The modern multimodal transportation system provides an extensive network for human mobility and commodity exchange around the globe. As a consequence these interactions are often accompanied by disease and other biological infectious agents. This dissertation highlights the versatility of network models in quantifying the combined impact transportation systems, ecological systems and social networks have on the epidemiological process. A set of predictive models intended to compliment the current mathematical and simulation based modeling tools are introduced. The main contribution is the incorporation of dynamic infection data, which is becoming increasingly available, but is not accounted for in previous epidemiological models. Three main problems are identified. The objective of the first problem is to identify the path of infection (for a specific disease scenario) through a social contact network by invoking the use of network based optimization algorithms and individual infection reports. This problem parallels a novel and related problem in phylodynamics, which uses genetic sequencing data to reconstruct the most likely spatiotemporal path of infection. The second problem is a macroscopic application of the methodology introduced in the first problem. The new objective is to identify links in a transportation network responsible for spreading infection into new regions (spanning from a single source) using regional level infection data (e.g. when the disease arrived at a new location). The new network structure is defined by nodes which represent regions (cites, states, countries) and links representing travel routes. The third research problem is applicable to vector-borne diseases; those diseases which are transmitted to humans through the bite of an infected vector (i.e. mosquito), including dengue and malaria. The role of the vector in the infection process inherently alters the spreading process (compared to human contact diseases), which must be addressed in prediction models. The proposed objective is to quantify the risk posed by air travel in the global spread of these types of diseases. / text

Viruses cause 60% of human infections and are probably the most common cause of infectious disease acquired indoors. Rapid spread of viral illness in indoor establishments facilitates disease morbidity and mortality. The goal of this dissertation is to clarify the role of fomites in the viral infection cycle. Research methods include investigation of published literature, and the use of polymerase chain reaction (PCR) for viral detection. The Appendix A study reviewed published literature to assess the significance of fomites in the transmission of ten common respiratory and enteric viruses (rhinovirus, respiratory syncytial virus (RSV), influenza A, parainfluenza 1 (HPIV1), coronavirus, rotavirus, calicivirus, hepatitis A virus (HAV), astrovirus and adenovirus). Results suggest that fomites play an important role in the transmission of common viral pathogens, and the use of disinfectants may limit the spread of viral disease. The Appendix B study examined PCR primer detection limits by determining the time length viruses can be isolated on fomites. Results indicated that poliovirus 1 and hepatitis A virus could be detected for up to 60 days. Parainfluenza 1 virus isolation yielded detection at 30 days and 50 days. Norovirus isolation yielded detection at 20 days and 30 days. Influenza virus isolation results were inconsistent, yielding no initial detection and detection up to 20 days. Appendix C assessed the occurrence of human parainfluenza 1 virus (HPIV1) on surfaces in office settings. HPIV1 was detected on 37% of fomites. HPIV1 was detected most on desktops (47%), and least on light switches (19%). Study results indicated a statistically significant difference between positive fomites in different buildings (Chi-square p < 0.011), and between building cubicles and conference room fomites (Chi-square p < 0.011). Appendix D evaluated the prevalence of influenza A virus on surfaces in day care and home settings. Influenza A was isolated on 23% of fall day care fomites and 53% of spring day care fomites. Influenza was isolated on 59% of home fomites sampled during March, and no influenza was detected on home fomites sampled during the summer. Overall, Influenza A virus was isolated on over 50% of fomites in homes and day care centers.

Infectious disease outbreaks can have a significant impact on healthcare resources and are disruptive to routine healthcare programs and services. There is very little literature on the economic burden of infectious disease outbreaks; thus, this research attempts to provide insight into the healthcare resources used to contain a mumps outbreak. The Nova Scotia 2007 mumps outbreak provides an opportunity to produce a costing framework to capture the economic burden an outbreak has on the Nova Scotia healthcare system. The costing framework for this study used an accounting model to costing; in particular, it used an activity-based costing approach. The total mumps outbreak cost is estimated at $2,478,500 or $3,511 per mumps case. Given the significant impact an infectious disease outbreak has on healthcare resources, more economic evaluations should be done to help guide policies around infectious disease prevention strategies, and to maximize the allocation of healthcare resources.

Host-pathogen investigations have conceptually evolved during the last two decades, from a basic and descriptive approach to a current hypothesis-driven and a more theoretical discipline shaped by evolutionary biology. Our deeper understanding of the elements influencing the mutual selective pressures that the host and the pathogens exert on each other, together with recent conceptual advances, currently position this field of research at the frontier between ecology and evolution. Recent theoretical considerations define hostpathogens systems as an evo-eco mosaic comprised of evolutionary and ecological attributes in turn underlying the context-dependent nature of the system dynamic. Therefore, investigations of host-pathogen interactions should integrate the diversity of the systems drivers by using an integrative approach in order to elucidate both coevolutionary trajectory and epidemiological dynamic of the system. In this thesis, such a framework is used to investigate Amphibian/ranavirus interactions. Ranaviruses are emerging pathogens known to have caused amphibian die-offs on five continents with the greatest number of reported mortality events documented in North America and Europe. Despite an increasing understanding of ranaviral disease properties, ranavirus disease dynamics in the environment remain poorly understood. For instance, the influence of potential abiotic and biotic mechanisms including temperature, local landscape features, larval developmental stages, host density and genetic variability as well as genotypic interactions between the host and the pathogen has on the prevalence and virulence of the virus remains to be elucidated. In order to improve our knowledge regarding these specific determinants of ranaviral disease, I designed a combination of manipulative laboratory experiments and a field mensurative survey using the ranid amphibian Lithobates (Rana) pipiens as the host model for this system. I observed that populations of amphibian hosts inhabiting urbanized landscapes suffered from significant decline in genetic diversity in turn promoting the accrued infection by the ranavirus (manuscript 1). Complementary analysis using two amphibian host species, L.pipiens and L.sylvaticus, and three ranavirus strains revealed significant variation among hosts for their susceptibility to ranavirus, and significant variation among ranavirus strains for infectivity. I also showed that specific amphibian/ranavirus interactions might have a tighter coevolutionary history than other combinations, resulting in sharper mutual coadaptations and the potential for frequency-dependent selection to operate in this system. However, the coevolutionary trajectories in this host-pathogen system are dependent on the temperature conditions in which the interaction takes place. Amphibian/ranavirus interactions outcomes iv are therefore temperature, host, and pathogen genotype-dependent suggesting that the range of infection outcomes in this system is potentially large (manuscript 2). Further, I observed that increasing animal holding density is detrimental for host fitness as mortality rate is higher, day of death earlier, development longer, and growth rate significantly lower when tadpoles are experimentally exposed to ranavirus in high holding density situations. These results paralleled a linear increase of detrimental effects when ranavirus doses increased in low density conditions, with control tadpoles having a significantly higher overall relative fitness. However, this pattern was not observed in high density conditions, where the effects of increasing ranavirus dose were limited, revealing non-trivial density-dependence of virulence expression (manuscript 3). Finally, ranavirus infection rate varied with the host developmental stage as the host immune system clears the infection over the course of individual host development. However the intensity of the clearing depends on both the timing and number of ranavirus exposures (manuscript 4). Overall the results described in my thesis suggest that ranavirus virulence depends on a diversity of ecological, epidemiological, and evolutionary determinants. The underlying complexity of ranavirus

The purpose of this research was to understand how the risks associated with West Nile virus (WNV) were presented by the Winnipeg Free Press. A detailed content analysis was completed on all Winnipeg Free Press articles and Manitoba Health news releases, between 1999 and 2008, containing information related to West Nile. Additional data included interviews with government and media representatives. Several recurring frames, including blame, controversy, rights and fairness, risk, and uncertainty were found in the newspaper data. Over time there was a decrease in both the coverage and prominence of WNV-related issues by the Winnipeg Free Press. In terms of the use of sources by media, the provincial government was found to be the most commonly used source in this context. Reporting of WNV-related issues by the Winnipeg Free Press has been relatively clear and balanced despite some initial alarmist coverage surrounding the uncertainty of the arrival of WNV.

The purpose of this research was to understand how the risks associated with West Nile virus (WNV) were presented by the Winnipeg Free Press. A detailed content analysis was completed on all Winnipeg Free Press articles and Manitoba Health news releases, between 1999 and 2008, containing information related to West Nile. Additional data included interviews with government and media representatives. Several recurring frames, including blame, controversy, rights and fairness, risk, and uncertainty were found in the newspaper data. Over time there was a decrease in both the coverage and prominence of WNV-related issues by the Winnipeg Free Press. In terms of the use of sources by media, the provincial government was found to be the most commonly used source in this context. Reporting of WNV-related issues by the Winnipeg Free Press has been relatively clear and balanced despite some initial alarmist coverage surrounding the uncertainty of the arrival of WNV.

No description available.

This cross-sectional study observed the association of smoke exposure and tuberculosis-related outcomes in Saskatchewan by individuals who had been exposed to someone with infectious TB. This study is unique in that we were quantifying the amount of smoke exposure that increases susceptibility to TB infection and/or active TB. Subjects who were at least 18 years old were enrolled into the study because they were contacts to infectious tuberculosis. The study involved a detailed interview. This interview involved questions on demographics, hair treatment (specifically, hair dying), tobacco smoke exposure, co-morbidities/risk factors, and alcohol consumption. After the interview was conducted, a small 10mg sample of hair was collected from each individual. This was to ensure a more accurate level of smoke exposure was attained. In total, 104 individuals were recruited to participate in this study. Linear regression analysis was used to compare cigarette consumption and nicotine concentration. A quadratic term was added to the linear model and the result was that reported cigarette consumption per day (x) was significantly associated with nicotine concentration (y) where y=0.91+1.35x-0.25x2 (p=0.001). A Fisher’s exact test was conducted to see if there was a relationship between smoking and TB disease; there was no statistically significant association between TB disease and smoking (OR= 3.28, 95%CI 0.37-29.1, p = 0.24). Logistic regression analysis was used to see if there was a relationship between smoking and TB infection. Of the five predictor variables, none were statistically significant. Smokers had an association with higher odds of TB infection (OR=2.03, 95%CI 0.71-5.80, p=0.19). Canadian-born Aboriginals had an association with lower odds of TB infection (OR=0.52, 95%CI 0.18-1.46, p=0.21). The results from this study could provide insight into creating a larger, more complex study involving TB and smoking.

The availability of attenuated, bitypic, genetic recombinant strains of herpes simplex virus (HSV) made possible the following investigations. The recombinant virus, D5E1, exhibited limited, short-lived replication in the central nervous system of mice and guinea pigs. Nevertheless, this virus was sufficient to stimulate substantial levels of neutralizing antibody and localized cellular immunity in genital tissue. Immunization with D5El protected mice and/or guinea pigs against (HSV) type l and 2 infections when the challenge virus was given by a variety of pathways. In particular, it reduced vaginal virus shedding, inflammation, and acute and latent infection of the regional ganglia. The degree of protection in mice was influenced by the strain of rodent, the route of challenge and type of wild virus. Vaccination of newborn mice with live, attenuated virus also resulted in protection against HSV-2 subsequently inoculated into the footpad. The ability of recombinant HSV strains to establish latent ganglionic infection was related to their virulence, the route of inoculation and the genetic strain of the mouse. The D5E1 vaccine failed to establish latent disease by itself, but nevertheless conferred good protection against HSV type 1 or 2 challenge of immunized mice or guinea pigs.

Cardiovascular disease (CVD) is a major cause of morbidity and mortality in the U.S. and worldwide. Atherosclerosis, the buildup of plaque in the arteries, is a common cause of CVD. For many years, research in atherosclerosis was focused on lipid metabolism and the accumulation of low-density lipoprotein in the arteries. While this research set public health guidelines for lipid management, lipid concentration was not the only factor influencing atherosclerosis and CVD events. Many scientists, as far back as the 1850’s recognized the role of inflammation in the progression of atherosclerotic disease. The continuous low levels of immune activation in the body contribute to atherosclerosis. Research in animal models and epidemiologic studies have shown the involvement of both the innate and the adaptive immune systems in plaque development and to elucidate the roles of monocytes and T cells. In addition to animal studies and epidemiologic research, CVD and atherosclerotic research has extended to genetic analysis in the search for associations with risk factors and outcomes. The first chapter is a review of the literature studying the immune system’s involvement in atherosclerosis. Beginning with an examination of the impact of CVD and atherosclerosis, the basic pathophysiology, and the involvement of the innate and adaptive immune systems through animal models and epidemiology. Some of the significant cohort studies in CVD and genome wide association studies are also discussed. Chapter 2 examines the associations of soluble interleukin 2 receptor alpha (sIL-2Rα) with clinical events in the Cardiovascular Health Study and genetic variants. Interleukin 2 (IL-2) and its receptor regulate both tolerance and immunity, IL-2 induces the proliferation and differentiation of T cells, part of the adaptive immune system. The results showed an association between sIL-2Rα and CVD events. The genome-wide association study found 52 variants to be significantly associated with sIL-2Rα in European Americans. Chapter 3 assesses the involvement of the innate immune system in atherosclerosis through the associations of soluble CD163 (sCD163). CD163 is a marker of macrophage activation, specifically associated with M2 macrophages. In CHS, sCD163 levels were analyzed for associations with cardiovascular events and genetic variants. sCD163 was found to be associated with CVD risk factors and with cardiovascular events. In a genome-wide association study six variants in European Americans and three variants in African Americans were found to be significant. Chapter 4 summarizes the results and discusses some bench to bedside translational science already seen in atherosclerosis treatment and prevention. Continued investigation of markers of T-cell and monocyte differentiation in animal models and cohort studies may lead to opportunities for the prevention of atherosclerosis and/or treatment through an increased understanding of the biology and genetics of the innate and adaptive immune.