Test-negative Case Control Research Articles

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.

Seasonal influenza vaccine effectiveness against medically attended influenza illness among children aged 6–59 months, October 2011–September 2012: A matched test-negative case–control study in Suzhou, China

BackgroundSeasonal influenza infections among young children in China lead to substantial numbers of hospitalizations and financial burden. This study assessed the seasonal influenza vaccine effectiveness (VE) against laboratory confirmed medically attended influenza illness among children in Suzhou, China, from October 2011–September 2012. MethodsWe conducted a test-negative case–control study among children aged 6–59 months who sought care at Soochow University Affiliated Children's Hospital (SCH) from October 2011–September 2012. A case was defined as a child with influenza-like illness (ILI) or severe acute respiratory infection (SARI) with an influenza-positive nasopharyngeal swab by rRT-PCR. Controls were selected from children presenting with ILI or SARI without laboratory confirmed influenza. We conducted 1:1 matching by age and admission date. Vaccination status was verified from the citywide immunization system database. VE was calculated with conditional logistic regression: (1−OR)×100%. ResultDuring the study period, 2634 children aged 6–59 months presented to SCH with ILI (1975) or SARI (659) and were tested for influenza. The vaccination records were available for 69% (1829; ILI: 1354, SARI: 475). Among those, 23% (427) tested positive for influenza, and were included as cases. Among influenza positive cases, the vaccination rates were 3.2% for SARI and 4.5% for ILI. Among controls, the vaccination rates were 13% for SARI, and 11% for ILI. The overall VE against lab-confirmed medically attended influenza virus infection was 67% (95% CI: 41–82). The VE for SARI was 75% (95% CI: 11–93) and for ILI was 64% (95% CI: 31–82). ConclusionsThe seasonal influenza vaccine was effective against medically attended lab-confirmed influenza infection in children aged 6–59 months in Suzhou, China in the 2011–12 influenza season. Increasing seasonal influenza vaccination among young children in Suzhou may decrease medically attended influenza-associated ILI and SARI cases in this population.

Moderate influenza vaccine effectiveness against hospitalisation with A(H3N2) and A(H1N1) influenza in 2013–14: Results from the InNHOVE network

ABSTRACTWe conducted a multicentre test negative case control study to estimate the 2013–14 influenza vaccine effectiveness (IVE) against hospitalised laboratory confirmed influenza in 12 hospitals in France, Italy and Spain. We included all ≥18 years hospitalised patients targeted by local influenza vaccination campaign reporting an influenza-like illness within 7 days before admission. We defined as cases patients RT-PCR positive for influenza and as controls those negative for all influenza virus. We used a logistic regression to calculate IVE adjusted for country, month of onset, chronic diseases and age. We included 104 A(H1N1)pdm09, 157 A(H3N2) cases and 585 controls. The adjusted IVE was 42.8% (95%CI: 6.3;65;0) against A(H1N1)pdm09. It was respectively 61.4% (95%CI: −1.9;85.4), 39.4% (95%CI: −32.2;72.2) and 19.7% (95%CI:-148.1;74.0) among patients aged 18–64, 65–79 and ≥80 years. The adjusted IVE against A(H3N2) was 38.1% (95%CI: 8.3;58.2) overall. It was respectively 7.8% (95%CI: −145.3;65.4), 25.6% (95%CI: −36.0;59.2) and 55.2% (95%CI: 15.4;76.3) among patients aged 18–64, 65–79 and ≥80 years. These results suggest a moderate and age varying effectiveness of the 2013–14 influenza vaccine to prevent hospitalised laboratory-confirmed influenza. While vaccination remains the most effective prevention measure, developing more immunogenic influenza vaccines is needed to prevent severe outcomes among target groups.

Effectiveness of seasonal influenza vaccine in preventing laboratory-confirmed influenza in primary care in the United Kingdom: 2014/15 end of season results.

The 2014/15 influenza season in the United Kingdom (UK) was characterised by circulation of predominantly antigenically and genetically drifted influenza A(H3N2) and B viruses. A universal paediatric influenza vaccination programme using a quadrivalent live attenuated influenza vaccine (LAIV) has recently been introduced in the UK. This study aims to measure the end-of-season influenza vaccine effectiveness (VE), including for LAIV, using the test negative case-control design. The overall adjusted VE against all influenza was 34.3% (95% confidence interval (CI) 17.8 to 47.5); for A(H3N2) 29.3% (95% CI: 8.6 to 45.3) and for B 46.3% (95% CI: 13.9 to 66.5). For those aged under 18 years, influenza A(H3N2) LAIV VE was 35% (95% CI: -29.9 to 67.5), whereas for influenza B the LAIV VE was 100% (95% CI:17.0 to 100.0). Although the VE against influenza A(H3N2) infection was low, there was still evidence of significant protection, together with moderate, significant protection against drifted circulating influenza B viruses. LAIV provided non-significant positive protection against influenza A, with significant protection against B. Further work to assess the population impact of the vaccine programme across the UK is underway.

Estimating influenza vaccine effectiveness in Spain using sentinel surveillance data.

We aimed to estimate influenza vaccine effectiveness (VE) against laboratory-confirmed influenza during three influenza seasons (2010/11 to 2012/2013) in Spain using surveillance data and to compare the results with data obtained by the cycEVA study, the Spanish component of the Influenza Monitoring Vaccine Effectiveness (I-MOVE) network. We used the test-negative case–control design, with data from the Spanish Influenza Sentinel Surveillance System (SISS) or from the cycEVA study. Cases were laboratory-confirmed influenza patients with the predominant influenza virus of each season, and controls were those testing negative for any influenza virus. We calculated the overall and age-specific adjusted VE. Although the number of patients recorded in the SISS was three times higher than that in the cycEVA study, the quality of information for important variables, i.e. vaccination status and laboratory results, was high in both studies. Overall, the SISS and cycEVA influenza VE estimates were largely similar during the study period. For elderly patients (> 59 years), the SISS estimates were slightly lower than those of cycEVA, and estimates for children (0–14 years) were higher using SISS in two of the three seasons studied. Enhancing the SISS by collecting the date of influenza vaccination and reducing the percentage of patients with incomplete information would optimise the system to provide reliable annual influenza VE estimates to guide influenza vaccination policies.

Evaluation of influenza vaccine effectiveness and description of circulating strains in outpatient settings in South Africa, 2014.

The effectiveness of the trivalent seasonal influenza vaccine during the 2014 season in South Africa was assessed using a test-negative case–control study design including 472 cases and 362 controls. Influenza A(H3N2) was the dominant strain circulating. The overall vaccine effectiveness estimate, adjusted for age and underlying conditions, was 43·1% (95% CI: −26·8–74·5). 2014 H3N2 viruses from South Africa were mainly in sublineage 3C.3 with accumulation of amino acid changes that differentiate them from the vaccine strain in 3C.1.

Case control study of rotavirus vaccine effectiveness in Portugal during 6 years of private market use.

Although recommended by the vaccine committee of the Portuguese Paediatric Society, rotavirus vaccines have not been included in the routine immunization schedule. They have been available privately since 2006 with estimated coverage reaching approximately 30%. However, unlike other European countries using the vaccine, sentinel surveillance has detected fluctuations but no clear trends in the rate of gastrointestinal disease presentations. In this study, we set out to establish the real world effectiveness of rotavirus immunization in this low vaccine coverage setting. We carried out a test-negative case control study on a population of children attending a regional pediatric hospital, between 2006 and 2012, with symptoms of acute gastroenteritis and producing a stool sample for routine rotavirus testing. We calculated exposure odds ratio (ratio of odds of antecedent vaccination among cases compared with controls) to derive vaccine effectiveness ([1 - adjusted odds ratio]/100) against both hospital attendance and admission. Vaccine effectiveness against attendance with rotavirus acute gastroenteritis was 83.7% (95% confidence interval: 73.9-89.8) and against hospital admission was 96.1% (95% confidence interval: 83.8-99.1). No significant difference between the 2 available vaccines was detected. Both rotavirus vaccines offer a high degree of individual protection in this population.

Effectiveness and knowledge, attitudes and practices of seasonal influenza vaccine in primary healthcare settings in South Africa, 2010-2013.

ObjectivesInfluenza vaccine effectiveness (VE) and coverage data for sub-Saharan Africa are scarce. Using a test-negative case–control design, we estimated influenza VE annually among individuals with influenza-like illness presenting to an outpatient sentinel surveillance programme in South Africa from 2010 to 2013. A knowledge, attitudes and practices (KAP) influenza vaccine survey of programme clinicians was conducted in 2013.SampleIn total, 9420 patients were enrolled in surveillance of whom 5344 (56.7%) were included in the VE analysis: 2678 (50.1%) were classified as controls (influenza test-negative) and 2666 (49.9%) as cases (influenza test-positive).ResultsMean annual influenza vaccine coverage among controls was 4.5% for the four years. Annual VE estimates adjusted for age, underlying medical conditions and seasonality for 2010-2013 were 54.2% (95% confidence interval (CI): 2.4–78.6%), 57.1% (95% CI: 15.5–78.2%), 38.4% (95% CI: −71.7–78.1%) and 87.2% (95% CI: 67.2–95.0%), respectively. The KAP survey showed that >90% of clinicians were familiar with the indications for and the benefits of influenza vaccination.ConclusionsOur study showed that the vaccine was significantly protective in 2010, 2011 and 2013, but not in 2012 when the circulating A(H3N2) strain showed genetic drift. Vaccine coverage was low despite good clinician knowledge of vaccination indications. Further studies are needed to investigate the reason for the low uptake of influenza vaccine.

Influenza vaccine effectiveness against medically-attended influenza illness during the 2012–2013 season in Beijing, China

BackgroundInfluenza vaccine coverage remains low in China, and there is limited information on the preventive value of local vaccination programs. MethodsAs part of influenza virological surveillance in Beijing, China during the 2012–2013 influenza season, we assessed the vaccine effectiveness (VE) of one or more doses of trivalent inactivated influenza vaccine (IIV3) in preventing medically-attended influenza-like-illness (ILI) associated with laboratory-confirmed influenza virus infection using a test-negative case–control design. Influenza vaccination was determined based on self-report by adult patients or the parents of child patients. ResultsOf 1998 patients with ILI, 695 (35%) tested positive for influenza viruses, including 292 (42%) A(H3N2), 398 (57%) A(H1N1)pdm09, and 5 (1%) not (sub)typed influenza viruses. The rate of influenza vaccination among all patients was 4% (71/1998). Among influenza positive patients, 2% (57/1303) were vaccinated compared to 4% (14/695) among influenza negative patients, resulting in VE for one or more doses of vaccine (adjusted for age, sex, week, and days since illness onset) against all circulating influenza viruses of 52% (95% CI=12–74%). A significant adjusted VE for one or more doses of vaccine for all ages against A(H1N1)pdm09 of 59% (95% CI, 8–82%) was observed; however, the VE against A(H3N2) was 43% (95% CI, −30% to 75%). The point estimate of VE was 59% (95% CI, 19–79%) for those aged <60 years, but a negative VE point estimate without statistical significance was observed among those aged ≥60 years. ConclusionsIIV3 conferred moderate protection against medically-attended influenza in Beijing, China during the 2012–2013 season, especially against the A(H1N1)pdm09 strain and among those aged <60 years old.

Ethnic disparities in acquiring 2009 pandemic H1N1 influenza: a case–control study

BackgroundNovel risk factors were associated with the 2009 pandemic A/H1N1 virus (pH1N1). Ethnicity was among these risk factors. Ethnic disparities in hospitalization and death due to pH1N1 were noted. The purpose of this study is to determine whether there are ethnic disparities in acquiring the 2009 pandemic H1N1.MethodsWe conducted a test-negative case–control study of the risk of pH1N1 infection using data from Ontario, Canada. Cases were laboratory confirmed to have influenza using reverse-transcriptase polymerase chain reaction (RT-PCR), and controls were obtained from the same population and were RT-PCR negative. Multivariate logistic regression was used to determine the association between ethnicity and pH1N1 infection, while adjusting for demographic, clinical and ecological covariates.ResultsAdult cases were more likely than controls to be self-classified as East/Southeast Asian (OR = 2.59, 95% CI 1.02-6.57), South Asian (OR = 6.22, 95% CI 2.01-19.24) and Black (OR = 9.72, 95% CI 2.29-41.27). Pediatric cases were more likely to be self-identified as Black (OR = 6.43, 95% CI 1.83-22.59). However, pediatric cases without risk factors for severe influenza infection were more likely to be South Asian (OR 2.92, 95% CI 1.11-7.68), Black (OR 16.02, 95% CI 2.85-89.92), and West Asian/Arab, Latin American or Multi-racial groups (OR 3.09 95% CI 1.06-9.00).ConclusionspH1N1 cases were more likely to come from certain ethnic groups compared to test-negative controls. Insights into whether these disparities arise due to social or biological factors are needed in order to understand what approaches can be taken to reduce the burden of a future influenza pandemic.

Effectiveness of the 2010 and 2011 Southern Hemisphere trivalent inactivated influenza vaccines against hospitalization with influenza‐associated acute respiratory infection among Thai adults aged ≥50 years

BackgroundInactivated influenza vaccine (IIV) effectiveness has been evaluated among older adults in high-income countries, but data on IIV effectiveness in low- and middle-income countries remain sparse. We conducted a test-negative case–control analysis to estimate 2010 and 2011 trivalent IIV effectiveness against hospitalization with influenza-associated acute respiratory infection (ARI) among persons aged ≥50 years in rural Thailand.MethodsDuring 2010–2011, active surveillance for ARI hospitalization was conducted in two provinces; patients were tested for influenza viruses by real-time RT-PCR. Vaccination status was obtained from vaccine registries. Case and control patients were patients with nasopharyngeal swabs positive and negative for influenza viruses, respectively. Vaccine effectiveness (VE) was estimated for the 6 months after vaccination began. Logistic regression was used to evaluate the association between case status and vaccination while adjusting for age, province, medical conditions, and time.ResultsDuring 2010–2011, there were 1545 patients with ARI, of whom 279 (18%) were influenza-positive case patients and 1266 (82%) were influenza-negative control patients. Of the 279 case patients, 247 (89%) had influenza A and 32 (11%) had influenza B. Fourteen of 279 (5%) case patients and 108 of 1266 (9%) control patients were vaccinated against influenza. The unadjusted IIV effectiveness against hospitalization with influenza-associated ARI was 43% (95% CI: 0–68%); adjusted VE was 47% (95% CI: 5–71%).ConclusionThe 2010 and 2011 IIVs were moderately effective against hospitalization with influenza-associated ARI among Thais aged ≥50 years, but IIV coverage was low. Additional efforts are warranted in Thailand to improve IIV uptake in this target group.

Effectiveness of seasonal influenza vaccine in preventing medically attended influenza infection in England and Wales during the 2010/2011 season: a primary care-based cohort study

Estimates of seasonal influenza vaccine effectiveness (VE) are affected by factors such as the strain of the current circulating influenza virus and characteristics of the host. The objective of this study was to provide VE estimates for the 2010/2011 seasonal trivalent influenza vaccine (TIV) in preventing medically attended influenza in England and Wales for the season 2010/2011. A cohort study design was employed using electronic health records extracted from 104 GP practices in the Royal College of General Practitioners (RCGP) primary care sentinel network. Endpoints included influenza-like illness (ILI), lower respiratory tract infection (LTRI) as well as PCR-confirmed influenza from patients swabbed from practices participating in a swabbing scheme. Adjustment was made for age, month, underlying chronic condition, region and number of consultations in the 12months prior to the study period. In addition to the cohort analysis, a nested test-negative case-control analysis (TNCC) was carried out using the swab-negative results as controls. In the cohort analysis, VE against LRTI was -0·5% [95% CI: (-7·0%, 7·5%)], against ILI was 37·8% [95% CI: (32·3%, 43·0%)] and against PCR-confirmed influenza was 50·0% [95% CI:(25·9%, 65·6%)] for type A and 44·4% [95% CI: (10·1%, 65·6%)] for type B. Using the TNCC design, the type A VE was 56·5% [95% CI: (30·4%, 72·7%)] and for type B was 54·0% [95% CI: (21·0%, 73·3%)]. This study shows that the 2010/2011 TIV provided moderate protection against the circulating influenza strains for the 2010/2011 season. It also suggests that VE against the less specific diagnosis of ILI can be found, but less specific endpoints such as LRTI are not useful.

Estimates of influenza vaccine effectiveness in primary care in Scotland vary with clinical or laboratory endpoint and method—Experience across the 2010/11 season

AimThis study examines estimation of seasonal influenza vaccine effectiveness (VE) for a cohort of patients attending general practice in Scotland in 2010/11. The study focuses on the variation in estimation of VE for both virological and clinical consultation outcomes and understanding the dependency on date of analysis during the season, methodological approach and the effect of use of a propensity score model. MethodsFor the clinical outcomes, three methodological approaches were considered; adjusted Poisson multi-level modelling splitting consultations in vaccinated individuals into those before and after vaccination, adjusted Cox proportional hazards modelling and finally the screening method. For the virological outcome, the test-negative case–control study design was employed. ResultsVE was highest for the most specific outcomes of ILI (Poisson end-of-season VE=47% (95% CI: −69%, 83%); Cox VE=34% (95% CI: −64%, 73.2%); Screening VE=52.8% (95% CI: 3.8%, 76.8%)) and a virological diagnosis (VE=54% (95% CI: −37%, 85%)). Using the Cox approach, adjusted for propensity score only gave VE=46.5% (95% CI: −30.4%, 78.0%). ConclusionOur approach illustrated the ability to achieve relatively consistent estimates of seasonal influenza VE using both specific and less specific outcomes. Construction of a propensity score and use for bias adjustment increased the estimate of ILI VE estimated from the Cox model and made estimates more similar to the Poisson approach, which models differences in consultation behaviour of vaccinated individuals more inherently in its structure. VE estimation for the same data was found to vary by methodology which should be noted when comparing results from different studies and countries.

Effectiveness of the trivalent influenza vaccine in Navarre, Spain, 2010–2011: a population-based test-negative case–control study

BackgroundSome studies have evaluated vaccine effectiveness in preventing outpatient influenza while others have analysed its effectiveness in preventing hospitalizations. This study evaluates the effectiveness of the trivalent influenza vaccine in preventing outpatient illness and hospitalizations from laboratory-confirmed influenza in the 2010–2011 season.MethodsWe conducted a nested case–control study in the population covered by the general practitioner sentinel network for influenza surveillance in Navarre, Spain. Patients with influenza-like illness in hospitals and primary health care were swabbed for influenza testing. Influenza vaccination status and other covariates were obtained from health care databases. Using logistic regression, the vaccination status of laboratory-confirmed influenza cases was compared with that of test-negative controls, adjusting for age, sex, comorbidity, outpatient visits in the previous 12 months, health care setting, time between symptom onset and swabbing, period and A(H1N1)pdm09 vaccination. Effectiveness was calculated as (1-odds ratio)x100.ResultsThe 303 confirmed influenza cases (88% for A(H1N1)pdm09 influenza) were compared with the 286 influenza test-negative controls. The percentage of persons vaccinated against influenza was 4.3% and 15.7%, respectively (p<0.001). The adjusted estimate of effectiveness was 67% (95% CI: 24%, 86%) for all patients and 64% (95% CI: 8%, 86%) in those with an indication for vaccination (persons age 60 or older or with major chronic conditions). Having received both the 2010–2011 seasonal influenza vaccine and the 2009–2010 pandemic influenza vaccine provided 87% protection (95% CI: 30%, 98%) as compared to those not vaccinated.ConclusionThe 2010–2011 seasonal influenza vaccine had a moderate protective effect in preventing laboratory-confirmed influenza.

Editorial Commentary: Influenza Vaccine: Glass Half Full or Half Empty?

In this issue of Clinical Infectious Diseases, Ohmit and colleagues report the results of an assessment of influenza vaccine effectiveness during the 2010–2011 influenza season, using a nonrandomized, prospectively followed cohort [1]. This intriguing study had 2 surprising findings. Remarkably, the rate of polymerase chain reaction–documented influenza illness was not substantially different between those subjects whoreceivedinfluenzavaccine and those who did not, and the study was unable to demonstrate statistically significant vaccine effectiveness even after adjustment for age and the presence of high-risk conditions. The second surprising finding is that receipt of influenza vaccination in a previous season may have impacted the effectiveness of the vaccine in the current season. The population under study was predominantly young healthy adults and children with a low frequency of chronic health conditions, the types of subjects that typically mount the best immune responses to vaccine. In addition, there was a close antigenic match between the vaccine and circulating viruses. As we are currently struggling through one of the most vigorous influenza seasons in recent memory, the apparent failure of influenza vaccine under optimal conditions seen in this study is indeed troubling. Influenza vaccines are unique among currently licensed vaccines in that the continuous antigenic evolution of the virus requires frequent updating, reformulation, and annual administration of the vaccine. Thus, each year’ si nfluenza season essentially represents a test of a new vaccine against a new virus. Partly for this reason, there has been substantial interest for developing systems to monitor the performance of influenza vaccines on an annual basis. Prospective, randomized controlled trials are the method that is least susceptible to bias as the assignment of vaccinated or unvaccinated groups is made randomly. Organizing such trials on an annual basis would be quite challenging, however. Alternatively, several large networks have been developed that monitor vaccine effectiveness using a test-negative casecontrol design. In these studies, selected persons seeking care for acute respiratory illness are tested using a sensitive and specific test for influenza, and the vaccination histories of those testing positive are compared to those testing negative. The selection of cases based on a prespecified case definition and diagnostic testing without knowledge of vaccine history may eliminate some of the biases inherentinotherobservationalstudies[2], but the assessment is typically limited to medically attended outcomes. Because the majority of influenza infections do not result in a medical visit, this provides a somewhat incomplete assessment of the impact of vaccination. The innovative prospective surveil

Decline in influenza vaccine effectiveness with time after vaccination, Navarre, Spain, season 2011/12

This study evaluates the influenza vaccine effectiveness (VE) in preventing laboratory-confirmed cases in Navarre, Spain, in the 2011/12 season in which the peak was delayed until week 7 of 2012. We conducted a test-negative case–control study. Patients with influenza-like illness in hospitals and primary healthcare were swabbed for testing by reverse transcription-polymerase chain reaction. Influenza vaccination status and other covariates were obtained from healthcare databases. The vaccination status of confirmed cases and negative controls was compared after adjusting for potential confounders. VE was calculated as (1-odds ratio)x100. The 411 confirmed cases (93% influenza A(H3)) were compared with 346 controls. Most characterised viruses did not match the vaccine strains. The adjusted estimate of VE was 31% (95% confidence interval (CI): -21 to 60) for all patients, 44% (95% CI: -11 to 72) for those younger than 65 years and 19% (95% CI: -146 to 73) for those 65 or older. The VE was 61% (95% CI: 5 to 84) in the first 100 days after vaccination, 42% (95% CI: -39 to 75) between 100 and 119 days, and zero thereafter. This decline mainly affected people aged 65 or over. These results suggest a low preventive effect of the 2011/12 seasonal influenza vaccine, and a decline in VE with time since vaccination.

Vaccine effectiveness of 2011/12 trivalent seasonal influenza vaccine in preventing laboratory-confirmed influenza in primary care in the United Kingdom: evidence of waning intra-seasonal protection

The 2011/12 season was characterised by unusually late influenza A (H3N2) activity in the United Kingdom (UK). We measured vaccine effectiveness (VE) of the 2011/12 trivalent seasonal influenza vaccine (TIV) in a test-negative case–control study in primary care. Overall VE against confirmed influenza A (H3N2) infection, adjusted for age, surveillance scheme and month, was 23% (95% confidence interval (CI): -10 to 47). Stratified analysis by time period gave an adjusted VE of 43% (95% CI: -34 to 75) for October 2011 to January 2012 and 17% (95% CI: -24 to 45) for February 2012 to April 2012. Stratified analysis by time since vaccination gave an adjusted VE of 53% (95% CI: 0 to 78) for those vaccinated less than three months, and 12% (95% CI: -31 to 41) for those vaccinated three months or more before onset of symptoms (test for trend: p=0.02). For confirmed influenza B infection, adjusted VE was 92% (95% CI: 38 to 99). A proportion (20.6%) of UK influenza A(H3N2) viruses circulating in 2011/12 showed reduced reactivity (fourfold difference in haemagglutination inhibition assays) to the A/Perth/16/2009 2011/12 vaccine component, with no significant change in proportion over the season. Overall TIV protection against influenza A(H3N2) infection was low, with significant intraseasonal waning.

Effectiveness of the 2010–11 seasonal trivalent influenza vaccine in Spain: cycEVA study

BackgroundIn Spain, the influenza vaccine effectiveness (VE) was estimated in the last three seasons using an observational study (cycEVA) conducted in the frame of the Spanish Influenza Sentinel Surveillance System. We aimed to measure the effectiveness of the seasonal trivalent vaccine in preventing influenza like illness (ILI) laboratory-confirmed influenza infection at the end of the season 2010–11. MethodsWe conducted a test-negative case–control study between weeks 50/2010 and 12/2011. Cases were ILI laboratory-confirmed influenza infection and controls were those testing negative. Sentinel physicians collected data on demographic and clinical characteristics, vaccination status, and on covariates related to confounding factors associating with influenza VE. We calculated adjusted odds ratios (OR), using logistic regression and computed influenza VE as (1−OR)×100. ResultsThe adjusted influenza VE against A(H1N1)pdm09 infection was 46% (95% confidence interval (95%CI): 0; 72). In A(H1N1)pdm09 infected patients who had received both 2010–11 trivalent influenza seasonal and 2009 monovalent pandemic vaccines, influenza VE was 74% (95%CI: 13; 93). The adjusted influenza VE against B infection was 23% (95%CI: −180; 79). ConclusionThe trivalent influenza vaccine 2010–11 showed a moderate VE for preventing ILI laboratory confirmed influenza infections. Influenza VE estimates were higher in patients who had received both 2010–11 seasonal trivalent and 2009 monovalent pandemic vaccines.

Assessing the impact of confounding (measured and unmeasured) in a case–control study to examine the increased risk of pandemic A/H1N1 associated with receipt of the 2008–9 seasonal influenza vaccine

This study examines the role of measured and unmeasured confounding in the relationship between the 2008-9 seasonal influenza vaccine and pandemic H1N1 (pH1N1) influenza virus. Data were taken from a test-negative case-control study of 462 lab confirmed pandemic A/H1N1 (pH1N1) cases and 484 test-negative controls. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were derived using multivariate logistic regression. The analysis was repeated using propensity matching. A sensitivity analysis was conducted to quantify the impact of a hypothetical unmeasured confounder. Cases were more likely to have received the seasonal influenza vaccine after adjusting for multiple confounders using multivariate regression (OR 1.82, 95% CI: 1.25-2.65), using propensity matching (OR 1.86, 95% CI: 1.19-2.92) and in subsequent sensitivity analyses. An unmeasured confounder would need a prevalence of 20%, an odds ratio with the vaccine and pH1N1 of ≥3.5 and ≥3.0 (respectively) to result in a non-significant association. Using a prevalence of 40% the respective associations were 3.0 and 2.5. A significant positive association between the seasonal influenza vaccine and lab confirmed pH1N1 was observed after considering multiple confounders and using different methods for confounder adjustment. This was not likely explained by an unmeasured confounder given the prevalence and strength of association needed to result in a non-significant association.

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.