Abstract Background Measles is a serious infectious disease that contributes significantly to the burden of disease in many developing countries. In most developed nations, such as Canada, endemic transmission of measles has been declared eliminated thanks to rigorous vaccination programs, but isolated outbreaks of the disease continue to happen. Therefore, a thorough understanding of the factors contributing to these outbreaks is necessary. Objectives There were two main objectives of this thesis. The first objective was to assess the geospatial distribution of reported measles cases in Ontario with a goal of identifying clusters of reported measles. For this objective, the main hypothesis was that measles cases would not be randomly distributed across Ontario and instead would cluster in certain regions. The second objective was to explore some of the factors that may be associated with measles clusters. For this objective, the main hypothesis was that the proportion of immigrants, population density, low-income prevalence and education level would be associated with measles clusters. Methods The first objective was achieved through a thorough geospatial analysis using SaTScan and R. Individual forward sortation areas were used as the spatial unit of analysis. The analysis leveraged data from multiple sources: 2016 Census data, Ontario measles cases data from iPHIS from 2008 to 2019, a shapefile of all forward sortation areas in Canada from Statistics Canada and centroid coordinates of forward sortation areas that were obtained using web scrapping techniques on the geolocation service of Natural Resources Canada. The maximal window size of the geospatial analysis was chosen using the maximum clustering heterogeneous set-proportion technique. The geospatial analysis was run with 99,999 Monte Carlo repetitions under a Poisson distribution using the purely spatial analysis. The Ontario population from the 2016 Census was used as the population at risk. Any cluster with a p ≤ 0.05 was deemed statistically significant. The second objective was achieved through a case-control study: Forward sortation areas that were within statistically significant measles clusters were considered as cases and the rest of the forward sortation areas were considered as controls. Demographic data necessary to assess the factors of interest were extracted from the 2016 Census. A univariable logistic regression model was run to compute the odds ratio and test the association between the factors of interest and measles clusters. 95% confidence intervals were computed for each odds ratio. Data-curation techniques and data analysis were performed in R 4.0.4. Results From 2008 through 2019, 178 measles cases were identified. 82% of cases lacked necessary vaccination or vaccination records against measles, 35% of cases were linked to traveling outside of Ontario, 20% of cases reported being in contact with a known case, and 72% of cases were less than 5 years old or older than 21. Ten measles clusters were identified of which six were deemed statistically significant. These six significant clusters represented 7% of the population at risk but contained nearly 40% of all reported measles cases between 2008 and 2019. Measles clusters had a strong association with the proportion of immigrants living within them, population density and prevalence of low-income. No association was found between education level and measles clusters. Conclusion The results indicate that most measles cases in Ontario are unvaccinated or lack proof of vaccination; arise through secondary transmission within the province; arise from undetected transmission; and are adults or infants. Additionally, it is possible to see that the risk of reported measles cases is not randomly distributed across the province, but instead measles cases tend to cluster in certain regions. Such clusters tend to be characterized by specific population-level factors that may be contributing to the risk of reported measles. Targeted and equitable interventions are needed as we continue on the path to eradication.

Anecdotal evidence indicated vaccine coverage disparities among foster-care (FCA) and natural-home adolescents (NHA). Arkansas laws require 5 vaccines for school entry (FVSE) to prevent 9 common childhood diseases. The study problem was that Pulaski County, Arkansas adolescent birth cohort (PCABC) immunization rates were low compared to U.S. adolescents for these FVSE. This study examined the extent to which (1) PCABC immunization rates were significantly different from those estimated for U.S. adolescents in 2006–2008, (2) NHA and FCA immunization rates were different in 2003– 2008; (3) sociodemographic variables mediate associations between home of residence (HOR), NHA or FCA, and up to date (UTD) status for FVSE; and (4) vaccination game theory (VGT) estimated deaths differ between individual-equilibrium and group-optimum behaviors. The methodologies applied were direct standardization, χ2, multiple logistic regressions, and VGT to analyze PCABC retrospective secondary data from the Arkansas immunization registry. The results revealed that U.S. adjusted UTD coverage rates for Hepatitis B, measles-mumps-rubella, and varicella were greater than those for PCABC. Race-adjusted FCA immunization rates were 120% higher than for NHA. Race mediated the association between HOR and UTD FVSE status, and African Americans had 80% greater odds of being UTD with FVSE compared to Caucasians. Group-optimum behavior was associated with fewer estimated deaths than individual equilibrium; thus, it is protective against disease outbreaks. Positive social change may occur among the PCABC when healthcare providers include these results in communications with parents at FCA and NHA community health clinics. Parental vaccine acceptance for their children may increase vaccinations and improve PCABC health and wellness.

This study investigated caregivers' perceptions with regard to vaccine-preventable diseases in terms of six constructs of the Health Belief Model. A qualitative research design that is explorative, descriptive and contextual in nature was employed in order to understand and describe the perceptions influencing access and utilisation of services that lead to missed immunisation opportunities and consequently outbreaks of vaccine-preventable diseases. The data-collection techniques were individual unstructured in-depth interviews, field notes and clinical records. The sample consisted of twenty two (N=22) caregivers who volunteered to be interviewed. The study has highlighted that caregivers' perceptions or cognitive factors play an important role for having children in completing immunisation schedule to protect the public from vaccine-preventable diseases. It is recommended that mass media programmes are needed to address the role of vaccines in reducing high morbidity and mortality rates caused by vaccine preventable diseases and improvement in access to immunisation services. / Health Studies / MPH (Health Studies)

This study investigated caregivers' perceptions with regard to vaccine-preventable diseases in terms of six constructs of the Health Belief Model. A qualitative research design that is explorative, descriptive and contextual in nature was employed in order to understand and describe the perceptions influencing access and utilisation of services that lead to missed immunisation opportunities and consequently outbreaks of vaccine-preventable diseases. The data-collection techniques were individual unstructured in-depth interviews, field notes and clinical records. The sample consisted of twenty two (N=22) caregivers who volunteered to be interviewed. The study has highlighted that caregivers' perceptions or cognitive factors play an important role for having children in completing immunisation schedule to protect the public from vaccine-preventable diseases. It is recommended that mass media programmes are needed to address the role of vaccines in reducing high morbidity and mortality rates caused by vaccine preventable diseases and improvement in access to immunisation services. / Health Studies / MPH (Health Studies)

Helper T cells direct the immunological response to foreign pathogens and cancer. To become activated, helper T cells must recognize unique peptides presented on major histocompatibility complex II (pMHCII) by antigen presenting cells (APCs) with their T cell receptor (TCR). While much is known about helper T cell activation signaling cascades and the subsequent roles of helper T cell subsets, the initiation of helper T cell activation by the TCR and other co-receptors is less well understood. Specifically, the affinity of the TCR for its pMHCII can change helper T cell subset fate, proliferation, and alter the risk for activation induced cell death. High affinity TCRs are attractive targets for immunotherapies, but little is known about how helper T cells respond to high affinity TCRs. Here we describe high affinity TCR activation thresholds for both full length TCRs and chimeric antigen receptor TCRs both with and without the presence of the coreceptor CD4 and propose a mechanism whereby CD4 inhibits T cell activation via Lck sequestration and a CD4-independent method. Dysregulated helper T cells play critical roles in the development and perpetuation of systemic lupus erythematosus (SLE), a systemic autoimmune disease that causes widespread inflammation and organ damage throughout the body. Chronic inflammation in SLE affects the immune response to viruses and the risk of developing cancer. However, in SLE patients, it is unclear if viruses initiate the development of cancer directly or if the effects are non-interacting and concomitant. Here we describe the interactions between SLE, viruses, and cancer risk revealing that viruses and SLE do interact to increase the both the overall cancer risk and the risk for hematological malignancies. Due to vaccine efficacy, vaccine preventable diseases (VPDs) are no longer commonly experienced or understood by the public. Vaccines are a victim of their own success and according to the World Health Organization (WHO), vaccine hesitancy (VH) is one of the top threats to global health. VH is the refusal to accept vaccinations and the reasons for VH vary across time, place, and vaccine. Refuting VH is difficult as directly confronting false assumptions can cause individuals to become more entrenched in their position resulting in confirmation bias. Adults with VH attitudes are often motivated by concerns over personal liberty, harm, independence, and body purity. Here we describe the results of a VPD interview- and education-based intervention geared towards promoting positive vaccine attitudes for young adults and demonstrate that education focused on VPDs is more effective than vaccine safety.