Dissertations / Theses: 'Infectious disease research'

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Rojek, Amanda. "Improving patient centred research during infectious disease outbreaks." Thesis, University of Oxford, 2017. https://ora.ox.ac.uk/objects/uuid:8a53052f-9585-4709-a06e-15586826efce.

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Emerging infectious diseases (EIDs) constitute an important global health security problem. During EID outbreaks, patient centred research can play a significant role in informing evidence-based care for patients, in calibrating public health responses, and in directing effective policy and research. However, to date, this type of research has been limited in impact. This thesis sets out to improve the value of patient centred research in combating EID outbreaks. It provides a structured analysis of what has previously constrained efforts to rapidly accumulate high-quality evidence. It provides primary data from research conducted during an outbreak, and conducted in an outbreak vulnerable setting. And it provides recommendations that aim to facilitate high-quality data collection in future events. This thesis contains four results chapters. Chapter 2 systematically reviews elements of the research response to two EID outbreaks of public health importance. Chapter 3 provides findings of a phase II clinical trial of an investigational therapy for Ebola virus disease (EVD), contextualises the utility of this and comparable work in improving patient care, and discusses the operational feasibility of such work during an epidemic. Chapter 4 focuses specifically on improving one element - disease characterisation - during EID outbreaks. It achieves this through presenting a systematic analysis of bias in the characterisation of EVD and recommends how to prioritise data gathering for high-risk pathogens. Chapter 5 exemplifies how clinical data collection practices can progress between outbreaks. It is the first stage of work undertaken to improve the clinical characterisation of communicable diseases in the vulnerable environment of refugee camps. This thesis demonstrates progress towards having higher quality clinical research conducted during the time frame of an epidemic. Future work can focus on the most important barriers to accelerating research, now that these have been more clearly defined.

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Korobeinikov, Andrei. "Stability and bifurcation of deterministic infectious disease models." Thesis, University of Auckland, 2001. http://wwwlib.umi.com/dissertations/fullcit/3015611.

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Autonomous deterministic epidemiological models are known to be asymptotically stable. Asymptotic stability of these models contradicts observations. In this thesis we consider some factors which were suggested as able to destabilise the system. We consider discrete-time and continuous-time autonomous epidemiological models. We try to keep our models as simple as possible and investigate the impact of different factors on the system behaviour. Global methods of dynamical systems theory, especially the theory of bifurcations and the direct Lyapunov method are the main tools of our analysis. Lyapunov functions for a range of classical epidemiological models are introduced. The direct Lyapunov method allows us to establish their boundedness and asymptotic stability. It also helps investigate the impact of such factors as susceptibles' mortality, horizontal and vertical transmission and immunity failure on the global behaviour of the system. The Lyapunov functions appear to be useful for more complicated epidemiological models as well. The impact of mass vaccination on the system is also considered. The discrete-time model introduced here enables us to solve a practical problem-to estimate the rate of immunity failure for pertussis in New Zealand. It has been suggested by a number of authors that a non-linear dependence of disease transmission on the numbers of infectives and susceptibles can reverse the stability of the system. However it is shown in this thesis that under biologically plausible constraints the non-linear transmission is unable to destabilise the system. The main constraint is a condition that disease transmission must be a concave function with respect to the number of infectives. This result is valid for both the discrete-time and the continuous-time models. We also consider the impact of mortality associated with a disease. This factor has never before been considered systematically. We indicate mechanisms through which the disease-induced mortality can affect the system and show that the disease-induced mortality is a destabilising factor and is able to reverse the system stability. However the critical level of mortality which is necessary to reverse the system stability exceeds the mortality expectation for the majority of human infections. Nevertheless the disease-induced mortality is an important factor for understanding animal diseases. It appears that in the case of autonomous systems there is no single factor able to cause the recurrent outbreaks of epidemics of such magnitudes as have been observed. It is most likely that in reality they are caused by a combination of factors.
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Evans, Jane A. (Jane Amanda). "Modeling social response to the spread of an infectious disease." Thesis, Massachusetts Institute of Technology, 2012. http://hdl.handle.net/1721.1/72647.

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Thesis (S.M.)--Massachusetts Institute of Technology, Sloan School of Management, Operations Research Center, 2012.
This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references (p. 85-88).
With the globalization of culture and economic trade, it is increasingly important not only to detect outbreaks of infectious disease early, but also to anticipate the social response to the disease. In this thesis, we use social network analysis and data mining methods to model negative social response (NSR), where a society demonstrates strain associated with a disease. Specifically, we apply real world biosurveillance data on over 11,000 initial events to: 1) describe how negative social response spreads within an outbreak, and 2) analytically predict negative social response to an outbreak. In the first approach, we developed a meta-model that describes the interrelated spread of disease and NSR over a network. This model is based on both a susceptible-infective- recovered (SIR) epidemiology model and a social influence model. It accurately captured the collective behavior of a complex epidemic, providing insights on the volatility of social response. In the second approach, we introduced a multi-step joint methodology to improve the detection and prediction of rare NSR events. The methodology significantly reduced the incidence of false positives over a more conventional supervised learning model. We found that social response to the spread of an infectious disease is predictable, despite the seemingly random occurrence of these events. Together, both approaches offer a framework for expanding a society's critical biosurveillance capability.
by Jane A. Evans.
S.M.

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Surujon, Defne. "Computational approaches in infectious disease research: Towards improved diagnostic methods." Thesis, Boston College, 2020. http://hdl.handle.net/2345/bc-ir:109089.

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Thesis advisor: Kenneth Williams
Due to overuse and misuse of antibiotics, the global threat of antibiotic resistance is a growing crisis. Three critical issues surrounding antibiotic resistance are the lack of rapid testing, treatment failure, and evolution of resistance. However, with new technology facilitating data collection and powerful statistical learning advances, our understanding of the bacterial stress response to antibiotics is rapidly expanding. With a recent influx of omics data, it has become possible to develop powerful computational methods that make the best use of growing systems-level datasets. In this work, I present several such approaches that address the three challenges around resistance. While this body of work was motivated by the antibiotic resistance crisis, the approaches presented here favor generalization, that is, applicability beyond just one context. First, I present ShinyOmics, a web-based application that allow visualization, sharing, exploration and comparison of systems-level data. An overview of transcriptomics data in the bacterial pathogen Streptococcus pneumoniae led to the hypothesis that stress-susceptible strains have more chaotic gene expression patterns than stress-resistant ones. This hypothesis was supported by data from multiple strains, species, antibiotics and non-antibiotic stress factors, leading to the development of a transcriptomic entropy based, general predictor for bacterial fitness. I show the potential utility of this predictor in predicting antibiotic susceptibility phenotype, and drug minimum inhibitory concentrations, which can be applied to bacterial isolates from patients in the near future. Predictors for antibiotic susceptibility are of great value when there is large phenotypic variability across isolates from the same species. Phenotypic variability is accompanied by genomic diversity harbored within a species. I address the genomic diversity by developing BFClust, a software package that for the first time enables pan-genome analysis with confidence scores. Using pan-genome level information, I then develop predictors of essential genes unique to certain strains and predictors for genes that acquire adaptive mutations under prolonged stress exposure. Genes that are essential offer attractive drug targets, and those that are essential only in certain strains would make great targets for very narrow-spectrum antibiotics, potentially leading the way to personalized therapies in infectious disease. Finally, the prediction of adaptive outcome can lead to predictions of future cross-resistance or collateral sensitivities. Overall, this body of work exemplifies how computational methods can complement the increasingly rapid data generation in the lab, and pave the way to the development of more effective antibiotic stewardship practices
Thesis (PhD) — Boston College, 2020
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Biology

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Sattar, Shahra. "Influence of HIV, smoking and hyperglycaemia on the reporting of TB symptoms in a TB prevalence survey." Master's thesis, University of Cape Town, 2013. http://hdl.handle.net/11427/3065.

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Includes abstract.
Includes bibliographical references.
Finding and treating cases [of tuberculosis] in the community before they present to health facilities, a strategy known as active-case-finding is gaining momentum as a way to decrease the infectious pool. This can be achieved through door-to-door community surveys using a TB symptom-screening questionnaire, and is an economical and practical tool to employ in poor, high burden areas. However, unlike for the high risk group of people infected with HIV, there is a lack of evidence supporting the adaptation of a symptom screening tool in the other high risk groups. In 2010, a TB prevalence survey was conduceted in 24 high TB and HIV burden communities in Zambia and the Western Cape, South Africa. This prevalence survey served as the endpoint for the Zambia and South Africa TB and AIDS Reduction study (ZAMSTAR). This survey made use of a questionnaire the collected, among other information, data regarding individual TB symptom reporting, HIV status, diabetes mellitus status and cigarette smoking.

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Ye, X., J. N. Van, F. M. Munoz, P. A. Revell, Claudia A. Korinetz, R. A. Krance, R. L. Atmar, M. K. Estes, and H. L. Koo. "Noroviruses as a Cause of Diarrhea in Immunocompromised Pediatric Hematopoietic Stem Cell and Solid Organ Transplant Recipients." Digital Commons @ East Tennessee State University, 2015. https://dc.etsu.edu/etsu-works/1490.

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Case reports describe significant norovirus gastroenteritis morbidity in immunocompromised patients. We evaluated norovirus pathogenesis in prospectively enrolled solid organ (SOT) and hematopoietic stem cell transplant (HSCT) patients with diarrhea who presented to Texas Children's Hospital and submitted stool for enteric testing. Noroviruses were detected by real-time reverse transcription polymerase chain reaction. Clinical outcomes of norovirus diarrhea and non-norovirus diarrhea patients, matched by transplanted organ type, were compared. Norovirus infection was identified in 25 (22%) of 116 patients, more frequently than other enteropathogens. Fifty percent of norovirus patients experienced diarrhea lasting ≥14 days, with median duration of 12.5 days (range 1–324 days); 29% developed diarrhea recurrence. Fifty-five percent of norovirus patients were hospitalized for diarrhea, with 27% requiring intensive care unit (ICU) admission. One HSCT recipient developed pneumatosis intestinalis. Three HSCT patients expired ≤6 months of norovirus diarrhea onset. Compared to non-norovirus diarrhea patients, norovirus patients experienced significantly more frequent ICU admission (27% vs. 0%, p = 0.02), greater serum creatinine rise (median 0.3 vs. 0.2 mg/dL, p = 0.01), and more weight loss (median 1.6 vs. 0.6 kg, p < 0.01). Noroviruses are an important cause of diarrhea in pediatric transplant patients and are associated with significant clinical complications.

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Kim, Louis Y. (Louis Yongchul). "Estimating network structure and propagation dynamics for an infectious disease : towards effective vaccine allocation." Thesis, Massachusetts Institute of Technology, 2014. http://hdl.handle.net/1721.1/91397.

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Thesis: S.M., Massachusetts Institute of Technology, Sloan School of Management, Operations Research Center, 2014.
76
Cataloged from PDF version of thesis.
Includes bibliographical references (pages 67-72).
In the event of a pandemic influenza outbreak, such as the 2009-2010 H1N1 "Swine Flu" episode, it is crucial to effectively allocate limited resources in order to minimize the casualties. Design of effective resource allocation strategies requires good understanding of the underlying contact network and of the propagation dynamics. In this thesis we develop a parameter estimation method that learns the network structure, among a family of graphs, and disease dynamics from the recorded infection curve, assuming that the disease dynamics follow an SIR process. We apply the method to data collected during the 2009-2010 H1N1 epidemic and show that the best-fit model, among a scale-free network and a small-world network, indicates the scale-free network. Given the knowledge of the network structure we evaluate different vaccination strategies. As a benchmark, we allow the vaccination decisions to depend on the state of the epidemic and we show that random vaccination (which is the current practice), does not efficiently halt the spread of influenza. Instead, we propose vaccine allocation strategies that exploit the underlying network structure and provide a reduction in the number of infections by over 6 times compared to the current practice. In addition, more realistic scenario involves random encounters between agents. To test this hypothesis, we introduced a dynamic network formation on top of the static network model. We apply the estimation method to the dynamic network model and show a small improvement in estimating the infection dynamics of the 2009-2010 H1N1 influenza.
by Louis Y. Kim.
S.M.

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Marmara, Vincent Anthony. "Prediction of Infectious Disease outbreaks based on limited information." Thesis, University of Stirling, 2016. http://hdl.handle.net/1893/24624.

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The last two decades have seen several large-scale epidemics of international impact, including human, animal and plant epidemics. Policy makers face health challenges that require epidemic predictions based on limited information. There is therefore a pressing need to construct models that allow us to frame all available information to predict an emerging outbreak and to control it in a timely manner. The aim of this thesis is to develop an early-warning modelling approach that can predict emerging disease outbreaks. Based on Bayesian techniques ideally suited to combine information from different sources into a single modelling and estimation framework, I developed a suite of approaches to epidemiological data that can deal with data from different sources and of varying quality. The SEIR model, particle filter algorithm and a number of influenza-related datasets were utilised to examine various models and methodologies to predict influenza outbreaks. The data included a combination of consultations and diagnosed influenza-like illness (ILI) cases for five influenza seasons. I showed that for the pandemic season, different proxies lead to similar behaviour of the effective reproduction number. For influenza datasets, there exists a strong relationship between consultations and diagnosed datasets, especially when considering time-dependent models. Individual parameters for different influenza seasons provided similar values, thereby offering an opportunity to utilise such information in future outbreaks. Moreover, my findings showed that when the temperature drops below 14°C, this triggers the first substantial rise in the number of ILI cases, highlighting that temperature data is an important signal to trigger the start of the influenza epidemic. Further probing was carried out among Maltese citizens and estimates on the under-reporting rate of the seasonal influenza were established. Based on these findings, a new epidemiological model and framework were developed, providing accurate real-time forecasts with a clear early warning signal to the influenza outbreak. This research utilised a combination of novel data sources to predict influenza outbreaks. Such information is beneficial for health authorities to plan health strategies and control epidemics.

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Kasaie, Sharifi Parasto Alsadat. "Agent-Based Simulation Modeling and Analysis of Infectious Disease Epidemics and Implications for Policy." University of Cincinnati / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1396531551.

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Hardison, Rachael Lake. "Haemophilus pathogenesis during otitis media: Influence of nutritional immunity on bacterial persistence and intracellular lifestyles." The Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu1540483623343597.

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Tay, Chin Hun. "In Vivo Regulation of Murine Cytomegalovirus Infections: The Role of Cell Surface Molecules and Mechanisms of Control by Natural Killer Cells: A Dissertation." eScholarship@UMMS, 1997. https://escholarship.umassmed.edu/gsbs_diss/64.

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The overall aim of this thesis was to determine how natural killer (NK) cells regulate virus infections in vivo. Anti-viral mechanisms by which NK cells control murine cytomegalovirus (MCMV) infection in the spleens and livers of adult C57BL/6 mice were first studied, revealing different mechanisms of control in different organs. Three days post-infection, MCMV titers in the spleens of perforin-deficient (perforin 0/0) mice were higher than in wild type controls, but no elevation of liver titers was found in perforin 0/0 mice. NK cell depletion in MCMV-infected perforin 0/0 mice resulted only in an increase in liver viral titers but not in spleen titers. Depletion of IFN-γ in adult C57BL/6 mice by injections with mAbs to IFN-γ resulted in an increase in viral titers in the liver but not in the spleen. Analyses using IFN-γ-receptor-deficient (IFN-γR0/0) mice, rendered chimeric with C57BL/6 bone marrow cells, indicated that even though the donor spleen cells could respond to IFN-γ, the depletion of NK cells in a recipient environment where the host cells could not respond to IFN-γ caused an increase in MCMV titers in the spleens but had little effect in the liver. IFN-γ has the ability to induce a variety of cells to produce nitric oxide (NO), and administrating the nitric oxide synthase (NOS) inhibitor Nω-monomethyl-L-arginine (L-NMA) into MCMV-infected adult C57BL/6 mice resulted in MCMV titer increases in the liver but not in the spleen. These data indicate that in adult C57BL/6 mice, there is a dichotomy in the mechanisms utilized by NK cells in the regulation of MCMV in different organs. In the spleen NK cells exert their effects in a perforin-dependent manner, suggesting a cytotoxic mechanism, whereas in the liver the production of IFN-γ by NK cells may be a predominant mechanism in the regulation of MCMV synthesis. These results may explain why the Cmv-1r (Cmv-1-resistant) locus, which maps closely to genes regulating NK cell cytotoxic function, confers an NK cell-dependent resistance to MCMV infection in the spleen but not in the liver. The ability of adoptively transferred cells to protect suckling mice from MCMV was another model used to study the mechanisms utilized by NK cells in the regulation of MCMV. Adoptive transfers of 129, C57BL/6 and perforin 0/0 spleen cells or lymphokine-activated killer (LAK) cells into 4 - 6 day old MCMV-infected C57BL/6 suckling mice significantly lowered the splenic MCMV titers in these mice compared to the infected controls. Adoptive transfers of C57BL/6 spleen cells into MCMV-infected 129 suckling mice also decreased the amount of MCMV in the 129 suckling mice, but C57BL/6 spleen cells could not regulate MCMV synthesis when adoptively transferred into 129/IFN-γR0/0 suckling mice. These results suggest that, in the suckling mouse model, the regulation of MCMV by the adoptively transferred NK cells is via an IFN-γ-dependent, perforin-independent, Cmv-1-independent mechanism. The Cmv-1 gene locus resides within the NK gene complex, in close proximity to the Ly49 NK cell receptor family. Analyses were carried out to determine if any of the 4 known Ly49 NK cell receptors (Ly49A, C, D and G2) played a role in the control of MCMV synthesis by NK cells. Studies comparing the expression of the different Ly49 NK cell subsets in the spleen and the peritoneal cavity revealed that there were differences in the distribution of the Ly49 receptors on NK1.1+ cells. Three days post-MCMV infection, the percentage of NK1.1+- Ly49+ NK cells in the spleen and the peritoneal cavity were different than in naive controls. Within the splenic NK1.1+ population, increases in NK1.1+ -Ly49A+ and NK1.1+-Ly49G2+ cells but decreases in NK1.1+-Ly49C+ and NK1.1+-Ly49D+ cells were observed. These changes in the spleen were accompanied by a concomitant decrease in NK1.1+ - Ly49A+ cells and increases in NK1.1+-Ly49C+, NK1.1+-Ly49D+ and NK1.1+-Ly49G2+ cells within the NK1.1+ population in the peritoneal cavity. These data suggest that 3 days post-MCMV infection, there may be movement of NK cells between the different organs. The role of Ly49 NK cell receptors in the regulation of MCMV was tested using adult C57BL/6 mice depleted of single or multiple Ly49 NK cell subsets. These in vivo depletions did not affect the ability of the residual NK cells to regulate MCMV synthesis. LAK cells sorted into the different Ly49 NK cell subsets and adoptively transferred into C57BL/6 suckling mice lowered the splenic MCMV titers in these mice. Together, these results indicate that even though there is a redistribution of the Ly49 NK cell subsets during MCMV infection, the presence or absence of anyone of the 4 tested Ly49 NK cell receptors does not affect the regulation of MCMV by NK cells. However, there remain a possibility that one of the undefined Ly49 receptors or an untested NK cell receptor may be important in the control ofMCMV. Most of the cloned NK cell receptors have been shown to bind to MHC class I molecules, and MHC class I antigens have been implicated as modulators of target cell sensitivity to NK cell-mediated lysis. The regulation of virus infections and the fate of NK cells and their natural targets was examined in β2-microglobulin-deficient mice [β2m (-/-)], which have defective MHC class I expression. Infections with either the NK cell-sensitive MCMV or the NK cell-resistant lymphocytic choriomeningitis virus (LCMV) significantly augmented NK cell activity in either C57BL/6 or β2m (-/-) mice. Depletion of NK cells in vivo with antiserum to asialo GM1 markedly enhanced the synthesis of MCMV but had no effect on the synthesis of LCMV in either strain of mouse. Adoptively transferred β2m (-/-) spleen cells lowered splenic MCMV titers in C57BL/6 suckling mice, not unlike adoptively transferred C57BL/6 spleen cells. Analysis of naturally NK cell-sensitive thymocyte targets from these virus-infected β2m (-/-) mice revealed no cell surface expression of class I MHC detectable by conformation-dependent or -independent antibodies, but the virus infections enhanced class I expression on thymocytes from C57BL/6 mice. The sensitivity of C57BL/6 thymocytes to NK cell-mediated lysis was markedly reduced after in vivo poly inosinic:cytidylic (poly I:C) treatment or viral infection; in contrast, the sensitivity of the β2m (-/-) thymocytes was significantly less affected by poly I:C or viral infection. These data indicate that the normal expression of MHC class I antigens on NK cells or their targets is not required for the anti-viral functions of NK cells against an NK-sensitive virus (MCMV) nor do they protect an NK-resistant virus (LCMV) from the anti-viral activity of NK cells. Together, the data presented in this thesis help to further our understanding of the mechanisms utilized by NK cells in the control ofMCMV in both adult and suckling mice, and also help clarify the roles played by Ly49 NK cell receptors and MHC class I molecules in the regulation of MCMV.

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Campbell, Regenia Beth Phillips. "Arrested and Aberrant: Effects of Amoxicillin in a Murine Model of Chlamydial Infection." Digital Commons @ East Tennessee State University, 2013. https://dc.etsu.edu/etd/2269.

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Chlamydia trachomatis is the most common sexually transmitted bacterial disease agent worldwide, and, though frequently asymptomatic, can cause extreme pathology including infertility. Chlamydial species exhibit a unique biphasic developmental cycle. Once attached to a cell surface, infectious elementary bodies (EB) are internalized within an inclusion, the membrane-bound structure in which EB transform to noninfectious, replicable reticulate bodies (RB). After multiple rounds of division, RB condense to form EB, which are released and can infect new host cells. In culture, exposure to stressors, such as beta-lactam antibiotics, induce chlamydiae to reversibly detour from normal development into a noninfectious, viable state termed persistence. Cell culture data suggest that persistent forms are resistant to azithromycin (AZM), a front-line antibiotic, and are able to alter the host transcriptome. Though persistence has been described in culture for over 50 years, whether or not it: i) occurs in vivo; and ii) influences chlamydial pathogenesis, transmission and therapy has remained unresolved. To address these questions, we developed an animal model of persistent chlamydial infection using amoxicillin (AMX) treatment. AMX exposure decreased shedding of infectious chlamydiae in C. muridarum-infected mice without affecting chlamydial viability, demonstrating the presence of persistent chlamydiae. Shedding of infectious EB resumed following AMX cessation. Shedding data and microarray analyses suggested that host immunity might limit chlamydia’s exit from persistence in our model. Thus, we hypothesized that cyclophosphamide (CTX) treatment would increase the magnitude of chlamydial shedding observed after AMX-treatment cessation. CTX treatment increased post-AMX shedding by more than 10-fold compared to AMX-only controls. To determine whether persistent chlamydiae are resistant to antibiotic eradication in vivo, we induced persistence by administering AMX and treated mice with various AZM dosing regimes. Persistently infected mice demonstrated increased treatment failure following AZM therapy compared to productively infected controls. These data suggest that persistent chlamydiae are refractory to treatment in vivo and provide an explanation for the observation that treatment fails in some patients. In addition to creating the first fully characterized, experimentally tractable, in vivo model of chlamydial persistence, these experiments provide evidence that persistent/stressed chlamydial forms may serve as a long-term reservoir of infectious organisms in vivo.

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Zelic, Matija. "The Role of RIPK1 Kinase Activity in Regulating Inflammation and Necroptotic Death." eScholarship@UMMS, 2018. https://escholarship.umassmed.edu/gsbs_diss/952.

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Necroptosis, a type of regulated necrotic cell death, involves cell membrane permeabilization and has been implicated in various acute and chronic pro-inflammatory diseases, including ischemia-reperfusion injury and neurodegenerative diseases. By using in vitro reconstitution studies and a chemical inhibitor, the kinase activity of the serine/threonine kinase RIPK1 had been shown to regulate necroptotic signaling downstream of TNF and Toll-like receptors (TLRs). To investigate the contribution of RIPK1 kinase activity to inflammation and necroptosis in vivo, we generated kinase inactive RIPK1 knock-in mice. Utilizing fibroblasts and macrophages from these mice, we demonstrate that RIPK1 kinase activity is required for necroptotic complex formation and death induction downstream of TNFR1 and TLRs 3 and 4. We show that RIPK1 kinase inactive mice are resistant to TNF-induced shock and exhibit impaired upregulation of TNF-induced cytokines and chemokines in vitro and in vivo. By using bone marrow reconstitution experiments, we demonstrate that RIPK1 kinase activity in a non-hematopoietic lineage drives TNF-induced lethality. We establish that RIPK1 kinase activity is required for TNF-induced increases in intestinal and vascular permeability and clotting, and implicate endothelial cell necroptosis as an underlying factor contributing to TNF/zVAD-induced shock. Thus, work in this thesis reveals that RIPK1 kinase inhibitors may have promise in treating shock and sepsis.

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Seedhom, Mina O. "Immunity, Pathogenesis, and Prevention of Poxvirus Infections: A Dissertation." eScholarship@UMMS, 2010. https://escholarship.umassmed.edu/gsbs_diss/514.

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Vaccinia virus (VAC) is the prototypical member of the orthopoxvirus genus of the poxvirus family and the virus used for smallpox vaccinations. The following describes the testing of VAC variants designed to have similar immuno-protective profiles with decreased pathogenicity, examines the immune response to VAC after lethal infection in wild type and lupus-prone mice, and describes a method that allows for the enumeration of VAC-specific CD8+ T in naïve and VAC-immune mice. The first part describes work examining VAC Wyeth (VAC-Wy) variants engineered to be less pathogenic in vivo. VAC-Wy variants included genes that code for three immunomodulatory proteins, an interferon-γ (IFNγ) binding protein (B8R), an interleukin 18 (IL-18) binding protein (C12L), and a complement binding protein (C3L, or C21L) or various combinations of the three knockouts, and a triple knockout (VAC-Wy -/-/-) in which all three genes were knocked out of a variant virus. The immunomodulatory effects of other IFNγ binding proteins on VAC-Wy pathogenesis in the mouse were also examined. Virus recombinants where the B8R gene was replaced with a truncated mouse IFNγ receptor gene or a gene that encodes a B8R/IFNγ fusion that allows for dimerization of the secreted IFNγ receptor were studied. As the knockouts and variants were made in the current vaccine VAC-Wy strain, only high dose (1x107 PFU’s) intra nasal (I.N.) infection of mice reliably resulted in detectable virus in the lungs. Further testing revealed that all knockout and variant viruses grew to similar levels after high dose I.N. infections. Protection induced by vaccination with the VAC-Wy variants was studied in comparison to immunizations with the VAC-Wy parental strain. Mice were immunized by tail skin scarification to mimic human immunizations, and this was followed months later by I.N. challenge with 20 LD50’s of VAC-WR. All VAC-Wy recombinants tested, including the VAC-Wy -/-/-, provided similar levels of protection as the parental VAC-Wy strain from a lethal VAC-WR I.N. infection. Mice immunized with the VAC-Wy -/-/- induced similar amounts of neutralizing antibody and similar numbers of CD8+ T cells specific to a subdominant determinant as VAC-Wy. While examining high dose, normally lethal, VAC-WR I.N. infections, a profound splenic CD8+ T cell immune suppression was noted that might have been caused by Fas dependent activation induced cell death (AICD). Using high dose intra-peritoneal (I.P.) and I.N. models of VAC-WR infection, decreased weight loss, decreased virus titers, and increased T cell numbers were found in Fas mutant (B6.MRL-Faslpr/J) mice in comparison to B6 wild type mice on day 6. It would be expected that Fas-deficient CD8+ T cells from B6.MRL-Faslpr/J mice (B6-lpr) would survive a high dose VAC-WR infection better than CD8+ T cells that could express Fas if T cells were being eliminated by Fas-dependent AICD, but co-adoptive transfer experiments using splenocytes from B6-lpr and B6.Cg- IgHaThy-1aGPi-1a/J (IgHa) wild type counterparts found no difference in the numbers or proliferation of donor CD8+ T cells at day 6. As the B6-lpr mice were better protected from VAC-induced weight loss early after lethal VAC-WR infections, it was possible that B6-lpr mice might be protected early in infection. In fact, Fas mutant mice had decreased virus loads in the fat pads, livers, and spleens in comparison to B6 wild type mice at days 2 and 3. In addition to the decreased virus titers, the severe splenic lymphocyte deficiency noted in B6 wild type mice as early as day 2 after high dose I.P. infection was ameliorated in B6-lpr mice. Further experiments demonstrated that uninfected B6-lpr mice had increased numbers of memory phenotype (CD44+) CD4+, CD8+ and γδ+ T cells, with an increased number of γδ+ T cells and NK cells in splenic lymphocytes in comparison to wild type B6 mice. Uninfected B6-lpr mice also had increased numbers of IFNγ+ CD8+ T cells after polyclonal stimulation with an antibody against CD3ε. In lymphocyte depletion experiments performed at day 3, antibody depletion of CD4, CD8, or NK or treatment with an antibody that was specific to the γδ+ TCR did not significantly alter virus loads in B6-lpr mice. In co-adoptive transfer experiments, splenocytes from wild type or B6-lpr mice survived high dose VAC-WR challenge similarly suggesting that B6- lpr splenocytes were not intrinsically better protected from lymphocyte depletion by lack of the Fas protein. On day 2 after high dose I.P. VAC-WR infection, B6- lpr mice had increased numbers of IFNγ+ NK cells, IFNγ+ CD8+ T cells, and IFNγ+ CD4+ T cells. B6-lpr and B6 mice treated with an antibody against IFNγ had significantly increased virus titers in the spleens and livers. Interestingly, there was no significant difference in liver or spleen virus titers when comparing anti- IFNγ antibody treated B6 mice or anti-IFNγ antibody treated B6-lpr mice. These results suggest that multiple leukocyte populations co-operatively or redundantly provide B6-lpr mice with increased protection from high dose VAC-WR infections through increased production of IFNγ. The third part of this work describes the enumeration of total numbers of pathogen-specific CD8+ T cells in a mouse through use of an in vivo limiting dilution assay (LDA). The extensive proliferation of virus-specific CD8+ T cells that occurs after virus infection was used to enumerate numbers of virus-specific CD8+ T cells in a naïve mouse. By transferring limiting amounts of carboxyfluorescein succinimidyl ester (CFSE)-labeled Thy1.1+Ly5.2+ heterogeneous CD8+ T cells into Thy1.2+Ly5.1+ hosts, CD8+ T cell precursor frequencies to whole viruses can be calculated. The calculations are based on finding the number of donor CD8+ T cells that results in CFSElo (i.e. proliferated) donor CD8 T cells in 50% of the hosts. Using probit or Reed and Muench 50% endpoint calculations, CD8+ T cell precursor determinations were made for naïve and immune states to a virus challenge. It was found that in naïve B6 mice, 1 in 1444 CD8+ T cells proliferated in response to VAC-WR (~13,852 VAC-WR-specific CD8+ T cells per mouse) and 1 in 2956 proliferated in response to lymphocytic choriomeningitis virus (LCMV) (~6,761 LCMV-specific CD8+ T cells per mouse). In mice immune to VAC-WR, the number of VAC-WR-specific LDA precursors, not surprisingly, dramatically increased to 1 in 13 (~1,538,462 VAC-WR- specific CD8+ T cells per mouse) consistent with estimates of VAC-WR-specific memory T cells. In contrast, precursor numbers to LCMV did not increase in VAC-WR-immune mice (1 in 4562, ~4384 LCMV-specific CD8+ T cells in a VAC-WR-immune mouse) consistent with the fact that VAC-WR provides no heterologous immunity to LCMV. Using H-2Db-restricted LCMV GP33-specific P14 transgenic T cells it was found that, after accounting for take of donor T cells, approximately every T cell transferred underwent a full proliferative expansion in response to an LCMV infection and a high efficiency was also seen in memory populations. This suggests that most antigen-specific T cells will proliferate in response to infections at limiting dilution. These results, which are discussed in comparison to other methods, show that naïve and memory CD8+ T cell precursor frequencies to whole viruses can be remarkably high. In total this work further advances knowledge of the immunity, pathogenesis, and prevention of poxvirus infections. This was accomplished by studying VAC-Wy recombinants as improved vaccines, by examining the mechanisms and cell types important in early protection from high dose poxvirus infections in B6 and B6-lpr mice, and by describing a method to enumerate total numbers of virus-specific CD8+ T cells in a mouse.

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15

Raval, Forum M. "Innate Signaling Pathways in the Maintenance of Serological Memory: A Dissertation." eScholarship@UMMS, 2012. https://escholarship.umassmed.edu/gsbs_diss/635.

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Long-term antiviral antibody responses provide protection from re-infection and recurrence of persistent viruses. Using a polyomavirus (PyV) mouse model, our lab has shown that MyD88-deficient mice generate low levels of virus-specific IgG after the acute phase of infection and that these IgG responses have a skewed isotype distribution with low levels of IgG2a/c. Moreover MyD88-deficient mice have reduced numbers of long-lived plasma cells in the bone marrow. These studies suggest an important role of MyD88-mediated signaling in long-term antiviral responses. Our lab has shown that T cell-deficient mice can also maintain long-term virus-specific IgG responses following PyV infection. The goal of this thesis is to evaluate the role of innate signaling pathways in maintaining serological memory to persistent virus infection and to elaborate on how long-term antiviral responses can be maintained in an immunocompetent or partially immune compromised, T cell-deficient host. Regarding T cell-dependent B cell responses, I set out to investigate the upstream and downstream components of the MyD88-mediated pathways required for normal antibody isotype and long-term humoral responses. IgG2a is a predominant immunoglobulin isotype in most virus infections. Wild type mice, in response to PyV infection, primarily induce antiviral IgG2a with some IgG1. MyD88-deficient mice in response to PyV infection display attenuated levels of virus-specific IgG2a, but normal levels of IgG1. Using Unc93B1 mutant mice (3d mice), which are defective in TLRs 3, 7 and 9 signaling, I show that 3d mice also generated low levels of virus-specific IgG2a following PyV infection. Studies in individual TLR3-/-, TLR7-/- or TLR9-/- mice displayed PyV-specific IgG2a responses similar to wild type responses. TLR7 and TLR9 double deficient mice generated similar skewed antibody isotype responses, where virus-specific IgG2a was reduced compared to wild type mice. This shows that TLR7 and TLR9-MyD88 mediated pathways are important in regulating IgG2a responses during a PyV infection. To investigate what components downstream of MyD88 are involved in mediating IgG2a responses, I worked with IRF5-deficient mice. IRF5 is a transcription factor that is activated upon stimulation of TLR7 or TLR9-MyD88-mediated pathways. Moreover, IRF5-deficient mice cannot generate autoantibodies specifically of the IgG2a isotype in a mouse lupus model, suggesting that IRF5 plays an important function in mediating class switching to IgG2a. In vitro studies where IRF5-/- B cells were stimulated with TLR7 or TLR9 ligands also generated low levels of γ2a germ-line transcripts, suggesting a B cell-intrinsic role for IRF5 in regulating γ2a germ-line transcription. PyV infection of IRF5-deficient mice resulted in similar skewed isotypes as observed in MyD88-deficient and 3d mice. To investigate a B cell-intrinsic role for IRF5 in regulating IgG2a responses in vivo upon PyV infection, I transferred IRF5-/- B cells and WT T cells into RAG KO mice prior to infection and compared the responses of these mice with mice reconstituted with wild type B6 B and T cells. Diminished numbers of IgG2a+ B cells and reduced levels of virus-specific IgG in mice reconstituted with IRF5-/- B cells were seen compared to mice reconstituted with wild type B cells. Regarding the defect in long-term IgG production in MyD88-/- mice upon PyV infection, I conducted studies in IRF5-/-, 3d, single TLR3-/-, TLR7-/-, TLR9-/- and TLR7/9 double deficient mice. These studies reveal an important and redundant role for TLR7- and TLR9-MyD88 signaling in maintaining long-term anti-PyV IgG responses. To determine how MyD88 signaling affects the generation of long-lived plasma cells and memory B cells, I investigated germinal center (GC) responses in MyD88-deficient mice. A defect in GC B cell numbers is observed in MyD88-deficient mice after the acute phase of infection. The GC reaction is essential for the generation and maintenance of long-lived plasma cells and memory B cells. T follicular helper (TFH) cells are absolutely required to generate normal GC. l found reduced numbers of TFH cells in MyD88-deficient mice. Lower numbers of T FH cells suggests that poor T cell help may contribute to the diminished number of GC B cells. However, interaction with B cells is required for the formation of fully differentiated TFH cells. Along with B cell function, MyD88 signaling can affect T cell and dendritic cell function as well. Thus, it is not clear at this point whether the requirement for intact MyD88 signaling for the formation and maintenance of long-term B cell populations is completely B cell-intrinsic. Some viruses can induce T cell-independent B cell responses, perhaps due to their complex arrays of repetitive antigenic epitopes on virions, coupled with the induction of innate cytokines. Nevertheless, T cell help is usually necessary for generating long-term antibody responses in the form of long-lived plasma cells and memory B cells. In contrast, our lab has found that T cell-deficient mice infected with PyV develop long-lasting, protective antiviral IgG responses. I questioned whether these mice could generate TI B cell memory cells or long-lived plasma cells. I show that long-lasting anti-PyV antibody in T cell-deficient mice was not due to the presence of long-lived plasma cells or memory B cell responses. TCRβδ deficient mice, which lack both CD4 and CD8 T cells, had ~10 a times higher virus load persisting in various organs. Therefore, I hypothesized that the high level of persistent PyV antigen, in completely T cell-deficient mice, may activate naïve B cell populations continuously, thereby maintaining the long-lasting IgG responses. Prior to PyV infection, T cell-deficient mice received wild type CD8 T cells, which reduced PyV loads, and this was associated with decreased levels of antiviral serum IgG over time. As in TCRβδ deficient mice, high PyV loads were detected in the bone marrow, which is the site for B cell lymphopoiesis, I questioned how B cells develop in the presence of PyV antigen and still stay responsive to PyV, generating long-term antiviral IgG responses in the periphery. Studies have shown that self-antigens that trigger both B cell receptor signaling and TLR-MyD88 signaling pathways in the bone marrow lead to the breaking of B cell tolerance and production of autoantibody in the periphery. Thus, we hypothesized that high PyV levels in the bone marrow signal through both B cell-receptors and TLRs, allowing continuous antiviral antibody production by B cells. Using mice that are deficient in T cells and MyD88 signaling, I found that PyV-specific TI IgG levels gradually decreased, supporting this hypothesis. Thus, high PyV loads and innate signaling together can break B cell tolerance. During a persistent virus infection this can result in sustaining long-term protective T cell-independent IgG responses.

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Prieto, Diana. "Modeling and Surveillance of Pandemic Influenza Outbreaks." Scholar Commons, 2011. http://scholarcommons.usf.edu/etd/3297.

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Pandemic outbreaks are unpredictable as to their virus strain, transmissibility, and impact on our quality of life. Hence, the decision support models for mitigation of pandemic outbreaks must be user-friendly and operational, and also incorporate valid estimates of disease transmissibility and severity. This dissertation research is aimed at 1) reviewing the existing pandemic simulation models to identify their implementation gaps with regard to usability and operability, and suggesting research remedies, 2) increasing operability of simulation models by calibrating them via an epidemiological model that estimates infection probabilities using viral shedding profiles of concurrent pandemic and seasonal influenza, and 3) developing a testing strategy for the state laboratories, with their limited capacities, to improve their ability to estimate evolving transmissibility parameters. Our review of literature (Aim 1) indicates the need to continue model enhancements in critical areas including updating of epidemiological data during a pandemic, smooth handling of large demographical databases, incorporation of a broader spectrum of social-behavioral aspects, and improvement of computational efficiency and accessibility. As regards the ease of calibration (Aim 2), we demonstrate that the simulation models, when driven by the infection probabilities obtained from our epidemiological model, accurately reproduce the disease transmissibility parameters. Assuming the availability of sufficient disease reporting infrastructure and strong compliance by both infected population and healthcare providers, our testing strategy (Aim 3) adequately supports characterization of real-time epidemiological parameters. Future research on this topic will be aimed at integrating the laboratory testing strategy with our modeling and simulation approach to develop dynamic mitigation strategies for pandemic outbreaks.

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Chen, Bojun. "Nitric Oxide Production: A Mechanism for Inhibition of Chlamydia Trachomatis Replication." Digital Commons @ East Tennessee State University, 1993. https://dc.etsu.edu/etd/2653.

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Chlamydia trachomatis (CT) replicates in macrophages, but is inhibited by IFN-$\gamma$ or LPS. IFN-$\gamma$ and/or LPS induced nitrite production in mouse peritoneal macrophages, macrophage cell lines (RAW264.7 and J774A.1) and McCoy cells. Kinetic studies indicated that peak production occurred 48 hours post-treatment. CT infection itself was insufficient to induce nitrite production, but resulted in enhancement of nitrite production in IFN-$\gamma$-treated cells. Treatment with IFN-$\gamma$ or LPS resulted in significant inhibition of CT replication in these cells. Strong correlation between nitrite production and inhibition of CT replication was observed in RAW264.7 and J774A.1 cells (correlation coefficients: $-$0.93 and $-$0.94, p $<$ 0.001). N$\sp{\rm g}$- monomethyl-L-arginine (L-NMMA) specifically inhibited nitrite production and partially reversed inhibition of CT replication in macrophage cell lines. NOS mRNA was measured in RAW264.7 cells by Northern blot and Dot blot hybridization. Strong correlation between NOS mRNA expression and inhibition of CT replication (correlation coefficient: $-$0.97, p $<$ 0.05) was observed. Anti-TNF-$\alpha$ antibody completely neutralized the biological activity of TNF-$\alpha$ secreted by LPS-treated RAW264.7 cells, yet the antibody neither reduced nitrite production nor restored CT replication. Combination of the antibody and L-NMMA significantly enhanced restoration of CT replication. In peritoneal macrophages, inhibition of CT replication induced by IFN-$\gamma$ was partially restored by L-NMMA or anti-TNF-$\alpha$ antibody. In McCoy cells, inhibition of CT replication induced by IFN-$\gamma$ and LPS was not significantly restored by L-NMMA. Great restoration of CT replication by 1 mM L-NMMA was observed in LPS-treated J774A.1 cells (31%), but not in IFN-$\gamma$-treated cells (5%). Our data indicate that (1) NO production is one of the mechanisms for inhibition of CT replication in IFN-$\gamma$-activated peritoneal macrophages and RAW264.7 cells; (2) NO plays a significant role in CT inhibition in LPS-treated macrophage cell lines, but not peritoneal macrophages; (3) TNF-$\alpha$ may be associated with inhibition, but the mechanism(s) may not involve NO production; (4) NO production may not be the mechanism for CT inhibition in McCoy cells treated with IFN-$\gamma$ and LPS.

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Mallick, Emily M. "A New Murine Model For Enterohemorrhagic Escherichia coli Infection Reveals That Actin Pedestal Formation Facilitates Mucosal Colonization and Lethal Disease: A Dissertation." eScholarship@UMMS, 2012. https://escholarship.umassmed.edu/gsbs_diss/601.

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Enterohemorrhagic Escherichia coli (EHEC) colonizes the intestine and produces the phage-encoded Shiga toxin (Stx) which is absorbed systemically and can lead to hemolytic uremic syndrome (HUS) characterized by hemolytic anemia, thrombocytopenia, and renal failure. EHEC, and two related pathogens, Enteropathogenic E. coli (EPEC), and the murine pathogen, Citrobacter rodentium, are attaching and effacing (AE) pathogens that intimately adhere to enterocytes and form actin “pedestals” beneath bound bacteria. The actin pedestal, because it is a unique characteristic of AE pathogens, has been the subject of intense study for over 20 years. Investigations into the mechanism of pedestal formation have revealed that to generate AE lesions, EHEC injects the type III effector, Tir, into mammalian cells, which functions as a receptor for the bacterial adhesin intimin. Tir-intimin binding then triggers a signaling cascade leading to pedestal formation. In spite of these mechanistic insights, the role of intimin and pedestal formation in EHEC disease remains unclear, in part because of the paucity of murine models for EHEC infection. We found that the pathogenic significance of EHEC Stx, Tir, and intimin, as well as the actin assembly triggered by the interaction of the latter two factors, could be productively assessed during murine infection by recombinant C. rodentium expressing EHEC virulence factors. Here we show that EHEC intimin was able to promote colonization of C. rodentium in conventional mice. Additionally, previous in vitro data indicates that intimin may have also function in a Tir-independent manner, and we revealed this function using streptomycin pre-treated mice. Lastly, using a toxigenic C. rodentium strain, we assessed the function of pedestal formation mediated by Tir-intimin interaction and found that Tir-mediated actin polymerization promoted mucosal colonization and a systemic Stx-mediated disease that shares several key features with human HUS.

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Seung, Edward. "CD40-CD154 Blockade Facilitates Induction of Allogeneic Hematopoietic Chimerism and Transplantation Tolerance: A Dissertation." eScholarship@UMMS, 2003. https://escholarship.umassmed.edu/gsbs_diss/103.

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Allogeneic hematopoietic chimerism leading to central tolerance has significant therapeutic potential. Establishment of hematopoietic chimerism created by stem cell transplantation has been shown to prevent and cure a number of autoimmune diseases and induce the most robust and long-lasting form of transplantation tolerance known. However, the realization of the vast clinical potential of hematopoietic chimerism for induction of transplantation tolerance has been impeded by the toxicity of the host conditioning regimen and the development of graft-versus-host disease (GVHD). This thesis describes the development of stem cell transplantation protocols that 1) reduce the host conditioning regimen; and 2) abrogate the development of GVHD. When applied to the treatment of autoimmune diabetic NOD mice, a model of type 1 diabetes, stem cell transplantation was able to 3) prevent autoimmune recurrence; and 4) permit curative pancreatic islet transplantation. I first describe a tolerance-based stem cell transplantation protocol that combines sub-lethal irradiation with transient blockade of the CD40-CD154 costimulatory pathway using an anti-CD154 antibody. With this protocol, I established hematopoietic chimerism in BALB/c mice transplanted with fully allogeneic C57BL/6 bone marrow. All chimeric mice treated with anti-CD154 antibody remained free of graft vs.host disease (GVHD) and accepted donor-origin but not third party skin allografts. It was similarly possible to create allogeneic hematopoietic chimerism in NOD/Lt mice with spontaneous autoimmune diabetes. Pancreatic islet allografts transplanted into chimeric NOD/Lt mice were resistant not only to allorejection but also to recurrence of autoimmunity. I conclude that it is possible to establish robust allogeneic hematopoietic chimerism in sub-lethally irradiated mice without subsequent GVHD by blocking the CD40-CD154 costimulatory pathway using as few as two injections of anti-CD154 antibody. I also conclude that chimerism created in this way generates donor-specific allograft tolerance and reverses the predisposition to recurrent autoimmune diabetes in NOD/Lt mice, enabling them to accept curative islet allografts. In order to further reduce the impediments associated with the implementation of allogeneic hematopoietic chimerism as a therapeutic modality, I adapted a costimulation blockade-based protocol developed for solid organ transplantation for use in stem cell transplantation. The protocol combines a donor-specific transfusion (DST) with anti-CD154 antibody to induce peripheral transplantation tolerance. When applied to stem cell transplantation, administration of DST, anti-CD154 antibody, and allogeneic bone marrow led to hematopoietic chimerism and central tolerance with no myeloablation (i.e. no radiation) and no GVHD in 3 different strains of mice. The development of donor-specific tolerance in this system was shown to involve deletion of both peripheral host alloreactive CD8+ T cells and nascent intrathymic alloreactive CD8+ T cells. In the absence of large numbers of host alloreactive CD8+ T cells, the cell transfusion that precedes transplantation need not be of donor-origin, suggesting that both allo-specific and non-allo-specific mechanisms regulate engraftment. Agents that interfere with peripheral transplantation tolerance partially impair establishment of chimerism. I conclude that robust allogeneic hematopoietic chimerism and central tolerance can be established in the absence of host myeloablative conditioning using a peripheral transplantation tolerance protocol.

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20

Potts, James A. "Description, Classification, and Prediction of Dengue Illnesses in a Thai Pediatric Cohort: A Dissertation." eScholarship@UMMS, 2010. https://escholarship.umassmed.edu/gsbs_diss/465.

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Dengue fever (DF) and dengue hemorrhagic fever (DHF) are emerging infectious diseases which are endemic in many regions of the globe, many of which are resource-poor areas. DHF and DF impose a severe economic health burden in tropical and subtropical areas. Dengue virus causes an acute febrile illness that can be a self-limited febrile illness, as seen in most cases of DF, or a life-threatening illness with plasma leakage and shock, as seen in cases of DHF. A systematic review of the literature revealed gaps in the knowledge base of clinical laboratory findings of dengue illness with regards to longitudinal dynamics and classification and predictive modeling of disease severity. The objective of this thesis was to investigate the utility of clinical laboratory variables for classification and prediction of disease outcomes. The data used in this investigation was derived from a prospective study of Thai children presenting to either of two study hospitals within 72 hours of onset of an acute febrile illness. Systematic data collection, including clinical laboratory parameters, and routine clinical management continued each day until 24 hours after the fever had subsided. A final diagnosis of DHF, DF, or other febrile illness (OFI) was assigned by an expert physician after chart review. The first research objective of this study was to describe the temporal dynamics of clinical laboratory parameters among subjects with DHF, DF, or OFI. Data were analyzed using lowess curves and population-average models. Quadratic functions of clinical variables over time were established and demonstrated significantly divergent patterns between the various diagnostic groups. The second research objective was to establish and validate tools for classification of illness severity using easily obtained clinical laboratory measures. Bivariate logistic regression models were established using data from one hospital in an urban area of Thailand as a training data set and validated with a second data set from a hospital in a rural area of Thailand. The validated models maintained a high sensitivity and specificity in distinguishing severe dengue illnesses without using the hallmark indicators of plasma leakage. The third research objective used classification and regression tree (CART) analysis to established diagnostic decisions trees using data obtained on the day of study enrollment, within the first 3 days of acute illness. Decision trees with high sensitivity were established for severe dengue defined either as: 1) DHF with evidence of shock (dengue shock syndrome, DSS); or 2) DSS or dengue with significant pleural effusion. This study expands existing knowledge of the potential utility of clinical laboratory variables during different phases of dengue illness. The application of the results of these studies should lead to promising opportunities in the fields of epidemiological research and disease surveillance to reduce the health burden, and improve the clinical management, of dengue illness. Future directions involve application of these algorithms to different study populations and age groups. Additionally, other analytical techniques, such as those involving CART analysis, can be explored with these data.

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Deshpande, Ketaki. "Profiling Populations Using Neutral Markers, Major Histocompatibility Complex Genes and Volatile Organic Compounds as Modeled in Equus caballus Linnaeus." FIU Digital Commons, 2016. http://digitalcommons.fiu.edu/etd/3044.

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Assessing the genetics of wild animal populations aims to understand selective pressures, and factors whether it be inbreeding or adaptation, that affect the genome. Although numerous techniques are available for assessing population structure, a major obstacle in studying wild populations is obtaining samples from the animals without having to capture them, which can lead to undue distress and injury. Therefore, biologists often use non-invasive sampling methods (i.e., collection of feces, hair) to extract host DNA. In this study, new DNA extraction protocols were developed that improved the quality and quantity of DNA obtained from fecal matter. Fecal samples aged up to Day 6 as well as field samples with unknown days since defecation were successful in individualization of the contributors using microsatellites and were further used to demonstrate kinship. Neutral markers such as short tandem repeat, and mitochondrial D-loop sequences are used for assessing relatedness and evolutionary relationships and can mutate without detrimental effects on the organism. Loci, such as the major histocompatibility complex (MHC), adapt more rapidly under selective pressure such as parasite load, or resistance to diseases and support natural selection processes. Analysis of the neutral microsatellites in Big Summit feral horse population demonstrated a population lacking diversity and trending towards being an inbred population. However, examination of the MHC genes showed maintenance of greater variation that may be the result of selection pressures. The MHC similarity and lower genetic demarcation between geographically separated horse populations further indicated effect of selection pressures in preserving diversity at the MHC genes. Although such molecular markers are used in profiling populations, the current study was also successful in demonstrating the use of individual odor profiles as an additional profiling tool. Volatile organic compounds (VOC) obtained from hair of domestic horses were able to individualize horses as well as differentiate between horse breeds and display kinship. The relation of genetics to odor phenotype is of interest as the inherent polymorphic nature of MHC genes has the potential to generate unique combinations of genotypes that presumably produce distinct odor phenotypes. Subsequently, this study was able to show a significant correlation between MHC genotypes and VOC odor profiles in horses. Understanding the relationship between MHC and odor using domestic horses with known relatedness provides evidence that these same correlations may be applicable to wild equids and dictates their harem hierarchal social structure.

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Cam, Binh Nguyen Thi. "The ethics of research in rapidly evolving epidemics : an international perspective." Thesis, University of Oxford, 2015. http://ora.ox.ac.uk/objects/uuid:a02a2401-eaff-4003-89cc-d3d03cc39eb1.

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Background: The world is at risk of epidemics of novel and reemerging infectious diseases. These may be national, regional or international as in the case of Nipah, African Viral Haemorrhagic Fevers, SARS and H1N1 respectively. It is crucial that public health and clinical research is conducted in such epidemics. Yet the conduct of heath research during rapidly evolving epidemics or disasters represents an enormous challenge. In addition to the large number of practical challenges to undertaking such research there are also major ethical issues to consider. However, there is very little understanding of these ethical issues and very little empirical evidence of the views of patients, their families, society and key stakeholders. Objective: To collect and analyse data on ethical considerations arising in the setting of research on rapidly evolving epidemics posed by the urgent and unpredictable nature of epidemics. Design: The study was conducted in Oxford University Clinical Research Unit (OUCRU), Viet Nam and 3 other hospitals in Viet Nam with experience of epidemics. Data were collected by semi-structured interviews with key stakeholders representing research staff, IRB members, patients/family members and study sponsors/funders who have participated in or reviewed research projects on infectious diseases including SARS, H5N1, H1N1, dengue and Hand, Foot, Mouth disease. Result: A total of 64 interviews with all key stakeholders were conducted. Analysis of the ethical problems/challenges discussed in the interviews led to the identification of three themes 1) International research collaboration, 2) IRB review and 3) Consent. These tended to arise at three levels of relationship: macro (between institutions internationally), meso (within and between institutions nationally) and micro (within institutions and between health professionals and patients). Conclusion: The issues and types of considerations and their relative importance were raised and/or valued differently by the members of different key stakeholder groups due to their role and experience in research participation. Some of the issues raised also related to health research in other settings. However, many were unique to the setting of rapidly evolving epidemics. Addressing these issues is crucial for successful and appropriate research in the context of epidemics. It is inevitable that epidemics of emerging and reemerging infectious diseases will occur in the future and there is a clear need to undertake crucial scientific research in such settings. It is therefore imperative that we understand the challenges and ethical issues surrounding such research. It is desirable that further research into the ethical challenges identified in this thesis takes place in the inter-epidemic period in order to better prepare for the next epidemic.

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23

Mcghan, Cheryl G. "Repeated acquisition of sexually transmitted infections feelings, perceptions, and explanations of adolescent girls /." [Gainesville, Fla.] : University of Florida, 2005. http://purl.fcla.edu/fcla/etd/UFE0009120.

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Thesis (Ph.D.)--University of Florida, 2005.
Typescript. Title from title page of source document. Document formatted into pages; contains 265 pages. Includes Vita. Includes bibliographical references.

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24

Goliath, René. "A review of recruitment strategies within the Clinical Infectious Diseases Research Initiative (Cidri) Group from 2007-2013, 4 studies." Master's thesis, University of Cape Town, 2018. http://hdl.handle.net/11427/29769.

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The Clinical Infectious Diseases Research Group [CIDRI] has conducted high impact research over the last decade in Cape Town specifically in the townships of Khayelitsha and Mannenberg. None of this research would have been possible without robust strategies to recruit and retain study participants. Four different completed studies with different study designs have been selected, which will show the different approaches to participant recruitment into clinical research. This review will evaluate this process in relation to the approved protocol recruitment strategy, the amendments, which were required for modifications, the ability to retain participants to the end and the composition of staff used to achieve study outcomes. This entire process has been recognised as a necessary research skill and the term recruitmentology has become a practice pivotal to the research process. Recruitmentology has been unpacked to illustrate how minorities have been recruited, overlooked and over researched in the United States (US), and that experience has given a new perspective to the processes involved. Although in the South African context we do not have the identical issues to the US, these ideas can be translated in our circumstances, as both research populations can be considered as marginalised. We are challenged in the township of Khayelitsha with service disparities, which are generally impacted by the presence of clinical research groups. Although Khayelitsha has three large Day Hospital facilities, a newly built 150 bedded secondary level hospital and 11 local clinics, offering a consistently high standard of care; it remains a challenge. The CIDRI group partnered with the health services, supporting them with extra staff in the way of nurses, doctors and clinical research workers, while in return benefiting from the health system by being able to conduct effective studies. This has been and continues to be a mutually beneficial relationship, as CIDRI has been supportive to health services and the service has been a research partner of many research protocols including one of the studies being reviewed. Through the process of reviewing the databases of these four different CIRDI studies, we can examine the successes, challenges and a possible model of recruitment in the township of Khayelitsha. These studies have been chosen as they have been successfully completed by CIDRI and the databases have been locked. Each study has a different study design, from a pragmatic randomised control study, a cross sectional study, a seasonal follow-up and longitudinal study. Close attention will be paid to proposed recruitment strategy as per approved protocols, amendments (which impacted the recruitment process), staff structure, time frames of recruitment, retention and impact on study outcomes. This review will attempt to answer the following: 1. Was the proposed recruitment strategy followed as per study design and approved study protocol? 2. Was the overall recruitment impacted by staffing structure and allocated recruitment time frames? 3. How were study outcomes impacted by recruitment and retention? 4. Tuberculosis/Human Immuno-deficiency Virus TB/HIV were the diseases of study in all four studies, do these two diseases have specific challenges which impact recruitment and retention?

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Gopalakrishna-Remani, Venugopal. "Information Supply Chain System for Managing Rare Infectious Diseases." Kent State University / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=kent1341245050.

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26

Robertson, James. "Polymersome mediated intracellular delivery : a tool for research and treatment of infectious and inflammatory diseases." Thesis, University of Sheffield, 2014. http://etheses.whiterose.ac.uk/7619/.

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27

Novak, Daniel. "Improving the prevention of sexually transmitted infections (STIs) : a study using Chlamydia trachomatis as a model infection." Doctoral thesis, Umeå : Public Health and Clinical Medicine, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-692.

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28

Forman, Daron. "Viral Abrogation of Stem Cell Transplantation Tolerance Causes Graft Rejection and Host Death by Different Mechanisms: A Dissertation." eScholarship@UMMS, 2002. https://escholarship.umassmed.edu/gsbs_diss/72.

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Tolerance-based stem cell transplantation using sub-lethal conditioning is being considered for the treatment of human disease, but safety and efficacy remain to be established. In order to study these two issues, we first established that mouse bone marrow recipients treated with sub-lethal irradiation plus transient blockade of the CD40-CD154 costimulatory pathway develop permanent hematopoietic chimerism across allogeneic barriers. Our conditioning regimen of 6 Gy irradiation, a short course of anti-CD154 mAb and 25 million fully allogeneic BALB/c bone marrow cells consistently produced long-term, stable, and multilineage chimerism in C57BL/6 recipients. Furthermore, chimeric mice displayed donor-specific transplantation tolerance, as BALB/c skin allografts were permanently accepted while third-party CBA/JCr skin allografts were promptly rejected. We next determined both the safety and efficacy of this protocol by infecting chimeric mice with lymphocytic choriomeningitis virus (LCMV) either at the time of transplantation or at several time points afterwards. Infection with LCMV at the time of transplantation prevented engraftment of allogeneic, but not syngeneic, bone marrow in similarly treated mice. Surprisingly, infected allograft recipients also failed to clear the virus and died. Post-mortem study revealed hypoplastic bone marrow and spleens. Hypoplasia and death in these mice required the combination of 6 Gy irradiation, LCMV infection on the day of transplantation, and an allogeneic bone marrow transplant but did not require the presence of anti-CDl54 mAb. Allochimeric mice infected with LCMV 15 days after transplantation were able to survive and maintain their bone marrow graft, indicating that the deleterious effects of LCMV infection on host and graft survival are confined to a narrow window of time during the tolerization and transplantation process. The final section of this thesis studied the mechanisms of graft rejection and death in sublethally irradiated recipients of allogeneic bone marrow and infection with LCMV at the time of bone marrow transplantation. Infection of interferon-α/β receptor knockout mice at the time of transplantation prevented the engraftment of allogeneic bone marrow, but the mice survived. Therefore, IFN-αβ is involved in the development of marrow hypoplasia and death, whereas a second mechanism is involved in blocking the development of chimerism in these mice. Through the use of depleting mAb's and knockout mice we demonstrate that three types of recipients survived and became chimeric after being given sublethal irradiation, anti-CD154 mAb, an allogeneic bone marrow transplant and a day 0 LCMV infection: mice depleted of CD8+ T cells, CD8 knockout mice, and TCR-αβ knockout mice. Our data indicate that the mediator of bone marrow allograft destruction in LCMV-infected mice treated with costimulatory blockade is a radioresistant CD8+ NK1.1- TCRαβ+ T cell. We conclude that a non-cytopathic viral infection at the time of transplantation can prevent engraftment of allogeneic bone marrow and result in the death of sub-lethally irradiated mice treated with costimulation blockade. The abrogation of allogeneic bone marrow engraftment is mediated by a population of CD8+ NK1.1- TCRαβ+ T cells and the mediator of hypoplasia and death is viral induction of IFN-αβ.

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Zhao, Helong. "Roles of Slit-Robo Signaling in Pathogenesis of Multiple Human Diseases: HIV-1 Infection, Vascular Endothelial Inflammation and Breast Cancer." The Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1428088097.

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Williams, Cheryl Sally-Anne. "Implementing an HIV/AIDS literacy programme in a grade 11 class: an action research study." Thesis, University of the Western Cape, 2006. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_3957_1255515298.

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This research study attempted to highlight an in-depth exploration of my own classroom practice as a teacher at a high school in the Western Cape. A key goal of this research study was the quest for professional development and the development of an HIV/AIDS literacy programme for curriculum development.

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Loiler, Scott A. "In Vitro and in vivo Studies of Murine Polytropic Retrovirus Infections: a Dissertation." eScholarship@UMMS, 2000. https://escholarship.umassmed.edu/gsbs_diss/119.

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Murine leukemia viruses (MuLV) are retroviruses that play important roles in the study of oncogenes, integration, transcriptional regulation and gene therapy. Mink cell focus-inducing (MCF) viruses are polytropic MuLVs that by definition infect cells from a wide variety of species. Their ability to infect human cells and their utility as gene therapy vectors were not well characterized. To address this issue, primary and immortalized human cells were tested for their ability to be infected by MCF packaged defective vectors as well as replication competent MCF virus. A new packaging cell line, called MPAC, was created to package defective retroviral vectors in virus particles with envelope proteins derived from a Moloney mink cell focus-inducing (Mo-MCF) virus. The cellular tropism of MPAC-packaged retroviral vectors was the same as replication competent MCF viruses. Testing various established cell lines showed some human cell lines could be infected with MPAC-packaged vectors while others cannot. In addition, I show that some human cells fully support MCF virus replication while others either partially or fully restrict MCF virus replication. This indicates that some human cells express a protein on their surface that acts as a receptor for MCF viruses and allows MCF viral entry. In addition, the human cells that express a receptor for MCF viral entry did not show any further block to viral replication. An important determinant in the pathogenic phenotype of MCF 247 has been mapped to the enhancer region of the retroviral long terminal repeat (LTR). Recombination of endogenous genetic elements with the 3' portion of envoccurs and incorporates unique LTR sequences. Most strongly pathogenic MCF viruses have a duplication of the enhancer element found in the LTR. AKR mice are an inbred strain of mice that develop spontaneous T-cell lymphomas between 6 and 12 months of age. 12-25 % of MCF induced early lymphomas of AKR mice show MCF viral integration's near c-myc in an opposite transcriptional orientation. A replication competent MCF virus containing a bacterial amber suppressor tRNA gene (supF) was used to investigate the changes in the enhancer region following injection of MCF containing one enhancer in the LTR. Newborn AKR mice were injected with the supF tagged replication competent virus and observed for signs of leukemia development (ruffled fur, lethargy, and tumor development). When these signs were detected, the animals were sacrificed and DNA was prepared from the isolated tumors. Thirty-one tumors DNA were analyzed for the presence of supF tagged virus and rearrangement of the c-myc locus. Nine supF tagged proviral LTRs integrated near c-myc from four animals were PCR amplified, sequenced, and/or cloned. All of the enhancer elements analyzed were derived from proviruses that integrated in a reverse orientation with respect to c-myc locus. Two of the isolated enhancer elements contained only a few base changes whereas the majority contained duplications of different sizes that encompassed different transcription factor binding sites. The duplicated enhancer regions contained duplications from 82-134 bp in length. One tumor contained a proviral enhancer with only 5 bp changes relative to the injected virus. This suggests that the enhancers need only a few specific base changes relative to the injected virus to accelerate leukemogenesis. The other three tumors contained proviral enhancers with various size duplications and additional transcription factor binding sites. These data suggest that the injected virus is not pathogenic unless the enhancer region is altered. One proviral integration site encompassing a duplicated enhancer region and 139 bp of the c-myc gene locus was PCR amplified, cloned and sequenced. A search of the current transcription factor database (Transfac 3.3) showed no known transcription factor binding site sequences were created at the junction of the enhancer duplications. The common motif of LVb, core NF-1, and GRE transcription factor binding sites, described by Golemis at al (57), was conserved throughout the isolated enhancers. Most of the enhancer elements contained additional NF-кB and/or GRE sites in close proximity to the conserved LVb-core region. These results support the hypothesis that additional NF-кB and/or GRE binding sites cooperatively interact with the conserved GRE-NF-1-LVb-core motif in c-myc induced leukemogenesis. In addition, two unique families of enhancer duplications were identified. The two families contained enhancers isolated from different tumors that displayed sequence homology and transcription factor binding site organization unique to each group.

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Copioli, Juan Carlos. "Alcoholismo y su relación con los niveles de inmunoglobulina a secretoria." Doctoral thesis, Copioli JC. Alcoholismo y su relación con los niveles de inmunoglobulina a secretoria [Internet]. Universidad Nacional de Córdoba; 1986 [citado el 13 de febrero de 2020]. Disponible en: https://rdu.unc.edu.ar/handle/11086/6860, 1986. http://hdl.handle.net/11086/6860.

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Tesis (Dr. Medicina)--Universidad Nacional de Córdoba. Facultad de Ciencias Médicas, 1986
Fil: Copioli, Juan Carlos. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Cátedra de Cínica Médica; Argentina.
Estudio realizado en el Instituto Provincial de Alcoholismo y Drogadicción y el Servicio de Clínica Médica N°II y Cátedra de Medicina III de la Universidad Nacional de Córdoba. Comprende un universo de 91 pacientes. Se analizan los factores que concurren para determinar la inmunodificiencia que padecen los alcoholistas y se investiga sobre los aspectos específicos del comportamiento del Sistema Inmune Humano ante la agresión alcohólica, como son los anticuerpos secretorios y séricos. Se arriba a la conclusión de que el consumo excesivo y prolongado de alcohol condiciona una deficiencia selectiva y transitoria de Inmunoglobulina A Secretoria, que tiene a normalizarse con la abstinencia prolongada del tóxico, aún en presencia de lesiones irreversibles ocasionadas por el mismo. Se estudia el comportamiento de los anticuerpos séricos, IgG, IgA e IgM, que sufren modificaciones relacionadas con lesiones del parenquima hepático ocasionados por el alcohol, aumentando los mismos en proporción directa a la severidad de las mismas. Se realizan observaciones sobre el comportamiento de la Inmunidad celular específica e inespecífica.

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Mazorodze, Tasara. "HIV-related stigma amongst service staff in Grahamstown a comparison of Hi-Tec security guards and Rhodes catering in the Eastern Cape." Thesis, Rhodes University, 2011. http://hdl.handle.net/10962/d1002525.

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Despite the acknowledged reality that HIV-related stigma is a major barrier to effective HIV prevention and treatment, and perhaps because it is complex in nature, few local empirical scales have been developed to measure stigma and to be able evaluate the impact of anti-stigma interventions. Whilst the development of two recent South African HIV-related stigma scales can be celebrated as a major breakthrough, the reliability and validity of these scales across contexts remains largely unknown. This research project employs these two local, and competing, HIV-related personal stigma scales - the first developed by Kalichman et al. (2005) and the second developed by Visser, Kershaw, Makin and Forsyth (2008)-to compare the psychometric properties of the scales and to obtain a measure of HIV-related stigma with a sample of 246 service staff employed at either Rhodes University Catering Division or the Hi-Tec Security company, both organisations located in Grahamstown, a small town in the Eastern Cape, South Africa. Both organisations are major employers of semi-skilled workers in this local context. The results suggest that the Visser et al. scale (2008) reports slightly better psychometric properties than the Kalichman et al. (2005) scale for this sample. Furthermore, the security guards appear to be more stigmatising than the caterers, and it is suggested that this might be a consequence of the combined influences of normative occupational roles and workplace context. Results also show that participants who practices safe sex, know someone with HIV and/or who have been tested for HIV show lower levels of HIV-related stigma. Finally, personal stigma scores are generally lower than attributed stigma scores, which might offer a useful point of intervention.

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Rodríguez, Fernando Marcos. "Estudio de la expresión y características biológicas de fenotipos inducidos in vitro de neutrófilos humanos." Doctoral thesis, Rodríguez FM. Estudio de la expresión y características biológicas de fenotipos inducidos in vitro de neutrófilos humanos. [Internet]. Universidad Nacional de Córdoba; 2019 [citado el 13 de febrero de 2020]. Disponible en: https://rdu.unc.edu.ar/handle/11086/11600, 2019. http://hdl.handle.net/11086/11600.

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Tesis-Doctor en Medicina y Cirugía-Universidad Nacional de Córdoba. Facultad de Ciencias Médicas, 2019 111 p.
Fil: Rodríguez, Fernando Marcos. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Biología Celular; Argentina.
Fil: Rodríguez, Fernando Marcos. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Cátedra de Biología Celular, Histología y Embriología; Argentina.
Los polimorfonucleares neutrófilos (PMN) desempeñan un rol clave en la inmunidad innata frente a infecciones especialmente bacterianas y fúngicas, pero en la actualidad estos leucocitos por su potencial versatilidad en cuanto a sus funciones, han sido propuestos como células moduladoras de la inmunidad adaptativa. Se han descripto algunos PMN neutrófilos en sitios de inflamación que expresan fenotipo de célula presentadora de antígenos (CPA) —se consideran a las moléculas B7 (B7-1, CD80 y B7-2, CD86) y a CMH clase II (HLA-DR) como marcadoras del fenotipo CPA de PMN neutrófilo— y este aspecto constituye un área de interés científico y ha motivado este trabajo de investigación científica. El objetivo de esta Tesis es el estudio de la expresión y características biológicas de fenotipos inducidos in vitro de PMN neutrófilos humanos. Materiales y métodos: En las muestras se realizaron ensayos con estimuladores clásicos y con uno no clásico para generar los fenotipos. La expresión de moléculas de los diferentes fenotipos y la liberación de trampas extracelulares neutrófilas (NETs) se evidenciaron mediante inmunofluorescencia. Las observaciones de interacciones celulares de contacto se realizaron mediante microscopía óptica y electrónica. Los fenotipos inducidos in vitro con estimuladores surgen de la comparación con el “fenotipo PMN neutrófilo control” de las muestras apareadas sin estimulación. Para el desarrollo del trabajo se utilizaron muestras donadas por el Banco de Sangre del Instituto de Hematología de la UNC, en anonimato, con consentimiento informado y aprobación del proyecto por el Comité de Ética del Hospital Nacional de Clínicas, FCM, UNC, registro 169/13. Resultados: se observaron las siguientes características del fenotipo inducido in vitro de “PMN neutrófilo-CPA”. a) expresa en superficie las moléculas HLA-DR (CMH) y moléculas coestimuladoras B7 (CD80 y CD86); b) presenta una vida media en cultivo que varía según los activadores (con LPS: 48 hs, con OVA: 60 hs); c) es capaz de generar NETs con activadores clásicos (LPSy fMLP) y no clásico (OVA); d) las NETs pueden contener moléculas coestimuladoras B7 (CD80 y CD86); e) las NETs que contienen moléculas coestimuladoras promueven aumento de sinapsis inmunes. Por otro lado, se evidenciaron las siguientes características del fenotipo inducido in vitro de “PMN neutrófilo CD4-CD45RO”: a) expresa en superficie las moléculas CD4 y CD45RO; b) presenta una vida media en cultivo de 30 minutos con los activadores LPS, fMLP y OVA; c) es capaz de generar NETs con activadores clásicos y uno no clásico; d) las NETs pueden contener moléculas CD4 y CD45RO. Conclusiones: Se considera que el desarrollo de este trabajo científico aporta nuevos datos sobre las importantes funciones inmunológicas que llevan a cabo las células implicadas. Los hallazgos con respecto a la expresión de moléculas características de las CPAs profesionales en PMN neutrófilos, permiten definirlos como potenciales CPAs. En este estudio sobre la expresión y características biológicas de fenotipos de PMN neutrófilos inducidos in vitro se halló la expresión de moléculas coestimuladoras B7 y del CMH II: HLA-DR en las NETs lo que otorga una nueva perspectiva a las trampas extracelulares influenciando en el entorno celular y adquiere gran importancia por la posibilidad de ruptura de la autotolerancia, tal como sucede en enfermedades autoinmunes. Estos resultados pueden ser tenidos en cuenta como posibles blancos terapéuticos. Además, por otra parte, el hallazgo de la expresión de moléculas no convencionales del fenotipo PMN neutrófilo-CD4, CD45RO y la liberación de NETs conteniendo dichas moléculas pueden sentar las bases de futuras investigaciones donde se evalúe su significado funcional. Esto tiene interés por ejemplo en el estudio de la infección por HIV ya que podría influir en la biodistribución del mismo, siendo CD4 el receptor primario de este virus. La posibilidad de los PMN neutrófilos que en determinadas condiciones desempeñen roles de CPA comprometiendo la vía de coestimulación B7-1 (CD80) / B7-2 (CD86): CD28 – CTLA 4 en las diferentes subpoblaciones de células T tendría importancia en la inmunoregulación y la patogénesis de diversas enfermedades donde las NETs también pueden estar implicadas.
Polymorphonuclear neutrophils (PMN) play a key role in innate immunity especially against bacterial and fungal infections, but at present these leukocytes, because of their potential versatility in their functions, have been proposed as modulators of adaptive immunity. Some PMN neutrophils have been described at sites of inflammation that express antigen-presenting cell (APC) phenotype —B7 molecules (B7-1, CD80 and B7-2, CD86) and MHC class II (HLA-DR) are considered as markers of the PMN neutrophil APC phenotype— and this aspect constitutes an area of scientific interest and has motivated this scientific research work. The objective of this thesis is the study of the expression and biological characteristics of phenotypes induced in vitro of human PMN neutrophils. Material and methods: In the samples, tests were performed with classic stimulators and with one non-classical stimulator to generate the phenotypes. The expression of molecules of the different phenotypes and the release of extracellular neutrophil traps (NETs) were evidenced by immunofluorescence. The observations of cellular contact interactions were made by optical and electronic microscopy. The phenotypes induced in vitro with stimulators arise from the comparison with the "control PMN neutrophil phenotype" of paired samples without stimulation. To the development of this investigation the samples were donated by the Blood Bank of the Hematology Institute of the UNC, in anonymity, with serology data, with informed consent with approval by the Ethics Committee of the Hospital Nacional de Clínicas, FCM, UNC, record 169/13. Results: the following characteristics of the in vitro induced phenotype of "PMN neutrophil-APC" were observed. a) They expresses on the surface the HLA-DR molecules (MHC) and costimulatory B7 molecules (CD80 and CD86); b) They have a half-life in culture that varies according to the activators (with LPS: 48 hours, with OVA: 60 hours); c) They are capable of generate NETs with classic (LPSy fMLP) and non-classical (OVA) activators; d) NETs may contain costimulatory B7 molecules (CD80 and CD86); e) NETs that contain costimulatory molecules promote an increase in immune synapses. On the other hand, the following characteristics of the in vitro induced phenotype of “PMN neutrophil CD4-CD45RO" were evidenced: a) They expresses on the surface the CD4 and CD45RO molecules; b) They have a half-life in culture of 30 minutes with LPS, fMLP and OVA activators; c) They are capable of generate NETs with classical activators and one non-classical activator; d) NETs may contain CD4 and CD45RO molecules. Conclusions: It is considered that the development of this scientific work provides new data on the important immunological functions carried out by the involved cells. The findings regarding the expression of characteristic molecules of professional APCs in PMN neutrophils allow us to define them as potential APCs. In this study on the expression and biological characteristics of PMN neutrophil phenotypes induced in vitro, we found the expression of costimulatory molecules B7 and CMH II: HLA-DR in NETs which gives a new perspective to extracellular traps influencing the cellular environment and it acquires great importance because of the possibility of rupture of self-tolerance, as it happens in autoimmune diseases. These results can be taken into account as possible therapeutic targets. In addition, on the other hand, the finding of the expression of non-conventional molecules of PMN neutrophil-CD4, CD45RO phenotype, and the release of NETs containing these molecules can lay the foundations for future investigations where their functional significance is evaluated. This is of interest, for example, in the study of HIV infection since it could influence its biodistribution, with CD4 being the primary receptor for this virus. The possibility of PMN neutrophils that under certain conditions play roles of APC compromising the costimulation pathway B7-1 (CD80) / B7-2 (CD86): CD28-CTLA 4 in the different subpopulations of T cells would be important in immunoregulation and the pathogenesis of various diseases where NETs may also be involved.
2021-05-24

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Brutkiewicz, Randy R. "Analysis of and Role for Effector and Target Cell Structures in the Regulation of Virus Infections by Natural Killer Cells: a Dissertation." eScholarship@UMMS, 1993. https://escholarship.umassmed.edu/gsbs_diss/137.

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The overall emphasis in this thesis is the study of the regulation of virus infections by natural killer (NK) cells. In initial analyses, vaccinia virus (VV)-infected cells were found to be more sensitive to NK cell-mediated lysis during a discrete period of time post-infection. This enhanced susceptibility to lysis correlated with enhanced triggering (but not binding) of the effector cells and a concomitant decrease in target cell H-2 class I antigen expression. Furthermore, VV-infected cells became resistant to lysis by allospecific cytotoxic T lymphocytes (CTL) at a time when they were very sensitive to killing by NK cells or VV-specific CTL. This suggested that alterations in class I MHC antigens may affect target cell sensitivity to lysis by NK cells. The hypothesis that viral peptide charging of H-2 class I molecules can modulate target cell sensitivity to NK cell-mediated lysis was tested by treating target cells with synthetic viral peptides corresponding to the natural or minimal immunodominant epitopes defined for virus-specific CTL, and then target cell susceptibility to NK cell-mediated lysis was assessed. None of the 12 synthetic viral peptides used were able to significantly alter target cell lysis by NK cells under any of the conditions tested. In order to determine if H-2 class I molecules were required in the regulation of a virus infection by NK cells in vivo, intact or NK depleted (treated with anti-asialo GM1 antiserum) β2-microglobulin-deficient [β2m (-/-)] mice, which possess a defect in H-2 class I antigen expression, were infected with the prototypic NK-sensitive virus, murine cytomegalovirus (MCMV). In anti-asialo GM1-treated β2m (-/-) mice, as well as in β2m + (H-2 class I normal) control mice also treated with anti-asialo GM1 a significant enhancement in splenic MCMV titers as compared to NK-intact animals, was observed. When thymocyte expression of H-2 class I molecules (H-2Db) in normal mice was analyzed, it was found that following MCMV infection, H-2Db expression was significantly greater than the low level of expression found in uninfected thymocytes. In marked contrast, thymocytes from β2m (-/-) mice did not display any detectable H-2Db before or after infection. These in vivoresults demonstrate that NK cells can regulate a virus infection, at least in the case of MCMV, independent of H-2 class I molecule expression. Thymocytes from uninfected normal mice were found to be very sensitive to NK cell-mediated lysis, whereas those from MCMV-infected animals were completely resistant, presumably due to the protective effects of MCMV-induced interferon (IFN). However, thymocytes from MCMV-infected β2m (-/-) mice were only slightly protected from lysis by NK cells, consistent with the inverse correlation between MHC class I antigen expression and sensitivity to NK cell-mediated lysis. These results provide in vivoevidence suggesting a requirement for MHC class I molecules in IFN-mediated protection from lysis by NK cells. In addition to the analysis of H-2 class I molecules on target cells, the identity of a molecule present on the surface of all NK cells and other cytotoxic effector cells, which is recognized by a monoclonal antibody (mAb) generated in this laboratory designated CZ-1, and can also modulate NK cell triggering, was also of interest. This laboratory has previously reported that this antigen is upregulated on cytotoxic (and other) lymphocytes following a virus infection in vivo, or upon activation in vitro. Using competitive FACS analysis and fibroblasts transfected with various isoforms of CD45, it was found that mAb CZ-1 recognizes a sialic acid-dependent epitope associated with a subpopulation of CD45RB molecules.

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Hart, Francis Charles. "The Effect of Environmental Variables on Local West Nile Virus Infection Rates in Culex Mosquitoes Using an 'Ecological Niche' Model." Ohio University / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1271699445.

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Shinkins, Bethany. "The evaluation and expansion of methodologies relating to the reporting and analyses of intermediate test results : improving the clinical utility of diagnostic research." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:2df7fc16-51f5-4978-80bd-b69efdf9c8a2.

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Background and objectives: It has been argued that the binary framework frequently adopted to analyse test accuracy does not represent the clinical reality of diagnostic practice, and the recognition of an intermediate category of test result could make the utility of diagnostic tests more transparent. The objective of this thesis is to explore the value of moving away from the binary framework when evaluating and interpreting quantitative diagnostic tests. Methods: This thesis starts with an overview of the key arguments against dichotomising quantitative test results and a summary of some of the alternative methods proposed. Four distinct studies are then reported: 1) a systematic review of the methods currently used to evaluate the accuracy of quantitative cancer biomarkers, 2) a survey of GPs exploring preferences for threshold guidance 3) an evaluation of existing methods for identifying an intermediate range of test values, and 4) an assessment of the feasibility of applying these methods to the results of a meta-analysis. Results: The binary framework remains the most common method for evaluating the accuracy of quantitative tests, despite the survey of GPs indicating that a single threshold interpretation is less helpful than identifying rule-in and rule-out thresholds. Existing methods for identifying an intermediate range of values require some adaptation to incorporate the cost trade-offs relating to different outcomes but, given complete reporting at the primary research, could be applied to the results of a meta-analysis. Conclusion: The 2 x 2 diagnostic framework frequently fails to capture many of the realities and complexities of clinical research questions. Standardised methods that facilitate complete reporting of test accuracy in primary diagnostic accuracy studies are required to allow for greater flexibility when producing threshold recommendations further down the evidence pathway.

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Thornton, Susan. "A portfolio of study practice and research : psychological variables and HIV infection; a study of their effect on disease progression among long term infected individuals." Thesis, University of Surrey, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.362328.

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Montague, Carl Thomas. "Developing a strategy for a centre of competence for HIV research and development in South Africa." Thesis, Stellenbosch : Stellenbosch University, 2008. http://hdl.handle.net/10019.1/892.

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Thesis (MBA (Business Management))--Stellenbosch University, 2008.
The government has identified the need to transform the South African economy from one that is primarily resource based to one that is knowledge-based and has formulated a 10 year plan in order to accomplish this objective. The plan involves the creation and funding of five theme-specific consortium-based centres of competence that focus on the five top national health priorities, linked to the growth of the local pharmaceutical industry. This research study proposed that if collaboration and communication between academic researchers and the biotechnology industry in South Africa was improved it would lead to an increase in the development of innovative products for HIV/AIDS prevention and treatment. The objective of the study was the development of a strategy for a centre of competence for HIV research and development that brings together academic researchers and industry in a public private partnership and that will enable the proposal to be tested. Centre of competence programmes in both developed and developing countries, including Sweden, Austria and Estonia, were reviewed. The success factors for the various programmes were discussed. The strategic planning analysis began by considering the mandate of the CoC for HIV R&D. The requirements and expectations of the DST in establishment of the centres of competence were examined. An analysis of the external environment relevant to the South African biotechnology industry was then performed. This involved a detailed macro-environmental analysis in which political, economic, social, technological and environmental factors were considered. It was followed by an analysis of the current biotechnology industry in South Africa. The industry’s dominant economic features were identified as were its future driving forces. In a competitive environment analysis the South African biotechnology industry was found to be extremely competitive. Two industry issues, price controls and access to capital, were identified and discussed. The industry key success factors identified included access to large and sustained capital, attracting and retaining talented employees, an efficient and high quality regulatory authority, continued government support, productive and appropriate partnerships and skilled intellectual property management. An internal environment analysis was performed which identified competencies and resource strengths of the CoC for HIV R&D, including the high level of academic research in the HIV/AIDS field and expertise in clinical trials of HIV/AIDS products. Competitive deficiencies and resource weaknesses identified included shortages of skills and talent and the lack of co-ordination for funding of HIV/AIDS research. The analysis of the internal environment continued with the examination of the internal value chain of the CoC for HIV R&D. This consisted of discovery, pre-clinical development and clinical development stages. Gaps in the value chain were identified, including the lack of facilities for high-throughput screening of compounds for anti-HIV activity, lack of pre-clinical testing facilities and lack of manufacturing plants capable of producing products for use in clinical trials. The results of the external and internal environment analysis were used in a SWOC analysis and a number of strategies were identified to capitalise on opportunities and to address challenges. A subsequent competitive strength assessment identified a competitive advantage in the formation of the CoC for HIV R&D. In addition a number of strategic issues facing the centre were identified and ways to address or manage the issues were proposed. The strategic planning process was completed by the selection of a strategic approach for the CoC for HIV R&D. The study concluded that a PPP of public and private organisations operating under a corporate strategy of related diversification developed and implemented by the CoC for HIV R&D, would be suitable for testing the Proposal. The study’s conclusion also highlighted the need to ensure that the CoC for HIV R&D receives a long term commitment of funding from public sources, and that is managed by an experienced team with strong leadership skills. Important strategies emerging from the study and specifically from the SWOC analysis were development of a national HIV research plan and funding of the highest priority projects; focusing research funding on research with greatest potential for generation of HIV/AIDS products; and establishment of new technology platforms to fill gaps in the value chain. Finally, a number of recommendations were made for implementation of the results of this study or as the basis for further study.

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Yoshikawa, Minako. "Research on Emerging and Re-emerging Mosquito-borne and Related Infectious Diseases in Southeast Asia: Prescriptions from the City-State of Singapore and a Tourist Destination of Bali, Indonesia." 京都大学 (Kyoto University), 2012. http://hdl.handle.net/2433/157864.

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Van, der Walt Corneli. "Forgiveness liberating or restraining? Exploring the constructions of forgiveness of people living with the Human Immunodeficiency Virus (HIV) /." Diss., Pretoria : [s.n.], 2006. http://upetd.up.ac.za/thesis/available/etd-09112007-091049.

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Bellini, Nara Regina. "Significações psicossociais do diagnostico de HIV e do impedimento da amamentação para as gestantes : um estudo clinico-qualitativo." [s.n.], 2008. http://repositorio.unicamp.br/jspui/handle/REPOSIP/308999.

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Orientadores: Egberto Ribeiro Turato, Helaine Maria Besteti Pires Mayer Milanez
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: O objetivo geral deste estudo foi interpretar as significações psicossociais relatadas pelas mulheres no momento da descoberta da infecção pelo HIV na gestação, durante consulta de pré-natal especializado no Centro de Atenção Integral à Saúde da Mulher da Universidade Estadual de Campinas (Caism/UNICAMP). Os objetivos específicos foram conhecer as angústias e conflitos gerados após a informação sobre a presença da infecção pelo HIV, e discutir os significados da maternidade e a impossibilidade do aleitamento materno no contexto da infecção pelo HIV. Sujeitos e Métodos: Estudo exploratório, na particular abordagem Clínico-Qualitativa. A amostra de sujeitos foi construída pela técnica de saturação de dados, através de entrevista semidirigida de questões abertas. O grupo de sujeitos foi composto por gestantes com 22 a 31 anos de idade, entre 15 e 38 semanas de gestação, e que receberam o diagnóstico de HIV no início da gestação, sendo a maioria multípara, com situação conjugal estável e ocupação do lar. Resultados e Discussão: Nas falas destas mulheres ficou evidente que o momento da revelação do diagnóstico de HIV durante a gestação é carregado de intensas emoções, seguidas de fantasias e sentimentos conflitantes, com resistência da aceitação dos mesmos e medo intenso da transmissão vertical, mesmo sabendo que, utilizando a terapia anti-retroviral, a chance de infectar o bebê seria mínima. Emergiram também sentimentos de angústia e estigma relacionados ao impedimento da amamentação. Considerações Finais: Acreditamos que estar grávida na presença da infecção pelo HIV exige um duplo trabalho de redefinição subjetiva, na medida em que a mulher precisa se reconhecer como mãe e como portadora do HIV. Os resultados apontam que essas mulheres se deparam com circunstâncias adversas que envolvem o desejo de amamentar e, ao mesmo tempo, preservar a saúde de seus filhos
Abstract: Objectives - The general purpose of this study was to interpret psycho-social conceptions reported by women as they discover an HIV-infection during prenatal care at a specialized facility in a Woman's Health Center (Centro de Atenção Integral à Saúde da Mulher) of the University of Campinas (Caism/UNICAMP). Specific objectives were to recognize conflicts and afflictions generated after receiving an HIV diagnosis and discuss meanings of motherhood and proscription of breastfeeding in the setting of HIV infection. Methods: Exploratory study conducted in a clinical-qualitative way; the sample size was defined by the saturation of collected information. The sample was composed of recently diagnosed HIVinfected pregnant women (ages from 22 to 31 years, gestational ages from 15 to 38 weeks, mostly multiparous, housewives, and reporting stable relationships. Results and Discussion: From the analyzed data, it became clear that the experience of a newly found HIV infection diagnosis during pregnancy gives rise to intense emotions, fantasies and conflicted feelings, along with resistance in accepting emotions and great fear of mother-to-child transmission of HIV, even in face of minimal risks achievable by antiretroviral prophylaxis. Also emerged feelings of affliction and stigmatization related to suppression of breastfeeding. Final Considerations: We believe that pregnancy in the setting of HIV infection demands double amounts of effort in redefining one's self, in the sense that the woman must acknowledge herself as both a mother and a carrier of HIV. Results show that these women are faced with adverse circumstances involving the desire to breastfeed and, concomitantly, to preserve the health of their children
Mestrado
Ciencias Medicas
Mestre em Tocoginecologia

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43

Gavanescu, Irina Catrinel. "Autoantibodies to Centrosomes are Diagnostic for Human Scleroderma and Can Be Induced by Experimental Mycoplasma Infection in Mice: A Dissertation." eScholarship@UMMS, 2002. https://escholarship.umassmed.edu/gsbs_diss/76.

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The overall objective of this thesis work was to develop new insights into the etiology of scleroderma, a human systemic autoimmune disease, by analyzing the autoantibodies to centrosome antigens that develop during the disease. Centrosomes are perinuclear organelles that form microtubule arrays, including mitotic spindles that ensure the faithful segregation of chromosomes during mitosis. These studies used a novel methodology to determine the prevalence of anti-centrosome autoantibodies in patients with scleroderma. Recombinant centrosome antigens were used to determine the antigenic specificity of anti-centrosome antibody subsets by immunoblotting. Centrosome marker antibodies were used in indirect immunofluorescence assays to distinguish centrosomes within the polymorphic staining pattern frequently given by scleroderma sera. We found that 43% of patients are autoreactive to centrosomes, a prevalence higher than has been reported for any other scleroderma autoantigen. Half of the centrosome-positive patients also had autoantibodies against other antigens used in scleroderma diagnosis. However, in the remaining half of these patients, anti-centrosome antibodies represented the sole class of autoantibodies that was detectable. Anti-centrosome antibodies were detected in only a small percentage of normal individuals and patients with other connective tissue diseases. These data suggest that anti-centrosome autoantibodies may represent a new diagnostic tool in scleroderma. Upon examination of anti-centrosome autoantibody development in an animal model, it appeared that this autoantibody specificity may develop in mice as a consequence of an infection. An infectious agent was isolated by plaque-formation from carrier mice. Further characterization of the infectious agent was undertaken to obtain information on its physical, morphological and cytopathological properties. The infectious agent was identified by sequence and unique antigenic properties to be homologous to the pig pathogen Mycoplasma hyorhinis. When reintroduced into naive mice, the murine mycoplasma triggered anti-centrosome autoantibody development. While anti-centrosome autoantibodies of IgM isotype are part of the repertoire of naive unimmunized mice, mycoplasma infection specifically triggered the development of anti-centrosome IgG. Moreover, centrosome autoreactivity was prevented by antibiotic treatment. The autoantibody response evolved to recruit additional specificities, having IgM isotypes, reactive to endoplasmic reticulum-associated autoantigens.

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Cruz, Serena. "In Search of Safety, Negotiating Everyday Forms of Risk: Sex Work, Criminalization, and HIV/AIDS in the Slums of Kampala." FIU Digital Commons, 2015. http://digitalcommons.fiu.edu/etd/2293.

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This dissertation offers an in-depth descriptive account of how women manage daily risks associated with sex work, criminalization, and HIV/AIDS. Primary data collection took place within two slums in Kampala, Uganda over the course of fourteen months. The emphasis was on ethnographic methodologies involving participant observation and informal and unstructured interviewing. Insights then informed document analysis of international and national policies concerning HIV prevention and treatment strategies in the context of Uganda. The dissertation finds social networks and social capital provide the basis for community formation in the sex trade. It holds that these interpersonal processes are necessary components for how women manage daily risks associated with sex work and criminalization. However, the dissertation also finds that women’s social connections can undermine the strategies they need to manage their HIV/AIDS prevention and treatment. This is because current HIV/AIDS policies prioritize individual behavioral change practices that undermine the complex interpersonal activities developed by women to stay alive. In response, this dissertation concludes that social networks are fundamental to the formation of sex work communities and to the survival of women in the sex trade and should be considered in future HIV policies and programs intending to intervene in the HIV epidemic of female commercial sex workers in Kampala, Uganda.

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Loots, Mathilda Christina. "'n Verkenning van opvoeders se mobilisering van bates ter ondersteuning van gemeenskapshantering van MIV/VIGS." Diss., Pretoria : [s.n.], 2005. http://upetd.up.ac.za/thesis/available/etd-09052005-122103/.

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Takaidza, Isaac. "Modelling the optimal efficiency of industrial labour force in the presence of HIV/AIDs pandemic." Thesis, Cape Peninsula University of Technology, 2012. http://hdl.handle.net/20.500.11838/1305.

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Thesis (DTech (Mechanical Engineering))--Cape Peninsula University of Technology, 2012
In this thesis, we investigate certain key aspects of mathematical modelling to explain the epidemiology of HIV/AIDS at the workplace and to assess the potential benefits of proposed control strategies. Deterministic models to investigate the effects of the transmission dynamics of HIV/AIDS on labour force productivity are formulated. The population is divided into mutually exclusive but exhaustive compartments and a system of differential equations is derived to describe the spread of the epidemic. The qualitative features of their equilibria are analyzed and conditions under which they are stable are provided. Sensitivity analysis of the reproductive number is carried out to determine the relative importance of model parameters to initial disease transmission. Results suggest that optimal control theory in conjunction with standard numerical procedures and cost effective analysis can be used to determine the best intervention strategies to curtail the burden HIV/AIDS is imposing on the human population, in particular to the global economy through infection of the most productive individuals. We utilise Pontryagin’s Maximum Principle to derive and then analyze numerically the conditions for optimal control of the disease with effective use of condoms, enlightenment/educational programs, treatment regime and screening of infectives. We study the potential impact on productivity of combinations of these conventional control measures against HIV. Our numerical results suggest that increased access to antiretroviral therapy (ART) could decrease not only the HIV prevalence but also increase productivity of the infected especially when coupled with prevention, enlightenment and screening efforts.

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Viljanen-Rollinson, S. L. H. "Expression and detection of quantitative resistance to Erysiphe pisi DC. in pea (Pisum sativum L.)." Lincoln University, 1996. http://hdl.handle.net/10182/1657.

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Characteristics of quantitative resistance in pea (Pisum sativum L.) to Erysiphe pisi DC, the pathogen causing powdery mildew, were investigated. Cultivars and seedlines of pea expressing quantitative resistance to E. pisi were identified and evaluated, by measuring the amounts of pathogen present on plant surfaces in field and glasshouse experiments. Disease severity on cv. Quantum was intermediate when compared with that on cv. Bolero (susceptible) and cv. Resal (resistant) in a field experiment. In glasshouse experiments, two groups of cultivars, one with a high degree of resistance and the other with nil to low degrees of resistance to E. pisi, were identified. This indicated either that a different mechanism of resistance applied in the two groups, or that there has been no previous selection for intermediate resistance. Several other cultivars expressing quantitative resistance were identified in a field experiment. Quantitative resistance in Quantum did not affect germination of E. pisi conidia, but reduced infection efficiency of conidia on this cultivar compared with cv. Pania (susceptible). Other epidemiological characteristics of quantitative resistance expression in Quantum relative to Pania were a 33% reduction in total conidium production and a 16% increase in time to maximum daily conidium production, both expressed on a colony area basis. In Bolero, the total conidium production was reduced relative to Pania, but the time to maximum spore production on a colony area basis was shorter. There were no differences between the cultivars in pathogen colony size or numbers of haustoria produced by the pathogen. Electron microscope studies suggested that haustoria in Quantum plants were smaller and less lobed than those in Pania plants and the surface area to volume ratios of the lobes and haustorial bodies were larger in Pania than in Quantum. The progress in time and spread in space of E. pisi was measured in field plots of cultivars Quantum, Pania and Bolero as disease severity (proportion of leaf area infected). Division of leaves (nodes) into three different age groups (young, medium, old) was necessary because of large variability in disease severity within plants. Disease severity on leaves at young nodes was less than 4% until the final assessment at 35 days after inoculation (dai). Exponential disease progress curves were fitted for leaves at medium nodes. Mean disease severity on medium nodes 12 dai was greatest (P<0.001) on Bolero and Pania (9.3 and 6.8% of leaf area infected respectively), and least on Quantum (1.6%). The mean disease relative growth rate was greatest (P<0.001) for Quantum, but was delayed compared to Pania and Bolero. Gompertz growth curves were fitted to disease progress data for leaves at old nodes. The asymptote was 78.2% of leaf area infected on Quantum, significantly lower (P<0.001) than on Bolero or Pania, which reached 100%. The point of inflection on Quantum occurred 22.8 dai, later (P<0.001) than on Pania (18.8 dai) and Bolero (18.3 dai), and the mean disease severity at the point of inflection was 28.8% for Quantum, less (P<0.00l) than on Pania (38.9%) or Bolero (38.5%). The average daily rates of increase in disease severity did not differ between the cultivars. Disease progress on Quantum was delayed compared with Pania and Bolero. Disease gradients from inoculum foci to 12 m were detected at early stages of the epidemic but the effects of background inoculum and the rate of disease progress were greater than the focus effect. Gradients flattened with time as the disease epidemic intensified, which was evident from the large isopathic rates (between 2.2 and 4.0 m d⁻¹) Some epidemiological variables expressed in controlled environments (low infection efficiency, low maximum daily spore production and long time to maximum spore production) that characterised quantitative resistance in Quantum were correlated with disease progress and spread in the field. These findings could be utilised in pea breeding programmes to identify parent lines from which quantitatively resistant progeny could be selected.

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Tsai, Wen-tang, and 蔡文堂. "Research on Peng-hu Medical Team Participation in Community Infectious Disease Prevention Programs." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/35008384458763969759.

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碩士
國立中山大學
公共事務管理研究所
95
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.

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Kou, Young-Sen, and 郭永森. "Kinmen County Legal Infectious Disease SARS Prevents and Cures The Research of the Tactics." Thesis, 2005. http://ndltd.ncl.edu.tw/handle/4aemzy.

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碩士
銘傳大學
公共事務學系碩士在職專班
93
Abstract SARS from March of 2003 to August wreaks havoc, the great wound of hard iron of causing the people to be healthy and social economy, the ones that cause the heart even more are extremely panic; In the face of the surprise attack of this new developing infectious disease, the government is forced in the information not to be clear, meet an enemy attack hurriedly under the insufficient situation of human resources , it is undoubtedly the great test to the thing that the government prevents and cures tactics management. In this SARS campaign, epidemic prevention system , public health and medical system in Kinmen county ,etc., medical resources in the subsidiary island are insufficient. In the face of this invisible enemy, there is not precedent that can be followed, the epidemic situation breaks through world, breaks through the fence among administrations of counties and cities before spreading fast, the treatment course of short four months, it is inconvenient to not merely test the health epidemic prevention system traffic of whole world, and open the finally unprecedented test under influence of the little three direct links, conspicuous government in should should prevent and cure management system to new developing infectious disease the accident tactics lack too. This text is trying to deal with and start the mechanism and conduct in epidemic situation of Kinmen county, including deal with the mechanism , medical unit''s epidemic prevention tactics of hygiene and working measure and summarize the argumentation first in county office level epidemic situation, and elaborate SARS prevention and cure tactics of restoring period after the county office , in order to probe into this pondering over , studying and rebuilding thinking to government department of epidemic situation further. In anticipated benefit of this research, expect to be able to prevent and cure the tactics with step and study the necessity that the speciality of the door combines by probing into SARS, and the crisis is prevented and communicated to the importance of epidemic prevention, and how to master the epidemic situation trends, build and construct it with the standard operation procedure (SOP ) in accordance with following , and carry on the exercise of SARS and prevent and cure the operation mechanism, all it is Kinmen the county government it is for making storm essential prevention and cure tactics in conformity with SARS with as reference. Study and propose that there are eight points: I. Build and construct the combining calamity emergency system. II. Sed and shut national resources in conformity with the interconnected system after the legal infectious disease patient of Kinmen. III. Infect the critically ill machine network system putting up three two sides. IV. SARS prevents and cures the setting-up of standard homework procedure and procedure . V. Should open the little three direct links and defend and stop up the external case to move in with all strength . VI. Ask the central authorities to set up unified epidemic prevention goods and materials and equipment parameter. VII. Establish the normality epidemic prevention of the whole county and command the general headquarters. VIII. Set up epidemic prevention standard and link up the system.

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Munkhbat, Buyannemekh. "A Computational Simulation Model for Predicting Infectious Disease Spread using the Evolving Contact Network Algorithm." 2019. https://scholarworks.umass.edu/masters_theses_2/790.

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Commonly used simulation models for predicting outbreaks of re-emerging infectious diseases (EIDs) take an individual-level or a population-level approach to modeling contact dynamics. These approaches are a trade-off between the ability to incorporate individual-level dynamics and computational efficiency. Agent-based network models (ABNM) use an individual-level approach by simulating the entire population and its contact structure, which increases the ability of adding detailed individual-level characteristics. However, as this method is computationally expensive, ABNMs use scaled-down versions of the full population, which are unsuitable for low prevalence diseases as the number of infected cases would become negligible during scaling-down. Compartmental models use differential equations to simulate population-level features, which is computationally inexpensive and can model full-scale populations. However, as the compartmental model framework assumes random mixing between people, it is not suitable for diseases where the underlying contact structures are a significant feature of disease epidemiology. Therefore, current methods are unsuitable for simulating diseases that have low prevalence and where the contact structures are significant. The conceptual framework for a new simulation method, Evolving Contact Network Algorithm (ECNA), was recently proposed to address the above gap. The ECNA combines the attributes of ABNM and compartmental modeling. It generates a contact network of only infected persons and their immediate contacts, and evolves the network as new persons become infected. The conceptual framework of the ECNA is promising for application to diseases with low prevalence and where contact structures are significant. This thesis develops and tests different algorithms to advance the computational capabilities of the ECNA and its flexibility to model different network settings. These features are key components that determine the feasibility of ECNA for application to disease prediction. Results indicate that the ECNA is nearly 20 times faster than ABNM when simulating a population of size 150,000 and flexible for modeling networks with two contact layers and communities. Considering uncertainties in epidemiological features and origin of future EIDs, there is a significant need for a computationally efficient method that is suitable for analyses of a range of potential EIDs at a global scale. This work holds promise towards the development of such a model.

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Dissertations / Theses on the topic 'Infectious disease research'

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