Summary of the Timing of the Annual Influenza A Epidemic across Canada and the United States.

<p>Weeks are numbered according to the calendar year with week 1 corresponding to the 1^st week of January and week 52 is one week earlier. Weeks run from Sunday to Saturday, and run continuously so that each week covers a 7 day period. The influenza season starts at week 35 or the 1st week of September and runs for a full year. Week 53 was not included in the legend as it only occurred in 2 out of 6 seasons. Only seasons where over 80% of the influenza strains characterized were antigenically similar are included in the summaries, namely, seasons shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0021471#pone-0021471-g001" target="_blank">Figure 1:</a> 1997/98, 1998/99, 1999/2000, 2000/01, 2001/02, and 2003/04. a) The average week of peak activity; b) The earliest week of peak influenza activity by Canadian province and American influenza surveillance region; c) The latest week of peak influenza A activity by Canadian province and American influenza surveillance region.</p

Degree of Synchronization¹ between the Major City² in each Province and other Communities.³

1<p>Includes seasons where over 80% of the influenza strains were antigenically similar.</p>2<p>The major city for each province was identified as the CMA reporting the most cases.</p>3<p>Communities (geographic units) which confirmed at least 50 positive cases in one season.</p>4<p>Cases from the rural area of each province and communities with less than 50 positive cases per season were combined into one local epidemic curve. Cases from rural areas accounted for the majority of cases in the ‘rest of the province’ epidemic curve.</p>5<p>The number of local epidemics meeting the inclusion criteria over the study period of 6 seasons. To compare sub-provincial synchronization at least 2 geographic units from one province must meet the inclusion criteria for the same season; that is at least 1 CMA/CA and one other community from the same province or the ‘rest of province’ aggregate must meet the criteria in the same season. Over the 6 seasons, 114 pairs were available to assess the degree of synchronization.</p><p>The Chi-squared value for a test of association is 2.3 on 4 degrees of freedom for a p-value of 0.67. Note that cell counts are given in cumulative format in this table and the categories of 3 weeks and 4 or more weeks were combined in the test of association due to small numbers.</p

Timing of the Annual Influenza A Epidemic across Canada and the United States, by Season.

<p>The temporal midpoint of each influenza A season where over 80% of the influenza strains were antigenically similar by Canadian province and American influenza surveillance region is shown in the chloropleth maps. The region reaching its midpoint first was identified as the reference region. In three out of the six seasons the epidemic appeared first in Canada. Considerable variability in the timing and direction of spread is noted.</p

Reference Region: Region with the Earliest Epidemic.

<p>Reference Region: Region with the Earliest Epidemic.</p

Strain type and composition.

<p>Seasons where over 80% influenza A strains were antigenically similar are shown in <b>BOLD</b>.</p

Attribution of Specimens Tested for Influenza and Reported to the RVDSS, Canada.

<p>The modelled attribution of the weekly number of specimens tested for influenza to influenza (A and B), and adenovirus, parainfluenza virus, and RSV combined is shown along with the numbers confirmed positive. The total is the number of weekly tests for influenza (most were likely panel tests). The baseline accounts for routine tests in the hypothetical absence of influenza, RVS, adenovirus and parainfluenza activity, and corresponds to the model estimate of the number of tests that were truly negative for all tested viruses. The blue area (light plus dark) corresponds to tests attributed to influenza, with the light blue area corresponding to tests confirmed positive for influenza. The purple area (light plus dark) corresponds to tests attributed to RSV, adenovirus or parainfluenza. The light purple area is the total number confirmed positive for these viruses.</p

Model predicted number of tests negative for influenza.

<p>The weekly number of influenza tests not confirmed positive for influenza was modelled as a function of viral identifications for influenza, RSV, adenovirus and parainfluenza, seasonality, and trend using Poisson regression. Identified outliers, corresponding to periods with irregular testing were excluded from the model. The baseline accounts for routine tests in the hypothetical absence of influenza, RVS, adenovirus and parainfluenza activity.</p

RVDSS viral identifications.

<p>Weekly number of specimens tested for influenza is shown with the number of tests confirmed positive for influenza (A and B), adenovirus, parainfluenza virus, and RSV. Data is presented ignoring co-infection and sequential testing, so the white area under the curve, which corresponds to 75% of tests, represents the minimum number of specimens that were negative for all 4 viruses.</p

Model Estimates of Sensitivity for Influenza A Testing as Reported to the RVDSS, by Influenza Season.

<p>Note: Estimates of sensitivity by influenza season were obtained by estimating separate β_5,y parameters, one for each season. Noting that the null value for sensitivity is 100%, as 100% sensitivity implies that there should no association between the number of influenza negative and influenza positive tests, the season specific estimates appear to be reasonably consistent. Season specific differences in the estimated sensitivity may be due to irregular reporting and the tendency of data irregularities to bias the model parameters β_5,y towards the null, or sensitivity towards 1. A value of 100% for sensitivity implies that there is no association between the number of influenza negative and influenza positive tests. The 2000/01 and 2002/03 season estimates (both H1N1/B seasons) were uninformative. This lack of statistical significance and wide confidence intervals were attributed to the relatively small number of influenza A positive specimens in these two H1N1 seasons. A shift in influenza A confirmations towards younger ages was noted during the H1N1 seasons. Testing a larger proportion of children may result in an improvement in the overall test sensitivity.</p><p>ns: Not statistically significant. The null value for sensitivity is 100%. With 100% sensitivity no association between the number of influenza negative and influenza positive tests would be expected.</p><p>n/a: Not available. Estimate was out of range and not statistically significant.</p

Cost-effectiveness of alternate strategies for childhood immunization against meningococcal disease with monovalent and quadrivalent conjugate vaccines in Canada

<div><p>Background</p><p>Public health programs to prevent invasive meningococcal disease (IMD) with monovalent serogroup C meningococcal conjugate vaccine (MCV-C) and quadrivalent meningococcal conjugate vaccines (MCV-4) in infancy and adolescence vary across Canadian provinces. This study evaluated the cost-effectiveness of various vaccination strategies against IMD using current and anticipated future pricing and recent epidemiology.</p><p>Methods</p><p>A cohort model was developed to estimate the clinical burden and costs (CAN$2014) of IMD in the Canadian population over a 100-year time horizon for three strategies: (1) MCV-C in infants and adolescents (MCV-C/C); (2) MCV-C in infants and MCV-4 in adolescents (MCV-C/4); and (3) MCV-4 in infants (2 doses) and adolescents (MCV-4/4). The source for IMD incidence was Canadian surveillance data. The effectiveness of MCV-C was based on published literature. The effectiveness of MCV-4 against all vaccination regimens was assumed to be the same as for MCV-C regimens against serogroup C. Herd effects were estimated by calibration to estimates reported in prior analyses. Costs were from published sources. Vaccines prices were projected to decline over time reflecting historical procurement trends.</p><p>Results</p><p>Over the modeling horizon there are a projected 11,438 IMD cases and 1,195 IMD deaths with MCV-C/C; expected total costs are$597.5 million. MCV-C/4 is projected to reduce cases of IMD by 1,826 (16%) and IMD deaths by 161 (13%). Vaccination costs are increased by $32 million but direct and indirect IMD costs are projected to be reduced by$46 million. MCV-C/4 is therefore dominant vs. MCV-C/C in the base case. Cost-effectiveness of MCV-4/4 was $111,286 per QALY gained versus MCV-C/4 (2575/206 IMD cases/deaths prevented; incremental costs$68 million).</p><p>Conclusions</p><p>If historical trends in Canadian vaccines prices continue, use of MCV-4 instead of MCV-C in adolescents may be cost-effective. From an economic perspective, switching to MCV-4 as the adolescent booster should be considered.</p></div