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Public health interventions have been implemented to mitigate the spread of coronavirus disease 2019 (COVID-19) in Ontario, Canada; however, the quantification of their effectiveness remains to be done and is important to determine if some of the social distancing measures can be relaxed without resulting in a second wave. We aim to equip local public health decision- and policy-makers with mathematical model-based quantification of implemented public health measures and estimation of the trend of COVID-19 in Ontario to inform future actions in terms of outbreak control and de-escalation of social distancing. Our estimates confirm that (1) social distancing measures have helped mitigate transmission by reducing daily infection contact rate, but the disease transmission probability per contact remains as high as 0.145 and case detection rate was so low that the effective reproduction number remained higher than the threshold for disease control until the closure of non-essential business in the Province; (2) improvement in case detection rate and closure of non-essential business had resulted in further reduction of the effective control number to under the threshold. We predict the number of confirmed cases according to different control efficacies including a combination of reducing further contact rates and transmission probability per contact. We show that improved case detection rate plays a decisive role to reduce the effective reproduction number, and there is still much room in terms of improving personal protection measures to compensate for the strict social distancing measures. [ABSTRACT FROM AUTHOR]

Social contact mixing plays a critical role in influencing the transmission routes of infectious diseases. Moreover, quantifying social contact mixing patterns and their variations in a rapidly evolving pandemic intervened by changing public health measures is key for retroactive evaluation and proactive assessment of the effectiveness of different age- and setting-specific interventions. Contact mixing patterns have been used to inform COVID-19 pandemic public health decision-making; but a rigorously justified methodology to identify setting-specific contact mixing patterns and their variations in a rapidly developing pandemic, which can be informed by readily available data, is in great demand and has not yet been established. Here we fill in this critical gap by developing and utilizing a novel methodology, integrating social contact patterns derived from empirical data with a disease transmission model, that enables the usage of age-stratified incidence data to infer age-specific susceptibility, daily contact mixing patterns in workplace, household, school and community settings; and transmission acquired in these settings under different physical distancing measures. We demonstrated the utility of this methodology by performing an analysis of the COVID-19 epidemic in Ontario, Canada. We quantified the age- and setting (household, workplace, community, and school)-specific mixing patterns and their evolution during the escalation of public health interventions in Ontario, Canada. We estimated a reduction in the average individual contact rate from 12.27 to 6.58 contacts per day, with an increase in household contacts, following the implementation of control measures. We also estimated increasing trends by age in both the susceptibility to infection by SARS-CoV-2 and the proportion of symptomatic individuals diagnosed. Inferring the age- and setting-specific social contact mixing and key age-stratified epidemiological parameters, in the presence of evolving control measures, is critical to inform decision- and policy-making for the current COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The elderly, especially those individuals with pre-existing health problems, have been disproportionally at a higher risk during the COVID-19 pandemic. Residents of long-term care facilities have been gravely affected by the pandemic and resident death numbers have been far above those of the general population. To better understand how infectious diseases such as COVID-19 can spread through long-term care facilities, we developed an agent-based simulation tool that uses a contact matrix adapted from previous infection control research in these types of facilities. This matrix accounts for the average distinct daily contacts between seven different agent types that represent the roles of individuals in long-term care facilities. The simulation results were compared to actual COVID-19 outbreaks in some of the long-term care facilities in Ontario, Canada. Our analysis shows that this simulation tool is capable of predicting the number of resident deaths after 50 days with a less than 0.1 variation in death rate. We modeled and predicted the effectiveness of infection control measures by utilizing this simulation tool. We found that to reduce the number of resident deaths, the effectiveness of personal protective equipment must be above 50%. We also found that daily random COVID-19 tests for as low as less than 10% of a long-term care facility's population will reduce the number of resident deaths by over 75%. The results further show that combining several infection control measures will lead to more effective outcomes.

We developed a stochastic optimization technology based on a COVID-19 transmission dynamics model to determine optimal pathways from lockdown toward reopening with different scales and speeds of mass vaccine rollout in order to maximize social economical activities while not overwhelming the health system capacity in general, hospitalization beds, and intensive care units in particular. We used the Province of Ontario, Canada as a case study to demonstrate the methodology and the optimal decision trees; but our method and algorithm are generic and can be adapted to other settings. Our model framework and optimization strategies take into account the likely range of social contacts during different phases of a gradual reopening process and consider the uncertainties of these contact rates due to variations of individual behaviors and compliance. The results show that, without a mass vaccination rollout, there would be multiple optimal pathways should this strategy be adopted right after the Province's lockdown and stay-at-home order; however, once reopening has started earlier than the timing determined in the optimal pathway, an optimal pathway with similar constraints no longer exists, and sub-optimal pathways with increased demand for intensive care units can be found, but the choice is limited and the pathway is narrow. We also simulated the situation when the reopening starts after the mass vaccination has been rolled out, and we concluded that optimal pathways toward near pre-pandemic activity level is feasible given an accelerated vaccination rollout plan, with the final activity level being determined by the vaccine coverage and the transmissibility of the dominating strain., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Xiao, Chen, Zhu, McCarthy, Bragazzi, Asgary and Wu.)

Background: School testing for SARS-CoV-2 infection has become an important policy and planning issue as schools were reopened after the summer season and as the COVID-19 pandemic continues. Decisions to test or not to test and, if testing, how many tests, how often and for how long, are complex decisions that need to be taken under uncertainty and conflicting pressures from various stakeholders., Method: We have developed an agent-based model and simulation tool that can be used to analyze the outcomes and effectiveness of different testing strategies and scenarios in schools with various number of classrooms and class sizes. We have applied a modified version of a standard SEIR disease transmission model that includes symptomatic and asymptomatic infectious populations, and that incorporates feasible public health measures. We also incorporated a pre-symptomatic phase for symptomatic cases. Every day, a random number of students in each class are tested. If they tested positive, they are placed in self-isolation at home when the test results are provided. Last but not least, we have included options to allow for full testing or complete self-isolation of a classroom with a positive case., Results: We present sample simulation results for parameter values based on schools and disease related information, in the Province of Ontario, Canada. The findings show that testing can be an effective method in controlling the SARS-CoV-2 infection in schools if taken frequently, with expedited test results and self-isolation of infected students at home., Conclusions: Our findings show that while testing cannot eliminate the risk and has its own challenges, it can significantly control outbreaks when combined with other measures, such as masks and other protective measures.

Background: Economic evaluations should form part of the basis for public health decision making on new vaccine programs. While Canada's national immunization advisory committee does not systematically include economic evaluations in immunization decision making, there is increasing interest in adopting them. We therefore sought to examine the extent and quality of economic evaluations of vaccines in Canada., Objective: We conducted a systematic review of economic evaluations of vaccines in Canada to determine and summarize: comprehensiveness across jurisdictions, studied vaccines, funding sources, study designs, research quality, and changes over time., Methods: Searches in multiple databases were conducted using the terms "vaccine," "economics" and "Canada." Descriptive data from eligible manuscripts was abstracted and three authors independently evaluated manuscript quality using a 7-point Likert-type scale scoring tool based on criteria from the International Society for Pharmacoeconomics and Outcomes Research (ISPOR)., Results: 42/175 articles met the search criteria. Of these, Canada-wide studies were most common (25/42), while provincial studies largely focused on the three populous provinces of Ontario, Quebec and British Columbia. The most common funding source was industry (17/42), followed by government (7/42). 38 studies used mathematical models estimating expected economic benefit while 4 studies examined post-hoc data on established programs. Studies covered 10 diseases, with 28/42 addressing pediatric vaccines. Many studies considered cost-utility (22/42) and the majority of these studies reported favorable economic results (16/22). The mean quality score was 5.9/7 and was consistent over publication date, funding sources, and disease areas., Conclusions: We observed diverse approaches to evaluate vaccine economics in Canada. Given the increased complexity of economic studies evaluating vaccines and the impact of results on public health practice, Canada needs improved, transparent and consistent processes to review and assess the findings of the economic evaluations of vaccines.

Antimicrobials are an effective treatment for many types of infections, but their overuse promotes the spread of resistant microorganisms that defy conventional treatments and complicate patient care. In 2009, an antimicrobial stewardship program was implemented at Mount Sinai Hospital (MSH, Toronto, Canada). Components of this program were to alter the fraction of patients prescribed antimicrobials, to shorten the average duration of treatment, and to alter the types of antimicrobials prescribed. These components were incorporated into a mathematical model that was compared to data reporting the number of patients colonized with Pseudomonas aeruginosa and the number of patients colonized with antimicrobial-resistant P. aeruginosa first isolates before and after the antimicrobial stewardship program. Our analysis shows that the reported decrease in the number of patients colonized was due to treating fewer patients, while the reported decrease in the number of patients colonized with resistant P. aeruginosa was due to the combined effect of treating fewer patients and altering the types of antimicrobials prescribed. We also find that shortening the average duration of treatment was unlikely to have produced any noticeable effects and that further reducing the fraction of patients prescribed antimicrobials would most substantially reduce P. aeruginosa antimicrobial resistance in the future. The analytical framework that we derive considers the effect of colonization pressure on infection spread and can be used to interpret clinical antimicrobial resistance data to assess different aspects of antimicrobial stewardship within the ecological context of the intensive care unit., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: In the face of an influenza pandemic, accurate estimates of epidemiologic parameters are required to help guide decision-making. We sought to estimate epidemiologic parameters for pandemic H1N1 influenza using data from initial reports of laboratory-confirmed cases., Methods: We obtained data on laboratory-confirmed cases of pandemic H1N1 influenza reported in the province of Ontario, Canada, with dates of symptom onset between Apr. 13 and June 20, 2009. Incubation periods and duration of symptoms were estimated and fit to parametric distributions. We used competing-risk models to estimate risk of hospital admission and case-fatality rates. We used a Markov Chain Monte Carlo model to simulate disease transmission., Results: The median incubation period was 4 days and the duration of symptoms was 7 days. Recovery was faster among patients less than 18 years old than among older patients (hazard ratio 1.23, 95% confidence interval 1.06-1.44). The risk of hospital admission was 4.5% (95% CI 3.8%-5.2%) and the case-fatality rate was 0.3% (95% CI 0.1%-0.5%). The risk of hospital admission was highest among patients less than 1 year old and those 65 years or older. Adults more than 50 years old comprised 7% of cases but accounted for 7 of 10 initial deaths (odds ratio 28.6, 95% confidence interval 7.3-111.2). From the simulation models, we estimated the following values (and 95% credible intervals): a mean basic reproductive number (R0, the number of new cases created by a single primary case in a susceptible population) of 1.31 (1.25-1.38), a mean latent period of 2.62 (2.28-3.12) days and a mean duration of infectiousness of 3.38 (2.06-4.69) days. From these values we estimated a serial interval (the average time from onset of infectiousness in a case to the onset of infectiousness in a person infected by that case) of 4-5 days., Interpretation: The low estimates for R0 indicate that effective mitigation strategies may reduce the final epidemic impact of pandemic H1N1 influenza.

Several models have rationalized the use of antiviral drugs as an early control measure for delaying the progression and limiting the size of outbreaks during an influenza pandemic. However, the strategy for use of these drugs is still under debate. We evaluated the impact of prophylaxis of healthcare workers (HCWs) through a mathematical model that considers attack rates in a range of 25-35% in the general population and 25-50% among HCWs. Simulations and uncertainty analysis using the demographics of the province of Ontario, Canada show that increasing prophylaxis coverage of HCWs has little impact on reducing the reproduction number of disease transmission and may not prevent the occurrence of an outbreak if expected. However, it does enable a high level of treatment, which substantially reduces morbidity and mortality in the population as a whole. Therefore, prophylaxis of HCWs should be considered an important part of public health efforts for minimizing influenza pandemic burden and its socio-economic disruption.

The isolation and treatment of symptomatic individuals, coupled with the quarantining of individuals that have a high risk of having been infected, constitute two commonly used epidemic control measures. Although isolation is probably always a desirable public health measure, quarantine is more controversial. Mass quarantine can inflict significant social, psychological, and economic costs without resulting in the detection of many infected individuals. The authors use probabilistic models to determine the conditions under which quarantine is expected to be useful. Results demonstrate that the number of infections averted (per initially infected individual) through the use of quarantine is expected to be very low provided that isolation is effective, but it increases abruptly and at an accelerating rate as the effectiveness of isolation diminishes. When isolation is ineffective, the use of quarantine will be most beneficial when there is significant asymptomatic transmission and if the asymptomatic period is neither very long nor very short.