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MacCormick, I. "Malarial retinopathy and neurovascular injury in paediatric cerebral malaria". Thesis, University of Liverpool, 2016. http://livrepository.liverpool.ac.uk/2049100/.
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Background Diseases of the brain are difficult to study because this organ is relatively inaccessible. Only one part of the central nervous system is available to direct, non-invasive observation – the retina. The concept of the retina as a window to the brain has created much interest in the retina as a source of potential markers of brain disease. Paediatric cerebral malaria is a severe neurological complication of infection with the parasite Plasmodium falciparum, which is responsible for death and disability in a significant number of children in sub-Saharan Africa. As with many neurological diseases, the precise mechanisms by which this infection causes damage to the brain remain unclear, and this hampers efforts to develop effective treatments. It may be that studying the retina in paediatric cerebral malaria could both illuminate pathogenesis specific to this disease, and also provide an illustration of how to approach retinal biomarkers in a new, and potentially more effective way. Methods I approached the aim of developing retinal features as markers of brain disease in paediatric cerebral malaria via several objectives. I made use of an existing clinical study to collect new retinal data from ophthalmoscopic examinations and fundus fluorescein angiograms from patients over three successive malaria seasons in Malawi, and added these to historical data obtained previously at the same site. I devised a new method for grading retinal images. I reviewed the biological plausibility of associations between retina and brain in cerebral malaria, and then considered analytical methods to interpret my retinal data effectively. Finally I estimated associations between retinal features, outcomes, and a radiological measure of brain swelling using combinations of regression models. Results My review of retinal and cerebral histopathology, vascular anatomy and physiology indicated that certain retinal and brain regions may be similarly prone to damage from sequestration as a result of interactions between aberrant rheology and microvascular geometry, such as branching patterns and arteriole to venule ratios. My review of evaluations of analogy and surrogacy suggested that biological similarities between retina and brain could be used to justify statistical evaluation of the amount of information the subject and object of the inference share about a common outcome, as used to assess surrogate end points for clinical trials. This kind of approach is able to address questions about whether a particular retinal feature is effectively equivalent to an analogous disease manifestation in the brain. I report analyses on three overlapping groups of subjects, all of whom had retinopathy positive cerebral malaria: children with admission ophthalmoscopy (n=817), children with admission fluorescein angiography (n=260), and children with admission angiography and MRI of the brain (n=134). Several retinal features are associated with death and longer time to recover consciousness in paediatric cerebral malaria. Broadly speaking, these features appear to reflect two processes: neurovascular sequestration (e.g. orange vessel discolouration and death), and neurovascular leakage (e.g. >5 sites of punctate leak and death). Respective adjusted odds ratios and 95% confidence intervals for these particular associations are: 2.88 (1.64-5.05); and 6.90 (1.52-31.3). Other related processes may also be important, such as ischaemia, which can be extensive. Associations between retina and brain are less clear, in part because of selection bias in the samples. Conclusions Neurovascular leak is important in fatal paediatric cerebral malaria, suggesting that fatal brain swelling may occur primarily as a result of vasogenic oedema. Other processes are also likely to be involved, particularly neurovascular sequestration, which is visible on retinal imaging as orange vessels or intravascular filling defects. Sequestration may plausibly cause leak through direct damage to tight junctions and by increasing transmural pressure secondary to venous congestion. Several types of retinal leakage are seen and some of these may represent re-perfusion rather than acute injury. Future work to investigate temporal changes in retinal signs may find clearer associations with radiological and clinical outcomes. The steps taken to evaluate retinal markers in cerebral malaria illustrate a more rigorous approach to retinal biomarkers in general, which can be applied to other neurological diseases.
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Herricks, Thurston E. "Malaria pathogenesis : deformability limits of malaria infected erythrocytes /". Thesis, Connect to this title online; UW restricted, 2007. http://hdl.handle.net/1773/8622.
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Abdullah, Mohamed Rusli. "Malaria and malaria control in Jeli Peninsular Malaysia". Thesis, University of Liverpool, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.266047.
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Huot, Chantheany Pornthep Chanthavanich. "Clinical manifestation of uncomplicated falciparum malaria and vivax malaria in Thai children /". Abstract, 2004. http://mulinet3.li.mahidol.ac.th/thesis/2547/cd363/4638516.pdf.
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Melzig, Daniela. "Malaria Epidemiologie, Klinik und Verläufe bei Patienten mit importierter Malaria /". [S.l.] : [s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=968578845.
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Kownatzki, Christine. "Malaria und Schwangerschaft". Diss., lmu, 2006. http://nbn-resolving.de/urn:nbn:de:bvb:19-54343.
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Ohashi, Taryn M. "Eradicating Malaria: Improving a Multiple-Timestep Optimization Model of Malarial Intervention Policy". Scholarship @ Claremont, 2013. http://scholarship.claremont.edu/scripps_theses/273.
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Malaria is a preventable and treatable blood-borne disease whose complications can be fatal. Although many interventions exist in order to reduce the impacts of malaria, the optimal method of distributing these interventions in a geographical area with limited resources must be determined. This thesis refines a model that uses an integer linear program and a compartmental model of epidemiology called an SIR model of ordinary differential equations. The objective of the model is to find an intervention strategy over multiple time steps and multiple geographic regions that minimizes the number of days people spend infected with malaria. In this paper, we refine the resolution of the model and conduct sensitivity analysis on its parameter values.
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Owusu-Ofori, Alex. "Transfusion-transmitted malaria and bacterial infections in a malaria endemic region". Thesis, University of Liverpool, 2012. http://livrepository.liverpool.ac.uk/6173/.
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Background and Methods: Blood transfusion saves lives and improves health but the presence of transfusion transmissible infections can have untoward consequences. When undetected, these infections can cause significant morbidity and mortality to transfusion recipients. On the other hand, a high prevalence of transfusion-transmitted infections (TTI) leading to rejection of a large proportion of donated blood can result in blood shortages and subsequent increase in mortality. Malaria and bacterial infections are transfusion transmissible but there is limited data concerning these infections in sub-Saharan Africa. Although the burden of transfusion-transmitted malaria in malaria endemic countries are unknown, it is recommended that all donated blood is screened for malaria parasites and presumptive treatment be given to transfusion recipients. Bacterial contamination in sub-Saharan Africa has been reported to occur in between 8 - 17% of stored blood but the effect of contamination on transfusion recipients has not been determined. Syphilis is currently the only bacterial infection for which routine screening is recommended but screening is not being performed in many blood centres including Komfo Anokye Teaching Hospital (KATH) in Kumasi, Ghana where this study took place. This study examined the effects of transfusion-transmitted malaria (TTM) and bacterial infections (including syphilis) on transfusion recipients in a malaria endemic area. Four malaria screening tests were compared to assess their usefulness in the context of African blood banks. Pregnant women, children and immune-compromised transfusion recipients from the Departments of Obstetrics and Gynaecology, Paediatrics, Medicine and Oncology in KATH were enrolled into the study. Results: Anti-malarial drugs were routinely prescribed with paediatric transfusions. Fifty patients were evaluated after receiving blood transfusions that were positive for P. falciparum by PCR and seven recipients developed PCR-detectable parasitaemia. In only one recipient (2%) was TTM confirmed. The prevalence of P. falciparum malaria in transfused blood was 4.7% (21/445) by microscopy, 13.7% (60/440) by rapid diagnostic test, 18% (78/436) by polymerase chain reaction and 22.2% (98/442) by enzyme immunoassay. Bacterial contamination was found in 11.5 %( 95% CI 7.0-16.0%) (23/200) of donated blood units but only half of the recipients were observed to developed adverse signs of transfusion related sepsis. The mean duration of storage of blood was 2 days. The prevalence of syphilis sero-positivity in donated blood was 8.0% (95% CI 4.3-11.7%). Seroconversion took place in an 8 year old girl, after receiving a syphilis sero-positive unit of blood. Conclusions: This thesis has shown that malaria parasites may be commonly detected in donor blood but TTM occurs infrequently in recipients living in malaria endemic areas. The high rate of bacterial contamination and its associated transfusion related sepsis poses a safety risk to transfusion recipients. Transfusion-transmitted syphilis remains a risk for transfusion recipients in blood centres with a high prevalence and short duration of storage of donor blood.
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Tek, F. Boray. "Computerised diagnosis of malaria". Thesis, University of Westminster, 2007. https://westminsterresearch.westminster.ac.uk/item/92068/computerised-diagnosis-of-malaria.
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Buitrago, Amanda Elena Maestre. "Immunity to malaria using the rodent malaria parasite Plasmodium chabaudi AS as a model of the human malaria Plasmodium falciparum". Thesis, University of Glasgow, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.298916.
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Hodgson, Susanne H. "Using the controlled human malaria infection model to investigate immunity to malaria". Thesis, University of Oxford, 2015. https://ora.ox.ac.uk/objects/uuid:b3c9a2eb-beab-4ef6-bd8d-483390f316b8.
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Controlled human malaria infection (CHMI) studies, where healthy volunteers are infected with Plasmodium falciparum have become a vital tool to accelerate vaccine and drug development. As CHMI trials are carried out in a controlled environment, they allow unprecedented, detailed evaluation of parasite growth dynamics and immunological responses to infection. Though commonly performed in malaria-naïve populations, CHMI trials have rarely been conducted in malaria-endemic regions and to date, have not been used to investigate naturally acquired immunity (NAI) to P. falciparum infection. This thesis describes the first CHMI study in Kenya and the first attempt to use the modern CHMI model to explore the dynamics and mechanisms of NAI. Using samples collected post-CHMI from both UK volunteers and Kenyan subjects with varying prior exposure to P. falciparum, this work reports and compares the findings of key in vitro assays including GIA, ADRB activity and changes in gene expression in order to understand the effect of NAI on these measures.
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Tegha, Gerald Loiswayo. "Detection and identification of plasmodium species causing malaria in Malawi using rapid diagnostic tests". Thesis, Nelson Mandela Metropolitan University, 2011. http://hdl.handle.net/10948/d1021240.
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Malaria represents one of the oldest documented diseases among humans and even today organisms in the genus Plasmodium kill more people than any other infectious disease, especially in tropical and subtropical areas. The four most common species which infect humans are Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale and Plasmodium malaria. Of these four species, Plasmodium falciparum and Plasmodium vivax account for 95 percent of infections globally. Microscopy has been used since early days for the diagnosis of malaria because this method is simple, does not require highly equipped facilities, and in most cases enables differentiation among the species causing malaria in humans when performed by skilled microscopy readers. However, this method has been misleading in identifying parasite species, especially in the case of low level parasitemia, a mixed parasite infection, or modification by drug treatment as well as in placental malaria. Malaria rapid diagnostic tests (RDT) have played a major role in malaria management; particularly in providing blood based diagnosis in remote locations where microscopy based diagnosis is unavailable. These diagnostic tests are fast and easy to perform and do not require electricity or specific equipment. As part of strengthening malaria diagnostics in Malawi, the Ministry of Health and Population strongly recommends the use of malaria RDT’s at all levels of the health care delivery system. However, malaria microscopy remains a gold standard test for malaria. All patients (regardless of age) with suspected uncomplicated malaria should have a confirmed diagnosis with malaria RDT before anti-malaria treatment is administered. Based on field performance evaluations that assessed performance, quality control and production capacities of the manufacturing companies of malaria RDT’s, the Ministry of Health and Population recommended two brands of Histidine Rich Protein 2 (HRP-2), RDT’s for use in Malawi. These are SD Bioline malaria Ag Pf and the New Paracheck malaria Ag Pf. All these RDT’s are able to detect only P. falciparum. However, other species have been reported to exist in the country and there is a need to find proper RDT’s which will be able to detect all other species including P. falciparum. The main aim of this study was to evaluate Paramax-3 Pf/Pv/Pan RDT (Zephyr Biomedicals, India), if used in Malawi, could be able to detect and identify the different species of Plasmodium causing malaria in Malawi. The study recruited a total of 250 adult and infants at Bwaila Hospital in Lilongwe, Malawi. Study results showed that the overall sensitivity and specificity of the Paramax-3 RDT used in the study were 100 percent and 83 percent respectively. However, it was observed that the RDT test was not able to identify the P. ovale, and in some cases, the RDT test was positive for P. falciparum when the PCR identified the species as P. ovale. No P. vivax was detected both by RDT and PCR. This study was able to detect and identify the presence of P. malaria and P. ovale in Malawi apart from the P. falciparum. There were no significant differences between microscopy results compared to both the RDT and the PCR, with 94 percent and 98 percent sensitivities of R1 and R2 compared to RDT, as well as 94 percent and 96 percent sensitivities for R1 and R2 compared to PCR respectively. Both R1 and R2 had low specificities for example, R1 had 72 percent and R2 had 80 percent compared to RDT. Comparing R1 and R2 to PCR, the sensitivities were 64.9 percent and 67.2 percent respectively. However, the readers had difficulties differentiating the different species microscopically. The history of anti-malaria treatment had no significant effect on the outcome of the results in both the RDT and PCR.
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Bernal, Acevedo Óscar Alberto. "Umbral epidémico en malaria". Doctoral thesis, Universitat Autònoma de Barcelona, 2006. http://hdl.handle.net/10803/4625.
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Este estudio analiza diferentes indicadores y propones umbrales epidémicos que pueden ayudar para una adecuada toma de decisiones. Para esto, se seleccionaron 4 epidemias en las que MSF ha intervenido en los últimos 5 años, por contar con suficiente información, en Angola, Etiopía, Tanzania y Burundi.Luego de una descripción de cada epidemia utilizando diferentes indicadores, se pudo observar que la incidencia semanal y la proporción de la malaria en la consulta externa son indicadores fáciles de recopilar, que detectan rápidamente un aumento en los casos de malaria y que sirven para ver la evolución de la misma.
Otros indicadores evaluados como la distribución por grupos de edad, letalidad por malaria o proporción de admisiones debido a la malaria, proporción de malaria confirmada, no cumplieron con los requisitos mencionados anteriormente.
Los umbrales se establecieron mediante las pruebas de normalidad de D'Agostino-Pearson y la curva ROC (Receiver Operating Characteristics), se validaron con las pruebas de Kappa y de Mc. Nemar, usando los programas estadístico MedCalc® (Schoonjans, 2006) y el SPSS® 12.0.
Teniendo en cuenta estas 4 epidemias hemos establecido unos umbrales sobre la base de una sensibilidad superior al 90% y una especificidad no inferior al 70%. Para la incidencia de malaria el umbral propuesto es de 600 casos por 100.000 habitantes por semana y para la proporción de la malaria se estableció en el 50% del total de las consultas en una semana sean debidas a la malaria.
Los niveles de alerta resultantes nos pueden ayudar a tomar decisiones que deben complementarse con un estudio del contexto, análisis de factores de riesgo, la capacidad de respuesta local y la posibilidad de ayuda externa.
This study analyses differing indicators and proposes epidemic thresholds that may be helpful in the decision-making process. To this end, four epidemics in which MSF had intervened in the last 5 years and therefore had sufficient information on were selected. These had occurred in Angola, Ethiopia, Tanzania and Burundi.
Following a description of each epidemic using a range of indicators, the weekly rate and proportion of malaria in outpatient clinics were found to be indicators that were easy to gather, rapidly detected a rise in malaria cases and could show the evolution of the disease.
Other indicators assessed such as age group distribution, fatality due to malaria and the proportion of malaria admissions and proportion of confirmed malaria did not meet the requisites mentioned above.
Thresholds were established using the D'Agostino-Pearson test and ROC (Receiver Operating Characteristics) curve and validated with the Kappa and de Mc. Nemar tests. The MedCalc® (Schoonjans, 2006) and SPSS® 12.0 statistical programmes were used to this end.
For these four epidemics, thresholds were established on the basis of sensitivity above 90% and specificity of at least 70%. The threshold proposed for the rate of malaria is 600 cases per 100,000 inhabitants per week and for the malaria proportion this was set at 50% of all consultations in one week due to malaria.
The resulting alert levels can be used to make decisions that should be complemented by a study of the context, analysis of risk factors, the capacity for a local response and the possibility of external aid.
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Müller, Tara Catharina. "Non-malaria febrile illness". Diss., lmu, 2013. http://nbn-resolving.de/urn:nbn:de:bvb:19-153855.
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Crooks, Lucy. "Gametocyte investment in malaria". Thesis, University of Edinburgh, 2004. http://hdl.handle.net/1842/13498.
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Gametocytes, the transmission stage of malaria parasites, are generally rare in infections. I explore whether this may be a parasite adaptation that paradoxically maximises fitness. I present an optimality analysis of gametocyte investment based on a discretely formulated within-host model. I show that low gametocyte investment is predicted as a result of the trade-off that exists between producing gametocytes and increasing parasite numbers. I predict that gametocyte investment should decrease as maximum asexual density occurs later in infections and also as parasite fecundity rises. I address statistical problems with estimating gametocyte investment from blood smears. I also consider the simpler case of estimating parasitaemias and gametocytaemias. Traditional methods of counting parasites in smears can produce biased estimates of parasitaemia, gametocytaemia and gametocyte conversion. I introduce an alternative method of counting based on inverse sampling. This method is unbiased, is consistently precise and the most time-efficient method of counting. I used the inverse sampling method to estimate gametocyte conversion (the observed outcome of investment) in P. chabaudi infections in mice, which had been manipulated to alter the time of maximum asexual density. Gametocyte conversion showed two peaks. The timing of the peaks depended on the time of maximum asexual density. Maximum conversion decreased as the time to maximum asexual density rose as predicted by my optimality analysis. An interesting finding was that gametocyte conversion decreased after reaching a maximum. This result is counter to most life history theory. I suggest this indicates that survival of infections into a chronic phase may be an important component of fitness. Maximum conversion occurred after maximum asexual density. This leads me to propose that contrary to the common view, gametocyte investment may be suppressed at times when there is a high risk of parasite clearance. Understanding the reasons for gametocyte rarity may help to predict how P. falciparum will respond to intervention and suggest new methods of malaria control.
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Russell, Clare. "Immunopotentiation of malaria vaccines". Thesis, University of Edinburgh, 2004. http://hdl.handle.net/1842/12892.
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Plasmids were constructed to encode C3d/PfEMP-1 fusions and expression of recombinant protein in mammalian cells in culture was assayed. Eukaryotic expression of P. falciparum proteins proved to be problematic and a re-condoning approach was adopted to address this. The production of polyclonal anti-PfEMP-1 antibodies in mice was assessed in immunofluorescence assays and in immunoblots with P. falciparum-infected erythrocytes. The data question the suitability of a DNA vaccine approach in the development of a PfEMP-1-based vaccine using C3d. In order to raise specific antibodies to PfEMP-1 and to develop a suitable assay to assess immunogenicity of this antigen, research efforts became focussed on the production of recombinant PfEMP-1 protein, with a view to immunising mice. A recombinant PfEMP-1 domain was expressed in mammalian cells and characterised, demonstrating it to be the ligand involved in binding uninfected erythrocytes. Its reactivity with immune sera and, therefore, its suitability as a malaria vaccine candidate was assessed. Findings highlight the need for further work on the development of methods to produce functionally active recombinant protein. They also show the necessity of improving methods of detecting surface expression of PfEMP-1. The suitability of the Saimiri monkey model for C3d-based vaccination and P. falciparum challenge experiments was assessed. In other species, the receptor for C3d is CR2, expressed on B cells. Saimiri B cells were characterised and their capacity to bind human C3d was demonstrated, indicating that Saimiri is potentially a suitable model for pre-clinical vaccination studies using human C3d-based immunoprotentiation.
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Spottiswoode, Natasha. "Hepcidin regulation in malaria". Thesis, University of Oxford, 2015. http://ora.ox.ac.uk/objects/uuid:ea5646aa-9c64-4158-9de8-1d6b7fc9d41d.
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Epidemiological observations have linked increased host iron with malaria susceptibility. At the same time, blood-stage malaria infection is associated with potentially life-threatening anemia. To improve our understanding of these relationships, this work presents an examination of the mechanisms controlling the upregulation of the hormone hepcidin, the master regulator of iron metabolism, in malaria infection. Chapter 2 presents data from a mouse model of malaria infection which indicate that hepcidin upregulation in malaria infection is associated with increased activity of the sons of mothers against decapentaplegic (Smad) signaling pathway. Although the canonical Smad pathway activators, bone morphogenetic proteins (Bmp) are not increased at the message level following infection, activin B, which has been recently shown to increase hepcidin through the Smad signaling pathway in conditions of inflammation and infection, is upregulated in the livers of malaria-infected mice. Chapter 3 shows that both activin B and the closely related protein activin A upregulate hepcidin in vitro and in vivo. Chapter 3 also explores the effects of the activin-binding protein follistatin in both systems and in the same malaria-infected mouse model as presented in Chapter 2. The work presented in Chapter 4 extends these studies to human infections by demonstrating that activin A protein co-increases with hepcidin in human serum during malaria infection. Taken together, these findings are consistent with a novel role for activin proteins in controlling hepcidin upregulation in the context of malaria infection. This work may form a basis for the development of novel therapeutics that speed recovery from malarial anemia by inhibiting activins’ actions. Chapter 5 examines the role of infected red blood cell-derived microparticles in the initial recognition of a P. falciparum malaria infection, and subsequent hepcidin upregulation. Microparticles stimulate production of cytokines from peripheral blood mononuclear cells (PBMC), which also upregulate activin A message in response to both microparticles and whole infected red blood cells. These data are consistent with a model in which malaria-derived stimuli such as microparticles trigger the systemic release of activin proteins, which then act on the liver to upregulate hepcidin. Evidence has shown that cytokine levels at birth are related to malaria risk. In Chapter 6, hepcidin is measured in cord blood samples from participants in a large-scale clinical study in a malaria-endemic area, and shown to be elevated in cord blood from neonates with a clinical history of placental malaria. Cord blood hepcidin is also compared to birth levels of iron markers and other cytokines, and future clinical outcomes. Finally, the contributions of DNA methylation levels to cord hepcidin and cytokine levels are assessed by comparison of CpG methylation, at sites in genes encoding hepcidin and cytokines, to the serum concentrations of the genes’ protein products. Several intriguing associations are noted which indicate a possible novel role for DNA methylation in the determination of birth cytokine and hepcidin levels. Chapter 7 synthesizes the data presented in this thesis, interprets the possible significance of the major findings, and offers suggestions for future work.
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Павличева, Світлана Володимирівна, Светлана Владимировна Павлычева, Svitlana Volodymyrivna Pavlycheva i O. Udoka. "Malaria epidemic in Nigeria". Thesis, Видавництво СумДУ, 2011. http://essuir.sumdu.edu.ua/handle/123456789/15950.
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The incidence of malaria is very high in Nigeria due to its tropical location. A number of factors appear to be contributing to the resurgence of malaria: rapid spread of resistance of malaria parasites to chloroquine and the other quinolines; frequent armed conflicts and civil unrest in many countries, forcing large populations to settle under difficult conditions, sometimes in areas of high malaria transmission
When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/15950
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Soe, Soe Win Polrat Wilairatana. "Hematological changes in malaria /". Abstract, 2006. http://mulinet3.li.mahidol.ac.th/thesis/2549/cd388/4838792.pdf.
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Thematic paper (M.C.T.M. (Clinical Tropical Medicine))--Mahidol University, 2006.LICL has E-Thesis 0012 ; please contact computer services. LIRV has E-Thesis 0012 ; please contact circulation services.
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Grieg, Rachel. "Immunopathogenesis of marine malaria". Thesis, London School of Hygiene and Tropical Medicine (University of London), 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.536855.
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Maestre, Buitrago Amanda Elena. "Immunity to malaria using the rodent malaria parasite Plasmodium chabaudi chabaudi AS as a model of the human malaria Plasmodium falciparum". Thesis, University of Glasgow, 1997. http://theses.gla.ac.uk/2036/.
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The role of IFN in acquisition of immunity against erythrocyte forms of P.c. chabaudi AS was studied. Inbred NIH mice given the construct 7 days before malaria infection, showed a significant delay in the onset and in the level of the recrudescent parasitaemia in comparison with controls. No differences, however, were observed in the recrudescent parasitaemia between the groups. NIH mice infected with malaria 3 days after or on the same day as the administration of the IFN construct, showed a primary peak of infection similar to controls, but the resolution of this patent parasitaemia occurred 1 or 2 days earlier in the experimental mice when compared with controls. In the same experiment, mice given the construct 10 days before malaria infection had a similar course of infection as controls. Simultaneous inoculation with two S. typhimurium constructs: IFN and TNF, 8 days before malaria infection resulted in a course of parasitaemia similar to that observed in mice given the IFN construct alone. On the other hand, inoculation of 'susceptible' inbred A/J mice with S. typhimurium/IFN 3 or 8 days before malaria infection had no effect on the course of the parasitaemia when compared with controls. The immune mechanisms involved in the better control of the malaria infection of NIH mice given S. typhimurium/ IFN, seem to be independent of nitric oxide (NO) production, since increased levels of the molecule were demonstrable around the peak of the primary parasitaemia in control groups but not in experimental mice. In the latter basal levels of serum NO were observed from the period after the S. typhimurium/ IFN inoculation until up to three days after the peak of the parasitaemia.
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Wipasa, Jiraprapa. "Induction and regulation of merozoite surface protein (MSP) 1-induced immunity to Malaria /". St. Lucia, Qld, 2002. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe16496.pdf.
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Devenport, Martin Phillip. "Isolation and characterisation of genes regulating development in the mosquito Anopheles gambiae". Thesis, University of Liverpool, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.367172.
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Vasconcelos, Nina-Maria. "Vaccine development strategies applied to the Plasmodium falciparum malaria antigen Pf332 /". Stockholm : Wenner-Gren Institute for Experimental Biology, Stockholm university, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-1263.
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Ghimire, Kabita. "Geographic distribution of malaria in Nepal". Diss., Kansas State University, 2016. http://hdl.handle.net/2097/34464.
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Doctor of PhilosophyDepartment of Geography
Douglas G. Goodin
The malaria burden has decreased in Nepal between 1988 and 2013. However, there are challenges to completely eradicating the disease. Malaria patterns in a few endemic districts have not changed, and higher malaria case rates have been detected within districts which otherwise were categorized as low endemic areas. Underlying biophysical, socioeconomic, and behavioral factors influence malaria transmission and create region-specific patterns. This research employs various concepts, tools, and techniques to understand the geographic distribution of malaria in Nepal. In this research, malaria prevalence patterns were investigated at multiple spatial and temporal scales. The study identifies malaria hot spots, describes their characteristics and examines shifts in malaria hot spots between 1988 and 2013. Within that 26-year time span, 267,121 confirmed malaria cases were recorded. Thirty-nine of 75 districts were identified as malaria hot spots in Nepal. Based on the frequency, persistence and proportion of caseloads each year, the identified hotspots were grouped into five categories; stable, disappearing, emerging, reemerging, and intermittent. The research also investigated the relationship between climatic factors and malaria frequency, and found that temperature and precipitation during the monsoon and non-monsoon seasons played significant roles in determining the absence and presence of malaria and low and high frequency of malaria distribution at the district level. The dissertation also presents the findings of a study that investigated malaria–related knowledge, perceptions and practices among adults in Nepal, specifically knowledge about its signs, symptoms, consequences, and the availability and use of prevention tools. Although a significant portion of respondents had heard of malaria there was wide variation in their knowledge about specific information related to the disease. Locality, age, household size, education, and income were significantly associated with malaria–related knowledge.
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Kaneko, Akira. "Malaria on islands : human and parasite diversities and implications for malaria control in Vanuatu /". Stockholm, 1999. http://diss.kib.ki.se/1999/19990927kane.
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Lynch, Caroline. "The impact of migration on malaria, Southwest Uganda : malaria in the highlands of Uganda". Thesis, London School of Hygiene and Tropical Medicine (University of London), 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.558361.
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Nisar, Samia. "Role of ATP2B4 and human malaria : looking for functional genetic variants associated with malaria". Thesis, Aix-Marseille, 2020. http://theses.univ-amu.fr.lama.univ-amu.fr/200911_NISAR_992dobfs271wcdsgy656twqjfn399ockic_TH.pdf.
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GWAS pour le paludisme grave identifié 30 variantes génétiques situées dans régions non codantes, avec seulement quelques associations répliquées dans des populations indépendantes. Dans cette étude, nous avons cherché à identifier les variantes génétiques potentielles situées dans ces loci et à démontrer leur activité fonctionnelle. Nous avons systématiquement étudié l'effet régulateur des SNP en déséquilibre liaison avec les tagSNPs associés au paludisme sévère dans plusieurs populations. L'annotation et priorisation ont conduit à l'identification d'une région régulatrice contenant 5 SNP ATP2B4 en déséquilibre liaison avec le tagSNP. Nous confirmé l'association de rs10900585 et trouvé des associations significatives de paludisme sévère avec nos candidats dans population sénégalaise. Nous montré que cette région avait à la fois une activité promoteur et un activateur et que l'individu et combinaison de SNP avaient un effet en utilisant des dosages de luciférase. En outre, la délétion médiée par CRISPR / Cas9 de cette région a diminué le transcrit ATP2B4 et les niveaux de protéines et a augmenté la concentration intracellulaire de Ca2+ dans les cellules K562. Ensemble, nos données montrent les variantes génétiques associées au paludisme grave modifient l'activité d'un promoteur avec une fonction d'activateur. Nous montré que cet amplificateur contrôle l'expression de l'ATP2B4 qui code l'ATPase 4 (PMCA4) transportant le calcium dans la membrane plasmique, qui est la principale pompe à calcium des globules rouges. La modification de l'activité de cet Epromoter affecte le risque de paludisme sévère probablement par l'effet de la concentration de calcium sur la parasitémieGenome-wide association studies (GWAS) for severe malaria have identified 30 genetic variants mostly located in non-coding regions, with only few associations replicated in independent populations. In this study, we aimed at identifying potential causal genetic variants located in these loci and demonstrate their functional activity. We systematically investigated the regulatory effect of the SNPs in linkage disequilibrium with the tagSNPs associated with severe malaria in several populations. Annotating and prioritizing genetic variants led to the identification of a regulatory region containing 5 ATP2B4 SNPs in linkage disequilibrium with the tagSNP rs10900585. We confirmed the association of rs10900585 and also found significant associations of severe malaria with our candidate SNPs (rs11240734, rs1541252, rs1541253, rs1541254, and rs1541255) in a Senegalese population. Then, we showed that this region had both a promoter and an enhancer activity and that both individual SNPs and the combination of SNPs had an effect using luciferase reporter assays. In addition, CRISPR/Cas9-mediated deletion of this region decreased ATP2B4 transcript and protein levels and increased Ca2+ intracellular concentration in K562 cell line. Taken together, our data show that severe malaria associated genetic variants alters the activity of a promoter with enhancer function. We showed that this enhancer controls the expression of ATP2B4 that encodes plasma membrane calcium-transporting ATPase 4 (PMCA4), which is the major calcium pump on red blood cells. Altering the activity of this Epromoter affects the risk of severe malaria probably through calcium concentration effect on parasitaemia
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Campino, Susana. "Genetic analysis of murine malaria". Doctoral thesis, Umeå universitet, Medicinsk biovetenskap, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-124.
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Malaria, an infectious disease caused by Plasmodium parasites, is one of the major world-scale health problems. Despite the efforts aimed at finding an effective way to control the disease, the success has been thwarted by the emergence of parasite drug resistance and mosquito resistance to insecticides. This thesis focuses on the genetic analysis of resistance to murine malaria induced by the lethal Plasmodium berghei ANKA using a wild-derived-inbred strain (WDIS). The aim of this thesis was to exploit the genetic diversity represented among WDIS for identifying loci contributing to resistance/susceptibility to murine malaria. The work included a genome-wide polymorphism survey using microsatellite markers performed on 10 WDIS. Comparisons of these strains to laboratory inbred strains confirmed a higher rate of polymorphism among the WDIS. We conclude that these WDIS represent repositories of unique naturally occurring genetic variability that may prove to be invaluable for the study of complex phenotypes. Next, we used the WDIS to search for novel phenotypes related to malaria pathogenesis. Whereas most laboratory strains were susceptible to experimental cerebral malaria (ECM) after infection with P. berghei ANKA, several WDIS were found to be resistant. To study the genetic inheritance of resistant/susceptibility to P. berghei ANKA infection we analysed backcross and F2 cohorts derived from crossing the WLA wild-derived strain with a laboratory mouse strain (C57BL/6). A novel phenotype represented by the cure of infection, clearance of parasitaemia and establishment of immunological memory was observed in the F2 progeny. The backcross progeny was used to genetically map one locus on chromosome 1 (Berr1) and one locus on chromosome 11 (Berr2) that mediate control of resistance to ECM induced by P. berghei ANKA. Genetic mapping using the F2 progeny showed that a locus on chromosome 1 (Berr1) and a locus on chromosome 9 (Berr3) were contributing to control survival time after infection with lethal Plasmodium. Finally, we identified, a locus on chromosome 4 (Berr4) that appears to control time of death due to hyperparasitaemia. This thesis underlines the value of using WDIS to reveal genetic factors involved in the aetiology of disease phenotypes. The characterisation of the genetic factors represented by the malaria resistance loci identified here are expected to provide a better understanding of the malaria pathology.
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Campino, Susana Gomes. "Genetic analysis of murine malaria /". Umeå : Univ, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-124.
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Thiên. "Glucose metabolism in falciparum Malaria". [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2004. http://dare.uva.nl/document/74040.
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Crawley, Jane Margaret Stewart. "Seizures in childhood cerebral malaria". Thesis, University College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.396249.
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Dennison, Jeremy M. T. J. "Cytoadhesion, cytokines and cerebral malaria". Thesis, University of Liverpool, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.337149.
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Ismail, Sabariah. "Drug conjugation pathways in malaria". Thesis, University of Liverpool, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.386782.
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Martino, Wenceslao Moreda. "Novel stains as malaria diagnostics". Thesis, University of Aberdeen, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.401409.
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Chapter One highlights the importance of the control of malaria and its significance to the health of the world population. The vital role of the diagnosis of malaria is discussed as are the advantages and disadvantages of the different diagnostic techniques. This Chapter also provides a brief introduction to the chemistry of synthetic dyes. Chapter Two reviews the mechanism of synthesis of cyanine dyes, as these are of particular importance in this research work. The characteristic properties of these dyes are discussed. Chapter Three deals with the spectroscopic properties of the dyes synthesised in this work. Chapter Four studies the use of theoretical calculations for the characterisation of the electronic and structural properties of the dyes as well as the relation of such properties to their biological activity. Chapter Five examines the effectiveness of the biological activity of the dyes as malaria diagnostics. The complex of dye molecule and DNA can be explained in terms of an intercalculation model. Chapter Six studies the redox behaviour of the dyes with complex metal hydrides, catalytic hydrogenation, and hydrogen peroxide. The electrochemical reduction/oxidation using cyclic voltammetry is described.
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Marijani, Theresia. "Modelling drug resistance in malaria". Thesis, Stellenbosch : University of Stellenbosch, 2009. http://hdl.handle.net/10019.1/4063.
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Mackinnon, Margaret J. "Evolutionary genetics of malaria parasites". Thesis, University of Edinburgh, 1998. http://hdl.handle.net/1842/15243.
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Two empirical studies on parasite virulence using the laboratory model of the rodent malaria parasite, Plasmodium chabaudi, in inbred mice, were conducted. In the first, the average virulence and transmissibility in eight parasite clones obtained from the wild were measured over four replicate experiments. Large amounts of genetic (between-clone) variation in virulence and transmissibility were observed. Virulence was strongly correlated, both phenotypically and genetically, to population growth rate (parasitaemia) and less strongly correlated to transmissibility. These results provide strong support for the basic tenet of most evolutionary models of parasite virulence, namely, that virulence is a by-product of the parasite's need to replicate fast in order to be transmitted. In the second study, between-host selection for high and low virulence was performed within two parasite clones. Over eleven generations, all the selection lines increased in virulence and transmissibility. Thus, despite artificial between-host selection, parasitic variation within clones coupled with inadvertent within-host selection, allowed the parasite to adapt to a novel host. Together, these studies show that virulence is strongly determined by parasite genetics. A large data set on disease severity from a 3-year longitudinal field study in Sri Lanka was analysed for the effects of host genetic variability, age, immune experience, parasite species (P. falciparum vs. P. vivax), bednet use, sex and other host or environmental factors. The results highlighted the importance of short-term acquired immunity in causing large between-host variation in virulence. This is consistent with the view that parasite variability is responsible for inefficient clinical immunity to malarial disease, although this could not be examined directly and alternative explanations are possible. Two theoretical models incorporating parasite population structure into population genetics were used to predict the probability and rate of evolution of multi-locus drug resistance. All of these studies suggest that parasite genetic variation plays a key role in the evolution of the malaria host-parasite association.
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Mayer, Christina. "Structural studies of malaria proteins". Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:29b4cdcb-8323-45d9-ae96-38826dd8aa56.
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Malaria is a disease of global importance, causing hundreds of thousand of deaths a year. The majority or deaths are caused by Plasmodium falciparum, a parasite transmitted by the mosquito Anopheles. Its pathogenicity largely results from an ability to transform infected erythrocytes by creating knob-like structures that result in endothelial adhesion. Two major components of these knob structures have been identified as P. falciparum erythrocyte membrane protein 1 (PfEMP1) and knob-associated histidine rich protein (KAHRP). The extracellular fragment of PfEMP1 is responsible for antigenic variability and cytoadherence while its intracellular domain (ATS) connects to the cytoskeleton via interactions with other plasmodium-encoded proteins. In addition, perforin-like proteins (PLPs) with a MACPF domain have been identified in the genome of Plasmodium. PLPs are highly conserved and are expressed in various life-cycle stages of the parasite. They are believed to form pores in membranes of the host cell but their structure is yet unknown. The aim of the work in this thesis was to obtain new information about the structure and role of malaria proteins, thus giving a better understanding of the disease and its possible treatment. Studies of numerous designed constructs of the ATS family were carried out using biophysical methods including high resolution NMR and CD. These revealed that ATS domains are mainly unstructured with a relatively small folded core, consisting of a bundle of α-helices. Surprisingly, no evidence could be found for ATS binding to KAHRP in solution conditions although previous pull-down data had indicated an interaction. Bioinformatics analysis and yeast-two-hybrid data suggested, however, that there is a conserved protein interaction epitope on the central flexible part of ATS. It was shown, using fluorescence anisotropy measurements, that this part of ATS associates with a parasite protein containing a PHIST (Plasmodium helical interspersed sub-telomeric) domain. Expression constructs of the PLP protein family were designed and manufactured, with the aim of enabling structural studies of this putative pore protein.
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Longley, Rhea Jessica. "Liver-stage vaccines for malaria". Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:b5c9821c-db32-4b66-a315-02541e62f566.
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The development of an efficacious P. falciparum malaria vaccine remains a top priority. Pre-erythrocytic vaccine efforts have traditionally focussed on two well- known antigens, CSP and TRAP, yet thousands of antigens are expressed throughout the liver-stage. The work described in this thesis aimed to assess the ability of other pre-erythrocytic antigens to induce an immune response and provide protective efficacy against transgenic parasites in a mouse model. Research undertaken in our laboratory has demonstrated the ability of prime-boost viral vectored sub-unit vaccination regimens to elicit high levels of antigen-specific T cells. Eight candidate antigens were therefore expressed individually in the viral vectors ChAd63 and MVA. Two antigens, PfLSA1 and PfLSAP2, were identified that confer greater protective efficacy in inbred mice than either CSP or TRAP. PfLSA1 was also able to induce almost complete sterile efficacy in outbred mice, suggesting this vaccine should be assessed in a clinical trial. Immune responses to the candidate antigens were also assessed in human volunteers following their first exposure to controlled malaria infection. The antigen TRAP was further characterised by epitope mapping in volunteers vaccinated with ChAd63-MVA ME-TRAP. However, no functional T cell assay exists to measure inhibition of P. falciparum liver-stage parasites. An improved murine in vitro T cell killing assay was developed, and preliminary experiments were conducted that demonstrate the potential and promise of a P. falciparum T cell killing assay. Such assays will not only allow mechanistic studies to be undertaken, but could also change the way we screen pre-clinical liver-stage vaccines.
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Thompson, Fiona Mary. "Malaria immunology and vaccine development". Thesis, University of Southampton, 2008. https://eprints.soton.ac.uk/67626/.
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This thesis describes work undertaken by the author at the University of Oxford. It begins by providing an introduction to malaria infection and pathophysiology, and a review of the latest attempts to produce an effective malaria vaccine. It goes on to describe the rationale behind the vaccines developed by the University of Oxford and others. A brief introduction to the process of planning and carrying out clinical trials of vaccines is then provided, and is followed by chapters describing two clinical trials, designed to test the safety, immunogenicity and then efficacy of candidate malaria vaccines. These trials were performed in Oxford, to examine two different vaccination approaches. The first intended to broaden the specificity of the vaccine induced immune response, by providing multiple antigens in one vaccine, aiming thereby to improve protection from malaria infection. The second regimen used a combination vaccine intending to induce both humoral and cellular immunity simultaneously, thereby providing enhanced efficacy against malaria infection. Neither approach was sufficient to provide protection from infection in the challenge studies described; however, some impact on the disease was detected in the second study. This is examined in detail. The laboratory work described studies background immune responses (both cellular and humoral) to vaccine antigens in a malaria exposed population, intended to support the inclusion of these antigens in the multi-antigen vaccine. The remaining chapters describe work in parasite life cycle modelling, undertaken to aid interpretation of results of these clinical trials, and finally an examination of the clinical course of malaria in the control volunteers who have taken part in the many challenge studies conducted in Oxford.
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Peery, Ashley Nicole. "Chromosomal Evolution of Malaria Vectors". Diss., Virginia Tech, 2016. http://hdl.handle.net/10919/71698.
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International malaria control initiatives such as the Roll Back Malaria Initiative (RBM) and the Medicines for Malaria Venture (MMV) mobilize resources and spur research aimed at vector control as well as the treatment and eventual eradication of the disease. These efforts have managed to reduce incidence of malaria by an estimated 37% worldwide since 2000. However, despite the promising success of control efforts such as these, the World Health Organization reports a staggering 438,000 deaths from malaria in 2015. The continuing high death toll of malaria as well as emerging insecticide and antimalarial drug resistance suggests that while encouraging, success in reducing malaria incidence may be tenuous. Current vector control strategies are often complicated by ecological and behavioral heterogeneity of vector mosquito populations. As an additional obstruction, mosquito genomes are highly plastic as evidenced by the wealth or chromosomal inversions that have occurred in this genus. Chromosomal inversions have been correlated with differences in adaptation to aridity, insecticide resistance, and differences in resting behavior. However, a good understanding of the molecular mechanisms for inversion generation is still lacking. One possible contributor to inversion formation in Anopheles mosquitoes includes repetitive DNA such as transposable elements (TEs), tandem repeats (TRs) and inverted repeats (IRs). This dissertation provides physical maps for two important malaria vectors, An. stephensi and An. albimanus (Ch.2 and Ch. 3) and then applies those maps to the identification of inversion breakpoints in malaria mosquitoes. Repeat content of each chromosomal arm and the molecular characterization of lineage specific breakpoints is also investigated (Ch. 2 and Ch.4). Our study reveals differences in patterns of chromosomal evolution of Anopheles mosquitoes vs. Drosophila. First, mosquito chromosomes tend to shuffle as intact elements via whole arm translocations and do not under fissions or fusions as seen in fruitflies. Second, the mosquito sex chromosome is changing at a much higher rate relative to the autosomes in malaria mosquitoes than in fruit flies. Third, our molecular characterization of inversion breakpoints indicates that TEs and TRs may participate in inversion genesis in an arm specific manner.Ph. D.
Malaria is a complex and devastating disease vectored by the bite of a female Anopheles mosquito. This disease claimed an estimated 438,000 lives in 2015. The mobilization of funding and resources as part of global malaria eradication initiatives have reduced the global incidence of malaria by 37% in the last 15 years. Deaths from malaria are also 60% lower vs. the year 2000. These promising gains are threatened by the ability of Anopheles mosquitoes to adapt in the face of malaria control efforts. Anopheles mosquito chromosomes are known to be highly plastic, as evidenced by numerous chromosomal inversions. Recent years have seen increases in insecticide resistance, and behavioral change in mosquito populations that allow them to avoid insecticides and remain prolific vectors of disease. This ability of mosquito vectors to adapt threatens to unravel recent progress towards a malaria free world. The projects presented in this dissertation explore mechanisms of chromosomal evolution, specifically the potential role of repetitive DNA in the generation of chromosomal inversions. The exploration of chromosomal inversions was facilitated by the creation of physical maps for Anopheles species. Prominent malaria vectors An. stephensi andAn. albimanus were physically mapped in Chapter 2 and Chapter 3 respectively. In chapter 1 and chapter 3 physical maps are utilized for the identification of chromosomal inversion breakpoints using 2 species (Ch. 2) and many species (Ch. 4). Repeat content was quantified along each chromosomal arm (Ch 2,4) and in inversion breakpoint regions (Ch 3). This dissertation presents physical maps for two important malaria species that have been applied to the study of chromosomal evolution and will also serve as community tools for further study of malaria mosquitoes. Our work on chromosomal evolution has revealed the Anopheles chromosomes tend to undergo translocations as intact elements and do not under fissions and fusions as seen in fruitflies. We also find that the malaria mosquito sex chromosome changes much more rapidly relative to the autosomes than in fruitflies. Additionally, repetitive DNA including transposable elements (TEs) and tandem repeats (TRs) may be encouraging chromosomal inversions but with differing roles on different chromosomal arms.
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Koka, Sai Sudha. "Suicidal erythrocyte death in malaria". [S.l. : s.n.], 2008.
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Rowlands, Jessica S. "Agent based modelling of Malaria". Thesis, Bangor University, 2013. https://research.bangor.ac.uk/portal/en/theses/agent-based-modelling-of-malaria(00252961-121d-463b-92e4-e08253519286).html.
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Malaria is a disease that affects millions of people each year, with 90% of deaths occurring in Africa alone. The subject of this dissertation is the agent based modelling of malaria in populations that are suffering mass migration , living in unsanitary conditions or undergoing other effects of impoverished circumstances. The research is important due to the large numbers of people affected by malaria globally, with about 3.3 billion at risk. A large proportion of those exposed to the risk live in Sub-Saharan African countries. Agent based modelling is a type of computational modelling which is commonly used for the simulation of interacting, autonomous agents. Using agent based modelling it is possible to assess the effects of interactions between individual agents and populations of agents on the whole system. There is a limited availability of associated documentation and quantifiable research data in many areas of malaria spread research. To address the problem, three models have been built that investigate different aspects of malaria transmission. The models are developed with flexibility and adaptability as important factors in their use, so that they can provide verifiable results with potentially limited availability of data. The three models produced are as follows. • Malaria in Displaced Populations. • Malaria in Peri-Urban Settlements. • Malaria and Human Immunodeficiency Virus (HIV) Dual Infection. The first model simulates malaria spread amongst a migratory population of agents. The second model simulates malaria spread amongst a settled population of agents living in peri-urban conditions with an associated mapping.
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Bhardwaj, Inayat. "Modelling antigenic variation in malaria". Electronic Thesis or Diss., Université de Montpellier (2022-....), 2024. http://www.theses.fr/2024UMONS003.
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La gestion et l'élimination du paludisme à Plasmodium falciparum se heurte à de nombreux défis dans les zones endémiques de forte transmission. Parmi eux, la présence de nombreuses infections asymptomatiques chroniques qui servent de réservoir à des infections symptomatiques plus graves. Ce fardeau est désormais principalement concentré en Afrique subsaharienne où d’autres maladies parasitaires sont également prévalentes, parfois d’origine zoonotiques. Le réservoir caché d'infections asymptomatiques chroniques est ici la conséquence non seulement d’un taux de transmission élevé, mais aussi d’un profil immunologique particulier chez les hôtes humains. Ceux-ci développent en effet une immunité spécifique non stérile contre un ensemble d’antigènes exprimés par le parasite, qui lui changera son répertoire d'antigène exprimé au cours du temps. Ce phénomène est connu sous le nom de variation antigénique.Dans le cas de Plasmodium falciparum cette variation antigénique est facilitée par plusieurs familles de gènes à multiples copies. La famille de gènes la plus étudiée est la famille des gènes var. Elle encode la protéine 1 de la membrane érythrocytaire de Plasmodium falciparum (PfEMP1), qui est la principale cible du système immunitaire de l'hôte lors d’une infection sanguine. L'immunité contre PfEMP1 a notamment été liée à la protection contre les maladies graves et à l'élimination du parasite. Chaque génome de parasite contient environ 45 à 60 copies de gènes var, réparties sur presque tous les chromosomes du parasite. Au cours d’une infection, le parasite a la capacité de changer la copie du gène var qui sera exprimé à la surface de l’érythrocyte infecté. Ce phénomène exerce une pression sur le système immunitaire de l’hôte qui doit en permanence produire de nouveaux antigènes pour de nouveaux gènes var. Cette course entre le système immunitaire de l’hôte et le parasite peut produire des infections chroniques asymptomatiques lorsque le parasite parvient a produire et exposer des antigènes plus rapidement que la capacité du système immunitaire a reconnaitre de nouveaux variants.Dans cette thèse, j’exploite des approches théoriques pour mieux comprendre les taux de changement des variants de gènes var et leurs relations à différents environnements. Premièrement j’analyse les taux de changement de gènes var via des modèles déterministes de chaines de Markov. Ces analyses sont conduites à la fois sur des échantillons ex vivo et in vitro. En supplément, des méthodes d'apprentissage automatique sont également développées afin de quantifier l'impact des réponses immunitaires spécifiques sur l'expression de var. Ces méthodes permettent également de prédire les résultats d'infection chez les individus en fonction de leur immunité anti-PfEMP1. En deuxième temps, la variation antigénique du paludisme est étudiée mathématiquement et numériquement. Je développe un modèle se basant sur la diversité antigénique afin d’explorer la persistance du parasite sous les effets de l'immunité de l'hôte. La dynamique hôte-pathogène est modélisée à l'aide d'équations différentielles ordinaires incorporant à la fois l'immunité spécifique et croisée contre la population de parasitesHigh transmission endemic areas pose a substantial challenge to falciparum malaria management and elimination due to the vast reservoir of chronic asymptomatic infections that sustain transmission. P. falciparum's worldwide burden is now concentrated only in fifteen high transmission endemic countries, primarily in Sub-Saharan Africa. Other vector-borne illnesses have a similar reservoir in endemic areas, resulting in a high prevalence of infection in domestic and animal hosts but minimal clinical symptoms.Hidden reservoirs of chronic asymptomatic infections are attributed not only to the high transmission rates in endemic regions, but also from non sterile specific immunity to pathogens that exhibit antigenic variation, which is facilitated by several multicopy gene families.In the case of falciparum malaria infections, the most famous multigene family responsible for mediating antigenic variation, is known as var and it encodes for the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) , which is the major target of host immunity during the blood stage infection. In addition to having a large copy number to enhance diversity, the var family also exhibits transcriptional switching across different variants across time. Immunity against PfEMP1 has been linked to protection against severe disease and parasite clearance. Each parasite genome contains about 45-60 copies of var genes, and they are distributed across the parasite chromosomes. This diversity in the number of antigenic variants mounts to huge pressure on the hosts' immune system and and enables the parasite to establish long infections as hosts might not have encountered most of the variants from the repertoire during previous infections.This existing diversity in the number of variants in supported by transcriptional switching, in way that parasites might switch the expression of their surface antigens before the immune system generates specific responses against a particular variant. Furthermore, there is experimental evidence of generation of new var variants by ectopic recombination over time, suggesting the generation of about sixty recombinants within a single year.In this thesis, we exploit theoretical approaches to gain insights into the switching rates of var variants in different environments: within the host and subsequently invitro after infection using deterministic estimates of Markov Chain Models. We also probe into quantifying the impact on existing specific responses on var gene expression in vivo and predicting infection outcomes in individuals based on anti-PfEMP1 immunity by implementing machine learning methods.Later, antigenic variation in malaria is then mathematically and numerically investigated in more detail using a model accounting for antigenic diversity to explore parasite persistence under the effects of host immunity. The host-pathogen dynamics are modelled using an ordinary differential equations-based model incorporating both specific and cross-reactive immunity against the parasite population
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Nordblom, Eva. "Experiences of malaria and attitudes to malaria prevention among nurses in Tanzania - An interview study". Thesis, Uppsala University, Department of Public Health and Caring Sciences, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-126034.
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The aim of this qualitative study was to explore experiences of malaria and attitudes to malaria prevention among nurses from Tanzania. Eleven nurses from three hospitals in northern Tanzania were interviewed. The analysis resulted in following categories: The malaria situation was so severe at that time, Being both nurse and parent, Hindrances in the battle, Sharing knowledge and There is a change. Ten out of eleven nurses had had malaria and all of them had been treated with anti-malarial drugs and many of them still had malaria regularly. They remembered times when the malaria situation was worse and the disease killed many more people. Having children resulted in constant worry. Being a nurse had advantages because they lived close to the hospitals so they could initiate early treatment and because they could afford to take preventive measures. Hindrances in the battle against malaria were other people’s lack of knowledge, poverty and difficulty to change lifestyle and environmental conditions. They were proud to be nurses and knowledge was their strength. There were geographical differences in how much hope they had for the future. The nurses in Zanzibar were the most optimistic. The nurses supported the governmental actions against malaria.
Syftet med denna kvalitativa studie var att undersöka vilka upplevelser sjuksköterskor från Tanzania hade av malaria och deras attityder till malariaförebyggande åtgärder. Elva sjuksköterskor från tre sjukhus i norra Tanzania intervjuades. Analysen resulterade i följande kategorier: Malariasituationen var så allvarlig på den tiden, Att vara sjuksköterska och förälder, Hinder i kampen, Att dela kunskap och Det har blivit en förändring. Tio av de elva sjuksköterskorna hade haft malaria och alla hade fått malariabehandling och flera av dem hade fortfarande malaria regelbundet. De hade minnen från när malariasituationen var värre och många fler människor dog av sjukdomen. Att vara förälder innebar konstant oro. Att vara sjuksköterska hade fördelar eftersom de bodde nära sjukhusen och därför kunde inleda snabb behandling och för att de hade råd att genomföra förebyggande åtgärder. Hinder i kampen mot malaria var andra människors okunskap, fattigdom och svårigheter att förändra livsstil. De var stolta över att vara sjuksköterskor och kunskap var deras styrka. Det fanns geografiska skillnader när det gällde deras framtidstro. Sjuksköterskorna på Zanzibar var de mest hoppfulla. Sjuksköterskorna stödde de statliga insatserna mot malaria.
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Saddler, Adam. "Evaluating insecticide-resistance in the malaria vector Anopheles gambiae and its implications for malaria transmission". Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/24434.
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Insecticide resistance, in the mosquito vector, threatens the efficacy of current methods to control malaria. Yet evidence of control failure due to insecticide resistance is sparse, despite over 50 years since resistance was identified in the mosquito. In this thesis, laboratory experiments with mosquitoes, as well as mathematical modelling, are used to improve our understanding of how insecticide resistance might impact malaria transmission. Firstly, demographic and environmental effects on the phenotypic expression of resistance are investigated. Decreasing expression of resistance with age and malaria infection, suggest resistance may not be as large a problem as once believed. Further factors that affect the phenotypic expression of resistance, such as infection by the microsporidian Vavria culicis and quantity of larval food, suggest that the phenotypic expression of resistance may even be manipulated to reduce its impact on disease transmission. Secondly, costs of resistance are explored as they may reduce the ability of a mosquito to transmit malaria. It is demonstrated that, under environmental stress from parasites, costs to longevity can be increased. Mosquito longevity is a key parameter in malaria transmission so any reduction in longevity, due to costs of resistance, will reduce the ability of the mosquito to transmit malaria. Finally, the thesis examines if the behavioural avoidance of insecticides can be changed through environmental manipulation. In summary, the phenotypic expression of resistance and the costs of resistance are two factors that will determine the threat insecticide-resistance poses to malaria control. It is demonstrated, in the laboratory, that these two factors can vary due to environmental and demographic factors, but to fully understand the threat of resistance these ideas have to be investigated in the field.
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Ashton, R. A. "Measuring low and unstable malaria transmission in Ethiopia : strategies for malaria surveillance and epidemic detection". Thesis, London School of Hygiene and Tropical Medicine (University of London), 2014. http://researchonline.lshtm.ac.uk/2025451/.
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In Ethiopia, malaria transmission is seasonal and epidemic-prone, with both Plasmodium falciparum and Plasmodium vivax being endemic. Such spatial and temporal clustering of malaria only serves to underscore the importance of regularly collecting up-to-date malaria surveillance data to inform decision-making in malaria control and improve responsiveness to potential epidemics. This thesis compares indicators and strategies used for the monitoring and surveillance of malaria in Ethiopia. Cross-sectional school-based surveys were conducted throughout Oromia Regional State, generating data on malaria prevalence by microscopy, risk factors for infection and intervention use. Filter paper blood samples collected during these school surveys were subsequently tested to determine exposure to malaria based on presence of anti-Plasmodium antibodies, and Bayesian geostatistical modelling was employed to predict P. falciparum and P. vivax seroprevalence across Oromia. In southern Ethiopia, a schoolbased syndromic surveillance system was piloted, exploring the utility of school absenteeism as a complementary indicator of malaria epidemics at community level. Finally, findings from the school surveys, measured and modelled seroprevalence, as well as data from the national Malaria Indicator Survey in 2011 were compared with spatially congruent estimates of malaria incidence collected from health facilities and to modelled parasite rate from the Malaria Atlas Project. Findings from this thesis demonstrate the limitations of microscopy as a primary indicator of malaria infection in cross-sectional surveys in areas of very low transmission. The work highlights the potential of serological indicators of Plasmodium exposure for inclusion in periodic large-scale malaria monitoring activities and develops a first ever geostatistical risk map based on serological indictors. This was supported by comparative analysis of a range of survey and modelling indicators against estimates of incidence from passive surveillance, indicating the inadequacy of cross-sectional surveys estimating population parasitaemia to reflect the spatial extent and temporal variability of transmission. The piloted syndromic surveillance system indicates that monitoring school absenteeism has potential as a complementary epidemic alert system, operating alongside the existing system at health posts, but is limited by low school enrolment in the piloted setting. The findings of this thesis indicate that existing periodic monitoring strategies and tools are insufficient to fully describe the extent of malaria in settings where Plasmodium transmission is spatially and temporally variable. Modifications to monitoring strategies are recommended, including incorporation of serological indicators and spatial modelling.
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Saweka, Delfina Ângela. "Factors influencing malaria care seeking behaviour in two Ghanaian communities : formal versus informal malaria care". Master's thesis, University of Cape Town, 2008. http://hdl.handle.net/11427/9456.
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Includes bibliographical references (leaves 101-110).The study primary objective was to investigate the determinants and extent of household’s reliance on the informal malaria care sector in two Ghanaians communities. The secondary objective wass to inform policy-makers and planners, especially from the public healthcare sector, on supply side issues that are likely to influence the current malaria care seeking patterns.
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Vittor, Amy Yomiko. "Deforestation and malaria associations between vegetation, vector ecology and malaria epidemiology in the Peruvian Amazon /". Available to US Hopkins community, 2003. http://wwwlib.umi.com/dissertations/dlnow/3080786.
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Briët, Olivier J. T. "Towards malaria prediction in Sri Lanka : modelling spatial and temporal variability of malaria case counts /". Basel : [s.n.], 2008. http://edoc.unibas.ch/diss/DissB_8750.
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