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Background: Randomized trials conducted in low- and middle-income settings demonstrated efficacy of influenza vaccination during pregnancy against influenza infection among infants <6 months of age. However, vaccine effectiveness (VE) estimates from settings with different population characteristics and influenza seasonality remain limited., Methods: We conducted a test-negative study in Ontario, Canada. All influenza virus tests among infants <6 months from 2010 to 2019 were identified and linked with health databases to ascertain information on maternal-infant dyads. VE was estimated from the odds ratio for influenza vaccination during pregnancy among cases versus controls, computed using logistic regression with adjustment for potential confounders., Results: Among 23 806 infants tested for influenza, 1783 (7.5%) were positive and 1708 (7.2%) were born to mothers vaccinated against influenza during pregnancy. VE against laboratory-confirmed infant influenza infection was 64% (95% confidence interval [CI], 50%-74%). VE was similar by trimester of vaccination (first/second, 66% [95% CI, 40%-80%]; third, 63% [95% CI, 46%-74%]), infant age at testing (0 to <2 months, 63% [95% CI, 46%-75%]; 2 to <6 months, 64% [95% CI, 36%-79%]), and gestational age at birth (≥37 weeks, 64% [95% CI, 50%-75%]; < 37 weeks, 61% [95% CI, 4%-86%]). VE against influenza hospitalization was 67% (95% CI, 50%-78%)., Conclusions: Influenza vaccination during pregnancy offers effective protection to infants <6 months, for whom vaccines are not currently available., Competing Interests: Potential conflicts of interest . During the conduct of this work, D. B. F. worked for the University of Ottawa and had academic appointments at the Children's Hospital of Eastern Ontario Research Institute and ICES; she is currently employed by Pfizer. K. W. is a cofounder and Chief Scientific Officer of CANImmunize, Inc; he served on the Independent Data Monitoring Committee for Medicago; and is a member of the Moderna Global Advisory Core Consultancy Group. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

BackgroundWaning immunity from seasonal influenza vaccination can cause suboptimal protection during peak influenza activity. However, vaccine effectiveness studies assessing waning immunity using vaccinated and unvaccinated individuals are subject to biases.AimWe examined the association between time since vaccination and laboratory-confirmed influenza to assess the change in influenza vaccine protection over time.MethodsUsing linked laboratory and health administrative databases in Ontario, Canada, we identified community-dwelling individuals aged ≥ 6 months who received an influenza vaccine before being tested for influenza by RT-PCR during the 2010/11 to 2018/19 influenza seasons. We estimated the adjusted odds ratio (aOR) for laboratory-confirmed influenza by time since vaccination (categorised into intervals) and for every 28 days.ResultsThere were 53,065 individuals who were vaccinated before testing for influenza, with 10,264 (19%) influenza-positive cases. The odds of influenza increased from 1.05 (95% CI: 0.91-1.22) at 42-69 days after vaccination and peaked at 1.27 (95% CI: 1.04-1.55) at 126-153 days when compared with the reference interval (14-41 days). This corresponded to 1.09-times increased odds of influenza every 28 days (aOR = 1.09; 95% CI: 1.04-1.15). Individuals aged 18-64 years showed the greatest decline in protection against influenza A(H1N1) (aOR per 28 days  = 1.26; 95% CI: 0.97-1.64), whereas for individuals aged ≥ 65 years, it was against influenza A(H3N2) (aOR per 28 days  = 1.20; 95% CI: 1.08-1.33). We did not observe evidence of waning vaccine protection for individuals aged < 18 years.ConclusionsInfluenza vaccine protection wanes during an influenza season. Understanding the optimal timing of vaccination could ensure robust protection during seasonal influenza activity.

Background: Older adults are recommended to receive influenza vaccination annually, and many use statins. Statins have immunomodulatory properties that might modify influenza vaccine effectiveness (VE) and alter influenza infection risk., Methods: Using the test-negative design and linked laboratory and health administrative databases in Ontario, Canada, we estimated VE against laboratory-confirmed influenza among community-dwelling statin users and nonusers aged ≥66 years during the 2010-2011 to 2018-2019 influenza seasons. We also estimated the odds ratio for influenza infection comparing statin users and nonusers by vaccination status., Results: Among persons tested for influenza across the 9 seasons, 54 243 had continuous statin exposure before testing and 48 469 were deemed unexposed. The VE against laboratory-confirmed influenza was similar between statin users and nonusers (17% [95% confidence interval, 13%-20%] and 17% [13%-21%] respectively; test for interaction, P = .87). In both vaccinated and unvaccinated persons, statin users had higher odds of laboratory-confirmed influenza than nonusers (odds ratios for vaccinated and unvaccinated persons 1.15 [95% confidence interval, 1.10-1.21] and 1.15 [1.10-1.20], respectively). These findings were consistent by mean daily dose and statin type. VE did not differ between users and nonusers of other cardiovascular drugs, except for β-blockers. We did not observe that vaccinated and unvaccinated users of these drugs had increased odds of influenza, except for unvaccinated β-blocker users., Conclusions: Influenza VE did not differ between statin users and nonusers. Statin use was associated with increased odds of laboratory-confirmed influenza in vaccinated and unvaccinated persons, but these associations might be affected by residual confounding., Competing Interests: Potential conflicts of interest. H. C., M. A. C., S. A. B., T. K., K. L. S., and J. C. K. report support from the Canadian Institutes of Health Research (CIHR; grant PJT 159516, paid to the institution). J. B. G. has received research grants from GSK and Hoffmann-LaRoche for antiviral resistance studies and from Pfizer to conduct microbiological surveillance of Streptococcus pneumoniae. J. B. G. also reports consulting fees from GIDEON Informatics, as a scientific editor, unrelated to the current work. A. J. M. reports research funds from GSK; grants or contracts from Sanofi, Merck, and Pfizer (paid to the institution); payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Merck, Biogen, and Moderna; and participation on a data safety monitoring board or advisory board for Pfizer, GlaxoSmithKline, Moderna, Medicago, Janssen, AstraZeneca, Novavax, and Sanofi. D. C. R. reports participation on a data safety monitoring board or advisory board for GlaxoSmithKline (advisory board meeting on monoclonal antibodies for coronavirus disease 2019 [COVID-19]). M. S. reports grants or contracts from CIHR, Air Canada (staff and reagent costs for the COVID in International Travelers Study), the Ontario Research Fund (equipment costs for COVID-19 automation), and the Juravinski Research Fund (staff and equipment for COVID-19 diagnostic testing). G. Z. reports support from CIHR (paid to grant administered by J. C. K.) and grants from Genome Atlantic and PHAC. Roche and Abbott contribute unrestricted educational funding to the Eastern Health Regional Health Authority for employees, which include G. Z., to attend virtual meetings and, in specific restricted circumstances, travel to educational, technical, and research meetings. G. Z. is also the previous president of the National Molecular Users Group. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Older adults are at increased risk of mortality from influenza infections. We estimated influenza vaccine effectiveness (VE) against mortality following laboratory-confirmed influenza., Methods: Using a test-negative design study and linked laboratory and health administrative databases in Ontario, Canada, we estimated VE against all-cause mortality following laboratory-confirmed influenza for community-dwelling adults aged >65 years during the 2010-2011 to 2015-2016 influenza seasons., Results: Among 54 116 older adults tested for influenza across the 6 seasons, 6837 died within 30 days of specimen collection. Thirteen percent (925 individuals) tested positive for influenza, and 50.6% were considered vaccinated for that season. Only 23.2% of influenza test-positive cases had influenza recorded as their underlying cause of death. Before and after multivariable adjustment, we estimated VE against all-cause mortality following laboratory-confirmed influenza to be 20% (95% confidence interval [CI], 8%-30%) and 20% (95% CI, 7%-30%), respectively. This estimate increased to 34% after correcting for influenza vaccination exposure misclassification. We observed significant VE against deaths following influenza confirmation during 2014-2015 (VE = 26% [95% CI, 5%-42%]). We also observed significant VE against deaths following confirmation of influenza A/H1N1 and A/H3N2, and against deaths with COPD as the underlying cause., Conclusions: These results support the importance of influenza vaccination in older adults, who account for most influenza-associated deaths annually., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

A number of countries have implemented vaccination in pregnancy as a strategy to reduce the burden of influenza and pertussis. The aim of this study was to assess the involvement of Canadian maternity care providers in administration of vaccines to their pregnant patients. A cross-sectional web-based survey was sent to family physicians, obstetricians-gynecologists, midwives, pharmacists, and nurses. A multivariable logistic regression model was used to determine variables independently associated with offering vaccination services in pregnancy in providers' practice. A total of 1,135 participants participated. Overall, 64% (n = 724) of the participants reported offering vaccines in their practice and 56% (n = 632) reported offering vaccines to pregnant patients. The main reasons reported for not offering vaccination services in pregnancy were the belief that vaccination was outside of the scope of practice; logistical issues around access to vaccines; or lack of staff to administer vaccines. In multivariable analysis, the main factors associated with vaccination of pregnant patients in practices where vaccination services were offered were: providers' confidence in counseling pregnant patients about vaccines, seeing fewer than 11 pregnant patients on average each week, and being a nurse or a family physician. Although the majority of participants expressed strong support for vaccination during pregnancy, half were not offering vaccination services in their practice. Many were not equipped to offer vaccines in their practice or felt that it was not their role to do so. To enhance vaccine acceptance and uptake in pregnancy, it will be important to address the logistical barriers identified in this study.

Background: Annual influenza immunization is recommended for people with chronic obstructive pulmonary disease (COPD) by all major COPD clinical practice guidelines. We sought to determine the seasonal influenza vaccine effectiveness (VE) against laboratory-confirmed influenza-associated hospitalizations among older adults with COPD., Methods: We conducted a test-negative study of influenza VE in community-dwelling older adults with COPD in Ontario, Canada using health administrative data and respiratory specimens collected from patients tested for influenza during the 2010-11 to 2015-16 influenza seasons. Influenza vaccination was ascertained from physician and pharmacist billing claims. Multivariable logistic regression was used to estimate the adjusted odds ratio of influenza vaccination in people with, compared to those without, laboratory-confirmed influenza., Results: Receipt of seasonal influenza vaccine was associated with an adjusted 22% (95% confidence interval [CI], 15%-27%) reduction in laboratory-confirmed influenza-associated hospitalization. Adjustment for potential misclassification of vaccination status increased this to 43% (95% CI, 35%-52%). Vaccine effectiveness was not found to vary by patient- or influenza-related variables., Conclusions: During the studied influenza seasons, influenza vaccination was at least modestly effective in reducing laboratory-confirmed influenza-associated hospitalizations in people with COPD. The imperfect effectiveness emphasizes the need for better influenza vaccines and other preventive strategies., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

IntroductionAnnual influenza vaccination is recommended for older adults, but evidence regarding the impact of repeated vaccination has been inconclusive.AimWe investigated vaccine effectiveness (VE) against laboratory-confirmed influenza and the impact of repeated vaccination over 10 previous seasons on current season VE among older adults.MethodsWe conducted an observational test-negative study in community-dwelling adults aged > 65 years in Ontario, Canada for the 2010/11 to 2015/16 seasons by linking laboratory and health administrative data. We estimated VE using multivariable logistic regression. We assessed the impact of repeated vaccination by stratifying by previous vaccination history.ResultsWe included 58,304 testing episodes for respiratory viruses, with 11,496 (20%) testing positive for influenza and 31,004 (53%) vaccinated. Adjusted VE against laboratory-confirmed influenza for the six seasons combined was 21% (95% confidence interval (CI): 18 to 24%). Patients who were vaccinated in the current season, but had received no vaccinations in the previous 10 seasons, had higher current season VE (34%; 95%CI: 9 to 52%) than patients who had received 1-3 (26%; 95%CI: 13 to 37%), 4-6 (24%; 95%CI: 15 to 33%), 7-8 (13%; 95%CI: 2 to 22%), or 9-10 (7%; 95%CI: -4 to 16%) vaccinations (trend test p = 0.001). All estimates were higher after correcting for misclassification of current season vaccination status. For patients who were not vaccinated in the current season, residual protection rose significantly with increasing numbers of vaccinations received previously.ConclusionsAlthough VE appeared to decrease with increasing numbers of previous vaccinations, current season vaccination likely provides some protection against influenza regardless of the number of vaccinations received over the previous 10 influenza seasons.

Background: Influenza causes significant annual morbidity and mortality, particularly in older adults, for whom influenza vaccine effectiveness (VE) is also lower. Immunizing one group (e.g., children) against influenza may indirectly protect another group (e.g., older adults) against influenza and its complications., Methods: We updated previous systematic reviews on indirect protection against influenza by searching MEDLINE and EMBASE for relevant human studies published until January 4, 2017. We abstracted and critically appraised English language publications that reported or provided information to calculate indirect VE against influenza, as a percentage, in non-institutional settings. We developed a term called 'estimated actual protection' to explore the relationship between indirect protection and the product of direct VE and relative vaccine coverage. We calculated estimated actual protection for a subset of studies that reported coverage and indirect VE for: laboratory-confirmed influenza; outpatient care for respiratory illness; influenza-associated emergency visits; or influenza-associated hospitalizations. We ran linear mixed models to compare estimated actual protection against indirect VE for the four outcomes, and graphed the data., Results: Of 2320 unique records identified, we abstracted and appraised 26 articles describing 24 studies. The majority of included studies reported at least one outcome suggesting that immunizing one group reduced influenza-related outcomes in another group. Critical appraisal of the abstracted studies identified recurring methodological weaknesses, such as lack of laboratory-confirmed influenza. Our exploratory analyses of 18 studies indicated a positive but not statistically significant relationship between estimated actual protection and indirect protection for each of the four outcomes., Conclusions: Our systematic review and exploratory analyses suggest influenza immunization provides some level of indirect protection. However, our critical appraisal highlights the need for a standardized and consistently applied approach to measuring indirect protection against influenza to fill existing knowledge gaps. Additionally, the concept of estimated actual protection requires validation., (Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.)

Purpose: Seasonal influenza vaccination is recommended for patients with cancer despite concerns of disease or treatment-associated immunosuppression. The objective of this study was to evaluate vaccine effectiveness (VE) against laboratory-confirmed influenza for patients with cancer., Patients and Methods: We conducted an observational test-negative design study of previously diagnosed patients with cancer 18 years of age and older who underwent influenza testing during the 2010-2011 to 2015-2016 influenza seasons in Ontario, Canada. We linked individual-level cancer registry, respiratory virus testing, and health administrative data to identify the study population and outcomes. Vaccination status was determined from physician and pharmacist billing claims. We used multivariable logistic regression to estimate VE, adjusting for age, sex, rurality, income quintile, cancer characteristics, chemotherapy exposure, comorbidities, previous health care use, influenza season, and calendar time., Results: We identified 26,463 patients with cancer who underwent influenza testing, with 4,320 test-positive cases (16%) and 11,783 (45%) vaccinated. Mean age was 70 years, 52% were male, mean time since diagnosis was 6 years, 69% had solid tumor malignancies, and 23% received active chemotherapy. VE against laboratory-confirmed influenza was 21% (95% CI, 15% to 26%), and VE against laboratory-confirmed influenza hospitalization was 20% (95% CI, 13% to 26%). For patients with solid tumor malignancies, VE was 25% (95% CI, 18% to 31%), compared with 8% (95% CI, -5% to 19%) for patients with hematologic malignancies ( P = .015). Active chemotherapy usage did not significantly affect VE, especially among patients with solid tumor cancer., Conclusion: Our results support recommendations for influenza vaccination for patients with cancer. VE was decreased for patients with hematologic malignancies, and there was no significant difference in VE among patients with solid tumor cancer receiving active chemotherapy. Strategies to optimize influenza prevention among patients with cancer are warranted.

Background: Linking data on laboratory specimens collected during clinical practice with health administrative data permits highly powered vaccine effectiveness (VE) studies to be conducted at relatively low cost, but bias from using convenience samples is a concern. We evaluated the validity of using such data for estimating VE., Methods: We created the Flu and Other Respiratory Viruses Research (FOREVER) Cohort by linking individual-level data on respiratory virus laboratory tests, hospitalizations, emergency department visits, and physician services. For community-dwelling adults aged > 65 years, we assessed the presence and magnitude of information and selection biases, generated VE estimates under various conditions, and compared our VE estimates with those from other studies., Results: We included 65,648 unique testing episodes obtained from 54,434 individuals during the 2010-11 to 2015-16 influenza seasons. To examine information bias, we found the proportion testing positive for influenza for patients with unknown interval from illness onset to specimen collection was more similar to patients for whom illness onset date was ≤ 7 days before specimen collection than to patients for whom illness onset was > 7 days before specimen collection. To assess the presence of selection bias, we found the likelihood of influenza testing was comparable between vaccinated and unvaccinated individuals, although the adjusted odds ratios were significantly greater than 1 for some healthcare settings and during some influenza seasons. Over 6 seasons, VE estimates ranged between 36% (95%CI, 27-44%) in 2010-11 and 5% (95%CI, -2, 11%) in 2014-15. VE estimates were similar under a range of conditions, but were consistently higher when accounting for misclassification of vaccination status through a quantitative sensitivity analysis. VE estimates from the FOREVER Cohort were comparable to those from other studies., Conclusions: Routinely collected laboratory and health administrative data contained in the FOREVER Cohort can be used to estimate influenza VE in community-dwelling older adults., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Importance: Recent observational studies report conflicting results regarding the effectiveness of live attenuated influenza vaccine (LAIV), particularly against influenza A(H1N1)pdm09., Objective: To compare the effectiveness of LAIV and inactivated influenza vaccine (IIV) against laboratory-confirmed influenza., Design, Setting, and Participants: A test-negative study to estimate influenza vaccine effectiveness (VE) using population-based, linked, individual-level laboratory, health administrative, and immunization data. Data were obtained from 10 169 children and adolescents aged 2 to 17 years (children) who were tested for influenza in inpatient or outpatient settings during periods when influenza was circulating based on a threshold level of 5% weekly test positivity for the province during the 4 influenza seasons spanning from November 11, 2012, to April 30, 2016, in Alberta, Canada. Logistic regression was used to estimate VE by vaccine type, influenza season, and influenza type and subtype. The relative effectiveness of each vaccine type was assessed by comparing the odds of laboratory-confirmed influenza infection for LAIV recipients with that for IIV recipients., Exposures: The primary exposure was receipt of LAIV or IIV before testing for influenza., Main Outcomes and Measures: The primary outcome was influenza case status as determined by reverse-transcriptase polymerase chain reaction testing., Results: A total of 10 779 respiratory specimens (from 10 169 children) collected and tested for influenza during the 4 influenza seasons were included, with 53.4% from males; the mean (SD) age was 7.0 (4.6) years. Across the 4 influenza seasons, 3161 children tested positive for influenza. Combining the 4 influenza seasons, the adjusted VE against influenza A(H1N1)pdm09 was 69% (95% CI, 56%-78%) for LAIV compared with 79% (95% CI, 70%-86%) for IIV. Vaccine effectiveness against influenza A(H3N2) was 36% (95% CI, 14%-53%) for LAIV and 43% (95% CI, 22%-59%) for IIV. Against influenza B, VE was 74% (95% CI, 62%-82%) for LAIV and 56% (95% CI, 41%-66%) for IIV. There were no significant differences in the odds of influenza infection for LAIV recipients compared with IIV recipients except for influenza B during the 2015-2016 season, when LAIV recipients had lower odds of infection than IIV recipients (odds ratio, 0.36; 95% CI, 0.17-0.76)., Conclusions and Relevance: There was no evidence to support the lack of effectiveness of LAIV against influenza A(H1N1)pdm09. These results support administration of either vaccine type in this age group.

Uncertainty remains regarding the magnitude of effectiveness of influenza vaccines for preventing serious outcomes, especially among young children. We estimated vaccine effectiveness (VE) against laboratory-confirmed influenza hospitalizations among children aged 6-59 months. We used the test-negative design in hospitalized children in Ontario, Canada during the 2010-11 to 2013-14 influenza seasons. We used logistic regression models adjusted for age, season, and time within season to calculate VE estimates by vaccination status (full vs. partial), age group, and influenza season. We also assessed VE incorporating prior history of influenza vaccination. We included specimens from 9,982 patient hospitalization episodes over four seasons, with 12.8% testing positive for influenza. We observed variation in VE by vaccination status, age group, and influenza season. For the four seasons combined, VE was 60% (95%CI, 44%-72%) for full vaccination and 39% (95%CI, 17%-56%) for partial vaccination. VE for full vaccination was 67% (95%CI, 48%-79%) for children aged 24-59 months, 48% (95%CI, 12%-69%) for children aged 6-23 months, 77% (95%CI, 47%-90%) for 2010-11, 59% (95%CI, 13%-81%) for 2011-12, 33% (95%CI, -18% to 62%) for 2012-13, and 72% (95%CI, 42%-86%) for 2013-14. VE in children aged 24-59 months appeared similar between those vaccinated in both the current and previous seasons and those vaccinated in the current season only, with the exception of 2012-13, when VE was lower for those vaccinated in the current season only. Influenza vaccination is effective in preventing pediatric laboratory-confirmed influenza hospitalizations during most seasons.

The Canadian National Vaccine Safety network (CANVAS) gathers and analyzes safety data on individuals receiving the influenza vaccine during the early stages of annual influenza vaccination campaigns with data collected via participant surveys through the Internet. We sought to examine whether it was feasible to use a mobile application (app) to facilitate AEFI reporting for the CANVAS network. To explore this, we developed a novel smartphone app, recruited participants from a hospital influenza immunization clinic and by word of mouth and instructed them to download and utilize the app. The app reminded participants to complete the CANVAS AEFI surveillance surveys ("AEFI surveys") on day 8 and 30, a survey capturing app usability metrics at day 30 ("usability survey") and provided a mechanism to report AEFI events spontaneously throughout the whole study period. All survey results and spontaneous reports were recorded on a privacy compliant, cloud server. A software plug-in, Lookback, was used to record the on-screen experience of the app sessions. Of the 76 participants who consented to participate, 48(63%) successfully downloaded the app and created a profile. In total, 38 unique participants completed all of the required surveillance surveys; transmitting 1104 data points (survey question responses and spontaneous reports) from 83 completed surveys, including 21 usability surveys and one spontaneous report. In total, we received information on new or worsening health conditions after receiving the influenza vaccine from 11(28%) participants. Of the usability survey responses, 86% agreed or strongly agreed that they would prefer to use a mobile app based reporting system instead of a web-based system. The single spontaneous report received was from a participant who had also reported using the Day 8 survey. Of Lookback observable sessions, an accurate transmission proportion of 100% (n=290) was reported for data points. We demonstrated that a mobile app can be used for AEFI reporting, although download and survey completion proportions suggest potential barriers to adoption. Future studies should examine implementation of mobile reporting in a broader audience and impact on the quality of reporting of adverse events following immunization.

It is unclear whether seasonal influenza vaccination results in a net increase or decrease in the risk for Guillain-Barré syndrome (GBS). To assess the effect of seasonal influenza vaccination on the absolute risk of acquiring GBS, we used simulation models and published estimates of age- and sex-specific risks for GBS, influenza incidence, and vaccine effectiveness. For a hypothetical 45-year-old woman and 75-year-old man, excess GBS risk for influenza vaccination versus no vaccination was -0.36/1 million vaccinations (95% credible interval -1.22% to 0.28) and -0.42/1 million vaccinations (95% credible interval, -3.68 to 2.44), respectively. These numbers represent a small absolute reduction in GBS risk with vaccination. Under typical conditions (e.g. influenza incidence rates >5% and vaccine effectiveness >60%), vaccination reduced GBS risk. These findings should strengthen confidence in the safety of influenza vaccine and allow health professionals to better put GBS risk in context when discussing influenza vaccination with patients.

Background:  Although annual influenza immunization is recommended for adults aged ≥65 years due to the substantial burden of illness, the evidence base for this recommendation is weak. Prior observational studies that examined influenza vaccine effectiveness against nonspecific serious outcomes suffered from selection bias and the lack of laboratory confirmation for influenza infection. The objective of this study was to determine the effectiveness of the 2010-2011 seasonal influenza vaccine against laboratory-confirmed influenza hospitalizations among community-dwelling elderly adults, a serious and highly specific outcome., Methods:  We conducted a test-negative study of community-dwelling adults aged >65 years in Ontario, Canada. Respiratory specimens collected between 1 December 2010 and 30 April 2011 from patients admitted to acute care hospitals were tested for influenza using nucleic acid amplification techniques. Influenza vaccination was ascertained from physician billing claims through linkage to health administrative datasets., Results:  Receipt of the 2010-2011 seasonal influenza vaccine was associated with a 42% (95% confidence interval, 29%-53%) reduction in laboratory-confirmed influenza hospitalizations. Vaccine effectiveness estimates were consistent across age groups, by sex, and regardless of outcome severity, timing of testing, and when considering individuals vaccinated <7 or <14 days prior to admission as unvaccinated., Conclusions:  Results of this study will better inform decision making regarding influenza vaccination of elderly adults. Similar analyses are needed annually due to antigenic drift and frequent changes in influenza vaccine composition. The linkage of routinely collected laboratory testing and health administrative data represents an efficient method for estimating influenza vaccine effectiveness that complements prospective studies.

Background: The possible risk of Guillain-Barré syndrome from influenza vaccines remains a potential obstacle to achieving high vaccination coverage. However, influenza infection might also be associated with Guillain-Barré syndrome. We aimed to assess the risk of Guillain-Barré syndrome after seasonal influenza vaccination and after influenza-coded health-care encounters., Methods: We used the self-controlled risk interval design and linked universal health-care system databases from Ontario, Canada, with data obtained between 1993 and 2011. We used physician billing claims for influenza vaccination and influenza-coded health-care encounters to ascertain exposures. Using fixed-effects conditional Poisson regression, we estimated the relative incidence of hospitalisation for primary-coded Guillain-Barré syndrome during the risk interval compared with the control interval., Findings: We identified 2831 incident admissions for Guillain-Barré syndrome; 330 received an influenza vaccine and 109 had an influenza-coded health-care encounter within 42 weeks before hospitalisation. The risk of Guillain-Barré syndrome within 6 weeks of vaccination was 52% higher than in the control interval of 9-42 weeks (relative incidence 1·52; 95% CI 1·17-1·99), with the greatest risk during weeks 2-4 after vaccination. The risk of Guillain-Barré syndrome within 6 weeks of an influenza-coded health-care encounter was greater than for vaccination (15·81; 10·28-24·32). The attributable risks were 1·03 Guillain-Barré syndrome admissions per million vaccinations, compared with 17·2 Guillain-Barré syndrome admissions per million influenza-coded health-care encounters., Interpretation: The relative and attributable risks of Guillain-Barré syndrome after seasonal influenza vaccination are lower than those after influenza illness. Patients considering immunisation should be fully informed of the risks of Guillain-Barré syndrome from both influenza vaccines and influenza illness., Funding: Canadian Institutes of Health Research., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Immunizing health care workers against influenza is important for preventing and reducing disease transmission in health care environments. We describe the ability of Canadian health care organizations to measure influenza immunization coverage among health care workers and identify factors associated with comprehensive influenza immunization measurement., Methods: A Web-based survey was distributed to influenza immunization campaign planners responsible for delivering the 2010-2011 influenza vaccine to health care workers working in acute care hospitals or long-term continuing care organizations. The primary outcome was the ability to comprehensively measure influenza immunization coverage., Results: Of the 1,127 health care organizations approached, 721 (64%) responded. Ninety-one percent had incomplete immunization coverage measurement; 7% could not measure coverage among any personnel. After multivariable adjustment, organizations with a written influenza immunization implementation plan (odds ratio, 2.0; 95% confidence interval, 1.1-3.5) or a policy or procedure describing how to calculate or report immunization rates (odds ratio, 2.1; 95% confidence interval, 1.2-3.9) were more likely to have comprehensive measurement of influenza immunization coverage than organizations without these practices., Conclusion: Most organizations demonstrated incomplete measurement of influenza immunization among health care workers. Given the use of influenza immunization coverage as a measure of quality of care, further work is needed to develop a standardized approach to improve its measurement., (Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.)

Background: The success of influenza vaccination campaigns may be suboptimal if subgroups of the population face unique barriers or have misconceptions about vaccination. We conducted a national study to estimate influenza vaccine coverage across 12 ethnic groups in Canada to assess the presence of ethnic disparities., Methods: We pooled responses to the Canadian Community Health Survey between 2003 and 2009 (n = 437 488). We estimated ethnicity-specific self-reported influenza vaccine coverage for the overall population, for people aged 65 years and older, and for people aged 12-64 years with and without chronic conditions. We used weighted logistic regression models to examine the association between ethnicity and influenza vaccination, adjusting for sociodemographic factors and health status., Results: Influenza vaccination coverage ranged from 25% to 41% across ethnic groups. After adjusting for sociodemographic factors and health status for people aged 12 years and older, all ethnic groups were more likely to have received a vaccination against influenza than people who self-identified as white, with the exception of those who self-identified as black (odds ratio [OR] 1.01, 95% confidence interval [CI] 0.88-1.15). Compared with white Canadians, Canadians of Filipino (OR 2.00, 95% CI 1.67-2.40) and Southeast Asian (OR 1.66, 95% CI 1.36-2.03) descent had the greatest likelihood of having received vaccination against influenza., Interpretation: Influenza vaccine coverage in Canada varies by ethnicity. Black and white Canadians have the lowest uptake of influenza vaccine of the ethnic groups represented in our study. Further research is needed to understand the facilitators, barriers and misconceptions relating to vaccination that exist across ethnic groups, and to identify promotional strategies that may improve uptake among black and white Canadians.

Background: During the 2010-2011 winter, a large number of outbreaks due to influenza A/H3N2 at long-term care facilities, including higher-than-expected attack rates among vaccinated staff, were reported in some regions of Canada. Interim analysis from the community-based sentinel surveillance system showed circulating H3N2 variants and suboptimal vaccine effectiveness (VE), assessed here for the entire season's data set., Methods: Nasal/nasopharyngeal swabs and epidemiologic details were collected from patients presenting to sentinel sites within 7 days of onset of influenza-like illness. Cases tested positive for influenza by real-time reverse-transcription polymerase chain reaction; controls tested negative. Odds ratios for medically attended, laboratory-confirmed influenza in vaccinated vs nonvaccinated participants were used to derive adjusted VE. Viruses were characterized by hemagglutination inhibition (HI), and the hemagglutinin genes of a subset were sequenced to explore vaccine relatedness., Results: Final 2010-2011 VE analysis included 1718 participants (half aged 20-49 years), 93 with A(H1N1)pdm09, 408 with A/H3N2, and 199 with influenza B. Among adults aged 20-49 years, adjusted VE was 65% (95% confidence interval [CI], 8%-87%) for A(H1N1)pdm09 and 66% (95% CI, 10%-87%) for influenza B. Vaccine effectiveness was substantially lower for A/H3N2, at 39% (95% CI, 0%-63%). Phylogenetic analysis identified 2 circulating H3N2 variant clades, A/HongKong/2121/2010 (87%) and A/Victoria/208/2009 (11%), bearing multiple amino acid substitutions at antigenic sites (12 and 8, respectively) compared with the H3N2 vaccine component used in Canada (A/Victoria/210/2009[NYMC X-187]). However, HI characterized all H3N2 isolates as well matched to the vaccine., Conclusions: Public health observations of increased facility H3N2 outbreaks were consistent with the sentinel network's detection of genetic variants and suboptimal VE but not with conventional HI characterization. We highlight the utility of a multicomponent sentinel surveillance platform that incorporates genotypic, phenotypic, and epidemiologic indicators into the assessment of influenza virus, new variant circulation, vaccine relatedness, and VE.

Background: Five observational studies from Canada found an association between seasonal influenza vaccine receipt and increased risk of pandemic influenza H1N1 2009 infection. This association remains unexplained. Although uncontrolled confounding has been suggested as a possible explanation, the nature of such confounding has not been identified. Observational studies of influenza vaccination can be affected by confounding due to healthy users and the influence of social determinants on health. The purpose of this study was to investigate the influence that these two potential confounders may have in combination with temporary immunity, using stratified tables. The hypothesis is that respiratory virus infections may activate a temporary immunity that provides short-term non-specific protection against influenza and that the relationship with being a healthy user or having a social determinant may result in confounding., Methods: We simulated the effect of confounding on vaccine effectiveness assuming that this could result from both social determinants and healthy user effects as they both influence the risk of seasonal influenza and non-influenza respiratory virus infections as well as the likelihood of being vaccinated. We then examined what impact this may have had on measurement of seasonal influenza vaccine effectiveness against pandemic influenza., Results: In this simulation, failure to adjust for healthy users and social determinants would result in an erroneously increased risk of pandemic influenza infection associated with seasonal influenza vaccination. The effect sizes were not however large., Conclusions: We found that unmeasured healthy user effects and social determinants could result in an apparent association between seasonal influenza vaccine and pandemic influenza infection by virtue of being related to temporary immunity. Adjustment for social determinants of health and the healthy user effects are required in order to improve the quality of observational studies of influenza vaccine effectiveness.

Objectives: To estimate influenza vaccine effectiveness (VE) for the 2007-2008 season and assess the sentinel surveillance system in Canada for monitoring virus evolution and impact on VE., Methods: Nasal/nasopharyngeal swabs and epidemiologic details were collected from patients presenting to a sentinel physician within 7 days of influenza-like illness onset. Cases tested positive for influenza A/B virus by real-time polymerase chain reaction; controls tested negative. Hemagglutination inhibition (HI) and gene sequencing explored virus relatedness to vaccine. VE was calculated as 1 minus the odds ratio for influenza in vaccinated versus nonvaccinated participants, with adjustment for confounders., Results: Of 1425 participants, 21% were vaccinated. Influenza virus was detected in 689 (48%), of which isolates from 663 were typed/subtyped: 189 (29%) were A/H1, 210 (32%) were A/H3, and 264 (40%) were B. Of A/H1N1 isolates, 6% showed minor HI antigenic mismatch to vaccine, with greater variation based on genetic identity. All A/H3N2 isolates showed moderate antigenic mismatch, and 98% of influenza B virus isolates showed major lineage-level mismatch to vaccine. Adjusted VE for A/H1N1, A/H3N2, and B components was 69% (95% confidence interval [CI], 44%-83%), 57% (95% CI, 32%-73%), and 55% (95% CI, 32%-70%), respectively, with an overall VE of 60% (95% CI, 45%-71%)., Conclusions: Detailed antigenic and genotypic analysis of influenza viruses was consistent with epidemiologic estimates of VE showing cross-protection. A routine sentinel surveillance system that combines detailed virus and VE monitoring annually, as modeled in Canada, may guide improved vaccine selection and protection.

Background: 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., Methods: 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., Results: 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., Conclusion: 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., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: In the fall of 2009, Canada undertook a mass vaccination campaign against pH1N1. This report provides an overview of self-reported pH1N1 vaccination coverage of the Ontario population, building on an existing random digit-dialling telephone survey, in which 9,010 Ontario adults participated. Based on the results, 34.5% of Ontario residents were vaccinated: 33.3% of adults aged 18 or older and 38.6% of children and adolescents younger than age 18. Respondents reporting high-risk chronic conditions were significantly more likely to report being vaccinated than were people who did not report such conditions. Determining vaccination uptake for the Ontario population is important in the evaluation of the province's pH1N1 prevention program.

Objectives: A critical component of the 2009 H1N1 vaccination campaign was the collection of immunization data at the point of care. To meet reporting requirements and to ensure timely availability of coverage information, many jurisdictions across Canada employed new or modified approaches to vaccine data collection. The objective of this study was to observe and characterize the range of influenza immunization data collection approaches used across Canada., Methods: As part of a multi-stage observational study, the research team visited immunization clinics at which tasks related to data collection and management were observed. Tasks included registration, medical history collection and review, vaccine record-keeping, proof of vaccination preparation, and data entry. Field notes were analyzed in order to understand the data collection mechanisms that comprised each information system as a whole., Results: Data collection mechanisms were grouped into two categories: electronic systems (9/38), in which all data were captured on computer; and hybrid systems (29/38), comprised of computerized and paper-based data collection tasks. Observed systems included stand-alone databases, immunization registries, and electronic health records. Organizations incorporated magnetic card reader technology, telephone registration, and pre-populated fields into data collection approaches. Electronic systems captured a greater number of data elements., Conclusion: Canadian jurisdictions employed a range of data collection approaches during the H1N1 vaccination campaign. System characteristics can have important implications for on-site efficiency and organization as well as program planning and evaluation. The systems observed have been described in detail to allow vaccine providers and planners to learn from what has been done elsewhere.

During the pandemic (H1N1) 2009 vaccination campaign, vaccine providers collected immunization data using hybrid (paper-based and electronic methods) and electronic data systems. We measured staff time in seconds spent on data collection tasks to compare system efficiencies. The sample consisted of 38 organizations across nine Canadian provinces/territories. The total mean data collection times per client were 104 s (electronic system), 143 s (hybrid system with electronic registration) and 172 s (hybrid system with paper registration). Electronic registration and record keeping were faster than paper-based methods; these findings should be used to improve data collection for future influenza seasons., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Objective: To assess the effectiveness of the pandemic influenza A/H1N1 vaccine used in Canada during autumn 2009., Design: Test negative incident case-control study based on sentinel physician surveillance system., Setting: Community based clinics contributing to sentinel networks in British Columbia, Alberta, Ontario, and Quebec, Canada., Participants: 552 patients who presented to a sentinel site within seven days of onset of influenza-like illness during the primary analysis period between 8 November and 5 December 2009; participants were mostly (>80%) children and adults under 50 years old., Interventions: Monovalent AS03 adjuvanted pandemic influenza A/H1N1 vaccine as the predominant formulation (>95%) distributed in Canada., Main Outcome Measures: Vaccine effectiveness calculated as 1-(odds ratio for influenza in vaccinated (received pandemic H1N1 vaccine at least two weeks before onset of influenza-like illness) versus unvaccinated participants), with adjustment for age, comorbidity, province, timeliness of specimen collection, and week of illness onset. Sensitivity analyses explored the influence of varying analysis periods between 1 November and 31 December, receipt of trivalent seasonal influenza vaccine, and restriction to participants without comorbidity., Results: During the primary analysis period, pandemic H1N1 was detected by reverse transcription polymerase chain reaction in 209/552 (38%) participants; rates were highest in children and young adults (40%) and lowest in people aged 65 or over (9%). Among the 209 cases, 35 (17%) reported comorbidity compared with 80/343 (23%) controls. Two (1%) cases had received pandemic H1N1 vaccine at least two weeks before the onset of illness, compared with 58/343 (17%) controls, all single dose. Adjusted vaccine effectiveness overall was 93% (95% confidence interval 69% to 98%). High estimates of vaccine protection-generally at least 90%-were maintained across most sensitivity analyses., Conclusions: Although limited by a small number of vaccine failures, this study suggests that the monovalent AS03 adjuvanted vaccine used in Canada during autumn 2009 was highly effective in preventing medically attended, laboratory confirmed pandemic H1N1 illness, with reference in particular to a single dose in children and young adults.

Background: In late spring 2009, concern was raised in Canada that prior vaccination with the 2008-09 trivalent inactivated influenza vaccine (TIV) was associated with increased risk of pandemic influenza A (H1N1) (pH1N1) illness. Several epidemiologic investigations were conducted through the summer to assess this putative association., Studies Included: (1) test-negative case-control design based on Canada's sentinel vaccine effectiveness monitoring system in British Columbia, Alberta, Ontario, and Quebec; (2) conventional case-control design using population controls in Quebec; (3) test-negative case-control design in Ontario; and (4) prospective household transmission (cohort) study in Quebec. Logistic regression was used to estimate odds ratios for TIV effect on community- or hospital-based laboratory-confirmed seasonal or pH1N1 influenza cases compared to controls with restriction, stratification, and adjustment for covariates including combinations of age, sex, comorbidity, timeliness of medical visit, prior physician visits, and/or health care worker (HCW) status. For the prospective study risk ratios were computed. Based on the sentinel study of 672 cases and 857 controls, 2008-09 TIV was associated with statistically significant protection against seasonal influenza (odds ratio 0.44, 95% CI 0.33-0.59). In contrast, estimates from the sentinel and three other observational studies, involving a total of 1,226 laboratory-confirmed pH1N1 cases and 1,505 controls, indicated that prior receipt of 2008-09 TIV was associated with increased risk of medically attended pH1N1 illness during the spring-summer 2009, with estimated risk or odds ratios ranging from 1.4 to 2.5. Risk of pH1N1 hospitalization was not further increased among vaccinated people when comparing hospitalized to community cases., Conclusions: Prior receipt of 2008-09 TIV was associated with increased risk of medically attended pH1N1 illness during the spring-summer 2009 in Canada. The occurrence of bias (selection, information) or confounding cannot be ruled out. Further experimental and epidemiological assessment is warranted. Possible biological mechanisms and immunoepidemiologic implications are considered.

Background: In August 2011, Ontario, Canada introduced a rotavirus immunization program using Rotarix™ vaccine. No assessments of rotavirus vaccine coverage have been previously conducted in Ontario. Methods: We assessed vaccine coverage (series initiation and completion) and factors associated with uptake using the Electronic Medical Record Administrative data Linked Database (EMRALD), a collection of family physician electronic medical records (EMR) linked to health administrative data. Series initiation (1 dose) and series completion (2 doses) before and after the program’s introduction were calculated. To identify factors associated with series initiation and completion, adjusted odds ratios (aOR) and 95% confidence intervals (95%CI) were calculated using logistic regression. Results: A total of 12,525 children were included. Series completion increased each year of the program (73%, 79% and 84%, respectively). Factors associated with series initiation included high continuity of care (aOR = 2.15; 95%CI, 1.61–2.87), maternal influenza vaccination (aOR = 1.55; 95%CI,1.24–1.93), maternal immmigration to Canada in the last five years (aOR = 1.47; 95% CI, 1.05–2.04), and having no siblings (aOR = 1.62; 95%CI,1.30–2.03). Relative to the first program year, infants were more likely to initiate the series in the second year (aOR = 1.71; 95% CI 1.39–2.10) and third year (aOR = 2.02; 95% CI 1.56–2.61) of the program. Infants receiving care from physicians with large practices were less likely to initiate the series (aOR 0.91; 95%CI, 0.88–0.94, per 100 patients rostered) and less likely to complete the series (aOR 0.94; 95%CI, 0.91–0.97, per 100 patients rostered). Additional associations were identified for series completion. Conclusions: Family physician delivery achieved moderately high coverage in the program’s first three years. This assessment demonstrates the usefulness of EMR data for evaluating vaccine coverage. Important insights into factors associated with initiation or completion (i.e. high continuity of care, smaller roster sizes, rural practice location) suggest areas for research and potential program supports. [ABSTRACT FROM AUTHOR]

The article offers information related to influenza vaccination coverage across ethnic groups in Canada. It states that coverage of influenza vaccination largely depends on ethnicity in Canada. It also mentions that black and white Canadians have the lowest uptake of influenza vaccine of the overall ethnic groups in the country.

Altamirano-Diaz L, West L, Humar A, Ely L, Urschel S, Gubbay J, Crowcroft N, Kumar D. Early post-transplant vaccination with pandemic influenza A/H1N1 vaccine in pediatric heart transplant recipients. Pediatr Transplantation 2011: 15:172-175. © 2010 John Wiley & Sons A/S. Pandemic influenza A/H1N1 virus has the potential to cause severe disease in pediatric transplant patients. A pandemic vaccine against H1N1 is effective in immunocompetent children. We investigated the immunogenicity of this vaccine when given in the first six months after heart transplantation. Four patients younger than two yr received two doses of vaccine and one patient older than seven yr received one dose. Titers were obtained using the HAI at baseline and after final immunization. Five patients were enrolled, ages 0.5-7 yr. Median age at the time of transplant was five months (range 3 wk-7 yr). All patients received induction with anti-thymoglobulin and maintenance immunosuppression with tacrolimus, MMF, and prednisone. Patients were immunized with the adjuvanted H1N1 vaccine after heart transplant at median time of nine wk (range 5-23 wk) post-transplant. Three of five developed protective titers against H1N1. A proportion of pediatric patients may respond to influenza vaccine even when immunized in the early post-transplant period. [ABSTRACT FROM AUTHOR]

• Consensus-based methods were used to improve vaccine product label information. • Stakeholders developed structure, language, and content for product labels. • Emergent methods exposed divergent understandings of the purpose of product labels. • Stakeholders were concerned about how product labels are regulated. • Developers of product label information should consider involving end users. Product labelling information describing the use of vaccines in pregnancy continues to contain cautionary language even after clinical and epidemiological evidence of safety becomes available. This language raises safety concerns among healthcare providers who may hesitate to recommend vaccines during pregnancy. To develop clear evidence-based language about vaccine safety and effectiveness in pregnancy for inclusion in vaccine product labels. We conducted a three-stage consensus-methods project with stakeholders, including: healthcare providers, vaccine regulators, industry representatives, and experts in public health, communication, law, ethics, and social sciences. Using qualitative and quantitative methods, we held a nominal group technique (NGT) meeting, followed by a Delphi survey, and then a consensus workshop with a subset of Delphi participants. We developed a methodological tool to analyse data for consensus. Stakeholders (N = 14) at the NGT meeting drafted product label statements for evaluation in the Delphi survey. Survey participants (N = 41) provided feedback on statements for five hypothetical vaccines. Workshop participants (N = 27) initiated discussions that demonstrated a lack of awareness that the regulatory purpose of product labels is to provide a scientific summary of product-specific pre-clinical and clinical trial data. Each stage of this project built on earlier stages until we achieved strong consensus on the language, structure, and types of data that stakeholders wanted to include in inactivated influenza vaccine (IIV) and tetanus-diphtheria-acellular pertussis (Tdap) vaccine product labels in Canada. The revised statements for IIV and Tdap aligned with workshop participants' goals that the product label be evidence-based, with a consistent structure and language that is easily understood by healthcare providers. Emergent methods uncovered stakeholder concerns about the regulatory purpose, content, and evidence used in product labels. Involving healthcare providers in the development and regular updating of product information could prevent interpretations of that information that contribute to vaccine hesitancy. [ABSTRACT FROM AUTHOR]