Decline in influenza-associated mortality among Dutch elderly following the introduction of a nationwide vaccination program
Introduction
Influenza epidemics are held responsible for substantial morbidity and mortality, particularly among the elderly [1], [2], [3], [4], [5]. Several observational cohort studies reported influenza vaccination to confer substantial reductions in hospitalisations for acute respiratory, cardiovascular, and cerebrovascular events and all-cause mortality during influenza seasons [6], [7], [8], [9], [10], [11]. It has therefore been hypothesized that increasing influenza vaccination coverage rates should lead to a decrease in influenza-associated mortality. Surprisingly, data from ecological trend studies conducted in the United States and Italy did not support this hypothesis [12], [13], and the benefits of vaccination have been questioned more and more. Yet, these studies may have been hindered by the major disparities in vaccination rates by geography as well as by socioeconomic, demographic, and health characteristics making it very difficult to estimate individual benefit from population-level data [6], [14].
The Netherlands encompass a rather homogeneous population, and influenza vaccination approximated 80% after the introduction of routine influenza vaccination among all elderly in 1996. The aim of the current study was to assess the impact of influenza vaccination on influenza-attributable mortality by comparing influenza-attributable mortality among elderly before and after the introduction of the vaccination program.
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Study population
Weekly all-cause mortality data of all Dutch citizens aged 65 years and older were obtained during the respiratory seasons 1992–2003 from Statistics Netherlands, Voorburg/Heerlen, the Netherlands. Each respiratory season started in week 27 of 1 year and lasted until week 26 of the next year.
The Dutch primary care Influenza vaccination program
Until the respiratory season 1996–1997, influenza vaccination was recommended only for persons with certain high-risk medical conditions in the Netherlands (such as chronic heart, lung and renal disease).
Results
In Fig. 3 the weekly mortality rate among persons aged 65 years and older is displayed and influenza virus- and RSV-active periods are indicated. Total winter excess mortality attributable to influenza increased about 10-fold from the age category 65–69 years to the category 80 years and older (Table 1, Table A1). Among all persons aged 65 years and older, influenza-associated mortality decreased over the period from 1992 to 2003 (Fig. 4; Table A2). In the seasons before the introduction of
Discussion
This nationally representative ecological study demonstrated a decline in influenza-associated mortality among elderly after the start of the large-scale influenza vaccination program in the Netherlands in 1996, notably in those aged 65–69 years.
Our methods bare some potential limitations. First of all, we based the estimates of deaths attributable to influenza on epidemiological data. These data naturally lack direct evidence for the cause of death. Additionally, we determined
Acknowledgements
Dr. Nichol reports having served as a consultant to the influenza vaccine manufacturers Sanofi Pasteur, MedImmune, GSK, and Novartis. Dr. Nichol has received or will receive grant support from Sanofi Pasteur and GSK. This study was funded by the Health Council of the Netherlands.
References (28)
- et al.
A meta-analysis of effectiveness of influenza vaccine in persons aged 65 years and over living in the community
Vaccine
(2002) - et al.
Impact of influenza vaccination on major cause-specific mortality
Vaccine
(2007) - et al.
Influenza-related mortality in the Italian elderly: no decline associated with increasing vaccination coverage
Vaccine
(2006) - et al.
Population-wide benefits of routine vaccination of children against influenza
Vaccine
(2005) - et al.
Antibody response to influenza vaccination in the elderly: a quantitative review
Vaccine
(2006) - et al.
The impact of influenza epidemics on mortality: introducing a severity index
Am J Public Health
(1997) - et al.
Pandemic versus epidemic influenza mortality: a pattern of changing age distribution
J Infect Dis
(1998) - et al.
Mortality associated with influenza and respiratory syncytial virus in the United States
JAMA
(2003) - et al.
Influenza-associated hospitalizations in the United States
JAMA
(2004) - et al.
Influenza- and respiratory syncytial virus-associated mortality and hospitalisations
Eur Respir J
(2007)
Effectiveness of influenza vaccine in the community-dwelling elderly
N Engl J Med
The health and economic benefits of influenza vaccination for healthy and at-risk persons aged 65–74 years old
Pharacoeconomics
Influence of high-risk medical conditions on the effectiveness of influenza vaccination among elderly members of 3 large managed-care organizations
Clin Infect Dis
Influenza vaccination and reduction in hospitalizations for cardiac disease and stroke among the elderly
N Eng J Med
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