Trends in Canadian infant pertussis hospitalizations in the pre- and post-acellular vaccine era, 1981-2016.

OBJECTIVE: The acellular pertussis vaccine was introduced into the routine childhood immunization schedule across Canada in 1997-98 and adolescent booster doses were added between 1999 and 2005. We sought to assess the impact of these changes on infant pertussis hospitalizations and admissions to intensive care units (ICU) in Canada. METHODS: Hospitalizations with a primary diagnosis of pertussis were extracted from the Canadian Discharge Abstract Database (DAD) for cases with hospital discharge dates between 1981 and 2016 using relevant ICD-9 and ICD-10 codes. Only cases with age less than one year at time of admission were included. Disease severity was assessed by admission to ICU. Cases were categorized into two periods: pre-program implementation period (1981-1995) and the post-program implementation period (2006-2016). Incidence rates, risk ratios, and rate differences were calculated for each period and comparisons for the two periods were done using chi-squared and t-tests. Quasi Poisson analysis was used to investigate trends. RESULTS: When comparing the pre- and post-implementation periods, the average annual hospitalization rates for infants less than 1 year declined from 165.1 (95% CI 161.3, 168.9) to 33.6 (95% CI 31.6, 35.6) pertussis-related admissions per 100,000 population, with a corresponding reduction in the risk ratio of 4.9 (95% CI 4.6, 5.2). The risk of admission into an ICU was 1.58 times higher in the pre- versus post-implementation period while the highest reduction in average annual hospitalizations was 263.3 admissions per 100,000 population in infants 2 months of age. In the post-implementation period, infants less than 1 month of age had the highest average annual hospitalization rate at 126.6 (95% CI 113.1, 140.1) hospitalizations per 100,000 infants. CONCLUSION: Infant pertussis hospitalizations have reduced greatly over time. Infants under 2 months of age remain the most at-risk age group for hospitalization and admission to ICU.

Burden of influenza, respiratory syncytial virus, and other respiratory viruses and the completeness of respiratory viral identification among respiratory inpatients, Canada, 2003-2014.

BACKGROUND: A regression-based study design has commonly been used to estimate the influenza burden; however, these estimates are not timely and many countries lack sufficient virological data. Alternative approaches that would permit a timelier assessment of the burden, including a sentinel surveillance approach recommended by the World Health Organization (WHO), have been proposed. We aimed to estimate the hospitalization burden attributable to influenza, respiratory syncytial virus (RSV), and other respiratory viruses (ORV) and to assess both the completeness of viral identification among respiratory inpatients in Canada and the implications of adopting other approaches. METHODS: Respiratory inpatient records were extracted from the Canadian Discharge Abstract Database from 2003 to 2014. A regression model was used to estimate excess respiratory hospitalizations attributable to influenza, RSV, and ORV by age group and diagnostic category and compare these estimates with the number with a respiratory viral identification. RESULTS: An estimated 33 (95% CI: 29, 38), 27 (95% CI: 22, 33), and 27 (95% CI: 18, 36) hospitalizations per 100 000 population per year were attributed to influenza, RSV, and ORV, respectively. An influenza virus was identified in an estimated 78% (95% CI: 75, 81) and 17% (95% CI: 15, 21) of respiratory hospitalizations attributed to influenza for children and adults, respectively, and 75% of influenza-attributed hospitalizations had an ARI diagnosis. CONCLUSIONS: Hospitalization rates with respiratory viral identification still underestimate the burden. Approaches based on acute respiratory case definitions will likely underestimate the burden as well, although each proposed method should be compared with regression-based estimates of influenza-attributed burden as a way of assessing their validity.

Leading Indicators and the Evaluation of the Performance of Alerts for Influenza Epidemics.

BACKGROUND: Most evaluations of epidemic thresholds for influenza have been limited to internal criteria of the indicator variable. We aimed to initiate discussion on appropriate methods for evaluation and the value of cross-validation in assessing the performance of a candidate indicator for influenza activity. METHODS: Hospital records of in-patients with a diagnosis of confirmed influenza were extracted from the Canadian Discharge Abstract Database from 2003 to 2011 and aggregated to weekly and regional levels, yielding 7 seasons and 4 regions for evaluation (excluding the 2009 pandemic period). An alert created from the weekly time-series of influenza positive laboratory tests (FluWatch, Public Health Agency of Canada) was evaluated against influenza-confirmed hospitalizations on 5 criteria: lead/lag timing; proportion of influenza hospitalizations covered by the alert period; average length of the influenza alert period; continuity of the alert period and length of the pre-peak alert period. RESULTS: Influenza hospitalizations led laboratory positive tests an average of only 1.6 (95% CI: -1.5, 4.7) days. However, the difference in timing exceeded 1 week and was statistically significant at the significance level of 0.01 in 5 out of 28 regional seasons. An alert based primarily on 5% positivity and 15 positive tests produced an average alert period of 16.6 weeks. After allowing for a reporting delay of 2 weeks, the alert period included 80% of all influenza-confirmed hospitalizations. For 20 out of the 28 (71%) seasons, the first alert would have been signalled at least 3 weeks (in real time) prior to the week with maximum number of influenza hospitalizations. CONCLUSIONS: Virological data collected from laboratories was a good indicator of influenza activity with the resulting alert covering most influenza hospitalizations and providing a reasonable pre-peak warning at the regional level. Though differences in timing were statistically significant, neither time-series consistently led the other.

Historical trends and projected hospital admissions for chronic hepatitis C infection in Canada: a birth cohort analysis.

BACKGROUND: Much of the recent increase in hospital admission rates and mortality associated with hepatitis C in Canada is believed to be because of a higher prevalence of hepatitis C virus infection among those born between 1945 and 1965 (the baby boomer generation). We explored the effects of birth cohort on the rates of and projected trends in hospital admissions associated with hepatitis C. METHODS: The hospital records of 17 344 inpatients with a diagnosis of chronic hepatitis C and liver disease, including liver cancer, were extracted from the Canadian Discharge Abstract Database for April 2004 to March 2011. For each 5-year birth cohort from 1915 to 1984, regression analysis was used to estimate the temporal trends associated with the average age of the cohort during the study period. Future hospital admissions were predicted based on the assumption that past trends would continue. RESULTS: Hospital admissions associated with hepatitis C and liver disease increased an average of 6.0% (95% confidence interval [CI] 4.4%-7.7%) a year over the study period. As of 2010, hospital admission rates were highest for the 1950-1954 and 1955-1959 birth cohorts, at 17.6 (95% CI 13.2-23.5) and 13.7 (95% CI 10.3-18.2) times the rate for the 1970-1974 birth cohort. The corresponding same-age rate ratios predicted under a status quo scenario were 3.6 (95% CI 2.3-4.9) and 3.4 (95% CI 2.1-4.7). Same-age rate ratios were significantly higher for the four 5-year birth cohorts between 1950 and 1969 compared with other birth cohorts. INTERPRETATION: Hospital admissions associated with chronic hepatitis C and liver disease were significantly higher for the 1950-1954 and 1955-1959 birth cohorts than for most other birth cohorts. Without further interventions, the disease burden associated with hepatitis C will continue to increase for most birth cohorts, likely peaking after age 70 years. The substantial disease burden emerging in younger birth cohorts should be monitored.

Estimating influenza deaths in Canada, 1992-2009.

BACKGROUND: Poisson regression modelling has been widely used to estimate the disease burden attributable to influenza, though not without concerns that some of the excess burden could be due to other causes. This study aims to provide annual estimates of the mortality and hospitalization burden attributable to both seasonal influenza and the 2009 A/H1N1 pandemic influenza for Canada, and to discuss issues related to the reliability of these estimates. METHODS: Weekly time-series for all-cause mortality and regression models were used to estimate the number of deaths in Canada attributable to influenza from September 1992 to December 2009. To assess their robustness, the annual estimates derived from different parameterizations of the regression model for all-cause mortality were compared. In addition, the association between the annual estimates for mortality and hospitalization by age group, underlying cause of death or primary reason for admission and discharge status is discussed. RESULTS: The crude influenza-attributed mortality rate based on all-cause mortality and averaged over 17 influenza seasons prior to the 2009 A/H1N1 pandemic was 11.3 (95%CI, 10.5 - 12.1) deaths per 100 000 population per year, or an average of 3,500 (95%CI, 3,200 - 3,700) deaths per year attributable to seasonal influenza. The estimated annual rates ranged from undetectable at the ecological level to more than 6000 deaths per year over the three A/Sydney seasons. In comparison, we attributed an estimated 740 deaths (95%CI, 350-1500) to A(H1N1)pdm09. Annual estimates from different model parameterizations were strongly correlated, as were estimates for mortality and morbidity; the higher A(H1N1)pdm09 burden in younger age groups was the most notable exception. INTERPRETATION: With the exception of some of the Serfling models, differences in the ecological estimates of the disease burden attributable to influenza were small in comparison to the variation in disease burden from one season to another.

Impact of seasonal and pandemic influenza on emergency department visits, 2003-2010, Ontario, Canada.

OBJECTIVES: Weekly influenza-like illness (ILI) consultation rates are an integral part of influenza surveillance. However, in most health care settings, only a small proportion of true influenza cases are clinically diagnosed as influenza or ILI. The primary objective of this study was to estimate the number and rate of visits to the emergency department (ED) that are attributable to seasonal and pandemic influenza and to describe the effect of influenza on the ED by age, diagnostic categories, and visit disposition. A secondary objective was to assess the weekly "real-time" time series of ILI ED visits as an indicator of the full burden due to influenza. METHODS: The authors performed an ecologic analysis of ED records extracted from the National Ambulatory Care Reporting System (NARCS) database for the province of Ontario, Canada, from September 2003 to March 2010 and stratified by diagnostic characteristics (International Classification of Diseases, 10th Revision [ICD-10]), age, and visit disposition. A regression model was used to estimate the seasonal baseline. The weekly number of influenza-attributable ED visits was calculated as the difference between the weekly number of visits predicted by the statistical model and the estimated baseline. RESULTS: The estimated rate of ED visits attributable to influenza was elevated during the H1N1/2009 pandemic period at 1,000 per 100,000 (95% confidence interval [CI] = 920 to 1,100) population compared to an average annual rate of 500 per 100,000 (95% CI = 450 to 550) for seasonal influenza. ILI or influenza was clinically diagnosed in one of 2.6 (38%) and one of 14 (7%) of these visits, respectively. While the ILI or clinical influenza diagnosis was the diagnosis most specific to influenza, only 87% and 58% of the clinically diagnosed ILI or influenza visits for pandemic and seasonal influenza, respectively, were likely directly due to an influenza infection. Rates for ILI ED visits were highest for younger age groups, while the likelihood of admission to hospital was highest in older persons. During periods of seasonal influenza activity, there was a significant increase in the number of persons who registered with nonrespiratory complaints, but left without being seen. This effect was more pronounced during the 2009 pandemic. The ratio of influenza-attributed respiratory visits to influenza-attributed ILI visits varied from 2.4:1 for the fall H1N1/2009 wave to 9:1 for the 2003/04 influenza A(H3N2) season and 28:1 for the 2007/08 H1N1 season. CONCLUSIONS: Influenza appears to have had a much larger effect on ED visits than was captured by clinical diagnoses of influenza or ILI. Throughout the study period, ILI ED visits were strongly associated with excess respiratory complaints. However, the relationship between ILI ED visits and the estimated effect of influenza on ED visits was not consistent enough from year to year to predict the effect of influenza on the ED or downstream in-hospital resource requirements.

Statistical estimates of respiratory admissions attributable to seasonal and pandemic influenza for Canada.

BACKGROUND: The number of admissions to hospital for which influenza is laboratory confirmed is considered to be a substantial underestimate of the true number of admissions due to an influenza infection. During the 2009 pandemic, testing for influenza in hospitalized patients was a priority, but the ascertainment rate remains uncertain. METHODS: The discharge abstracts of persons admitted with any respiratory condition were extracted from the Canadian Discharge Abstract Database, for April 2003-March 2010. Stratified, weekly admissions were modeled as a function of viral activity, seasonality, and trend using Poisson regression models. RESULTS: An estimated 1 out of every 6.4 admissions attributable to seasonal influenza (2003-April 2009) were coded to J10 (influenza virus identified). During the 2009 pandemic (May-March 2010), the influenza virus was identified in 1 of 1.6 admissions (95% CI, 1.5-1.7) attributed to the pandemic strain. Compared with previous H1N1 seasons (2007/08, 2008/09), the influenza-attributed hospitalization rate for persons <65 years was approximately six times higher during the 2009 H1N1 pandemic, whereas for persons 75 years or older, the pandemic rate was approximately fivefold lower. CONCLUSIONS: Case ascertainment was much improved during the pandemic period, with under ascertainment of admissions due to H1N1/2009 limited primarily to patients with a diagnosis of pneumonia.

The geographic synchrony of seasonal influenza: a waves across Canada and the United States.

BACKGROUND: As observed during the 2009 pandemic, a novel influenza virus can spread globally before the epidemic peaks locally. As consistencies in the relative timing and direction of spread could form the basis for an early alert system, the objectives of this study were to use the case-based reporting system for laboratory confirmed influenza from the Canadian FluWatch surveillance program to identify the geographic scale at which spatial synchrony exists and then to describe the geographic patterns of influenza A virus across Canada and in relationship to activity in the United States (US). METHODOLOGY/PRINCIPAL FINDINGS: Weekly laboratory confirmations for influenza A were obtained from the Canadian FluWatch and the US FluView surveillance programs from 1997/98 to 2006/07. For the six seasons where at least 80% of the specimens were antigenically similar, we identified the epidemic midpoint of the local/regional/provincial epidemics and analyzed trends in the direction of spread. In three out of the six seasons, the epidemic appeared first in Canada. Regional epidemics were more closely synchronized across the US (3-5 weeks) compared to Canada (5-13 weeks), with a slight gradient in timing from the southwest regions in the US to northeast regions of Canada and the US. Cities, as well as rural areas within provinces, usually peaked within a couple of weeks of each other. The anticipated delay in peak activity between large cities and rural areas was not observed. In some mixed influenza A seasons, lack of synchronization sub-provincially was evident. CONCLUSIONS/SIGNIFICANCE: As mixing between regions appears to be too weak to force a consistency in the direction and timing of spread, local laboratory-based surveillance is needed to accurately assess the level of influenza activity in the community. In comparison, mixing between urban communities and adjacent rural areas, and between some communities, may be sufficient to force synchronization.

Statistical estimates of absenteeism attributable to seasonal and pandemic influenza from the Canadian Labour Force Survey.

BACKGROUND: As many respiratory viruses are responsible for influenza like symptoms, accurate measures of the disease burden are not available and estimates are generally based on statistical methods. The objective of this study was to estimate absenteeism rates and hours lost due to seasonal influenza and compare these estimates with estimates of absenteeism attributable to the two H1N1 pandemic waves that occurred in 2009. METHODS: Key absenteeism variables were extracted from Statistics Canada's monthly labour force survey (LFS). Absenteeism and the proportion of hours lost due to own illness or disability were modelled as a function of trend, seasonality and proxy variables for influenza activity from 1998 to 2009. RESULTS: Hours lost due to the H1N1/09 pandemic strain were elevated compared to seasonal influenza, accounting for a loss of 0.2% of potential hours worked annually. In comparison, an estimated 0.08% of hours worked annually were lost due to seasonal influenza illnesses. Absenteeism rates due to influenza were estimated at 12% per year for seasonal influenza over the 1997/98 to 2008/09 seasons, and 13% for the two H1N1/09 pandemic waves. Employees who took time off due to a seasonal influenza infection took an average of 14 hours off. For the pandemic strain, the average absence was 25 hours. CONCLUSIONS: This study confirms that absenteeism due to seasonal influenza has typically ranged from 5% to 20%, with higher rates associated with multiple circulating strains. Absenteeism rates for the 2009 pandemic were similar to those occurring for seasonal influenza. Employees took more time off due to the pandemic strain than was typical for seasonal influenza.

A composite epidemic curve for seasonal influenza in Canada with an international comparison.

BACKGROUND: Empirical data on laboratory-confirmed seasonal influenza is limited by very low and possibly non-systematic case ascertainment as well as geographical variation. OBJECTIVE: To provide a visual representation of an influenza epidemic at the community and regional level using empirical data and to describe the epidemic characteristics. METHODS: Weekly influenza A confirmations were obtained from the Canadian FluWatch program and American FluView program for the 1997/1998-2006/2007 seasons; 1- year data were also available for Europe (FluNet, WHO). For seasons where at least 80% of the influenza A strains were antigenically similar, a composite epidemic curve was created by centring the local epidemics relative to their epidemic midpoint. RESULTS: The range in timing of the regional peaks varied from 5 to 13 weeks. Once the epidemic curves were centred relative to their peak, the composite epidemic curves were similar for Canada, the United States and Europe, and the epidemic growth rates were similar for most subgroups (city size; regions; H1N1 versus H3N2 seasons). During the exponential growth period, the number of cases increased by a factor of 1.5-2.0 per week, averaging 1.8. Exponential growth was evident approximately 10 weeks before the peak. Evidence of sustained transmission occurred from mid-September to early June. DISCUSSION: The shape of the composite curve created in this study clearly demonstrates a consistency in the epidemic pattern across geographically disparate locales. Laboratory confirmation will likely play an increasing role in the development of better methods for early detection and summary measures of influenza activity.

Estimating sensitivity of laboratory testing for influenza in Canada through modelling.

BACKGROUND: The weekly proportion of laboratory tests that are positive for influenza is used in public health surveillance systems to identify periods of influenza activity. We aimed to estimate the sensitivity of influenza testing in Canada based on results of a national respiratory virus surveillance system. METHODS AND FINDINGS: The weekly number of influenza-negative tests from 1999 to 2006 was modelled as a function of laboratory-confirmed positive tests for influenza, respiratory syncytial virus (RSV), adenovirus and parainfluenza viruses, seasonality, and trend using Poisson regression. Sensitivity was calculated as the number of influenza positive tests divided by the number of influenza positive tests plus the model-estimated number of false negative tests. The sensitivity of influenza testing was estimated to be 33% (95%CI 32-34%), varying from 30-40% depending on the season and region. CONCLUSIONS: The estimated sensitivity of influenza tests reported to this national laboratory surveillance system is considerably less than reported test characteristics for most laboratory tests. A number of factors may explain this difference, including sample quality and specimen procurement issues as well as test characteristics. Improved diagnosis would permit better estimation of the burden of influenza.

Co-morbidities associated with influenza-attributed mortality, 1994-2000, Canada.

The elderly and persons with specific chronic conditions are known to face elevated morbidity and mortality risks resulting from an influenza infection, and hence are routinely recommended for annual influenza vaccination. However, risk-specific mortality rates have not been established. We estimated age-specific influenza-attributable mortality rates stratified by the presence of chronic conditions and type of residence based on deaths of persons who were admitted to hospital with a respiratory complication captured in our national database. The majority of patients had chronic heart or respiratory conditions (80%) and were admitted from the community (80%). Influenza-attributable mortality rates clearly increase with age for all risk groups. Our influenza-specific estimates identified higher risk ratios for chronic lung or heart disease than have been suggested by other methods. These estimates identify groups most in need of improved vaccines and for whom the use of additional strategies, such as immunization of household contacts or caregivers should be considered.

Role of influenza and other respiratory viruses in admissions of adults to Canadian hospitals.

OBJECTIVE: We sought to estimate age-specific hospitalization rates attributed to influenza and other virus for adults. METHODS: Admissions from Canada's national hospitalization database (Canadian Institute of Health Information), from 1994/95 to 1999/2000, were modeled as a function of proxy variables for influenza, respiratory syncytial virus (RSV) and other viral activity, seasonality and trend using a Poisson regression model and stratified by age group. RESULTS: The average annual influenza-attributed hospitalization rate for all adults, 20 years of age or older, over the study period, which included three severe seasons, was an estimated 65/100,000 population (95% CI 63-67). Among persons aged 65 and over, 270-340 admissions per 100,000 population per year were attributed to influenza, while 30-110, 60-90 and 130-350 per 100,000 were attributed to RSV, parainfluenza (PIV) and other respiratory viruses, respectively. Although marked season-to-season variation in age-specific hospitalization rates attributable to influenza was observed in persons 50 years of age and older, increasing risk with age was preserved at all time periods. CONCLUSIONS: Influenza, RSV, PIV and other respiratory viruses were all associated with morbidity requiring hospitalization, while influenza was responsible for peak respiratory admissions. The burden of health care utilization associated with respiratory viruses is appreciable beginning in the sixth decade and increases significantly with age.

Influenza-attributed hospitalization rates among pregnant women in Canada 1994-2000.

BACKGROUND: Although it is recommended that pregnant women at risk for influenza complications receive influenza vaccine, it is not clear if healthy pregnant women are at increased risk for adverse outcomes. We aimed to estimate the rate of hospitalization attributable to influenza for healthy pregnant women and for those with known co-morbidities. METHODS: Hospital admission records of women admitted from 1994 to 2000 with a respiratory condition during pregnancy were extracted from the hospitalization database (Canadian Institute of Health Information). Admissions for childbirth were excluded. Weekly admissions, stratified by the presence of co-morbid conditions, were modelled as a function of viral activity, seasonality, trend, and holiday effects using Poisson regression with proxies for influenza and other viral activity developed previously for similar age-specific models of influenza-attributed hospital admissions. RESULTS: Approximately 300 hospitalizations of pregnant women per year were attributed to influenza, of which 140 were in women with co-morbidities. This hospitalization rate corresponds to 150 (95% CI 140-170) hospitalizations per 100,000 pregnant women per year. An estimated 1 in 1000 healthy pregnant women were hospitalized due to influenza per year. Asthma was the most important risk factor, accounting for an estimated 450 (95% CI 300-600) admissions per 100,000 pregnant women. Admission rates in pregnant women were relatively constant across multiple influenza seasons of varying severity among older adults. During the four weeks of peak influenza activity, 60% of respiratory-related admissions of otherwise healthy pregnant women could be attributed to influenza. CONCLUSION: Healthy pregnant Canadian women have consistently higher rates of hospital admission attributable to influenza infection than their non-pregnant peers. The admission rate for healthy pregnant women corresponds to the rate for men and women aged 65 to 69 years, which suggests that this population may benefit from annual influenza immunization.

Hospitalization attributable to influenza and other viral respiratory illnesses in Canadian children.

BACKGROUND: We sought to estimate the incidence of hospitalization attributable to influenza virus infection in Canadian children while controlling for the impact of other respiratory viruses. METHODS: Hospital admissions for children and youth 0 to 19 years of age, 1994-2000, were modeled as a function of proxy variables for influenza, respiratory syncytial virus (RSV) and other respiratory viral activity, seasonality and trend, using a Poisson regression model with a linear link. These proxy variables were developed from influenza mortality and laboratory test results for influenza, RSV and other viruses. Various checks for consistency, model fit and robustness were conducted and guided model development. RESULTS: Overall, 1.5% of all pediatric respiratory admissions could be attributed to influenza (18 admissions per 100,000 per year). The largest burden was seen in infants 6 to 11 months of age with rates of 200 per 100,000 infants and approximately equivalent to the rate for adults aged 65 to 69. During peak influenza activity, 7% of respiratory admissions were attributable to influenza as were 35% of febrile seizure admissions. RSV and parainfluenza (PIV) were the major viral causes of hospital admission with rates of 130 and 160 per 100,000, respectively. Another 70 per 100,000 admissions were attributed to other influenza-like illnesses. CONCLUSIONS: Influenza is a significant cause of morbidity leading to hospitalization in Canadian children, particularly for those under 2 years of age. RSV, PIV and other respiratory viruses were found to be major causes of respiratory illness leading to hospital care, surpassing influenza.

HIV/AIDS mortality in trends in Canada, 1987-1998.

OBJECTIVE: To monitor Canadian HIV/AIDS mortality following the introduction of antiretroviral therapies in 1996, and to compare this with the US experience. METHODS: Deaths were extracted by underlying cause of death, age, sex, marital status and place of residence at time of death. Age-specific leading causes of death, potential years of life lost before age 65, and rates are presented. RESULTS: HIV deaths peaked in 1995 at 1,764, representing 1% of all deaths, 15% of male deaths aged 25-44, and the second leading cause of death for males age 25-44, trailing suicides. From 1995 to 1997, HIV deaths dropped by 66% for males and 43% for females. Rates for Toronto, Vancouver and Montreal were 6 times higher than in rural areas, and 2.5 times higher than in other Census Metropolitan Areas. CONCLUSIONS: As of 1998, HIV still was a leading cause of premature mortality. The trend in Canadian HIV mortality was similar to that in the US, though US rates remain double the Canadian rates. The drop in HIV deaths may not be sustained in the long term, as antiretroviral therapy is not a cure and the number of people living with HIV is increasing.