A multi-country investigation of influenza vaccine coverage in pregnant individuals, 2010-2016.

BACKGROUND: Many countries recommend influenza vaccination during pregnancy. Despite this recommendation, influenza vaccine among pregnant individuals remains under-utilized and uptake varies by country. Factors associated with influenza vaccine uptake during pregnancy may also vary across countries. METHODS: As members of the Pregnancy Influenza Vaccine Effectiveness Network (PREVENT), five sites from four countries (Australia, Canada, Israel, and the United States) retrospectively identified cohorts of individuals aged 18-50 years who were pregnant during pre-defined influenza seasons. Influenza vaccine coverage estimates were calculated for the 2010-11 through 2015-16 northern hemisphere and the 2012 through 2015 southern hemisphere influenza seasons, by site. Sites used electronic health records, administrative data, and immunization registries to collect information on pregnancy, health history, demographics, and vaccination status. Each season, vaccination coverage was calculated as the percentage of individuals who received influenza vaccine among the individuals in the cohort that season. Characteristics were compared between those vaccinated and unvaccinated, by site. RESULTS: More than two million pregnancies were identified over the study period. Influenza vaccination coverage ranged from 5% to 58% across sites and seasons. Coverage increased consistently over the study period at three of the five sites (Western Australia, Alberta, and Israel), and was highest in all seasons at the United States study site (39-58%). Associations with vaccination varied by country and across seasons; where available, parity >0, presence of a high-risk medical condition, and urban residence were consistently associated with increased likelihood of vaccination. CONCLUSIONS: Though increasing, uptake of influenza vaccine among pregnant individuals remains lower than recommended. Coverage varied substantially by country, suggesting an ongoing need for targeted strategies to improve influenza vaccine uptake in this population.

Pre-Vaccine Positivity of SARS-CoV-2 Antibodies in Alberta, Canada during the First Two Waves of the COVID-19 Pandemic.

We systematically evaluated SARS-CoV-2 IgG positivity in a provincial cohort to understand the local epidemiology of COVID-19 and support evidence-based public health decisions. Residual blood samples were collected for serology testing over 5-day periods monthly from June 2020 to January 2021 from six clinical laboratories across the province of Alberta, Canada. A total of 93,993 individual patient samples were tested with a SARS-CoV-2 nucleocapsid antibody assay with positives confirmed using a spike antibody assay. Population-adjusted SARS-CoV-2 IgG seropositivity was 0.92% (95% confidence interval [CI]: 0.91 to 0.93%) shortly after the first COVID-19 wave in June 2020, increasing to 4.63% (95% CI: 4.61 to 4.65%) amid the second wave in January 2021. There was no significant difference in seropositivity between males and females (1.39% versus 1.27%; P = 0.11). Ages with highest seropositivity were 0 to 9 years (2.71%, 95% CI: 1.64 to 3.78%) followed by 20 to 29 years (1.58%, 95% CI: 1.12 to 2.04%), with the lowest rates seen in those aged 70 to 79 (0.79%, 95% CI: 0.65 to 0.93%) and >80 (0.78%, 95% CI: 0.60 to 0.97%). Compared to the seronegative group, seropositive patients inhabited geographic areas with lower household income ($87,500 versus $97,500; P < 0.001), larger household sizes, and higher proportions of people with education levels of secondary school or lower, as well as immigrants and visible minority groups (all P < 0.05). A total of 53.7% of seropositive individuals were potentially undetected cases with no prior positive COVID-19 nucleic acid test (NAAT). Antibodies were detectable in some patients up to 9 months post positive NAAT result. This seroprevalence study will continue to inform public health decisions by identifying at-risk demographics and geographical areas. IMPORTANCE Using SARS-CoV-2 serology testing, we assessed the proportion of people in Alberta, Canada (population 4.4 million) positive for COVID-19 antibodies, indicating previous infection, during the first two waves of the COVID-19 pandemic (prior to vaccination programs). Linking these results with sociodemographic population data provides valuable information as to which groups of the population are more likely to have been infected with the SARS-CoV-2 virus to help facilitate public health decision-making and interventions. We also compared seropositivity data with previous COVID-19 molecular testing results. Absence of antibody and molecular testing were highly correlated (95% negative concordance). Positive antibody correlation with a previous positive molecular test was low, suggesting the possibility of mild/asymptomatic infection or other reasons leading individuals from seeking medical attention. Our data highlight that the true estimate of population prevalence of COVID-19 is likely best informed by combining data from both serology and molecular testing.

A multisite study of pertussis vaccine effectiveness by time since last vaccine dose from three Canadian provinces: A Canadian Immunization Research Network study.

BACKGROUND: Pertussis remains poorly controlled relative to other diseases targeted by childhood vaccination programs. We combined estimates from four population-based studies of pertussis vaccine effectiveness (VE) in three Canadian provinces using a meta-analytic approach to improve precision and explore regional variation in VE and durability of protection. METHODS: Studies were conducted in Alberta, Manitoba, and Ontario over periods ranging from 1996 to 2015. Adjusted log odds ratios (OR; VE = 100*[1-OR]) of the effect of vaccination on pertussis risk were estimated by time since last vaccination in each study and pooled using DerSimonian and Laird random-effects models. We used the I2 statistic to estimate between-study heterogeneity and assessed methodological and clinical heterogeneity through subgroup analyses of study design and age. RESULTS: Data on 3,270 pertussis cases and 23,863 controls were available. Pertussis VE declined from 86% (95% CI 79%-90%, I2 = 81.5%) at < 1 year since last vaccination to 51% (11%-74%, I2 = 80.9%) by ≥ 8 years. Effect estimates were the most heterogeneous in the least and most elapsed time periods since last vaccine dose. This was attributable mostly to variation between provinces in the distribution of age groups and number of vaccine doses received within time periods, as well as study design and small numbers in the most elapsed time period. INTERPRETATION: Consistent trends of decreasing pertussis VE with increasing time since last vaccination across three Canadian provinces indicate the need for immunization schedules and vaccine development to optimize protection for all individuals, especially for adolescents and young adults at greatest risk of infection.

A Call for Caution in Use of Pertussis Vaccine Effectiveness Studies to Estimate Waning Immunity: A Canadian Immunization Research Network Study.

BACKGROUND: Vaccine effectiveness (VE) studies provide essential evidence on waning vaccine-derived immunity, a major threat to pertussis control. We evaluated how study design affects estimates by comparing 2 case-control studies conducted in Ontario, Canada. METHODS: We compared results from a test-negative design (TND) with a frequency-matched design (FMD) case-control study using pertussis cases from 2005-2015. In the first study, we identified test-negative controls from the public health laboratory that diagnosed cases and, in the second, randomly selected controls from patients attending the same physicians that reported cases, frequency matched on age and year. We compared characteristics of cases and controls using standardized differences. RESULTS: In both designs, VE estimates for the early years postimmunization were consistent with clinical trials (TND, 84%; FMD, 89% at 1-3 years postvaccination) but diverged as time since last vaccination increased (TND, 41%; FMD, 74% by 8 years postvaccination). Overall, we observed lower VE and faster waning in the TND than the FMD. In the TND but not FMD, controls differed from cases in important confounders, being younger, having more comorbidities, and higher healthcare use. Differences between the controls of each design were greater than differences between cases. TND controls were more likely to be unvaccinated or incompletely vaccinated than FMD controls (P < .001). CONCLUSIONS: The FMD adjusted better for healthcare-seeking behavior than the TND. Duration of protection from pertussis vaccines is unclear because estimates vary by study design. Caution should be exercised by experts, researchers, and decision makers when evaluating evidence on optimal timing of boosters.

Baseline assessment of and linkage to care for newly diagnosed patients with chronic hepatitis B.

Background: Patients with chronic hepatitis B (CHB) are at risk of complications and require lifelong monitoring. We evaluated the care of newly diagnosed CHB patients. Methods: Adult CHB cases newly diagnosed in Alberta between January 1, 2008, and December 31, 2012, were identified, with follow-up through June 1, 2014. Rates of completion of baseline investigations, receipt of antiviral therapy when indicated, and adherence to hepatocellular carcinoma (HCC) screening recommendations in a cohort of high-risk patients were compared between those who did or did not see a CHB specialist. Results: Of 3,333 patients with CHB, 87.1% (n = 2,904) received non-specialty care. Specialty assessment was associated with higher completion of alanine aminotransferase, hepatitis B e antigen (HBeAg), anti-HBe, and hepatitis B DNA (p <0.0001) and all four parameters (86.5%) compared with non-specialist care (42.7%; p <0.0001). In a subgroup of high-risk patients for HCC, specialty care was associated with higher completed baseline abdominal ultrasounds (n = 44; 89.8%,) compared with non-specialist care (62.5%; n = 320; p = 0.0001) and greater adherence to annual surveillance (30.6% versus 15.2%; p = 0.0057). Patients in the HBeAg-positive chronic hepatitis phase meeting criteria for antiviral therapy were more likely to receive treatment under specialty care (n = 6; 75.0%) than non-specialty care (n = 27; 33.3%; p = 0.0478). Conclusions: Our study highlights inadequate care among newly diagnosed CHB patients in Alberta. Specialty assessment was associated with improved quality of care. Interventions are needed to improve linkage to specialty care.

Using population-wide administrative and laboratory data to estimate type- and subtype-specific influenza vaccine effectiveness: a surveillance protocol.

INTRODUCTION: The appropriateness of using routinely collected laboratory data combined with administrative data for estimating influenza vaccine effectiveness (VE) is still being explored. This paper outlines a protocol to estimate influenza VE using linked laboratory and administrative data which could act as a companion to estimates derived from other methods. METHODS AND ANALYSIS: We will use the test-negative design to estimate VE for each influenza type/subtype and season. Province-wide individual-level records of positive and negative influenza tests at the Provincial Laboratory for Public Health in Alberta will be linked, by unique personal health numbers, to administrative databases and vaccination records held at the Ministry of Health in Alberta to determine covariates and influenza vaccination status, respectively. Covariates of interests include age, sex, immunocompromising chronic conditions and healthcare setting. Cases will be defined based on an individual's first positive influenza test during the season, and potential controls will be defined based on an individual's first negative influenza test during the season. One control for each case will be randomly selected based on the week the specimen was collected. We will estimate VE using multivariable logistic regression. ETHICS AND DISSEMINATION: Ethics approval was obtained from the University of Alberta's Health Research Ethics Board-Health Panel under study ID Pro00075997. Results will be disseminated by public health officials in Alberta.

Comparing methods to estimate incremental inpatient costs and length of stay due to methicillin-resistant Staphylococcus aureus in Alberta, Canada.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is an opportunistic bacterial organism resistant to first line antibiotics. Acquisition of MRSA is often classified as either healthcare-associated or community-acquired. It has been shown that both healthcare-associated and community-acquired infections contribute to the spread of MRSA within healthcare facilities. The objective of this study was to estimate the incremental inpatient cost and length of stay for individuals colonized or infected with MRSA. Common analytical methods were compared to ensure the quality of the estimate generated. This study was performed at Alberta Ministry of Health (Edmonton, Alberta), with access to clinical MRSA data collected at two Edmonton hospitals, and ministerial administrative data holdings. METHODS: A retrospective cohort study of patients with MRSA was identified using a provincial infection prevention and control database. A coarsened exact matching algorithm, and two regression models (semilogarithmic ordinary least squares model and log linked generalized linear model) were evaluated. A MRSA-free cohort from the same facilities and care units was identified for the matched method; all records were used for the regression models. Records span from January 1, 2011 to December 31, 2015, for individuals 18 or older at discharge. RESULTS: Of the models evaluated, the generalized linear model was found to perform the best. Based on this model, the incremental inpatient costs associated with hospital-acquired cases were the most costly at $31,686 (14,169 - 60,158) and $47,016 (23,125 - 86,332) for colonization and infection, respectively. Community-acquired MRSA cases also represent a significant burden, with incremental inpatient costs of $7397 (2924 - 13,180) and $14,847 (8445 - 23,207) for colonization and infection, respectively. All costs are adjusted to 2016 Canadian dollars. Incremental length of stay followed a similar pattern, where hospital-acquired infections had the longest incremental stays of 35.2 (16.3-69.5) days and community-acquired colonization had the shortest incremental stays of 3.0 (0.6-6.3) days. CONCLUSIONS: MRSA, and in particular, hospital-acquired MRSA, places a significant but preventable cost burden on the Alberta healthcare system. Estimates of cost and length of stay varied by the method of analysis and source of infection, highlighting the importance of selecting the most appropriate method.

The association between influenza vaccination and socioeconomic status in high income countries varies by the measure used: a systematic review.

BACKGROUND: The purpose of this paper is to systematically review the literature on the relationship between socioeconomic status (SES) and influenza immunization and to examine how certain measures of SES may influence interpretations of this relationship. METHODS: We conducted a systematic review of existing peer-reviewed literature to evaluate the above relationship in the general population. Electronic databases (MEDLINE and EMBASE) were searched from January 2012 to May 2017 to identify English-language studies relevant to this review. Studies were included where influenza vaccination was explicitly reported as the dependent variable and SES as the independent variable. We limited our review to measures of SES that focus on education, income, social class, occupation, and deprivation. Studies that measured SES using other variables (e.g., race, ethnicity, geographic location, rural or urban status, or insurance status) were excluded. Studies were also excluded if they did not report on the human population or did not analyze original data. The population of interest included all age groups, levels of health status, and sociodemographic backgrounds. The review was also limited to World Bank high-income countries. Two authors independently screened full-text articles after obtaining a Kappa score of K = 0.867. The methodological quality of manuscripts was assessed using the appraisal tools developed by the Joanna Briggs Institute. Results were qualitatively reported and synthesized. RESULTS: Of the 42 articles included in this review, 52.4% (n = 22) found that higher levels of SES resulted in higher levels of influenza vaccination; 4.5% (n = 2) reported a negative association; and 14.3% (n = 6) found no association. Just over a quarter (26.2%, n = 12) of articles reported mixed results. CONCLUSIONS: There was consistently a relationship between SES and influenza immunization, which varied according to how SES was measured. It is recommended that authors be explicit in defining the SES concept they are trying to capture and that they utilize multiple measures of SES (e.g., education, income, class).

Acellular pertussis vaccine effectiveness and waning immunity in Alberta, Canada: 2010-2015, a Canadian Immunization Research Network (CIRN) study.

BACKGROUND: Pertussis is still frequently reported in Canada. In Alberta, pertussis incidence ranged from 1.8 to 20.5 cases per 100,000 persons for 2004-2015. Most cases occurred in those aged <15 years. In Alberta, acellular formulations replaced whole-cell in 1997. We investigated pertussis vaccine effectiveness (VE) using a test-negative design (TND) study. METHODS: We included all persons who had a real-time PCR laboratory test for Bordetella pertussis between January 1, 2010 and August 31, 2015, in the province of Alberta, Canada. Vaccination history was obtained from Alberta's immunization repository. Vaccination status was classified as complete, incomplete, or unvaccinated, based on the province's vaccination schedule. Persons who had received ≥one dose of whole cell vaccine were excluded from analysis. Multivariable logistic regression models were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) for pertussis infection by time since last vaccination. We adjusted for vaccination status, age, sex, neighbourhood income, urban/rural status, and the presence of a co-morbid condition. VE was calculated as [(1 - aOR) * 100]. RESULTS: Of the 12,149 tests available, 936 (7.7%) were positive for Bordetella pertussis. Among the full cohort, VE was 90% (95% CI 87-92%) at 1 year, 81% (95% CI 77-85%) at 1-3 years, 76% (95% CI 68-82%) at 4-7 years, and 37% (95% CI 11-56%) at 8 or more years since a last dose of acellular pertussis vaccine. CONCLUSIONS: Pertussis VE was highest in the first year after vaccination, then declined noticeably as years since a last vaccination increased. Our results suggest that a large number of adolescents and adults are susceptible to infection with Bordetella pertussis. Regular boosters throughout childhood, adolescence, and during pregnancy may be needed.

Pertussis vaccine effectiveness in a frequency matched population-based case-control Canadian Immunization Research Network study in Ontario, Canada 2009-2015.

BACKGROUND: Resurgences of pertussis have occurred in several high-income countries, often linked to waning of immunity from acellular pertussis vaccines. The degree of waning observed has varied by study design and setting. In Ontario, pertussis has not shown a substantial resurgence in the past decade. The routine immunization schedule comprises three priming doses in infancy, toddler and pre-school doses, and an adolescent dose at 14-16 years of age. METHODS: We estimated pertussis vaccine effectiveness (VE) through a case-control study of 1335 cases statutorily reported to public health in Ontario and occurring between January 1, 2009 and March 31, 2015, compared with 5340 randomly selected population controls, frequency-matched by age, primary-care provider and year of diagnosis. Pertussis cases met provincial confirmed or probable case definitions. We used multivariable logistic regression to estimate crude and adjusted odds ratios (aOR). RESULTS: VE against pertussis was sustained between 92% (95% confidence interval (95%CI) 88-95%) in 2-3 year olds and 90% (95%CI: 80-95%) in 8-9 year olds, but fell rapidly to 49% (95%CI: 2-73%) in children 12-13 years of age. VE following the teenage booster given at 14-16 years in Ontario reached 76% (95%CI: 52-88%) in 14-16 year olds and 78% (95%CI: -31 to 96%) in those 16-22 years old. For children who were up-to-date with the immunization schedule, VE declined from 87% (95%CI: 84-90%) during the first year to 74% (95%CI: 63-82%) after 8 or more years following their last dose of immunization. CONCLUSIONS: VE is high during the first decade of life but then falls rapidly. Protection is not fully restored by the teenage booster. Our findings are consistent with the localized outbreaks we observe in high school children and underline the importance of additional policies to protect infants.

Estimating Vaccine Effectiveness Against Hospitalized Influenza During Pregnancy: Multicountry Protocol for a Retrospective Cohort Study.

BACKGROUND: Although pregnant women are believed to have elevated risks of severe influenza infection and are targeted for influenza vaccination, no study to date has examined influenza vaccine effectiveness (IVE) against laboratory-confirmed influenza-associated hospitalizations during pregnancy, primarily because this outcome poses many methodological challenges. OBJECTIVE: The Pregnancy Influenza Vaccine Effectiveness Network (PREVENT) was formed in 2016 as an international collaboration with the Centers for Disease Control and Prevention; Abt Associates; and study sites in Australia, Canada, Israel, and the United States. The primary goal of this collaboration is to estimate IVE in preventing acute respiratory or febrile illness (ARFI) hospitalizations associated with laboratory-confirmed influenza virus infection during pregnancy. Secondary aims include (1) describing the incidence, clinical course, and severity of influenza-associated ARFI hospitalization during pregnancy; (2) comparing the characteristics of ARFI-hospitalized pregnant women who were tested for influenza with those who were not tested; (3) describing influenza vaccination coverage in pregnant women; and (4) comparing birth outcomes among women with laboratory-confirmed influenza-associated hospitalization versus other noninfluenza ARFI hospitalizations. METHODS: For an initial assessment of IVE, sites identified a retrospective cohort of pregnant women aged from 18 to 50 years whose pregnancies overlapped with local influenza seasons from 2010 to 2016. Pregnancies were defined as those that ended in a live birth or stillbirth of at least 20 weeks gestation. The analytic sample for the primary IVE analysis was restricted to pregnant women who were hospitalized for ARFI during site-specific influenza seasons and clinically tested for influenza virus infection using real-time reverse transcription polymerase chain reaction. RESULTS: We identified approximately 2 million women whose pregnancies overlapped with influenza seasons; 550,344 had at least one hospitalization during this time. After restricting to women who were hospitalized for ARFI and tested for influenza, the IVE analytic sample included 1005 women. CONCLUSIONS: In addition to addressing the primary question about the effectiveness of influenza vaccination, PREVENT data will address other important knowledge gaps including understanding the incidence, clinical course, and severity of influenza-related hospitalizations during pregnancy. The data infrastructure and international partnerships created for these analyses may be useful and informative for future influenza studies. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/11333.

Correction to: Comparing methods to estimate incremental inpatient costs and length of stay due to methicillin-resistant Staphylococcus aureus in Alberta, Canada.

In the original publication of this article [1], the authors want to add the following sentence in the Acknowledgement section.

Vaccine coverage of children in care of the child welfare system.

OBJECTIVE: To assess vaccine coverage for a cohort of children who have been in the care of the child welfare system compared to children in the general population. METHODS: This retrospective cohort study used population-based administrative health data for a 2008 birth cohort of children from Alberta, Canada. We assessed coverage at ages 2 (n = 44,206) and 7 (n = 42,241) for three vaccines with different administration schedules for children in care (at any period before the age of assessment) and those who had never been in care, comparing them using risk differences and relative risks (RRs). We similarly assessed coverage for children not in care who shared characteristics of children in care. RESULTS: At age two, vaccination coverage for children in care ranged from 54.3% to 81.4%, depending on vaccine. In comparison, coverage for those not in care ranged from 74.2% to 87.4%. At age seven, coverage for children in care ranged from 53.1% to 65.3%, compared to 76.6% to 83.4% for those not in care. For all vaccines at both ages, the risk for being under-vaccinated was higher for children in care (e.g., diphtheria, pertussis, tetanus, polio, Haemophilus influenzae type b at age 7: RR 2.01, 95% confidence interval [CI] (1.74-2.32). Even for children not in care who had characteristics similar to children in care, we found children in care had lower coverage. CONCLUSION: Children in care have consistently lower vaccine coverage than children not in care. Policies and practices should promote optimal access to vaccination for these children.

Influenza Vaccine Effectiveness in Preventing Influenza-associated Hospitalizations During Pregnancy: A Multi-country Retrospective Test Negative Design Study, 2010-2016.

BACKGROUND: To date, no study has examined influenza vaccine effectiveness (IVE) against laboratory-confirmed influenza-associated hospitalizations during pregnancy. METHODS: The Pregnancy Influenza Vaccine Effectiveness Network (PREVENT) consisted of public health or healthcare systems with integrated laboratory, medical, and vaccination records in Australia, Canada (Alberta and Ontario), Israel, and the United States (California, Oregon, and Washington). Sites identified pregnant women aged 18 through 50 years whose pregnancies overlapped with local influenza seasons from 2010 through 2016. Administrative data were used to identify hospitalizations with acute respiratory or febrile illness (ARFI) and clinician-ordered real-time reverse transcription polymerase chain reaction (rRT-PCR) testing for influenza viruses. Overall IVE was estimated using the test-negative design and adjusting for site, season, season timing, and high-risk medical conditions. RESULTS: Among 19450 hospitalizations with an ARFI discharge diagnosis (across 25 site-specific study seasons), only 1030 (6%) of the pregnant women were tested for influenza viruses by rRT-PCR. Approximately half of these women had pneumonia or influenza discharge diagnoses (54%). Influenza A or B virus infections were detected in 598/1030 (58%) of the ARFI hospitalizations with influenza testing. Across sites and seasons, 13% of rRT-PCR-confirmed influenza-positive pregnant women were vaccinated compared with 22% of influenza-negative pregnant women; the adjusted overall IVE was 40% (95% confidence interval = 12%-59%) against influenza-associated hospitalization during pregnancy. CONCLUSION: Between 2010 and 2016, influenza vaccines offered moderate protection against laboratory-confirmed influenza-associated hospitalizations during pregnancy, which may further inform the benefits of maternal influenza vaccination programs.

Are we speaking the same language? an argument for the consistent use of terminology and definitions for childhood vaccination indicators.

Vaccination indicators are used to measure the health status of individuals or populations and to evaluate the effectiveness of vaccination programs or policies. Ensuring that vaccination indicators are clearly and consistently defined is important for effective communication of outcomes, accurate program evaluation, and comparison between different populations, times, and contexts. The purpose of this commentary is to describe commonly used vaccination indicators and to highlight inconsistencies in how childhood vaccine researchers use and define these terms. The indicators we describe are vaccine coverage, uptake, and rate; vaccination status, initiation, and completion; and up-to-date, timely, partial, and incomplete vaccination. We conclude that many vaccination indicators are not explicitly defined within published research studies and/or are used quite differently across studies. We also note that the choice of indicator in a given study is often driven by program or vaccine specific factors, may be constrained by data availability, and should be chosen to best reflect the outcome of interest. We conclude that the use of consistent language and definitions would promote more effective communication of research findings. We also propose some standardized definitions for common indicators, with the goal of provoking discussion and debate on the issue.

Effectiveness of Live Attenuated vs Inactivated Influenza Vaccines in Children During the 2012-2013 Through 2015-2016 Influenza Seasons in Alberta, Canada: A Canadian Immunization Research Network (CIRN) Study.

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.

Under-reporting of pertussis in Ontario: A Canadian Immunization Research Network (CIRN) study using capture-recapture.

INTRODUCTION: Under-reporting of pertussis cases is a longstanding challenge. We estimated the true number of pertussis cases in Ontario using multiple data sources, and evaluated the completeness of each source. METHODS: We linked data from multiple sources for the period 2009 to 2015: public health reportable disease surveillance data, public health laboratory data, and health administrative data (hospitalizations, emergency department visits, and physician office visits). To estimate the total number of pertussis cases in Ontario, we used a three-source capture-recapture analysis stratified by age (infants, or aged one year and older) and adjusting for dependency between sources. We used the Bayesian Information Criterion to compare models. RESULTS: Using probable and confirmed reported cases, laboratory data, and combined hospitalizations/emergency department visits, the estimated total number of cases during the six-year period amongst infants was 924, compared with 545 unique observed cases from all sources. Using the same sources, the estimated total for those aged 1 year and older was 12,883, compared with 3,304 observed cases from all sources. Only 37% of infants and 11% for those aged 1 year and over admitted to hospital or seen in an emergency department for pertussis were reported to public health. Public health reporting sensitivity varied from 2% to 68% depending on age group and the combination of data sources included. Sensitivity of combined hospitalizations and emergency department visits varied from 37% to 49% and of laboratory data from 1% to 50%. CONCLUSIONS: All data sources contribute cases and are complementary, suggesting that the incidence of pertussis is substantially higher than suggested by routine reports. The sensitivity of different data sources varies. Better case identification is required to improve pertussis control in Ontario.

Is varicella vaccination associated with pediatric arterial ischemic stroke? A population-based cohort study.

BACKGROUND AND PURPOSE: Varicella disease is a risk factor for pediatric Arterial Ischemic Stroke (AIS). Isolated case reports have emerged suggesting that varicella vaccination may also pose a risk for AIS. METHODS: This retrospective population-based cohort study assessed the risk of AIS in children who received a varicella-containing vaccine, as compared to those who did not. The study cohort consisted of children born between January 1, 2006 and December 31, 2013, in the Canadian province of Alberta, where all routine childhood vaccinations are publicly-funded, and recorded in a central immunization repository. These data were linked with hospital discharge abstract data to identify children diagnosed with AIS. A Cox proportional hazard model assessed the risk of AIS in the 12 months following vaccination for children receiving a varicella vaccine between 11 and 23 months of age, as compared to non-vaccinated children. RESULTS: Of the 368,992 children in the cohort, 325,729 were vaccinated with a varicella-containing vaccine between 11 and 23 months of age. The rate of AIS was 7.8 (95% CI 4.8-10.9) per 100,000 person years at risk in the 12 months following varicella vaccination, as compared to 6.8 (95% CI 1.3-12.2) for children who did not receive a varicella vaccine. The adjusted Hazard Ratio for the risk of AIS, controlling for other AIS risk factors, in vaccinated children as compared to non-vaccinated children was 1.6 (95% CI 0.7-3.7) in the 12 months following vaccination and 1.7 (95% CI 0.5-4.9) in the 30 days following vaccination. CONCLUSIONS: Our study found no evidence of an increased risk of AIS following varicella vaccination. This population-based cohort study provides reassurance to parents and clinicians regarding the safety of varicella vaccination.

The effectiveness of shingles vaccine among Albertans aged 50 years or older: A retrospective cohort study.

PURPOSE: We assessed the effectiveness of shingles vaccine in preventing incident shingles among Alberta residents aged 50 years or older over the period 2009 - 2015, using administrative health data. METHODS: The cohort comprised of Albertans from the Alberta Health Care Insurance Plan Registry (AHCIP) as of June 30, 2009 and aged 50 years or older. Those who received shingles vaccine were identified from the provincial pharmaceutical information network. The occurrence of incident shingles was identified through both inpatient and outpatients/community care data. Incident shingles was defined as the earliest dated record of ICD 9-CM 053 or ICD-10-CA B02. Starting on November 1, 2009, individuals with no history of shingles or shingles vaccination were followed until Nov 1, 2015 (6 years), or until shingles incidence, death, or AHCIP cancellation (including leaving Alberta). Vaccine effectiveness (VE) was estimated as the inverse of the relative risk of developing incident shingles in each year following vaccination compared to time at risk without vaccination, while adjusting for age, sex, income quintile, and immune compromising conditions (identified from physician claims, inpatient, and cancer registry data). RESULTS: There were 1,094,236 individuals in the cohort, with 85,439 (7.80%) vaccinated individuals. The shingles incidence rate was 9.03 [95% CI: 8.95, 9.11] cases per 1,000 person years (49,243 cases). Adjusted VE in the first year following immunization was 50.02% [95% CI: 44.71%, 54.83%] against incident shingles, decreasing to no effect by the fifth year (VE = 14.00% [95% CI: -20.99%, 38.88%]). CONCLUSIONS: Our findings are consistent with observations from other population based studies and provide population level data for policy-makers to review when making decisions related to public funding of shingles vaccine.