoietic Stem Cells
Chen et al.
Sci Signal 2009;2:ra75-ra75.
ABSTRACT | FULL TEXT  

The Need for Validation of Statistical Methods for Estimating Respiratory Virus-Attributable Hospitalization
Gilca et al.
Am J Epidemiol 2009;170:925-936.
ABSTRACT | FULL TEXT  

Influenza in long-term care facilities: Preventable, detectable, treatable
Mossad
Cleveland Clinic Journal of Medicine 2009;76:513-521.
ABSTRACT | FULL TEXT  

Influenza Vaccination and Mortality: Differentiating Vaccine Effects From Bias
Fireman et al.
Am J Epidemiol 2009;170:650-656.
ABSTRACT | FULL TEXT  

Effects of annual influenza vaccination on winter mortality in elderly people with chronic heart disease
de Diego et al.
Eur Heart J 2009;30:209-216.
ABSTRACT | FULL TEXT  

Influenza vaccine in the over 65s
Jordan and Hawker
BMJ 2008;337:a2545-a2545.
FULL TEXT  

Induction of CD56 and TCR-Independent Activation of T Cells with Aging
Lemster et al.
J. Immunol. 2008;180:1979-1990.
ABSTRACT | FULL TEXT  

Epidemiologic Characterization of the 1918 Influenza Pandemic Summer Wave in Copenhagen: Implications for Pandemic Control Strategies
Andreasen et al.
The Journal of Infectious Disease 2008;197:270-278.
ABSTRACT | FULL TEXT  

Effectiveness of influenza vaccination and its impact on health inequalities
Antunes et al.
Int J Epidemiol 2007;36:1319-1326.
ABSTRACT | FULL TEXT  

Influenza vaccination and mortality: prospective cohort study of the elderly in a large geographical area
Ortqvist et al.
Eur Respir J 2007;30:414-422.
ABSTRACT | FULL TEXT  

Commentary: Observational studies and the art of accurately measuring influenza vaccine benefits
Simonsen
Int J Epidemiol 2007;0:dym084v1-2.
FULL TEXT  

Seasonality of Influenza in Brazil: A Traveling Wave from the Amazon to the Subtropics
Alonso et al.
Am J Epidemiol 2007;165:1434-1442.
ABSTRACT | FULL TEXT  

Prevaccine Determination of the Expression of Costimulatory B7 Molecules in Activated Monocytes Predicts Influenza Vaccine Responses in Young and Older Adults
van Duin et al.
The Journal of Infectious Disease 2007;195:1590-1597.
ABSTRACT | FULL TEXT  

Hospitalizations and Deaths from Diarrhea and Rotavirus among Children <5 Years of Age in the United States, 1993-2003
Fischer et al.
The Journal of Infectious Disease 2007;195:1117-1125.
ABSTRACT | FULL TEXT  

Prevention of Influenza Episodes With Colostrum Compared With Vaccination in Healthy and High-Risk Cardiovascular Subjects: The Epidemiologic Study in San Valentino
Cesarone et al.
CLIN APPL THROMB HEMOST 2007;13:130-136.
ABSTRACT  

Influenza Vaccination and Risk of Mortality Among Adults Hospitalized With Community-Acquired Pneumonia
Spaude et al.
Arch Intern Med 2007;167:53-59.
ABSTRACT | FULL TEXT  

Influenza vaccination: policy versus evidence: Vested interests will always trump evidence
Hall
BMJ 2006;333:1021-1021.
FULL TEXT  

Influenza vaccination: policy versus evidence: Policy is in the lead
Doshi
BMJ 2006;333:1020-1021.
FULL TEXT  

Epidemiology of Seasonal Influenza: Use of Surveillance Data and Statistical Models to Estimate the Burden of Disease
Thompson et al.
The Journal of Infectious Disease 2006;194:S82-S91.
ABSTRACT | FULL TEXT  

Influenza vaccination: policy versus evidence.
Jefferson
BMJ 2006;333:912-915.
FULL TEXT  

Interdisciplinary Epidemiologic and Economic Research Needed to Support a Universal Childhood Influenza Vaccination Policy
Coleman et al.
Epidemiol Rev 2006;28:41-46.
ABSTRACT | FULL TEXT  

Insights into the Interaction between Influenza Virus and Pneumococcus
McCullers
Clin. Microbiol. Rev. 2006;19:571-582.
ABSTRACT | FULL TEXT  

Bias in studies of influenza vaccine effectiveness: the authors reply to Hak et al.
JACKSON et al.
Int J Epidemiol 2006;35:799-800.
FULL TEXT  

Safety of high doses of influenza vaccine and effect on antibody responses in elderly persons.
Keitel et al.
Arch Intern Med 2006;166:1121-1127.
ABSTRACT | FULL TEXT  

T Cell Responses Are Better Correlates of Vaccine Protection in the Elderly
McElhaney et al.
J. Immunol. 2006;176:6333-6339.
ABSTRACT | FULL TEXT  

Evidence of bias in estimates of influenza vaccine effectiveness in seniors
Jackson et al.
Int J Epidemiol 2006;35:337-344.
ABSTRACT | FULL TEXT  

Commentary: Benefits of influenza vaccine in US elderly--new studies raise questions
Glezen and Simonsen
Int J Epidemiol 2006;35:352-353.
FULL TEXT  

Viral Pneumonia in Older Adults
Falsey and Walsh
Clinical Infectious Diseases 2006;42:518-524.
ABSTRACT | FULL TEXT  

Patterns of Influenza-associated Mortality among US Elderly by Geographic Region and Virus Subtype, 1968-1998
Greene et al.
Am J Epidemiol 2006;163:316-326.
ABSTRACT | FULL TEXT  

US flu mortality estimates are based on solid science
Simonsen et al.
BMJ 2006;332:177-178.
FULL TEXT  

Mortality due to Influenza in the United States--An Annualized Regression Approach Using Multiple-Cause Mortality Data
Dushoff et al.
Am J Epidemiol 2006;163:181-187.
ABSTRACT | FULL TEXT  

Pneumonia in Older Adults: Reversing the Trend
File and Tan
JAMA 2005;294:2760-2763.
FULL TEXT  

Reply to Reichert and Christensen
Viboud et al.
The Journal of Infectious Disease 2005;192:1860-1862.
FULL TEXT  

Influenza Vaccine Confusion: A Call for an Alternative Evidence-Based Approach
Yogev
Pediatrics 2005;116:1214-1215.
FULL TEXT  

Vaccinate Schoolchildren to Reduce Influenza Toll
Ross
Arch Intern Med 2005;165:2038-2038.
FULL TEXT  

Influenza Vaccination Among the Elderly in the United States--Reply
Simonsen et al.
Arch Intern Med 2005;165:2039-2040.
FULL TEXT  

Influenza Vaccination and Mortality in the United States
Kelly et al.
Arch Intern Med 2005;165:2037-2038.
FULL TEXT  

Influenza Vaccination Among the Elderly in the United States
Thompson et al.
Arch Intern Med 2005;165:2038-2039.
FULL TEXT  

Intake of n-6 and n-3 fatty acids and fish and risk of community-acquired pneumonia in US men
Merchant et al.
Am J Clin Nutr 2005;82:668-674.
ABSTRACT | FULL TEXT  

Multinational Impact of the 1968 Hong Kong Influenza Pandemic: Evidence for a Smoldering Pandemic
Viboud et al.
The Journal of Infectious Disease 2005;192:233-248.
ABSTRACT | FULL TEXT