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Beck, Melinda Annetta. "Regulation of cell-mediated immunity during reinfection with influenza virus /." The Ohio State University, 1987. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487324944212867.
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Leibler, Jessica H. "Characterizing the contribution of industrial food animal production to the transmission and emergence of influenza A viruses." Thesis, The Johns Hopkins University, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3579515.
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<p> The goal of my dissertation is to characterize the contribution of industrial food animal production to between-farm transmission of zoonotic influenza A viruses and transmission of these viruses from industrial food animals to humans. The intention of this research is to improve the capacity of public health policies in the United States to prevent the emergence of pandemic influenza viruses.</p><p> Preventing and controlling outbreaks within animal populations and avoiding human infection with zoonotic influenza A viruses can reduce the risk of emergence of pandemic influenza viruses in human populations. Industrial food animal production, which dominates the market in the United States and much of the developed world – and increasingly, the developing world as well – has long been considered biosecure. However, emerging research indicates that these industrial systems are vulnerable to disease incursions and suggests that they may play a central role in driving the emergence of zoonotic diseases. The implications of these industrial systems for human influenza risk, particularly the emergence of novel zoonotic influenza A viruses, remains largely unaddressed in the current literature and in health policy strategies in the United States. </p><p> Chapter 1 of this dissertation outlines my research goals and provides background on my central research themes and topics. Chapter 2 documents the limits of biosecurity within industrial systems, highlighting risks to food animal workers. Chapter 3 details a cross-sectional serology study of a cohort of industrial poultry workers and community members (n=99) in the Delmarva Peninsula, a tri-state area of intense poultry production in the Mid-Atlantic region of the United States. No evidence of infection with avian influenza viruses is observed in this population.</p><p> Chapter 4 contains a quantitative modeling study to estimates risk of between-farm transmission of avian influenza viruses among industrial poultry farms. This study concluded that company affiliation was a significant source of exposure risk from vehicular transmission. Chapter 5 is a policy analysis of the limitations of current pandemic preparedness policy in the United States to adequately incorporate primary prevention. The central results of this dissertation, their significance to public health and opportunities for further research are highlighted in Chapter 6.</p>
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Huneycutt, Brandon Scott. "Functional characterization and distribution of lymphokine secreting cells following influenza virus infection /." The Ohio State University, 1990. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487683049375098.
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Smith, Tammie. "The 2009 H1N1 influenza A “swine flu” virus presentation in Virginia 2009." VCU Scholars Compass, 2009. http://scholarscompass.vcu.edu/etd/1990.
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Objective: 2009 H1N1 influenza was first detected in the Northern Hemisphere in April 2009. National data have suggested that the novel influenza virus disproportionately causes severe illness in children and young adults, a somewhat different presentation from traditional seasonal flu which normally strikes hardest in the very young and older adults. This may or may not be the case in Virginia, which, if it is different, may suggest a need to alter flu prevention messages and vaccine policy as the outbreak continues through the fall 2009-10 influenza season. This report examined the early presentation of the new influenza virus in Virginia, compared with the seasonal flu presentation. Methods: Surveillance data of influenza-like illness (ILI) visits to hospital emergency departments and urgent care centers for the period Oct. 2008 to Aug. 2009 were obtained from the Virginia Department of Health. The period from Oct. 2008-March 2009 was considered to be the normal flu season, while April-Aug. 2009 was considered as the 2009 (novel) H1N1 flu season. Descriptive statistics looked for differences by age, region and sex with respect to the proportion of visits that were for influenza-like illness compared to all reported illness for the normal and H1N1 flu seasons. Chi square and p-values were used to assess the level and significance of differences between flu seasons. Results: While the 2009 H1N1 influenza was a novel virus that, like all influenza viruses, could mutate and change into a form causing more severe illness, during the early months of the epidemic/pandemic, the virus did not appear to cause more illness as a percent of all illness compared to the preceding months of influenza in Virginia. Though it was unexpected to have influenza-like illness in the amount seen during April-August 2009, with several exceptions the level of flu-like illness compared to all illness was not higher than during the normal flu season immediately preceding the appearance of the 2009 H1N1 influenza. Conclusion: During the early months of the novel influenza H1N1 epidemic/pandemic in Virginia, the novel influenza virus caused levels of illness that were lower than levels of illness seen during the preceding normal flu season. Further study that examines the novel influenza virus through the end of the 2009-10 season may help to quantify the impact of the new virus. Flu-like illness reports spiked, for instance, as schools and colleges returned for fall 2009 semesters.
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Wu, Cheng Ying. "Characterization of innate immune response to «Nicotiana benthamiana»-derived Influenza H5 virus-like particles." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=119400.
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Current influenza vaccine manufacturing processes using chicken-embryonated egg technology is a time-consuming and laborious process, and is currently the major drawback in counteracting pandemic influenza strain. One solution to that problem is the use of plants to generate vaccine antigen. Virus-like particles (VLP), produced from the tobacco plant Nicotiana benthamiana, represent a cost-effective, alternative platform for influenza vaccine production. Previous studies have shown that the immunization with VLP expressing the hemagglutinin (HA) protein from influenza virus H5N1 (H5-VLP) produced in N. benthamianainduce protective immunity against challenge of cross-clade virus in mice and ferrets. In this study, we used human peripheral blood mononuclear cells (PBMC) to characterize the innate immune response to plant-derived influenza H5-VLP ex vivo. We successfully demonstrate the mitogenic property of H5-VLP on PBMC ex vivo. Furthermore, we detect up-regulation of activation marker in B cells and NK cells, and some T cells. Cytokine profile of the supernatant from VLP-stimulated sample suggests that inflammatory response dominates the innate immunity within first 48 hours and is produced by CD14+ monocytes. Our study demonstrates that tobacco plant-derived influenza VLP are capable of generating innate immune responses in naïve human PBMC, helping us to better understand the immunostimulatory nature of this potential vaccine candidate.<br>A l'heure actuelle, la plupart des vaccins contre les infections par le virus influenza sont produits à partir d'œufs de poule fécondés. Ce procédé long et fastidieux constitue l'un des principaux obstacles à la production rapide d'un vaccin lors d'une pandémie. Une solution à ce problème consiste en l'utilisation de plantes afin de générer les antigènes nécessaires à l'élaboration du vaccin. Les pseudovirus ou Virus-like particles (VLP) produites à partir de la plante de tabac Nicotiana benthamiana représentent une alternative moins couteuse et plus rapide pour la production de vaccins antigrippaux. Des études préalables ont démontré qu'une immunisation avec les VLP exprimant l'hémagglutinine (HA) du virus influenza H5N1 (H5-VLP) induisaient une immunité protective lors d'une infection par ce virus chez la souris et le furet. Dans notre étude, nous avons utilisé les cellules mononuclées du sang périphérique humain (PBMC) afin de préciser la réponse immunitaire innée suite à l'exposition ex vivo aux H5-VLP produites dans N. benthamiana. Nous avons démontré les propriétés mitogéniques des H5-VLP sur les PBMC ainsi qu'une activation des lymphocytes B, des cellules NK et de certaines sous populations de lymphocytes T. L'analyse des cytokines sécrétées dans le surnageant des PBMC exposés ex vivo aux VLP suggère qu'une réponse pro-inflammatoire prédomine 48h après exposition et semble résulter essentiellement d'une activation des monocytes CD14+. Notre étude démontre que les VLP produites à partir de la plante de tabac génèrent une réponse immunitaire innée dans les PBMC provenant de patients naïfs, nous permettant ainsi de mieux comprendre les propriétés immunostimulantes de ce nouveau type de vaccin.
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Vo, Ho Hong Hai. "Élaboration de nouvelles stratégies thérapeutiques à l'encontre du virus de la grippe." Phd thesis, Université Claude Bernard - Lyon I, 2011. http://tel.archives-ouvertes.fr/tel-00903685.
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Les virus influenza provoquent chaque année la grippe saisonnière qui peut toucher 5 à 15 % de la population. Les médicaments antiviraux sont un moyen important complémentaire à la vaccination pour le traitement et la prévention de la grippe. Actuellement, deux classes d'antiviraux ont été approuvées, l'une pour inhiber l'étape de décapsidation (l'inhibiteur du canal ionique M2), et l'autre pour empêcher la libération de néo-virions (l'inhibiteur de la neuraminidase). Cependant, de plus en plus de virus sont nativement résistants aux inhibiteurs de la protéine M2. Des virus résistants aux inhibiteurs de la neuraminidase ont également circulé durant les hivers 2008 - 2009. Le développement de nouveaux médicaments afin de substituer ou de compléter ces inhibiteurs est donc crucial dans la lutte contre les virus de la grippe. L'accent mis ces dernières années sur l'activité biologique des sucres (oligosaccharides/polysaccharides) montre une voie pour l'étude de l'activité antivirale d'une des plus importantes biosources. Dans le but d'évaluer le potentiel antigrippal des molécules dérivées de sucres, nous avons effectué un criblage à partir d'une bibliothèque de 245 composés de polysaccharides et d'oligosaccharides, dont la plupart proviennent d'algues et de végétaux supérieurs. Plusieurs molécules actives réparties dans différentes familles de sucres ont été mises en évidence. Parmi les candidats d'intérêt, l'oligosaccharide sulfaté 152, appartenant à la famille des arabinogalactanes de l'espèce Codium fragile, a présenté une activité inhibitrice vis-à-vis des deux virus influenza de type A et de type B in vitro. Le mécanisme d'action de cet oligosaccharide a été caractérisé. Il montre que les deux glycoprotéines de surface, l'hémagglutinine et la neuraminidase, sont les cibles virales de cette molécule
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Romijn, Phyllis Catharina. "Studies on porcine influenza viruses." Thesis, University of Surrey, 1989. http://epubs.surrey.ac.uk/847965/.
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A number of different cell cultures were examined for their susceptibility to the influenza virus A/swine/Weybridge/86(H1N1) and A/swine/Weybridge/87(H3N2). PK1 (porcine kidney) was found to be the most susceptible to the viruses, and MDCK (canine kidney), the best cell line for primary isolation. A method of infectivity assay by immunoperoxidase in microplate cultures of MDCK cells was developed which was simple enough for routine use and practically as sensitive as the egg infectivity test. The potential risks of accidental importation of influenza infection in pig was assessed by determining the survival time of the porcine influenza virus H1N1 in pig tissues. It was found that the virus may keep its infectivity in frozen (-20°C) pig tissues for up to 15 days. The interspecies transmission of porcine influenza viruses was studied using turkeys infected with porcine influenza isolates. Although both A/swine/Weybridge/86 and A/swine/Weybridge/87 were transmitted from infected turkeys to pigs, only A/swine/Weybridge/86(H1N1) infected turkeys presented clinical signs of disease. More than 50% of the pigs presented the virus in the nostrils and/or faeces, at some time during the experiment, and all seroconverted. Transmission from these pigs to newly introduced turkeys was not observed, nor was seroconversion detected. Influenza epidemiology in Brazil was investigated by serological studies using pig sera collected in different areas of that country, using human, porcine and avian isolates of influenza viruses. Highest antibody titres were found against A/Leningrad/86(H3N2) (19%) and A/Port Chalmers/73(H3N2) (17%), but not against specific porcine isolates. Only serological evidence was found to suggest that reassortant influenza viruses occur in English pig herds. However, interspecies transmission of influenza viruses between man and pigs, and the maintenance of human strains in English pig herds was demonstrated by the isolation of two H3N2 influenza viruses very similar to A/Port Chalmers/73, present in the human population in the 1970s.
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Wong, Yuen-ting, and 黃婉婷. "Burden and severity of influenza viruses." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/207194.
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Background: The seriousness of human influenza virus infection, in combination with the transmissibility of the virus, determines the impact that the virus will have in a population. However, the uncertainty surrounding the seriousness and changes in seriousness hindered the calibration of the early public health response.
Methods: I applied statistical models to population-based mortality data and hospitalizations among patients with laboratory-confirmed H1N1pdm09. I estimated the disease burden, retrospectively and prospectively determined seriousness of influenza virus infections including the risk of death on a per-infection basis (IFR) and on a per-hospitalization (HFR) of H1N1pdm09, and investigated changes in seriousness. I used serologic surveillance data to estimate the cumulative incidence of infection in a population, and used it as the denominator of the IFR. I also conducted systematic reviews and meta-analysis to summarize published estimates of the risk of death among cases (CFR) and HFR of the pandemic influenza H1N1pdm09 virus.
Results: I estimated that the first wave of H1N1pdm09 was associated with approximately 232 (95% confidence interval: 136, 328) excess deaths in all ages in Hong Kong, which was around 4 times the observed number of laboratory-confirmed deaths of H1N1pdm09. The point estimates for the IFR and HFR increased substantially with age. I included 77 estimates for the CFR from 50 published studies; whereas I included 187 estimates for the HFR from 184 published studies. The CFR was widely used to assess seriousness but the variation of a ‘case’ varied considerably in the literature. Variability in published estimates of the HFR was much less than variability in the CFR.
Conclusions: Early in the next pandemic, estimation of the HFR, IFR or symptomatic CFR may provide a timely picture of the seriousness of infection, particularly if presented in comparison between two influenza virus infections in the same setting. Ongoing monitoring of mortality and influenza activity could permit identification of changes in seriousness of influenza virus infections.<br>published_or_final_version<br>Public Health<br>Doctoral<br>Doctor of Philosophy
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Mamlouk, Aymen. "Etude de la transmission du virus influenza au sein de populations d'Anatidae." Phd thesis, Université de Grenoble, 2011. http://tel.archives-ouvertes.fr/tel-00656003.
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Les virus influenza A ont suscité à partir de l'année 1997 un intérêtsanitaire et économique mondial considérable après l'émergence d'une formehautement pathogène d'un virus influenza aviaire H5N1. Cette épizootie a misen évidence le danger majeur que constitue la proximité entre espècessensibles sauvages et domestiques. En effet, pouvant présenter lescaractéristiques de réservoirs de ces virus, les canards étaient les plussoupçonnés de transmettre l'infection, grâce à une pratique migratoireimportante et d'un portage asymptomatique fréquent. Ce portage associe dans la plupart des cas des virus faiblement pathogènesde sous-types multiples. Ces virus peuvent se transmettre aux volaillesdomestiques et émerger en épizootie à virus hautement pathogène dans le casparticulier des sous-types H5 et H7. Ces épizooties peuvent avoir desconséquences économiques considérables, avec une mortalité avoisinant les100%, et sanitaire avec un possible passage à l'homme. Notre projet vise à caractériser l'infection et la transmission des virusinfluenza faiblement pathogènes, après inoculation expérimentale à unepopulation de canards de surface et plongeurs. Il répond également à lanécessité d'établir des méthodes de surveillance des virus influenzaaviaires à l'arrivé des oiseaux migrateurs dans des zones humides à richepatrimoine ornithologique, et situées à proximité de régions à fortpotentiel en matière de production avicole (La Dombes comme exemple).
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Noble, Simon. "Studies on DI influenza A viruses and the antigenic characterisation of swine influenza isolates." Thesis, University of Warwick, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.282535.
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Hunzeker, John T. "Differential effects of stress on the immune response to influenza A/PR8 virus infection in mice." Connect to this title online, 2004. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1080588837.
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Thesis (Ph. D.)--Ohio State University, 2004.<br>Title from first page of PDF file. Document formatted into pages; contains xvi, 231 p.; also includes graphics Includes bibliographical references (p. 211-231). Available online via OhioLINK's ETD Center
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Sribanditmongkol, Vorachai. "Effects of Psychological Stress on Glucocorticoid Sensitivity of Inflammatory Response to Influenza Vaccine Challenge in Healthy Military College Students." The Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1366195257.
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Htway, Zin. "The Burden of Avian Influenza Viruses in Community Ponds in California." ScholarWorks, 2014. https://scholarworks.waldenu.edu/dissertations/89.
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Emerging influenza viruses continue to challenge public health. The problem is public health science professionals have been battling emerging human influenza diseases with tactile and reactionary methods because there is a lack of knowledge and data at the human-animal interface. This research was a baseline study of the proportion of influenza A virus (IAV) in urban and rural communities in California. The population was artificial recirculating water ponds in the geographic locations of rural and urban Californian communities. Surface water samples [N = 182] were collected from artificial recirculating ponds in California. Positivity for IAV was verified by real time RT-PCR, MDCK cells for virus infectivity, nucleotide sequencing of the RNA genome, and phylogenic analysis of IAV H5N1 strains. The proportion of IAV in rural and urban ponds favored the greater burden of IAV in urban ponds over rural ponds. The presence of waterfowl and IAV M gene sequence positivity were found not to be significantly related. The geochemical properties--pH, salinity, and water temperature at time of collection--were not predictors of IAV infectivity. This baseline research study validated these water ponds as resource sites for IAV surveillance and monitoring. The social change implications of this study can be recognized at the national and international levels, to the population level, and to the individual level by providing geospatial analysis and spatial-temporal data for IAV surveillance, initiating biosecurity measures to protect poultry industries in the United States and Brazil, and contributing to the current IAV strain library. Contributions to the IAV strain library may be used to develop vaccines against human pandemics.
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Szablewski, Christine Marie. "Evolution of Influenza A Viruses in Exhibition Swine and Transmission to Humans, 2013-2015." The Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu151388886442666.
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Jameson, Julie Marie. "The CTL Memory Responses to Influenza A Viruses in Humans: a Dissertation." eScholarship@UMMS, 1999. https://escholarship.umassmed.edu/gsbs_diss/134.
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Influenza A virus infections are a major cause of morbidity and mortality in the United States and throughout the world. The current vaccine elicits primarily a humoral response that is specific for the external glycoproteins hemagglutinin (HA) and neuraminidase (NA). However, these are the viral proteins that are most susceptible to antigenic shift and drift, and can evade the humoral response. Cytotoxic T lymphocytes (CTL) recognize and lyse virus-infected cells and are important in clearing influenza A virus infections. CTL can recognize epitopes on both the external glycoproteins and the more conserved internal viral proteins. This thesis investigates the hypothesis that there is a broad CTL memory response in humans, and, if boosted by vaccines, these CTL may help clear influenza A virus strains of different subtypes.
The CTL repertoire specific for influenza A viruses reported in inbred mice is extremely limited and has focused on a few immunodominant epitopes. We perfonned preliminary bulk culture chromium release assays using human peripheral blood mononuclear cells (PBMC) stimulated with influenza virus strain A/PR/8/34 (H1N1) in vitro. CTL activity was observed against autologous B-lymphoblastoid cell lines (B-LCL) infected with vaccinia constructs that expressed several influenza A viral proteins, including nucleoprotein (NP), matrix (M1), nonstructural 1 (NS1) and polymerase (PB1). This was more diverse than the limited response reported in inbred mice. To further characterize the CTL repertoire in humans, PBMC from healthy adult donors were stimulated and CTL were cloned by limiting dilution. Isolated cell lines were further characterized by their CD4/CD8 surface expression, histocompatibility leukocyte antigen (HLA) restriction, cross-reactive or subtype-specific influenza A subtype recognition, and epitope recognition.
CTL lines isolated from three donors recognized epitopes on many different influenza virus proteins. The ELISPOT assay was used to identify the number of IFN-γ- secreting cells and determine the precursor frequency of the CTL specific for the epitopes that were mapped. The precursor frequency of IFN-γ producing CTL ranged from 1 in 4,156 PBMC to 1 in 31,250 PBMC. The precursor frequency for one epitope was below the level of detection of this assay, but most of the memory CTL were readily detected. The cross-reactive or subtype-specific recognition of various human influenza A subtypes by these T cell lines was determined by chromium release assays. Most of the CTL lines recognized B-LCL infected with any of the three influenza A subtypes that have caused epidemics in the last century (H1N1, H2N2, and H3N2) and recognized epitopes on conserved internal influenza viral proteins. Most of the subtype-specific cell lines recognized the surface HA or NA glycoproteins, which are not well conserved between influenza subtypes.
Although most of the T cell lines that were characterized were cross-reactive with influenza viruses of human origin, infection of humans with a divergent swine or avian derived strain could cause a global pandemic. To study the human CTL responses to non-human influenza viruses, B-LCL were infected with an Hsw1N1 influenza A virus of swine origin, and cell lines were tested for recognition of these targets in a chromium release assay. Most cell lines lysed the targets infected With the Hsw1N1 subtype to the same degree as targets infected with the human H1N1 strain. Two influenza viruses of duck origin were also tested and were recognized by many of the cell lines. The subtypes of these duck strains were Hav1N1 and H5N2. The isolates of influenza A virus from the Hong Kong outbreak of 1997 were also used to infect targets and analyze recognition by these CTL. We found that approximately 50% of the human T cell lines tested recognized both of the Hong Kong isolates, 25% recognized at least one isolate, and 25% recognized neither isolate to the same degree as the A/PR/8/34 (H1N1) virus. We analyzed the amino acid (aa) changes in the epitopes of the T cells lines from the 25% of cell lines that did not recognize either Hong Kong virus isolate. Non-conservative mutations were found in all of the epitopes that lost recognition by the human CTL lines. Bulk cultures of PBMC from three donors that were stimulated with A/PR/8/34 (H1N1) influenza A virus of human origin recognized all of the non-human virus strains tested. Thus, humans have memory CTL that recognize influenza viruses of avian and swine species. This may provide a second line of defense against influenza infection in case of exposure to a novel influenza A virus derived from these species.
These results made it clear that humans have broad CTL memory to influenza A virus. In order to determine whether these T cells could be boosted in a vaccine, immune-stimulatory complexes (Iscom) incorporating inactivated influenza particles were tested in vitro. Iscoms containing inactivated influenza A vaccine (Flu-Iscom) were used to pulse autologous B-LCL overnight that were then used as targets in chromium release assays with human CTL lines as effectors. A CD8+ HA-specific CTL line lysed these targets, but not targets pulsed with Iscoms alone or with inactivated influenza A vaccine alone. An NS1-specific cell line recognized targets pulsed with NS1 protein and Iscoms, but not targets pulsed with Iscoms or NS1 protein alone. Therefore, CTL could recognize in vitrotarget cells that were exposed to the Iscom vaccines containing their specific epitope.
Flu-Iscom and Iscom mixed with inactivated influenza virus particles (Flu-Iscomatrix) were then used as vaccines in a clinical trial to test CTL and neutralizing antibody induction against influenza. Fifty-five donors were bled pre-vaccination, and on days 14 and day 56 post-vaccination. Bulk culture chromium release assays were performed using targets infected with live vaccine strain viruses. There were significantly more increases in the influenza A specific CTL activity in the PBMC of donors that were vaccinated with the Flu-Iscom and Flu-Iscomatrix vaccines than in recipients of the standard vaccine. In order to determine whether these increases in cytotoxicity were due to an increase in the precursor frequency of influenza specific CTL, the PBMC were used in ELISPOT assays to assess the changes pre-and post-vaccination. When there was an increase in the level of cytotoxicity detected in bulk culture CTL, there was often also an increase in the precursor frequency of influenza-specific CTL. Peptide-specific increases in the number of CTL that recognize epitopes such as M1 aa 58-66 were detected in several donors confirming the increase in influenza-specific CTL post-vaccination.
Another type of T cell that may be involved in defense against viruses is the γδ T cell. T cells expressing the γδ T cell receptor (TCR) have been found extensively in mucosal tissues in mice and humans. Influenza A viruses enter via the airway tract, infecting the epithelial cells at the mucosal surface. These epithelial cells have been shown in vitro to be targets for influenza-specific cytolytic recognition of αβ T cells. To analyze whether γδ T cells can respond to influenza A-infected APCs, PBMC were stimulated with influenza A virus. Intracellular IFN-γ staining was used to determine whether γ/δ T cells can secrete IFN-γ in response to the influenza A virus infection. We observed an increase in the percentage of γ/δ T cells secreting IFN-γ post-influenza A virus infection of PBMC compared to uninfected or allantoic fluid-stimulated cultures. These T cells also upregulated CD25 and CD69 in response to live influenza A virus. We focused on the responses in the CD8- population of γδ T cells, which are the majority of γδ T lymphocytes. Furthermore, the increases in IFN-γ production and activation marker expression were much more clear in the CD8- γδ+ T cells. The level of CD8- γδ T cell activation with inactivated influenza A virus was much less, and in some cases no higher than uninfected PBMC. The CD8+ αβ and γδ responses could be partially blocked by anti-class I antibodies, but the CD8- γδ responses could not. Vaccinia virus infection did not activate the CD8- γδ T cells to the same degree as influenza virus infection. γδ T cells are thought to have a regulatory role that includes the secretion of cytokines and epithelial growth factors to help restore tissue back to health.
Humans have broad multi-specific T lymphocyte responses by αβ T cells to influenza A viruses and those responses are cross-reactive with human, avian, and swine virus strains. These CTL can be activated in vitro and boosted in number in vivo by Iscom incorporating vaccines. There is also a population of γδ+ T lymphocytes in humans that responds to influenza virus infection by producing cytokines and becoming activated. Increasing memory CTL as a second line of defense against influenza A viruses may be important in future vaccine development.
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Slater, Tessa. "Bat lung epithelial cells show variable species-specific susceptibility to human and avian influenza viruses." Thesis, University of Nottingham, 2018. http://eprints.nottingham.ac.uk/49403/.
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The recent identification of two novel influenza-like viruses in bats, H17N10 and H18N11 virus, and the discovery of serologically positive Eidolon helvum bats in Ghana for avian H9 virus prompted my hypothesis that, in addition to the large repertoire of zoonotic viruses hosted, bats may serve as asymptomatic reservoir species to conventional influenza A viruses found in birds and mammals. To begin to test this hypothesis, the susceptibility of three bat cell lines, derived from lung epithelial cells of Eidolon helvum, Carollia perspicillata and Tadarida brasiliensis (TB1-Lu), to low pathogenicity avian viruses (H2N3 [A/mallard duck/England/7277/06] virus and H6N1 virus [A/turkey/England/198/09] virus), and human viruses (USSR H1N1 virus [A/USSR/77] and pandemic H1N1 2009 virus [A/California/07/2009]) was determined. All three species of bat epithelial cells were found to be more robust and resistant to influenza virus infections than permissive MDCK cells. Infected bat cells produced lower levels of viral RNA and viral progeny, and were more viable than correspondingly treated MDCK cells. Interestingly, bat cells were more susceptible and replication permissive to avian than human influenza viruses. Among the bat cells, TB1-Lu cells were the least susceptible to influenza virus infection and that appears to be related to a lack of sialic acid α2,6-Gal receptors, mammalian virus-preferred host receptors, which were present in the other two bat species. The innate mechanisms underlying resistance to influenza virus infection in bats remains to be determined, however, inhibition of the JAK/STAT pathway was found not to affect virus production from infected bat cells suggesting that JAK/STAT signalling may not have a major role in influenza virus resistance in bat cells. Modulation of NF-κB signalling was found to affect virus production suggesting that tight regulation of NF-κB may be key in controlling the pro-inflammatory response to influenza infection in bat cells and warrants further investigation.
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Cole, Suzanne Lois. "Contribution of monocytes to immunopathology during influenza A virus infection." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:db927890-61de-405e-8681-8f5c33f08591.
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Brown, Ian Hamer. "Epizootiology of influenza in pigs in Great Britain with emphasis on characterisation of viruses isolated since 1986." Thesis, Open University, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.336800.
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Wu, Muzo. "Innate Immunity Immunomodulators in Post-Influenza Bacterial Pneumonia." Thesis, Harvard University, 2015. http://nrs.harvard.edu/urn-3:HUL.InstRepos:16121158.
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Post-influenza bacterial pneumonia is a major cause of morbidity and mortality worldwide. One mechanism for enhanced susceptibility to bacterial infection after influenza is down-regulation of a major phagocytic receptor on alveolar macrophages, macrophage receptor with collagenous structure (MARCO), by interferon- (IFN-), which leads to diminished bacterial clearance. Nrf2, a transcription factor that regulates expression of antioxidant genes, is one of the regulators of MARCO expression. We show that the Nrf2 activator sulforaphane improves MARCO expression and bacterial phagocytosis in alveolar macrophage (AM)-like human monocyte-derived macrophages (HMDMs). It also improves host survival by up-regulating MARCO in a murine model of post-influenza pneumococcal pneumonia.
MARCO is spontaneously restored and upregulated in the later phase of influenza virus infection. Initially, elevated IFN levels following influenza infection coincide with attenuated MARCO expression in the lungs. However, as IFN levels returned to normal levels on post-influenza day 11, there was a striking 4.86-fold increase of MARCO expression compared to the low level observed on day 9. To identify regulatory mechanisms underlying this rebound or enhanced post-influenza MARCO expression, we performed RNA sequencing analysis of purified lung macrophages from post-influenza day 9 and 11. Among the differentially expressed genes between post-influenza day 9 and day 11 macrophages were MARCO and Akt. The Akt activator SC79 significantly increased MARCO expression on IFN-treated AM-like HMDMs, whereas the Akt inhibitor perifosine reduced MARCO expression on HMDMs. SC79 treatment significantly improved mouse survival in post-influenza pneumococcal pneumonia.
Transcription factor E-box (TFEB) is one of the overrepresented transcription factors binding to candidate genes in our RNA sequencing analysis. SC79-induced MARCO expression in IFN-treated HMDMs was abrogated in TFEB knockdown cells compared to controls. The results suggest that Akt regulates MARCO expression through effects on the transcription factor TFEB.
In summary, immunomodulators like Nrf2 activators and Akt activators may promote MARCO expression and host survival in post-influenza bacterial pneumonia, and provide effective preventive and therapeutic strategies against a common and important complication of influenza. Further elucidation of the Akt-TFEB-MARCO pathway may inform therapies to reduce susceptibility to post-influenza bacterial pneumonia.<br>Environmental Health
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Chui, Cecilia. "Memory T cell responses in influenza A infection and vaccination in humans." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:47660117-917b-48a8-81aa-b3448cf8ec0f.
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Protective immunity against influenza virus infection is believed to be mediated by neutralising antibodies. Despite substantial evidence in animal models which suggests critical roles for T cells in viral clearance, the precise role of cellular immunity in human influenza immunity remains uncertain. The first aim of this project was to determine cellular immune responses in seronegative human volunteers following nasal challenge with live seasonal H3N2 or H1N1 viruses. T cell responses before and during infection were mapped. A large increase in both breadth and magnitude in influenza-specific CD4<sup>+</sup> T cell responses was seen in the blood by day 7, when virus was completely cleared from nasal samples and serum antibodies were still undetectable. These acutely expanded T cells were shown to be highly activated (CD38<sup>+</sup>) and proliferating (Ki-67<sup>+</sup>). Pre-existing CD4<sup>+</sup> T cells, but not CD8<sup>+</sup>, specific to internal proteins nucleoprotein and matrix proteins, were associated with lower virus shedding and less severe illness. These influenza-specific T cells also responded to A/California/07/2009 (H1N1) peptides, were able to kill antigen-loaded autologous B cell lines in vitro and were polyfunctional in cytokine production. The second aim was to assess the cellular immune responses to unadjuvanted, inactivated seasonal and pandemic A/California/07/2009 (H1N1) influenza vaccines. 151 healthy adult volunteers were vaccinated: modest influenza-specific T cell responses were induced, and specific responses to HA and NA peptide pools were found to be mediated by CD4<sup>+</sup> T cells. Activated and proliferating cells induced during vaccination were found to be of a central memory phenotype. Lastly, I explored the link between antibody production and CD4<sup>+</sup> T cells. The ability of CXCR5<sup>+</sup> CD4<sup>+</sup> T cells from peripheral blood to support antibody production was examined and antigen-specific CD4<sup>+</sup> T cells with helper functions could be found in the peripheral blood of healthy volunteers with memory influenza-specific T cells. This thesis suggests that influenzaspecific CD4<sup>+</sup> T cells have an important role in limiting the severity of influenza infection in the absence of specific antibody responses through a number of mechanisms. This work provides information on how cellular immunity can be targeted in conferring broad protection against different subtypes of influenza A viruses in the development of universal flu vaccine.
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Paparone, Pamela A. "Leadership and Attitudes on Adopting Evidence-Based Practice for Influenza Vaccination." Thesis, Walden University, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3619606.
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<p> The United States has set a 90% benchmark for influenza vaccinations for healthcare personnel. Unfortunately, healthcare personnel fall far short of that mark with current rates as low as 62%. Low vaccination rates are responsible for influenza, nosocomial influenza, influenza-like illness, and mortality during influenza season. The purpose of this quantitative correlational study was to understand the relationship between leadership styles, attitudes towards evidence-based practice, and vaccination intention among New Jersey registered nurses (RNs). Diffusion of innovations theory was the theoretical foundation. The 3 instruments used were the Multifactor Leadership Questionnaire, Evidence Based Practice Attitude Scale, and Behavioral Intention Scales, which measured independent variables such as transformational leadership and attitudes toward evidence-based practice. Vaccination intent was the dependent variable. The results showed that transformational leadership was positively related to vaccination intent <i>r</i>(353) = .16, <i>p</i> < .01. There was no relationship between transactional leadership and vaccination intent <i>r</i>(353) = .01, <i>p</i> > .05 nor between attitudes toward evidence-based practice and vaccination intent <i> r</i>(353) = .09, <i>p</i> > .05. The implication of the study is that the effects of transformational leadership constitute a predictive tool to identify how an organization can increase vaccination rates among RNs. Implementing the recommendations of the study could promote social change by providing nursing leadership with tools to facilitate increased vaccination rates among health care personnel. Increasing vaccination rates for healthcare personnel will decrease vaccine-preventable illnesses and improve outcomes for hospitalized patients.</p>
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Lam, Po-Po. "Approaches to implementing an influenza vaccine decision aid for healthcare personnel." Thesis, University of Ottawa (Canada), 2010. http://hdl.handle.net/10393/28608.
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The Ottawa Influenza Decision Aid (OIDA) is a newly developed tool to assist healthcare personnel (HCP) make an informed decision regarding the seasonal influenza vaccine. The primary objective of this thesis is to determine approaches to implementing the OIDA into healthcare organizations by 1) conducting a systematic review of influenza immunization campaigns for HCP; 2) facilitating consultation meetings with healthcare organizers to collect their ideas on using the OIDA within their workplace; and 3) develop an OIDA implementation questionnaire based on the findings from the systematic review and consultation meetings. The systematic review results suggest that education-only campaigns only have a minimal impact on immunization rates. Future studies require improved reporting on the follow-up of HCP and calculation of HCP immunization rates. The consultation meetings identified ten approaches to implementing the OIDA within a healthcare setting. The OIDA Implementation Questionnaire was designed and a survey implementation approach recommended.
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Lorbach, Joshua. "Gaps in Human Immunity Against Swine Origin Influenza A Viruses and the Use of Swine Vaccination to Reduce Public Health Threat." The Ohio State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu1587727549815743.
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Chartrand, Caroline. "Rapid influenza diagnostic tests: a meta-analysis of 127 studies." Thesis, McGill University, 2011. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=104871.
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BACKGROUND: Timely diagnosis of influenza is important to administer appropriate antiviral therapy, institute proper infection control measures, and decrease ancillary test usage. While viral culture or reverse-transcriptase polymerase chain reaction (RT-PCR) are considered the most accurate diagnostic tests, a vast array of rapid influenza diagnostic tests (RIDTs) is available and could potentially impact patient management at the point-of-care. OBJECTIVE: To summarize, using meta-analysis, available evidence on the diagnostic accuracy of RIDTs compared to a reference standard in adults and children with influenza-like illness and to evaluate patient and test factors associated with higher accuracy.METHODS: Four databases (MEDLINE, EMBASE, Biosis, Web of Science) were searched up to and including September 2010 for studies on RIDTs' accuracy compared to a reference standard of either RT-PCR (first choice) or viral culture. Sensitivity and specificity were pooled using a bivariate random effects regression model and investigation of heterogeneity was done using subgroup analyses and meta-regression using an extension of the summary receiver operating characteristic curve (SROC) model. RESULTS: A total of 100 articles, comprising 127 studies were identified. The pooled sensitivity of all RIDTs was 64.5% (95% CI: 60.6, 68.6), while the pooled specificity was 98.1% (95% CI: 97.3, 98.6). Sensitivity estimates were highly heterogeneous. Some of this heterogeneity was explained by significantly higher sensitivity in children (71.1%, 95% CI: 65.6, 76.1) than in adults (51.6%, 95% CI: 43.9, 59.1). Virus type also accounted for some of the heterogeneity in sensitivity (68.0%, 95% CI: 62.3, 73.1, for influenza A versus 51.8%, 95% CI: 42.8, 60.6, for influenza B) as well as the circulating strain of influenza A (56.9%, 95% CI: 50.9, 62.6, for influenza A/H1N1/2009 versus 72.8%, 95% CI: 65.9-78.8, for other seasonal influenza A strains). Finally, RIDTs performed better when compared against culture as the reference standard (sensitivity of 71.0%, 95% CI: 65.9, 75.6) than when compared against RT-PCR (sensitivity of 56.0%, 95% CI: 49.7, 62.1). Few studies reported duration of symptoms before testing, but studies that did showed a trend toward better accuracy at 24-48h with a rapid decline thereafter. When a meta-regression was conducted including several study-level covariates, only age remained significant with a relative diagnostic odds ratio (RDOR) of 2.67 (95% CI: 1.17, 6.11) for children versus adults.CONCLUSION: RIDTs have modest sensitivity and high specificity, but heterogeneity in sensitivity is a concern. While they are more accurate in children than adults, and for influenza A compared to influenza B, these factors do not completely explain the heterogeneity in sensitivity. Because of their high specificity, RIDTs may be useful to rule in influenza. However, a negative test cannot be used to rule out influenza and should be confirmed by one of the reference standard tests. Further work is needed to summarize the clinical impact of RIDTs on patient management and patient-important outcomes.<br>INTRODUCTION: Poser rapidement le diagnostic d'influenza permet d'administrer une thérapie antivirale appropriée, de débuter en temps opportun des mesures de prévention des infections et de diminuer le recours à d'autres tests diagnostiques. Bien que la culture virale et le RT-PCR demeurent les outils diagnostiques les plus fiables, il existe une vaste gamme de tests de diagnostic rapide de l'influenza (TDRI) pouvant potentiellement avoir un impact sur la prise en charge des patients. OBJECTIFS: Résumer, par le biais d'une méta-analyse, l'ensemble des données disponibles sur la sensibilité et la spécificité des TDRIs comparés à un test de référence, chez les adultes et les enfants souffrant d'un syndrome d'allure grippal, ainsi qu'évaluer les facteurs liés au test ou au patient qui sont associés à une plus grande fiabilité. MÉTHODES: Nous avons cherché à travers quatre bases de données (PubMed, EMBASE, Biosis, Web of Science), jusqu'en septembre 2010, pour des études sur la fiabilité des TDRIs comparés au RT-PCR (1er choix) ou à la culture virale. Nous avons méta-analysé la sensibilité et spécificité des TDRIs au moyen d'un bivariate random effect regression model et tenté d'expliquer l'hétérogénéité des résultats au moyen d'analyses de sous-groupes et d'une méta-régression, via une extension du modèle SROC (summary receiver operating characteristic curve).RÉSULTATS: Nous avons identifiés 100 articles, comprenant 127 études. La sensibilité globale des TDRIs était de 64.5% (95% CI: 60.6, 68.6), alors que leur spécificité globale était de 98.1% (95% CI: 97.3, 98.6). Par contre, on a retrouvé une grande hétérogénéité au niveau de la sensibilité. Une partie de cette hétérogénéité pourrait être expliquée par une sensibilité significativement plus élevée lorsque le test est utilisé chez les enfants (71.1%, 95% CI: 65.6, 76.1) plutôt que chez les adultes (51.6%, 95% CI: 43.9, 59.1). La sensibilité des TDRIs variait également en fonction du type de virus (68.0%, 95% CI: 62.3, 73.1, pour l'influenza A versus 51.8%, 95% CI: 42.8, 60.6, pour l'influenza B) ainsi que de la souche d'influenza A en circulation (56.9%, 95% CI: 50.9, 62.6, pour l'influenza A/H1N1/2009 versus 72.8%, 95% CI: 65.9-78.8, pour les autres souches saisonnières d'influenza A). Finalement, les TDRIs affichaient une meilleure performance lorsque comparés à la culture virale (sensibilité: 71.0%, 95% CI: 65.9, 75.6) plutôt qu'au RT-PCR (sensibilité: 56.0%, 95% CI: 49.7, 62.1). Peu d'études ont évalué l'effet de la durée des symptômes sur la fiabilité des TDRIs, mais les quelques études qui se sont penchées sur le sujet tendaient à démontrer une meilleure sensibilité 24-48h après le début des symptômes suivi d'un déclin rapide. Lorsque plusieurs de ces variables furent analysées en même temps, au moyen d'une méta-régression, seulement l'âge est demeuré significativement associé à la fiabilité des TDRIs, avec un rapport de cotes diagnostiques de 2.67 (95% CI: 1.17, 6.11) pour les enfants versus les adultes.CONCLUSION: Les TDRIs ont une sensibilité modeste et une bonne spécificité, mais une grande hétérogénéité au niveau de la sensibilité demeure une préoccupation. Bien que les TDRIs soient plus fiables chez les enfants que chez les adultes et pour détecter l'influenza A versus l'influenza B, ces facteurs ne suffisent pas à expliquer l'hétérogénéité notée au niveau de la sensibilité. Puisqu'ils sont très spécifiques, les TDRIs sont utiles pour confirmer le diagnostic d'influenza. Cependant, un TDRI négatif n'est pas suffisant pour infirmer le diagnostic d'influenza et devrait être confirmé au moyen d'un des tests de référence. D'autres études sont nécessaires pour résumer l'impact clinique des TDRIs sur la prise en charge des patients.
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Brien, Stephanie. "Determinants of 2009 pandemic A/H1N1 influenza vaccination in Montreal." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=106462.
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To develop successful vaccination programs for influenza pandemics, it is essential to understand the neighborhood-level factors that influence vaccination. Few studies have used an immunization registry to examine the neighborhood determinants of pandemic influenza vaccination among the general population. Using individual-level vaccination data and census, survey and administrative data to estimate the population at risk, an ecological study of the neighborhood determinants of 2009 pandemic A/H1N1 influenza vaccination in Montreal was conducted. Using logistic regression, accounting for spatial autocorrelation, the neighborhood socioeconomic and demographic determinants of pandemic influenza vaccination were identified among the total population and stratified by priority group. In Montreal, 918,733 (49.9%) residents were vaccinated against pandemic A/H1N1 influenza. Coverage was greater among females compared to males and varied by age with greatest coverage among infants. Coverage also differed by priority group with greatest coverage among healthcare workers. Neighborhood variation in coverage was observed and ranged from 33.6% to 71.0%, with low coverage clustered in neighborhoods in Eastern Montreal. Among the total population, high neighborhood proportions of immigrants and material deprivation were significantly associated with lower neighborhood vaccine coverage. These results will help public health authorities implement priority group specific vaccination strategies to increase vaccination during future influenza pandemics.<br>Pour bien développer des programmes de vaccination contre les pandémies de grippe, la compréhension des éléments de voisinage qui influence la vaccination est essentielle. Très peu d'études ont été effectuées en utilisant un registre d'immunisation dans le but d'explorer les déterminants du voisinage relatifs à la vaccination. En utilisant des données individuelles, des données de recensement, de sondages et des données administratives pour estimer la population à risque, une étude écologique des déterminants de voisinage lors de la vaccination de la grippe pandémique A/H1N1 fut effectuée. En utilisant la régression logistique, en tenant compte de l'autocorrélation spatiale, les déterminants socio-économiques et démographiques pour la vaccination ont été identifiés et classés par groupe de priorité. À Montréal, un total de 918,733 (49,9%) habitants furent vaccinés contre la grippe A/H1N1. Le taux de vaccination était plus important parmi les femmes comparativement aux hommes. Il a varié selon l'âge, le plus haut taux était parmi les enfants de moins de cinq ans. Le taux a aussi vu une croissance parmi les gens travaillant dans le secteur des soins de santé. Dans les différents quartiers de Montréal, les taux de vaccination ont variés de 33,6% à 71,0%. Les taux les plus bas furent retrouvés dans les quartiers de l'Est de Montréal. Dans la population générale, l'immigration et les milieux défavorisés ont été des facteurs significatifs associés aux bas taux de vaccination. Ces résultats vont aider les autorités des soins de santé à implanter des stratégies spécifiques aux divers groupes de priorité lors des futures pandémies de grippe.
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Preis, Julia Kay. "Market incentives for pandemic influenza vaccines." Thesis, Massachusetts Institute of Technology, 2012. http://hdl.handle.net/1721.1/78155.
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Thesis (S.M. in Health Sciences and Technology)--Harvard-MIT Program in Health Sciences and Technology, 2012.<br>Cataloged from PDF version of thesis.<br>Includes bibliographical references (p. 60-61).<br>It has been estimated that 100 million plus individuals could perish if a virulent influenza pandemic were to occur. In wake of the 2009-10 H1N1 pandemic and in an era of economic austerity, however, industry lacks clear incentives to invest in vaccines for other high-risk strains. The cyclic nature of pandemics also means we can expect another influenza pandemic within the next 20 years. In this environment, design of incentive mechanisms for funding development of vaccines against strains with known pandemic potential, but for whom vaccine technology is currently lacking, would be welcomed. This research explores which novel incentive mechanisms could induce investment in and development of processes for production of vaccines for these high risk strains. Interviews with vaccine developers and funding agencies and analysis of the pipeline of influenza vaccines in development were conducted. This thesis finds that there is a dearth of vaccines against influenza strains of known pandemic potential, such as H2, H7 and H9; that current pandemic preparedness efforts are not focused on these strains; that funding for pandemic preparedness efforts in H2, H7 and H9 would help incentivize development of vaccines against these strains; and that support for seasonal influenza, regulatory changes, alignment of public and private sector goals, and increased vaccine acceptance are also required to incentivize the development of vaccines against strains of known pandemic potential such as H2, H7 and H9. Furthermore, this thesis recommends that policy makers increase funding for pandemic preparedness so that programs may be initiated or expanded to include additional high risk influenza strains; that US and EU regulatory regimes for pandemic influenza vaccines be harmonized; and that governments promote public awareness of the importance of influenza vaccination.<br>by Julia Kay Preis.<br>S.M.in Health Sciences and Technology
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Alfieri, Carolina. "Proposal of an ethics-based framework for prioritization of scarce resources during an influenza pandemic." Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=97886.
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The goal of pandemic influenza planning is to minimize health and economic losses in the event of a future pandemic. One of the numerous challenges associated with this goal is the need to ration limited medical supplies such as vaccines and antivirals. This thesis seeks to formulate an ethical framework for priority access to these resources. Prioritization strategies must be consistent with the goal of pandemic planning and should reflect societal norms for equitable distribution. According to an ethics framework based on the principles of utility and equity, three groups were granted highest priority for influenza vaccine, namely health care workers, emergency service workers, and high-risk individuals predisposed to severe outcomes following influenza infection. In the case of antivirals, the expectation is that there will be competition between treatment and prophylaxis uses of these drugs. The resulting dilemma---providing primary access to the critically ill in respect of the medical profession's duty of care or prioritizing prophylaxis of health care workers in respect of their right to protection---is the major question which the framework presented in this thesis seeks to resolve.
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Farsi, Nada. "Risk factors of head and neck cancer: highlighting the importance of human papilloma viruses." Thesis, McGill University, 2011. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=97185.
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Objective: To investigate Head and Neck cancer (H&NC) risk factors, and whether they varied by anatomical site or HPV-status. Methods: Data from 150 H&NC cases and 161 controls were drawn from an ongoing hospital-based case-control study: "HeNCe". Socio-demographic, behavioural and environmental characteristics were collected through questionnaires. HPV was detected from oral cells. Results: Logistic regression models identified smoking [(OR=1.01, 95%CI:1.00-1.02) per pack-year], low education [(OR=2.58,95%CI:1.28-5.20) high school or less vs. university], HPV-infection [(OR=4.84,95%CI:2.56-9.14) any vs. no-HPV] and higher number of missing teeth [(OR=2.25,95%CI:1.22-4.17) >9 vs. 0-9] as the strongest H&NC risk factors. Forty-three percent of the cases were HPV-positive, with predominance for HPV-16. The main risk factors for pharyngeal, laryngeal and oral cancers tended to differ. The main risk factors for HPV-negative H&NC were smoking and number of missing teeth, while for HPV-positive H&NC they were sexual behaviour and low education. Conclusion: H&NC risk factors varied by site and HPV-status.<br>Objectif: Étudier les facteurs de risque du cancer des voies aérodigestives supérieures (CVADS), et selon le site anatomique ou l'infection au VPH. Méthode: Les données concernant 150 cas de CVADS et 161 témoins (étude cas-témoin hospitalière « HeNCe ») comprenaient : caractéristiques sociodémographiques, comportementales, environnementales recueillies par entrevue; détection du VPH des cellules buccales. Résultats: Les facteurs de risque du CVADS identifiés par régression logistique étaient : tabagisme [Rapport de cotes (RC=1.01, 95%IC:1.00-1.02)/paquet-année], éducation [(RC=2.58, 95%IC:1.28-5.20) secondaire vs.université], VPH [(RC=4.84, 95%IC:2.56-9.14)] et nombre de dents manquantes [(RC=2.25, 95%IC:1.22-4.17) >9 vs.0-9]. Quarante-trois pourcent des cas étaient infectés au VPH, majoritairement VPH-16. Les facteurs de risque principaux différaient par site (pharynx, larynx, cavité buccale). Les CVADS VPH-négatifs étaient associés au tabagisme et nombre de dents manquantes; les CVADS VPH-positifs étaient liés au comportement sexuel et à l'éducation. Conclusion: Les facteurs de risque du CVADS différaient selon le site et l'infection au VPH.
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Vesterberg, Beatrice. "Characterisation of viruses present in tumour samples of non-Hodgkinlymphoma." Thesis, Örebro universitet, Institutionen för medicinska vetenskaper, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-66977.
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Bliss, Nola Terra. "Determining the Incoming Prevalence of Type A Influenza in Exhibition Swine and Characterizing the On-Farm Swine Management Practices Associated with Type A Influenza." The Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1428671459.
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Smith, Tiffany. "Applying Current Methods for Estimating Influenza Burden to an Academic Health Sciences Centre." Thèse, Université d'Ottawa / University of Ottawa, 2012. http://hdl.handle.net/10393/23197.
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Public health planning for influenza is based on morbidity and mortality estimates derived from statistical models. Lower than anticipated 2009 H1N1 pandemic death estimates have raised questions about the method. Examining the statistical method is important for future policy and program development. We compared the main methods of estimating influenza burden through a systematic literature review and by comparing statistical estimates of influenza-attributable burden at the Ottawa Hospital (TOH) to clinical estimates validated through chart review. We identified heterogeneity in methods used to estimate influenza-attributable mortality in the literature which resulted in within-season estimate variation by study. We found statistical estimates of influenza burden at TOH to be 4-8 times greater than clinically validated data. We also found no significant association between the outcomes examined and epidemic periods at TOH. The findings of this study suggest discordance between model estimates by model approach and between model estimates and validated findings. Examining reasons for these discordances should be pursued.
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Chan, Emily. "Evaluating the use of physician billing data for age and setting specific influenza surveillance." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=32402.
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Syndromic surveillance has emerged as a novel, automated approach to monitoring diseases using pre-diagnostic but often non-specific data sources. However, there is little consensus about the best data sources. Using physician billing data from community-based care settings and emergency departments in Quebec, Canada during 1998-2003, we evaluated the lead-lag relationship between ambulatory medical visits for influenza-like illnesses (ILI) and pneumonia and influenza (P& I) hospitalizations by age-group, visit setting, and influenza season. To do so, we applied ARIMA modeling methodology and computed the cross-correlation function (CCF) using the residuals. ILI visits in community settings by children aged 5-17 years tended to provide the greatest lead times (at least 2 but up to 3 weeks) over P&I hospitalizations. Lead times varied each season, possibly due to the circulation of different strains each season. These findings have important implications for syndromic surveillance of influenza, as well as epidemic control strategies such as vaccination and school closure policies.<br>La surveillance syndromique a émergé comme une nouvelle approche automatisée pour le contrôle des maladies avec des sources de données pré-diagnostic, mais qui sont souvent non-spécifiques. Pourtant, il y a peu de consensus concernant les meilleures sources de données. En utilisant des factures médicales émises entre 1998 et 2003, et provenant de centres communautaire et de services d'urgence au Québec, Canada, nous avons évalué par tranche d'âge, le cadre des visites, et la saison de la grippe la relation d'avance-décalage entre les visites médicales ambulatoires pour le syndrome d'allure grippale (SAG) et les hospitalisations pour la pneumonie et la grippe. Pour ce faire, nous avons appliqué la méthodologie des modèles d'ARIMA et calculé la fonction de contre-corrélation (CCF) avec les résidus. Les visites communautaires reliée au SAG par des enfants âgés de 5-17 ans ont eu tendance à pourvoir les plus grandes avances (au moins 2 semaines, mais quelques fois jusqu'à 3 semaines) contre des hospitalisations pour la pneumonie et la grippe. Les avances ont varié chaque année, peut-être à cause de la circulation des souches différentes chaque saison. Ces résultats ont des implications importantes pour la surveillance syndromique de la grippe, ainsi que pour des stratégies de lutte contre l'épidémie, comme la vaccination et la fermeture d'écoles.
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Francisco, Priscila Maria Stolses Bergamo 1973. "Fatores associados a vacinação contra influenza e doença pulmonar em idosos." [s.n.], 2006. http://repositorio.unicamp.br/jspui/handle/REPOSIP/311104.
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Orientador: Maria Rita Donalisio Cordeiro<br>Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas<br>Made available in DSpace on 2018-08-07T11:53:53Z (GMT). No. of bitstreams: 1
Francisco_PriscilaMariaStolsesBergamo_D.pdf: 1732128 bytes, checksum: e40308a72ae69b30999c757a5f111ac4 (MD5)
Previous issue date: 2006<br>Resumo: O aumento da proporção de idosos no país associado à maior longevidade modificou o perfil de saúde da população com considerável aumento da demanda por prevenção e assistência à saúde nas faixas etárias mais avançadas. Neste contexto, destaca-se a importância relativa das doenças respiratórias nos idosos, com impacto econômico e social. O objetivo deste estudo foi investigar os fatores associados à vacinação contra influenza e doença pulmonar em idosos, com a utilização de diferentes técnicas de análise em estudos transversais de delineamento complexo. Os dados foram obtidos do "Inquérito de saúde de base populacional em municípios do Estado de São Paulo" (ISA-SP), cuja coleta foi realizada entre 2001 e 2002, e se referem a 1.958 registros de indivíduos de 60 anos e mais, analisados por meio de regressão logística e regressão de Poisson. Os resultados desta tese são apresentados em capítulos que se referem a três artigos publicados em revistas científicas. No primeiro artigo, "Fatores associados à vacinação contra influenza em idosos", os achados apontaram maior adesão à vacinação contra influenza entre os indivíduos com idade igualou superior a 70 anos (OR = 1,47; IC 95%: 1,09 -:- 1,99) e entre os hipertensos (OR = 1,39; IC 95%: 1,03 - 1,87), enquanto os idosos com nove anos ou mais de estudo referiram menor adesão à vacinação (OR = 0,64; IC 95%: 0,41 - 0,98). No segundo trabalho, "Vacinação contra influenza em idosos por área de residência: prevalência e fatores associados", pôde-se verificar diferenças no perfil do idoso quanto à referência de vacinação segundo subgrupos específicos e locais de residência. Nos municípios mais populosos apenas a menor escolaridade esteve associada à vacinação referida (RP = 1,26; IC 95%: 1,02-1,54), já na área composta pelos municípios menos populosos, idade mais avançada (RP = 1,15; IC 95%: 1,02-1,31), hipertensão arterial (RP = 1,21; IC 95%: 1,02-1,45), diabetes (RP = 1,16; IC 95%: 1,01-1,33) e doença crônica de pulmão (RP = 1,30; IC 95%: 1,03-1,64) referidas, estiveram associadas. No estudo, "Fatores associados à doença pulmonar em idosos", os resultados indicaram associação independente entre doença pulmonar referida e tabagismo (RP = 2,03; IC 95%: 1,39 - 2,97), uso de medicamentos (RP = 2,05; IC 95%: 1,11 - 3,79), auto-avaliação do estado de saúde atual como ruim ou muito ruim (RP = 1,89; IC 95%: 1,20 - 2,96) e depressão, ansiedade ou problemas emocionais (RP = 1,86; IC 95%: 1,11 - 3,10). Com o envelhecimento e a crescente importância das doenças respiratórias entre os idosos, os achados desse estudo apontam para a necessidade de ações que priorizem a manutenção da saúde do idoso, por meio de programas de promoção e prevenção que considerem as especificidades desse segmento<br>Abstract: The increase in the proportion of elder1y persons in Brazil, associated to increased longevity, has modified the health profile of the population, with a considerable increase in the demand for prevention and healthcare among the older age groups. In this context, the relative importance of respiratory diseases among the elder1y, along with its social and economic impact, is worthy of note. The aim of the present study was to investigate the factors associated with influenza vaccination and pulmonary disease in the elder1y population, using different analytical techniques in cross-sectional studies with complex design.The data were obtained from the Population-based survey of municipalities of the State of Sao Paulo (ISA-SP), whose data collection took place between 2001 and 2002 and inc1uded 1.958 records of subjects aged 60 years or older, and were analyzed using logistic regression and Poisson regression.The results of the present thesis are presented as chapters that refer to artic1es published in scientific journals. In the first article, "Factors associated with influenza vaccination among elderly persons", our findings indicate greater adherence to influenza vaccination among subjects aged 70 years or older (OR = 1.47; 95%CI: 1.09 - 1.99) and among subjects with hypertension (OR = 1.39; 95%CI: 1.03 - 1.87), whereas elder1y subjects with nine or more years of schooling reported lesser adherence to vaccination (OR = 0.64; 95%CI: 0.41- 0.98). In the second paper, "Influenza vaccination among elderly persons according to place of residence: prevalence and associated factors", we observed differences in subject profile in tenns of self-reported vaccination according to specific subgroups and places of residence. In more populous municipalities, only lesser schooling (PR = 1.26; 95%CI: 1.02-1.54) was associated with vaccination. Among the less densely populated municipalities, older age (pR = 1.15; 95%CI: 1.02-1.31) and 'reported hypertension .(PR = 1.21; 95%CI: 1.02-1.45), diabetes (pR = 1.16; 95%CI: 1.01-1.33), and chronic pulmonary disease (PR = 1.30; 95%CI: 1.03-1.64) were associated with the outcome. In the paper entitled "Factors associated with pulmonary disease among the elderly," our results indicate independent associations between self-reported pulmonary disease and smoking (pR = 2.03; 95%CI: 1.39 - 2.97), medication use (pR = 2.05; 95%CI: 1.11 - 3.79), self-perception of current health status as poor or very poor (RP = .1.89; 95%CI: 1.20 2.96), and depression, anxiety, or emotional disorders (pR = 1.86; 95%CI: 1.11 - 3.10).With the aging of the population, and the increasing importance of respiratory diseases among the elderly, the findings of the present study indicate a need for measures that prioritize the maintenance of health among this population, through promotion and prevention programs that take into account the specificities of this segment<br>Doutorado<br>Epidemiologia<br>Mestre em Saude Coletiva
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Cho, Sungyoo. "Immune evasion of CD1d molecules and NKT cells in the innate immune response against viruses." [Bloomington, Ind.] : Indiana University, 2005. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:3185405.
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Thesis (Ph.D.)--Indiana University, 2005.<br>Source: Dissertation Abstracts International, Volume: 66-08, Section: B, page: 4071. Chair: Randy R. Brutkiewicz. Title from dissertation home page (viewed Oct. 10, 2006).
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Olin, Tracy C. "Design and synthesis of 2,4,9-trithiaadamantane derivatives as anti-influenza A drug candidates." Thesis, The University of Akron, 2015. http://pqdtopen.proquest.com/#viewpdf?dispub=3687126.
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<p> The objective of this dissertation is to describe the design, synthesis, and characterization of 7-substituted-2,4,9-trithiaadamantane (tripod) derivatives as new anti-influenza drug candidates, specifically blockers for the M2 ion channel of the influenza A virus. Of the four current FDA-approved anti-influenza chemotherapeutics, only two function by blocking the M2 ion channel of the virus. However, due to the developed mutations of certain amino acid residues lining the interior pore of the ion channel, the two drugs, amantadine and rimantadine, now have little to no effect on the most common virus strains. The recently elucidated structure of the M2 proton channel has provided structural insight and new knowledge leading to the development of these novel drug candidates that may have an enhanced affinity for mutated ion channels and also a shorter biodistribution time, decreasing host toxicity. The drugs described within this work have incorporated sulfur atoms into the base of the molecule accommodating the larger diameter of the mutated pore and allowing an ease of biodegradation. </p><p> Chapter 1 of this work gives an introduction to the influenza virus, the ion channel structure and function, as well as new drug developments and previous work with trithiaadamantanes. Also discussed will be some current antiviral drugs used to treat influenza, and possible drug candidates currently being developed by other research groups. The rationale for drug design based on specific mutations believed to occur in the most abundant influenza strains will be looked at in context of designing new drug candidates.</p><p> Chapter 2 of this dissertation describes the multi-step syntheses of the novel 2,4,9-trithiaadamantan-7-amine and 1-(2,4,9-trithiaadamantan-7-yl)ethan-1-amine derivatives as possible influenza A ion channel blockers. Also discussed are attempted synthetic routes to these molecules.</p><p> The starting material to the synthesized drug candidates is not commercially available and is made via a six-step route, which yields a mere 10-20% at best, and requires several purification steps. Chapter 3 will focus on several new routes that were explored for the improved synthesis of this starting material, methyl-2,4,9-trithiaadamantan-7- carboxylate, as well as the synthesis of other molecules that could serve as enhanced starting compounds.</p>
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Wallace, LeShonda. "Acceptance and Uptake of Influenza Vaccination by Health Care Workers." ScholarWorks, 2015. https://scholarworks.waldenu.edu/dissertations/1557.
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Influenza is a preventable infectious disease, against which vaccination is the primary means of protection. Health care workers (HCW) are among the most vulnerable to the illness and are likely to be sources of infection transmission while caring for patients. Circumstantial evidence suggests higher rates of vaccination coverage by HCW will coincide with a lower incidence of influenza transmission, yet a gap remains in the literature regarding governing health agencies' (i.e., licensing boards, medical and nursing associations) influence on the influenza vaccination practices of their constituents. Moreover, discrepancies exist between governing health agencies' and the National Vaccine Advisory Committee's recommendations on mandatory influenza vaccination for HCW. The main purpose of this quantitative cross-sectional study was to explore the relationship between influenza vaccination uptake by HCW and guidance from governing health agencies to vaccinate. The health belief model and social cognitive theory were used to identify the most influential determinant for HCW to vaccinate against influenza. The sample consisted of 388 HCW who provided direct patient care at the same hospital. Data were analyzed using Fisher's exact test. Study findings suggest that a workplace mandate for influenza vaccination has an influence on HCW uptake of the vaccine and that governing agencies' lack of uniformity on the matter has minimal impact on their constituents' beliefs and behavior. It is recommended that a universal policy be adopted for health agencies' implementation of an influenza vaccine mandate, which could lead to positive social change by supporting preventive self-care practices, minimizing spread of the disease to workers and patients, and maintaining workplace productivity.
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Placzek, Hilary. "A Population-Based Epidemiological Description of Socio-Demographic Characteristics and Predictors of Severity Among Hospitalized 2009 H1N1 Influenza Cases in Massachusetts: A Dissertation." eScholarship@UMMS, 2012. https://escholarship.umassmed.edu/gsbs_diss/602.
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The spread of pandemic influenza A (2009 H1N1 influenza) virus resulted in a global influenza pandemic in 2009. During the early stages of the pandemic, population surveillance was crucial. However, officials around the world realized that many of our surveillance and reporting systems were not prepared to respond in a coordinated, integrated way, which made informed public health decision-making very difficult. More accurate estimates of the total number of hospitalized 2009 H1N1 influenza cases were required to calculate population-based 2009 H1N1 influenza-associated mortality, morbidity and hospitalization rates. For instance, how many people were hospitalized with 2009 H1N1 influenza in Massachusetts? Of these, how many were admitted to the ICU and how many died? Compared to seasonal influenza, were some race/ethnic and age groups affected more than others, and what types of characteristics led to more severe manifestations of 2009 H1N1 influenza among these groups in Massachusetts?
To address the above questions, I proposed a retrospective cohort study using data from the Hospital Discharge Database (HDD), which contains data for all inpatients discharged from 76 acute care hospitals in Massachusetts, as well as Census information to provide a measure of socioeconomic status (SES). My specific aims are as follows: 1. Develop methods to identify influenza cases precisely and describe characteristics of those hospitalized with ILI in MA between April 26-Sept 30, 2009; 2. Conduct analyses to identify race/ethnicity-related trends in reference to 2009 H1N1 influenza-related hospitalizations; 3. Conduct analyses to identify age-related trends in reference to 2009 H1N1 influenza-related hospitalizations.
First, I established influenza case selection criteria using hospital discharge data. I addressed limitations in the published methods on defining cases of influenza using administrative databases, and evaluated ICD-9 codes that correspond with common and relatively serious respiratory infections and influenza using a ‘maximum’ and ‘minimum’ approach. Results confirmed that 2009 H1N1 influenza affected a younger population, and disproportionately affected racial minorities in Massachusetts. There were also higher rates of ICU admission compared to seasonal influenza.
I then presented epidemiological data indicating race/ethnic disparity among 2009 H1N1 influenza cases in Massachusetts. I found that Hispanics had significantly lower odds of 2009 H1N1 influenza-related ICU stay. SES gradients calculated using five-digit zip code information did not account for these differences. Within race/ethnic strata, Hispanics
Finally, I presented epidemiological data indicating differences among 2009 H1N1 influenza cases by age group in Massachusetts. I calculated measures of Diagnostic Cost Group (DxCG) comorbidity for the study population to provide a comorbidity measure at baseline. Main results indicate that although comorbidity scores were similar between the 2009 H1N1 influenza and seasonal influenza groups, 2009 H1N1 influenza caused more severe disease in younger age groups.
This is the first study to report population-based statewide outcomes in all acute care centers in MA. In this dissertation I address challenges surrounding influenza surveillance to create case selection criteria within an administrative database. Using my case selection criteria, I then provide data related to fatality and severity of 2009 H1N1 influenza in Massachusetts in reference to sociodemographic variables such as racial/ethnicity and age groups, and provide evidence for patient-level interventions to those hardest hit by influenza. These findings provide valuable information about using large administrative databases to describe pandemic influenza cases and guide resource allocation to reduce disparities in relation to pandemic influenza preparedness.
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Gustafsson, Alice. "Clinical effectiveness of influenza vaccination and infectionoutcome in cancer patients treated with checkpoint inhibitors." Thesis, Örebro universitet, Institutionen för medicinska vetenskaper, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-82478.
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Tam, John. "Expression of the membrane fusion protein of measles virus in insect and mammalian cells using recombinant viruses." Thesis, McGill University, 1993. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=69521.
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The fusion (F) protein of measles virus is responsible for viral penetration at the plasma membrane and syncytia formation. In order to facilitate future structure/function studies, the F protein was expressed in insect cells using recombinant baculovirus, and in mammalian cells using both vaccinia and adenovirus recombinants. The baculovirus system exhibited the highest levels of recombinant protein expression, but the majority of the product was found to be in the form of detergent-insoluble precursors. Replacing the signal peptide of the F protein with insect-derived sequences did not enhance posttranslational processing. Also, expression of truncated, anchor-minus forms of the F protein did not result in improved solubility or secretion. The vaccinia virus recombinant VF exhibited higher levels of expression than measles virus-infected cells. However, the majority of the F protein was expressed as insoluble precursors. The biologically active portion, represented by the proteolytically cleaved F protein, was found to be soluble. The vP455 vaccinia virus recombinant and the AdF adenovirus recombinant expressed similar levels of processed F as in measles virus-infected cells. The products of these recombinants were found to be soluble. F protein expressed by vaccinia virus recombinants in primate and murine cells were observed to cause syncytia formation in the absence of measles virus hemagglutinin (H) co-expression. This H-independent fusion could not be inhibited by Z-D-Phe-L-Phe-Gly. When the adenovirus system was used, F protein could not facilitate fusion unless measles virus hemagglutinin was present as well.
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Tallon, Benjamin. "The influence of killer immunoglobulin-like receptor genotypes on protection from human immunodeficiency virus-1 infection in exposed seronegative individuals." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=110465.
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Natural killer (NK) cells are among the earliest responders to viral infections and serve as a link between the innate and adaptive immune systems. Elevated NK cell activity has been observed in individuals who are classified as HIV-exposed seronegative (HESN). The functional response of these cells is determined by an integration of activating and inhibitory signals delivered to the NK cell through surface receptors. The killer immunoglobulin-like receptor (KIR) family comprises nine inhibitory receptors, six activating receptors and two pseudogenes. KIR bind to human leukocyte antigen (HLA)-class I molecules and are able to sense their down-regulation on transformed and virally infected cells. Epidemiological evidence has linked carriage of certain KIR-HLA genotypes with both delayed progression to AIDS and protection from HIV infection. We have screened a cohort of HIV-susceptible and HIV-resistant subjects (HESN) for both KIR and HLA genes. Here we report that KIR2DS4, a gene which codes for an activating receptor, is found at lower frequency in the HESN population compared to HIV-susceptible subjects. KIR2DS4 can be divided into alleles that are expressed on the cell surface and those that are not. We find that the expressed allele group alone and in combination with its ligands occurs less frequently in the HESN population compared to HIV-susceptible subjects, suggesting that carriage of this is not protective against HIV infection. We also report that homozygosity at the KIR3DS1 locus, another activating receptor and a genotype that has previously been associated with protection from HIV infection, associates with a decreased incidence of seroconversion over time in a longitudinal study of seroconvertors and HESN subjects. Additionally, the combination of KIR3DS1 with its putative ligand, shown previously to associate with delayed progression to AIDS, does not associate with protection from infection. These results suggest that through KIR, NK cells may protect against HIV infection in individuals carrying certain KIR-HLA genotypes.<br>Les cellules tueuses naturelles (Natural Killer [NK]) sont parmi les premières cellules qui répondent aux infections virales et servent de lien entre les systèmes immunitaires innés et acquis. Une activité plus accrue des cellules NK a été observée chez les individus classés comme séronégatifs exposés au VIH (HIV Exposed SeroNegative [HESN]). La réponse fonctionnelle de ces cellules est déterminée par l'intégration des signaux activateurs et inhibiteurs transmis à la cellule NK par les récepteurs de surface. La famille des récepteurs KIR (Killer Immunoglobulin-like Receptor) comprend neuf récepteurs inhibiteurs, six récepteurs activateurs et deux récepteurs non exprimés encodés par des pseudogènes. Les KIRs inhibiteurs interagissent avec des ligands encodés par des gènes du complexe majeur d'histocompatibilité classe I (HLA). Ces KIRs détectent la régulation des antigènes HLA à la baisse sur les cellules transformées ou infectées par des virus. Des données épidémiologiques ont démontré que certains génotypes HLA-KIR sont associés avec une progression retardée vers le SIDA et la protection contre l'infection par le VIH. Nous avons comparé la fréquence de génotypes KIR et KIR-HLA chez les sujets de cohortes HESN et VIH infectés (c'est-à-dire susceptibles au virus). Nous avons trouvé que KIR2DS4, un gène qui code pour un récepteur d'activation, est moins fréquent dans la population HESN comparativement aux sujets susceptibles au VIH. KIR2DS4 encode des allèles exprimées et non exprimées à la surface cellulaire. Le groupe d'allèles exprimées seules et en combinaison avec leurs ligands est moins fréquent dans la population HESN que dans celle susceptible au VIH. Ceci suggère que le fait de porter ce génotype ne protège pas contre l'infection par le VIH. Nous avons aussi trouvé dans une étude longitudinale avec des sujets en séroconversion et des sujets HESN que les personnes exposées au VIH qui portent le génotype homozygote KIR3DS1 ont une incidence plus faible à être infectées que celles portant d'autres génotypes du locus KIR3DL1/S1. KIR3DS1 encode aussi un récepteur activateur et ce génotype a déjà été identifié comme étant associé à une protection contre l'infection par le VIH. La combinaison de KIR3DS1 avec son ligand putatif, associé précédemment à une progression au SIDA retardée, n'est pas associé avec la protection contre l'infection. Ces résultats suggèrent que, grâce à KIR, les cellules NK peuvent protéger contre l'infection par le VIH chez les personnes portant certains génotypes KIR ou KIR-HLA.
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Kalp, Ericka Lynne. "Predictors of Influenza Vaccination Compliance Among Union and Nonunion Workers in a Pennsylvania Health Care System." ScholarWorks, 2016. https://scholarworks.waldenu.edu/dissertations/2318.
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To improve U.S. residents' health, advocates are focusing their efforts on workplace health. Researchers have found that unionization is a positive influence on workers' participation in health promotion programs relating to smoking and obesity prevention. However, the effect of union membership on other health promotion initiatives, such as influenza vaccination compliance among health care workers, has not been examined. The purpose of this quantitative study was to address this knowledge gap between a union and a nonunion health care facility in the U.S. state of Pennsylvania. The health belief model was used to determine if different domains of influenza vaccination perception predicted vaccination behaviors among union and nonunion health care workers. A secondary analysis was performed on the 2013-2014 Influenza Vaccination Survey, which was completed by 2,480 health care workers. While a chi-square analysis showed that vaccination compliance was not statistically different between facilities, a binary logistic regression revealed a significant difference in predicted vaccination behaviors for each domain of influenza vaccination perceptions. Among union health care workers, perceived barriers yielded the highest positive predictability of vaccination compliance, whereas perceived benefits were positively associated with vaccination compliance among nonunion workers. These study findings affect social change by identifying vaccine compliance predictors among union and nonunion health care workers. By focusing on these predictors, health care facilities may be able to improve levels of vaccination compliance and achieve the Joint Commissions' vaccination goal of 90% compliance amongst all healthcare workers.
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Boyle, Christine Margaret. "DNA Immunization: Basic Mechanisms of the DNA-Raised Antibody Response Using an Influenza Hemagglutinin-Expressing Plasmid: A Dissertation." eScholarship@UMMS, 2000. https://escholarship.umassmed.edu/gsbs_diss/151.
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In DNA immunization a plasmid expressing an antigen of interest is inoculated into an animal and antigen-specific humoral and cellular immune responses are raised. In this dissertation we sought to further our understanding of antibody responses raised following DNA inoculation. Specifically, we examined the role of lymphoid tissue in the initiation and maintenance of the long-term antibody response, the role of CD4+ and CD8+ T cells in the DNA-raised antibody response, the longevity of functional antigen expression, and the nature of the antigen presenting cell. In all of these studies mice were immunized with an influenza hemagglutinin-expressing plasmid and plasmid was delivered by either the gene gun or intramuscular routes of inoculation.
To examine the role of lymphoid tissue in the initiation and maintenance of the long-term antibody response, responses raised in gene gun immunized mice were compared to responses raised in mice primed with an influenza infection. Antibody and antibody secreting cell (ASC) responses were analyzed at various times following immunization or sublethal infection for as long as 1.5 years. We found that the antibody response raised with a single gene gun immunization was similar in longevity to that raised in infection-primed mice. The long-term maintenance of the antibody response was associated with the localization of the majority of antibody secreting cells to the bone marrow. The kinetics of ASC bone marrow localization was 4-to-8 weeks slower in DNA-immunized than infection primed mice. This corresponded to a slower rise in the antibody response to plateau levels in DNA-immunized mice. We hypothesize that it is possible that the difference in kinetics may be linked to differences in the time course and dose of antigen expression following DNA immunization and a natural infection.
Antibody and ASC responses were also compared following a challenge influenza virus infection. We found that DNA-immunized and infection-primed mice responded similarly in the acute post challenge phase with increases in antibody secreting cells in the mediastinal lymph nodes. While only DNA-immunized mice had post challenge increases in antibody, the antibody response remained 3-to-4 fold lower than post challenge responses in infection primed mice. We suggest that despite post challenge increases in these responses in DNA-immunized mice that the immune response raised with DNA immunization efficiently limited replication of the challenge virus and thus limited the post challenge antibody response.
We also addressed the role that CD4+ and CD8+ T cells played in the ability to prime and boost the DNA-raised antibody response. To answer this question mice were in vivo depleted of CD4+ or CD8+ T cells for 3 weeks prior to through 2 weeks following DNA immunization or boost. Antibody responses were measured 4 and 8 weeks after DNA prime and 2 weeks after DNA boost. For both the gene gun and intramuscular routes of inoculation, the antibody response was independent of CD8+ T cells, but dependent on CD4+ T cells. The presence of CD4+ T cells was required at the time of DNA immunization, but not at the time of DNA boost. The absence of CD4+ T cells at the time of DNA delivery resulted in a four week delay in the appearance of antibody. Since influenza hemagglutinin has been characterized as a T-dependent antigen the requirement for CD4+ T cells at the time of DNA prime was not surprising, but the appearance of a delayed H1-specific antibody response suggested that DNA-expressed antigen had continued to be available to prime CD4+ T cells as they reappeared following the disappearance of depleting antibody. The independence of the antibody response on the presence of CD8+ T cells suggested that DNA-primed H1-specific CD8+ T cells did not limit the plateau level of response or the ability to boost a suboptimal response.
The results from our CD4+ T cell depletion experiment suggested that DNA-expressed antigen continued to be available for an extended period of time following immunization. To examine the duration of functional antigen expression for raising an antibody response, mice lacking α/β T cells (TCR-/-) were immunized with DNA or immunized with hemagglutinin protein. Naive T cells from TCR+/+ mice were transferred into the immunized TCR-/- mice on various days post DNA or protein immunization. The results from these studies show that antigen is available to raise antibody longer following DNA immunization than following a protein immunization. This result is likely due to continued expression of plasmid DNA.
We found differences in the longevity of antigen expression following gene gun and intramuscular routes of inoculation. For gene gun immunizations, not intramuscular immunizations, approximately 90% of functional antigen was lost within one week of immunization. We suggest that this is consistent with a role for antigen expression by transfected cells within the target site, the epidermis, which is largely lost by 1-2 weeks following gene gun immunization. We also found that following intramuscular immunization the dominant IgG isotype changed with time of TCR+/+ T cell transfer. By contrast, there was no change in the dominant isotype following gene gun immunizations. These results suggest that the factor(s) that contribute to the development of the Th1-bias seen following intramuscular DNA immunizations are lost early.
To examine the nature of the antigen presenting cell following DNA immunization, dendritic cells were sorted from the inguinal lymph nodes and spleens of gene gun or intramuscularly immunized mice on various days following DNA delivery. The dendritic cell (CD11c+) and non-dendritic cell (CD11c-) populations were used in restimulation assays with H1-specific T cell clones. Despite similar titers of raised antibody in gene gun and intramuscularly immunized mice, H1-specific antigen presenting dendritic cells were isolated from the inguinal lymph nodes and spleens of gene gun, but not intramuscularly immunized mice. Antigen presentation by dendritic cells was detected for as long as 21 days following gene gun delivery. We hypothesize that the inability to detect dendritic cell presentation of antigen following intramuscular DNA delivery may be due to a more broad distribution of antigen presenting cells, different properties of antigen presenting cells, and/or the contribution of other non-dendritic cells to antigen presentation following intramuscular, but not gene gun, immunizations.
We present our results within a model for the initiation and maintenance of DNA-raised antibody responses. Within this model our data specifically contribute to understanding the initiation and generation of the DNA-raised antibody response within lymphoid tissue and the maintenance of the DNA-raised antibody response.
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Boyle, Christine Margaret. "DNA Immunization: Basic Mechanisms of the DNA-Raised Antibody Response Using an Influenza Hemagglutinin-Expressing Plasmid: A Dissertation." eScholarship@UMMS, 2003. http://escholarship.umassmed.edu/gsbs_diss/151.
Full textAbstract:
In DNA immunization a plasmid expressing an antigen of interest is inoculated into an animal and antigen-specific humoral and cellular immune responses are raised. In this dissertation we sought to further our understanding of antibody responses raised following DNA inoculation. Specifically, we examined the role of lymphoid tissue in the initiation and maintenance of the long-term antibody response, the role of CD4+ and CD8+ T cells in the DNA-raised antibody response, the longevity of functional antigen expression, and the nature of the antigen presenting cell. In all of these studies mice were immunized with an influenza hemagglutinin-expressing plasmid and plasmid was delivered by either the gene gun or intramuscular routes of inoculation.
To examine the role of lymphoid tissue in the initiation and maintenance of the long-term antibody response, responses raised in gene gun immunized mice were compared to responses raised in mice primed with an influenza infection. Antibody and antibody secreting cell (ASC) responses were analyzed at various times following immunization or sublethal infection for as long as 1.5 years. We found that the antibody response raised with a single gene gun immunization was similar in longevity to that raised in infection-primed mice. The long-term maintenance of the antibody response was associated with the localization of the majority of antibody secreting cells to the bone marrow. The kinetics of ASC bone marrow localization was 4-to-8 weeks slower in DNA-immunized than infection primed mice. This corresponded to a slower rise in the antibody response to plateau levels in DNA-immunized mice. We hypothesize that it is possible that the difference in kinetics may be linked to differences in the time course and dose of antigen expression following DNA immunization and a natural infection.
Antibody and ASC responses were also compared following a challenge influenza virus infection. We found that DNA-immunized and infection-primed mice responded similarly in the acute post challenge phase with increases in antibody secreting cells in the mediastinal lymph nodes. While only DNA-immunized mice had post challenge increases in antibody, the antibody response remained 3-to-4 fold lower than post challenge responses in infection primed mice. We suggest that despite post challenge increases in these responses in DNA-immunized mice that the immune response raised with DNA immunization efficiently limited replication of the challenge virus and thus limited the post challenge antibody response.
We also addressed the role that CD4+ and CD8+ T cells played in the ability to prime and boost the DNA-raised antibody response. To answer this question mice were in vivo depleted of CD4+ or CD8+ T cells for 3 weeks prior to through 2 weeks following DNA immunization or boost. Antibody responses were measured 4 and 8 weeks after DNA prime and 2 weeks after DNA boost. For both the gene gun and intramuscular routes of inoculation, the antibody response was independent of CD8+ T cells, but dependent on CD4+ T cells. The presence of CD4+ T cells was required at the time of DNA immunization, but not at the time of DNA boost. The absence of CD4+ T cells at the time of DNA delivery resulted in a four week delay in the appearance of antibody. Since influenza hemagglutinin has been characterized as a T-dependent antigen the requirement for CD4+ T cells at the time of DNA prime was not surprising, but the appearance of a delayed H1-specific antibody response suggested that DNA-expressed antigen had continued to be available to prime CD4+ T cells as they reappeared following the disappearance of depleting antibody. The independence of the antibody response on the presence of CD8+ T cells suggested that DNA-primed H1-specific CD8+ T cells did not limit the plateau level of response or the ability to boost a suboptimal response.
The results from our CD4+ T cell depletion experiment suggested that DNA-expressed antigen continued to be available for an extended period of time following immunization. To examine the duration of functional antigen expression for raising an antibody response, mice lacking α/β T cells (TCR-/-) were immunized with DNA or immunized with hemagglutinin protein. Naive T cells from TCR+/+ mice were transferred into the immunized TCR-/- mice on various days post DNA or protein immunization. The results from these studies show that antigen is available to raise antibody longer following DNA immunization than following a protein immunization. This result is likely due to continued expression of plasmid DNA.
We found differences in the longevity of antigen expression following gene gun and intramuscular routes of inoculation. For gene gun immunizations, not intramuscular immunizations, approximately 90% of functional antigen was lost within one week of immunization. We suggest that this is consistent with a role for antigen expression by transfected cells within the target site, the epidermis, which is largely lost by 1-2 weeks following gene gun immunization. We also found that following intramuscular immunization the dominant IgG isotype changed with time of TCR+/+ T cell transfer. By contrast, there was no change in the dominant isotype following gene gun immunizations. These results suggest that the factor(s) that contribute to the development of the Th1-bias seen following intramuscular DNA immunizations are lost early.
To examine the nature of the antigen presenting cell following DNA immunization, dendritic cells were sorted from the inguinal lymph nodes and spleens of gene gun or intramuscularly immunized mice on various days following DNA delivery. The dendritic cell (CD11c+) and non-dendritic cell (CD11c-) populations were used in restimulation assays with H1-specific T cell clones. Despite similar titers of raised antibody in gene gun and intramuscularly immunized mice, H1-specific antigen presenting dendritic cells were isolated from the inguinal lymph nodes and spleens of gene gun, but not intramuscularly immunized mice. Antigen presentation by dendritic cells was detected for as long as 21 days following gene gun delivery. We hypothesize that the inability to detect dendritic cell presentation of antigen following intramuscular DNA delivery may be due to a more broad distribution of antigen presenting cells, different properties of antigen presenting cells, and/or the contribution of other non-dendritic cells to antigen presentation following intramuscular, but not gene gun, immunizations.
We present our results within a model for the initiation and maintenance of DNA-raised antibody responses. Within this model our data specifically contribute to understanding the initiation and generation of the DNA-raised antibody response within lymphoid tissue and the maintenance of the DNA-raised antibody response.
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Gadarowski, Jennifer. "Advisory Committee on Immunization Practices Recommendations, Socioeconomics, Demographics, and Influenza Vaccine Uptake." ScholarWorks, 2019. https://scholarworks.waldenu.edu/dissertations/6431.
Full textAbstract:
Seasonal influenza outbreaks are associated with morbidity and mortality in the United States. Though children are the most susceptible to influenza infection and are most likely to transmit the illness to others, many children are not vaccinated. The purpose of this study was to examine the relationship between seasonal influenza vaccination Advisory Committee on Immunization Practices (ACIP) recommendations, demographic characteristics, socioeconomic factors, and vaccine type among children over 3 consecutive flu seasons. This quantitative cross-sectional study was guided by the social ecology of health model. Secondary data from 3 consecutive flu seasons (2014-2015, 2015-2016, and 2016-2017) provided by the National Health Interview Survey was used for this study. Binary logistic regression and chi-square were used to analyze the data. A relationship between socioeconomic status, demographics (age, race, and family income) and vaccine type (live-attenuated influenza vaccine [LAIV]/inactivated influenza vaccine) was established among U.S. children; those who received LAIV were most likely to be White elementary school age children with a higher family income. Demographic and socioeconomic status was not considered influential in LAIV uptake for race, health insurance status, or family income. ACIP recommendations by age and year had the greatest impact on flu vaccine choice for this sample population. The results of this study can lead to social change by providing information for policy that can increase vaccine uptake, which can result in lower health cost and reduced illness and death rates associated with the flu, especially for those most at risk.
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Couto, Carla Renata. "Viroses respitarórias após vacinação contra influenza em profissionais de saúde (Projeto Tira-teima)." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/5/5134/tde-27052010-161855/.
Full textAbstract:
INTRODUÇÃO: A adesão à vacinação contra influenza é historicamente baixa entre profissionais da área da saúde (PAS) (2 a 36%). A ocorrência de sintomas respiratórios após vacinação é freqüentemente interpretada como falha vacinal. No Hospital das Clínicas da FMUSP, um estudo preliminar mostrou que as principais razões para não adesão são a percepção da ineficácia da vacina e o medo de reações adversas. OBJETIVOS: Identificar a incidência de eventos adversos pós-vacinação e identificar os vírus respiratórios (VR) responsáveis por eventuais episódios de infecção de via aérea superior (IVAS) que ocorram entre indivíduos vacinados. MÉTODOS: Foi seguida uma coorte de 398 PAS vacinados objetivando verificar a ocorrência de eventos adversos até 48 h após a vacinação. Durante 4 meses, 337 PAS foram seguidos 2 vezes por semana para avaliar a ocorrência de sintomas respiratórios. Lavados nasais foram coletados na presença de sintomas para pesquisa de VR. A técnica de imunofluorescência direta foi usada para diagnosticar vírus sincicial respiratório, influenza A e B, adenovírus e parainfluenza. PCR foi utilizada para detectar picornavírus e coronavírus e PCR em tempo real para diagnosticar metapneumovírus. Para assegurar melhor sensibilidade, influenza A e B foi também detectado pela PCR em tempo real e adenovírus pela PCR. RESULTADOS: Eventos adversos foram relatados por 30% dos PAS, predominando cefaléia (15,1%), mialgia (14,3%) e mal estar (13,6%). Nenhum evento adverso grave foi observado. Cento e vinte e um PAS (35,9%) desenvolveram sintoma respiratório durante o seguimento e lavado nasal foi colhido em 93 dos 192 episódios apresentados. Vírus influenza A foi detectado em 5 dos 93 episódios (5,3%) e outros vírus respiratórios em 26 (27,9%). No restante dos 61 episódios (65,6%) nenhum vírus foi encontrado. A densidade de incidência de infecção pelo vírus influenza foi de 4,3 episódios por 100 pacientes-mês enquanto que a densidade de infecção por outros vírus respiratórios foi de 10,8 episódios por pacientes-mês. CONCLUSÃO: Vacina da influenza é segura. O medo de eventos adversos grave parece injustificado, bem como, a percepção da ineficácia da vacina. O presente estudo evidencia que IVAS após vacinação é predominantemente causada por outros vírus respiratórios (28%) e não pelo vírus influenza (5%)<br>INTRODUCTION: Compliance with influenza vaccination has been historically poor among health care workers (HCW), ranging from 2 to 36% world around. The occurrence of respiratory symptoms following influenza vaccination is frequently taken as vaccine failure which reinforces vaccine disbelief. A preliminary study conducted at Hospital das Clínicas, University of São Paulo School of Medical Sciences, showed that the main reasons for non-compliance with influenza vaccination were the perception of vaccine inefficacy and fear of adverse events. OBJECTIVES: To determine the incidence of adverse events after seasonal influenza vaccination and identify other respiratory viruses causing upper respiratory infections in vaccinated HCWs. METHODS: A cohort of 398 vaccinated HCWs was prospectively surveyed for the occurrence of any adverse event in the first 48h after vaccination. A subset of the original cohort (337 HCWs) was followed up during four months, twice a week, for the detection of respiratory symptoms. Nasal washes were taken if respiratory symptoms occurred. Direct immunofluorescent assay (DFA) was performed for the detection of respiratory syncytial virus (RSV), influenza (INF) A and B, parainfluenza (PIV) 1, 2 and 3, and adenovirus (ADV). PCR was performed for the detection of human rhinoviruses (HRV), ADV and coronaviruses (hCoV); and real time PCR for the detection of human metapneumovirus (hMPV). To assure greatest sensitivity of influenza diagnosis, real time PCR was added to the diagnostic tools of influenza viruses. RESULTS: Adverse events were reported by 30% of the HCWs, being headache and myalgia reported by 50% and 47% of the participants, respectively. No severe adverse event was observed. One hundred and twenty-one HCWs (35.9%) developed 192 episodes of respiratory symptoms during follow-up and nasal washes were taken in 93 of them. Influenza A virus was detected in five of the 93 episodes (5.3%) and other respiratory viruses in 26 (27.9%). In the remaining 61 episodes (65.6%) no respiratory virus was identified. The incidence density of influenza was 4.3 episodes per 100 HCW-month, while the incidence density of other respiratory viruses was 10.8 episodes per HCW-month. CONCLUSIONS: Influenza vaccine is safe. The fear of adverse events as well as the perception of vaccine inefficacy seems to be unjustified in this population. The present study showed that the occurrence of upper respiratory infection during the four months following seasonal influenza vaccination of HCWs is generally caused by other respiratory viruses (28%) and not by influenza viruses (5%)
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Howson-Santana, Delia Roxanne. "A Phenomenological Inquiry into the Low Rates of Influenza Vaccination Among Older African Americans." ScholarWorks, 2015. https://scholarworks.waldenu.edu/dissertations/7451.
Full textAbstract:
Influenza vaccination is recommended for persons with high-risk health conditions such as chronic diseases to prevent flu-related complications and death. African Americans 65 years and older have consistently been reported to have the lowest influenza vaccination rates compared to all other racial groups, despite having higher rates of chronic diseases. A review of the literature indicated that there is a dearth of qualitative studies examining the grounds for these low rates. In this study, 15 African Americans 65 years and older were interviewed to explore the factors that contribute to low rates of flu vaccination among this racial group. Research questions using the constructs of the theory of planned behavior gathered the behavioral beliefs, normative beliefs (social norm), and control beliefs affecting low influenza vaccination uptake among older African Americans. Data analysis yielded 5 major themes: (a) fear of illness, (b) vaccine does not work, (c) self-advocacy, (d) have access to flu vaccine, and (e) education needed. These findings suggest that older African Americans would benefit from system, organization, and policy changes that support improved provider efforts and community interventions specifically targeting their concerns about flu vaccination. Implementation of strategies supported by evidence found in this study may improve understanding of flu vaccination from the perspective of older African Americans, and potentially increase the rates of influenza vaccination among this racial group to bring about positive social change.
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Meei-Yun, Lin. "Evolution of the T Cell Receptor Repertoire during and after Viral Infection: a Dissertation." eScholarship@UMMS, 1999. https://escholarship.umassmed.edu/gsbs_diss/244.
Full textAbstract:
The overall goal of this thesis is to examine how the T cell receptor (TCR) repertoire evolves during and after viral infections. Previous studies had examined TCR usage of selected virus-specific T cell clones, but little was known about how a diverse T cell repertoire changes during the transition between an acute infection and a memory response. It was also unclear how the T cell repertoire evolves under conditions of persistent infections associated with clonal exhaustion. To address these issues I used as a model system the lymphocytic choriomeningitis virus (LCMV) infection of mice, for which the T cell response is well-characterized. LCMV, strain Armstrong (LCMV-ARM), infection induces a strong CD8+ T cell response, which clears the virus and converts to a memory response. In contrast, high doses of LCMV clone 13 leads to persistent infections associated with T cell clonal exhaustion. These two extremes of T cell responses enable one to compare the evolution of the TCR repertoire under conditions where an acute T cell response converts to a memory response with that of T cell clonal exhaustion. In this thesis I analyzed the TCR repertoire usage directly ex vivo by the technique of CDR3 length spectratyping throughout the acute LCMV infection, into memory, after modulation by subsequent heterologous and homologous viral infections, and under conditions of T cell clonal exhaustion.
Kinetic studies on the frequencies of precursor cytotoxic T lymphocytes (PCTL) to the three LCMV immunodominant peptides had suggested that the virus-specific T cell repertoire becomes fixed by day 7 postinfection, when the virus is cleared. The pCTL data also showed that a high frequency of the LCMV-specific memory T cells remained stable throughout the lifetime of the mouse. To examine any changes of the TCR repertoire usage that may develop during the acute LCMV infection and into memory, the Vβ8 population was subjected to spectratype analyses, because Vβ8 represented a substantial amount of the LCMV-induced CD8+ T cells recognizing several LCMV-encoded peptides. Analyses of the Vβ8.1 spectratype showed that genetically identical mice generated remarkably different T cell responses, as reflected by different spectratypes and different TCR sequences in same-sized spectratype bands; a conserved CDR3 motif was, however, found within some same-sized bands. This indicated that meaningful studies on the evolution of the T cell repertoire required longitudinal studies within individual mice instead of comparisons between mice. Such longitudinal studies with peripheral blood (PB) samples showed that the virus-induced T cell repertoire changed little after viral clearance and during the silencing phase of the T cell response and that dominant spectratype peaks were preserved into long term memory. To determine the effect of secondary LCMV infection on the spectratype, the recalled LCMV-induced spectratypes were analyzed. Most of the dominant peaks detected in the primary infections remained present in the secondary infection. Some new peaks were also detected for the first time in the secondary infection, suggesting a further selection of the virus-induced T cell repertoire. The spectratype data support the concepts that the LCMV-induced T cell repertoire remains unchanged during the silencing phase after clearance of the virus and that the LCMV infection dramatically skews the host T cell repertoire in the memory state long after the virus is cleared.
Studies had shown that high doses of LCMV clone 13 induce a transient anti-viral CTL response followed by clonal exhaustion of T cells. To determine how the TCR repertoire evolves under conditions of persistent infections associated with T cell clonal exhaustion, the Vβ8.1 spectratypes were analyzed at various time points after the infection. In contrast to the stable LCMV-induced spectratype after viral clearance, continuous selection of the T cell repertoire occurred under conditions of persistent infections, as the T cell clones appeared and disappeared at different rates. The T cell repertoire ultimately returned to a Gaussian distribution under conditions of clonal exhaustion, indicating that clonal deletion occurs in the great majority of the virus-induced T cells.
To test the stability of the LCMV-induced TCR repertoire under conditions of subsequent heterologous viral infections, the recalled LCMV-induced spectratypes were examined in the presence or absence of intervening heterologous viruses. The results showed that the intervening heterologous viruses disrupted the recalled Vβ8.1-Jβ1.3 spectratype on secondary LCMV infection; this otherwise remained stable in the absence of intervening heterologous viruses. This result supports the hypothesis that subsequent heterologous viral infections disrupt the stable LCMV-induced T cell repertoire. To detennine whether a subset of the memory T cells was deleted by the IFN-induced apoptosis of memory T cells, the LCMV-immune spectratypes were analyzed before and after the injection of the IFN inducer, poly I:C. The LCMV-immune spectratypes remained relatively stable after poly I:C injection, suggesting that there is no selective protection or deletion of discrete memory T cell clones during the IFN-induced apoptosis.
In summary, the data in this thesis show that (i) the virus-induced T cell repertoire changes little after viral clearance and during the silencing phase of the T cell response, (ii) the LCMV infection dramatically skews the host T cell repertoire in the memory state, (iii) the evolution of the T cell repertoire occurs during secondary infections and under conditions of clonal exhaustion associated with persistent infections, (iv) genetically identical hosts generate different T cell responses to the same virus, and (v) intervening heterologous viral infections disrupt the recalled LCMV-induced T cell repertoire, but the LCMV-immune repertoire remained relatively stable upon the treatment of the IFN inducer, poly I:C.
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Lamb, David Sebastian. "Identifying Nodes of Transmission in Disease Diffusion Through Social Media." Scholar Commons, 2017. http://scholarcommons.usf.edu/etd/6883.
Full textAbstract:
The spread of infectious diseases can be described in terms of three interrelated components: interaction, movement, and scale. Transmission between individuals requires some form of interaction, which is dependent on the pathogen, to occur. Diseases spread through the movement of their hosts; they spread across many spatial scales from local neighborhoods to countries, or temporal scales from days to years, or periodic intervals. Prior research into the spread of disease have examined diffusion processes retrospectively at regional or country levels, or developed differential equation or simulation models of the dynamics of disease transmission. While some of the more recent models incorporate all three components, they are limited in the way they understand where interactions occur. The focus has been on home or work, including contact with family or coworkers. The models reflect a lack of knowledge about how transmissions are made at specific locations in time, so-called nodes of transmission. That is, how individuals’ intersections in time and space function in disease transmission.
This project sought to use the three factors of interaction, movement, and scale to better understand the spread of disease in terms of the place of interaction called the node of transmission. The overarching objective of this research was: how can nodes of transmission be identified through individual activity spaces incorporating the three factors of infectious disease spread: interaction, movement, and scale?
This objective fed into three main sub-objectives: defining nodes of transmission, developing an appropriate methodology to identifying nodes of transmission, and applying it using geotagged social media data from Twitter. To develop an appropriate framework, this research relied on time geography, and traditional disease. This particularly relied on the idea of bundling to create the nodes, and a nesting effect that integrated scale.
The data source used to identify nodes of transmission was collected from Twitter for the Los Angeles County, USA, area from October 2015 to February 2016. Automated text classification was used to identify messages where users self-reported an influenza-like-illness. Different groupings were created that combined both the syndrome and the symptoms of influenza, and applied to the automated classification. The use of Twitter for small-area health analysis was evaluated along with different text classification methodologies.
A space-time hierarchical clustering technique was adapted to be applied towards the twitter data in both identifying nodes of transmission and identifying spatiotemporal contact networks. This clustering data was applied to the classified Twitter data to look at where interaction between the classified users were occurring. This pointed to six nodes that were typically densely populated areas that saw the merging of large groups of people in Los Angeles (e.g. Disneyland and Hollywood Boulevard).The movement of these individuals were also examined by using a edit distance to compare their visits to different clusters and nodes.
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Yip, Ronald H. N. "Mechanisms of induction and modulation of the pro-inflammatory cytokine interleukin-1beta." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:14e4bd37-d3f3-4419-b2f0-564c22df4d09.
Full textAbstract:
Interleukin (IL)-1beta is a powerful pro-inflammatory cytokine with important roles in directing both innate and adaptive immunity. As a result, its production is tightly controlled, with the synthesis of an inactive form (pro-IL-1beta) and the requirement of a second signal. This induces the formation of the inflammasome, a macromolecular complex which mediates the maturation of IL-1beta into the bioactive cytokine. Given its significance, it is important to identify mechanisms of IL-1beta induction and modulation. Firstly, we describe serum amyloid A (SAA), an acute phase protein with immunomodulatory properties, as a novel inducer of IL-1beta. Using cells from genetically modified mice, the molecular mechanisms responsible were dissected, demonstrating the receptors TLR2 and NLRP3 as required for this effect. By instilling SAA into mice, we also show that SAA is able to induce IL-1beta production in vivo. Invariant natural killer T (iNKT) cells have also been shown to be important modulators of immunity, mediating both pro- and anti-inflammatory responses. iNKT cells are non-conventional T lymphocytes which recognise glycolipid in the context of CD1d, with the ability to interact with immature antigen presenting cells in an autoreactive manner. We link the regulatory ability of iNKT cells with IL-1beta production, showing that a low activation signal leads to the induction of an IL-13-dominated cytokine profile, as well as weak engagement of the CD40-CD40L pathway. We show for the first time that through these mechanisms, iNKT cells are able to dampen the secretion of IL-1beta upon subsequent stimulation of dendritic cells. We hypothesise that this effect of iNKT cells is important in controlling inflammatory responses in vivo, and demonstrate exacerbated IL-1beta production and inflammation during influenza virus infection of iNKT cell-deficient animals. This novel anti-inflammatory property of iNKT cells may be harnessed in the therapeutic intervention of inflammatory disorders.
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Jansson, Öhlén Linn. "Fear of influenza vaccination in the event of an epidemic : Perceptions of threat and trust in two socioeconomically different areas of Stockholm." Thesis, Södertörns högskola, Miljövetenskap, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:sh:diva-39222.
Full textAbstract:
In recent history, four influenza pandemics have occurred causing worldwide suffering. It is only a matter of time when a fifth pandemic will emerge. The willingness of the public to perform recommended precautionary actions is central for successful outbreak management, where the most important measure is vaccination. Trust in the health care system as well as personal perceptions of the threat of a pandemic can influence the publics willingness to perform precautionary actions. Aims: This study seeks to analyze how the public in two socioeconomically different areas of Stockholm perceive the threat of a possible future epidemic, their level of trust in the health system and what precautionary actions they are willing to perform. Methods: questioners with respondents from two socioeconomically different areas in Stockholm (Tensta and Danderyd) were gathered and have been statistically analyzed and interpreted using the health belief model and theories about trust. Results: The study showed that a higher level of perceived benefits of precautionary actions and a higher level of worriedness to get seriously ill if infected during an influenza epidemic were correlated with a higher level of willingness to follow precautionary actions. A significant association between unwillingness to vaccinate and perceived barriers to vaccination (that it can be harmful to the health) was also found. Trust in the health system was significantly lower in Tensta compared to Danderyd and higher trust in the health system was found to lead to higher perceived benefits of precautionary actions. Additionally, respondents with higher trust in information from the health care were generally more willing to vaccinate. Finally, no demographic determinants except age was shown to influence perceptions about precautionary actions and threat. Conclutions: Willingness to perform precautionary actions were influenced by worriedness, perceived benefits, perceived barriers, age and trust in the health care. Efforts might thus be needed to increase the trust in the health system in socioeconomically weak areas, as well as to increase the trust in influenza vaccination in general.