Rapid assessment of influenza vaccine effectiveness: analysis of an internet-based cohort

The effectiveness of influenza vaccination programmes is seldom known during an epidemic. We developed an internet-based system to record influenza-like symptoms and response to infection in a participating cohort. Using self-reports of influenza-like symptoms and of influenza vaccine history and uptake, we estimated vaccine effectiveness (VE) without the need for individuals to seek healthcare. We found that vaccination with the 2010 seasonal influenza vaccine was significantly protective against influenza-like illness (ILI) during the 2010-2011 influenza season (VE 52%, 95% CI 27-68). VE for individuals who received both the 2010 seasonal and 2009 pandemic influenza vaccines was 59% (95% CI 27-77), slightly higher than VE for those vaccinated in 2010 alone (VE 46%, 95% CI 9-68). Vaccinated individuals with ILI reported taking less time off work than unvaccinated individuals with ILI (3.4 days vs. 5.3 days, P<0.001).     

Effectiveness of H1N1/09 monovalent and trivalent influenza vaccines against hospitalization with laboratory-confirmed H1N1/09 influenza in Australia: a test-negative case control study

We aimed to estimate the effectiveness of H1N1/09 containing influenza vaccines against hospitalization from influenza in Australia. We performed a test-negative case control study in patients hospitalized in 15 sentinel Australian hospitals between March and November 2010, comparing influenza vaccination (H1N1/09 monovalent or 2010 seasonal trivalent) in hospitalized patients with PCR-confirmed influenza compared to PCR-negative controls. Between March and November 2010, 1169 hospitalized patients were tested for suspected influenza, of which influenza vaccine status was ascertained in 165/238 patients with H1N1/09 influenza, 40/64 with seasonal influenza and 558/867 test negative controls; 24% of H1N1/09 cases, 43% of seasonal influenza cases and 54% of controls were vaccinated. VE against hospitalisation with H1N1/09 influenza after adjusting for age, medical comorbidities and pregnancy status was estimated at 49% (95% CI: 13%, 70%). Influenza vaccination was associated with a reduction in hospitalisation caused by H1N1/09 influenza in the 2010 southern hemisphere winter season.     

Influenza vaccine effectiveness against influenza-associated hospitalization in 2015/16 season,Beijing, China

BackgroundVaccination is recommended to prevent influenza virus infection and associated complications. This study aimed to estimate the influenza vaccine effectiveness (VE) against hospitalization in the 2015/16 season in Beijing.MethodsPatients who were hospitalized in the 5 study hospitals between 1 Oct 2015 and 15 May 2016 were recruited. Influenza vaccination status was obtained for PCR-confirmed influenza patients and the selected controls who tested negative for the virus. Conditional logistic regression was used to estimate the influenza VE matching by calendar week, and adjusting for age, study sites, underlying medical conditions, smoking status, and hospital admissions over the past 12 months.ResultsThe overall VE was −37.9% (95% CI: −103.3, 6.5) against laboratory-confirmed influenza-associated hospitalization. The 2015–16 seasonal vaccine was had −61.9% (95% CI: −211.9, 15.9), −5.4% (95% CI: −108.1, 46.6) and −45.2% (95% CI: −152.6, 16.5) effectiveness to prevent infection from A(H1N1)pdm09, A(H3N2) and influenza B, respectively.ConclusionsInfluenza vaccination did not show effective protection against hospitalization with influenza in 2015/16 season in Beijing.     

Vaccine effectiveness in preventing influenza hospitalizations in Navarre, Spain, 2010-2011: cohort and case-control study

We evaluated the 2010-2011 seasonal influenza vaccine effectiveness in preventing hospitalizations. Using healthcare databases we defined the target population for vaccination in Navarre, Spain, consisting of 217,320 people with major chronic conditions or aged 60 years and older. All hospitalized patients with influenza-like illness (ILI) were swabbed for influenza testing. A total of 269 patients with ILI were hospitalized and 61 of them were found positive for influenza virus: 58 for A(H1N1)2009 and 3 for B virus. The incidence rates of hospitalization with laboratory-confirmed influenza were compared by vaccination status. In the Cox regression model adjusted for sex, age, children in the household, urban/rural residence, comorbidity, pandemic vaccination, pneumococcal vaccination, outpatient visits and hospitalization in the previous year, the seasonal vaccine effectiveness was 58% (95% CI: 16-79%). The nested test-negative case-control analysis gave an adjusted estimate of 59% (95% CI: 4-83%). These results suggest a moderate effect of the 2010-2011 seasonal influenza vaccine in preventing hospitalization in a risk population. The close estimates obtained in the cohort and the test-negative case-control analyses suggest good control of biases.     

Influenza pandemic (H1N1) 2009 activity during summer 2009. Effectiveness of the 2008-9 trivalent vaccine against pandemic influenza in Spain

Introduction

The Spanish influenza surveillance system (SISS) maintained its activity during the summer of 2009 to monitor the influenza pandemic.

Objectives

To describe pandemic influenza activity from May to September 2009 and to estimate the effectiveness of the 2008-9 seasonal influenza vaccine against laboratory-confirmed pandemic (H1N1) 2009 influenza.

Methods

Data from the SISS were used to identify the trend of pandemic (H1N1) 2009 influenza outside the influenza season. For the effectiveness study, we compared the vaccination status of notified cases [influenza-like illnesses (ILI) laboratory confirmed as pandemic influenza] with that of the test-negative controls.

Results

The first laboratory-confirmed case of the pandemic virus was notified in the system in week 20/2009. The ILI rate increased gradually in the study period, exceeding basic activity in week 38. The proportion of pandemic (H1N1) 2009 influenza viruses detected by the system represented 14% in week 20/2009 and rapidly increased to 90% in week 34. The adjusted vaccine effectiveness of the 2008-9 seasonal vaccine against laboratory-confirmed pandemic influenza was 12% (-30; 41).

Conclusions

The SISS became an essential tool for pandemic monitoring in Spain. The improved SISS will provide more accurate information on influenza activity in future seasonal or pandemic waves. Using surveillance data, we could not demonstrate the effectiveness of the seasonal 2008-9 vaccine against laboratory-confirmed pandemic influenza.     

Efficacy of dual vaccination of pandemic H1N1 2009 influenza and seasonal influenza on institutionalized elderly: a one-year prospective cohort study

Background

The influenza A (H1N1) 2009 pandemic was declared by the WHO in April 2009. In Hong Kong, the vaccination program began in December 2009 in addition to the annual seasonal trivalent influenza vaccination program. The clinical efficacy of dual vaccination was unknown.

Method

From December 2009 to November 2010, a prospective 12-month cohort study on institutionalized elderly of nine nursing homes was conducted. Elderly persons who were followed up by the Hong Kong West Community Geriatric Assessment Team and had been vaccinated by the Department of Health were included. Outcome measures included all cause mortality, all cause hospitalization, hospitalization for fever on admission and hospitalization for pneumonia based on ICD-9-CM.

Results

711 elderly persons were included. 274 received both seasonal influenza vaccine and (H1N1) 2009 vaccine (H1N1-TIV), 368 received seasonal influenza vaccine only (TIV alone) and 69 received no vaccination (unvaccinated). Baseline characteristics were well matched between the groups, except there were fewer females in the TIV alone. The 12-month mortality rates of the H1N1-TIV, TIV alone and unvaccinated were 10.6%, 19.8% and 29%, respectively. Multivariate analysis demonstrated that dual vaccination in the institutionalized elderly significantly reduced all cause mortality by 54% (Hazard Ratio [HR] 0.46; 95% confidence interval [CI] 0.29-0.72; p < 0.001) and 74% (HR 0.26; CI 0.13-0.49; p < 0.001), compared with vaccination of seasonal vaccination alone and no vaccination, respectively. Dual vaccination also reduced all cause hospitalization, hospitalization for fever on admission and hospitalization for pneumonia compared with seasonal vaccination alone and the unvaccinated group.

Conclusion

Dual vaccination with both H1N1 and seasonal vaccinations provided additional protection to institutionalized elderly in reducing mortality and hospitalization.     

No effect of 2008/09 seasonal influenza vaccination on the risk of pandemic H1N1 2009 influenza infection in England

This study reports effectiveness of trivalent influenza vaccine (TIV) against confirmed pandemic influenza infection in England using a retrospective test-negative case-control study. Cases and controls were frequency matched by age, swabbing-week and region. On univariable and multivariable analysis adjusted for underlying clinical risk factors, cases were no more or less likely than controls to be vaccinated with 2008-09 or 2007-08 season TIV. Adjusted vaccine effectiveness for the former was −6% (−43% to 22%). Vaccine effectiveness did not differ significantly by age-group or hospitalisation status. There was no evidence prior vaccination with TIV significantly altered subsequent risk of pandemic influenza H1N1 2009 infection.     

The effectiveness of influenza vaccination in preventing hospitalisation in children in Western Australia

BackgroundThere is increasing evidence demonstrating influenza vaccine effectiveness (VE) in the prevention of influenza in children, including the very young. Data demonstrating the effectiveness against severe disease, including hospitalisation, are limited. We aimed to determine the VE of the southern hemisphere trivalent inactivated influenza vaccine (TIV) in preventing laboratory-confirmed influenza-associated hospitalisation in children.Patients and MethodsLaboratory records were used to identify children with confirmed influenza hospitalised (i.e., cases) during a 5 year period (2008, 2010–2013) at the only tertiary paediatric facility in Western Australia. Cases and time, age and ward matched controls were retrospectively reviewed to determine risk factors, vaccination status and outcome. Adjusted odds ratios and VE estimates were derived using conditional logistic regression models.ResultsThree hundred and eighty five cases were identified (Influenza A, 64.9%; Influenza B, 35.1%). Influenza-like illness and pneumonia were the most frequent presentation (74.5% and 23.9%, respectively). The median length of stay was 2 days (Interquartile range 1–4 days). Twenty children (5.2%) required admission to the intensive care unit. Vaccine uptake in cases and controls was low (4.9% and 8.5%, respectively). Three hundred and six case-control pairs were included in the VE analysis, of which 19 pairs were informative with discrepant vaccination status. VE (fully vaccinated vs. unvaccinated) was estimated to be 62.3% (95% CI: −6.6%, 86.7%).ConclusionIn this study, the point estimate for the effectiveness of TIV in preventing influenza-associated hospitalisation in children was similar to that reported for emergency or outpatient attended, laboratory-confirmed influenza, yet confidence intervals were wide. Vaccine uptake remains low. Studies, enroling larger numbers of children, ideally with higher vaccine uptake, are needed to provide additional evidence on TIV protection against influenza hospitalisation in children.     

Influenza vaccine effectiveness against hospitalization with laboratory-confirmed influenza in Greece: A pooled analysis across six seasons, 2013–2014 to 2018–2019

BackgroundMonitoring seasonal influenza Vaccine Effectiveness (VE) is key to inform vaccination strategies and sustain uptake. Pooling data across multiple seasons increases precision and allows for subgroup analyses, providing more conclusive evidence. Our aim was to assess VE against hospitalization with laboratory-confirmed influenza in Greece over six seasons, from 2013 to 2014 to 2018–2019, using routinely collected surveillance data.MethodsSwab samples from hospitalized patients across the country were tested for influenza by RT-PCR. We used the test-negative design, with patients testing positive for influenza serving as cases and those testing negative serving as controls. VE was calculated as one minus the Odds Ratio (OR) for influenza vaccination, estimated by mixed-effects logistic regression and adjusted for age, sex, hospitalization type (being in intensive care or not), time from symptom onset to swabbing, and calendar time. Stratified estimates by age and hospitalization type were obtained, and also subgroup estimates by influenza type/subtype and season. Antigenic and genetic characterization of a subset of circulating influenza strains was performed.ResultsA total of 3,882 test-positive cases and 5,895 test-negative controls were analyzed. Across all seasons, adjusted VE was 45.5% (95% CI: 31.6–56.6) against all influenza, 62.8% against A(H1N1)pdm09 (95% CI: 40.7–76.7), 28.2% against A(H3N2) (95% CI: 12.0–41.3) and 45.5% against influenza B (95% CI: 29.1–58.1). VE was slightly lower for patients aged 60 years and over, and similar between patients hospitalized inside or outside intensive care. Circulating A(H1N1)pdm09 and B strains were antigenically similar to the vaccine strains, whereas A(H3N2) were not.ConclusionOur results confirm the public health benefits from seasonal influenza vaccination, despite the suboptimal effectiveness against A(H3N2) strains. Continued monitoring of VE is essential, and routinely collected surveillance data can be valuable in this regard.     

Pandemic and seasonal vaccine coverage and effectiveness during the 2009–2010 pandemic influenza in an Italian adult population

Objectives

To evaluate the response to pandemic vaccination and seasonal and pandemic vaccine effectiveness (VE) in an Italian adult population, during the 2009?C2010 influenza season.

Methods

Data were recorded by interviewing 19,275 subjects (??35?years), randomly recruited from the general population of the Moli-sani project. Events [influenza-like illness (ILI), hospitalization and death], which had occurred between 1 November 2009 and 31 January 2010 were considered. VE was analyzed by multivariable Poisson regression analysis.

Results

Pandemic vaccine coverage was very low (2.4%) in subjects at high-flu risk, aged 35?C65?years (N?=?8,048); there was no significant preventive effect of vaccine against ILI. Seasonal vaccine coverage was 26.6% in the whole population (63% in elderly and 21.9% in middle-aged subjects at high-flu risk). There was a higher risk to develop ILI in middle-age [VE: ?17% (95% CI: ?35,?1)] or at high flu-risk [VE: ?17% (95% CI: ?39, 2)] vaccinated groups.

Conclusions

Coverage of pandemic vaccine was very low in a Southern Italy population, with no protective effect against ILI.     

Influenza vaccine effectiveness against influenza-associated hospitalization in children in Hong Kong, 2010–2020

BackgroundInfluenza virus infections can cause hospitalizations in children, and annual vaccination of children can provide protection against influenza.MethodsWe analyzed a test-negative design study with data spanning from 2010/11 through 2019/20 to evaluate influenza vaccine effectiveness (VE) against influenza hospitalization in children by age group, influenza type/subtype and time period within each season. We enrolled children admitted to hospital with acute febrile respiratory illnesses. Nasopharyngeal aspirates were tested by culture and/or RT-PCR to determine influenza status, and vaccination status was obtained by interviewing parents or legal guardians and was verified where possible. VE was estimated by conditional logistic regression model adjusting for sex, age and age-squared, matching on week.ResultsInfluenza seasons in Hong Kong are prolonged with influenza-associated hospitalizations occurring in almost every month of the year during the study period. Influenza vaccination was effective in preventing influenza-associated hospitalizations in children of all ages. Influenza VE was higher in younger children than in older children, and higher against hospitalization due to influenza A(H1N1)pdm09 than A(H3N2) and B.ConclusionsThe childhood influenza vaccination program in Hong Kong has prevented influenza-associated hospitalizations particularly in younger children. Our findings support the use of influenza vaccines in children as an effective approach to influenza control and prevention.     

Bias of influenza vaccine effectiveness estimates from test-negative studies conducted during an influenza pandemic

Test-negative (TN) studies have become the most widely used study design for the estimation of influenza vaccine effectiveness (VE) and are easily incorporated into existing influenza surveillance networks. We seek to determine the bias of TN-based VE estimates during a pandemic using a dynamic probability model. The model is used to evaluate and compare the bias of VE estimates under various sources of bias when vaccination occurs after the beginning of an outbreak, such as during a pandemic. The model includes two covariates (health status and health awareness), which may affect the probabilities of vaccination, developing influenza and non-influenza acute respiratory illness (ARI), and seeking medical care. Specifically, we evaluate the bias of VE estimates when (1) vaccination affects the probability of developing a non-influenza ARI; (2) vaccination affects the probability of seeking medical care; (3) a covariate (e.g. health status) is related to both the probabilities of vaccination and developing an ARI; and (4) a covariate (e.g. health awareness) is related to both the probabilities of vaccination and of seeking medical care. We considered two outcomes against which the vaccine is supposed to protect: symptomatic influenza and medically-attended influenza.When vaccination begins during an outbreak, we found that the effect of delayed onset of vaccination is unpredictable. VE estimates from TN studies were biased regardless of the source of bias present. However, if the core assumption of the TN design is satisfied, that is, if vaccination does not affect the probability of non-influenza ARI, then TN-based VE estimates against medically-attended influenza will only suffer from small (<0.05) to moderate bias (≥0.05 and <0.10). These results suggest that if sources of bias listed above are ruled out, TN studies are a valid study design for the estimation of VE during a pandemic.     

Monitoring pandemic influenza A(H1N1) vaccination coverage in Germany 2009/10 - results from thirteen consecutive cross-sectional surveys

To monitor pandemic influenza A(H1N1) vaccine uptake during the vaccination campaign in Germany 2009/10, thirteen consecutive cross-sectional telephone-surveys were performed between November 2009 and April 2010. In total 13,010 household-interviews were conducted. Vaccination coverage in persons >14 years of age remained low, both in the general population (8.1%; 95%CI: 7.4-8.8) and in specific target groups such as healthcare workers and individuals with underlying chronic diseases (12.8%; 95%CI: 11.4-14.4). Previous vaccination against seasonal influenza was a main factor independently associated with pandemic influenza vaccination (Odds ratio = 8.8; 95%CI: 7.2-10.8). The campaign failed to reach people at risk who were not used to receive their annual seasonal influenza shot.     

A follow-up comparative safety analysis of pandemic H1N1 vaccination during pregnancy and risk of infant birth defects among U.S. military mothers

ObjectiveTo update a previous assessment of birth defects among infants born to active duty U.S. military mothers who received the 2009–2010 pandemic H1N1 vaccine, in comparison to the 2008–2009 seasonal influenza vaccine, during pregnancy. Here, we updated the previous comparative analyses with a more refined definition for birth defects using an additional year of follow-up data from both inpatient and outpatient medical encounters.MethodsThe study population included 15,510 live born infants born to active duty mothers vaccinated during pregnancy with either the 2009–2010 pandemic H1N1 vaccine (n = 9033) or the 2008–2009 seasonal influenza vaccine (n = 6477). Birth defect cases were defined as those infants who received a birth defect diagnosis on one inpatient record or two outpatient records on different days within the first year of life. Multivariable logistic regression models were conducted to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for the association between birth defects and maternal vaccination during pregnancy with pandemic H1N1 vaccine versus seasonal influenza vaccine.ResultsInfants born to mothers vaccinated during pregnancy with the pandemic H1N1 vaccine, versus the seasonal influenza vaccine, were not at increased odds of birth defects in univariable (OR: 1.13, 95% CI: 0.95–1.34) or multivariable (OR: 1.14, 95% CI: 0.96–1.35) models. Findings were not significant when further limited to first trimester exposure. Multivariable models were adjusted for infant sex and plurality; maternal age, race/ethnicity, marital status, service branch, military rank, and occupation; timing of vaccination; and receipt of vaccination(s) not routinely recommended during pregnancy.ConclusionComparable to our previous analyses assessing birth defects diagnosed at birth, no significant association was found between the pandemic H1N1 vaccination during pregnancy and birth defects, versus the seasonal influenza vaccine. These findings are reassuring and provide additional support for H1N1-containing seasonal influenza vaccination during pregnancy.     

Vaccination against pandemic influenza A/H1N1 among healthcare workers and reasons for refusing vaccination in Istanbul in last pandemic alert phase

Coverage of the HCWs as target population is one of the important determinants for the impact of vaccination. To determine the vaccination against the pandemic influenza A/H1N1 among HCWs, we conducted a cross-sectional questionnaire survey in a public hospital in Istanbul from December 7 to December 22, 2009. Out of total 941 HCWs 718 (76.3%) completed the questionnaires. Nearly one-fourth (23.1%) of the participants were vaccinated against pandemic influenza A/H1N1. Occupation (being a doctor), receiving seasonal influenza vaccine in 2009, agreement with safety of pandemic influenza A/H1N1 vaccine and being comprehend that HCWs have a professional responsibility for getting vaccinated was the strongest independent predictive factor for accepting the pandemic influenza A/H1N1 vaccine (p < .0001). The most frequent reasons for refusing pandemic vaccine were fear of side effects and doubts about vaccine efficacy. Among HCWs 59.6% were recommending pandemic influenza vaccination to a patient even if indicated. In conclusion vaccination against pandemic influenza A/H1N1 is insufficient among HCWs. Misinformed or inadequately informed HCWs are important barrier to pandemic influenza vaccine coverage of the general public also. Educational campaigns concerning HCWs should include evidence based and comprehensible information about possible adverse effects and their incidence besides the advantages of vaccine.     

Predictors of IV behaviors during and after the 2009 influenza pandemic in France

Background

Controversies about the 2009 H1N1 pandemic influenza vaccination might have impacted the motivational processes that underlie individual immunization against seasonal influenza. The purpose of this article is to investigate correlates of vaccine uptake during and after the pandemic.

Methods

Data from the 1174 subjects of the CoPanFlu France cohort aged 15 and over were used. We used logistic regression models to identify social and behavioral predictors of getting vaccinated against seasonal influenza in 2009–2010 and in 2010–2011 and against H1N1 influenza in 2009–2010.

Results

This study points out that correlates of vaccination behaviors varied according to the vaccine. Respondents under 65 years who adopted the seasonal influenza vaccine were, as usual, more likely to belong to a target group and have a lower education, contrary to subjects who chose the pandemic vaccine. Exceptionally during the pandemic, a higher socioeconomic status also led to adoption of either vaccine. Motivational processes differed by vaccine. Uptaking the “new” pandemic vaccine was the result of a deliberative decision-making process, influenced by cognitive factors related to the pandemic context (such as perceived severity of the H1N1 flu strain and trust in public health authorities). In contrast, respondents got the seasonal flu vaccine without relying on explicit justifications, but instead through habit of performing this behavior in the past.

Conclusions

Target groups for seasonal influenza but not those for pandemic influenza were more likely to adopt the pandemic vaccine, which is a cause for great concern. This may be due to large extent to the automatic and habitual nature of influenza vaccination decisions. Public health authorities, should pay more attention to situational than informational cues to facilitate vaccine uptake among priority groups, especially in case of mild pandemic influenza.     

Increased extent of and risk factors for pandemic (H1N1) 2009 and seasonal influenza among children, Israel

During the pandemic (H1N1) 2009 outbreak in Israel, incidence rates among children were 2× higher than that of the previous 4 influenza seasons; hospitalization rates were 5× higher. Children hospitalized for pandemic (H1N1) 2009 were older and had more underlying chronic diseases than those hospitalized for seasonal influenza.     

Deaths averted by influenza vaccination in the U.S. during the seasons 2005/06 through 2013/14

BackgroundExcess mortality due to seasonal influenza is substantial, yet quantitative estimates of the benefit of annual vaccination programs on influenza-associated mortality are lacking.MethodsWe estimated the numbers of deaths averted by vaccination in four age groups (0.5 to 4, 5 to 19, 20 to 64 and ≥65 yrs.) for the nine influenza seasons from 2005/6 through 2013/14. These estimates were obtained using a Monte Carlo approach applied to weekly U.S. age group-specific estimates of influenza-associated excess mortality, monthly vaccination coverage estimates and summary seasonal influenza vaccine effectiveness estimates to obtain estimates of the number of deaths averted by vaccination. The estimates are conservative as they do not include indirect vaccination effects.ResultsFrom August, 2005 through June, 2014, we estimated that 40,127 (95% confidence interval [CI] 25,694 to 59,210) deaths were averted by influenza vaccination. We found that of all studied seasons the most deaths were averted by influenza vaccination during the 2012/13 season (9398; 95% CI 2,386 to 19,897) and the fewest during the 2009/10 pandemic (222; 95% CI 79 to 347). Of all influenza-associated deaths averted, 88.9% (95% CI 83 to 92.5%) were in people ≥65 yrs. old.ConclusionsThe estimated number of deaths averted by the US annual influenza vaccination program is considerable, especially among elderly adults and even when vaccine effectiveness is modest, such as in the 2012/13 season. As indirect effects (“herd immunity”) of vaccination are ignored, these estimates represent lower bound estimates and are thus conservative given valid excess mortality estimates     

Vaccine effectiveness for laboratory-confirmed influenza in children 6-59 months of age, 2005-2007

To estimate the effectiveness of influenza vaccine against medical care visits for laboratory-confirmed influenza in young children we conducted a matched case-control study in children with acute respiratory illness or fever from 2005-2007. Influenza vaccine effectiveness (VE) was calculated using cases with laboratory-confirmed influenza and controls who tested negative for influenza. The effectiveness of influenza vaccine in fully vaccinated children 6-59 months of age was 56% (95% CI: 25%-74%); a significant VE was not found for partial vaccination.