Influenza vaccine effectiveness against hospitalisation with influenza in adults in Australia in 2014

We provide estimates of the influenza vaccine protection against hospitalisation with laboratory-confirmed influenza in the 2014 Australian season where the A/H1N1/pdm09 strain predominated. This was performed using a case-test negative study design as part of a national sentinel surveillance system in Australia. Vaccine effectiveness was estimated as (1-OR) × 100% where the odds ratio of vaccination in cases vs test negative participants was estimated from a conditional logistic regression. Between April and November, 1692 adult patients were admitted with laboratory-confirmed influenza. Vaccine effectiveness was estimated from 1283 patients with influenza and 1116 test negative patients where vaccination status was ascertained. Vaccination was associated with a reduction in the risk of hospitalisation with influenza of 51.5% (95% CI: 41.6%, 59.7%) in all patients, and a reduction of 50.7% (95% CI: 40.1%, 59.3%) in the target population for vaccination. We estimate that the influenza vaccine was moderately protective against hospitalisation with laboratory-confirmed influenza during the 2014 influenza season in Australia.     

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.     

Influenza vaccine effectiveness for hospital and community patients using control groups with and without non-influenza respiratory viruses detected,Auckland, New Zealand 2014

BackgroundWe aimed to estimate the protection afforded by inactivated influenza vaccine, in both community and hospital settings, in a well characterised urban population in Auckland during 2014.MethodsWe used two different comparison groups, all patients who tested negative for influenza and only those patients who tested negative for influenza and had a non-influenza respiratory virus detected, to calculate the vaccine effectiveness in a test negative study design. Estimates were made separately for general practice outpatient consultations and hospitalised patients, stratified by age group and by influenza type and subtype. Vaccine status was confirmed by electronic record for general practice patients and all respiratory viruses were detected by real time polymerase chain reaction.Results1039 hospitalised and 1154 general practice outpatient consultations met all the study inclusion criteria and had a respiratory sample tested for influenza and other respiratory viruses. Compared to general practice patients, hospitalised patients were more likely to be very young or very old, to be Māori or Pacific Islander, to have a low income and to suffer from chronic disease. Vaccine effectiveness (VE) adjusted for age and other participant characteristics using all influenza negative controls was 42% (95% CI: 16 to 60%) for hospitalised and 56% (95% CI: 35 to 70%) for general practice patients. The vaccine appeared to be most effective against the influenza A(H1N1)pdm09 strain with an adjusted VE of 62% (95% CI:38 to 77%) for hospitalised and 59% (95% CI:36 to 74%) for general practice patients, using influenza virus negative controls. Similar results found when patients testing positive for a non-influenza respiratory virus were used as the control group.ConclusionThis study contributes to validation of the test negative design and confirms that inactivated influenza vaccines continue to provide modest but significant protection against laboratory-confirmed influenza.     

Influenza vaccine effectiveness against laboratory-confirmed influenza in a vaccine-mismatched influenza B-dominant season

BackgroundThe 2017–2018 influenza season in Israel was characterized by the predominance of influenza B Yamagata, with a lesser circulation of influenza A(H1N1)pdm09 and influenza A(H3N2). We estimated vaccine effectiveness (VE) of the inactivated influenza vaccine which was selected for use that season.MethodsEnd-of-season VE and 95% confidence intervals (CI) against laboratory-confirmed influenza-like illness (ILI) were estimated by means of the test-negative design. Age-specific VE analysis was carried out using a moving age interval.ResultsSpecimen were obtained from 1,453 community ILI patients; 610 (42.0%) were influenza-positive, among which 69.7% were B, 17.2% A(H1N1)pdm09 and 13.4% A(H3N2). A 98.6% of molecularly characterized influenza B belonged to the Yamagata lineage. Of the sampled individuals, 1320 were suitable for VE analysis. Of those vaccinated, 90.6% received the inactivated trivalent influenza vaccine (TIV) containing a Victoria lineage influenza B-like virus. VE against influenza A differed by age, with the highest VE of 72.9% (95%CI 31.9–89.2%) observed in children 0.5–14 years old, while all ages VE was 46.6% (95%CI 10.4–68.2%). All ages VE against influenza B was 23.2% (95%CI −10.1–46.4%) with age-specific analysis showing non-significant VE estimates. Utilizing a moving age interval of 15 years, afforded a detailed age-specific insight into influenza VE against the influenza viruses circulating during the 2017–2018 season.ConclusionsThe moderate-high 2017–2018 influenza A VE among children and adolescents, supports seasonal influenza vaccination at a young age. The low VE against influenza B in Israel, is most likely the result of influenza B/TIV-mismatch.     

Influenza vaccine effectiveness in hospitalised Hong Kong children: Feasibility of estimates from routine surveillance data

BackgroundHong Kong has a high burden of influenza hospitalisation. This study estimated influenza vaccine effectiveness in hospitalised Hong Kong children aged 6 months to below 6 years using data potentially obtainable from routine surveillance sources.MethodsThis ‘test-negative’ case-control study was conducted over two summer and one winter influenza seasons in five public Hong Kong hospitals during 2015 and 2016. Patients admitted for febrile and/or respiratory-associated illnesses who met inclusion criteria were invited to participate. Case-patients were respiratory-associated admissions with nasopharyngeal aspirate or nasopharyngeal swab specimens obtained during the first 48 h of hospitalisation that tested positive for influenza A or B, whereas control-patients were those with specimens that tested negative for both influenza A and B. Reliability of a routinely collected influenza immunisation status form was evaluated. Vaccine effectiveness for administration of full or partial series of influenza vaccination was calculated as 1 minus the odds ratio for influenza vaccination history for case-patients versus control-patients.Results2900 eligible subjects had influenza vaccination status available. A simple record form, designed to collect upon admission information on influenza vaccination status, was found to be reliable when compared to confirmed vaccination status from immunisation records and guardians’ self-reports. Influenza vaccine effectiveness for preventing influenza A or B hospitalisation in children aged from 6 months to below 6 years during the period June 2015 to November 2016 was 68% (95% confidence interval [CI]: 55%, 77%) from unconditional analyses and 64% (95% CI: 46%, 75%) from conditional analyses.ConclusionsSeasonal influenza vaccine was effective in preventing hospitalisation from influenza A or B in young Hong Kong children during 2015 and 2016. As influenza vaccination status is not currently routinely recorded, implementation of an influenza immunisation status form in all paediatric wards, and centralising the data in Hong Kong's central computerised database, could provide real-time monitoring of influenza vaccine effectiveness.     

Influenza vaccine effectiveness in preventing laboratory-confirmed influenza in outpatient settings: A test-negative case-control study in Beijing,China, 2016/17 season

BackgroundThe objective of this study was to estimate influenza vaccine effectiveness (VE) for the 2016/17 epidemic of co-circulating influenza A(H1N1)pdm09 and A(H3N2) viruses in Beijing, the capital of China.MethodsThe surveillance-based study included all swabbed patients through influenza virological surveillance, between November 2016 and April 2017. A test-negative case-control design was used to estimate influenza VE against medically-attended laboratory-confirmed influenza in outpatient settings. Cases were influenza-like illness (ILI) patients who tested positive for influenza, and controls were influenza negative patients.ResultsA total of 10,496 ILI patients were enrolled and swabbed. Among them, 735 tested positive for influenza A(H1N1)pdm09, 1851 for A(H3N2), and 40 for type B. Of the 45 randomly selected specimens out of 1851 influenza A(H3N2) viruses, 2(4.4%) belonged to the H3N2 3C.2a1 clade, and 43(95.6%) belonged to A/Hong Kong/4801/2014-like 3C.2a clade. Among the 43 viruses of the 3C.2a clade, 32 viruses clustered in one subgroup carrying T131K, R142K and R261Q substitutions. The adjusted VE against all influenza was low at 25% (95% confidence interval (CI): 0–43%), with 54% (95%CI: 22–73%) for influenza A(H1N1)pdm09, and 2% (95%CI: −35% to 29%) for influenza A(H3N2).ConclusionsOur study suggested a moderate VE against influenza A(H1N1)pdm09, but low VE against influenza A(H3N2) in Beijing, 2016/17 season. Amino acid substitutions in the hemagglutinin may contribute to the low VE against influenza A(H3N2) for this season.     

Influenza vaccine effectiveness estimates for Western Australia during a period of vaccine and virus strain stability, 2010 to 2012

During 2010–2012 the strain composition of the influenza vaccine in the Southern Hemisphere did not change, but the circulating virus type/subtype did. We pooled data for these years from the Western Australian sentinel medical practice surveillance system for influenza to estimate vaccine effectiveness (VE) by influenza virus type and subtype. A case test-negative design was used with VE estimated as (1-odds ratio) × 100%. There were 2182 patients included in the analysis across the 3 years studied. The predominant subtype was A/H1pdm09 in 2010 and 2011, and A/H3 in 2012. The overall adjusted VE estimate against all influenza for 2010–2012 was 51% (95% CI: 36, 63). Estimates were highest against A/H1pdm09 at 74% (95% CI: 47, 87), followed by 56% (95% CI: 33, 71) for influenza B and lowest against A/H3 at 39% (95% CI: 13, 57). When analyses were restricted to compare influenza-positive patients with patients who tested positive for a non-influenza virus, overall adjusted VE was 59% (95% CI: 39, 72). These results suggest moderate protection against influenza by vaccination in Western Australia over the period 2010–2012, and are consistent with findings from other settings.     

Influence of disease attenuation on relative influenza vaccine effectiveness by vaccine type

Benefit conferred by “enhanced” influenza vaccines is often measured by relative vaccine effectiveness, (rVE), which compares disease risk among groups of people who received alternative vaccines. Differences in attenuation of illness severity by vaccine types could manifest as differences in rVE. Using a simulated VE study and cohort of adults aged ≥ 65 years, we examined how rVE varied with assumptions about attenuation of disease severity conferred by standard and enhanced vaccines and how this variation could lead to differing estimates of rVE for prevention of moderate (i.e., outpatient) versus severe (i.e., inpatient) influenza illness. We found that if enhanced vaccines attenuated severe illness more than moderate illness, then rVE observed against severe disease could be higher than rVE observed against moderate disease. Thus, if differences in disease attenuation by vaccine type occurs, estimates of rVE may vary for influenza outcomes of differing levels of severity.     

Influenza vaccine effectiveness among adult patients in a University of Lyon hospital (2004-2009)

The aim of this study was to estimate influenza vaccine effectiveness (IVE) against laboratory-confirmed influenza among hospitalized patients. A case-control investigation was based on the prospective surveillance of influenza-like illness (ILI) during five flu seasons. We compared influenza-positive cases and influenza-negative controls. Unadjusted overall IVE was 62% (95% confidence interval 24% to 81%). We found that IVE was lower during the 2004-05 flu season (11%; 95% CI −232% to 76%) when the vaccine and circulating viruses were mismatched. Expansion of the study to other hospitals could provide IVE estimates earlier in the season, for different age groups and emerging virus strains.     

The test-negative design for estimating influenza vaccine effectiveness

Objective

The test-negative design has emerged in recent years as the preferred method for estimating influenza vaccine effectiveness (VE) in observational studies. However, the methodologic basis of this design has not been formally developed.

Methods

In this paper we develop the rationale and underlying assumptions of the test-negative study. Under the test-negative design for influenza VE, study subjects are all persons who seek care for an acute respiratory illness (ARI). All subjects are tested for influenza infection. Influenza VE is estimated from the ratio of the odds of vaccination among subjects testing positive for influenza to the odds of vaccination among subjects testing negative.

Results

With the assumptions that (a) the distribution of non-influenza causes of ARI does not vary by influenza vaccination status, and (b) VE does not vary by health care-seeking behavior, the VE estimate from the sample can generalized to the full source population that gave rise to the study sample. Based on our derivation of this design, we show that test-negative studies of influenza VE can produce biased VE estimates if they include persons seeking care for ARI when influenza is not circulating or do not adjust for calendar time.

Conclusions

The test-negative design is less susceptible to bias due to misclassification of infection and to confounding by health care-seeking behavior, relative to traditional case-control or cohort studies. The cost of the test-negative design is the additional, difficult-to-test assumptions that incidence of non-influenza respiratory infections is similar between vaccinated and unvaccinated groups within any stratum of care-seeking behavior, and that influenza VE does not vary across care-seeking strata.     

Influenza vaccination effectiveness in preventing influenza hospitalization in children,Hong Kong,winter 2019/20

The winter influenza season 2019/20 in Hong Kong was predominated by influenza A(H1N1)pdm09. We analysed an on-going test-negative design study consisting of 1227 children admitted for febrile acute respiratory illness from 3 November 2019 (week 45) to 21 March 2020 (week 12). We estimated influenza vaccine effectiveness of 65% (95% CI: 46 – 78) against hospitalization due to influenza A and B combined, and 74% (95% CI: 54 – 85) against hospitalization due to influenza A(H1N1)pdm09.     

2017－2018年流感流行季儿童接种流感疫苗效果社区队列研究

目的 评价6~72月龄儿童接种流感疫苗效果。方法 采用社区队列研究设计,2017年10-12月,从浙江省永康和义乌两市10家儿童接种门诊招募了1 752名6~72月龄儿童。每名儿童入队列后,完成知情同意和问卷调查,并随访至2018年4月30日,观察记录流感样病例（ILI）发病、门诊就诊和自行服药及流感疫苗接种情况。以ILI、门诊就诊和自行服药的发生次数为因变量,采用广义线性模型（GLM）拟合,估算流感疫苗效果（VE）值。结果 1 752名儿童中,男童925名（52.80%）,月龄M=30.00月,累计随访观察308 166人天,平均每天有5.27‰发生ILI、3.41‰因ILI去医院门诊就诊、1.45‰因ILI自行服药治疗;共有643名儿童接种了流感疫苗,与未接种儿童相比,流感疫苗对ILI、门诊就诊和自行服药的VE值分别为23.5%（95% CI：15.1%~31.1%）、19.3%（95% CI：8.2%~29.1%）和25.8%（95% CI：9.3%~39.3%）。643名接种儿童,接种后与接种前比,流感疫苗针对36~72月龄儿童ILI、门诊就诊和自行服药的VE值分别为31.9%（95% CI：12.7%~46.9%）、32.6%（95% CI：8.6%~50.3%）和44.3%（95% CI：11.9%~64.8%）,而对6~35月龄儿童,VE值均无统计学意义。2016-2018年流感疫苗不同接种暴露VE值评估,两个流感流行季均有接种史的,仅2017-2018年流感流行季有接种史的,流感疫苗VE值,均有统计学意义;仅2016-2017年流感流行季有接种史的,VE值均无统计学意义。结论 流感流行季接种流感疫苗一定程度可预防ILI发病、门诊就诊和自行服药,且对36~72月龄儿童保护效果优于6~35月龄儿童。     

Waning protection of influenza vaccine against mild laboratory confirmed influenza A(H3N2) and B in Spain,season 2014–15

IntroductionThe 2014/15 influenza season in Spain was dominated by the circulation of drifted A(H3N2) and co-circulation of B viruses. We present the final estimates of influenza vaccine effectiveness (IVE) against confirmed influenza A(H3N2) and B its evolution along the season and with time since vaccination.MethodsWe used data collected on influenza like illness patients (ILI), systematically swabbed for the presence of influenza viruses within the Spanish Influenza Sentinel Surveillance System (SISS) and a restricted observational study (cycEVA). We used a test negative case–control design to compare influenza confirmed cases with negative controls. We estimated the IVE through a logistic regression model adjusting for potential confounders. The evolution of IVE was studied in early and late stages of the epidemic, and in different time intervals between receiving influenza vaccination and the onset of symptoms.ResultsAt the end of the season we have found low and moderate IVE point estimates against influenza A(H3N2) and B, respectively, in all ages and target groups for vaccination. An IVE decreased from an early value of 37% to a late of −76% against influenza A(H3N2), and similarly, 84% vs −4% against Influenza B. When the onset of symptoms occurred more than three months after vaccination, the decrease of IVE was slower and milder against influenza B than against influenza A(H3N2). No significant change in the percentage of circulating drifted influenza A(H3N2) strains belonging to the 3c.2a and 3c.3a clades could be identified through the season.ConclusionsIn a season dominated by drifted A(H3N2) circulating virus, the vaccine offered little or no protection against A(H3N2) infection but had a moderate protective effect against influenza B. Efforts should be put in developing influenza vaccines that maintain their protective capabilities throughout the season and could stimulate a potentially broad immune response against diverse influenza strains.     

Influenza vaccine effectiveness against influenza-associated hospitalization in children: A systematic review and meta-analysis

Vaccination remains the most effective way to prevent influenza infection, albeit vaccine effectiveness (VE) varies by year. Compared to other age groups, children and elderly adults have the highest risk of developing influenza-related complications and requiring hospitalization. During the last years, “test negative design” (TND) studies have been implemented in order to estimate influenza VE. The aim of this systematic review and meta-analysis was to summarize the findings of TND studies reporting influenza VE against laboratory-confirmed influenza-related hospitalization in children aged 6 months to 17 years. We searched the PubMed and Embase databases and identified 2615 non-duplicate studies that required detailed review. Among them, 28 met our inclusion criteria and we performed a random-effects meta-analysis using adjusted VE estimates. In our primary analysis, influenza vaccine offered significant protection against any type influenza-related hospitalization (57.48%; 95% CI 49.46–65.49). When we examined influenza VE per type and strain, VE was higher against H1N1 (74.07%; 95% CI: 54.85–93.30) and influenza B (50.87%; 95% CI: 41.75–59.98), and moderate against H3N2 (40.77%; 95% CI: 25.65–55.89). Notably, influenza vaccination offered higher protection in children who were fully vaccinated (61.79%; 95% CI: 54.45–69.13), compared to those who were partially vaccinated (33.91%; 95% CI: 21.12 – 46.69). Also, influenza VE was high in children less than 5 years old (61.71%; 95% CI: 49.29–74.12) as well as in children 6–17 years old (54.37%; 95% CI: 35.14–73.60). In conclusion, in the pediatric population, influenza vaccination offered significant protection against influenza-related hospitalization and complete annual vaccination should be encouraged.     

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.     

The impact of selection bias on vaccine effectiveness estimates from test-negative studies

IntroductionEstimates of vaccine effectiveness (VE) from test-negative studies may be subject to selection bias. In the context of influenza VE, we used simulations to identify situations in which meaningful selection bias can occur. We also analyzed observational study data for evidence of selection bias.MethodsFor the simulation study, we defined a hypothetical population whose members are at risk for acute respiratory illness (ARI) due to influenza and other pathogens. An unmeasured “healthcare seeking proclivity” affects both probability of vaccination and probability of seeking care for an ARI. We varied the direction and magnitude of these effects and identified situations where meaningful bias occurred. For the observational study, we reanalyzed data from the United States Influenza VE Network, an ongoing test-negative study. We compared “bias-naïve” VE estimates to bias-adjusted estimates, which used data from the source populations to correct for sampling bias.ResultsIn the simulation study, an unmeasured care-seeking proclivity could create selection bias if persons with influenza ARI were more (or less) likely to seek care than persons with non-influenza ARI. However, selection bias was only meaningful when rates of care seeking between influenza ARI and non-influenza ARI were very different. In the observational study, the bias-naïve VE estimate of 55% (95% CI, 47-–62%) was trivially different from the bias-adjusted VE estimate of 57% (95% CI, 49-–63%).ConclusionsIn combination, these studies suggest that while selection bias is possible in test-negative VE studies, this bias in unlikely to be meaningful under conditions likely to be encountered in practice. Researchers and public health officials can continue to rely on VE estimates from test-negative studies.     

Validity of the estimates of oral cholera vaccine effectiveness derived from the test-negative design

BackgroundThe test-negative design (TND) has emerged as a simple method for evaluating vaccine effectiveness (VE). Its utility for evaluating oral cholera vaccine (OCV) effectiveness is unknown. We examined this method's validity in assessing OCV effectiveness by comparing the results of TND analyses with those of conventional cohort analyses.MethodsRandomized controlled trials of OCV were conducted in Matlab (Bangladesh) and Kolkata (India), and an observational cohort design was used in Zanzibar (Tanzania). For all three studies, VE using the TND was estimated from the odds ratio (OR) relating vaccination status to fecal test status (Vibrio cholerae O1 positive or negative) among diarrheal patients enrolled during surveillance (VE =  (1 − OR)×100%). In cohort analyses of these studies, we employed the Cox proportional hazard model for estimating VE (=1 − hazard ratio)×100%).ResultsOCV effectiveness estimates obtained using the TND (Matlab: 51%, 95% CI:37–62%; Kolkata: 67%, 95% CI:57–75%) were similar to the cohort analyses of these RCTs (Matlab: 52%, 95% CI:43–60% and Kolkata: 66%, 95% CI:55–74%). The TND VE estimate for the Zanzibar data was 94% (95% CI:84–98%) compared with 82% (95% CI:58–93%) in the cohort analysis. After adjusting for residual confounding in the cohort analysis of the Zanzibar study, using a bias indicator condition, we observed almost no difference in the two estimates.ConclusionOur findings suggest that the TND is a valid approach for evaluating OCV effectiveness in routine vaccination programs.     

Understanding influenza vaccine protection in the community: An assessment of the 2013 influenza season in Victoria,Australia

BackgroundThe influenza virus undergoes frequent antigenic drift, necessitating annual review of the composition of the influenza vaccine. Vaccination is an important strategy for reducing the impact and burden of influenza, and estimating vaccine effectiveness (VE) each year informs surveillance and preventative measures. We aimed to describe the influenza season and to estimate the effectiveness of the influenza vaccine in Victoria, Australia, in 2013.MethodsRoutine laboratory notifications, general practitioner sentinel surveillance (including a medical deputising service) data, and sentinel hospital admission surveillance data for the influenza season (29 April to 27 October 2013) were collated in Victoria, Australia, to describe influenza-like illness or confirmed influenza during the season. General practitioner sentinel surveillance data were used to estimate VE against medically-attended laboratory confirmed influenza. VE was estimated using the case test negative design as 1 − adjusted odds ratio (odds of vaccination in cases compared with controls) × 100%. Cases tested positive for influenza while non-cases (controls) tested negative. Estimates were adjusted for age group, week of onset, time to swabbing and co-morbidities.ResultsThe 2013 influenza season was characterised by relatively low activity with a late peak. Influenza B circulation preceded that of influenza A(H1)pdm09, with very little influenza A(H3) circulation. Adjusted VE for all influenza was 55% (95%CI: −11, 82), for influenza A(H1)pdm09 was 43% (95%CI: −132, 86), and for influenza B was 56% (95%CI: −51, 87) Imputation of missing data raised the influenza VE point estimate to 64% (95%CI: 13, 85).ConclusionsClinicians can continue to promote a positive approach to influenza vaccination, understanding that inactivated influenza vaccines prevent at least 50% of laboratory-confirmed outcomes in hospitals and the community.     

Assessing the effectiveness of high-dose influenza vaccine in preventing hospitalization among seniors,and observations on the limitations of effectiveness study design

BackgroundThe availability of high-dose (HD) influenza vaccine for seniors should decrease influenza-related hospitalization. Studies to date show a range of mostly moderate increased HD vaccine effectiveness (VE). While a ‘healthy vaccinee’ phenomenon can inflate VE, for influenza and particularly an HD vaccine targeted at frailer adults, an ‘at-risk vaccinee’ bias may deflate VE estimates. We assessed senior HD vaccine effectiveness against influenza-related hospitalization by linking immunization registry records to hospitalizations. We also examined whether adding strata typically ignored in case-control matching schemas, such as residence areas, exact age, and provider biases, would increase VE.MethodsFor the 2016–17 influenza season in the Portland metropolitan area, the differential VE for the HD vaccine in preventing PCR-confirmed influenza hospitalization was assessed by a nested series of models across matching strata. For an exact match for high-dose and standard-dose seniors, matching elements included exact age, gender, residence type, race-ethnicity, provider bias, and residence area (zipcode).ResultsAs a first step, a simple aggregate comparison of influenza-related hospitalization risk showed no added HD effectiveness. For the nested models, adding strata increased VE. In the final model, among 23,712 matched pairs of HD to SD vaccinated seniors, the HD vaccine was 30.7% (95%CI: 8–48%) more effective in preventing influenza-related hospitalization.ConclusionFor this study, the high-dose influenza vaccine provided superior protection for seniors against influenza hospitalization. Including matching elements as exact year of age and residence zipcode all added to the calculation of VE. As a warning, non-matched or overly simple matched VE study designs may substantially under-estimate VE.