Effectiveness of Influenza Vaccination in Institutionalized Older Adults: A Systematic Review

IntroductionInfluenza infection is common among institutionalized older adults. Many nonrandomized observational studies on influenza vaccination suggested that it could reduce influenza-related hospitalizations and mortality in institutionalized older adults. Criticism regarding the effectiveness of influenza vaccine estimated by nonrandomized observational studies include the frailty selection bias and use of nonspecific outcome, such as all-cause mortality.MethodsWe conducted a systematic review of studies of influenza vaccination in institutionalized older adults to determine the effects on clinical outcomes. We searched for studies from 3 databases from 1946 to June 2013 assessing effectiveness against influenza infection. We selected studies with good comparability between vaccine group and control group. We expressed vaccine effectiveness (VE) as a proportion, using the formula VE = 1–relative risk or 1–odds ratio. We focused on the following outcomes: influenza-like illness (ILI), laboratory confirmed influenza, hospitalizations due to ILI, or pneumonia and death due to influenza or pneumonia. We did not include all-cause mortality.ResultsEleven studies that satisfied the inclusion criteria were identified, representing 11,262 institutionalized older adults. After meta-analysis, we found a significant reduction in pneumonia (VE: 37%, 95% confidence interval [CI]: 18%–53%, P = .001) and death due to pneumonia or influenza (VE: 34%, CI: 10%–53%, P = .01). There was no significant heterogeneity between studies. There was no significant publication bias.ConclusionInfluenza vaccination in institutionalized older adults could reduce pneumonia and death due to pneumonia or influenza. Influenza vaccination is recommended for institutionalized older adults.     

Change in the efficacy of influenza vaccination after repeated inoculation under antigenic mismatch: A systematic review and meta-analysis

ObjectivesTo examine the effects of repeated influenza vaccination on medically-attended influenza (MAI) and acute respiratory illness (ARI) risk according to the antigenic matching between vaccine and circulating virus strains.MethodsWe performed a systematic review and meta-analysis of randomized studies that compared the risk of MAI and ARI between subjects who had been vaccinated for two consecutive seasons (multiple vaccine group) and those who had been vaccinated in the current season and not in the previous season (single vaccine group).ResultsOf 1467 articles identified, eight studies covering ten seasons were included in meta-analyses. Six studies assessed efficacy against MAI in children, yielding the risk ratios (RR) of 2.04 (95% CI 1.29–3.22) when circulating strains mismatched vaccine strains, and 0.64 (0.33–1.22) when circulating strains matched vaccine strains. When stratified by vaccine types, the reduced efficacy was significant for live-attenuated influenza vaccine only. Three studies investigated efficacy against ARI in children, with the RR of 0.96 (0.81–1.15). The results on adults and the elderly were scarce.ConclusionsInfluenza vaccine efficacy against mismatch strains was lower in repeatedly vaccinated children as compared with those vaccinated for the current season only. The scarcity of available studies may call for further randomized controlled trials on repeated influenza vaccination.     

Cell-mediated protection in influenza infection

Current vaccine strategies against influenza focus on generating robust antibody responses. Because of the high degree of antigenic drift among circulating influenza strains over the course of a year, vaccine strains must be reformulated specifically for each influenza season. The time delay from isolating the pandemic strain to large-scale vaccine production would be detrimental in a pandemic situation. A vaccine approach based on cell-mediated immunity that avoids some of these drawbacks is discussed here. Specifically, cell-mediated responses typically focus on peptides from internal influenza proteins, which are far less susceptible to antigenic variation. We review the literature on the role of CD4+ and CD8+ T cell-mediated immunity in influenza infection and the available data on the role of these responses in protection from highly pathogenic influenza infection. We discuss the advantages of developing a vaccine based on cell-mediated immune responses toward highly pathogenic influenza virus and potential problems arising from immune pressure.     

Does influenza vaccination attenuate the severity of breakthrough infections? A narrative review and recommendations for further research

The effect of influenza vaccination on influenza severity remains uncertain. We reviewed the literature for evidence to inform the question of whether influenza illness is less severe among individuals who received influenza vaccination compared with individuals with influenza illness who were unvaccinated prior to their illnesses. We conducted a narrative review to identify published findings comparing severity of influenza outcomes by vaccination status among community-dwelling adults and children ≥ 6 months of age with laboratory-confirmed influenza illness. When at least four effect estimates of the same type (e.g., odds ratio) were available for a specific outcome and age category (children versus adults), data were pooled with meta-analysis to generate a summary effect estimate. We identified 38 published articles reporting ≥ 1 association between influenza vaccination status and one of 21 indicators of severity of influenza illness among individuals with laboratory-confirmed influenza. Study methodologies and effect estimates were highly heterogenous, with only five severity indicators meeting criteria for calculating a combined effect. Among eight studies, influenza vaccination was associated with 26% reduction in odds of ICU admission among adults with influenza-associated hospitalization (OR = 0.74, 95% CI 0.58, 0.93). Among five studies of adults with influenza-associated hospitalization, vaccinated patients had 31% reduced risk of death compared with unvaccinated patients (OR = 0.69, 95% CI 0.52, 0.92). Among four studies of children with influenza virus infection, vaccination was associated with an estimated 45% reduction in the odds of manifesting fever (OR = 0.55, 95% CI 0.42, 0.71). Vaccination was not significantly associated with receiving a clinical diagnosis of pneumonia among adults hospitalized with influenza (OR = 0.92, 95% CI 0.82, 1.04) or with risk of hospitalization following outpatient influenza illness among adults (OR = 0.60, 95% CI 0.28, 1.28). Overall, our findings support the hypothesis that influenza vaccination may attenuate the course of disease among individuals with breakthrough influenza virus infection.     

Assessment of influenza vaccine effectiveness in a sentinel surveillance network 2010–13, United States

BackgroundInfluenza vaccines are now widely used to reduce the burden of annual epidemics of influenza virus infections. Influenza vaccine effectiveness (VE) is monitored annually to determine VE against each season's circulating influenza strains in different groups such as children, adults and the elderly. Few prospective surveillance programs are available to evaluate influenza VE against medically attended illness for patients of all ages in the United States.MethodsWe conducted surveillance of patients with acute respiratory illnesses in 101 clinics across the US during three consecutive influenza seasons. We analyzed laboratory testing results for influenza virus, self-reported vaccine history, and patient characteristics, defining cases as patients who tested positive for influenza virus and controls as patients who tested negative for influenza virus. Comparison of influenza vaccination coverage among cases versus controls, adjusted for potential confounders, was used to estimate VE as one minus the adjusted odds ratio multiplied by 100%.ResultsWe included 10,650 patients during three influenza seasons from August 2010 through December 2013, and estimated influenza VE in children 6m–5y of age (58%; 95% CI: 49%–66%), children 6–17y (45%; 95% CI: 34%–53%), adults 18–49y (36%; 95% CI: 24%, 46%), and adults ≥50y (34%, 95% CI: 13%, 51%). VE was higher against influenza A(H1N1) compared to A(H3N2) and B.ConclusionsOur estimates of moderate influenza VE confirm the important role of vaccination in protecting against medically attended influenza virus infection.     

Background review for diagnostic test development for Zika virus infection

ObjectiveTo review the state of knowledge about diagnostic testing for Zika virus infection and identify areas of research needed to address the current gaps in knowledge.MethodsWe made a non-systematic review of the published literature about Zika virus and supplemented this with information from commercial diagnostic test kits and personal communications with researchers in European preparedness networks. The review covered current knowledge about the geographical spread, pathogen characteristics, life cycle and infection kinetics of the virus. The available molecular and serological tests and biosafety issues are described and discussed in the context of the current outbreak strain.FindingsWe identified the following areas of research to address current knowledge gaps: (i) an urgent assessment of the laboratory capacity and capability of countries to detect Zika virus; (ii) rapid and extensive field validation of the available molecular and serological tests in areas with and without Zika virus transmission, with a focus on pregnant women; (iii) monitoring the genomic diversity of circulating Zika virus strains; (iv) prospective studies into the virus infection kinetics, focusing on diagnostic sampling (specimen types, combinations and timings); and (v) developing external quality assessments for molecular and serological testing, including differential diagnosis for similar viruses and symptom clusters. The availability of reagents for diagnostic development (virus strains and antigens, quantified viral ribonucleic acid) needs to be facilitated.ConclusionAn international laboratory response is needed, including preparation of protocols for prospective studies to address the most pressing information needs.     

Safety of vaccines used for routine immunization in the United States: An updated systematic review and meta-analysis

BackgroundUnderstanding the safety of vaccines is critical to inform decisions about vaccination. Our objective was to conduct a systematic review of the safety of vaccines recommended for children, adults, and pregnant women in the United States.MethodsWe searched the literature in November 2020 to update a 2014 Agency for Healthcare Research and Quality review by integrating newly available data. Studies of vaccines that used a comparator and reported the presence or absence of key adverse events were eligible. Adhering to Evidence-based Practice Center methodology, we assessed the strength of evidence (SoE) for all evidence statements. The systematic review is registered in PROSPERO (CRD42020180089).ResultsOf 56,603 reviewed citations, 338 studies reported in 518 publications met inclusion criteria. For children, SoE was high for no increased risk of autism following measles, mumps, and rubella (MMR) vaccine. SoE was high for increased risk of febrile seizures with MMR. There was no evidence of increased risk of  intussusception with rotavirus vaccine at the latest follow-up (moderate SoE), nor of diabetes (high SoE). There was no evidence of increased risk or insufficient evidence for key adverse events for newer vaccines such as 9-valent human papillomavirus and meningococcal B vaccines. For adults, there was no evidence of increased risk (varied SoE) or insufficient evidence for key adverse events for the new adjuvanted inactivated influenza vaccine and recombinant adjuvanted zoster vaccine. We found no evidence of increased risk (varied SoE) for key adverse events among pregnant women following tetanus, diphtheria, and acellular pertussis vaccine, including stillbirth (moderate SoE).ConclusionsAcross a large body of research we found few associations of vaccines and serious key adverse events; however, rare events are challenging to study. Any adverse events should be weighed against the protective benefits that vaccines provide.     

Impact of influenza vaccination on healthcare utilization – A systematic review

IntroductionAlthough a vaccine-preventable disease, influenza causes approximately 3–5 million cases of severe illness and about 290,000–650,000 deaths worldwide, which occur primarily among people 65 years and older. Nonetheless, prevention of influenza and its complications rely mainly on vaccination. We aimed to systematically evaluate influenza vaccine effectiveness at reducing healthcare utilization in older adults, defined as the reduction of outpatient visits, ILI and influenza hospitalizations, utilization of antibiotics and cardiovascular events by vaccination status during the influenza season.MethodsWe searched MEDLINE, EMBASE, CINAHL, Cochrane Library and considered any seasonal influenza vaccine, excluding the pandemic (2009–10 season) vaccine. Reviewers independently assessed data extraction and quality assessment.ResultsOf the 8308 citations retrieved, 22 studies were included in the systematic review. Overall, two studies (9%) were deemed at moderate risk of bias, thirteen (59%) at serious risk of bias and seven (32%) at critical risk of bias. For outpatient visits, we found modest evidence of protection by the influenza vaccine. For all-cause hospitalization outcomes, we found a wide range of results, mostly deemed at serious risk of bias. The included studies suggested that the vaccine may protect older adults against influenza hospitalizations and cardiovascular events. No article meeting our inclusion criteria explored the use of antibiotics and ILI hospitalizations. The high heterogeneity between studies hindered the aggregation of data into a meta-analysis.ConclusionThe variability between studies prevented us from drawing a clear conclusion on the effectiveness of the influenza vaccine on healthcare utilization in older adults. Overall, the data suggests that the vaccine may result in a reduction of healthcare utilization in the older population. Further studies of higher quality are necessary.     

Estimating the annual attack rate of seasonal influenza among unvaccinated individuals: A systematic review and meta-analysis

IntroductionSeasonal influenza affects millions of people globally each year, causing significant morbidity and mortality. However, there remains substantial uncertainty about the attack rate (incidence) of influenza, particularly in unvaccinated individuals.MethodsWe undertook a systematic review of vaccine randomised controlled trials (RCTs) that reported on laboratory-confirmed seasonal influenza in the placebo arm. We calculated the influenza attack rate from included studies as the number of laboratory-confirmed positive seasonal influenza cases in the placebo arm divided by the total number of subjects in this arm. A random effects meta-analysis was conducted to estimate the influenza attack rate among unvaccinated individuals (both symptomatic only as well as symptomatic and asymptomatic combined).ResultsWe included 32 RCTs that had a total of 13,329 participants. The pooled estimates for symptomatic influenza were 12.7% (95%CI 8.5%, 18.6%) for children (<18 years), 4.4% (95%CI 3.0%, 6.3%) for adults, and 7.2% (95%CI 4.3%, 12.0%) for older people (65 years and above). The pooled estimates for symptomatic and asymptomatic influenza combined for all influenza were 22.5% (95%CI 9.0%, 46.0%) for children and 10.7% (95%CI 4.5%, 23.2%) for adults. Only one study was identified for symptomatic and asymptomatic combined in older people which had a rate of 8.8% (95%CI 7.0%, 10.8%). There was substantial heterogeneity between studies.ConclusionOverall, we found that approximately 1 in 5 unvaccinated children and 1 in 10 unvaccinated adults were estimated to be infected by seasonal influenza annually, with rates of symptomatic influenza roughly half of these estimates. Our findings help to establish the background risk of seasonal influenza infection in unvaccinated individuals.     

HIV infection and routine childhood immunization: a review

Some significant studies reported in the world literature which provide a scientific basis for immunization policy for those children known to be infected with human immunodeficiency virus (HIV) are reviewed. The review covers current experience with immunization of children infected with HIV along with relevant data on immunization of HIV-infected adults and in vitro studies with vaccine antigens and HIV-infected cells. Live vaccines have been contraindicated in children with immunodeficiency diseases because of the potential for disseminated infection with either the viral or bacterial vaccine strain. The assessment of a similar risk in HIV-infected children is complicated by the fact that it is not always known whether HIV-infected children actually are immunodeficient when immunized. Generally, inactivated vaccines are not considered to present a risk to immunodeficient children, but questions have been raised regarding the potential for any immunization to accelerate the course of HIV infection. Consequently, the safety of inactivated vaccines must be considered also. Local reactions and disseminated disease have been describe in HIV-infected individuals. The rate of dissemination of BCG cannot be determined from the available case reports, but they suggest the possibility of an increased risk for this otherwise unusual complication of BCG immunization. Limited data suggest that live measles vaccine doses not cause severe complications in children with HIV infection. Both reports from the US and Europe have failed to document adverse reactions to either live oral or inactivated polio vaccines. No side effects of DPT vaccine were noted in 2 published reports from Europe and the US. Available data on immunogenicity in children and adults show that both primary and secondary antibody responses to immunization are attenuted in the presence of HIV infection. This is particularly the case when immunodeficiency is present. It has been difficult to assess vaccine efficacy in HIV-infected children from industrialized nations due to the relatively low incidence of both vaccine-preventable disease and HIV infection. Only preliminary studies on vaccine efficacy are available from developing nations. This review offers some general support for the recommendations on immunizations of HIV-infected children that were developed by the World Health Organization and the Advisory Committee on Immunization Practices of the US Public Health service. For asymptomatic HIV-infected children, both groups recommend continued administration of standard vaccines. For symptomatic HIV-infected children, both groups recommend continued administration of inactivated vaccines but differ in their recommendations on live vaccines.     

Efficacy,immunogenicity, and safety of available vaccines in children on biologics: A systematic review and meta-analysis

Vaccinations are essential for preventing infectious diseases in children with chronic diseases as they have increased risk of infection from frequent use of biologics. Response to immunizations in this group is not well known.ObjectiveA systematic review was performed to evaluate three primary outcomes: efficacy; immunogenicity; and safety of vaccines in children with chronic conditions treated with biologics.MethodsThe protocol for our systematic review and meta-analysis was registered and published with PROSPERO. We searched electronic bibliographic databases for studies published from 2009 to 2019, focusing on vaccinations in children with chronic conditions treated with biologics.ResultsWe retrieved 532 records. Thirty-one full-text articles were selected, and 14 were included in the meta-analysis. No significant publication bias was found. Efficacy: limited data are available regarding the efficacy of vaccination, as most studies have focused on immunogenicity as surrogate outcome for efficacy. Immunogenicity: patients receiving anti-TNF-alpha therapy had a statistically significant risk of poor seroconversion (p = 0.028) and seroprotection by the serotype B influenza vaccine [inflammatory bowel disease (IBD) p = 0.013; juvenile idiopathic arthritis (JIA) p = 0.004]. We found adequate responses with H1N1 and H3N2 serotypes. Few studies existed for pneumococcal, hepatitis A virus, hepatitis B virus, varicella-zoster virus, Measles Mumps Rubella virus, and multiple vaccine administration. Safety: vaccine administration was not associated with serious side effects, but JIA patients on anti-TNF alpha therapy had a statistically significant risk of presenting with myalgia or arthralgia postinfluenza vaccine (p = 0.014).ConclusionsMore evidence concerning efficacy, immunogenicity, and safety of vaccinations is needed to guide physicians in the vaccine decision process for this pediatric population.     

Exploring indirect protection associated with influenza immunization – A systematic review of the literature

BackgroundInfluenza causes significant annual morbidity and mortality, particularly in older adults, for whom influenza vaccine effectiveness (VE) is also lower. Immunizing one group (e.g., children) against influenza may indirectly protect another group (e.g., older adults) against influenza and its complications.MethodsWe updated previous systematic reviews on indirect protection against influenza by searching MEDLINE and EMBASE for relevant human studies published until January 4, 2017. We abstracted and critically appraised English language publications that reported or provided information to calculate indirect VE against influenza, as a percentage, in non-institutional settings.We developed a term called ‘estimated actual protection’ to explore the relationship between indirect protection and the product of direct VE and relative vaccine coverage. We calculated estimated actual protection for a subset of studies that reported coverage and indirect VE for: laboratory-confirmed influenza; outpatient care for respiratory illness; influenza-associated emergency visits; or influenza-associated hospitalizations. We ran linear mixed models to compare estimated actual protection against indirect VE for the four outcomes, and graphed the data.ResultsOf 2320 unique records identified, we abstracted and appraised 26 articles describing 24 studies. The majority of included studies reported at least one outcome suggesting that immunizing one group reduced influenza-related outcomes in another group. Critical appraisal of the abstracted studies identified recurring methodological weaknesses, such as lack of laboratory-confirmed influenza.Our exploratory analyses of 18 studies indicated a positive but not statistically significant relationship between estimated actual protection and indirect protection for each of the four outcomes.ConclusionsOur systematic review and exploratory analyses suggest influenza immunization provides some level of indirect protection. However, our critical appraisal highlights the need for a standardized and consistently applied approach to measuring indirect protection against influenza to fill existing knowledge gaps. Additionally, the concept of estimated actual protection requires validation.     

Effect of inactivated influenza vaccination on human coronavirus infection: Secondary analysis of a randomized trial in Hutterite colonies

BackgroundAlthough influenza vaccines provide protection against influenza viruses, concern has been raised that they may increase susceptibility to non-influenza respiratory viruses. As pandemic lockdowns end, temporal overlap of circulation of seasonal influenza viruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is expected. Understanding the impact of influenza vaccination on risk of coronavirus infection is therefore of considerable public health importance.MethodsWe performed a secondary analysis of a randomized trial where children and adolescents in Canadian Hutterite colonies were randomly assigned by colony to receive the 2008–2009 seasonal inactivated trivalent influenza vaccine (TIV) or a control hepatitis A (HepA) vaccine. All 3273 colony members (vaccinated children and nonvaccine recipients) were followed for the primary outcome of RT-PCR confirmed seasonal coronavirus infection. Serum collected pre- and post-vaccination was analyzed for titers of IgG antibodies towards human coronaviruses (HCoV).ResultsThe incidence of coronavirus infection was 0·18/1000 person-days in the colonies that received TIV vs 0.36/1000 person-days in the control group, hazard ratio (HR) 0.49 [0.21–1.17]. The risk reduction among non-vaccine recipients in the TIV group compared to the control group was HR 0.55 [0.24–1.23]. There was an increase in the geometric mean fold change of HCoV-OC43 antibody titers following TIV compared to HepA vaccine (mean difference 1.2 [0.38–2.06], p = 0.007), and an increase in geometric mean HCoV-NL63 antibody titers post-TIV (262.9 vs 342.9, p = 0.03).ConclusionThe influenza vaccine does not increase the risk of a coronavirus infection. Instead, the influenza vaccine may reduce the rate of coronavirus infections by inducing cross-reactive anti-coronavirus IgG antibodies.     

Knowledge,attitudes and practices related to the influenza virus and vaccine among older adults in Eastern China

BackgroundThis study aims to assess the association between socio-demographic and health characteristics of older adults in Eastern China and knowledge, attitudes, and practices (KAP) about the influenza virus and vaccine.MethodsA prospective cohort of 1506 older adults (aged ≥60 years) was enrolled from November to December 2015 in Jiangsu Province. We examined the association between demographics, health and functional status, and cognitive impairment at enrollment with awareness of influenza virus and vaccine and KAP items focused on five Health Belief Model domains. At a 12-month follow-up interview we assessed change in awareness and readiness to be vaccinated.ResultsOne in five older adults was aware of the influenza virus (21%) or vaccine (20%); even fewer reported having at least “a little” knowledge of the virus and vaccine (7% and 4%, respectively); less than 1% reported ever receiving an influenza vaccine. Retirement, higher education and income, and normal cognitive status were consistently associated with both awareness and knowledge of influenza virus. The odds of having at least “a little” knowledge of the vaccine was 2.9-fold (95% CI = 1.6–5.3) higher among older adults with at least some secondary schooling. Among the 108 with knowledge of the virus, 55% said they “worry about getting the flu this season.” Among the 73 with knowledge of the vaccine, 92% believed the vaccine was at least somewhat effective and less than half (43%) thought that influenza vaccination was safe. At a 12-month follow-up interview, 33% (442/1333) increased from no knowledge to at least “a little”.ConclusionsIf and when influenza vaccines become widely available to older adults in China, our results indicate that influenza vaccination campaigns with basic information on the virus and vaccine could be beneficial for all older adults, especially those with less education and/or more cognitive impairment.     

Vaccinations in prison settings: A systematic review to assess the situation in EU/EEA countries and in other high income countries

IntroductionIn 2016, more than 600,000 persons were being held in EU/EEA correctional facilities on a given day. People in prison may be at risk of vaccine-preventable diseases. While vaccination recommendations for people in prison exist, little is known on coverage and implementation options.MethodsWe performed a systematic review on existing evidence on vaccination in prison settings in the EU/EEA. We searched peer-reviewed and grey literature following international methodology and reporting standards, to gather records published between 1980 and 2016 in all languages. We analysed quantitative (acceptance, uptake, cost-effectiveness) and qualitative (barriers) outcomes.ResultsOut of 7041 identified records, 19 full-text articles were included from peer-reviewed literature and two from grey literature. Of these, 18 reported on hepatitis A and/or B virus (HAV/HBV), two on influenza and one on MMR vaccination. Two studies on HAV vaccine reported varying acceptance (5–91%) and uptake rates (62.9–70.5%). Seven studies reported on HBV vaccination. A comparative study showed a significantly higher uptake of the third HBV vaccine dose with the very rapid (63%) compared to the standard schedule (20%). HBV vaccination was generally well accepted (54–100%), whereas uptake was variable (dose 1:23–100%, dose 2:48–92%, dose 3:19–80%). One study on the combined HAV/HBV vaccine reported an acceptance rate of 34%, and declining uptake following dose 1. One study on influenza vaccine showed an uptake of 42–46%, while another reported a MMR vaccine acceptance of 80% and an uptake of 74%. Overall, main reasons for non-vaccination included release from/or transfer between prisons, and refusal.ConclusionsThis systematic review highlighted important knowledge gaps and operational challenges for vaccination in prison settings. Vaccination is an effective measure that warrants comprehensive and tailored implementation to reduce the preventable disease burden, avoid risks of large outbreaks of vaccine-preventable diseases, and contribute to health equity for people in prison.     

Importance and value of adjuvanted influenza vaccine in the care of older adults from a European perspective – A systematic review of recently published literature on real-world data

BackgroundThere is an urgent need for improved influenza vaccines especially for older adults due to the presence of immunosenescence. It is therefore highly relevant to compare enhanced influenza vaccines with traditional influenza vaccines with respect to their effectiveness.ObjectiveTo compare vaccine efficacy and effectiveness of adjuvanted influenza vaccines (aTIV/aQIV) vs. non-adjuvanted standard-dose (TIV/QIV) and high-dose (TIV-HD/QIV-HD) influenza vaccines regarding influenza-related outcomes in older adults, complementing findings from the European Centre for Disease Prevention and Control (ECDC)’s systematic review of enhanced seasonal influenza vaccines from February 2020.MethodsA systematic literature search was conducted in Embase and MEDLINE to identify randomised controlled trials, observational studies and systematic reviews, published since ECDC’s systematic review (between 7 February 2020 and 6 September 2021). Included studies were appraised with either the Cochrane Risk of Bias tool, ROBINS-I or AMSTAR 2.ResultsEleven analyses from nine real-world evidence (RWE) studies comprising ～53 million participants and assessing the relative vaccine effectiveness (rVE) of aTIV vs. TIV, QIV and/or TIV-HD in adults aged ≥65 years over the 2006/07–2008/09 and 2011/12–2019/20 influenza seasons were identified. Nine analyses found that aTIV was significantly more effective than TIV and QIV in reducing influenza-related outcomes by clinical setting and suspected influenza outbreaks (rVE ranging from 7.5% to 25.6% for aTIV vs. TIV and 7.1% to 36.3% for aTIV vs. QIV). Seven analyses found similar effectiveness of aTIV vs. TIV-HD in reducing influenza-related medical encounters, inpatient stays and hospitalisations/emergency room visits. In three analyses, aTIV was significantly more effective than TIV-HD in reducing influenza-related medical encounters and office visits (rVE ranging from 6.6% to 16.6%). Risk of bias of identified studies was moderate to high.ConclusionsOur study suggests that both adjuvanted and high-dose vaccines are effective alternatives for vaccination programmes in older adults and preferable over conventional standard-dose vaccines.     

Assessment of the effectiveness of the 2003-04 influenza vaccine among children and adults--Colorado, 2003

The 2003-04 influenza season was characterized by the early onset of influenza activity, reports of severe illness, particularly in children, and predominant circulation of an influenza A (H3N2) virus strain that was antigenically different from the influenza A (H3N2) vaccine strain. In 2003, a retrospective cohort study among children and a case-control study among adults in Colorado were conducted to provide preliminary data on the effectiveness of the 2003-04 influenza vaccine. This report summarizes the results of those studies, which indicated vaccine effectiveness (VE) among both adults and children, differing from results of a previous study that did not indicate effectiveness among adults.