Influenza vaccine effectiveness to prevent influenza-related hospitalizations and serious outcomes in Canadian adults over the 2011/12 through 2013/14 influenza seasons: A pooled analysis from the Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance (SOS Network)

BackgroundOngoing assessment of influenza vaccine effectiveness (VE) is critical to inform public health policy. This study aimed to determine the VE of trivalent influenza vaccine (TIV) for preventing influenza-related hospitalizations and other serious outcomes over three consecutive influenza seasons.MethodsThe Serious Outcomes Surveillance (SOS) Network of the Canadian Immunization Research Network (CIRN) conducted active surveillance for influenza in adults ≥16 years (y) of age during the 2011/2012, 2012/2013 and 2013/2014 seasons in hospitals across Canada. A test-negative design was employed: cases were polymerase chain reaction (PCR)-positive for influenza; controls were PCR-negative for influenza and were matched to cases by date, admission site, and age (≥65 y or <65 y). All cases and controls had demographic and clinical characteristics (including influenza immunization status) obtained from the medical record. VE was estimated as 1-OR (odds ratio) in vaccinated vs. unvaccinated patients × 100%. The primary outcome was VE of TIV for preventing laboratory-confirmed influenza-related hospitalization; secondary outcomes included VE of TIV for preventing influenza-related intensive care unit (ICU) admission/mechanical ventilation, and influenza-related death.ResultsOverall, 3394 cases and 4560 controls were enrolled; 2078 (61.2%) cases and 2939 (64.5%) controls were ≥65 y. Overall matched, adjusted VE was 41.7% (95% Confidence Interval (CI): 34.4–48.3%); corresponding VE in adults ≥65 y was 39.3% (95% CI: 29.4–47.8%) and 48.0% (95% CI: 37.5–56.7%) in adults <65 y, respectively. VE for preventing influenza-related ICU admission/mechanical ventilation in all ages was 54.1% (95% CI: 39.8–65.0%); in adults ≥65 y, VE for preventing influenza-related death was 74.5% (95% CI: 44.0–88.4%).ConclusionsWhile effectiveness of TIV to prevent serious outcomes varies year to year, we demonstrate a statistically significant and clinically important TIV VE for preventing hospitalization and other serious outcomes over three seasons. Public health messaging should highlight the overall benefit of influenza vaccines over time while acknowledging year to year variability.ClinicalTrials.gov Identifier: NCT01517191.     

Increasing influenza vaccine uptake in children: A randomised controlled trial

BackgroundInfluenza vaccine is not included in the Hong Kong Government’s universal Childhood Immunisation Programme but eligible children can receive subsidised vaccine through the private sector using the Vaccination Subsidy Scheme (VSS). This study examined whether a simple intervention package can increase influenza vaccine uptake in Hong Kong children.MethodsTwo study samples were enrolled: families of children who had participated in a previous knowledge, attitudes and practices study; and mother-infant pairs recruited from postnatal wards. Control groups received publicly available leaflets about VSS. Intervention groups additionally received: (1) a concise information sheet about influenza and its vaccine; (2) semi-completed forms to utilise the subsidy; (3) contacts of VSS clinics that did not charge above the subsidy; and (4) text message reminders for vaccination. Enrolled mothers were contacted when children were approximately 1 and 2 years old to determine influenza vaccination status of the families and their plan to vaccinate their children. Mothers’ attitudes towards influenza vaccine were assessed at enrolment and at the end of the study.ResultsA total of 833 eligible mother-infant pairs were enrolled from the two samples. The intervention package improved influenza vaccine uptake by 22% at one year and 25% at two years of age. Maternal influenza vaccine uptake in intervention group was higher during this two-year period in those who had never been previously vaccinated. Mothers’ self-efficacy regarding the use of influenza vaccine in her child i.e. belief and confidence in her own ability to make a good decision, was also improved with the intervention.ConclusionsA four-component intervention package could improve influenza vaccine uptake in Hong Kong children and their mothers during the first two years of life and depending on vaccine effectiveness could potentially reduce influenza-associated hospital admissions in children below 2 years old by 13–24%.     

Influenza vaccine effectiveness against laboratory confirmed influenza in Greece during the 2013–2014 season: A test-negative study

BackgroundIn 2013–2014 Greece experienced a resurgence of severe influenza cases, coincidental with a shift to H1N1pdm09 predominance. We sought to estimate Vaccine Effectiveness (VE) for this season using available surveillance data from hospitals (including both inpatients and outpatients).MethodsSwab samples were sent by hospital physicians to one of three laboratories, covering the entire country, to be tested for influenza using RT-PCR. The test-negative design was employed, with patients testing positive serving as cases and those testing negative serving as controls. VE was estimated using logistic regression, adjusted for age group, sex, region and calendar time, with further adjustment for unknown vaccination status using inverse response propensity weights. Additional age group stratified estimates and subgroup estimates of VE against H1N1pdm09 and H3N2 were calculated.ResultsOut of 1310 patients with known vaccination status, 124 (9.5%) were vaccinated, and 543 patients (41.5%) tested positive for influenza. Adjusted VE was 34.5% (95% CI: 4.1–55.3%) against any influenza, and 56.7% (95% CI: 22.8–75.7%) against H1N1pdm09. VE estimates appeared to be higher for people aged 60 and older, while in those under 60 there was limited evidence of effectiveness. Isolated circulating strains were genetically close to the vaccine strain, with limited evidence of antigenic drift.ConclusionsThese results suggest a moderate protective effect of the 2013–2014 influenza vaccine, mainly against H1N1pdm09 and in people aged 60 and over. Vaccine coverage was very low in Greece, even among groups targeted for vaccination, and substantial efforts should be made to improve it. VE can and should be routinely monitored, and the results taken into account when deciding on influenza vaccine composition for next season.     

The European I-MOVE Multicentre 2013–2014 Case-Control Study. Homogeneous moderate influenza vaccine effectiveness against A(H1N1)pdm09 and heterogenous results by country against A(H3N2)

BackgroundIn the first five I-MOVE (Influenza Monitoring Vaccine Effectiveness in Europe) influenza seasons vaccine effectiveness (VE) results were relatively homogenous among participating study sites. In 2013–2014, we undertook a multicentre case-control study based on sentinel practitioner surveillance networks in six European Union (EU) countries to measure 2013–2014 influenza VE against medically-attended influenza-like illness (ILI) laboratory-confirmed as influenza. Influenza A(H3N2) and A(H1N1)pdm09 viruses co-circulated during the season.MethodsPractitioners systematically selected ILI patients to swab within eight days of symptom onset.We compared cases (ILI positive to influenza A(H3N2) or A(H1N1)pdm09) to influenza negative patients. We calculated VE for the two influenza A subtypes and adjusted for potential confounders. We calculated heterogeneity between sites using the I² index and Cochrane's Q test. If the I² was <50%, we estimated pooled VE as (1 minus the OR) × 100 using a one-stage model with study site as a fixed effect. If the I² was >49% we used a two-stage random effects model.ResultsWe included in the A(H1N1)pdm09 analysis 531 cases and 1712 controls and in the A(H3N2) analysis 623 cases and 1920 controls. For A(H1N1)pdm09, the Q test (p = 0.695) and the I² index (0%) suggested no heterogeneity of adjusted VE between study sites. Using a one-stage model, the overall pooled adjusted VE against influenza A(H1N1)pdm2009 was 47.5% (95% CI: 16.4–67.0).For A(H3N2), the I² was 51.5% (p = 0.067). Using a two-stage model for the pooled analysis, the adjusted VE against A(H3N2) was 29.7 (95% CI: −34.4–63.2).ConclusionsThe results suggest a moderate 2013–2014 influenza VE against A(H1N1)pdm09 and a low VE against A(H3N2). The A(H3N2) estimates were heterogeneous among study sites. Larger sample sizes by study site are needed to prevent statistical heterogeneity, decrease variability and allow for two-stage pooled VE for all subgroup analyses.     

Waning vaccine protection against influenza A (H3N2) illness in children and older adults during a single season

BackgroundRecent studies have suggested that vaccine-induced protection against influenza may decline within one season. We reanalyzed data from a study of influenza vaccine effectiveness to determine if time since vaccination was an independent predictor of influenza A (H3N2).MethodsPatients with acute respiratory illness were actively recruited during the 2007–2008 season. Respiratory swabs were tested for influenza, and vaccination dates were determined by a validated immunization registry. The association between influenza RT-PCR result and vaccination interval (days) was examined using multivariable logistic regression, adjusting for calendar time, age and other confounders.ResultsThere were 629 vaccinated participants, including 177 influenza A (H3N2) cases and 452 test negative controls. The mean (SD) interval from vaccination to illness onset was 101.7 (25.9) days for influenza cases and 93.0 (29.9) days for controls. There was a significant association between vaccination interval and influenza result in the main effects model. The adjusted odds ratio (aOR) for influenza was 1.12 (CI 1.01, 1.26) for every 14 day increase in the vaccination interval. Age modified the association between vaccination interval and influenza (p = 0.005 for interaction). Influenza was associated with increasing vaccination interval in young children and older adults, but not in adolescents or non-elderly adults. Similar results were found when calendar week of vaccine receipt was assessed as the primary exposure variable.ConclusionsIdentification of influenza A (H3N2) was associated with increasing time since vaccination among young children and older adults during a single influenza season.     

Basic principle of population-based cohort study to evaluate influenza vaccine effectiveness among elderly Japanese

Influenza vaccines minimize the risk of influenza-related morbidity, complication, and death in elderly people. Although evaluating vaccine effectiveness (VE) is important for promoting immunization programs and coping with influenza epidemics, it is difficult to evaluate its effectiveness in Japan, where no frameworks to use large databases, such as a vaccination registry and health maintenance organization datasets, are available. Therefore, another analytic epidemiological investigations to evaluate VE in Japan are required. Herein, we describe the basic principles of a cohort study, which might be the most comprehensive, but expensive, study design. It is particularly important to be aware of the potential bias and confounding factors that should be minimized in the study design and analysis. We focus on “laboratory-confirmed influenza” and “influenza-like illness”, and discuss why it is important to follow up with equal intensity, and how to control for bias; problems that often arise in population-based observational cohort studies.     

Influenza vaccination: Uptake and associations in a cross-sectional study of children with special risk medical conditions

ObjectiveTo determine uptake of influenza vaccination in children with special risk medical conditions (SRMC) and to explore associations with vaccination.DesignCross-sectional study.Setting/participantsParents of children with a SRMC attending either outpatient department clinics or being an inpatient at the Women’s and Children’s Hospital (WCH), Adelaide, Australia from September 2015 to February 2016 were recruited using convenience sampling.MethodsData were collected using a face-to-face survey. Influenza vaccination was verified with providers. Characteristics associated with uptake were explored using univariable and multivariable analyses.ResultsThere were 410 participants with complete data. Confirmed influenza vaccination at least once in the last two years was 50%, annual uptake was 32.8%. 63.9% of parents were aware of the vaccination recommendation and 57.9% had been recommended by a specialist or general practitioner (GP). Characteristics strongly associated with uptake included: receiving a recommendation from a specialist or GP and having a parent receive the influenza vaccine annually.ConclusionsDespite a long standing funded program, influenza vaccination uptake in children with SRMC is suboptimal. Parental vaccination behaviour, along with medical practitioner recommendation, particularly specialist recommendation, appear to be key influences in facilitating vaccination. Potential interventions could target the family rather than just the individual child. Understanding the barriers to recommendation from the perspective of general medical practitioners and specialists who treat these children is needed.     

Impact and effectiveness of childhood varicella vaccine program in Queensland,Australia

BackgroundIn November 2005, Australia introduced a publicly funded single dose of varicella vaccine for children aged 18-months. We describe the impact of this program on varicella hospitalisations in Queensland and provide the first assessment of single-dose varicella vaccine effectiveness in Australia since the program commenced.MethodsAge-standardised varicella hospitalisation rates were calculated for 2000–2014 and pre- and post-public funding period rates compared. Case-control studies were conducted to investigate the association between vaccine receipt and both varicella hospitalisations and uncomplicated varicella emergency department presentations. Cases were matched to controls from a population-based register by date of birth and state of residence. Vaccine effectiveness was calculated as (1 – odds ratio) × 100%.ResultsCompared to the pre-funded period (2000–2003), age-standardised varicella hospitalisation rates declined by more than 70% in 2011–2014 with varicella principal diagnosis rates declining from 5.7 to 1.6 per 100,000 population per year. Varicella vaccine effectiveness at preventing hospitalisation with a principal diagnosis of varicella among children aged 19-months to 6-years was 81.9% (95% confidence interval: 61.8–91.4%), while for emergency department presentations among children aged 19-months to 8-years it was 57.9% (95% confidence interval: 48.5–65.5%).ConclusionsIn Australia, the single-dose varicella vaccination program has substantially reduced varicella morbidity. The single-dose varicella vaccine schedule is moderately-to-highly effective against hospitalisation, but appears less effective against emergency department presentations.     

Why do we not want to recommend influenza vaccination to young children? A qualitative study of Australian parents and primary care providers

IntroductionInfluenza vaccination has been shown to be safe and effective against influenza and in the prevention of complicating secondary respiratory illnesses. However, its uptake in young children remains low. This study explored the views, attitudes and practices of parents and primary care providers (PCPs) on their knowledge and acceptance of influenza vaccination in children under 5.MethodsUsing a cross-sectional qualitative research design, we conducted 30 in-depth interviews with PCPs (i.e., general practitioners, practice nurses, maternal and child health nurses, and pharmacists) and five focus groups with parents (n = 50) between June 2014 and July 2015 in Melbourne, Australia. Data were thematically analysed.ResultsParents thought the vaccine could cause influenza, and influenza vaccination was not necessary for their children as they needed to build their own ‘immunity’. Parents said that they would consider vaccinating their children if recommended by their GP and if the influenza vaccine was part of the immunisation schedule. PCPs also expressed concerns regarding the efficacy of the vaccine as well as out-of-pocket costs incurred by families, and uncertainty regarding the mortality and morbidity of influenza in otherwise healthy children. However, they said they would recommend the vaccine to high-risk groups (e.g. children with chronic disease(s), and asthma).ConclusionDespite the established safety of influenza vaccines, barriers to uptake include concerns regarding the iatrogenic effects of vaccination, its administration schedule, and knowledge of influenza severity. Updated information on influenza and the efficacy of the vaccine, and incorporating influenza vaccination into the immunisation schedule may overcome some of these barriers to increase influenza vaccination in this vulnerable cohort.     

Cost-effectiveness and public health impact of alternative influenza vaccination strategies in high-risk adults

PurposeHigh-dose trivalent inactivated influenza vaccine (HD-IIV3) or recombinant trivalent influenza vaccine (RIV) may increase influenza vaccine effectiveness (VE) in adults with conditions that place them at high risk for influenza complications. This analysis models the public health impact and cost-effectiveness (CE) of these vaccines for 50–64 year-olds.MethodsMarkov model CE analysis compared 5 strategies in 50–64 year-olds: no vaccination; only standard-dose IIV3 offered (SD-IIV3 only), only quadrivalent influenza vaccine offered (SD-IIV4 only); high-risk patients receiving HD-IIV3, others receiving SD-IIV3 (HD-IIV3 & SD-IIV3); and high-risk patients receiving HD-IIV3, others receiving SD-IIV4 (HD-IIV3 & SD-IIV4). In a secondary analysis, RIV replaced HD-IIV3. Parameters were obtained from U.S. databases, the medical literature and extrapolations from VE estimates. Effectiveness was measured as 3%/year discounted quality adjusted life year (QALY) losses avoided.ResultsThe least expensive strategy was SD-IIV3 only, with total costs of $99.84/person. The SD-IIV4 only strategy cost an additional $0.91/person, or $37,700/QALY gained. The HD-IIV3 & SD-IIV4 strategy cost $1.06 more than SD-IIV4 only, or $71,500/QALY gained. No vaccination and HD-IIV3 & SD-IIV3 strategies were dominated. Results were sensitive to influenza incidence, vaccine cost, standard-dose VE in the entire population and high-dose VE in high-risk patients. The CE of RIV for high-risk patients was dependent on as yet unknown parameter values.ConclusionsBased on available data, using high-dose influenza vaccine or RIV in middle-aged, high-risk patients may be an economically favorable vaccination strategy with public health benefits. Clinical trials of these vaccines in this population may be warranted.     

Immunogenicity and safety of an AS03-adjuvanted H5N1 pandemic influenza vaccine in Korean adults: A phase IV,randomized, open-label,controlled study

BackgroundAS03-adjuvanted H5N1 pandemic influenza vaccines have been assessed in an extensive clinical development program conducted in North America, Europe, and Asia including children from 6 months of age, adults, and elderly adults. We evaluated AS03-H5N1 in Korean adults 18 through 60 years of age.MethodsThis Phase IV, randomized, study was conducted to assess the immunogenicity, reactogenicity, and safety of two doses (3.75 μg of hemagglutinin antigen) of A/Indonesia/5/2005 (H5N1) adjuvanted with AS03 given 21 days apart in Korean adults. Antibody responses were assessed using hemagglutination-inhibition (HI) assays against the vaccine strain and a vaccine-heterologous strain (A/Vietnam/1194/2004) 21 days after the second dose. A control group (safety) received a licensed seasonal inactivated trivalent influenza vaccine (TIV). Reactogenicity was assessed for 7 days after each vaccination, and unsolicited adverse events were assessed for 182 days following vaccination in both study groups (NCT01730378).ResultsAS03-H5N1 was immunogenic and elicited robust HI antibody responses with seroconversion rates of 100% for the vaccine strain and 69.1% for the heterologous strain (N = 81). HI antibody responses fulfilled the European licensure criteria for immunogenicity (primary endpoint). The incidence of local and systemic solicited adverse events (reactogenicity) was higher with AS03-H5N1 than TIV. There was no apparent difference in the rate of unsolicited adverse events in the AS03-H5N1 and TIV groups.ConclusionThe results indicate that AS03-H5N1 vaccine is immunogenic with reactogenicity and safety findings that are consistent with the established profile of AS03-H5N1 vaccine.     

Immunogenicity and safety of double versus standard dose of the seasonal influenza vaccine in solid-organ transplant recipients: A randomized controlled trial

BackgroundThe use of vaccines with higher doses of antigen is an attractive strategy to improve the immunogenicity of influenza vaccination in transplant recipients. However, the effect of vaccination with a double-dose (DD) containing 30 µg of antigen in this population remains unknown.MethodsWe performed a randomized controlled trial to compare the immunogenicity and safety of DD (30 µg) vs. standard dose (SD, 15 µg) of a trivalent inactivated influenza vaccine in kidney and liver transplant recipients. Immunogenicity was assessed by hemagglutination-inhibition assay. Vaccine response was defined as seroconversion to at least one viral strain 2 weeks after vaccination and seroprotection as a titer ≥40.ResultsSixty-three kidney and 16 liver transplant recipients were enrolled. Forty patients received the DD and 39 the SD vaccine. Overall, 40% of patients in the DD compared to 26% in the SD group (P = 0.174) responded to vaccine. In the DD arm, more patients were seroprotected to all viral strains after vaccination (88% vs 69%, P = 0.048). Post vaccination geometric mean titers of antibodies were 131.9 vs. 89.7 (P = 0.187) for H1N1, 185.4 vs. 138.7 (P = 0.182) for H3N2, and 96.6 vs. 68.8 (P = 0.081) for influenza B with the DD vs. SD. In both groups, most of the adverse events were mild and no vaccine-related severe adverse events were observed.ConclusionDouble-dose influenza vaccine is safe and may increase antibody response in transplant recipients. In this population, DD vaccination could be an alternative when high-dose vaccine is not available. NCT02746783.     

Rationale for two influenza B lineages in seasonal vaccines: A meta-regression study on immunogenicity and controlled field trials

B lineage mismatch prompted introduction of quadri-valent influenza vaccines (QIV) with two influenza B viruses representing distinct antigenic lineages. To explore the impact on antibody induction and vaccine effectiveness predicted from antibody (VEab), we performed a systematic literature search on immunogenicity studies conducted to assess antibody superiority of QIV over trivalent influenza vaccine (TIV). Thirteen relevant articles described 31 trials from 2007 and 2013. Log-transformed GMT trial estimates and their variances were converted to clinical protection rates predicted from antibody (PRab). VEab estimates were calculated from pre- and post-vaccination PRab. Without specific pre-vaccination immunity, average VEab was 69% for match, and −4% for lineage mismatch. With increasing pre-vaccination seropositivity, mismatch impact declined to 2%. We also performed an umbrella literature search for randomised controlled trials and test-negative case-control trials with TIV, and estimated vaccine effectiveness against laboratory-confirmed influenza B (VEf). Sixty-eight eligible clinical articles described 110 season-trials from 1965 to 2012, covering seasons with B lineage match (n = 52), lineage drift (n = 15) and lineage mismatch (n = 43). With no pre-vaccination antibody levels determined, we used chance of previous exposure to influenza B (Ppe) as pre-seasonal immunity measure. When Ppe was 0%, average VEf for matched seasons was 67%, and for mismatched seasons 35%, indicating a moderate, yet significant mismatch impact on VEf. With increasing Ppe, mismatch impact declined to 3%. Thus serological and field trials indicate that B lineage mismatch impact is negatively related to pre-seasonal immunity and that the gain of QIV over TIV most benefits infants and children not yet exposed to influenza B.     

The cost-effectiveness of trivalent and quadrivalent influenza vaccination in communities in South Africa,Vietnam and Australia

BackgroundTo inform national healthcare authorities whether quadrivalent influenza vaccines (QIVs) provide better value for money than trivalent influenza vaccines (TIVs), we assessed the cost-effectiveness of TIV and QIV in low-and-middle income communities based in South Africa and Vietnam and contrasted these findings with those from a high-income community in Australia.MethodsIndividual based dynamic simulation models were interfaced with a health economic analysis model to estimate the cost-effectiveness of vaccinating 15% of the population with QIV or TIV in each community over the period 2003–2013. Vaccination was prioritized for HIV-infected individuals, before elderly aged 65+ years and young children. Country or region-specific data on influenza-strain circulation, clinical outcomes and costs were obtained from published sources. The societal perspective was used and outcomes were expressed in International$ (I$) per quality-adjusted life-year (QALY) gained.ResultsWhen compared with TIV, we found that QIV would provide a greater reduction in influenza-related morbidity in communities in South Africa and Vietnam as compared with Australia. The incremental cost-effectiveness ratio of QIV versus TIV was estimated at I$4183/QALY in South Africa, I$1505/QALY in Vietnam and I$80,966/QALY in Australia.ConclusionsThe cost-effectiveness of QIV varied between communities due to differences in influenza epidemiology, comorbidities, and unit costs. Whether TIV or QIV is the most cost-effective alternative heavily depends on influenza B burden among subpopulations targeted for vaccination in addition to country-specific willingness-to-pay thresholds and budgetary impact.     

Completion and compliance of childhood vaccinations in the United States

BackgroundThe Advisory Committee on Immunization Practices recommends routine childhood vaccination by age 2 years, yet evidence suggests that only 2% to 26% of children receive vaccine doses at age-appropriate times (compliance). The objective of this study was to estimate vaccine completion and compliance rates between birth and age 2 years using recent, nationally representative data.MethodsUsing a sample of children aged 24 to 35 months from the 2012 National Immunization Survey (NIS), the present study examined completion and compliance of recommended childhood vaccines. A state-specific examination of vaccine completion and compliance was also conducted.ResultsAn unweighted sample of 11,710 children (weighted to 4.1 million) was selected. Approximately 70% of children completed all doses of six recommended vaccines by 24 months of age. Completion rates varied by antigen, ranging from 68% completing two or three doses of rotavirus vaccine to 92% completing three doses of inactivated poliovirus vaccine. Vaccine completion rates also varied at different measurement periods, with the lowest rates observed at 18 months. Approximately 26% of children received all doses of six recommended vaccines on time. Among the 74% of children who received at least one late dose, 39% had >7 months of undervaccination. Patterns of completion and compliance also varied by geographic region.ConclusionsCompletion of individual antigens approached Healthy People 2020 targets. However, overall completion of the recommended vaccine series and compliance with the recommended vaccination dosing schedule were low, indicating few children received vaccines at age-appropriate times. Additional clinical, policy, and educational interventions are needed to increase receipt of vaccines at optimal ages.     

Improved immunogenicity of high-dose influenza vaccine compared to standard-dose influenza vaccine in adult oncology patients younger than 65 years receiving chemotherapy: A pilot randomized clinical trial

PurposePatients undergoing chemotherapy often fail to develop robust responses to influenza vaccination. Compared to standard-dose influenza vaccine (SD), high-dose influenza vaccine (HD) has shown improved immunogenicity and protection against influenza illness in adults 65 years and older. This study compared the immunogenicity and tolerability of HD to SD in adults younger than 65 years of age receiving chemotherapy.MethodsThis double-blind study randomized patients receiving chemotherapy to vaccination with either SD or HD influenza vaccine. Hemagglutination inhibition assays (HAI) were performed prior to and 4 weeks after vaccination. HAI were summarized as geometric mean titers (GMT), seroconversion rates, and seroprotection rates.ResultsA total of 105 subjects were enrolled in the trial (51 received SD and 54 received HD). Subjects were well matched for demographic and medical conditions. Both vaccines were well tolerated with no SAEs. Of the 100 subjects with evaluable data, seroconversion rates for all 3 influenza antigens & post-vaccination GMTs for H3N2 & B strains were significantly improved with HD compared to SD. Seroprotection was excellent and equivalent in both groups.ConclusionsTrivalent high-dose influenza vaccine can be safely administered to patients receiving chemotherapy with improved immunogenicity and seroconversion compared to standard-dose vaccine. Post-vaccination seroprotection rates were similar in both groups. A larger study is needed to show clinical benefits with HD in this population.This study was registered at ClinicalTrials.gov as NCT01666782.     

Predictors of influenza vaccination in the U.S. among children 9–13 years of age

Background and objectivesU.S. estimates of seasonal influenza (flu) vaccine uptake in 2014–2015 were 62% for 5–12 year olds, dropping to 47% for 13–17 year olds. The Healthy People 2020 goal for these age groups is 80%. It is important to understand factors associated with influenza vaccination, especially for those ages where rates begin to decline. The objective of this study was to identify factors associated with influenza vaccination acceptance in 9–13 year old children.MethodsAn online U.S. survey of mothers of children aged 9–13 assessed children's influenza vaccine uptake in the previous season, healthcare utilization, sociodemographics, and vaccine attitudes. Multivariable logistic regression identified independent predictors of influenza vaccine status.ResultsThere were 2363 respondents (Mean age = 38 years old). Referent children were 57% female and 66% non-minority race/ethnicity with a mean age of 10.6 years. By maternal report, 59% of children had received an influenza vaccine in the previous season. Predictors of influenza vaccine uptake included a recommendation or strong recommendation from a health care provider, seeing a health care provider in the past year, positive attitudes regarding the influenza vaccine, and being a minority race. Child gender, age, insurance coverage, and whether the child had a regular healthcare provider were not associated with influenza vaccine uptake (p = n.s.).ConclusionsThis sample reported overall rates of influenza vaccine uptake similar to national surveillance data, but still lower than national goals. Provider recommendations along with health attitudes and seeing a health care provider were associated with vaccine uptake. Promising interventions may include more directive physician messaging for influenza vaccine uptake in youth, encouraging more regular well-child visits during the adolescent years, and promoting influenza vaccination at alternative sites.     

Association of spontaneous abortion with receipt of inactivated influenza vaccine containing H1N1pdm09 in 2010–11 and 2011–12

IntroductionInactivated influenza vaccine is recommended in any stage of pregnancy, but evidence of safety in early pregnancy is limited, including for vaccines containing A/H1N1pdm2009 (pH1N1) antigen. We sought to determine if receipt of vaccine containing pH1N1 was associated with spontaneous abortion (SAB).MethodsWe conducted a case-control study over two influenza seasons (2010–11, 2011–12) in the Vaccine Safety Datalink. Cases had SAB and controls had live births or stillbirths and were matched on site, date of last menstrual period, and age. Of 919 potential cases identified using diagnosis codes, 485 were eligible and confirmed by medical record review. Exposure was defined as vaccination with inactivated influenza vaccine before the SAB date; the primary exposure window was the 1–28 days before the SAB.ResultsThe overall adjusted odds ratio (aOR) was 2.0 (95% CI, 1.1–3.6) for vaccine receipt in the 28-day exposure window; there was no association in other exposure windows. In season-specific analyses, the aOR in the 1–28 days was 3.7 (95% CI 1.4–9.4) in 2010–11 and 1.4 (95% CI 0.6–3.3) in 2011–12. The association was modified by influenza vaccination in the prior season (post hoc analysis). Among women who received pH1N1-containing vaccine in the previous influenza season, the aOR in the 1–28 days was 7.7 (95% CI 2.2–27.3); the aOR was 1.3 (95% CI 0.7–2.7) among women not vaccinated in the previous season. This effect modification was observed in each season.ConclusionSAB was associated with influenza vaccination in the preceding 28 days. The association was significant only among women vaccinated in the previous influenza season with pH1N1-containing vaccine. This study does not and cannot establish a causal relationship between repeated influenza vaccination and SAB, but further research is warranted.     

Characteristics and health behaviors of diabetic patients receiving influenza vaccination

ObjectiveEpidemiological research has posited a ‘healthy user’ bias in patients receiving influenza vaccination; thus we sought to evaluate potential healthy-user attributes and their associations with influenza vaccination.Research design & methodsBetween 2011 and 2013, adults with type 2 diabetes were enrolled in a prospective cohort in Alberta, Canada. Information collected included sociodemographics, diabetes-related data (e.g., duration, complications), health behaviors (e.g., smoking status), functional health status, and satisfaction with healthcare. Data were collected by a mailed, self-administered survey. Multivariable logistic regression analyses were used to identify potential healthy-user attributes independently associated with influenza vaccination.ResultsFrom a cohort of 2040 patients, 1287 (63%) reported receiving the influenza vaccine in the previous year. Average age of the cohort was 64 years (standard deviation 11) and 55% were male. In multivariable analysis, attributes independently associated with influenza vaccination included receiving preventive medications: aspirin (64% vs 44%; adjusted odds ratio, aOR 1.65, 95% CI 1.34–2.04); blood pressure medications (76% vs 56%; aOR 1.36, 95% CI 1.07–1.71); and cholesterol-lowering medications (74% vs 53%; aOR 1.50, 95% CI 1.19–1.89), as well as having a healthcare professional check feet for lesions (47% vs 31%; aOR 1.39, 95% CI 1.12–1.74). Additional covariates independently associated with influenza vaccination included: age over 65 years, respiratory disease, the number of additional comorbidities, and higher ratings of healthcare experience.ConclusionVaccinated diabetic patients exhibit many postulated attributes of ‘healthy users’, which has implications for the interpretation of epidemiological studies of influenza vaccine effectiveness, as well as targeting future vaccination campaigns.     

Enhanced humoral response to influenza vaccine in aged mice with a novel adjuvant,rOv-ASP-1

Immunization is the best way to prevent seasonal epidemics and pandemics of influenza. There are two kinds of influenza vaccines available in the United States: an inactivated vaccine (TIV) and an attenuated vaccine; however, only TIV is approved for immunization of the elderly population. While the aged population has the highest rate of influenza vaccination, the protective efficacy is low as evidenced by elderly individuals having the highest mortality associated with influenza. Recently, we reported that an adjuvant derived from the helminth parasite Onchocerca volvulus, named O. volvulus activation-associated secreted protein-1 (Ov-ASP-1), can significantly enhance the protective efficacy of an inactivated vaccine (TIV) in young adult mice. In the current study, we examined whether this recombinant Ov-ASP-1 (rOv-ASP-1) can enhance the efficacy of TIV in aged mice as well. While primary immunization with TIV alone produced only a low level of influenza-specific antibodies (total IgG, IgG1, and IgG2c) in aged mice, the antibody levels were significantly increased after immunization with TIV + rOv-ASP-1. More importantly, the level of the total IgG in aged mice administered TIV + rOv-ASP-1 was comparable to that of young adult mice immunized with TIV alone. Co-administration of rOv-ASP-1 induced a low level of cross-reactive antibody and enhanced the protective efficacy of TIV in aged mice, reflected by significantly increased survival after challenge with a heterologous influenza virus. rOv-ASP-1 was also superior to the conventional adjuvant alum in inducing specific IgG after TIV immunization in aged mice, and in conferring protection after challenge. These results demonstrate that rOv-ASP-1 may serve as a potential adjuvant for influenza vaccine to improve the efficacy of protection in the elderly.