Julie Foisy

Humoral and Cell-Mediated Immunity to Pandemic H1N1 Influenza in a Canadian Cohort One Year Post-Pandemic: Implications for Vaccination

We evaluated a cohort of Canadian donors for T cell and antibody responses against influenza A/California/7/2009 (pH1N1) at 8-10 months after the 2nd pandemic wave by flow cytometry and microneutralization assays. Memory CD8 T cell responses to pH1N1 were detectable in 58% (61/105) of donors. These responses were largely due to cross-reactive CD8 T cell epitopes as, for those donors tested, similar recall responses were obtained to A/California 2009 and A/PR8 1934 H1N1 Hviruses. Longitudinal analysis of a single infected individual showed only a small and transient increase in neutralizing antibody levels, but a robust CD8 T cell response that rose rapidly post symptom onset, peaking at 3 weeks, followed by a gradual decline to the baseline levels seen in a seroprevalence cohort post-pandemic. The magnitude of the influenza-specific CD8 T cell memory response at one year post-pandemic was similar in cases and controls as well as in vaccinated and unvaccinated donors, suggesting that any T cell boosting from infection was transient. Pandemic H1-specific antibodies were only detectable in approximately half of vaccinated donors. However, those who were vaccinated within a few months following infection had the highest persisting antibody titers, suggesting that vaccination shortly after influenza infection can boost or sustain antibody levels. For the most part the circulating influenza-specific T cell and serum antibody levels in the population at one year post-pandemic were not different between cases and controls, suggesting that natural infection does not lead to higher long term T cell and antibody responses in donors with pre-existing immunity to influenza. However, based on the responses of one longitudinal donor, it is possible for a small population of pre-existing cross-reactive memory CD8 T cells to expand rapidly following infection and this response may aid in viral clearance and contribute to a lessening of disease severity.

Seroprevalence of Pandemic Influenza H1N1 in Ontario from January 2009–May 2010

Background We designed a seroprevalence study using multiple testing assays and population sources to estimate the community seroprevalence of pH1N1/09 and risk factors for infection before the outbreak was recognized and throughout the pandemic to the end of 2009/10 influenza season. Methods Residual serum specimens from five time points (between 01/2009 and 05/2010) and samples from two time points from a prospectively recruited cohort were included. The distribution of risk factors was explored in multivariate adjusted analyses using logistic regression among the cohort. Antibody levels were measured by hemagglutination inhibition (HAI) and microneutralization (MN) assays. Results Residual sera from 3375 patients and 1024 prospectively recruited cohort participants were analyzed. Pre-pandemic seroprevalence ranged from 2%–12% across age groups. Overall seropositivity ranged from 10%–19% post-first wave and 32%–41% by the end of the 2009/10 influenza season. Seroprevalence and risk factors differed between MN and HAI assays, particularly in older age groups and between waves. Following the H1N1 vaccination program, higher GMT were noted among vaccinated individuals. Overall, 20–30% of the population was estimated to be infected. Conclusions Combining population sources of sera across five time points with prospectively collected epidemiological information yielded a complete description of the evolution of pH1N1 infection.

The Social Determinants of Health and Pandemic H1N1 2009 Influenza Severity

OBJECTIVES We explored the effects of social determinants of health on pandemic H1N1 2009 influenza severity and the role of clinical risk factors in mediating such associations. METHODS We used multivariate logistic regression with generalized estimating equations to examine the associations between individual- and ecological-level social determinants of health and hospitalization for pandemic H1N1 2009 illness in a case-control study in Ontario, Canada. RESULTS During the first pandemic phase (April 23-July 20, 2009), hospitalization was associated with having a high school education or less and living in a neighborhood with high material or total deprivation. We also observed the association with education in the second phase (August 1-November 6, 2009). Clinical risk factors for severe pandemic H1N1 2009 illness mediated approximately 39% of the observed association. CONCLUSIONS The main clinical risk factors for severe pandemic H1N1 2009 illness explain only a portion of the associations observed between social determinants of health and hospitalization, suggesting that the means by which the social determinants of health affect pandemic H1N1 2009 outcomes extend beyond clinically recognized risk factors.

Why collect individual-level vaccination data?

CMAJ • FEBRUARY 23, 2010 • 182(3)

Time and motion study to compare electronic and hybrid data collection systems during the pandemic (H1N1) 2009 influenza vaccination campaign.

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.

Perceptions of immunization information systems for collecting pandemic H1N1 immunization data within Canada's public health community: A qualitative study

BackgroundImmunization information systems (IISs) are electronic registries used to monitor individual vaccination status and assess vaccine coverage. IISs are currently not widely used across Canada, where health jurisdictions employ a range of approaches to capture influenza immunization information. Conducted in advance of the 2009 H1N1 vaccination campaign, the objectives of this study were to understand the perceived value of individual-level data and IISs for influenza control, identify ideal system functions, and explore barriers to implementation.MethodsIn July and August 2009, semi-structured interviews were conducted with key informants engaged in vaccine delivery and/or pandemic planning at regional, provincial/territorial and federal levels across Canada. Key informants were recruited using a combination of convenience and snowball sampling methodologies. Qualitative analysis was used to extract themes from interview content.ResultsPatient management, assessment of vaccine coverage, and evaluation of safety and effectiveness were identified as public health priorities that would be achieved in a more timely manner, and with greater accuracy, through the use of an IIS. Features described as ideal included system flexibility, rapid data entry, and universality. Financial and human resource constraints as well as coordination between immunization providers were expressed as barriers to implementation.ConclusionsIISs were perceived as valuable by key informants for strengthening management capacity and improving evaluation of both seasonal and pandemic influenza vaccination campaigns. However, certain implementation restrictions may need to be overcome for these benefits to be achieved.

Pan-Canadian assessment of pandemic immunization data collection: study methodology

BackgroundThe collection of individual-level pandemic (H1N1) 2009 influenza immunization data was considered important to facilitate optimal vaccine delivery and accurate assessment of vaccine coverage. These data are also critical for research aimed at evaluating the new vaccines safety and effectiveness. Systems used to collect immunization data include manual approaches in which data are collected and retained on paper, electronic systems in which data are captured on computer at the point of vaccination and hybrid systems which are comprised of both computerized and manual data collection components. This studys objective was to compare the efficiencies and perceptions of data collection methods employed during Canadas pandemic (H1N1) 2009 influenza vaccination campaign.Methods/DesignA pan-Canadian observational study was conducted in a convenience sample of public health clinics and healthcare institutions during the H1N1 vaccination campaign in the fall of 2009. The study design consisted of three stages: Stage 1 involved passive observation of the sites layout, processes and client flow; Stage 2 entailed timing site staff on 20 clients through five core immunization tasks: i) client registration, ii) medical history collection, iii) medical history review, iv) vaccine administration record keeping and v) preparation of proof of vaccine administration for the client; in Stage 3, site staff completed a questionnaire regarding perceived usability of the sites data collection approach. Before the national study began, a pilot study was conducted in three seasonal influenza vaccination sites in Ontario, to both test that the proposed methodology was logistically feasible and to determine inter-rater reliability in the measurements of the research staff. Comparative analyses will be conducted across the range of data collection methods with respect to time required to collect immunization data, number and type of individual-level data elements collected, and clinic staff perceptions of the usability of the method employed at their site, using analysis of variance (ANOVA).DiscussionVarious data collection methods were employed at immunization sites across Canada during the pandemic (H1N1) 2009 influenza vaccination campaign. Our comparison of methods can facilitate planning an efficient, coordinated approach for collecting immunization data in future influenza seasons.

A cost comparison of electronic and hybrid data collection systems in Ontario during pandemic and seasonal influenza vaccination campaigns.

BackgroundDuring the pandemic (H1N1) 2009 influenza vaccination campaign, health regions in Canada collected client-level immunization data using fully electronic or hybrid systems, with the latter comprising both electronic and paper-based elements. The objective of our evaluation was to compare projected five-year costs associated with implementing these systems in Ontario public health units (PHUs) during pandemic and seasonal influenza vaccination campaigns.MethodsSix PHUs provided equipment and staffing costs during the pandemic (H1N1) 2009 influenza vaccination campaign and staffing algorithms for seasonal campaigns. We standardized resources to population sizes 100,000, 500,000 and 1,000,000, assuming equipment lifetime of five years and public health vaccine administration rates of 18% and 2.5% for H1N1 and seasonal campaigns, respectively. Two scenarios were considered: Year 1 pandemic and Year 1 seasonal campaigns, each followed by four regular influenza seasons. Costs were discounted at 5%.ResultsAssuming a Year 1 pandemic, the five-year costs per capita for the electronic system decrease as PHU population size increases, becoming increasingly less costly than hybrid systems (

Perceptions of frontline staff regarding data collection methodologies used during the 2009 A H1N1 influenza immunization campaign in Canada.

4.33 vs.

Approaches to Immunization Data Collection Employed Across Canada During the Pandemic (H1N1) 2009 Influenza Vaccination Campaign

4.34 [100,000],