BACKGROUND:Canada eliminated measles in 1998, but the risk of outbreaks remains due to sub-optimal vaccine coverage and imported cases. To address limitations of vaccine coverage data, we measured measles seroprevalence among a convenience sample of individuals serologically tested in Ontario, Canada. METHODS:We linked measles IgG serology data from 349,451 individuals tested during 2014-2016 to health administrative databases and used a cross-sectional design to measure measles IgG seroprevalence. We estimated seroprevalence overall and by sociodemographic factors. FINDINGS:Using the manufacturer-recommended threshold of ≥275 mIU/mL, measles seroprevalence was 83.5 % (95% CI, 83.4-83.6 %), below the 90-95 % herd immunity threshold. However, using the often cited >120 mIU/mL threshold, seroprevalence was 97.1 % (95% CI, 97.0-97.1 %). Using a threshold of ≥275 mIU/mL, seroprevalence varied by age, with the lowest observed among adolescents aged 12-19 years (75.3 %; 95% CI, 74.8-75.7 %) and young adults aged 20-29 years (75.8 %; 95% CI, 75.5-76.1 %), and highest among the oldest cohorts aged ≥50 years (96.9 %; 95% CI, 96.8-97.0 %). When using a lower threshold of protection (>120 mIU/mL), large differences in seroprevalence by age were not observed. Among individuals born in or after 1985, immigrants had lower seroprevalence (≥275 mIU/mL) (71.0 %; 95% CI, 70.6-71.5 %) compared to those born in Canada (77.8 %; 95% CI, 77.6-78.1 %). INTERPRETATION:The uncertainty of the exact correlate of protection for measles complicates the interpretation of seroprevalence data when assessing whether this convenience sample of individuals serologically tested for measles is adequately protected to prevent future outbreaks. Measles seroprevalence varied significantly by age and immigrant status, with highest seronegativity (<275 mIU/mL) observed among adolescents, young adults, and young immigrants. It is possible that sustaining measles elimination in Ontario will be challenging in the face of ongoing measles importations from abroad, and immunity gaps in some population groups.

Background and aim: Coronavirus disease 2019 (COVID-19) is causing a tremendous health burden globally. Identification of the determinants of COVID-19 severity is important for prevention and intervention. This study aims to explore long-term exposure to ambient air pollution as a potential contributors to COVID-19 severity given its known impact on the pulmonary system. Methods: Using a cohort of all confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases aged ≥20 years and not residing in a long-term care facility in Ontario, Canada during 2020, we evaluated the association between long-term exposure to fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ground-level ozone (O3) and risk of COVID-19-related hospitalization, intensive care unit (ICU) admission and death separately. Participants' long-term exposures to each air pollutant were ascertained based on their residential addresses from 2015 to 2019. We used logistic regression and adjusted for confounding and selection bias using various individual and contextual covariates obtained through data linkage. Results: Among the 151,105 confirmed SARS-CoV-2 cases in 2020, we observed 8,630 hospitalizations, 1,912 ICU admissions and 2,137 deaths related to COVID-19. For each interquartile range increase in exposure to PM2.5 (1.70 µg/m3), we estimated ORs of 1.06 (95% confidence interval (CI): 1.01 to 1.12), 1.09 (95% CI: 0.98 to 1.21) and 1.00 (95% CI: 0.90 to 1.11) for hospitalization, ICU admission and death, respectively. Estimates were smaller for NO2 but larger for O3. Conclusions: In this large population-based study in Ontario during 2020, we found that chronic exposure to air pollution may contribute to severe outcomes following SARS-CoV-2 infection, with stronger evidence found with O3. Keywords: COVID-19 severity, long-term exposure to air pollution, death, hospitalization, intensive care unit admission

Background: The tremendous global health burden related to COVID-19 means that identifying determinants of COVID-19 severity is important for prevention and intervention. We aimed to explore long-term exposure to ambient air pollution as a potential contributor to COVID-19 severity, given its known impact on the respiratory system. Methods: We used a cohort of all people with confirmed SARS-CoV-2 infection, aged 20 years and older and not residing in a long-term care facility in Ontario, Canada, during 2020. We evaluated the association between long-term exposure to fine particulate matter (PM2.5), nitrogen dioxide (NO2) and ground-level ozone (O3), and risk of COVID-19-related hospital admission, intensive care unit (ICU) admission and death. We ascertained individuals’ long-term exposures to each air pollutant based on their residence from 2015 to 2019. We used logistic regression and adjusted for confounders and selection bias using various individual and contextual covariates obtained through data linkage. Results: Among the 151 105 people with confirmed SARS-CoV-2 infection in Ontario in 2020, we observed 8630 hospital admissions, 1912 ICU admissions and 2137 deaths related to COVID-19. For each interquartile range increase in exposure to PM2.5 (1.70 μg/m3), we estimated odds ratios of 1.06 (95% confidence interval [CI] 1.01–1.12), 1.09 (95% CI 0.98–1.21) and 1.00 (95% CI 0.90–1.11) for hospital admission, ICU admission and death, respectively. Estimates were smaller for NO2. We also estimated odds ratios of 1.15 (95% CI 1.06–1.23), 1.30 (95% CI 1.12–1.50) and 1.18 (95% CI 1.02–1.36) per interquartile range increase of 5.14 ppb in O3 for hospital admission, ICU admission and death, respectively. Interpretation: Chronic exposure to air pollution may contribute to severe outcomes after SARS-CoV-2 infection, particularly exposure to O3.

Background: Air pollution has been associated with increased mortality. However, updated evidence from cohort studies with detailed information on various risk factors is needed, especially in regions with low air pollution levels. We investigated the associations between long-term exposure to air pollution and mortality in a prospective cohort. Methods: We studied 88,615 participants aged >= 30 years from an ongoing cohort study in Ontario, Canada from 2009 to 2017. Exposure to ambient fine particulate matter (PM2.5) and nitrogen dioxide (NO2) was estimated at participants' residence. Cox proportional hazard models were used to investigate the associations between air pollution and non-accidental, cardiovascular, and respiratory mortality, adjusted for a wide array of individuallevel and contextual covariates. Potential effect modification by socio-demographic and behavioral factors was also examined in exploratory stratified analyses. Results: The fully adjusted hazard ratios (HRs) per 1 & micro;g/m3 increment in PM2.5 were 1.037 [95% confidence interval (CI): 1.018, 1.057]& cedil; 1.083 (95% CI: 1.040, 1.128) and 1.109 (95% CI: 1.035, 1.187) for non-accidental, cardiovascular, and respiratory mortality, respectively. Positive associations were also found for NO2; the corresponding HRs per 1 ppb increment were 1.027 (95% CI: 1.021, 1.034), 1.032 (95% CI: 1.019, 1.046) and 1.044 (95% CI: 1.020, 1.068). We found suggestive evidence of stronger associations in physically active participants, smokers, and those with lower household income. Conclusions: Long-term exposure to PM2.5 and NO2 was associated with increased risks for non-accidental, cardiovascular, and respiratory mortality, suggesting potential benefits of further improvement in air quality even in low-exposure environments.

Abstract Background Community-acquired pneumonia (CAP) causes substantial morbidity and mortality. There is a lack of data on the comprehensive burden of CAP across the life span in Canada. We estimated the incidence of all-cause CAP in all age groups in Ontario and British Columbia (BC), Canada. Methods We identified hospitalized and outpatient CAP episodes from the Discharge Abstract Database (DAD) and physician billing claims databases (Ontario Health Insurance Plan in Ontario and Medical Services Plan in BC) in both provinces. The National Ambulatory Care Reporting System was used to identify CAP episodes from emergency department visits in Ontario. CAP recorded with a primary or secondary diagnosis was identified using International Classification of Diseases 9 (480–486, 510, 513) and 10 (J10.0, J11.0, J12–J18, J86.9, J85.1) codes. We estimated the age and sex adjusted annual incidence of CAP overall, and by age groups (0–4, 5–17, 18–39, 40–64, 65–74, 75–84 and ≥85 years) according to routine childhood pneumococcal conjugate vaccine (PCV) immunization periods from 2005–2018 in Ontario and from 2002–2018 in BC. Poisson regression models were fitted with population denominators from Statistics Canada to estimate the incidence rates. Results Ontario had 3,607,186 CAP episodes from 2005–2015 with a mean annual incidence of 2,801 (95% confidence interval [CI]: 2,748, 2,854) per 100,000 population; incidence declined from 3,077/100,000 in 2005 to 2,604/100,000 in 2010 before increasing to 2,843/100,000 in 2018. BC had 1,146,172 CAP episodes from 2002–2008, with a mean annual incidence of 2,146 (95% CI: 2105, 2189); the incidence increased from 2,005 /100,000 in 2002 to 2,199/100,000 in 2018. A high incidence of CAP was observed in children aged 0–4 years and older adults, particularly in adults aged ≥85 years in both provinces across all PCV program periods (Figure 1). Figure 1: Age group-specific incidence of all-cause community-acquired pneumonia according to childhood pneumococcal conjugate vaccine (PCV) program periods in Ontario (PCV7 [1 Jan 2005–30 Sep 2009]), PCV10 [1 Oct 2009–31 Oct 2010] and PCV13 [1 Nov 2010–31 Dec 2018]) and British Columbia (PCV7 [1 Sep 2003–31 May 2010] and PCV13 [1 Jun 2010–31 Dec 2018]), Canada Conclusion CAP continues to be a public health burden in Canada despite publicly funded pneumococcal vaccination programs. Ontario seems to have higher CAP burden than British Columbia that warrants further investigation. The youngest cohort of children and older adults contribute significantly to the CAP burden. Disclosures Manish Sadarangani, BM BCh, DPhil, GlaxoSmithKline (Grant/Research Support)Merck (Grant/Research Support)Pfizer (Grant/Research Support)Sanofi Pasteur (Grant/Research Support)Seqirus (Grant/Research Support)Symvivo (Grant/Research Support)VBI Vaccines (Research Grant or Support) Allison McGeer, MSc,MD,FRCPC,FSHEA, GlaxoSmithKline (Advisor or Review Panel member)Merck (Advisor or Review Panel member, Research Grant or Support)Pfizer (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member) James D. Kellner, MD, FRCPC, FIDSA, Pfizer, Merck, GSK, Moderna (Grant/Research Support) Shaun Morris, MD, MPH, DTM&H, FRCPC, FAAP, GSK (Speaker’s Bureau)Pfizer (Advisor or Review Panel member)Pfizer (Grant/Research Support) Shaza A. Fadel, PhD MPH, Merck (Other Financial or Material Support, Salary is paid by the University of Toronto via a donation by Merck to the Centre for Vaccine Preventable Diseases to support educational and operational activities.) Fawziah Marra, BSc(Pharm), PharmD, Pfizer Canada (Research Grant or Support)

To determine incidence-based healthcare costs attributable to nontuberculous mycobacterial (NTM) pulmonary disease (PD) and NTM pulmonary isolation (PI), from the healthcare payer perspective, we conducted a population-based matched cohort study in Ontario, Canada. We established cohorts of patients with incident NTM-PD and NTM-PI during 2001-2012 by using individually linked laboratory data and health administrative data, matched to unexposed persons from the general population. To estimate attributable costs for acute and long-term illness, we used a phase-of-care approach. Costs were stratified by age, sex, and healthcare resource, and reported in 2018 Canadian dollars (CAD) and US dollars (USD), standardized to 10 days. Costs were highest during the before-death phase (NTM-PD CAD $1,352 [USD $1,044]; NTM-PI CAD $731 [USD $565]). The cumulative mean attributable 1-year costs were CAD $14,953 (USD $11,541) for NTM-PD and CAD $8,729 (USD $6,737) for NTM-PI. Costs for patients with NTM-PD and NTM-PI were higher than those for unexposed persons.

Canada eliminated measles in 1998. We conducted a sero-epidemiology study to estimate population immunity to measles in the province of Ontario, Canada and to identify groups at higher risk of outbreaks. We used a previously developed modified enzyme immunoassay to test 1,199 residual sera from patients aged 1-39 years. We re-tested negative and equivocal sera using a plaque reduction neutralization assay. We interpreted our results in the context of Ontario's immunization program and vaccine coverage data. Of 1,199 sera, 1035 (86.3%, 95% confidence interval (CI) 84.4, 88.2) were above the measles threshold for protection, 70 (5.8%, 95% CI 4.5, 7.2) were equivocal and 94 (7.8%, 95% CI 6.3, 9.4) were negative. The proportion of positive sera was highest for those 1-5 years, with 180/199 (90.5%, 95% CI 86.4, 94.5) positive sera, and lowest for those age 12-19 years, at 158/199 (79.4%, 95% CI 73.8, 85.0). Adjusted for age, females were more likely than males to have antibody titers above the threshold of protection (odds ratio = 1.60, 95% CI 1.14, 2.24). Most of the study cohort were eligible for two measles vaccine doses, and vaccine uptake in Ontario is >90% for school-aged cohorts. We observed a higher than expected proportion of sera with antibody levels below the threshold of protection, suggesting that immunity in some Ontario age-groups may be waning, despite high vaccine coverage. Alternatively, the traditional measles correlates of protection may not be an appropriate measure of population protection in measles-eliminated settings.

Abstract Background West Nile virus (WNV) is a mosquito-borne flavivirus, first detected in the Western Hemisphere in 1999 and spread across North America over the next decade. Though endemic in the most populous areas of North America, few studies have estimated the healthcare costs associated with WNV. The objective of this study was to determine direct healthcare costs attributable to WNV illness in Ontario, Canada. Methods We conducted a cost-of-illness study on incident laboratory confirmed and probable WNV infected subjects identified from the provincial laboratory database from Jan 1, 2002 through Dec 31, 2012. Infected subjects were linked to health administrative data and matched to uninfected subjects. We used phase-of-care methods to calculate costs for 3 phases of illness: acute infection, continuing care, and final care prior to death. Mean 10-day attributable costs were reported in 2014 Canadian dollars, per capita. Sensitivity analysis was conducted to test the impact of WNV neurologic syndromes on healthcare costs. Results One thousand five hundred fifty-one laboratory confirmed and probable WNV infected subjects were ascertained; 1540 (99.3%) were matched to uninfected subjects. Mean age of WNV infected subjects was 49.1 ± 18.4 years, 50.5% were female. Mean costs attributable to WNV were $1177 (95% CI: $1001, $1352) for acute infection, $180 (95% CI: $122, $238) for continuing care, $11,614 (95% CI: $5916, $17,313) for final care - acute death, and $3199 (95% CI: $1770, $4627) for final care - late death. Expected 1-year costs were $13,648, adjusted for survival. Three hundred seventeen infected subjects were diagnosed with at least one neurologic syndrome and greatest healthcare costs in acute infection were associated with encephalitis ($4710, 95% CI: $3770, $5650). Conclusions WNV is associated with increased healthcare resource utilization across all phases of care. High-quality studies are needed to understand the health system impact of vector-borne diseases and evaluate the cost effectiveness of novel WNV interventions.

The objective of this study was to determine healthcare costs attributable to laboratory‐confirmed Lyme disease (LD) from the healthcare payer perspective in Ontario, Canada. A cost‐of‐illness study was conducted for incident LD subjects from 1 January 2006 through 31 December 2013 ascertained from provincial laboratory and reportable disease databases, linked to health administrative data. All LD subjects included were laboratory‐confirmed, according to provincial case definitions. Incident LD subjects were propensity‐score matched to uninfected subjects on age, sex, comorbidities and urban/rural status. We used phase‐of‐care methods to calculate attributable costs for two phases of illness: initial care (≤30 days following “index date”) and continuing care (>30 days after index date to the end of the follow‐up period). A total of 663 incident, confirmed LD subjects were identified from 2006 through 2013. Mean age was 44.2 ± 20.1 years; 339 (51.1%) were female; and 31 (4.7%) were hospitalized ≤30 days after index date. Six hundred fifty‐eight (99.2%) LD subjects were matched to uninfected subjects; mean follow‐up time was 3.3 years. Mean attributable costs per case during the initial care phase and continuing care were $277 (95% CI: $197, $357) and −$5 (−$27, $17), respectively. Attributable costs per LD subject aged 5–14 years were $440 ($132, $747), greater than the costs observed for other age strata. Expected 1‐year attributable costs were $832, given continuing care costs were negligible. Limitations to our study include estimating costs using a cohort of only laboratory‐confirmed LD cases, introducing selection bias for diagnosed and treated patients who may have a lower risk of developing sequelae. In conclusion, the initial care phase of LD is associated with increased healthcare costs, but without significant costs attributable to LD infection after 30 days. Estimates of costs attributable to LD are important for healthcare resource prioritization and the evaluation of novel interventions.

Background: Extreme cold weather alert programs have been implemented in some areas to address the significant health impacts of exposure to cold. One such program is the Toronto Cold Weather Program (TCWP) that was implemented in the City of Toronto since 1996 to protect the public from extreme weather conditions. In this paper, we aim to evaluate the effectiveness of the TCWP in reducing mortality and morbidity outcomes related to cold temperatures. Methods: We applied a quasi-experimental study design using the Difference-in-Differences method coupled with propensity-score-matching to determine the effect of the TCMP on daily hospitalizations and deaths due to cardiovascular disease (CVD), coronary heart disease (CHD) or cerebrovascular disease, using two complementary analytical approaches. Results: Overall, the analysis did not detect an impact on reduced mortality/morbidity in the City of Toronto from the TCMP. For example, we obtained a Risk Difference (RD) of -0.88 (per 1,000,000 people) (95% CI: -3.27 to 1.51) and a Risk Ratio (RR) of 0.98 (95% CI: 0.91 to 1.05) people for CVD hospitalizations. Conclusions: The TCWP was not found to be effective in reducing cold related mortality and morbidity which demonstrates the importance of improving existing policies related to cold in Canada and other countries.

Effects of Heat and Cold Temperature on Cause-Specific Mortality between 1996 and 2010 in Ontario, CanadaAbstract Number:1841 Hong Chen*, Abderrahmane Yagouti, Richard Foty, Eric Lavigne, Richard Burnett, Mark Goldberg, Paul Villeneuve, Sabit Cakmak, John Wang, and Ray Copes Hong Chen* Public Health Ontario, Canada, E-mail Address: [email protected] , Abderrahmane Yagouti Health Canada, Canada, E-mail Address: [email protected] , Richard Foty Public Health Ontario, Canada, E-mail Address: [email protected] , Eric Lavigne Health Canada, Canada, E-mail Address: [email protected] , Richard Burnett Health Canada, Canada, E-mail Address: [email protected] , Mark Goldberg McGill University, Canada, E-mail Address: [email protected] , Paul Villeneuve Carleton University, Canada, E-mail Address: [email protected] , Sabit Cakmak Health Canada, Canada, E-mail Address: [email protected] , John Wang Public Health Ontario, Canada, E-mail Address: [email protected] , and Ray Copes Public Health Ontario, Canada, E-mail Address: [email protected] AbstractBACKGROUND: Extreme ambient temperature, especially heat, is associated with mortality; however, heat-related mortality risk has not been quantified systematically in Ontario, the largest province in Canada. Less is known about cold-related risk in this population. METHOD: This study comprised all residents of Ontario who died during 1996-2010 (1.3 million deaths). A time-stratified case-crossover analysis was applied to assess the relation between temperature change and cause-specific mortality (e.g., respiratory, myocardial infarction (MI), diabetes) for warm season (June to August) and cold season (Dec. to Feb.), separately, adjusting for selected meteorological factors, air pollutants, daily physician's visits for influenza, and holidays. County-specific effect estimates were obtained first, and then pooled across Ontario. We examined various exposure metrics (e.g., apparent and air temperature) and lagged exposure periods (lag 1-6). We also assessed the effect of extreme heat and cold episodes, defined as daily mean temperature in the upper or lower 5th (or 1st) percentile of a county's temperature distribution for 1, 2, or 3 consecutive days.RESULTS: A 5oC increase in mean daily apparent temperature in warm season was associated with a 1.5% increase in same-day deaths for nonaccidental causes (95% confidence interval (CI)=0.3%-2.7%) and a 3.6% increase for respiratory deaths (95%CI=0-7.5%) across Ontario. Extreme heat episodes were seen to increase respiratory deaths by 30% to 47% (depending on episode definitions), relative to other days. Cold-related mortality was most associated with exposure over a 6-day lag period, with a 3.1% increase in nonaccidental deaths (95%CI=1.8%-4.5%) and a 8.2% in MI-related deaths (95%CI=3.5%-13.2%) per 5oC decrease in apparent temperature. There was little evidence of increased risks with extreme cold episodes.CONCLUSIONS: Heat contributed to excess deaths in Ontario. There were also important mortality risks from cold.