The efficacy, effectiveness and cost-effectiveness of inactivated influenza virus vaccines

doi:10.1016/S0264-410X(03)00070-7

Vaccine

Volume 21, Issue 16, 1 May 2003, Pages 1769-1775

https://doi.org/10.1016/S0264-410X(03)00070-7 Get rights and content

Abstract

Influenza is a major cause of morbidity and mortality worldwide. Currently available inactivated influenza virus vaccines are safe and effective in preventing influenza. Substantial health benefits are seen across all age and risk groups. Studies assessing the economic benefits of vaccination suggest that vaccination is highly cost effective and in many cases cost saving among the elderly. Influenza vaccination has also been associated with significant economic benefits in younger adults and children. Additional health economic studies from developing countries and from tropical/subtropical regions will be vitally important for better understanding of the global burden of influenza and potential benefits of vaccination.

Introduction

Inactivated influenza virus vaccines have been available for more than 50 years. These vaccines have an excellent safety profile [1] and hundreds of millions of doses are used worldwide each year. The World Health Organization recommends annual vaccination on a priority basis to groups at high-risk for serious complications from influenza such as the elderly and persons with chronic underlying medical conditions [2]. However, when major outbreaks are expected, all individuals should ideally have the opportunity to be vaccinated. This report will summarize the data on the efficacy, effectiveness and cost-effectiveness of inactivated influenza virus vaccines in three target groups: the elderly, healthy working adults and children.

Section snippets

The elderly

The elderly are among the groups at highest risk for the serious complications of influenza such as secondary bacterial pneumonia and exacerbations of underlying chronic medical conditions that result in hospitalization or death. Thus, they are included among the priority groups targeted for vaccination.

In a recent randomized controlled trial among 1838 persons ages 60 and older conducted in The Netherlands, the efficacy of influenza vaccine against laboratory confirmed influenza illness was

Healthy younger adults

There is increasing interest in understanding the benefits of influenza vaccination for healthy, working adults. While this group is not at increased risk for serious complications, influenza is not a trivial illness in this group. Prominent manifestations include increased work absenteeism, impaired work productivity when ill and interference with leisure time activities.

The efficacy of inactivated influenza virus vaccines in healthy younger adult populations has been evaluated in several

Children

Children have generally not been included among the groups targeted for annual influenza vaccination unless they have specific chronic medical conditions such as cardiac disease, asthma or diabetes mellitus that increase the risk for influenza-associated complications. Nevertheless, there is great interest in the role of children in the spread of influenza in communities and in the potential benefits that might be realized if children were routinely immunized. Furthermore, very young children

Conclusion

Influenza is a major cause of illness and suffering in all age groups. Currently, licensed inactivated influenza virus vaccines are safe and highly effective in preventing acute illness and serious complications. In addition to providing substantial health benefits, vaccination may also be associated with significant economic benefits, not only among the elderly but also among healthy working adults and even children. Whenever studies have been available from different countries, they have

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Cited by (233)

Cost-effectiveness of adult vaccinations: A systematic review
2019, Vaccine
Coverage levels for many recommended adult vaccinations are low. The cost-effectiveness research literature on adult vaccinations has not been synthesized in recent years, which may contribute to low awareness of the value of adult vaccinations and to their under-utilization. We assessed research literature since 1980 to summarize economic evidence for adult vaccinations included on the adult immunization schedule.
We searched PubMed, EMBASE, EconLit, and Cochrane Library from 1980 to 2016 and identified economic evaluation or cost-effectiveness analysis for vaccinations targeting persons aged ≥18 years in the U.S. or Canada. After excluding records based on title and abstract reviews, the remaining publications had a full-text review from two independent reviewers, who extracted economic values that compared vaccination to “no vaccination” scenarios.
The systematic searches yielded 1688 publications. After removing duplicates, off-topic publications, and publications without a “no vaccination” comparison, 78 publications were included in the final analysis (influenza = 25, pneumococcal = 18, human papillomavirus = 9, herpes zoster = 7, tetanus-diphtheria-pertussis = 9, hepatitis B = 9, and multiple vaccines = 1). Among outcomes assessing age-based vaccinations, the percent indicating cost-savings was 56% for influenza, 31% for pneumococcal, and 23% for tetanus-diphtheria-pertussis vaccinations. Among age-based vaccination outcomes reporting $/QALY, the percent of outcomes indicating a cost per QALY of ≤$100,000 was 100% for influenza, 100% for pneumococcal, 69% for human papillomavirus, 71% for herpes zoster, and 50% for tetanus-diphtheria-pertussis vaccinations.
The majority of published studies report favorable cost-effectiveness profiles for adult vaccinations, which supports efforts to improve the implementation of adult vaccination recommendations.
Immune responses to intradermal and intramuscular inactivated influenza vaccine among older age group
2017, Vaccine
Influenza viruses cause substantial morbidity, especially in older age groups. Thus, they are amongst high priority groups for routine vaccination. However, vaccine-induced immune responses and effectiveness were reported as relatively low. This study aims to systemically compare the immune responses elicited by intramuscular (IM) and intradermal (ID) injections with inactivated seasonal influenza vaccine among the older age group.
A prospective, open-label, randomized study with a total of 221 adults (>60 years) were enrolled and randomized into 2 groups. Group I (n = 111) received an IM inactivated seasonal influenza vaccine while Group II (n = 110) received the same vaccine ID. Demographics and co-morbidity were collected at baseline. Safety data was collected 3 days post-vaccination using diary card. HAI, NAb and NAI titers were assessed prior to vaccination and at 30, 45, and 60 days post-vaccination. Data was analyzed using SPSS 11.5.
Both groups had similar BMI and co-morbidity. For ID and IM groups, significant differences were observed for seroconversion rate measured using HAI against H1N1 and H3N2 (58/111 vs 44/110 and 68/111 vs 54/110, respectively) being higher for those aged 60–65 years. However, no differences in HI antibody against B/Phuket were seen. For ID route, history of hyperlipidemia and hypertension were factors associated with high seroconversion rate towards influenza A (p = .001). The seroconversion rate risk ratio were 1.31 and 1.25 (p < .05) against A/California/07/09(H1N1) and A/Songkha/308/13 (H3N2), respectively. Interestingly, the GMT (95% CI) of baseline NAI antibodies among both groups were high (56.57 and 54.01 in the ID and IM groups, respectively). A 4-fold increase measured by NAI against A/California/07/09 (H1N1) were detected in 16.67% and 20% of participants who received ID or IM vaccination, respectively.
The seroconversion rates of HAI, NAb and NAI were modest, especially in those >65 years of age. However, it was higher in the ID group as compared to the IM group.
Clinical trial registration: NCT02101749
The seasonal flu vaccination among caregivers in geriatric units: Up-to-date
2016, Revue d'Epidemiologie et de Sante Publique
La vaccination antigrippale des professionnels de santé semble représenter l’une des actions préventives des plus efficaces face à une pathologie à haut risque d’épidémie nosocomiale et potentiellement grave en milieu gériatrique. Ce travail avait pour objectif de faire une mise au point sur le statut vaccinal antigrippal chez le personnel soignant en gériatrie et les raisons expliquant leur réticence vis-à-vis de cette vaccination, afin d’émettre des propositions d’amélioration de la couverture vaccinale.
Une recherche bibliographique des articles publiés depuis 2000 dans le domaine de la gériatrie, des maladies infectieuses ou de la pneumologie a été réalisée, essentiellement sur PubMed. Les principaux mots-clés utilisés pour la recherche étaient « caregivers », « elderly », « flu », « influenza », « nosocomial » et « vaccination ». Tous les résumés en anglais ou en français, issus de cette première sélection, ont été lus par les auteurs afin d’écarter les articles hors sujet. Au final, 64 articles ont été cités dans la bibliographie de cette mise au point.
Malgré les recommandations officielles, la littérature révèle une couverture vaccinale de ce personnel insuffisante à l’échelle nationale et internationale. La couverture vaccinale apparaît plus faible chez le personnel féminin, plus jeune et non médical. Les déterminants pour la vaccination sont le désir de se protéger soi-même, de protéger sa famille et les patients/résidents, ainsi que le vécu grippal antérieur. Les facteurs d’opposition à la vaccination sont complexes, liés à la peur des effets secondaires, au recours à d’autres moyens préventifs, au sentiment d’inefficacité vaccinale, à la mauvaise connaissance de la maladie et du vaccin et aux problèmes organisationnels. Les campagnes de promotion vaccinale, destinées à responsabiliser le professionnel de santé, doivent être multidimensionnelles et fortement incitatives. Le message pédagogique doit être centré sur le bénéfice individuel et adapté selon les catégories socio-professionnelles. Les stratégies incitatives mobiles au sein des services sont déjà une déclinaison pragmatique de ce défi. Le médecin traitant est un pivot incontournable, ainsi que le médecin du travail en lien avec les services d’hygiène hospitalière.
La vaccination antigrippale doit s’inscrire dans l’éducation et la formation du personnel soignant.
Flu vaccinations for healthcare professionals seems to be one of the most effective preventive actions in the face of a disease that carries a high risk of a potentially serious nosocomial epidemic in a geriatric environment. The aim of this study was to take stock of the flu vaccination status among caregivers in the geriatric units and to understand the reasons for their reluctance to be vaccinated, in order to put forward proposals to improve vaccination coverage.
A literature search of articles published since 2000 in the area of geriatrics, infectious diseases or pneumology was mainly conducted on PubMed using the keywords “caregivers”, “elderly”, “flu”, “influenza”, “nosocomial” and “vaccination”. After reading all abstracts in English or French and ruling out irrelevant articles, only 64 relevant articles have been listed in bibliography section.
Despite official recommendations, the literature reveals insufficient vaccination coverage of healthcare personnel at both the national and international level. Vaccination coverage seems to be lower among younger female non-medical staff. The factors that determine the likelihood of vaccination are the wish to protect one's self, one's family and patients/residents, as well as the experience of earlier bouts of flu. Factors that oppose vaccination are complex and related to the fear of side effects, the use of other preventive measures, the feeling that vaccination is ineffective, poor understanding of the disease and the vaccine, forgetfulness and problems of organization. Campaigns to promote vaccination that target healthcare professionals must be multidimensional and very incentive. The pedagogical message must be centered on the benefits to the individual and adjusted to socio-professional categories. Mobile strategies in the different departments to encourage staff are a pragmatic solution to this challenge. The referring doctor has an essential role to play, as does the occupational doctor in association with the hospital hygiene services.
Flu vaccinations must be included in the education and training of caregivers.
The free vaccination policy of influenza in Beijing, China: The vaccine coverage and its associated factors
2016, Vaccine
Citation Excerpt :
People aged 65 years and over are at great risk of severe illness and possibly even death [2]. Thus, the elderly are included among the priority groups targeted for vaccination because of their high risk of serious complications due to influenza resulting in hospitalizations or death [3]. To defend against influenza, the major strategy for controlling influenza is yearly immunizations [4] as recommended by the World Health Organization (WHO).
In order to improve influenza vaccination coverage, the coverage rate and reasons for non-vaccination need to be determined. In 2007, the Beijing Government published a policy providing free influenza vaccinations to elderly people living in Beijing who are older than 60. This study examines the vaccination coverage after the policy was carried out and factors influencing vaccination among the elderly in Beijing.
A cross-sectional survey was conducted through the use of questionnaires in 2013. A total of 1673 eligible participants were selected by multistage stratified random sampling in Beijing using anonymous questionnaires in-person. They were surveyed to determine vaccination status and social demographic information.
The influenza vaccination coverage was 38.7% among elderly people in Beijing in 2012. The most common reason for not being vaccinated was people thinking they did not need to have a flu shot. After controlling for age, gender, income, self-reported health status, and the acceptance of health promotion, the rate in rural areas was 2.566 (95% confidence interval [CI], 1.801–3.655, P < 0.010) times greater than that in urban areas. Different mechanisms of health education and health promotion have different influences on vaccination uptake. Those whom received information through television, community boards, or doctors were more likely to get vaccinated compared to those who did not (Odds Ratio [OR] = 1.403, P < 0.010; OR = 1.812, P < 0.010; OR = 2.647, P < 0.010).
The influenza vaccine coverage in Beijing is much lower than that of developed countries with similar policies. The rural–urban disparity in coverage rate (64.1% versus 33.5%), may be explained by differing health provision systems and personal attitudes toward free services due to socioeconomic factors. Methods for increasing vaccination levels include increasing the focus on primary care and health education programs, particularly recommendations from doctors, to the distinct target populations, especially with a focus on expanding these efforts in urban areas.
Enhancement of the safety of live influenza vaccine by attenuating mutations from cold-adapted hemagglutinin
2016, Virology
In our previous study, X-31ca-based H5N1 LAIVs, in particular, became more virulent in mice than the X-31ca MDV, possibly by the introduction of the surface antigens of highly pathogenic H5N1 influenza virus, implying that additional attenuation is needed in this cases to increase the safety level of the vaccine. In this report we suggest an approach to further increase the safety of LAIV through additional cold-adapted mutations in the hemagglutinin. The cold-adaptation of X-31 virus resulted in four amino acid mutations in the HA. We generated a panel of 7:1 reassortant viruses each carrying the hemagglutinins with individual single amino acid mutations. We examined their phenotypes and found a major attenuating mutation, N81K. This attenuation marker conferred additional temperature-sensitive and attenuation phenotype to the LAIV. Our data indicate that the cold-adapted mutation in the HA confers additional attenuation to the LAIV strain, without compromising its productivity and immune response.
Preserved Cellular Immunity Upon Influenza Vaccination in Most Patients with Common Variable Immunodeficiency
2020, Journal of Allergy and Clinical Immunology: In Practice
Citation Excerpt :
In contrast, van Assen et al20 showed in their cohort of 15 patients with CVID neither an increase in A/H1N1- or A/H3N2-specific antibodies in hemagglutination inhibition assay nor an adequate increase in IFN-γ–producing CD4+ T cells by flow cytometry in comparison to healthy controls. Influenza vaccines provide protection by generating high-affinity antibodies against viral hemagglutinin,21,22 which depend on T follicular helper (TFH) cell activity within the germinal center (GC) reaction.23-25 Therefore, Bentebibel et al26 used elevated expression of the inducible costimulator (ICOS) on a subset of circulating TFH cells 1 week after vaccination as readout for a positive influenza vaccine response.
Vaccination against influenza is recommended for patients with common variable immunodeficiency (CVID), although humoral immune responses in these patients are impaired and the evidence of effective T-cell responses in CVID is not well established.
To determine plasmablast and T-cellular vaccination responses against influenza in patients with CVID.
Patients with CVID and healthy controls were vaccinated with the quadrivalent vaccine Influsplit Tetra 2018/2019. Before and 1 week after vaccination plasmablasts and circulating inducible costimulator–expressing T follicular helper cells were measured to determine positive vaccine responses in these patients. In addition, antigen-specific T cells were determined by their upregulation of CD25 and OX40 after in vitro restimulation with the vaccine.
Most healthy controls but only 1 patient with CVID mounted a positive humoral immune response, measured by an increase in plasmablasts 1 week after vaccination. In contrast, most patients with CVID showed an increase in inducible costimulator⁺ T follicular helper cells and/or an increase in antigen-specific CD25⁺OX40⁺ T cells 1 week after vaccination, demonstrating a positive T-cellular immune response.
Despite the remaining challenge of accurately assessing the complexity of T-cell responses, the recommendation of vaccinating patients with CVID against influenza is reasonable.

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The efficacy, effectiveness and cost-effectiveness of inactivated influenza virus vaccines

Abstract

Introduction

Section snippets

The elderly

Healthy younger adults

Children

Conclusion

Lancet

Vaccine

Vaccine

Vaccine

Vaccine

Health Policy

Vaccine

Vaccine

Sem. Pediatr. Infect. Dis.

Vaccine

The efficacy of influenza vaccination in elderly individuals. A randomized double-blind placebo-controlled trial

JAMA

Influenza vaccination programs for elderly persons: cost-effectiveness in a health maintenance organization

Ann. Intern. Med.

Influenza vaccine effectiveness in preventing hospitalization for pneumonia in the elderly

Am. J. Epidemiol.

Influenza vaccine effectiveness in preventing hospitalization among the elderly during influenza type A and type B seasons

Int. J. Epidemiol.

Benefits of influenza vaccination for low-, intermediate-, and high-risk senior citizens

Arch Intern. Med.

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.

Clinical effectiveness of influenza vaccination in Manitoba

JAMA

Effectiveness of influenza vaccination in reducing hospital admissions during the epidemic of 1989–1990

Epidemiol. Infect.

Study of the effectiveness of influenza vaccination in the elderly in the epidemic of 1989–1990 using a general practice database

Epidemiol. Infect.

Reduction in hospital admission for pneumonia in non-institutionalised elderly people as a result of influenza vaccination: a case–control study in Spain

J. Epidemiol. Community Health

Effectiveness of influenza vaccination in the elderly in a community in Italy

Eur. J. Epidemiol.

Influence of high-risk medical conditions on the effectiveness of influenza vaccination among elderly members of 3 large managed-care organizations

Clin. Infect. Dis.

The efficacy of influenza vaccine in elderly persons: a meta-analysis and review of the literature

Ann. Intern. Med.

Cost-effective analysis of influenza vaccination in the elderly

Age

Prevention and control of type A influenza infections in nursing homes. Benefits and costs of four approaches using vaccination and amantadine

Ann. Intern. Med.

The costs and benefits of preventing influenza in Ontario’s elderly

Can. J. Public Health

Economic evaluation of influenza vaccination. Assessment for The Netherlands

Pharmacoeconomics

Economic evaluation of vaccination against influenza in New Zealand

Pharmacoeconomics

Control of influenza

Med. J. Aust.