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Ashby, Nichola Jane. "Student nurses, stigma and infectious diseases : a mixed methods study." Thesis, University of Birmingham, 2016. http://etheses.bham.ac.uk//id/eprint/6536/.
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Individuals or groups will form impressions of another based upon a series of traits, which may be relied upon when forming behaviour pattern towards others (Asch, 1946; Crocker and Major, 1989; Pinel, 1999; Albon, 2002; Corrigan and Wassel, 2008). These traits will depict the reception individuals receive within healthcare and may depend upon learnt and inherited ‘perceived’ ideals affecting the working and personal relationships experienced by positively diagnosed healthcare workers, predisposing stigma responses to others (Asch, 1946). A mixed method study investigating the potential existence of stigmatising values from student nurses towards positively diagnosed healthcare workers with Pulmonary Tuberculosis (PTB), Human Immunodeficiency Virus (HIV), Methicillin-resistant Staphylococcus Aureus (MRSA), Hepatitis C and Diabetes type 2, was undertaken. Analysis provided exploration of the stigmatising attitudes and values of 482 student nurses undertaking an education programme. Interpretation of the findings explored the participants views at course commencement, midpoint and completion considering variables of education (theoretical and clinical), personal and professional influences. Findings indicated that stigmatising values and attitudes return to those identified precourse and underpin the need for implementation of a change to nurse education within this area. The development of a longitudinal education model for healthcare workers considering disease processes and influencing factors psychologically, socially and physically, will provide opportunities to reduce the existence of stigmatisation for positively diagnosed healthcare workers.
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Corrah, Tumena Wandifa. "A study of the phenotype and function of HLA-C restricted CD8 T cells in HIV-1 infection." Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:456f2b57-55de-42ed-83ac-bcbd1d869bd0.
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A recent study showed that a polymorphism ~35kb upstream of the HLA-C gene (-35 SNP) correlates with host control of HIV-1 in Caucasians, with the minor allele (C) associating with significantly lower set point viral loads than the major allele (T). A link between viral load and HLA-C is suggested by linkage of the two SNP alleles with different HLA-C alleles and by the fact that HLA-C, in contrast to HLA-A and -B, is not down-regulated by HIV-1 Nef protein. In addition, the -35C variant has been shown to associate with higher HLA-C messenger RNA expression in EBV-transformed B cell lines. We initially propose that increased surface expression of HLA-C in subjects with the protective SNP leads to increased breadth and magnitude of HLA-C restricted T cell responses, explaining the decrease in viral load in these subjects. This study initially investigates whether the -35 SNP correlates with the surface level of HLA-C using the monoclonal antibodies DT9, which recognises both HLA-C and HLA-E, and 3D12, which is specific for HLA-E. The lymphocytes from -35 CC subjects expressed a significantly higher level of surface HLA-C when compared to those from -35 TT subjects, but this difference in HLA-C expression can be attributed primarily to the very low expression of a single allelic product, HLA-Cw*07. Increased surface HLA-C should translate to functional differences between CC and TT subjects. This study confirmed that HLA-C restricted CD8 T cell responses against HIV-1 do exist, even for HLA-Cw*07, but represent a minority of total T cell responses. They were detected in all -35 SNP genotypes but there were no functional differences, making it unlikely that the protective effect of this SNP on viral load set point could be accounted for solely by HLA-C restricted T cell responses. Finally, a viral suppression assay was used to investigate the capacity of CD8 T cells to suppress HIV-1 replication in Caucasian and African subjects. We provide evidence that the -35 SNP effect on viral load is indeed T cell mediated. However, we suggest that the protective effect of the -35 SNP on viral load set point manifests as a result of linkage disequilibrium of this polymorphism with both favourable and unfavourable HLA-B and HLA-C alleles.
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Xia, Shang. "A computational study on vaccination decision making for infectious disease control." HKBU Institutional Repository, 2013. http://repository.hkbu.edu.hk/etd_ra/1527.
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Sahle, Mesfin. "An epidemiological study on the genetic relationships of foot-and-mouth disease viruses in East Africa." Thesis, University of Pretoria, 2004. http://hdl.handle.net/2263/27222.
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Within East African countries many of the known infectious diseases of animals occur commonly and are poorly controlled. Foot-and-mouth disease (FMD) is one of the contagious viral diseases that has great impact on economic development both in terms of direct and indirect losses. The epidemiology of the disease is complex due to the presence of six of the seven serotypes and the presence of large numbers of both wild and domestic susceptible animals in the region. Decision-making to determine the importance of FMD control relative to the economic consequences and what FMD control strategies should be applied based on the epidemiological information is required. In this regard the first step is to investigate the genetic relationships/variability of East African isolates and their phylogeographic distribution. These can provide base-line information for designing control strategies by vaccination as well as the determination of the sources of infection. Sufficient genetic information on the FMO serotypes O, SAT-1 and SAT-2 are lacking and therefore the number of viral Iineages and genotypes or topotypes from East African countries could not be determined. Published studies on the relative occurrence and genotype distribution of FMO are largely confined to the southern and western part of the continent. In this study, the genetic profile of the 3 most prevalent serotypes (0, SAT-2 and SAT-1) recovered from outbreaks in East Africa between 1957 and 2003 was addressed. Phylogenetic analysis of partial and complete sequences of the 10 gene revealed the presence of distinct lineages and genotypes for East Africa as well as historical relationships of some of the genotypes with isolates from other regions. A great variation in the occurrence and distribution of these serotypes were found. All the African and the Middle East/South East Asian isolates of serotype O included in this study clustered into one lineage having 8 distinct topotypes. These results indicated that between countries as well as inter-regional (east and west Africa) spread of viruses occurred in the past. Inter-regional spread of the virus between eastern Africa and western Africa was also confirmed for SAT-1 viruses. The fact that phylogenetic links are found with both serotypes implies that the spread of viruses was possibly associated with unrestricted animal movement due to nomadic movement in Africa. The phylogenetic relationships of SAT-1 viruses are more diversified in Africa. Eight lineages and 11 genotypes were identified when the optimal nucleotide sequence differences of ≥ 23% for lineages and ≥ 6% for genotypes were used as a cut-off values. It was observed that viruses from Uganda are evolving independently from viruses elsewhere on the continent and clustered into 3 discrete lineages. In contrast, viruses from countries neighbouring Uganda, Kenya and Tanzania, clustered into one lineage. Uganda also harboured 3 topotypes of SAT-2 virus isolates, one is distinct for Uganda and the other are shared with Kenya and Zaire (DRC). This study highlighted distinct lineages found in Uganda and needs further investigation. Within SAT-2, 67 isolates from 22 African countries and Saudi Arabia clustered into 5 lineages which consisted of 15 genotypes. Clustering of viruses into distinct genotypes (topotypes) according to year of isolation and geographical origin was observed showing countries with common boundaries shared common epizootics in the past. These results also showed a link between eastern and southern African countries. Attempts were also made to investigate the incidence of FMD in Ethiopia using sera collected from cattle, small ruminants and wildlife. The results obtained from the liquid phase blocking ELISA and the 3ABC ELISA indicated the presence of SAT-1 and SAT-2 in buffalo populations in the southern part of Ethiopia while results from small ruminants and other wildlife were not indicative of any significant role in the epidemiology of FMD. Serological results also indicated that SAT-1 is present in cattle, although this serotype has not been previously identified. The cumulative molecular epidemiological results from this and previous studies indicated that genetic variability of FMD viruses can be independently maintained within country/countries or regions as well as inter-regions of Africa. The serological results from buffaloes in East Africa are also suggestive of a possible reservoir of the SAT types FMD in the region which has a great impact on the control of the disease. Furthermore, the numerous lineages and genotypes of FMD virus isolates in Africa having distinct or overlapping distributions as well as the genetic linkage between regions will complicate the epidemiology of the disease. Therefore, it is strategically important to consider a regional approach and the use of a vaccine which contains a cocktails of antigens of FMD virus strains.Thesis (PhD)--University of Pretoria, 2004.
Veterinary Tropical Diseases
unrestricted
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Ssebuliba, Doreen. "Mathematical modelling of the effectiveness of two training interventions on infectious diseases in Uganda." Thesis, Stellenbosch : Stellenbosch University, 2013. http://hdl.handle.net/10019.1/85637.
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Thesis (PhD)--Stellenbosch University, 2013.ENGLISH ABSTRACT: Nurses, midwives and clinical officers referred to as Mid-level Practioners (MLPs) play an important role in the health care system especially in rural Africa. With particular reference to rural Uganda, due to the large shortage of doctors, MLPs handle most of the duties usually meant for doctors, at health centre IV(s). From 2009 to 2011, two training interventions of MLPs were performed at 36 sites in Uganda by the Integrated Infectious Disease Capacity Building Evaluation (IDCAP). The two interventions were: Integrated Management of Infectious Diseases (IMID) and On-site Support Services (OSS) which aimed at improving MLPs’ case management for four diseases: HIV, TB, pneumonia and malaria. In this thesis, we have developed three mathematical models to investigate the effect of the two training interventions on these infectious diseases. All the models are formulated using systems of ordinary differential equations which are structured in three age groups: [0, 5), [5, 14) and [14, 50). We explored the effect of the two training interventions in the context of malaria-pneumonia, HIV-TB co-infections and the four diseases together. Our analysis shows that: i) For malaria-pneumonia, both IMID and the combination of IMID and OSS reduce the number of cases, deaths and prevalence of disease but have no effect on the incident episodes of disease. ii) Results from the HIVTB model propose that HIV and TB testing are important steps in quality of health care and are capable of offsetting slightly negative effects of reduction in ART enrollment and provision of treatment. iii) The HIV-TB-malaria-pneumonia (HTMP) model concurs with the results of the first two models and its results demonstrate that high coverage levels of the training interventions increase the positive effects that the interventions have on mortality and morbidity. Overall, our results suggest that training of MLPs is much more effective for the short term duration diseases such as malaria and pneumonia, where the baseline values for most of the performance indicators are ≥ 0.6, but not so much for long term duration diseases such as HIV and TB, whose baseline values for most of the performance indicators are < 0.6. The results further highlight that problems such as case detection and drug stock-outs need to be addressed in order for training to have substantial impact, especially in instances where the performance indicator proportions are low.
AFRIKAANSE OPSOMMING: Verpleegsters, vroedvroue en kliniese beamptes wat gesamentlik na verwys word as midvlak praktisyns (MVPs) , speel n belangrike rol in die gesondheidsorg sisteem, veral in landelike dele van Afrika. Met spesifieke verwysing na gesondheid sentrums in Uganda, waar daar te min dokters is, hanteer MVPs die meeste van die pligte wat eintlik deur dokters verrig moet word. Vanaf 2009 tot 2011 is twee opleidingsprogramme vir MVPs by 36 fasiliteite in Uganda deur die Integrated Infectious Disease Capacity Building Evaluation (IDCAP) organisasie aangebied. Die twee programme staan bekend as: Integrated Management of Infectious Diseases (IMID) and On-site Support Services (OSS). Beide die programme stel ten doel om die MVPs se pasint bestuur vir die siektes MIV, tuberkulose (TB), longontsteking en malaria te verbeter. Drie wiskundige modelle word in hierdie tesis ontwikkel om die effek van die opleidingsprogramme op hierdie oordraagbare siektes te ondersoek. Al die modelle word geformuleer deur gebruik te maak van stelsels van gewone differensiaal vergelykings wat gestruktureer is in drie ouderdomsgroepe: [0, 5), [5, 14) en [14, 50). Die effek van die opleidings programme word in die konteks van longontstekingmalaria mede-infeksie, MIV- TB mede-infeksie en al vier siektes gelyk, ondersoek. Die analise wys dat: i) Vir longontsteking-malaria mede-infeksie het beide IMID en die kombinasie van IMID en OSS die aantal siekte-gevalle, sterftes en die prevalensie van die siektes verminder, maar het geen effek op die insidensie van siekte-gevalle nie. ii) Resultate van die MIV-TB model dui aan dat MIV en TB toetsing n belangrike aspek van die gehalte van sorg is en dat dit die effense negatiewe effek van die afname in ART inskrywing en voorsiening van behandeling, teenstaan. iii) Die MIV-TB-longontsteking-malaria model (HTMP) stem ooreen met die resultate van die bogenoemde twee modelle en demonstreer dat ho dekking van die opleidingsprogramme die positiewe effek van die programme op mortaliteit en morbiditeit verhoog. In geheel stel die resultate van hierdie studie voor dat die opleiding van MVPs baie meer effektief is vir die korttermyn siektes soos malaria en longontsteking waarvoor die meeste van die beginwaardes van die prestasie-aanwysers ≥ 0.6 is, maar nie soveel vir lang-termyn siektes soos MIV en TB waarvoor die meeste van die beginwaarde van die prestasie-aanwysers < 0.6 is. Die resultate dui verder aan dat opleiding nie voldoende is wanneer die prestasie-aanwysers < 0.6 is nie en dat probleme soos die opsporing van siekte-gevalle en n gebrek aan medisyne by die klinieke aangespreek moet word vir opleiding om aansienlike impak te hê.
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Duijts, Liesbeth. "Infectious diseases and immune system in infants risk factors and consequences : the generation R study /." [S.l.] : Rotterdam : [The Author] ; Erasmus University [Host], 2008. http://hdl.handle.net/1765/13276.
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Kwong, Kim-hung, and 鄺劍雄. "Spatio-temporal transmission modelling of an infectious disease: a case study of the 2003 SARS outbreak in Hong Kong." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B45693900.
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Hatch, Steven. "Maternally Derived Anti-Dengue Antibodies and Risk of DHF in Infants: A Case-Control Study." eScholarship@UMMS, 2010. https://escholarship.umassmed.edu/gsbs_diss/476.
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This study proposes to directly test the hypothesis that antibody-dependent enhancement (ADE) is the critical factor in the development of dengue hemorrhagic fever (DHF) in infants. DHF occurs in two distinct clinical settings: a) in children and adults with secondary DENV infection, and b) in infants with primary DENV infection born to mothers with prior DENV infection. The ADE hypothesis proposes that pre-existing serotype-cross-reactive non-neutralizing anti-DENV antibodies bind the heterotypic DENV during secondary infection and enhance its uptake into immune cells, leading to increased viral load and DHF. This model suggests that DHF in DENV-infected infants is caused by the enhancing effect of waning maternal anti-DENV antibodies, thus causing a “physiologic secondary infection” during an infant’s primary infection and thereby increasing the infant’s risk for DHF.
The effect of maternal immunity on DHF in infants has been studied exclusively in Southeast Asia. However, the maternal DENV seroprevalence approaches 100% in this part of the world. As a consequence, the ADE model of infant DHF cannot truly be tested in Southeast Asia, because all infants possess anti-DENV antibody at birth. In the Western Hemisphere, by contrast, women may have experienced either a single DENV infection, more than one DENV infection, or no DENV infection at all. The ability to include DENV-seronegative mothers as controls allows for the ADE hypothesis to be directly tested in a clinical study. To our knowledge, no such study has been previously conducted.
This thesis presents a case-control study designed to evaluate the influence of positive maternal dengue seroprevalence on the risk of DHF in infants. As the MSCI program provides instruction in study design, this thesis does not present findings. The clinical trial described herein began in May 2010 and enrollment is expected to continue through May 2012 (see Table 4).
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Gelabert, Xirinachs Pere 1991. "Paleogenomics applied to the study of ancient infectious diseases : tracing the signals of the eradicated European malaria." Doctoral thesis, Universitat Pompeu Fabra, 2018. http://hdl.handle.net/10803/665491.
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La malària és una malaltia infecciosa causada per diverses espècies de protozous del gènere Plasmodium, capaces d’infectar eritròcits humans. La malària és probablement la patologia infecciosa que ha causat més morts al llarg de tota la història de l’espècie humana. Encara avui dia és un problema de salut pública global, agreujat per la creixent aparició de soques de Plasmodium resistents als tractaments farmacològics. L'origen de la majoria d’espècies de Plasmodium és africà. Espècies com P. vivax s’han expandit arreu per mitjà de moviments migratoris complexes, els quals romanen encara parcialment desconeguts degut a la manca de seqüències de Plasmodium europeus. Aquesta expansió probablement originada en el Neolític, ha seguit sempre moviments migratoris humans, deixant variants de resistència al Plasmodium en les poblacions humanes que hi han estat exposades. En aquest treball es presenta la seqüència de les soques europees de P. vivax i P. falciparum que han estat usades per traçar els moviments migratoris dels patògens així com per datar l’expansió del P. vivax. No gens menys el genotipat de variants de resistència en individus europeus antics mostra un impacte genètic limitat de la malària, suggerint amb una introducció recent del Plasmodium al continent.Malaria is an infectious disease caused by several protozoa species of the Plasmodium genus, capable to infect human erythrocytes. Malaria is probably the infectious pathology responsible of the larger amount of deaths among all human history. Still nowadays it is a major public health concern, which is aggravated due to the emergence and spread of Plasmodium strains resistant to current drug treatments. Most of Plasmodium species have an African origin. Parasites like P. vivax have colonized the world following complex migrating movements, partially unclear due to the lack of European Plasmodium genomes. The Plasmodium expansion, probably associated with the Neolithic onset, has been a strong selective pressure for the exposed human populations. Here we present the genomes of eradicated European strains of P. vivax and P. falciparum, which have been used to trace the migrating movements of these pathogens, as well as for dating the P. vivax dispersal. A genetic screen of malaria resistance variants in ancient European populations has revealed very low rates of genetic adaptive variants, which might be explained by a very recent introduction of malaria in Europe.
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Tsai, Chen Hsuan Sherry. "The study of candidate sialometabolism genes and sialometabolism gene regulation in Haemophilus influenzae." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:656c6197-b37e-4fba-8544-fbcdd74b549d.
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Sialic acid (SA) is a known major virulence factor of Haemophilus influenza (Hi). This study aims to analyse the functions of some candidate sialometabolism genes, and to further our current understanding on the Hi sialometabolism gene regulation. Two candidate sialometabolism genes (HI0227 and HI0148) and their adjacent ORFs (HI0228, HI0148.1 and HI0149) were studied. HI0148.1 and HI0149 are transcribed as a single gene in screened NTHi strains, and we refer to the combined ORF as NTHI0236 (the designation in strain 86-028NP). Across Hi strains screened, the sequences of HI0227, HI0148 and NTHI0236 are conserved. However, the sequence of HI0228 is heterogeneous. Mutants that lack the functions of HI0227, HI0228, HI0148 and NTHI0236 were compared to their respective wild type parent strains for ability to grow on SA (in aerobic and microaerophilic conditions), their ability to sialylate LPS and their ability to resist complement mediated killing. The mutants did not exhibit major differences in the tested aspects of sialometabolism compared to their respective wild type strains. Changes observed in some of the mutants in serum bactericidal assays and LPS profiles were due to the effect of phase variable genes. The sialometabolism functions of HI0227, HI0148, and NTHI0236 remain obscure, and we postulate that HI0228 is a pseudogene. Investigation of Hi sialometabolism gene regulation was conducted using mutants that lack different steps of the Neu5Ac catabolism pathway and the Neu5Ac activation pathway. The expression of nanE and siaP, respectively representing the Neu5Ac catabolism and transport operons, were assessed using RT-PCR and qPCR. We investigated a temporal/concentration effect of Neu5Ac on the expression of sialometabolism operons, which highlights the importance of studying the Hi sialometabolism gene regulation as a dynamic process. We further demonstrated that GlcN-6P, a Neu5Ac intermediate from the catabolism pathway, is likely the SIS sugar that interacts with SiaR, the repressor protein of the Hi sialometabolism operons. We postulate that upon binding of GlcN-6P to SiaR, the SiaR-mediated repression on the Hi sialometabolism operons is relieved, resulting in the induction of the expression of Neu5Ac catabolism and transport genes.
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Adeyemi, Emmanuel Olusola. "Predictors of Malaria-Anemia Comorbidity among Under Five Children in Nigeria: A Cross Sectional Study." Digital Commons @ East Tennessee State University, 2021. https://dc.etsu.edu/asrf/2021/presentations/71.
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Anemia is known to worsen treatment outcomes in malaria, but there are not many studies to identify the predictors of anemia in Nigerian children with malaria. The objective of this study is to identify some of those predictors. Socio-demographic variables are predictors of anemia among under five children in Nigeria was the hypothesis tested. This is a cross-sectional study that used the 2018 demographic health survey (DHS) data from Nigeria to explore some of the factors that determine the presence of malaria-anemia co-morbidity in Nigerian children less than five years (N= 265). The outcome variable was anemia status in children under five with malaria and the explored predictors include age, sex, residential type, region of residence, mother’s education status and family’s wealth index. The study analyzed unweighted and weighted frequencies of the variables and conducted comparison of the outcome groups based on the predictor variables using Chi-square. Univariable and multivariable logistic regression was used to explore the strength of relationship between the outcome variable and the significant predictor variables in bivariate analysis. SAS 9.4 was used for the statistical analysis. Analysis of weighted frequencies showed that 55% of the children were less than 2 years of age while the sex was almost equally distributed between males and females (50.9% vs 49.1%). Just over two-thirds lived in a rural area, 63.2% resided in the Northern part of the country, 59.1% had a rich family and majority (69.1%) had anemia. When cross-tabulated with the outcome variable of anemia status, there was a significant difference in the categories of age (P=0.0048), residential type (P=0.0031), mother’s education status (P=0.0210) and family’s wealth index (P=0.0010). Univariable logistic regression showed that children less than 2 years had over two times higher odds of developing anemia when infected with malaria compared to older children aged 3-4 years (OR:2.17, 95% CI:1.26-3.74, P=0.0052). Urban-dwelling children had 57% reduced odds of developing anemia compared to rural-dwelling children (OR:0.43, 95% CI:0.25-0.76, P=0.0034). Children of educated mothers had 50% reduced odds of developing anemia compared to children of uneducated mothers (OR:0.50, 95% CI:0.28-0.91, P=0.0222), while children in poor families had 165% increased odds of developing anemia compared to those born into rich families (OR:2.65, 95% CI 1.47-4.78, P=0.0012). Once adjusted for all significant variables in the bivariate analysis, only age remained significant as a predictor of anemia in children under five years with malaria (OR:2.29, 95% CI:1.31-4.02, P=0.0039). Younger age seems to be an important predictor of anemia in Nigerian children with malaria in real life settings given its significance on the multivariable model. This finding should inform clinicians on the need to pre-empt and treat anemia in Nigeria’s younger children with malaria for better treatment outcome.
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Oppenheimer, Stephen James. "Iron deficiency and susceptibility to infection : a prospective study of the effects of iron deficiency and iron prophylaxis in infants in Papua New Guinea." Thesis, University of Oxford, 1987. http://ora.ox.ac.uk/objects/uuid:1891d054-1564-47f5-b2e0-b6da5f60e996.
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Investigation of the relationship between iron deficiency, iron supplementation and susceptibility to infection, was suggested by the author's initial observations of an association of anaemia with serious bacterial infections in infancy in Papua New Guinea. The bulk of previous longitudinal clinical intervention studies in infancy showed beneficial effects of iron supplementation. However, defects of control and design and recording in these studies and contradictory anecdotal reports left the question unresolved. A prospective, placebo-controlled, randomised, double-blind trial of iron prophylaxis (3ml intramuscular iron dextran = 150mg Fe) to two month old infants was carried out on the North Coast of Papua New Guinea where there is high transmission of malaria. A literature review, pilot studies, protocol, demography, geography and laboratory methods developed are described. Findings indicate that the placebo control group became relatively iron deficient over the first year of life and that the iron dextran group had adequate, although not excessive iron stores and a higher mean haemoglobin; however, the prevalence and effects of malaria recorded in the field were higher in the iron dextran group. Analysis of field and hospital infectious morbidity in the trial indicated a deleterious association with iron dextran for all causes including respiratory infections (the main single reason for admission). Total duration of hospitalisation was significantly increased in the iron dextran group. Analysis of other factors showed (1) a higher admission rate associated with low weight-for-height recorded at the start of the trial; (2) a significant positive correlation between birth haemoglobin and hospital morbidity rates; (3) increased malaria rates in primiparous mothers of the cohort infants who received iron infusion during pregnancy; (4) lower relative risk of malaria associated with iron prophylaxis in individuals with alpha thalassaemia, which was found to be highly prevalent in this region. In conclusion, it is suggested that policies of iron supplementation, total dose iron injection and routine presumptive iron therapy for anaemia which are widely in practice in malaria endemic areas should be closely reviewed.
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Hesterberg, Uta Walburga. "A serological prevalence study of important infectious diseases of cattle in rural areas of Kwa Zulu Natal, South Africa." Diss., Access to E-Thesis, 2007. http://upetd.up.ac.za/thesis/available/etd-05062008-081645.
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Williams, Ramone. "Role of Trimethoprim-Sulfamethoxazole Prophylaxis Against the Infectious Complications of Rituximab Treatment in Autoimmune Blistering Diseases – a Retrospective Descriptive Study." Thesis, Harvard University, 2015. http://nrs.harvard.edu/urn-3:HUL.InstRepos:17295871.
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Background: Rituximab has emerged as a highly successful treatment in patients with severe-refractory autoimmune blistering diseases (AIBD) including pemphigus vulgaris. Marked clinical responses have been documented within just a few weeks of therapy and response rates as high as 97% have been reported. The B cell depleting action of rituximab occurs within 2 weeks of the first infusion and persists for an average of 11 months. Patients with AIBD on rituximab, often receive concurrent therapy with steroids and immunosuppressive agents. Thus, the B cell depleting action of rituximab occurs in the setting of glucocorticoid-mediated T cell suppression. Severe infection after rituximab treatment has been reported in up to 10% of patients, some fatal. This study investigates the rate and spectrum of infectious complications of rituximab in AIBD and potential role of trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis.
Methods: We performed a retrospective cohort study of 30 patients with AIBD treated with rituximab. Patients received varying protocols of rituximab treatment. All patients received concurrent systemic corticosteroids and/ or immunosuppressive agents. We analyzed the incidence and spectrum of infectious complications as well as the use of antibiotic prophylaxis in the cohort.
Results: Seventy-seven percent of patients received antibiotic prophylaxis. Thirty-three percent of patients developed at least one infectious complication of rituximab, 7% of infections were fatal. TMP-SMX was the agent of choice. The mean duration of antibiotic prophylaxis was 9 months. No adverse effects of TMP-SMX were observed. There was a decreased rate of infectious complications in patients who received antibiotic prophylaxis (RR 0.4; p 0.05), however this trend was not statistically significant.
Conclusion: Even in the absence of published guidelines, physicians frequently administer TMP-SMX as prophylaxis for infections in patients with AIBD on rituximab, during treatment and in subsequent periods of B cell depletion. Based on our findings and existing guidelines for patients long term prednisone, we advocate for the use of TMP-SMX prophylaxis in patients with AIBD on rituximab and concurrent steroid-immunosuppressive therapy.
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Eyre, David William. "Quantitative study of Clostridium difficile transmission using extensive epidemiological data and whole genome sequencing." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:a7197605-6da6-4dbc-9bec-171d6e683eb1.
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Clostridium difficile is a leading healthcare-associated infection, which causes diarrhoea, and is almost exclusively precipitated by antibiotic exposure. Traditionally C. difficile infection (CDI) has been considered predominantly transmitted within hospitals. However, endemic spread hampers identification of the source of infections, and therefore control and prevention of disease. A cohort of consecutive hospital and community CDI cases in Oxfordshire from September 2007 to March 2011 was investigated. For each case hospital admission, ward movement and demographic data were available allowing contact events between cases to be reconstructed. Initially 944 cases to March 2010 underwent multilocus sequence typing (MLST), subdividing the endemic cases into 69 distinct lineages and demonstrating unexpectedly that ward-based contact with known symptomatic CDI cases only accounts for <25% of disease. To better determine the extent of transmission arising from symptomatic patients, irrespective of the route transmission, isolates from 1223 cases to March 2011 underwent whole genome sequencing. Serially sampled patients with recurrent or on-going disease were used to estimate rates of C. difficile evolution and within-host diversity and to show 0-2 single nucleotide variants (SNVs) are expected between transmitted isolates obtained <124 days apart (95% prediction interval). Mixed infection with more than one strain was investigated, but probably plays only a minor role in onward transmission. In the Oxfordshire CDI cohort, 333/957 (35%) CDI from April 2008 – March 2011 were within 2 SNVs of ≥1 previous case since September 2007 (consistent with transmission). 428/957 (45%) were >10SNVs from all previous cases: these distinct subtypes continued to be identified consistently throughout the study, suggesting cases arise from a considerable reservoir of C. difficile. Surprisingly, declines in the incidence of genetically-related CDI were similar to those in genetically distinct CDI suggesting interventions not just targeting symptomatic individuals, e.g. antimicrobial stewardship, have played a significant role in recent CDI declines. Finally, the feasibility of studying asymptomatic inpatients as potential source of the unexplained transmission was investigated. This thesis provides convincing evidence, in a setting with typical CDI incidence and infection control practice, that only the minority of CDI arises from other symptomatic cases. It demonstrates that much CDI arises from genetically diverse reservoirs, with each exposure resulting in relatively few secondary cases. Future control strategies therefore need to focus on identifying these reservoirs, one of which is plausibly asymptomatic inpatients, and also on interventions that prevent the transition from exposure and colonisation to disease, such as antimicrobial stewardship.
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Ning, Jia, and 宁嘉. "Study of epstein-barr virus (EBV)-specific polyfunctional T cells responses in long term carriers and patients with infectious mononucleosis and haemophagocytic lymphohistiocytosis." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/196482.
Full textAbstract:
Effective control of chronic viral infections may require the generation of polyfunctional T cells (PFCs) which are capable of producing multiple cytokines and possess cytotoxic function. In this study, I investigate (i) whether PFCs play an important role in the long term immune control of a persistent human virus, Epstein-Barr virus (EBV), (ii) the relationship between the development of immunodominance and functionality during the evolution of the anti-viral T cell responses, and (iii) whether PFCs can be generated in patients with EBV-associated haemophagocytic lymphohistiocytosis (HLH).
To tackle the first question, I established a 9-color flow cytometry assay to characterize the co-expression of four cytokines (interferon-f [IFN-[], macrophage inflammatory protein 1-] [MIP1-[], tumour necrosis factor-] [TNF- ] and interleukin-2 [IL-2]) and degranulation marker (CD107a) by both EBV lytic and latent peptide-specific CD4+ and CD8+ T cells in 20 healthy long term viral carriers. Two patients with EBV-associated post-transplant lymphoproliferative disorder (PTLD) were studied for comparison. Both CD4+ and CD8+ PFCs were readily generated in the long term carriers with the immunodominant EBV proteins apparently stimulating higher proportions of PFCs than the subdominant viral proteins. The PFCs producing greater amount of cytokines per cell than the single functional T cells. In contrast, EBV-specific PFCs were hardly generated in the patients with PTLD.
To investigate the relationship between the development of immunodominance and functionality, I performed a longitudinal study of CD4+ and CD8+ T cell responses in 10 children with infectious mononucleosis (IM) and 4 asymptomatic individuals (AS) with primary EBV infection from the time of diagnosis to one year post-infection. Viral peptide-specific T cells were examined for the co-expression of three cytokines (IFN-t, TNF-T and IL-2), perforin and CD107a upon stimulation with overlapping peptide pools of lytic and latent proteins, respectively. PBMC viral loads were reduced gradually in both IM and AS subjects. Whilst lytic and latent peptide-specific PFCs were still detectable at the acute stage of infection, they showed an increase in functionality over time in response to peptide pools of immunodominant proteins. From acute to persistent infection stage, the CD8+ T cell responses shifted from reactivities against the lytic peptides to those against the latent EBNA3A and 3B peptides with concurrent increase in functionality. Change in CD4+ T cell responses is less obvious, apparently from reactivities towards broad range to EBNA1 peptides.
Finally, we found that two patients with the life-threatening EBV-associated haemophagocytic lymphohistiocytosis (HLH) had very high viral loads at the onset of disease. The clinical symptoms improved and viral loads were gradually reduced by the immunosuppressive drug therapy. Interestingly, EBV lytic and latent peptide-specific PFCs could be subsequently generated post-treatment with sustained resolution of clinical symptoms and clearance of plasma viral loads .
In conclusion, lytic and latent peptide-specific CD4+ and CD8+ PFCs may confer long term immune control to EBV. The PFCs may be generated concurrent with the establishment of immunodominance hierarchy during the evolution of viral-specific T cell responses. Long term polyfunctional T cell responses to EBV can be formed in patients with EBV-associated HLH.published_or_final_version
Paediatrics and Adolescent Medicine
Doctoral
Doctor of Philosophy
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Forster, William Paul. "Risk, modernity and the H5N1 virus in action in Indonesia : a multi-sited study of the threats of avian and human pandemic influenza." Thesis, University of Sussex, 2012. http://sro.sussex.ac.uk/id/eprint/38647/.
Full textAbstract:
This thesis examines the Influenza A/H5N1 virus in action through an ethnographic study focused on the entwined concepts of risk and modernity. The objective is to explain why the response to the virus has been challenged in Indonesia. Concerned with policy formulation, and everyday practice, the thesis argues that assemblages of historical, political, institutional and knowledge‐power processes create multiple hybrid constructions of risk and modernity, which challenge technical responses based on epistemological positions and institutional arrangements that do not allow for such hybridity. The thesis is organised into four sections. The first section (chapters 1 – 3) introduces the virus and its terrain, outlines a constructivist position, and argues that conceptually risk and modernity have multiple, dynamic, power‐laden forms. The second section (chapters 4 – 6) contrasts constructions of risk and modernity among the actors and networks responding to the emergence, spread and persistence of the H5N1 virus, with the constructions of affected people in Indonesia. The third section (chapters 7 – 9) investigates the multi‐directional processes that occur when ‘global' policies and practices encounter ‘local' social and political settings, and vice versa, through three empirical case studies of the response to H5N1 in Indonesia between 2005 and 2010. The final section (chapter 10) provides a set of reflections and conclusions. Given the conceptual plurality of risk and modernity, and the multiple overlapping interacting hybrid constructions that have been empirically demonstrated in the case of H5N1, it is concluded that reductive, science‐based, governmentally‐orientated responses which treat nature as a matter of separate, fixed identity do not allow for such hybridity. The virus in action in Indonesia shows that any divide between nature and society is artificial and deceiving. Technical disease control responses need to incorporate understandings which accept the dynamics of culture, politics, and power.
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Habayeb, Mazen. "Nora virus as a model to study persistent infection in Drosophila melanogaster." Doctoral thesis, Molecular Biology, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-22129.
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Drosophila melanogaster has been widely used as a model organism to study the immune responses against bacteria, fungi, parasites and viruses. Here, I present a D. melanogaster virus as a model to study persistent virus infections. I have discovered and characterized the Nora virus, a small picorna-like RNA virus able to persistently infect D. melanogaster. The Nora virus genome encodes four open reading frames; a feature not present in other picorna-like viruses. The Nora virus is not closely related to any other virus family, but rather is the first virus in a new family of picorna-like viruses. The major replicative proteins of this virus are encoded in the second open reading frame and the capsid proteins are encoded in the fourth open reading frame. The sequence of the capsid proteins are not obviously related to any other previously described protein. By looking at expressed sequence tags (EST) projects, we identified an EST sequence from the parasitic wasp Nasonia which appears to encode proteins that have sequence similarity to the Nora virus capsid proteins. I have shown that the Nora virus persists in the fly intestine however I did not observe serious pathological effects in the infected flies. The virus is shed through feces and the transmission occurs horizontally via the ingestion of virus-contaminated food. Moreover, I observed variability in the viral titers among single flies of the same infected stock. Some flies are able to clear the Nora virus but not others and this phenomenon seems to be titer-dependent. Surprisingly, none of the known Drosophila antiviral responses play a role against the Nora virus. In conclusion, my work shows that studying the Nora virus interaction with the Drosophila immune system can lead to new findings on viral persistence mechanisms of RNA viruses and of Drosophila viral innate immunity.
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Carvalho, António Jorge da Silva. "Calicivirose felina : um estudo retrospetivo." Master's thesis, Universidade de Lisboa, Faculdade de Medicina Veterinária, 2020. http://hdl.handle.net/10400.5/20689.
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Dissertação de Mestrado Integrado em Medicina VeterináriaAs Doenças do Trato Respiratório Superior em Felídeos (DTRSF) apresentam diversos agentes etiológicos, destacando-se pela sua relevância clínica e contagiosidade, o Calicivírus Felino (FCV), o Herpesvírus Felino Tipo 1 e Chlamydophyla felis. Os animais admitidos no Hospital Escolar da FMV ULisboa com suspeita ou confirmação de DTRSF são hospitalizados na Unidade de Isolamento e Contenção Biológica (UICB). O estudo retrospetivo teve dois objetivos: quantificar e investigar a frequência de episódios clínicos de FCV em gatos internados na UICB, de outubro de 2013 a julho de 2019; identificar e caracterizar os fatores determinantes de doença associados ao hospedeiro e ao meio ambiente em gatos infetados com FCV; tendo sido investigados os seguintes parâmetros: proveniência, distrito de residência, estilo de vida, coabitação com outros animais de companhia, raça, idade, género, estatuto reprodutivo, estatuto vacinal, apresentação clínica, resultados dos exames complementares de diagnóstico, presença de doenças concomitantes, duração de internamento, número de hospitalizações e desfecho clínico. Foram hospitalizados com DTRSF no período em estudo 110 gatos com quadro clínico de DTRSF, 26 gatos (24%) foram RT-PCR positivos para FCV. A maioria dos gatos infetados era do género feminino (61,5%), não castrados (57,7%) e de raça indeterminada (92,3%). A idade média foi de 3,8±4,6 anos. Os gatos jovens, de idade inferior ou igual a 2 anos, apresentaram a maior frequência de infeção (53,9%). Detetaram-se elevadas proporções de calicivirose felina em gatos com estilo de vida livre ou semilivre (69,2%), em gatos originários da rua (50,0%) e em gatos não vacinados ou com o plano vacinal atrasado (65,4%). A maioria dos felídeos (88,5%) coabitava com pelo menos outro animal de companhia e 53,9% tinha uma doença concomitante. A duração média de internamento foi de 3,8±2,9 dias. As úlceras linguais, os corrimentos nasais, os corrimentos oculares purulentos e a gengivo-estomatite foram os sinais clínicos específicos mais frequentes. Vinte e dois gatos (88%) tiveram alta clínica, apenas 12,0% faleceram devido à calicivirose felina, mas 87,5% foram considerados portadores crónicos nas consultas de seguimento. Todos os gatos investigados residiam no distrito de Lisboa. Julho foi o mês com maior frequência de casos de FCV (38,5%) e o verão a estação do ano com maior frequência de gatos internados com FCV (46,2%). A castração revelou-se um fator de proteção (p=0,0055; OR=0,22; 0,08
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Onyambu, Frank Gekara. "Study of Platelet-mediated clumping adhesion phenotypes in Plasmodium falciparum malaria." Thesis, University of Oxford, 2015. http://ora.ox.ac.uk/objects/uuid:2bc489a9-121e-41ab-8830-1cb07e5b01f2.
Full textAbstract:
Platelet-mediated clumping of Plasmodium falciparum-infected erythrocytes (IEs) is a common property of field isolates associated with severe disease (Pain, Ferguson et al. 2001). Platelet receptors CD36 (Pain, Ferguson et al. 2001), P-Selectin (Wassmer, Taylor et al. 2008) and gC1qR (Biswas, Hafiz et al. 2007) mediate clumping. To characterize the molecular specificities of the clumping phenotype, I cloned clumping parasite line IT/C10 by limiting dilution. I characterized var gene expression in the IT/C10 clones using generic primers for the DBL tag region (Bull, Berriman et al. 2005). Clumping assays were conducted in the presence of specific reagents to delineate host factors hypothesized to contribute to development of the clumping phenotype. Finally, I conducted a clinical study with isolates from children with malaria in Kilifi, Kenya. This study shows that in parasite line IT/C10, platelet-mediated clumping is associated with Itvar30 suggesting a prominent role for the PfEMP-1 encoded by this var gene in development of platelet-mediated clumping. For IT/C10 parasites, platelet activation appears to be involved in platelet-mediated clumping. Platelet P-Selectin appears to mediate clumping using lectin-dependent interactions. To further elucidate the mechanisms that mediate clumping by host platelets, I have used a panel of platelet antagonists to delineate specific platelet activation pathways. Our results show that platelet activation plays an important role in platelet-mediated clumping. Finally, in this study, platelet-mediated clumping was associated with parasitaemia, but not with disease severity.
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Waddington, Claire Shelley. "Understanding typhoid disease : a controlled human infection model of typhoid fever." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:679ef7ec-b871-47a8-adea-d3fb3478e4b9.
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Typhoid disease, caused by infection with S. Typhi, is a significant cause of mortality and morbidity in resource–poor countries. Efforts have been made to generate a new generation of vaccines that are efficacious and can be given to infants, but have been hindered by a poor understanding of the protective immune response to S. Typhi infection, and in particular by the absence of a correlate of protection. Controlled human infection studies (‘challenge studies’) provide a model for investigating infectious diseases and appraising novel vaccines, including in typhoid disease. This DPhil described the development of a human challenge model of typhoid fever using
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Beugin, Marie-Pauline. "The European wildcat as a model for the study of wildlife : focus on hybridization and the circulation of viruses." Thesis, Lyon, 2017. http://www.theses.fr/2017LYSE1275/document.
Full textAbstract:
L'hybridation et les maladies infectieuses sont deux problématiques majeures pour la conservation de la faune sauvage à travers le monde. Le Chat sauvage européen Felis silvestris silvestris, à travers ses interactions avec son proche apparenté le Chat domestique Felis silvestris catus, représente un modèle intéressant pour l'étude de ces deux problématiques et de leurs interactions. Le fait que le Chat sauvage soit touché par ces deux phénomènes, combiné à la variabilité des habitats dans lesquels il vit en Europe, permet de conduire des études comparées et de comprendre quels déterminants environnementaux influencent les flux de gènes et de pathogènes. Ici, nous proposons deux nouvelles approches méthodologiques basées sur l'analyse de marqueurs génétiques, pour une meilleure comparabilité entre études et une détection rapide des hybrides respectivement. Nous avons recherché les hybrides et regardé la distribution spatiale des individus apparentés dans deux populations locales divergeant principalement sur le niveau de fragmentation de l'environnement. Dans l'une de ces populations, nous avons également conduit une étude sérologique pour déterminer si les chats sauvages et domestiques échangeaient certains des virus communs du Chat domestique (PVF, HVF, CVF, VIF). Nous avons observé un taux d'hybridation plus élevé dans l'environnement le plus fragmenté. Malgré la ceinture de chats domestiques infectés à haute prévalence autour d'elle, la population de chats sauvages de ce même environnement n'était infectée par aucun des virus. La présence de barrières génétiques et/ou comportementales expliquerait ce résultat dans un environnement fragmenté permettant par ailleurs le maintien de souches généralistes. L'échantillonnage local présenté ici nous a permis de comprendre les mécanismes à la base de l'hybridation et de la circulation des virus. Présentement, le Chat sauvage européen ne semble pas menacé par le Chat domestique. Toutefois, des mesures préventives devraient être adoptées pour éviter que cela ne devienne le casHybridization and infectious diseases are two major issues for wildlife conservation worldwide. The European wildcat Felis silvestris silvestris, through its interactions with its close relative the domestic cat Felis silvestris catus, represents a valuable model for the study of these two issues and their interactions. The European wildcat is both threatened by hybridization and infectious diseases. This, combined with the high diversity of environments where it lives throughout Europe, allows to lead comparative studies and to understand which environmental determinants impact gene and pathogen flows. Here we propose two new methodological developments for the detection of hybrids based on genetic markers allowing for a better comparability between studies and leading to a fast detection of hybrids respectively. Hybrid detection and assessment of spatial relatedness pattern were carried out in two local populations of European wildcats differing mostly on the level of fragmentation of their environment. On one of this population, we led a serological survey to investigate whether domestic cats and wildcats exchange some of the most common viruses of the domestic cat (FPV, FHV, FCV, FIV). We found a higher rate of hybridization in the most fragmented environment. There, the wildcat population, in spite of the domestic cats surrounding it that were infected at high prevalence with the viruses, was not infected by any of the viruses. The presence of genetic or behavioral barriers may explain this result in an environment that is not incompatible with the persistence of generalist strains. The local sampling achieved in this work allowed us to investigate mechanisms behind hybridization and viruses’ circulation. At the time, the European wildcat does not seem threatened by domestic cats. However, preventive measures should be taken to prevent a future increase in frequency of the phenomenon both for the control of gene and virus flows
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Singleton, Michael David. "Nonlinear Hierarchical Models for Longitudinal Experimental Infection Studies." UKnowledge, 2015. http://uknowledge.uky.edu/epb_etds/7.
Full textAbstract:
Experimental infection (EI) studies, involving the intentional inoculation of animal or human subjects with an infectious agent under controlled conditions, have a long history in infectious disease research. Longitudinal infection response data often arise in EI studies designed to demonstrate vaccine efficacy, explore disease etiology, pathogenesis and transmission, or understand the host immune response to infection. Viral loads, antibody titers, symptom scores and body temperature are a few of the outcome variables commonly studied. Longitudinal EI data are inherently nonlinear, often with single-peaked response trajectories with a common pre- and post-infection baseline. Such data are frequently analyzed with statistical methods that are inefficient and arguably inappropriate, such as repeated measures analysis of variance (RM-ANOVA). Newer statistical approaches may offer substantial gains in accuracy and precision of parameter estimation and power. We propose an alternative approach to modeling single-peaked, longitudinal EI data that incorporates recent developments in nonlinear hierarchical models and Bayesian statistics. We begin by introducing a nonlinear mixed model (NLMM) for a symmetric infection response variable. We employ a standard NLMM assuming normally distributed errors and a Gaussian mean response function. The parameters of the model correspond directly to biologically meaningful properties of the infection response, including baseline, peak intensity, time to peak and spread. Through Monte Carlo simulation studies we demonstrate that the model outperforms RM-ANOVA on most measures of parameter estimation and power. Next we generalize the symmetric NLMM to allow modeling of variables with asymmetric time course. We implement the asymmetric model as a Bayesian nonlinear hierarchical model (NLHM) and discuss advantages of the Bayesian approach. Two illustrative applications are provided. Finally we consider modeling of viral load. For several reasons, a normal-errors model is not appropriate for viral load. We propose and illustrate a Bayesian NLHM with the individual responses at each time point modeled as a Poisson random variable with the means across time points related through a Tricube mean response function. We conclude with discussion of limitations and open questions, and a brief survey of broader applications of these models.
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Thomas, Sarah Elizabeth. "A Prevalence Study of Southeast Origin Sale Barn Beef Cattle, Comingled in Warren County, Kentucky, Persistently Infected with Bovine Viral Diarrhea Virus, including the Effects of Season and Body Weight." TopSCHOLAR®, 2011. http://digitalcommons.wku.edu/theses/1070.
Full textAbstract:
Bovine viral diarrhea (BVD) is an economically important disease of cattle. Calves persistently infected (PI) with the bovine viral diarrhea virus (BVDV) are a powerful agent for spread of the virus. A total of 24,423 southeast origin beef cattle comingled at three Warren County, Kentucky locations were tested from November 2007 to June 2010 for PI BVDV. A total of 97 head tested positive for PI BVDV, giving an average overall prevalence of 0.397%. Calves tested were subdivided into categories for additional calculations of dependence. A total of 8,910 were categorized by weight range upon testing (300-399 lbs, 400-499 lbs, 500-599 lbs, and 600-699 lbs). Prevalence does show a dependence on weight, with a higher prevalence found in lower weight classes, especially 300-399 lb calves (P<0.001). A total of 24,423 were categorized by season at time of testing (Fall, Winter, Spring, Summer). Prevalence does not show a dependence on season (P>0.05). Although eradication programs are not likely to be organized in the United States, several control programs have been developed. These findings can be used as additional support for PI testing of calves, especially those in lighter weight classes, as part of a BVD control program.
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Lövström, Tora. "An epidemiological study of Swedish Campylobacter jejuni isolates from humans and broilers using multilocus sequence typing." Thesis, University of Kalmar, School of Pure and Applied Natural Sciences, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:hik:diva-2186.
Full textAbstract:
Campylobacter jejuni is the main cause of bacterial diarrhoeal illness in developed countries, with ~7000 cases being reported each year in Sweden. C. jejuni has received growing attention since it’s recognition as a human pathogen in the 1970s, but its epidemiology is complex and much still remains unknown. There are several potential reservoirs for C. jejuni, including environmental sources as water and soil, wild and domesticated animals, particularly poultry, but also other livestock and pets. In this study 348 Swedish C. jejuni isolates from the year 2000 from humans (n = 164) and broilers (n = 184) were characterized with multilocus sequence typing (MLST) with the aim of comparing the population structures and diversity of C. jejuni between isolates from the two hosts. MLST is a method for characterization of bacterial isolates that indexes the variation in DNA sequence of multiple protein encoding housekeeping genes. A secondary aim in this study was to compare populations of C. jejuni from 11 subgroups of isolates based on location of the sampling. The overlap between the populations was analyzed numerically based on genotypes detected and with analysis of phylogeny, gene flow and molecular variation. It was shown that the population structure of C. jejuni isolates from broilers and humans show a high degree of similarity, supporting broilers as an important source of human infection. However, even though the population structure of human and broiler C. jejuni were almost genetically indistinguishable other sources of C. jejuni infections in humans cannot be ruled out since the same genotypes can be found in other sources as well. Analysis of the 11 subgroups suggested that there may be a difference in populations infecting humans in different Swedish regions, and between populations of C. jejuni in broilers from different slaughterhouses. But this could be a result of chance since most of the subgroups were small. Future studies to improve the understanding of C. jejuni epidemiology, for which MLST has proven itself as a valid method, is important to develop control strategies to prevent infection with this common cause of diarrhoeal illness.
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Kloprogge, Frank Lodewijk. "Pharmacokinetics and pharmacodynamics of antimalarial drugs in pregnant women." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:79ce1a37-3ba2-45e4-9f80-0692a66837f1.
Full textAbstract:
Malaria is the most important parasitic disease in man and it kills approximately 2,000 people each day. Pregnant women are especially vulnerable to malaria with increased incidence and mortality rates. There are indications that pregnancy alters the pharmacokinetic properties of many antimalarial drugs. This is worrisome as lower drug exposures might result in lowered efficacy and lower drug exposures can also accelerate the development and spread of resistant parasites. The aim of this research was to study the pharmacokinetics and pharmacodynamics of the most commonly used drugs for the treatment of uncomplicated Plasmodium falciparum malaria during the second and third trimester of pregnancy using a pharmacometric approach. This thesis presents a number of important findings that increase the current knowledge of antimalarial drug pharmacology and that may have an impact in terms of drug efficacy and resistance. (1) Lower lumefantrine plasma concentrations at day 7 were evident in pregnant women compared to that in non-pregnant patients. Subsequent in-silico simulations with the final pharmacokinetic-pharmacodynamic lumefantrine/desbutyl-lumefantrine model showed a decreased treatment failure rate after a proposed extended artemether-lumefantrine treatment. (2) Dihydroartemisinin exposure (after intravenous and oral administration of artesunate) was lower during pregnancy compared to that in women 3 months post-partum (same women without malaria). Consecutive in-silico simulations with the final model showed that the underexposure of dihydroartemisinin during pregnancy could be compensated by a 25% dose increase. (3) Artemether/dihydroartemisinin exposure in pregnant women was also lower compared to literature values in non-pregnant patients. This further supports the urgent need for a study in pregnant women with a non-pregnant control group. (4) Quinine pharmacokinetics was not affected by pregnancy trimester within the study population and a study with a non-pregnant control group is needed to evaluate the absolute effects of pregnancy. (5) Finally, a data-dependent power calculation methodology using the log likelihood ratio test was successfully used for sample size calculations of mixed pharmacokinetic study designs (i.e. sparsely and densely sampled patients). Such sample size calculations can contribute to a better design of future pharmacokinetic studies. In conclusion, this thesis showed lower exposures for drugs used to treat uncomplicated Plasmodium falciparum malaria during the second and third trimester of pregnancy. More pharmacokinetic studies in pregnant women with a non-pregnant control group are urgently needed to confirm the current findings and to enable an evidence-based dose optimisation. The data-dependent power calculation methodology using the log likelihood ratio test can contribute to an effective design of these future pharmacokinetic studies.
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Spivey, Justin, Heather Sirek, Robert Wood, Kalpit Devani, Billy Brooks, and Jonathan Moorman. "Retrospective Cohort Study of the Efficacy of Azithromycin Vs. Doxycycline as Part of Combination Therapy in Non-Intensive Care Unit Veterans Hospitalized with Community-Acquired Pneumonia." Digital Commons @ East Tennessee State University, 2017. https://dc.etsu.edu/etsu-works/3177.
Full textAbstract:
The IDSA Community-Acquired Pneumonia (CAP) Guideline recommends ceftriaxone in combination with doxycycline as an alternative to combination therapy with ceftriaxone and azithromycin for non-intensive care unit (ICU) patients hospitalized with CAP. This is an attractive alternative regimen due to recent concerns of increased cardiovascular risk associated with azithromycin. The objective of this study was to compare the clinical outcomes of azithromycin and doxycycline each in combination with ceftriaxone for non-ICU Veterans hospitalized with CAP.
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Dungu-Kimbenga, B. "Study on the effects of a natural Maedi visna virus infection on sheep productivity." Diss., University of Pretoria, 2000. http://hdl.handle.net/2263/25380.
Full textAbstract:
A cohort study was conducted in order to measure the effect of the chronic indurative lymphocytic mastitis caused by the South African strain ofMaedi visna virus (SA-OMVV) on the pre-weaning growth of lambs born of naturally infected and uninfected ewes kept under similar conditions. 50 naturally infected ewes and 40 controls from an MVV-free source were purchased and kept separately. All ewes were of the same breed - the Dorper¬and 3 to 4 years old. From the adaptation period, through mating, pregnancy and lactation periods they were monitored for MVV antibodies and managed under similar conditions. The lambs were weighed at birth and thereafter every two weeks until the age of 90 days, when they were weaned. The ewes were slaughtered, their udders examined histologically and the lesions were assessed by counting typical lymphocytic follicles. Although the observed values indicated a correlation between the number of follicles in the udder and the reduction in the growth rate of the lambs, this was not statistically significant. Similarly, despite higher counts of lymphoid follicles in the udder of sero-positive ewes as compared to sero-negatives and the observed lower ewe productivity indexes (EPI) in infected ewes, no statistically significant differences were found in the EPI of ewes in different follicle categories. The present study was a first attempt to evaluate the effect of the SA-OMVV infection on sheep productivity in South Africa.Dissertation (MSc)--University of Pretoria, 2000.
Production Animal Studies
Unrestricted
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Kuret, Teresa. "A pre- and post-test study on the knowledge of grade 6 to 9 learners on HIV/AIDS and sexually transmitted infections." Thesis, Nelson Mandela Metropolitan University, 2005. http://hdl.handle.net/10948/389.
Full textAbstract:
In 1981, a number of reports of death from immune system failure began to cause alarm in medical circles. The Human Immunodeficiency Virus (HIV) was identified as the cause of a condition known as Acquired Immune Deficiency Syndrome (AIDS). To date, there is no cure for AIDS, and as a result it is perceived as the deadliest medical condition of the century. While intensive research remains focused on development of a vaccine, there has been a strong move toward a more preventative approach that is holistic in nature, and encompasses behavioural and social components as being of equal importance. Going hand in hand with HIV/AIDS are Sexually Transmitted Infections (STIs). STIs are increasing around the world and in South Africa at a remarkable rate. Like HIV/AIDS, STIs are also transmitted during sex, more specifically through body contact during sex. Research has identified adolescents as a group that is particularly vulnerable to HIV and STI infection. Life-skills programmes use experiential learning to engage learners and are particularly popular because they empower individuals to make responsible, well thought out decisions based on well developed values and beliefs. There are however, various variables and agents that impact upon the success of HIV/AIDS and STI education. It is therefore suitable to adopt a biopsychosocial approach to underlie a HIV/AIDS and STI life-skills programme. Health models, such as the AIDS Risk Reduction Model, based on this approach should take into consideration important psychological variables to cope with changes in behaviour, as well as prepatory behaviours inclined towards preventing risky behaviour. The Ubuntu Education Fund is a non-government, international organisation that offered a life skills programme in HIV/AIDS, STIs, Rape and Child Abuse to learners in Grades 6 - 9. This study focused on HIV/AIDS and STIs. The sample size was 260 learners from the Nelson Mandela Metropolitan Region. A quasiexperimental one group pre-and post-test design was used to determine if there was a difference between the knowledge of these learners pre- and post- the life skills programme. The results of the study indicate that there was a small increase in knowledge after the life-skills programme intervention. In some schools there was even a decrease in knowledge. This study suggests that the life-skills programme was flawed and that it needs to be reviewed. The implications of these findings are discussed with suggestions for future interventions.
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Collins, Ann. "A review and retrospective study of some major bacterial orofacial infections." University of Sydney, 1990. http://hdl.handle.net/2123/4209.
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Master of Dental SurgeryHistory has recorded the antiquity of serious infections in the region of the head and neck. Today, our community still experiences major life-threatening infections in these anatomical locations, which pose significant management difficulties to the oral and maxillofacial surgeon. The aim of this thesis is to review the aetiology, diagnosis and treatment of some bacterial infections involving structures of the head and neck. Such infections may spread, causing serious complications with severe morbidity and occasionally death. This theses deals only with infections of bacterial origin and does not attempt to cover viral, or fungal agents or the chronic specific diseases of tuberculosis and syphilis, and makes no attempt to address the old question of focal infection. The literature review relates especially to Ludwig’s Angina which was first described so dramatically in 1836. To this day it remains as a clinically potentially lethal disease despite the progress of modern medicine. Numerous descriptions in the literature warn of the rapid appearance of symptoms and the danger of respiratory obstruction when management of the airway is not satisfactorily undertaken. Both odontogenic and non-odontogenic causes of orofacial and neck infections are reviewed. Odontogenic problems are given special emphasis as they are now of major concern. The significance of the potential fascial spaces in the face and neck which allow the spread of dental infections is also highlighter. A thorough knowledge of these anatomical relationships is still of the utmost importance to the surgeon if he is to be successful in treatment. The principle of surgical drainage of pus is as important in 1990 as it was 150 years ago. The biological basis for the onset and progress of such fulminating infections in the head and neck region is still poorly understood. One constant need is that the bacteria, both aerobic and anaerobic, be correctly identified. Microbiological techniques are constantly improving and provide an important adjuvant investigation, which then allows the surgeon to provide the most appropriate antimicrobial therapy. Principal to the many aspects of treatment is the ability to maintain the airway of the patient and to provide the depth of anaesthesia necessary to undertake the required surgery. Major bacterial orofacial infections may have severe local and far-reaching systemic effects. Such complications are discussed in all their ramifications. It should be realised that the presentation of these patients at a late stage, when complications have already supervened, may make diagnosis difficult. There is always a necessity to ensure that the underlying cause of the disease is accurately defined and that complication are not allowed to progress further. Finally, a retrospective study of the management of 90 patients with major bacterial orofacial infections who have been treated at Westmead Hospital is presented. The outcome of this study of some major bacterial orofacial infections of the head and neck is the need to stress the importance of urgent surgical management and maintenance of the airway, together with the microbiological determination of the causative organisms and their sensitivities, so that other than empirical antibiotics can be instituted early. This must be combined with an upgrading of the patients’ medical and dental status. It was demonstrated that, in the majority of these patients, ignorance and fear combined with a lack of routine dental care resulted in major infections arising from relatively simple odontogenic causes such as dental caries, periodontal disease and pericoronal infection related to impacted teeth. Without doubt, the immediate care of these patients demanded intensive management. However, it is important to recognise that dental education forms an integral part not only of the recovery programme for the afflicted patient, but also as a community health preventive measure of profound significance.
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Maciag, Paulo Cesar. "Infecções por papilomavírus humano e neoplasia do colo uterino: efeito do polimorfismo dos genes HLA-DRB1 E -DQB1 e respostas linfoproliferativas contra peptídeos virais." Universidade de São Paulo, 2002. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-31082018-143208/.
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Infecção persistente por tipos oncogênicos de papilomavírus humano (HPV) é considerada como o principal fator de risco para desenvolvimento de carcinoma invasivo do colo uterino (CCU) e de lesões intraepiteliais cervicais (SIL). Fatores genéticos do hospedeiro, como o polimorfismos de genes HLA (human leukocyte antigen), também têm sido implicados na suscetibilidade a estas patologias e à infecção por (HPV), como observado em diversos estudos caso-controle. Neste estudo investigou-se em uma coorte de mulheres (Ludwig-McGill cohort) se a variabilidade dos genes HLA-DRB1 e -DQB1 influenciam na história natural das infecções por HPV e no risco de SIL. A tipificação de DRB1 e DQB1 foi realizada em 620 amostras provenientes de um estudo epidemiológico prospectivo. A positividade para HPV foi testada em amostras da mesma paciente coletadas a cada 4 meses, obtidos durante o primeiro ano de seguimento, enquanto os resultados de citologia perfazem os 2 primeiros anos de seguimento. Infecções persistentes de curta ou longa duração foram definidas como 2 e 3 resultados consecutivos positivos para o mesmo tipo de HPV, respectivamente. As associações foram estimadas através de razões de chance e intervalos de confiança de 95%, ajustadas para potenciais fatores de confusão. Os resultados obtidos indicam que a prevalência da infecção por HPV e o risco de persistência variam dependendo do haplótipo HLA. O haplótipo DRB1*0301-DQB1*0201 mostrou-se protetor contra a infecção por HPV, e DRB1*1102-DQB1 *0301 contra infecções persistentes. Já os haplótipos DRB1*1601-DQB1*0502 e DRB1 *0807-DQB1*0402 foram fatores de risco para infecções persistentes por HPV. Não foi observada uma forte concordância entre risco de infecção por HPV e risco de SIL associados a determinado HLA, em parte porque o número de pacientes com SIL foi um fator limitante neste estudo. Um risco aumentado de SIL, independente da infecção por HPV, foi associado com DRB1*0301 e DR12. Portadoras de DR4 e DQB1*0601 tiveram uma maior probabilidade de desenvolver SIL e HSIL, respectivamente. Uma associação negativa entre o alelo DQB1*0301 e HSIL foi verificada. Análise do dimorfismo na posição 86 da cadeia β de HLA-DR mostrou que valina nesta posição tem um efeito protetor para prevalência e persistência de infecção por HPV, e maior risco de SIL no grupo com infecções transitórias por HPV. Em outra análise, investigamos a distribuição de grupos alélicos de DRB1 em uma série independente de amostras provenientes de pacientes com CCU. Observamos um risco diminuído de desenvolvimento de CCU associado a DR3. Por outro lado, DR4 e DR8/12 mostraram-se fatores de risco para o CCU nesta população. Estes resultados sugerem que o polimorfismo de HLA desempenha um papel na história natural das infecções por HPV, SIL e CCU. Também analisamos respostas linfoproliferativas em pacientes com CCU, contra peptídeos derivados de E6 e E7 de HPV16. As respostas positivas foram mais freqüentes contra peptídeos de E6 do que E7. Não observamos resposta contra um peptídeo ou região em particular. Parte desta diversidade nas respostas linfoproliferativas pode ser relacionada com o polimorfismo de genes HLA e seu papel na seleção de epítopos.Persistent infection with oncogenic human papillomavirus (HPV) is the major risk factor for the development of malignant lesions in the uterine cervix. Host factors have also been implicated in the pathogenesis of these diseases. Associations between human leukocyte antigen (HLA) polymorphisms and cervical cancer, precursor lesions or HPV infections have been reported by case-control studies in several populations. This study investigated through cohort analysis if human leukocyte antigen (HLA)-DRB1 and DQB1 variability is related to human papillomavirus (HPV) infection and squamous intraepithelial lesions (SIL) prevalence and persistence. HLA-DRB1 and DQB1 genes were typed in 620 samples from the Ludwig-McGill cohort. HPV positivity was tested in specimens collected every 4 months during the first year of follow-up. Persistent and long-term infections were defined as at least 2 or 3 consecutive positive results for the same HPV type, respectively. Analysis of SIL included data obtained during the two first years of follow-up. The magnitudes of associations were estimated by unconditional logistic regression analysis adjusted for potential confounders. Certain HLA alleles and haplotypes were associated with HPV either HPV prevalence or persistence. The DRB1*0301-DQB1*0201 haplotype was associated with a lower risk for HPV infection and DRB1*1102-DQB1*0301 for HPV persistence. DRB1*1601-DQB1*0502 and DRB1*0807-DQB1*0402 were associated with a increased risk for persistent HPV infection. It was not observed a strong concordance between the associations verified for HPV prevalence/persistence and SIL, possibly due to the limited number of SIL specimens. A higher risk for SIL, independent of HPV infection, was observed for DRB1*0301 and DR12. DR4 and DQB1*0601 carriers showed a higher frequency of SIL and HSIL, respectively. A negative association between DQB1*0301 and HSIL was verified. Valine at position 86 of the DRβ chain was associated with reduced risks of HPV positivity and persistence, as compared to glycine carriers. However, valine carriers had a higher risk of SIL if transiently infected by HPV. We also analyzed an independent sample of patients with invasive cervical, and a protective effect was observed for DR3. On the other hand, DR4 and DR8/12 were associated with a higher risk for cervical cancer in this population. Our results suggest that HLA class II polymorphisms and pocket 1 profile are involved in clearance and maintenance of HPV infection and the risk of SIL and CCU, consistent with the hypothesis that genetic background is important in the natural history of HPV infections and associated lesions. We also analyzed lymphoproliferative responses against HPV16 E6 and E7 peptides, in patients with invasive cervical cancer. Lymphoproliferative responses were more frequent for E6 peptides than for E7 peptides. The responses were not restricted to a particular peptide, which is expected based on HLA variability observed among patients.
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Van, de Vuurst Victoria Paige. "Climate change and disease at the human-wildlife interface." Thesis, Virginia Tech, 2021. http://hdl.handle.net/10919/104158.
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Recent research has shown that climate change had and will likely continue to have impacts on biological processes, including the propagation of infectious and zoonotic diseases. Assessments of local level impacts at the human-wildlife interface are imperative for stakeholders and policy makers, and empirical review of such research is undoubtedly necessary to understand the current state of the field, gaps of knowledge, and to identify future lines of research. In that vein, this thesis focuses on the impacts of climate change on disease at the human-wildlife interface. Specifically, my thesis works to quantify the recent temporal and spatial distribution of empirical research linking climate change with changes in the burden of infectious diseases (Chapter 2). This retrospective scoping of the last five years of empirical research identified if, and to what extent, there are biases in the diseases, species, or geographic areas studied within this scientific field. My study revealed both geographic and topical biases within the scope of recent literature, with an overwhelming emphasis on vector-borne diseases in temperate areas. There was also unequal representation in publication demographics of authors and institutions with most research originating from well developed countries. As a proof-of-concept case study, my thesis provides an empirical assessment of the plausible climatic drivers of a wildlife-disease transmission risk in an understudied region (Chapter 3), which could function to fill some of the identified research gaps in Chapter 2. Therein, my work assessed the impacts of climate variation from the last century on the environmental suitability of the rabies host Desmodus rotundus (common vampire bat) in Latin America. Findings revealed that average and standard deviation of temperature were the most important drivers of D. rotundus geographic distribution according to species' records between 1901 and 2019. Nevertheless, high uncertainty was detected regarding the predictability of D. rotundus environmental suitability across the United States-Mexico border and in the Andes Mountains of Chile. The overall modeling efforts did, however, reveal a northward distributional shift of the rabies reservoir as a likely response to climate change. Together, studies contained in this thesis provide empirical, retrospective evidence that demonstrates the effects of climate change on the increased risk of disease transmission at the human-wildlife interface.Master of Science
Climate change is understood as the change in global or regional climate patterns, including variations of temperature and humidity factors beyond normal ranges, mostly attributed to increased levels of atmospheric carbon dioxide. Climate change is expected to influence many biological systems and presents an imminent threat to almost all organisms and geographic areas across the globe. Previous studies suggest that climate change will increase the burden of infectious diseases, including those originating from wildlife. This thesis aims to assess the availability of empirical evidence supporting the idea of a link between climate change and infectious diseases of wildlife origin. Chapter 2 examines recent scientific literature assessing climate change and infectious disease, and identifies biases in the diseases, species, and geographic areas commonly studied. This study found that literature generally focused on diseases transmitted by arthropods (e.g., insects, arachnids, or crustaceans) in temperate areas. There was little focus on diseases transmitted directly (e.g., via bites) or in non-temperate areas (e.g., tropics). Chapter 3 attempts to address issues detected in Chapter 2 by studying a directly-transmitted infectious disease in the tropics. More specifically, Chapter 3 assessed the impacts of climate variation from the last century on the distribution of the common vampire bat (Desmodus rotundus), which is a known rabies host in Latin America. Chapter 3 revealed that temperature variables were the largest drivers of common vampire bat distribution. Nevertheless, high uncertainty was detected regarding the vampire bat's ability to invade new areas such as the continental United States-Mexico border or the lowlands to the Andes Mountains in Chile. Together, studies contained in this thesis provide support for current and future research on the study of climate change as an amplifier for the risk of infectious diseases.
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朱祖順 and Cho-shun Chu. "A clinical, microbiological and radiological study of primary endodontic infections." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B38628788.
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Pogreba-Brown, Kristen. "Using Case-Case Study Designs to Study Foodborne Enteric Infections." Diss., The University of Arizona, 2013. http://hdl.handle.net/10150/293418.
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Case-control studies are the traditional ways in which foodborne enteric diseases are studied and outbreaks are investigated. This method has some significant limitations and biases for diseases with low efficiency reporting rates, such as Campylobacter, a common foodborne disease. Case-case methodologies have been explored for these studies but have been implemented without any clear strategy. This dissertation aims to first, determine the common risk factors for Campylobacter in Arizona using the traditional case-control study design, second, to systematically compare case-case studies to the more common case-control studies, and third, to simultaneously compare the results of a community outbreak of Campylobacter using both case-control and case-case study designs. Results from these studies identified some unique risk factors for routine Campylobacter infection in Arizona that will be used to enhance surveillance for the disease in the state. A systematic review of case-case studies used for enteric diseases found that there are specific recommendations that can be put into place in determining what comparison cases should be selected based on the primary aims and goals of the study. Finally, the results of the simultaneous case-case and case-control studies of a Campylobacter outbreak showed that these methods may work best in conjunction with one another and in doing so, the most accurate depiction of the source of infection can be determined.
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Novak, Daniel. "Improving the prevention of sexually transmitted infections (STIs) : a study using Chlamydia trachomatis as a model infection." Doctoral thesis, Umeå : Public Health and Clinical Medicine, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-692.
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Hobbs, Henriëtte Renée. "Preparation and evaluation of polymer microspheres for enhanced lateral flow immunoassay: the case study for malaria." Thesis, University of Cape Town, 2015. http://hdl.handle.net/11427/33228.
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We proposed that the development of a new high capacity polymer microsphere technology, termed ReSyn, could be developed as viable detection reagents for lateral flow technology. This body of work outlines the development of this new high capacity polymer microsphere technology for suitability to flow on lateral flow membranes, and highly specific biomarker detection for immunoassay development. Proof-of-concept was achieved using hCG (pregnancy biomarker) and validated for detection of pLDH and HRP2 as biomarkers of malaria. The sensitivity, stability and multiplex capability of these microspheres were further explored and compared against the current ‘gold' standard detection agent for lateral flow, colloidal gold. Malaria was selected as a suitable target for evaluation of the microsphere technology since it is considered to be a global epidemic that can benefit greatly from improved point-of-care diagnostics. Malaria affects almost half of the world's population and is responsible for causing approximately 655 000 deaths per annum in 2010, with 90% of these deaths occurring in Africa and 85% of these deaths occurring in children under 5 years of age (del Prado et al., 2014; Kokwaro, 2009; White et al., 2014; WHO, 2009). Febrile disease diagnosis at point-of-care is often based on symptomatic diagnosis rather than on the use of validated diagnostic technologies, and is considered one of the major contributing factors for the high morbidity and mortality rate of malaria (Chandler et al., 2008; Kain et al., 1998; Kokwaro, 2009). Improved diagnostic technologies, allowing for sensitive and accurate diagnosis at the point-of-care, could assist alleviating these problems through the improved management of disease (Bell et al., 2006). Lateral flow rapid diagnostic tests are the preferred method for point-of-care diagnostics in resource constrained areas but have several limitations including sensitivity and stability in resource constrained settings (Bell et al., 2006). Improvements in detection agents are seen as a viable approach to improving these features of diagnostic assays. The results of this study show that the polymer microspheres provide improved stability to immobilised antibodies, with potential for translation into improved stability for diagnostic assays in tropical malaria endemic regions. The polymer microspheres offered high specificity and comparable visual sensitivity to the market leader colloidal gold and is therefore considered as alternate detector agents in lateral flow assays. Additionally, the microspheres can be dyed various colours (red and blue in this study), allowing for specific and sensitive multiplex detection of multiple analytes in a single sample. This increases the versatility of the microspheres for lateral flow diagnostic application, and improves the interpretation of lateral flow diagnostic technology at the point-of-care.
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Scorza, Breanna M. "Interaction of human keratinocytes with Leishmania spp.: a comparative study of Leishmania infantum and Leishmania major." Diss., University of Iowa, 2017. https://ir.uiowa.edu/etd/5847.
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Leishmaniasis refers to the group of diseases caused by pathogenic protozoan parasites of the genus Leishmania. Nearly all human Leishmania spp. infections are initiated in mammalian skin through the bite of the phlebotomine sand fly vector. However, clinical manifestations vary greatly with infecting species. Leishmania major establish infection locally within the skin and cause chronic ulcerating skin lesions at the local cutaneous site of inoculation, in a syndrome known as Cutaneous Leishmaniasis (CL) Leishmania infantum parasites metastasize from the site of skin infection via unknown mechanisms, and establish infection within visceral organs usually without inducing skin pathology, resulting in the potentially fatal disseminated disease, Visceral Leishmaniasis (VL). Mouse studies suggest early responses at the skin infection site are critical determinants of subsequent adaptive immune responses in leishmaniasis, yet few studies address the role of keratinocytes, the most abundant immunoactive cell in the epidermis. We hypothesize that Leishmania infection causes keratinocytes to produce immunomodulatory factors that influence the outcome of infection.
Incubation of primary or immortalized human keratinocytes with L. infantum or L. major elicited dramatically different responses. Keratinocytes incubated with L. infantum significantly increased expression of pro-inflammatory genes IL6, IL8, TNF, and IL1B by RT-qPCR; whereas keratinocytes exposed to L. major did not. Similar to live parasites, L. infantum-derived exosomes induced more IL8 mRNA compared to control or L. major-derived exosomes. Western blotting confirmed NFkBp65 phosphorylation in keratinocytes exposed to L. infantum but not L. major. However, no evidence of L. major inhibition of TNF-induced NFkBp65 phosphorylation was observed in simultaneously treated keratinocytes. To examine whether keratinocytes influence proximal host cells, L. infantum-infected human monocytes were co-cultured with keratinocytes across a transwell membrane. These studies suggested L. infantum-exposed keratinocytes release soluble factors that enhance monocyte control of intracellular L. infantum replication. L. major-exposed keratinocytes had no comparable effect. These data suggest L. infantum and L. major differentially activate keratinocytes to release factors that limit infection in monocytes.
Microarray analyses performed on human keratinocytes exposed to either L. infantum or L. major promastigotes identified a limited number of transcripts increased by parasite exposure. Consistent with RT-qPCR observations, several inflammatory cytokine and chemokine genes were more strongly induced in L. infantum-exposed keratinocytes compared to L. major-exposed keratinocytes. Pathway analyses of genes induced by L. infantum-treated keratinocytes suggested that this interaction may induce neutrophil recruitment. Notably, AP1 transcription factor subunit genes were significantly down regulated in L. major-treated compared with L. infantum-treated or control keratinocytes. This suggests L. major may actively inhibits this keratinocyte activation, which might affect its ability to establish infection within host skin. In addition, ex vivo intradermal infection of human skin explants was explored as a method to compare keratinocyte responses to L. infantum or L. major in the context of whole skin tissue and the effects of vector salivary gland components are considered.
The response of keratinocytes found in these studies using L. infantum and L. major may give insight into the local host pathologic responses to different Leishmania species leading to visceralizing versus cutaneous manifestations to infection. We propose that Leishmania spp. elicit or evade a pro-inflammatory response by keratinocytes at the site of infection, generating a microenvironment uniquely tailored to each Leishmania species.
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White, Lisa Jane. "A theoretical study of the effects of immunity on infectious disease transmission." Thesis, University of Warwick, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.343535.
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Singh, Rajeshree. "Criminal liability for wilful HIV/AIDS infection: a comparative study." Thesis, Nelson Mandela Metropolitan University, 2012. http://hdl.handle.net/10948/d1012686.
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South Africa‘s high prevalence of HIV/AIDS coupled with a high crime rate and incidence of sexual violence necessitated the enquiry and study into the role of criminal law to address the wilful transmission of HIV.1 This study shows that criminal law can be used to punish offenders for wrongdoing and therefore finds application in the wilful transmission of HIV.2 The study distinguishes the dividing line between the justifiable use of criminal law and where use of the criminal law becomes discriminatory in nature and counterproductive to public health measures. The United Nations (hereinafter referred to as the UN) laid down guiding principles for countries to adopt when using the criminal law and stated that countries should use existing criminal law offences to prosecute intentional HIV infections.3 The South African Law Commission (hereinafter referred to as the SALC) endorses this approach. South Africa‘s use of the criminal law, in response to harmful HIV behaviour is in line with the UN recommendations as it uses the existing common law offences to prosecute the wilful transmission of HIV, namely murder, attempted murder and assault. Drawing from the writer‘s comparative study in Chapter Six below, South Africa, members of the Zimbabwean parliament, Canada, as well as the American Bar Association have all concluded that the use of specific HIV-related legislation creates some a form of stigmatization towards people living with HIV and is therefore not warranted. This study shows that criminal law has a role to play in the wilful transmission of HIV; however the creation of HIV specific legislation is not recommended and existing criminal law offences should be used to address harmful HIV related behaviour. Such an approach is in line with the guiding principles laid down by the UN and SALC.
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Penfold, Sonya. "A molecular biological study on Campylobacter pylori." Master's thesis, University of Cape Town, 1989. http://hdl.handle.net/11427/25731.
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C. pylori have been shown to be associated with gastritis and peptic ulceration, but the mechanism of their pathogenicity is unknown. Since a number of virulence factors are known to be plasmid mediated, it was decided to study the plasmids of C. pylori. A variety of techniques were used to establish the best method of plasmid extraction from C. pylori. The method of alkaline lysis as described by Birnboim and Doly was shown to give the most consistent results and the greatest plasmid yield. Plasmid DNA was found in 54% (26 out of 48) of the isolates examined and the plasmids varied in size from 3,4kb to greater than 137kb. The majority (21 out of 26) of isolates had unique plasmid profiles, but 5 isolates showed common ones. Three of these 5 isolates were studied in more detail. The evidence presented here suggests that all 3 plasmid bands visible in these three isolates were different conformations of the same plasmid which has a molecular weight of 6, 2 kilo bases. The plasmids appeared labile and covalently closed circular DNA was rarely isolated. Restriction enzyme digestion was done with a variety of enzymes, but only 3 of the enzymes used digested the DNA. EcoRI and HindIII partially digested the DNA, while Sau3A digested the plasmids completely, generating 2 fragments of 2,2kb and 2,4kb, and a number of smaller fragments. The DNA was shown to be methylated and the fragments generated by Sau3A digestion suggest that the plasmids may contain a repetitive element. Chromosomal DNA was also isolated and digested with a variety of enzymes. The chromosomal DNA restriction pattern was shown to be affected by methylation, which may be important when using restriction enzyme patterns to differentiate between strains. Plasmid restriction fragments were end-labelled to detect bands which were poorly visible by ethidium bromide staining. This technique was shown to be more sensitive than ethidium bromide staining of DNA, but the inability to obtain complete digestion of C. pylori DNA made it impossible to construct a restriction enzyme map of the plasmids. Hybridization experiments showed the plasmids of C. pylori to be related and was also used to detect bands which were not easily visible after ethidium bromide staining. Attempts were made to clone C. pylori DNA into pUC18 and pUC19, but no recombinant plasmids containing C. pylori DNA were obtained.
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Williams, Cheryl Sally-Anne. "Implementing an HIV/AIDS literacy programme in a grade 11 class: an action research study." Thesis, University of the Western Cape, 2006. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_3957_1255515298.
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This research study attempted to highlight an in-depth exploration of my own classroom practice as a teacher at a high school in the Western Cape. A key goal of this research study was the quest for professional development and the development of an HIV/AIDS literacy programme for curriculum development.
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Mideo, Nicole. "Integrating theory and experimentation in the study of malaria." Thesis, Kingston, Ont. : [s.n.], 2009. http://hdl.handle.net/1974/5093.
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Lo, Monique (Monique Chun-Ying) 1978. "Modeling and study of infectious disease : stochastic modeling for antibiotic resistance and treatment strategies." Thesis, Massachusetts Institute of Technology, 2001. http://hdl.handle.net/1721.1/68377.
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Thesis (M.C.P.)--Massachusetts Institute of Technology, Dept. of Urban Studies and Planning, 2001.Includes bibliographical references (leaf 46).
Antibiotic-resistant bacteria pose a serious threat to immuno-compromised individuals in Intensive Care Units (ICU). This study examines several cycling treatments (7,14,30,60,120,240-day cycle) and random fraction treatment (50-50,60-40,80-20,100-0) strategies in ICU and finds that no single strategy will outperform all others. Human, hospital and pathogen conditions such as admission/departure rate, transmission rate, drug application rate, and incoming patients' characteristics influence the selection of the optimal treatment strategy. Random fraction treatment is generally favored when admission/departure rate is large. Cycling treatment is generally favored when admission/departure rate is small. When transmission rates are high, longer cycle period are preferred. When transmission rates are low, random fraction treatments are preferred. For cycling treatments, longer cycle periods is associated with lower drug application rates whereas shorter cycle periods are associated with larger drug application rates.Antibiotic-resistant bacteria pose a serious threat to immuno-compromised individuals in Intensive Care Units (ICU). This study examines several cycling treatments (7,14,30,60,120,240-day cycle) and random fraction treatment (50-50,60-40,80-20,100-0) strategies in ICU and finds that no single strategy will outperform all others. Human, hospital and pathogen conditions such as admission/departure rate, transmission rate, drug application rate, and incoming patients' characteristics influence the selection of the optimal treatment strategy. Random fraction treatment is generally favored when admission/departure rate is large. Cycling treatment is generally favored when admission/departure rate is small. When transmission rates are high, longer cycle period are preferred. When transmission rates are low, random fraction treatments are preferred. For cycling treatments, longer cycle periods is associated with lower drug application rates whereas shorter cycle periods are associated with larger drug application rates.
by Monique Lo.
M.C.P.
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Lawson, Adam. "A study of the natural history of hepatitis C infection within a geographically determined population (Trent HCV study)." Thesis, University of Nottingham, 2012. http://eprints.nottingham.ac.uk/12477/.
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The epidemiology and natural history of Hepatitis C has been studied in a large geographically determined population (Trent HCV study). It has previously been suggested that patients with Hepatitis C and a persistently normal Alanine aminotransferase (PNALT) represent a group of patients with mild disease and at low risk of disease progression. Patients with PNALT were, therefore, compared to those with an elevated ALT. The majority of patients initially fulfilling the definition of a PNALT had an abnormal ALT within 3 years of follow-up. They also demonstrated similar rates of fibrosis progression as a sub-group of HCV infected patients with an elevated ALT who were re-biopsied prior to any institution of therapy. They, therefore, warrant the same consideration with regard to treatment. The morbidity and mortality associated with Hepatitis C with severe fibrosis was assessed in a group of patients with a liver biopsy demonstrating Ishak fibrosis stage 4. A worse prognosis than previously reported was observed for this patient population. Once decompensation develops, HCV infection is associated with a high mortality rate. Indicators of poor synthetic liver function and hypergammaglobulinaemia were important prognostic factors for mortality, while combination antiviral therapy was associated with improved survival. The majority of HCV infected patients (75%) diagnosed with hepatocellular carcinoma (HCC) were known to have cirrhosis at least 6 months prior to diagnosis of HCC and were, therefore, amenable to surveillance. There was a variable application of surveillance, however, and no significant improvement in survival was demonstrated. Age, duration of infection and immunoglobulin G levels were associated with an increased risk of HCC in cirrhotic patients in the univariate analysis. Achieving an SVR was associated with a reduced risk. No variable in cirrhotic patients was shown to be independently associated with HCC in the multivariate analysis. A comparison of disease progression and treatment outcome in White and Asian (Indian subcontinent) patients was made. Asian patients generally presented at an older age and with more severe disease on biopsy. The patient’s ethnic group was not associated with the likelihood of either an SVR or completion of therapy. Instead cirrhosis and a raised GGT were associated with a failure to achieve SVR in the multivariate analysis. The platelet count is a surrogate marker for the severity of liver fibrosis and correlates with the Ishak fibrosis stage. An analysis of factors associated with an SVR was performed. In the multivariate model, age at start of treatment was the only independent predictor of SVR in Genotype 1, while estimated duration of infection and Ishak stage were predictors in genotype 2/3 patients. The platelet count was not an independent predictor of SVR or completion of therapy.
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Walulu, Rosemary N. "Mothers living with HIV disease : a grounded theory study : a dissertation /." San Antonio : UTHSC, 2007. http://proquest.umi.com.libproxy.uthscsa.edu/pqdweb?did=1490071031&sid=2&Fmt=2&clientId=70986&RQT=309&VName=PQD.
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Dissertation (Ph.D.).--University of Texas Graduate School of Biomedical Sciences at San Antonio, 2007.Vita. Briscoe Library received only one copy of this dissertation. It is shelved in the Archives for safekeeping. Includes bibliographical references.
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Lambert, Tania. "The perceptions of grade eight and nine learners of a life skills programme on HIV/AIDS, sexually transmitted infections, rape and child abuse." Thesis, Nelson Mandela Metropolitan University, 2005. http://hdl.handle.net/10948/390.
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Worldwide millions of children are victims of neglect and physical and mental harm, including sexual abuse and exploitation. South Africa, however, is widely believed to have not only one of the highest incidences of rape in the world, but also one of the highest levels of Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS) transmission. With research findings showing that HIV and other Sexually Transmitted Infections (STIs) are rapidly increasing globally, young people are, and continue to be, at the forefront of the AIDS pandemic. Therefore, it is suggested that prevention programmes should be aimed particularly at the young. Schools have specifically been recognized as the setting for preventative Life Skills Programmes, having the potential to reach billions of children worldwide. The aim of this study is to explore and describe the perceptions of grade eight and nine learners with regard to the Life Skills Programme that focuses on HIV/AIDS and STI's, rape and child abuse education in the Port Elizabeth region. In order to fulfil the above aim, a qualitative study was undertaken within an exploratory descriptive approach. A non-probability sample of four schools was selected. Focus groups, utilising an unstructured interview, were used to gather qualitative data on the learners' perceptions of the Life Skills Programme. The focus groups consisted of 10 - 12 grade eight and nine learners who were selected using simple random sampling. The data was thematically analysed using Tesch's approach. The major findings of the present study, based on the six general themes, include the following: 1. Most of the learners perceived the educators, as well as the teaching methods utilised by the educators, positively. 2. Although the learners perceived the presenters of the Life Skills Programme positively, it was suggested that teachers, health care professionals, family members and peers should be involved in presenting the Life Skills Programme. 3. Learners reported various levels of comfort discussing different topics presented in the Life Skills Programme. 4. Learners of all the schools perceived the Life Skills Programme to be very relevant. 5. Learners recommended that more children, especially children from deprived communities, should be included in the programme. In addition, learners felt that counselling services should be available in conjunction with the Life Skills Programme. 6. Differences were noted in completing the first and the second questionnaire. Learners reported that they felt more comfortable completing the second questionnaire. They perceived the interviewing process positively.
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Dungu-Kimbenga, Baptiste. "Study on the effects of a natural Maedi visna virus infection on sheep productivity." Pretoria : [s.n.], 2009. http://upetd.up.ac.za/thesis/available/etd-01052007-100419/.
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Deitcher, Rebecca Ulman. "Health locus of control and HIV : a study of beliefs, attitudes, and high-risk behaviours among homosexual men attending a general medical clinic." Thesis, McGill University, 1993. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=39806.
Full textAbstract:
Acquired immunodeficiency syndrome (AIDS) remains an epidemic illness with no known cure. Survival time after infection with the human immunodeficiency virus (HIV), has been lengthened considerably. Rates of new infection among the at-risk male homosexual populations have decreased. Prevention is possible through effective, targeted interventions. This study is an exploration of the role or health locus of control, an individual difference construct from the area of social learning theory, in the maintenance of health-oriented behaviours, co-risk indicative behaviours, and high-risk behaviours in a population of adult male homosexuals attending a general medical clinic. The findings result in distinctly different past histories and present patterns of homosexual behaviours among the two serostatus subpopulations. Low internal expectancy of control over health repeatedly relates in distinctive patterns with the areas of level of happiness, condom usage, and hish-risk sexual behaviours. High internal expectancy of control relates significantly to knowledge-related variables. The physician plays a pivotal role as the source of useful information in this at-risk population. The study population as a whole reports accurate knowledge about HIV and AIDS. The men have reduced high-risk behaviours, increased safer sexual behaviours, and implemented the changes advocated. Serostatus differentiates for many high-risk behavioural patterns. There remains a small core of men among the study participants who continue to participate in high-risk sexual behaviours.
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Ching, Chi-yun Johannes. "Study of host genetic susceptibility to severe acute respiratory syndrome (SARS) infection." Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B40687648.
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Younus, Muhammad. "Risk factors for sporadic non-typhoidal Salmonella infections in Michigan children a population-based case-control study /." Diss., Connect to online resource - MSU authorized users, 2008.
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