This study deals with the history of smallpox in Sweden between 1750 and 1900 and the two preventive measures that were used against it: inoculation during the eighteenth and vaccination during the nineteenth Century. Between 1750 and 1800 300,000 children died from smallpox in Sweden. During the nineteenth Century smallpox death rates decreased considerably and by the end of the Century the disease was very rare. The purpose of this study has been to examine the occurrence of smallpox at local, regional and national levels and to explain the changes in the light of general models of the epidemiologic transition. Smallpox mortality has been analyzed by demographic variables such as age, sex, and social class. The adaptation and practise of inoculation and vaccination has been examined by using a model of preventive health care behaviour. When smallpox mortality decreased sharply at the beginning of the nineteenth century, a greater proportion of adults were represented. More men than women died. Due to diminished immunity most of those who were vaccinated became susceptible about ten years later. There is only a slight tendency that smallpox impaired a persons fertility. Sterility, however, often resulted from an infection. Disfiguring facial pockmarks were also a serious complication of smallpox infection. Those who had been infected from smallpox married later in life than those who were susceptible or vaccinated. Inoculation was never widely accepted in eighteenth-century Sweden since a fatalistic attitude did not encourage preventive measures. The physicians monopoly and a general lack of organization were other important impediments. Vaccination was successfully implemented in 1802 and became the single most important factor for the decrease in smallpox mortality. By employing the clergy and allowing everyone to practise vaccination a great majority of the new-born were immunized. Vaccination rates were raised further when the method was made compulsory in 1816. Since there were no risks involved and after experiencing the advantages of vaccination during smallpox epidemics the inhabitants of Sweden were easily to persuaded of its benefits. By then smallpox had changed from a fatal killer to a rare disease. / digitalisering@umu

The purpose of this study was to describe the reasons of Peng-hu medical team participation in infectious disease prevention program. The study discussed the awareness of importance for medical team engaged in disease prevention of community, and obstacles and intervention faced by medical team self-participation in community infectious disease prevention programs. At the end, it discussed cooperated relationships and the essential factors of public-private partnership and also provided conclusion and suggestion to perfect the abilities for medical team self-participation in community infectious disease prevention programs and to have positive functions. The purposes of this study are as follows: (1)to discuss the awareness of importance and advantages and disadvantages of medical team self-participation in community infectious disease prevention programs (2)to know the obstacles of Peng-hu medical team participation in community infectious disease prevention programs. (3)to study the cooperative relationship and essential factors of public-private partnership participation in community infectious disease prevention programs. (4)to conclude the related factors of medical team participation in community infectious disease prevention programs and to compare with the strategies for motivating community infectious disease prevention programs. This study adopted a quality perspective and in-depth interviews. In the research we use the purposive sampling which aims at medical clinic, institute of pharmacy, leaders of medical team member, directors of public healthy center and the head nurses. Besides, we also visited and asked delegates, town or city mayors, principals of school, director generals of community development association and chiefs of village for their advises on medial team who participated in community infectious disease prevention programs in Peng-hu. The conclusions are as follows: (1) it is important for medical team member to participate in community infectious disease prevention programs, because they have professional knowledge and they are at the cutting edge of disease prevention; public healthy center also has to take the responsibility for such program. However, the medical team is usually more utilitarian, so it is necessary to focus on their medical ethic program. (2) The largest benefit for the participation process is that medical team can learn from each other. (3) The obstacles for medical team to participate in infectious disease prevention programs are insufficient manpower, lack of protective equipment, and insufficient finances; therefore, they need help for these three aspects as well. (4) When medical team member promote community infectious disease prevention programs, patients who refuse to go to hospital and cover their condition will be the big obstruction for the program. (5) The understanding of infectious disease and the threat to health are both main factors to affect clinic in participating disease prevention. For public healthy center, the problems are unclear guidelines and political interventions for entire disease prevention. (6) The cross-professional corporation team has to be established and be conducted and integrated by public sector before reaching the goal of disease prevention program. According to the results given above, we suggest that supervisor of healthy care needs to direct and integrate all medical team member and other relevant sectors to organize a corporative team for disease prevention. The information of infectious disease should be announced widely and update frequently. Disease prevention program should be made compulsory in education and medical ethics should be emphasized. Moreover, Organizations without real functioning should be considered abolished for releasing more manpower in the programs.

<p>Linker for activation of T cells (LAT) is a transmembrane adaptor protein that is crucial in linking TCR engagement to downstream signaling events, such as calcium flux and Ras-MAPK pathway. Following TCR engagement, LAT is phosphorylated at its membrane-distal tyrosine residues, which mediates the binding of Grb2/Sos, PLC-&#61543;1, and GADS/SLP-76 complexes. This multi-protein signaling complex initiates signaling cascades eventually leading to the activation of transcription factors that regulate the genes required for T cell proliferation and effector functions. The indispensable role of LAT in thymocyte development has been evidenced as LAT-deficient mice completely lack peripheral T cells. To study the function of LAT in mature T cells, our lab previously generated a conditional knock-in mouse line in which the lat gene can be deleted by Cre recombinase. Deletion of LAT in mature T cells revealed the critical role of LAT in T cell activation. Here, we used this inducible LAT deletion mouse line crossed with the OT-I transgenic mice to study the role of LAT in mature CD8 T cells. </p><p>To analyze the contribution of LAT in CD8 T cells during the course of pathogen infection, we infected mice with Listeria monocytogenes-expressing Ova to elicit activation of antigen-specific CD8 T cells, and then inducibly deleted LAT in these cells at different stages of infection under the control of tamoxifen treatment. We show that LAT is important for maintaining CD8 T cell expansion during the priming phase; however, it is not required for CD8 T cell contraction. In addition, memory CD8 T cell can persist in the absence of LAT, suggesting that LAT-signaling is not necessary for memory maintenance. Nonetheless, these LAT-deficient memory T cells were unable to proliferate or produce cytokines upon secondary infection. Moreover, LAT deficiency accelerates memory differentiation during the effector-to-memory transition, leading to a higher frequency of KLRG1lowIL-7RhighCD62Lhigh memory T cells. Together, these data demonstrate that, while it is dispensable for contraction and memory maintenance, LAT-signaling regulates CD8 T cell memory differentiation and is essential for the memory response against pathogens.</p><p>The fundamental activity of CD8 T cells is to elicit cytotoxicity toward target cells that express foreign antigens, and this is mediated through granule-dependent and Fas ligand-dependent mechanisms. The signaling events that regulate these processes remain unclear. We showed that LAT-deficient cytotoxic T cells (CTLs) failed to upregulate FasL and produce IFN-&#61543; after engagement with target cells. Moreover, they displayed reduced granule-mediated killing. We further dissected the effect of the LAT deletion on each step of granule exocytosis. LAT-deficiency led to altered synapse formation, subsequently causing unstable T cell:APC conjugates. MTOC polarization and granule reorientation were also impaired by LAT-deficiency, leading to reduced granule delivery. Despite these defects, granule release was still observed in LAT-deficient CTLs due to residual calcium flux and PLC activity. This revealed an unexpected finding that CTL function is not entirely dependent on LAT. Collectively, these data indicate that the signaling circuits governing CTLs are programmed to adopt multiple pathways, allowing CTLs to effectively eliminate various pathogens during adaptive immune responses.</p><p>&#8195;</p> / Dissertation

With over 35 million people currently infected, the World Health Organization considers HIV a global pandemic. HIV is characterized by a high mutation rate, which allows it to evade the host immune system and develop resistance to drugs. However, this extraordinary adaptive ability may also be the key to HIV’s demise. Through the field of phylodynamics, the evolutionary behavior of the virus is being studied in an attempt to control the epidemic. In this thesis, three papers are presented in which we analyze sequences generated through the Canadian HIV Strain and Drug Resistance Surveillance program. In chapter 2 we validate a classifier which distinguishes between recent and established infections based on the proportion of mixed bases observed in population-based pol sequences. Our results will help identify recent infections and improve incidence calculations. In chapter 3, we investigate immune-induced patterns in HIV that are shared by patients of the same ethnicity. An understanding of the forces shaping HIV evolution is instrumental to the development of a vaccine relevant to the Canadian epidemic. In chapter 4, we present preliminary results of a historical reconstruction of HIV across the provinces of Canada. This analysis will highlight strategies that have succeeded or failed in controlling the epidemic. Furthermore, our work will establish whether non-B subtypes of HIV are an increasing threat to Canadian public health. Overall, this thesis provides the first country-wide evolutionary and phylogenetic analysis of the HIV epidemic.

In this thesis, we applied local analysis tools (eigenvalue and eigenvalue elasticity analysis, global function elasticity/sensitivity analysis), and global analysis tools (deriving the location and stability of fixed points) to both aggregate and individual-level dynamic models of infectious diseases. We sought to use these methods to gain insight into the models and to evaluate the use of these methods to study their short-term and long-term dynamics and the influences of arameters on the models.<p> We found that eigenvalues are effective for understanding short-term behaviours of a nonlinear system, but less effective in providing insights of the long-term impacts of a parameter change on its behaviours. In term of disease control, local changes of behaviours, yielded from the changes of parameters based on eigenvalue elasticity, are able to alter behaviours in a short-term, especially in the period of a disease outbreak. While eigenvalue elasticity analysis can be helpful for understanding the impact of parameter changes for simple aggregate models, such analyses prove unwieldy and complicated, particularly for models with large number of state variables; and easily fall prey to eigenvalue multiplicity problems for large individual-based models, and istracting artifacts associated with small denominators. In response to these concerns, we introduced other local methods (global function elasticity/sensitivity analyses) that capture many of the advantages of eigenvalue elasticity methods with much greater simplicity. Unfortunately, parameter changes guided by these local analysis techniques are often insufficient to alter behaviours in the longer-term, such as when system behaviours approach stable endemic equilibria. By contrast, the global analytic tools, such as fixed point location and stability analysis, are effective for providing insights into the global behaviours of disease spread in the long-term, as well as their dependence on parameters. Using all of the above analysis as a toolset, we gained some possible insights into combination of local and global approaches. Choice of applying local or global analysis tools to infectious disease models is dependent on the specific target of policy makers as well as model type.

Research has shown that maximal exercise has a significant effect on cells of the immune system. Specifically, lymphocyte count increases during exercise and decreases to a value lower than baseline following an acute exhaustive bout of exercise. The overall lymphocyte response is well characterized, however, the ability of exercise to affect lymphocyte subfractions is unknown to our knowledge. The purpose of this study was to assess and evaluate the affects of a simulated tennis match across two sessions on lymphocyte subsets. Initial measurements such as age, height, weight, skinfold analysis, and heart rate were recorded for each player, as well as blood samples being obtained by a finger prick before and after the tennis sessions. The tennis protocol started with five serves to the deuce court and five serves to the ad court, then individuals hit twenty-four forehands and twenty-four backhands against an oscillating ball machine. Each bout of serves and ground strokes were repeated ten times, with one minute rests in between each session. Before and immediately after completing the tennis trial, subjects were pricked with a lancet on the non dominant hand so to obtain at least two capillary tubes of blood. Whole blood was then added to the antibody cocktail, which is mixed according to the antibodies that were tested, which were CD4, CD8, CD19, CD95, and CX3CR1. Whole blood was added to red blood cell lysis buffer and fixation buffer, and the blood solution was incubated with antibodies specific to cell phenotype. The main results of this study indicated that there was a decrease in mainly post cell counts in pre and post CD19/CD95 measurements (P= .007), an increase in CD8/CX3CR1 in pre counts and an increase then decrease in post counts without wearing the bionic glove (P= .042), and a decrease in CD4 in the post count measurement with the bionic tennis glove (P= .043). The study’s can assist in making recommendations for after match treatment such as health and diet suggestions. Knowledge of prevention and treatment methods are low in the field of tennis and immune functions, so findings in this area could prevent elite athletes from contracting infections between matches.

With over 35 million people currently infected, the World Health Organization considers HIV a global pandemic. HIV is characterized by a high mutation rate, which allows it to evade the host immune system and develop resistance to drugs. However, this extraordinary adaptive ability may also be the key to HIV’s demise. Through the field of phylodynamics, the evolutionary behavior of the virus is being studied in an attempt to control the epidemic. In this thesis, three papers are presented in which we analyze sequences generated through the Canadian HIV Strain and Drug Resistance Surveillance program. In chapter 2 we validate a classifier which distinguishes between recent and established infections based on the proportion of mixed bases observed in population-based pol sequences. Our results will help identify recent infections and improve incidence calculations. In chapter 3, we investigate immune-induced patterns in HIV that are shared by patients of the same ethnicity. An understanding of the forces shaping HIV evolution is instrumental to the development of a vaccine relevant to the Canadian epidemic. In chapter 4, we present preliminary results of a historical reconstruction of HIV across the provinces of Canada. This analysis will highlight strategies that have succeeded or failed in controlling the epidemic. Furthermore, our work will establish whether non-B subtypes of HIV are an increasing threat to Canadian public health. Overall, this thesis provides the first country-wide evolutionary and phylogenetic analysis of the HIV epidemic.

In this thesis, we applied local analysis tools (eigenvalue and eigenvalue elasticity analysis, global function elasticity/sensitivity analysis), and global analysis tools (deriving the location and stability of fixed points) to both aggregate and individual-level dynamic models of infectious diseases. We sought to use these methods to gain insight into the models and to evaluate the use of these methods to study their short-term and long-term dynamics and the influences of arameters on the models.<p> We found that eigenvalues are effective for understanding short-term behaviours of a nonlinear system, but less effective in providing insights of the long-term impacts of a parameter change on its behaviours. In term of disease control, local changes of behaviours, yielded from the changes of parameters based on eigenvalue elasticity, are able to alter behaviours in a short-term, especially in the period of a disease outbreak. While eigenvalue elasticity analysis can be helpful for understanding the impact of parameter changes for simple aggregate models, such analyses prove unwieldy and complicated, particularly for models with large number of state variables; and easily fall prey to eigenvalue multiplicity problems for large individual-based models, and istracting artifacts associated with small denominators. In response to these concerns, we introduced other local methods (global function elasticity/sensitivity analyses) that capture many of the advantages of eigenvalue elasticity methods with much greater simplicity. Unfortunately, parameter changes guided by these local analysis techniques are often insufficient to alter behaviours in the longer-term, such as when system behaviours approach stable endemic equilibria. By contrast, the global analytic tools, such as fixed point location and stability analysis, are effective for providing insights into the global behaviours of disease spread in the long-term, as well as their dependence on parameters. Using all of the above analysis as a toolset, we gained some possible insights into combination of local and global approaches. Choice of applying local or global analysis tools to infectious disease models is dependent on the specific target of policy makers as well as model type.

Contagious Bovine Pleuropneumonia (CBPP), caused by Mycoplasma mycoides mycoides small colony (MmmSC), is a devastating respiratory disease of cattle in Africa, Asia and the Middle East. Little investigation has been done on molecular disease pathogenesis and host response beyond soluble cytokine detection. This study developed and characterized models for three strains of MmmSC of varying severity. Strains used were Gladysdale, Ondangwa and Shawawa. Samples of bronchoalveolar lavage fluid, bronchial biopsy, nasal epithelial cells and blood were obtained prior to and at weekly time points post-infection. Microarray analysis of RNA extracted from samples revealed host cellular pathways and genes important in the pathogenesis of CBPP, including multiple immune system and inflammatory response pathways. A number of pathways whose influence on disease pathogenesis was not immediately clear were also activated, including pathways involved in amino acid synthesis, fat metabolism, and endocrine hormone responses. Microarray results were confirmed with real-time polymerase chain reaction (RT-PCR) of selected genes. Comparative RT-PCR analysis of selected genes between the three strains of MmmSC revealed genes possibly responsible for differential strain virulence, including interleukins 1B, 6, 8, and 18 and the gene nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha (NFKBIA). A similar analysis of selected genes between survivors and nonsurvivors of the virulent Gladysdale strain of MmmSC suggested genes involved in survival, including interleukin 8, calmodulin 2 (CALM2), and NFKBIA. Avenues of additional study were identified.

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