Dissertations / Theses: 'Tb'

1

MacNaughton, April Dawn. "Tuberculosis (TB) storytelling : improving community nursing TB program delivery." Thesis, University of British Columbia, 2015. http://hdl.handle.net/2429/56178.

Full text

Abstract:

This study explores the effectiveness of the traditional First Nations practice of storytelling as a tool in improving Community Health Nurse (CHN) continuing education, regarding tuberculosis (TB) programming in First Nations communities. The first part of this study involves a critical analysis of literature regarding the evolution of Canada’s First Nations policies and health care, and the use of storytelling as a learning tool in Western and First Nations contexts. Informed by critical social justice as a theoretical lens, and decolonising perspectives in health care, the analysis of the literature focuses on (a) shifting factors and societal values shaping the evolution of health care policy and regimes in First Nations health, and (b) the use of storytelling as an educational tool for CHNs working in First Nations communities. The analysis indicates that generations of inequities have resulted in First Nations mistrust of the Western health care system and a widening gap between the health status of First Nations and that of the broader Canadian population. The analysis also reveals that storytelling is an essential component of traditional First Nations education. Finally, the literature shows that there is increasing recognition by current health care policy makers that narrowing the gap in health outcomes requires that First Nations health care programming reflects First Nations input and community needs. The second part of this study evaluates the use of storytelling in CHN TB continuing education. TB continuing education sessions for CHNs included first person accounts by First Nations Elders, as part of the TB Tapestries Project, after which 70 CHNs were invited to provide written feedback. Thematic analysis of this feedback reveals increased appreciation for First Nations traditional storytelling as an important tool in provision of First Nations health care; recognition of the effectiveness of storytelling compared to other teaching methods; and a desire to change future TB programming by including storytelling. Based on the analysis of literature and CHN responses to the TB continuing education sessions, the primary recommendation of this study is to incorporate storytelling into TB education sessions for CHNs and broader health care programming for First Nations communities. Applied Science, Faculty of Nursing, School of Graduate

APA, Harvard, Vancouver, ISO, and other styles

2

Dinic, Lana. "Molecular Diagnosis of TB and MDR-TB in HIV-Coinfection in Nigeria." Thesis, Harvard University, 2012. http://dissertations.umi.com/gsas.harvard:10387.

Full text

Abstract:

Tuberculosis (TB) is the most common opportunistic infection in HIV-infected patients and the emergence of drug-resistant tuberculosis (DR-TB) is a growing problem in resource-limited settings (RLS). TB diagnosis in most RLS still depends on smear microscopy for acid-fast bacilli (AFB) while adequate infrastructure for testing drug sensitivity is unavailable. However, molecular diagnostics that detect Mycobacterium tuberculosis (Mtb) DNA and its genetic markers of drug resistance were recently developed. In this thesis I describe the use of a molecular diagnostic, Genotype MTBDRplus, for characterizing DR-TB and patterns of tuberculosis-like infection in two cities in south-west and north-central Nigeria. I found high rates of DR-TB in Nigerian HIV-infected individuals (9.3% for RIF or INH) with significantly different amounts by location (18.18% in south-west vs. 3.91% in north-central Nigeria, p=0.01). RIF resistance, indicative of MDR-TB, was found in 5.52% treatment-naïve patients, far exceeding the WHO predictions (0-4.3%). Furthermore, RIF resistance was genetically distinct, suggesting location-specific transmission of drug resistance (p=0.04). Genotype MTBDRplus correctly identified the drug-resistant samples compared to sequencing in 96.8% of cases. Mtb was confirmed in 56% of patients and was less likely to be found in patients on ART, while controlling for other relevant demographic characteristics (OR 0.29, P=0.02). Only abnormal respiratory findings on auscultation and the direct sputum smear grade greater than 3/100 were significant predictors of Mtb infection (OR 3.28, P=0.03; OR 6.40, p<0.01 respectively). Concentrated sputum smear was not significantly correlated with Mtb infection, except at the highest grades (>2+). Furthermore, in 49% of samples that were not confirmed for Mtb other actinomycetes were found: atypical Mycobacteria (ATM), Rhodococcus spp., Nocardia spp., Corynebacterium spp. I conclude that concentrated sputum AFB smears may misidentify bacteria as Mtb in a subset of HIV-infected patients. These individuals may have a different, even uncharacterized, actinomycete infection in the respiratory tract. Furthermore, total DR-TB in HIV-infection is high and transmission of DR-TB in HIV-infected patients in Nigeria is higher than estimated by the WHO. Molecular diagnostics are a rapid method for identifying Mtb and monitoring DR-TB, and can guide appropriate treatment decisions for respiratory infections in RLS with a high HIV burden.

APA, Harvard, Vancouver, ISO, and other styles

3

Kajunguri, Damian. "Modelling the impact of TB superinfection on the dynamics of HIV-TB coinfection." Thesis, Stellenbosch : University of Stellenbosch, 2009. http://hdl.handle.net/10019.1/4070.

Full text

Abstract:

Thesis (MSc (Mathematics))--University of Stellenbosch, 2009. ENGLISH ABSTRACT: In this thesis, a mathematical model describing the interaction between HIV and TB in the presence of TB superinfection is presented. The model takes into account two strains of Mycobacterium tuberculosis (MTB), where one strain is drug-sensitive and the other is resistant to at least one of the first-line anti-tuberculosis drugs. The impact of TB superinfection on the incidence and prevalence of TB in HIV-negative and HIVTB coinfected individuals is evaluated. Various control measures such as condom use, antiretroviral therapy, isoniazid preventive therapy and increased TB detection are studied using this model. Numerical results show that TB superinfection increases the prevalence and incidence of TB and its impact is more in HIV-negative than HIV-TB coinfected individuals. The results also show that TB superinfection promotes strain coexistence and increases the associated HIV mortality. Increased condom use was found to have a high positive impact towards the control of the two epidemics. Antiretroviral therapy decreases the TB notification rate and its impact on HIV prevalence increases with the coverage and efficacy. Isoniazid preventive therapy has a clear effect on the TB prevalence. Finally, increased TB detection was found to have a less impact on the TB incidence in HIV-TB coinfected individuals AFRIKAANSE OPSOMMING: In hierdie verhandeling word ´n wiskundige model vir die interaksie tussen MIV en TB, in ´n situasie met TB superinfeksie voorgelˆe. Die model neem twee variante van TB in ag. Een van die variante is sensitief vir MTB behandeling, terwyl die ander weerstandig is vir ten minste een van die eerste-linie TB behandenings. Die impak van TB superinfeksie op die insidensie and prevalensie van TB in MIV negatiewe en MIV-TB ko-ge˜ınfekteerde individu word ondersoek. Veskeie beheer maatreels soos kondoom gebruik, anti-retrovirale behandeling (vir MIV) en isonazid voorkomende behandeling en verhoodge TB deteksie (vir TB) word ondersoek. Numeriese resultate wys TB superinfeksie verhoog die prevalense en insidensie van TB en dat dit ´n groter bydrae maak by MIV negatief as by MIV-TB ko-geinfekteerde individu. Die resultate wys veder TB superinfeksie promofeer variant kohabitasie en verhoog MIV verwante mortalitieit. Verhoogde kondoom gebruik is gevind om ´n positiewe bydrae te maak tot die beheer van beide epidemies. Anti-retrovirale terapie verlaag die TB aanmeldings koers en die impak van ART verhoog saam met ´n verhoging in die dekking en effektiwiteit daarvan. Voorkomende behandeling het ´n beduidende impak op TB prevalensie. Ons vind dat TB deteksie ´n beperkte impak maak op TB insidensie by MIV-TB ko-geinfekteerde individu

APA, Harvard, Vancouver, ISO, and other styles

4

FRANCISCO, Samuel Nuno Furtado da Conceição. "Aplicação de sistemas moleculares na detecção rápida de MDR-TB e XDR-TB." Master's thesis, Instituto de Higiene e Medicina Tropical, 2011. http://hdl.handle.net/10362/5625.

Full text

Abstract:

Mycobacterium tuberculosis é o agente etiológico da tuberculose em humanos e segundo as estimativas da Organização Mundial da Saúde, um terço da população mundial está infectada com esta bactéria, calculando-se que no ano de 2008 aproximadamente 9,4 milhões de pessoas contraíram tuberculose activa. Associada a esta tendência, encontra-se o aumento alarmante da incidência de tuberculose resistente aos antibióticos, mais propriamente da tuberculose multirresistente e extensivamente resistente. Nesta Dissertação estudaram-se três sistemas de detecção molecular (INNO-LiPA Rif. TB, Innogenetics, Ghent, Bélgica, MTBDRplus e MTBDRsl, GenoType, GmbH, Nehren, Alemanha), que permitem detectar o complexo M. tuberculosis e as mutações mais comuns associadas à resistência aos antibióticos de primeira e segunda linha. Para o efeito, na primeira parte do trabalho os três sistemas em estudo foram testados em 21 isolados clínicos pertencentes à colecção do Laboratório de Micobactérias do Instituto de Higiene e Medicina Tropical (IHMT, UNL), com o propósito de avaliar a sua capacidade para identificar o complexo M. tuberculosis e detectar mutações ligadas à resistência aos fármacos de primeira e segunda linha. Na segunda parte do trabalho, os sistemas INNO-LiPA Rif. TB e MTBDRplus foram testados em 33 amostras respiratórias com baciloscopia positiva, com o propósito de aferir a “performance” destes sistemas para a detecção directa de tuberculose multirresistente em amostras respiratórias. Na primeira parte do trabalho os três sistemas em estudo apresentaram elevada sensibilidade na identificação do complexo M. tuberculosis em culturas, bem como na detecção de mutações ligadas à resistência aos antibióticos de primeira linha, com excepção do etambutol. No que diz respeito à detecção da resistência aos antibióticos de segunda linha, não foi possível calcular os valores de sensibilidade e especificidade. Na segunda parte do trabalho, o INNO-LiPA Rif. TB demonstrou ser o sistema mais robusto para a análise directa de amostras respiratórias com baciloscopia positiva, para um diagnóstico precoce de tuberculose e detecção de resistência à rifampicina. O MTBDRplus não se mostrou uma alternativa viável ao INNO-LiPA Rif. TB, pois apresentou baixa sensibilidade para a identificação do complexo M. tuberculosis e vários problemas no passo de amplificação. O MTBDRsl não foi testado, por não ter sido detectada nenhuma amostra multirresistente. Mycobacterium tuberculosis is the etiologic agent of tuberculosis in humans and, according to the World Health Organization, one-third of the world’s population is infects with this bacteria, with an estimated 9.4 million incident cases of tuberculosis globally in 2008. Associated with this alarming trend is a frightening increase in the incidence of M. tuberculosis resistant to antibiotics, more specifically multidrug-resistant tuberculosis and extremely drug-resistant tuberculosis. In this Thesis, we studied three molecular detection systems (INNO-LiPA Rif. TB, Innogenetics, MTBDRplus and MTBDRsl, GenoType), which allow the molecular identification of the M. tuberculosis complex and the detection of mutations most often associated with antibiotic resistance. In the first phase of the work the three systems were tested in 21 clinical isolates belonging to the collection of the Mycobacteria Laboratory of IHMT, UNL, with the aim to assess their ability for identifying the M. tuberculosis complex and to detect mutations related to the resistance to first and second line antibiotics. In the second stage of the study, the INNO-LiPA Rif. TB and the MTBDRplus were tested in acid-fast positive respiratory specimens, to assess their performance to detect directly M. tuberculosis and mutations related to rifampicin resistance in these specimens. In the first part of the work the three systems showed high sensitivity for the identification of the M. tuberculosis complex and for detection of resistance to first line antibiotics, except for ethambutol. Regarding the detection of resistance in second line antibiotics, we could not calculate the sensitivity and specificity. In the second part of the work the INNO-LiPA Rif. TB assay proved to be the system of choice for use directly in acid-fast positive respiratory specimens in the early diagnosis of tuberculosis and the detection of rifampicin resistance. The MTBDRplus was not a good alternative to the INNO-LiPA Rif. TB due to its low sensitivity in the identification of the M. tuberculosis complex and the occurrence of several problems in the amplification step. The MTBDRsl was not used because no multidrug resistant samples were detected.

APA, Harvard, Vancouver, ISO, and other styles

5

Sillah, Dolly Jackson. "Early changes in T cell responses in TB patients during chemotherapy for TB." Thesis, London School of Hygiene and Tropical Medicine (University of London), 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.536815.

Full text

APA, Harvard, Vancouver, ISO, and other styles

6

Bistline, Kathryn Lou. "Does the inclusion of the cost and burden of adverse drug reactions associated with drug-resistant TB treatment affect the incremental cost-effectiveness of new treatment regimens? A case study from the introduction of bedaquiline in South Africa National TB Programme." Doctoral thesis, University of Cape Town, 2018. http://hdl.handle.net/11427/28441.

Full text

Abstract:

South Africa has one of the world’s highest burdens of TB, HIV/TB co-infection, and drug-resistant TB. Second-line TB treatment is less effective, more expensive, and more toxic than treatment for drug-sensitive TB. Nearly 1 in every 5 persons who starts treatment for drug-resistant TB in South Africa will die; 1 in every 3 persons who survives treatments experiences permanent, profound hearing loss. For decades there was little progress in TB research, however, and so treatment with old regimens continued despite safety concerns. In 2012 the US and European regulatory authorities approved a new drug, bedaquiline, but only for treatment in cases with no other options. In 2015, the South African Medicines Control Council approved bedaquiline for drug-resistant TB, but only a limited number of doses were approved in the 2016/2017 annual budget and the focus, again, was only for the patients who had no other options. In order to inform policy makers in planning and budgeting for drug-resistant TB treatment, the aim of this thesis was to determine whether the simple calculation that bedaquiline was too expensive relative to standard regimens using kanamycin was too simple. Particularly, given the high burden of adverse drug reactions (ADR) associated with kanamycin, would the inclusion of the cost and burden of ADR affect the incremental cost effectiveness ratio of a new treatment regimen where bedaquiline replaces kanamycin? Analysis of the national drug-resistant TB case register showed that mortality during second-line treatment was early, primarily in the first 6 months of treatment, even when patients do not have extensive drug resistance. HIV-positive patients not on anti-retroviral therapy (ART) at initiation of drug-resistant TB treatment have the highest risk of mortality. The high early mortality is a real risk that clinicians have to balance when deciding to initiate ART and effective second-line TB treatment both as quickly as possible. Daily injections coupled with taking more than 10 pills each day are a heavy burden for patient compliance, but also pose concerns in terms of overlapping and compounding toxicities; this burden was confirmed through a meta-analysis of the pooled frequency of adverse events among cohorts with at least 25% of the patients HIV-positive. A competing risk analysis of a cohort of drug-resistant TB patients from Johannesburg – addressing the reality that patients may not have experienced an ADR because they died rather than because they were at lower risk – indicated that HIV-infected patients who are not yet stable on ART and second-line TB treatment are at the highest risk of ADR. A Markov model built and parameterized using the data from the South African national TB programme indicates that bedaquiline for all drug-resistant TB led to a small gain in effectiveness at a cost that was under the costs of the drug itself, due to savings from daily injection visits. While cost-effective, it was not clear that South African policy makers needed to move beyond the offer of bedaquiline for patients with extensive drug resistance. However, the calculation, and the decision point, were different once the costs and disability associated with ADRs was included in the analysis. Bedaquiline-based regimens offer a cost-saving and more effective alternative to an injection-based regimen for drug-resistant TB patients treated in the public sector in South Africa.

APA, Harvard, Vancouver, ISO, and other styles

7

Denis, Marie F. "Extrapulmonary tuberculosis in HIV-positive and HIV-negative children in Haiti : a hospital-based Investigation." [Tampa, Fla] : University of South Florida, 2005. http://purl.fcla.edu/usf/dc/et/SFE0001404.

Full text

APA, Harvard, Vancouver, ISO, and other styles

8

Brent, Andrew. "The Kilifi Improving Diagnosis and Surveillance of Childhood TB Study : the KIDS TB Study." Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/14399.

Full text

Abstract:

Improving diagnosis and surveillance of childhood TB are key research priorities. We established intensified case finding and state of the art TB diagnostics to investigate the performance of clinical and laboratory tools for childhood TB diagnosis at 2 hospitals in Kenya. We estimated the community incidence of childhood TB using a continuous demographic surveillance survey and detailed surveillance sensitivity analysis. 2041 children were investigated for suspected TB. 70 (3.4%) had bacteriologically confirmed TB, 63 (3.1%) had clinically highly probable TB, and a further 144 (7.1%) were treated for TB based on their clinical presenting features. 107/133 (80%) confirmed/highly probable TB (CHPTB) cases had pulmonary TB. CHPTB was associated with HIV infection (OR 2.1, 95% CI 1.3-3.2), malnutrition (1.5, 1.0-2.1) and close TB contact (5.7, 3.8-8.5). The population attributable fraction of a known close TB contact was 38.8-52.5%. The estimated community incidence of CHPTB locally and nationally was 46 and 83 per 100,000 per year, respectively. The performance of published clinical diagnostic tools varied widely, but the accuracy of all was limited. We derived and independently validated a simple KIDS TB Score that ruled out TB in 2/3 suspects with 98.8% negative predictive value, stratifying other children into groups of increasing risk. Bacteriological yield was highest for the Mycobacterial Growth Inhibitor Tube (MGIT) method (sensitivity 34%, 29-39%, among CHPTB patient samples), and lower for the Microscopic Observation Drug Susceptibility (MODS) assay (30%, 24-35%). The study provides the first comprehensive description from the region of the clinical spectrum of childhood TB, and the only prospective incidence estimates. It suggests up to half of all cases are potentially preventable by implementing current recommendations for isoniazid chemoprophylaxis. The diagnostic performance of clinical and laboratory methods should inform development of future clinical guidelines and laboratory capacity.

APA, Harvard, Vancouver, ISO, and other styles

9

Wasuna, Antonina. "Repositioning fusidic acid for tuberculosis: semi-synthesis of analogues and impact of mycobacterial biotransformation on antibiotic activity." Doctoral thesis, University of Cape Town, 2018. http://hdl.handle.net/11427/28154.

Full text

Abstract:

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is one of the leading causes of death globally, especially in low and middle-income countries. TB is primarily a curable disease, with chemotherapy predicated on a combination of four drugs. The increase in multiple forms of drug-resistant TB is a major cause for concern, underpinning the importance of a continuous pipeline of new anti-TB agents. Drug repositioning - that is, the optimization of existing drugs for new therapeutic indications - has shown promise in expanding the therapeutic options for TB chemotherapy. Fusidic acid (FA), a natural product-derived antibiotic, has modest in vitro antimycobacterial activity. Through a multi-disciplinary approach combining aspects of chemistry and biology, this study investigated the pharmacological and physicochemical properties of FA that might be exploited for optimization of FA as a lead compound for TB drug discovery. FA is a weak carboxylic acid, and it was hypothesised that the carboxylic acid moiety limits its permeation of the complex mycobacterial cell wall. Therefore, this study aimed to identify novel FA analogues with improved permeation properties and designed to act as potential prodrugs. By modifying the C-3 hydroxyl and the carboxylic acid moiety, alkyl and aminoquinoline derivatives were covalently fused to FA through ester and amide coupling reactions to generate hybrids and/or potential prodrugs.

APA, Harvard, Vancouver, ISO, and other styles

10

de, Jager Veronique Rejean. "Trends in the presenting clinical profile of patients with pulmonary tuberculosis in the Western Cape, 1991 - 2009." University of the Western Cape, 2017. http://hdl.handle.net/11394/6455.

Full text

Abstract:

Magister Public Health - MPH (Public Health) Over the past two decades, despite a growing tuberculosis (TB) epidemic, the South African health system and National TB Programme (NTP) have taken significant steps to ensure improved clinical awareness, early diagnosis, prompt treatment initiation and follow-up of treatment outcomes in cases of TB. The effects of these programmatic measures over time on changes in the severity of disease and presenting clinical profile of patients with pulmonary TB have not been studied. Doing so may provide another window on the impact of TB control initiatives in South Africa.

APA, Harvard, Vancouver, ISO, and other styles

11

Wanyama, Barasa Alex. "Determinants of TB treatment adherence among patients on anti-TB treatment in Tororo District, Uganda." University of the Western Cape, 2017. http://hdl.handle.net/11394/6066.

Full text

Abstract:

Magister Public Health - MPH (Public Health) To address this challenge, our study was to ascertain the extent of poor adherence to anti-TB treatment, to describe the demographic factors of patients on anti-TB treatment, to investigate the factors associated with poor adherence to anti-TB treatment in Tororo district, and to make respective recommendations to improve adherence to anti-TB treatment in order to contribute to the reduction of the TB burden in the world.

APA, Harvard, Vancouver, ISO, and other styles

12

Trottier, Danielle. "Mécanismes de transfert d'énergie Eu²⁺ - Tb³⁺ et Ce³⁺ - Tb³⁺ dans des fluorures de type KYF." 63-Aubière : Impr. U.E.R. Sci, 1986. http://catalogue.bnf.fr/ark:/12148/cb361103639.

Full text

APA, Harvard, Vancouver, ISO, and other styles

13

Kakili, Tuwilika. "Factors that contribute to treatment defaulting amongst tuberculosis patients in Windhoek district, Namibia." Thesis, University of the Western Cape, 2010. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_2049_1363356699.

Full text

Abstract:

Background: Tuberculosis (TB) is a resurgent disease in many parts of the world, fuelled by HIV/AIDS and poverty. According to WHO, over two billion people were estimated to be infected by TB globally, 9.4 million new cases of TB were reported, while about 1.7 million people were estimated to have lost their lives to TB in 2009 (WHO, 2010). The&nbsp global defaulter rate for TB was estimated at about 9% in 2007 (WHO, 2007). With Africa remaining the global epicentre of the TB epidemic, the epidemic in Sub-Saharan Africa,&nbsp one of the worst affected areas in the world, shows no evidence of decline (WHO, 2008). According to the 2009 MOHSS annual report, 1300 people lost their lives to TB in&nbsp Namibia (MOHSS, 2010). The introduction of TB treatment saves many lives globally. However, despite this effort, TB patients have been reported to default treatment in many&nbsp parts of the world including Namibia. Namibia reported a defaulter rate of 10% above the national target of less than 5% (Maletsky, 2008). Aim: This study aimed to investigate&nbsp the factors that contribute to treatment defaulting amongst TB patients at a major health centre in Windhoek district, Namibia. Methodology: A descriptive qualitative study using&nbsp in-depth interviews was conducted among ten TB defaulters. Key informant interviews were also conducted with the two TB nurses based at the health centre. Eligible&nbsp participants were purposively selected. A thematic content analysis of transcribed data was conducted where themes related to patient&rsquo s experiences of the illness socio- economic community, family, cultural and religious as well as health system factors were drawn out. Results: The study results indicate that defaulting TB treatment is a big challenge to TB management. The reasons for defaulting given by respondents were complex and included patient factors such as medication related factors, lack of knowledge and information as well as alcohol abuse. The findings also revealed unemployment as a major socio-economic factor that contributes to defaulting. In addition, the study shows that community, family, religious and cultural factors such as poor family support, work-related factors and religious and cultural beliefs have an influence on defaulting. Accessibility to health care services, sharing of the TB department with ART patients and attitudes of health workers were identified as health service&nbsp factors that influence treatment defaulting. This study also highlights the relationship between some of these factors. Conclusion: The study concludes that no single factor contributed to treatment defaulting amongst TB patients in the selected health centre in&nbsp Windhoek district and this concurred with the literature. There are many different factors at different levels that have an influence on TB treatment defaulting. An interrelationship between personal, socio- economic, community, family, religious and cultural as well as health services- related factors was evident What makes it more complex is that these&nbsp factors also impact on each other and therefore a holistic approach in the management of TB is required to address these factors. Recommendations based on the findings of the&nbsp study are made.

APA, Harvard, Vancouver, ISO, and other styles

14

Deffur, Armin. "The transciptomic landscape of HIV-TB." Doctoral thesis, University of Cape Town, 2013. http://hdl.handle.net/11427/3377.

Full text

Abstract:

Includes abstract. Includes bibliographical references. The thesis consists of four main parts. In Part 1 of this thesis I provide a broad overview of HIVTB with an emphasis on systems approaches followed by an overview of a systems-level study aiming at addressing hypotheses relating to transcriptional differences in active tuberculosis and HIV-1 infection, measured in blood and the site of disease in tuberculous pericarditis. The final chapter in this part describes the methods used to generate and analyse the systems-level data, with emphasis on microarray data generation and analysis. Part 2 first presents analysis of transcriptional data generated by RT-PCR at the site of disease compared to blood in study subjects with tuberculous pericarditis, with results showing clear evidence of transcriptional differences between compartments. A Technical Results chapter then provides an overview of the microarray data, and an analytic paradigm based on sample embedding in high-dimensional phenotype space is developed. I then assess the overall quality of the dataset and exclude large-scale systematic bias, while comparison of the IMPI-MA data to exiting TBtranscriptomic data shows a close match. Part 2 concludes with a description of a comprehensive analytic framework developed for the IMPI-MA data. Part 3 presents the results of the analytic pipeline as applied to the transcriptional response in blood to active tuberculosis in an HIV-1 uninfected population. A signature of active tuberculosis is described, and deconvolution analysis finds significant NK cell activation in active tuberculosis. Cell-type specific differential expression identifies CD4 T cells, NK cells and neutrophils as the most likely contributors to the overall “signature” of active tuberculosis. Weighted gene co-expression network analysis reveals multiple modules, whose expression is shown to be differentially regulated based on disease category. Part 4 summarises the results of analysing contrasts in three main contexts: tuberculosis, HIV-1 infection and compartment. Two novel results are presented: Firstly, NK cells are shown to be functionally downregulated at the site of disease, suggesting a possible defence mechanism by M. tuberculosis, and secondly, large-scale metabolic pathway dysregulation at the site of disease, possibly favouring M. tuberculosis, is demonstrated. Part 5 concludes the thesis with a summary and outlines future work.

APA, Harvard, Vancouver, ISO, and other styles

15

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

Full text

Abstract:

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

APA, Harvard, Vancouver, ISO, and other styles

16

Mabhula, Amanda N. "Investigating permeation of anti-mycobacterial agents in Mycobacterium tuberculosis and M. tuberculosis-infected macrophages in vitro as a model for early stage tuberculosis drug discovery." Doctoral thesis, Faculty of Science, 2021. http://hdl.handle.net/11427/33768.

Full text

Abstract:

Tuberculosis (TB) is the leading cause of death due to a single infectious disease and remains a major threat to global public health. The increasing emergence of multi-drug resistance to current anti-TB drugs, exacerbated by the long treatment duration, highlights the need for new effective treatments or strategies to shorten the treatment duration, improve patient adherence and curb the alarming rates of resistance. A key challenge to current strategies employed in the development of anti-TB drugs is the complexity in TB disease pathology which presents as a wide spectrum of lesions in patients presenting with the disease. These lesions occur at different anatomical loci in the same individual and at different stages as the disease progresses. In addition, the interaction between the causative agent, Mycobacterium tuberculosis, and its obligate human host induces physiologic and metabolic changes in the infecting bacillus that are specific to each lesion compartment, and dynamic. This is likely to influence M. tuberculosis susceptibility to antibiotic treatment and, consequently, affect treatment duration and possibly the development of drug resistance. A major limitation in current strategies to address this problem is translation of in vitro compound potency to in vivo efficacy. To reach the target site, a drug must first distribute and accumulate in the lesion microenvironments where bacteria reside: the macrophage host cell and the caseum. This thesis focused on the development of an in vitro infection model that could be used to predict drug penetration into M. tuberculosis-infected macrophages. Of particular interest was the extent to which host intracellular drug concentrations translate into effective antimycobacterial activity. To this end, the thesis comprised three key aspects: (i) characterization of physicochemical properties, antimycobacterial activities and M. tuberculosis-mediated metabolism of selected antiTB compounds; (ii) determination of intracellular drug permeation in resting, activated and foamy macrophages; and (iii) determination of the correlation (or not) between intracellular drug concentration and effective M. tuberculosis growth inhibition. The highly lipophilic natural product, fusidic acid (FA), its known human metabolite, 3-ketofusidic (3-ketoFA or GKFA37), and two C-3 alkyl esters (GKFA16 and GKFA17) as FA prodrugs were utilized in the study. In addition, another chemical class, the less lipophilic benzoxazole-based oxime derivatives were also investigated. Moxifloxacin (MXF), levofloxacin (LVF), bedaquiline (BDQ), rifampicin (RIF) and clofazimine (CFZ) were included for reference as known anti-TB drugs with varying lipophilicities. In chapter 2, FA and derivatives showed potent antimycobacterial activity (~1 µM) with selectivity indices (SI) >20 against the THP-1 macrophage cell line. Predicted artificial membrane permeability assay (PAMPA) results suggested that FA and derivatives would readily permeate the cell membrane. M. tuberculosis metabolized the C-3 alkyl-ester prodrug GKFA17 to form both FA and 3-ketoFA, with complete hydrolysis of the prodrug. FA was metabolized to 3-ketoFA, but the low levels of the metabolite suggested that another unidentified metabolite, presumed to be 3-epifusidic acid (3-epiFA), was formed. In vitro assays revealed that the potent benzoxazole-based oxime carbamates (PMN1-201, PMN1-136 and PMN2-09) were rapidly hydrolyzed by M. tuberculosis and were also susceptible to spontaneous degradation in media, forming the poorly active corresponding free oximes (PMN1-199, PMN1-135 and PMN1-157). In chapter 3, the in vitro macrophage drug uptake assay showed that FA C-3 alkyl prodrugs, GKFA16 and GKFA17, accumulated in significantly higher amounts in resting macrophages in comparison to FA and GKFA37. Accumulation of MXF was comparable to the least accumulated FA derivative, GKFA37, and showed steady state intracellular concentrations over a 6-day period. While GKFA16 and GKFA17 showed continued increasing accumulation, intracellular concentrations of FA and GKFA37 decreased after 48 hours, suggesting a likely susceptibility to macrophage efflux. In infected macrophages, the presence of intracellular bacteria or increasing bacterial burden did not affect the host cell ability to accumulate the drugs. FA and derivatives exhibited bacteriostatic inhibition of intracellular mycobacterial growth. MXF showed a potent bactericidal effect, reducing intracellular bacterial counts significantly at 10x MIC, with complete sterilization at 50x MIC even though MXF accumulation was significantly less than that of FA alkyl esters. These results suggested that both the inherent activity of a compound and ability to accumulate within host cells drive cellular efficacy. Given that the C-3 alkyl ester prodrugs accumulated at significantly higher concentrations than FA and GKFA37, this demonstrates the limitations of this assay in ascertaining the impact of intracellular concentration on drug efficacy for bacteriostatic drugs while highlighting its ability to correlate drug penetration and intracellular activity for cidal drugs. The prodrug GKFA17 was shown to undergo metabolism in resting host cells and during infection to form FA and then 3-ketoFA. Therefore, the prodrug strategy could be used to increase intracellular exposure of FA as GKFA17 showed superior macrophage accumulation. Benzoxazole-based oxime carbamates and their corresponding free oximes failed to accumulate in host macrophages and this was corroborated by their failure to control host cell bacterial growth despite the potent in vitro activity against M. tuberculosis of the carbamates, suggesting that they are poorly permeable. Chapter 4 investigated drug permeation in different macrophage phenotypes known to exist in the granuloma during TB disease, including foamy and activated macrophages. The activation state of the host cell did not affect the ability to accumulate anti-TB drugs such as RIF and BDQ. However, FA and its prodrug GKFA17 were significantly reduced in M1 activated macrophages. Despite the significantly reduced intracellular concentration, activated macrophages treated with FA and derivatives showed superior intracellular M. tuberculosis growth inhibition, suggesting that macrophage activation potentiates the activity of these compounds. In order to assess the effect of foamy macrophage lipid bodies (LBs) on drug uptake and intracellular localization, oleic acid-induced foamy macrophages were treated with selected antiTB drugs and experimental compounds. FA and derivatives showed early increased accumulation in foamy cells compared to resting macrophages, while MXF, BDQ and RIF levels were not significantly changed. Intracellular:extracellular (I/E) ratios increased with increase in lipophilicity, with FA C-3 alkyl prodrugs exhibiting the highest I/E ratios of >100. Despite exhibiting increased foamy macrophage concentrations, FA and derivatives exhibited a similar reduction (bacteriostatic) in bacterial counts in both resting and foamy macrophages. The intracellular activity of RIF was also not affected by presence of LBsin foamy macrophages. BDQ, LVF and MXF, however, showed reduced intracellular efficacy against M. tuberculosis in foamy macrophages compared to resting macrophages, suggesting a role for LBs to impact intracellular drug distribution. In conclusion, this thesis demonstrates the potential utility in combining advanced analytical methods and an in vitro infection model to determine cellular drug permeation profiles that might be applied to prioritize compounds and combinations optimized for distribution to target bacterial populations. This will facilitate well-informed decision-making processes in progression of lead compounds in pre-clinical development and, therefore, may offer the potential to reduce high rates of attrition of compounds which enter clinical phase of development.

APA, Harvard, Vancouver, ISO, and other styles

17

Blomberg, Thomas R. "Heat conduction in two and three dimensions : computer modelling of building physics applications /." Lund : Dept. of Building Physics [Institutionen för byggnadsteknik], Univ, 1996. http://www.byfy.lth.se/Publikationer/1000pdf/TB-1008.pdf.

Full text

APA, Harvard, Vancouver, ISO, and other styles

18

Davies, Helen Catherine. "Bovine TB in badgers : a spatial analysis." Thesis, University of Bristol, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.289778.

Full text

APA, Harvard, Vancouver, ISO, and other styles

19

Fryatt, Robert John. "Cost effectiveness of TB services in Nepal." Thesis, Imperial College London, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.243793.

Full text

APA, Harvard, Vancouver, ISO, and other styles

20

Routin, Eddy. "Local Tb theorems and Hardy type inequalities." Phd thesis, Université Paris Sud - Paris XI, 2011. http://tel.archives-ouvertes.fr/tel-00656023.

Full text

Abstract:

In this thesis, we study local Tb theorems for singular integral operators in the setting of spaces of homogeneous type. We give a direct proof of the local Tb theorem with L^2 integrability on the pseudo- accretive system. Our argument relies on the Beylkin-Coifman-Rokhlin algorithm applied in adapted Haar wavelet basis and some stopping time results. Motivated by questions of S. Hofmann, we extend it to the case when the integrability conditions are lower than 2, with an additional weak boundedness type hypothesis, which incorporates some Hardy type inequalities. We study the possibility of relaxing the support conditions on the pseudo-accretive system to a slight enlargement of the dyadic cubes. We also give a result in the case when, for practical reasons, hypotheses on the pseudo-accretive system are made on balls rather than dyadic cubes. Finally we study the particular case of perfect dyadic operators for which the proof gets much simpler. Our argument gives us the opportunity to study Hardy type inequalities. The latter are well known in the Euclidean setting, but seem to have been overlooked in spaces of homogeneous type. We prove that they hold without restriction in the dyadic setting. In the more general case of a ball B and its corona 2B\B, they can be obtained from some geometric conditions relative to the distribution of points in the homogeneous space. For example, we prove that some relative layer decay property suffices. We also prove that this property is implied by the monotone geodesic property of Tessera. Finally, we give some explicit examples and counterexamples in the complex plane to illustrate the relationship between the geometry of the homogeneous space and the validity of the Hardy type inequalities.

APA, Harvard, Vancouver, ISO, and other styles

21

Rocha, Chrystianne. "Gap filler adaptativo para sistema ISDB-Tb." Universidade Presbiteriana Mackenzie, 2014. http://tede.mackenzie.br/jspui/handle/tede/1440.

Full text

Abstract:

Made available in DSpace on 2016-03-15T19:37:50Z (GMT). No. of bitstreams: 1 Chrystianne Rocha.pdf: 2924776 bytes, checksum: a1d74db138a8b87f0518f3a6ef67c404 (MD5) Previous issue date: 2014-08-07 This master thesis presents the proposal of assigning the cognitive ability to a gap filler. Differently from the usual repeaters found on the market, the adaptive gap filler is able to automatically monitor tuned channels with the intention of verifying if the protection ratio described in Resolution nº398 from Anatel is being respected. Spectrum sensing techniques and the concepts related to coverage area will be addressed. Tests were carried out on the Matlab and GNU Radio Software with the purpose of analyzing the adaptive gap filler performance on real channels. Este trabalho apresenta a proposta de atribuir ao gap filler a capacidade cognitiva . Diferentemente dos repetidores encontrados no mercado, o gap filler adaptativo tem como função monitorar, de forma autônoma, os canais sintonizados para verificar se a relação de proteção descrita na Resolução nº 398 da Anatel está sendo respeitada. Como fundamentos dessa proposta são abordadas as técnicas de sensoriamento do espectro e os conceitos relacionados às áreas de cobertura. Em uma abordagem prática, os testes foram desenvolvidos no Matlab e no GNU Radio, em que se analisa a atuação do gap filler adaptativo em canais reais.

APA, Harvard, Vancouver, ISO, and other styles

22

Kolotylo, T. R. "Clinical features of combined HIV/TB infection." Thesis, БДМУ, 2021. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/18885.

Full text

APA, Harvard, Vancouver, ISO, and other styles

23

Marsay, Leanne. "Evaluation of immune correlates to TB vaccines." Thesis, University of Oxford, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.572645.

Full text

Abstract:

Development of an improved TB vaccine is hindered by the lack of a correlate of ,~.-r protection. Efficacy of TB vaccines in humans can only be a"S~essed by expensive and time consuming trials within TB endemic areas, which are limited; therefore, it is critical that vaccines with the greatest potential to protect are selected for these trials. Mycobacterial growth inhibition assays (MGIAs) have been developed with the hope that these in vitro functional assays will correlate with protection, which could aid in the selection of the best vaccine candidates. Work in this thesis describes the development and evaluation of different MGIAs for their ability to detect TB vaccine induced mycobacterial growth inhibition. The mycobacterial growth indicator tube (MGIT) MGIA reproducibly demonstrated mycobacterial growth inhibition in splenocytes from BCG vaccinated compared with naive mice, which corresponded with in vivo protection from M. tb challenge. This assay also discriminated between PBMC from naive and BCG/BCG-MVA85A vaccinated macaques. Microarray data showed extensive differential gene expression in splenocyte responses to ex-vivo BCG stimulation between naive and BCG vaccinated mice. T H 1 responses including IFN-y with NOS2 expression were enhanced in BCG vaccinated mice, indicating a possible mechanism for mycobacterial growth inhibition in BCG vaccinated mice. Further investigation into whether the MGIT assay can be used as a correlate of protection from M. tb in humans and animals is warranted.

APA, Harvard, Vancouver, ISO, and other styles

24

Ali, Hanan M. "Development of new diagnostic devices for TB." Thesis, Bangor University, 2015. https://research.bangor.ac.uk/portal/en/theses/development-of-new-diagnostic-devices-for-tb(5a962fb1-76f7-45ec-b9d6-4b7e30749136).html.

Full text

Abstract:

The main objective of the work was to develop an analytical method for the diagnosis of human and bovine TB+ and para-TB by finding the best Ag with high Ab binding signal. This was achieved in five parts. First, the synthesis of S,S-trans-alkene-methoxy mycolic acid (I) from M. tb was achieved successfully. This led to the synthesis of its glycolipid derivatives (TDM, TMM, GroMM, GMM and ArM). The second part was the analysis of a range of other synthetic Ags using TB+ and TB- human serum samples in ELISA assays. The best combinations of sensitivity and specificity were observed with TDM (160) (100 and 78%), ArM (179) (100 and 73%) and ArM (158) (100 and 86%). Combining the results from synthetic TDM (160), ArM (158) and GMM (180) gave 100 and 94% sensitivity and specificity. These represent very much better values than those reported with many recognised assays. The third part involved the serodiagnostic evaluation of the sugar esters of MA (I). High biological activity was observed with TDM (44). This also gave high distinction between TB+ and TB- human serum samples, the best combinations of sensitivity and specificity (100, 73%) and high area under the ROC curve (0.929) in contrast with other derivatives. The fourth part achived using four different sets of bovine serum samples, including one set of animals diagnosed with active bTB. Statistical analysis using multidimensional scaling (MDS) analysis and the Random Forest (RF) analysis showed that the ELISA assay can distinguish between different categories of serum sample. Combining the results from a set of Ags using mean decrease accuracy and mean decrease Gini illustrated that the synthetic Ags gave responses higher than the natural Ags. The best area under the ROC curves, sensitivity and specificity were observed with TDM (156) 0.959, 100 and 86 % respectively. Finally, a range of antigens were studied in ELISA assays using serum from cattle infected with MAP.

APA, Harvard, Vancouver, ISO, and other styles

25

Liu, Miaomiao. "Actinomycetes Sourced From Unique Environments as a Promising Source of New TB-Active Natural Products." Thesis, Griffith University, 2017. http://hdl.handle.net/10072/366523.

Full text

Abstract:

Tuberculosis (TB) is the leading cause of death from infectious diseases in the world, affecting more than ten million patients each year. However, multi-drug resistance (MDR-TB) threatens progress achieved in TB care and control, and there are few drugs available to treat MDR-TB. Our overall aim was to identify anti-TB natural products from microbes sourced from unique environments. This thesis presents efforts to achieve an effective approach to identify anti-TB microbial natural products with the combination of one strain many compounds (OSMAC) strategy, NMR fingerprint and principal component analysis. The thesis begins with an introduction of TB and the current anti-TB drugs and candidates. It also covers a review on anti-TB natural products from marine microbe and endophyte origin and analysis of their physicochemical properties using Lipinski’s rule of five as well as the ChemGPS tool. As part of a research program aiming to identify anti-TB microbial constituents, a cell-based screening assay was developed to screen 2562 crude extracts. Among the active hits, 46 actinomyces isolated from marine, desert or Traditional Chinese Medicines were selected for further chemical investigation according to their chemical profiles or anti-TB activities. The results are presented in chapters 2 to 7. Thesis (PhD Doctorate) Doctor of Philosophy (PhD) School of Natural Sciences Science, Environment, Engineering and Technology Full Text

APA, Harvard, Vancouver, ISO, and other styles

26

Cornick, Ruth. "'You must tune your TB programme well...' : integrating TB, HIV and ARV care in Cape Town primary care setting." Master's thesis, University of Cape Town, 2007. http://hdl.handle.net/11427/9328.

Full text

Abstract:

Includes bibliographical references (leaves 86-91). This study occurred in the context of three problems that have arisen within the South African HIV/AIDS crisis: the prevalent HIV and tubertulosis (TB) co-epidemic, the concern that antiretroviral (ARV) provision might compromise the existing TB control programme, and that the Western Cape's current limited vertical model of ARV roll-out will soon reach capacity. This study evaluated whether and how TB control changed following ARV introduction in a Cape Town primary care TB clinic and explored the process of integration of the TB and ARV services in the clinic.

APA, Harvard, Vancouver, ISO, and other styles

27

Akpabio, Ubon S. "A description of patients with recurrence of pulmonary tuberculosis in TB hospital, Ermelo." Thesis, Stellenbosch : University of Stellenbosch, 2015. http://hdl.handle.net/10019.1/97199.

Full text

Abstract:

South Africa is one of the high burden countries for TB in Sub Sahara in Africa with Mpumalanga as one of the provinces with a high burden of disease. Data available on tuberculosis in Msukaligwa indicate the following: Cure Rate 40%; Smear conversion at the end of intensive phase 35% and Defaulter Rate 27.5%. The problem of TB is made worse by the twin epidemic of HIV, with a prevalence of 38.9% in our district -the highest among the 3 districts in the province. Retreatment TB carries the risk of developing TB drug resistance with severe consequences for the patient and the population. Understanding the characteristics of these patients will help in designing interventions to prevent the problem, promote a high cure rate for patients with TB in our health care system and reduce to minimum the burden of re-treatment pulmonary TB on our health care facilities and community. One critical precondition for Retreatment TB is non adherence to TB treatment. Factors responsible for non adherence could be classified as individual patient factors; Co-morbid conditions; Health system; treatment related and Community factors. The outcomes of Retreatment TB could be, cure, and death and failure of treatment leading to drug resistance. The Setting of this study is the 58-bedded TB hospital in Ermelo. The Aim of the study was to describe the occurrence, characteristics and management outcome of Retreatment Pulmonary Tuberculosis in patients in the Ermelo TB hospital. The specific Objectives were to describe the socio-demographic, behavioural and clinical factors related to recurrence of the TB in patients; to determine the contribution of non adherence to treatment on recurrence of TB in the study population; to identify the prevalence of resistance to TB medication among patients with Retreatment TB ; to identify treatment outcomes in patients who have been followed up for the duration of Retreatment TB and finally to make recommendations to the Department of Health, Mpumalanga towards minimizing Retreatment TB and improving the overall TB programme. The Study design is cross sectional and descriptive; the study population comprised of patients admitted with TB at Ermelo TB hospital aged 15 years and older between 1 January 2005 and 31 December 2007.No specific probability sampling was applied in the selection of the patients. Data Collection involved visits to the TB hospital during the period and extracting the relevant information from the patient medical records and the TB register using a predesigned data collection form. Data analysis was done by the statistician from the Centre for Statistical Consultation, University of Stellenbosch. Being a descriptive study, the data analysis expresses the prevalence of various factors associated with retreatment TB. This study met the Ethical approval of the University of Stellenbosch as well as the Research Ethics Committee of the Department of Health & Social Services, Mpumalanga. Findings All the three hundred and eighty eight patient records with retreatment TB forming 19.6% of TB patients admitted between 2005 and 2007 were reviewed. The distributions of the patients were: males 66%; mean age of 41.4 years; females 34%; mean age 35.3 years. They were mostly unemployed; primary education 93%; unmarried 43% and married 34%.Retreatment TB was diagnosed with sputum smear microscopy in 71% with bacilli load of 3+ in 45%.The sources of referral to TB hospital were: public hospital 71 %; private doctors 2%. 74% of the patients have had TB 1-3 years before the episode under study. Retreatment TB categories were: after treatment completed 69%; default 19%; after cure 8% and treatment failure 4%. 98% of patients tested had +ve HIV status; the median CD4 cell count was 106 cells/µl at the time of retreatment; very few (5%) were on ART. Drug resistance to primary TB drugs was as follows: Rifampicin 16%; Isoniazid 29%; Ethambutol 19% and Streptomycin 23%. The treatment outcomes for those whom data were available were: successful 49.1%, death 23.8%; treatment default 22.9%. MDR-TB complicated 3.3% of the patients. Conclusion: Majority of the retreatment TB patients were males with an average age of 41years and unemployed. More than two thirds of the patient had completed TB treatment previously and default on treatment accounted for less than one quarter of retreatment categories. The process of care was better in terms of diagnosis of TB with sputum smear. Improvement in the documentation of key factors like smoking, alcohol, drug use among patients and co-morbidity as well as counselling and testing for HIV and provision of ARTs is required. Treatment outcomes with regards to successful outcome need to be monitored and improved upon.

APA, Harvard, Vancouver, ISO, and other styles

28

Al, Qublan Hamzeh. "Development and testing of recombinant B. abortus RB51 vaccine strains carrying M. tuberculosis protective antigens." Diss., Virginia Tech, 2015. http://hdl.handle.net/10919/73696.

Full text

Abstract:

Tuberculosis, caused by Mycobacterium tuberculosis, is one of the most prevalent infectious diseases inflicting humankind. The World Health Organization estimates that one third of the world's population, approximately 2.2 billion people, is infected with TB with a mortality of 1.7 million people annually. Currently, the WHO estimates that each year more than 9 million people develop TB. Bacille Calmette-Guérin (BCG), an attenuated strain of M. bovis, is the only licensed TB vaccine in the world. Clinical studies have shown childhood vaccination with BCG to be protective against disseminating and meningeal forms of TB. However, the efficacy of BCG against pulmonary TB in adults has been variable and inconsistent (0-80%). The objective of this study is to develop and test the efficacy of the B. abortus vaccine strain RB51 as a platform for expression of M. tuberculosis antigens (Ag85B, ESAT6 and Rv2660c) and induction of a protective immune response against M. tuberculosis and B. abortus challenge in mice. Here we report the construction of two recombinant strains of B. abortus vaccine strain RB51 capable of expressing mycobacterial antigens Ag85B, ESAT6 and Rv2660c. Our studies show that expression of mycobacterial antigens in strain RB51 lead to induction of antigen-specific immune responses characterized by secretion of IgG2a antibodies as well as of IFN- and TNF-α. Mice immunized with a combination of two strains of RB51 in equal numbers, one carrying Rv2660c-ESAT6 and another carrying Ag85B, led to a 0.90 log reduction in CFU burden with significance nearly reaching borderline (p = 0.052). However, when mice were primed with the same strains of RB51 and boosted with proteins Ag85B and ESAT6, a significant level of protection (1 log reduction) compared to the PBS vaccinated group was achieved. The protection levels conferred by this vaccination strategy was similar to that conferred by BCG vaccine. In conclusion, we have shown that recombinant RB51 strains expressing mycobacterial protective antigens result in stimulation of antigen specific immune response without altering the vaccine efficacy in protecting against the more virulent strain of B. abortus 2308. These recombinant vaccines could potentially be used to protect against M. tuberculosis infection. Ph. D.

APA, Harvard, Vancouver, ISO, and other styles

29

Adebanjo, Omotayo David. "Knowledge, attittudes and practices of healthcare workers about prevention and control of multidrug-resistant tuberculosis at Botsabelo Hospital Maseru, Lesotho." Thesis, University of Limpopo ( Medunsa Campus), 2011. http://hdl.handle.net/10386/423.

Full text

Abstract:

Thesis (MPH)--University of Limpopo, 2011. Background: Tuberculosis is one of the major public health problems in Lesotho. With the occurrence of multi-drug resistant tuberculosis, little is known about the views of health care workers on this disease. The aim of this study was to investigate the knowledge, attitudes, and practices of healthcare professionals about prevention and control of MDR-TB at Botsabelo hospital, situated in Maseru, Lesotho. Methods: This study was conducted by means of a semi-structured, anonymous, and self-administered questionnaire that was sent to health care workers. Returned questionnaires were collected through designated boxes stationed at selected places at the study site from 23rd September to 13th October 2010. The investigator and his assistants collected the returned questionnaires on the 15th October 2010. Results: The results of this study indicate that, overall, less than half (47.3%) of respondents had good level of knowledge about MDR-TB; but the overwhelming majority of them held negative attitude towards patients with MDR-TB. Further analysis showed that the level of knowledge did not affect the attitude towards patients suffering from MDR-TB but it influenced their practices. Having good level of knowledge about MDR-TB was associated with good practices such as the use of protective masks and MDR-TB guidelines and involvement in educating patients about MDR-TB. Moreover, the findings of this study showed also that the attitude of respondents towards patients suffering from MDR-TB did not influence their practices. Conclusion: In conclusion, less than half of respondents had good level of knowledge about MDR-TB, but over 85.5% of them held negative attitude towards patients suffering from MDR-TB. Although the level of knowledge about MDR-TB was found not to have influenced the attitude of respondents towards patients suffering from MDR-TB; and that xi their attitude did not influence practices, good level of knowledge was positively associated with safer practices such as using protective masks, educating patients on MDR-TB, and referring to the MDR-TB guidelines manual. An educational remedial intervention is recommended.

APA, Harvard, Vancouver, ISO, and other styles

30

Knight, Lauren Kerry. "Evaluation of the costs of managing cutaneous adverse drug reactions to first-line TB therapy in South African TB patients." Master's thesis, University of Cape Town, 2018. http://hdl.handle.net/11427/27821.

Full text

Abstract:

Background: Optimal tuberculosis (TB) treatment remains the backbone of effective TB control programmes. However, TB drugs are often associated with adverse drug reactions (ADR) that affect treatment adherence and cure. Cutaneous adverse drug reactions (CADR) are more commonly associated with Human Immunodeficiency Virus (HIV)/TB co-infection, occurring in up to 7% of patients. If severe, CADR require treatment interruption and hospitalisation. There are no standardised guidelines for managing CADR to TB therapy. Current practice in South Africa involves drug rechallenge, a process, which aims to identify the offending drug and modify the treatment regimen. This practice can carry significant risks that need to be weighed against the benefits. Despite significant resources required to manage CADR, there is no available data regarding their economic impact. Alternate strategies to manage TB therapyassociated CADRs and their cost have never been evaluated. The purpose of this study is to evaluate the economic impact of TB therapy-associated CADRs in South Africa and compare the cost of drug rechallenge with alternative strategies. Methods: Data was obtained from 97 patients, admitted to the Groote Schuur Hospital dermatology ward with TB therapy-associated CADR. Clinical data pertaining to hospitalisation, diagnostic/monitoring tests and drug prescriptions was extracted from patient medical records. Healthcare and patient-related costs were obtained from financial department records, interviews and hospital admission records. Alternative drug regimens for CADR management were derived from literature and expert clinical advice. Costs were estimated using an ingredient's approach in 2016 US dollars. A cost-comparative analysis was performed comparing the cost of the current practice with alternative options. Univariate sensitivity analysis was used to investigate the uncertainties around cost components. Results: The cost of managing a TB therapy-associated CADR was $6,525 per patient. Within this population the average cost of managing a CADR in a patient with DS-TB was $5,831 (95% CI: 8438; 10727). The main contributor of CADR costs was hospitalisation amounting to $3,638/patient (62% of total cost). Alternative CADR management strategies using outpatient-initiated second-line regimens containing rifabutin, bedaquiline and delamanid cost 44-55% less than drug rechallenge depending on the drug regimen used ($2,651/patient to $3,276/patient). Sensitivity analyses indicated that drug rechallenge was most sensitive to hospitalisation costs, whereas second-line treatment strategies were sensitive to TB drug costs. The average total loss experienced by patients as a result of the CADR was $530 (25% of their annual income), as compared to an estimated loss in the alternate regimens of $154 (10% of their annual income). Societal costs with alternate regimens were also lower at 46-66% that of current cost of $6,134. Conclusion: CADR to TB treatment represent a significant economic burden to the healthcare system and affected patient. The alternate strategy of outpatient-initiated second-line therapy provides an economically feasible option by implementing an ambulatory practice of care despite using more expensive drugs. Shorter hospitalisation reduces patient and healthcare costs. This data should inform policy makers on optimal resource use within the healthcare system. Once the effectiveness and risk of drugresistance of these strategies has been determined, further research should estimate their cost-effectiveness.

APA, Harvard, Vancouver, ISO, and other styles

31

Maserumule, Matsopiane Charlotte. "The development of aptamer-based probes for the detection of TB antigens ESAT-6.CFP-10 potential TB diagnostic tools." Master's thesis, University of Cape Town, 2013. http://hdl.handle.net/11427/3425.

Full text

Abstract:

Includes abstract. Includes bibliographical references. Lack of point-of-care (PoC) diagnostic tools for TB hinders control of the disease, particularly in resource-limited, high HIV and TB prevalence countries. Therefore, there is a need for simple, rapid, accurate, and affordable PoC diagnostics to detect active TB early enough for opportune intervention. To develop TB detection probes that will constitute such diagnostics, our research group recently isolated DNA aptamers that bind to a putative marker for active TB; the ESAT-6.CFP-10 heterodimer. Aptamers are highly specific artificial mimics of antibodies that have shown great prospects in diagnostic applications. The aim of this study was to characterise the anti-ESAT-6.CFP-10 aptamers, and to optimise them into more specific and affordable detection probes for the development of potential PoC TB diagnostic tools.

APA, Harvard, Vancouver, ISO, and other styles

32

Ncube, Wenzokuhle S. "People’s understanding of TB in a setting of high HIV/TB prevalence: case studies in Gugulethu Township, Western Cape Province." University of the Western Cape, 2014. http://hdl.handle.net/11394/4170.

Full text

Abstract:

Magister Artium (Development Studies) - MA(DVS) Tuberculosis (TB) infection is present in many people but it is sometimes latent until one’s immune system is compromised. As such, it increasingly manifests in people, especially those whose immune system has been compromised by e.g. HIV, as an opportunistic disease. TB is thus closely interlinked with HIV and efforts to eradicate TB have been integrated with the fight against HIV in South Africa. The study revealed that factors such as poverty and stigma - be it enacted or perceived - has an impact on how people with TB deal with the burden of having the disease. Using qualitative research as the choice of methodology and collecting data using observations, in-depth interviews and structured interviews among 18 participants the study focused on the ways in which people understand TB in an area that is known to have high HIV prevalence. The researcher explored people’s experiences with TB and investigated their understanding of the disease as well as explored how people on Directly Observed Treatment Strategy (DOTS) make sense of and interact with this programme in Gugulethu Township. During the study it emerged that people have significant understanding of TB and its symptoms but their initial reaction to those symptoms is selfmedication and this results in delayed treatment seeking. TB is stigmatised in Gugulethu despite some people acknowledging that the environment itself is partly to blame for the rapid spread of the disease. The study revealed that there is good healthcare provision in Gugulethu and it is accessible but the burden of suffering from TB is a difficult one that requires family support, financial support and good relations with clinic and hospital staff in order for one to adhere to treatment and recover from TB.

APA, Harvard, Vancouver, ISO, and other styles

33

Olandim, Richard John Lintulahti. "Diversidade espacial na recepção em sistemas ISDB-Tb." Universidade Presbiteriana Mackenzie, 2015. http://tede.mackenzie.br/jspui/handle/tede/1464.

Full text

Abstract:

Made available in DSpace on 2016-03-15T19:37:57Z (GMT). No. of bitstreams: 1 RICHARD JOHN LINTULAHTI OLANDIM.pdf: 2276167 bytes, checksum: 0d3c0536034c612074740ab02558a1be (MD5) Previous issue date: 2015-06-25 In Brazil, the broadcasting system for television content in high definition is the ISDB-Tb. Although robust, the content transmission in this system, like in any radio frequency propagation, can suffer from external attenuating factors, such as distortion by multipath propagation. One of the techniques used in radio communications for minimizing the effects of this type of distortion is the spatial diversity reception, which uses multiple antennas connected to a single receiver. The signals, received by different antennas, are combined, in a technique known as MRC or Maximal Ratio Combiner, so that the output signal-to-noise ratio is greater than the individual signal-to-noise ratios, allowing the successfully decoding of the received content, even though the individual signal in each antenna does not have sufficient quality to be decoded independently. This study aims to establish a method of spatial diversity in receiving television signals in ISDB-Tb, pondering between the advantages and disadvantages of their use in edge regions of coverage, where the reception of the Brazilian digital TV system is not yet total. No Brasil, o sistema de radiodifusão para conteúdos televisivos em alta definição é o ISDB-Tb. Apesar de robusto, a transmissão de conteúdos neste sistema, como qualquer propagação em radiofrequência, pode sofrer com fatores externos atenuantes, como por exemplo a distorção por propagação em multi-percurso. Uma das técnicas utilizadas em radiocomunicação para que se minimizem os efeitos deste tipo de distorção é a diversidade espacial na recepção, que utiliza múltiplas antenas conectadas a um mesmo receptor. Os sinais, recebidos pelas diferentes antenas, são trabalhados em uma técnica conhecida como MRC ou Combinação de Máxima Razão, de modo que a relação sinal-ruído de saída seja maior do que as relações sinal-ruído individuais, permitindo a decodificação do conteúdo com sucesso, mesmo que os sinais individuais em cada antena não tenham qualidade suficiente para serem decodificados independentemente. Este estudo tem como objetivo propor um método de diversidade espacial na recepção de sinais televisivos no padrão brasileiro ISDB-Tb, ponderando entre as vantagens e desvantagens de sua utilização em regiões de borda de cobertura, onde a recepção do sistema brasileiro de TV digital ainda não é total.

APA, Harvard, Vancouver, ISO, and other styles

34

Monedero, Recuero Ignacio. "Hacia un mejor control de la tuberculosis multidrogorresistente en países en desarrollo." Doctoral thesis, Universitat Autònoma de Barcelona, 2013. http://hdl.handle.net/10803/401285.

Full text

Abstract:

Introducción La tuberculosis multidrogorresistente (TB-MDR) está incrementando su prevalencia a escala mundial principalmente como consecuencia del mal manejo de los casos sensibles y transmisión primaria. La mayoría de pacientes proceden de países en desarrollo con sistemas de salud insuficientes para el manejo de a sus enfermos. Objetivos El objetivo general de esta tesis doctoral es profundizar en el tema de la TB-MDR en países en desarrollo y aportar nuevos conocimientos que colaboren en la prevención de resistencias medicamentosas y a tratar con mejores resultados a aquellos pacientes que ya tienen enfermedad con resistencias. Hipótesis El uso más eficiente de los actuales conocimientos y herramientas podría contribuir a la creación de estrategias de mayor impacto. Se identifican 3 hipótesis: • Hipótesis 1. Los medicamentos combinados en dosis fijas (MCFs) pueden tener similar eficacia que los medicamentos sueltos a un menor coste y con potenciales ventajas operativas y en prevención de resistencias. • Hipótesis 2. Los tratamientos estandarizados para TB-MDR pueden aportar similares resultados que los individualizados también con ventajas operativas y menor coste. • Hipótesis 3. Es posible crear herramientas y documentos de calidad técnica para acelerar la formación de clínicos en el manejo de TB-MDR. Métodos: Se ha trabajado en 3 líneas de investigación principales: 1. Revisión sistemática de la eficacia de los MCFs respecto a medicamentos sueltos. 2. Estudio de cohortes de pacientes en tratamiento para TB-MDR. Evaluación de eficacia, efectividad, recaídas y efectos adversos respecto al uso de regímenes estandarizados e individualizados. 3. Creación de documentos sencillos de alta calidad técnica para aumentar el acceso al conocimiento del manejo de la TB con resistencias orientado a los clínicos de países en desarrollo. Resultados: Estudio 1: Revisión sistemática de eficacia de los MCFs. El 100% de los estudios encontrados en que se comparan MCFs y medicación separada, los resultados en eficacia de conversión de cultivo y curación son similares. Las recaídas parecen ser similares. Adherencia, aceptación y capacidad para reducir resistencias están a favor de los MCFs. Otras ventajas operativas y precio también favorecen el uso de MCFs. Estudio 2: Estudio de cohortes y evaluación de todos los pacientes con TB-MDR tratados en República Dominicana entre agosto 2006 y junio 2010. No hubo diferencias estadísticamente significativas entre regimenes estandarizados e individualizados en cuanto a conversión de cultivo o éxito terapéutico en los pacientes con tratamientos terminados (74% vs. 66%, p>0,05). Cada enfermo presentó una mediana de 5 efectos adversos. Cavitación en radiografía de tórax y no negativizar el cultivo antes del segundo mes fueron encontrados factores de riesgo para resultado desfavorable. La tasa de recaídas fue aproximadamente de un 1% tras un año de seguimiento. Estudio 3: Se llevo a cabo una revisión crítica acerca del manejo de pacientes con TB resistente. Listado y presentación de las bases bacteriológicas del tratamiento y mínimos conocimientos para un correcto manejo de casos. Estudio 4: Elaboración de un artículo científico abordando de forma simplificada el correcto manejo de pacientes con coinfección TB-MDR y VIH en contextos africanos de escasos recursos. Estudio 5: Se analizaron las diferencias en presentación y manejo de pacientes con TB-MDR procedentes de países ricos y pobres. Las soluciones de países ricos probablemente no sean extrapolables a países pobres. Conclusión: Los artículos científicos incluidos suponen un respaldo científico fundamental para las políticas sanitarias de uso masivo de MCFs en el tratamiento para la TB sensible y tratamientos estandarizados para TB-MDR. También se han creado artículos que facilitan el acceso a formación de clínicos en países en vías de desarrollo. Esta tesis doctoral aporta información científica relevante para un mejor control de la tuberculosis multidrogoresistente en países en desarrollo. Introduction The prevalence of Multidrug resistant Tuberculosis (MDR-TB) is globally increasing. Transmission of resistant strains into the community is jeopardizing global TB control. The vast majority of cases are from developing countries where health systems are insufficient to diagnose, treat and support the patients. Object The main objective of this doctoral thesis is to analyze in deep the MDR-TB problem in developing countries and provide new knowledge in resistance prevention and better MDR-TB treatment results. Hypothesis The more efficient use of current knowledge and tools may contribute to the creation of health policies with impact on resistance prevention and better cure rates. Three different hypotheses were identified: • Hypothesis 1.The anti-TB fixed dose combinations (FDCs) may obtain similar efficacy than single drugs with operative advantages, reduced cost and reducing the resistance acquisition. • Hypothesis 2. Standardized MDR-TB treatments may obtain similar results than individualized also with operative advantages and less cost. • Hypothesis 3. It is possible to create scientific and quality documents for quick self-training and up date of clinicians in the management of MDR-TB. Methods According to the objective and hypothesis formulated, this thesis had worked in three research lines: 1. Systematic review on the FDCs efficacy for the TB treatment respect to single drugs 2. Cohort study and evaluation in terms of efficacy, effectiveness side effects and relapses of MDR-TB patients under standardized and individualized regimens 3. Creation of simple but high quality documents to increase the access of developing countries clinicians to most relevant knowledge regarding MDR-TB to avoid therapeutic errors and resistance amplification. Results Study 1: Systematic review on FDCs efficacy. The 100% of the studies found revealed equal efficacy in terms of culture convertion and cure. Relapses appear to be similar. Adherence acceptance and capacity to reduce resistance acquisition go in favour of FDCs. Other operative and logistic advantages and cost favour FDCs as well. Study 2: Cohort study and evaluation of all MDR-TB patients treated in Dominican Republic between august 2006 and June 2010. There were not found significative statistically differences in culture conversion regarding standardized or individualized treatments. Concerning patients with ended treatments, standardized obtained a treatment success rate of 74% whereas 66% was obtained for individualized. Each patient presented a median of 5 side effects. Cavitation on the chest x ray and more than 2 months for culture conversion were found as risk factor for unfavourable result. Relapse rate was close to 1%. Study 3: Creation of a review article on the subject of drug resistant TB management. List and presentation of the bacteriological bases for TB treatment and minimum requirements and knowledge to take into account to achieve high cure rates. Study 4: Scientific article addressing the simplification of the most correct and updated management of co-infected patients with MDR-TB and HIV in African scarce therapeutic and diagnose resource contexts. Study 5: Perspective article showing the differences on the presentation and management of MDR-TB patients coming from rich and poor countries. Solutions from rich countries, usually the only ones available on the literature or the gold standard are probably not the best solutions or can not be extrapolated to poor countries. Conclusion The articles included represent a scientific back up for anti-TB FDCs massive introduction and the use of standardized regimens for MDR-TB. Simple and quality articles have been created to increase access to MDR-TB management knowledge oriented to clinicians in developing countries. This doctoral thesis provides relevant scientific information towards a better control of MDR-TB in developing countries.

APA, Harvard, Vancouver, ISO, and other styles

35

Baker, Allison Rees. "SNP Associations with Tuberculosis Susceptibility in a Ugandan Household Contact Study." Case Western Reserve University School of Graduate Studies / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=case1274893954.

Full text

APA, Harvard, Vancouver, ISO, and other styles

36

Caldwell, Judy. "A programme evaluation of the effects of an intensified TB screening strategy on changes in facility level TB case finding in City Health PHC facilities in Cape Town." University of the Western Cape, 2018. http://hdl.handle.net/11394/6852.

Full text

Abstract:

Master of Public Health - MPH Background: In South Africa, tuberculosis (TB) detection remains a major problem, as notified cases are estimated to account for only 68% of all incident cases. Health services have relied on passive case finding and this leads to missed or delayed diagnosis. In Cape Town, City Health has embarked on an active surveillance programme to systematically screen all adults seeking health care at PHC facilities for active TB, in order to identify undiagnosed incident TB cases and avert missed opportunities for treating TB. Aim: The aim of this study was to evaluate the effects of an intensified TB screening strategy on changes in facility level TB case finding in City Health PHC facilities in Cape Town.

APA, Harvard, Vancouver, ISO, and other styles

37

Frigati, Lisa Jane. "The impact of isoniazid preventative therapy and antiretroviral therapy on tuberculosis (TB) in HIV-infected children in a high TB incidence setting." Master's thesis, University of Cape Town, 2011. http://hdl.handle.net/11427/10467.

Full text

Abstract:

The aim of this study is to investigate the combined effect of IPT [INH preventative therapy] and ART [antiretroviral therapy] on TB incidence in HIV-infected children. A cohort analysis will be performed using data from a prospective, double-blinded placebo controlled trial of INH versus placebo in HIV-infected children in Cape Town, South Africa.

APA, Harvard, Vancouver, ISO, and other styles

38

Ntinginya, Nyanda Elias [Verfasser], and Michael [Akademischer Betreuer] Hölscher. "Evaluation of potential surrogate markers to determine TB treatment response among TB patients in Mbeya, Tanzania / Nyanda Elias Ntinginya ; Betreuer: Michael Hölscher." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2017. http://d-nb.info/1131040376/34.

Full text

APA, Harvard, Vancouver, ISO, and other styles

39

ALENCAR, Suelene Suassuna Silvestre de. "Translocação e bactérias marcadas com 99m técnécio na icterícia obstrutiva experimental em ratos." Universidade Federal de Pernambuco, 2001. https://repositorio.ufpe.br/handle/123456789/19708.

Full text

Abstract:

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2017-07-17T14:33:57Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Dissertação de Mestrado - Suelene Suassuna Silvestre Alencar.pdf: 1698152 bytes, checksum: 7bc449edbb1386a1875057dc6f3f376f (MD5) Made available in DSpace on 2017-07-17T14:33:58Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Dissertação de Mestrado - Suelene Suassuna Silvestre Alencar.pdf: 1698152 bytes, checksum: 7bc449edbb1386a1875057dc6f3f376f (MD5) Previous issue date: 2001-01-10 Estudo realizado com o objetivo de avaliar a translocação bacteriana (TB) do trato gastrointestinal para órgãos viscerais em ratos submetidos à ligadura do ducto colédoco e submetidos à administração por via oral (gavagem) de E.coli marcada com 99mTecnécio (99mTc-E.coli). Quatro grupos de ratos foram estudados: grupo I (n=10) ligadura do colédoco, grupo II (n=10) controle ou “sham operation”, grupo III (n=12) ligadura do colédoco e gavagem com 99mTcE.coli e grupo IV (n=5) controle ou “sham operation”e gavagem com 99mTc-E.coli. Usando técnica asséptica e sob anestesia, os ratos foram submetidos à laparotomia. Nos ratos dos grupos I e III realizou-se ligadura do colédoco com fio de seda nº 3 zeros e nos ratos dos grupos II e IV apenas manipulação do colédoco com pinça de Adison (sham operation). Após sete dias de observação, os animais dos grupos I e II foram mortos e ressecados fígado, baço, linfonodos mesentéricos e pulmões para exame microbiológico (meios Agar-sangue e Agar Mac Conkey) e exame histopatológico (coloração H.E. e Tricrômico de Masson) por análise morfométrica. O nível de bilirrubina nos grupos ictéricos foi elevado em relação aos do grupo controle. A incidência de bactérias translocadas foi maior no grupo I comparada ao controle p 0,05. Nos animais dos grupos III e IV, após sete dias de observação, foi administrada por via oral (gavagem) 99mTcE.coli e após 24 Hs, os ratos de ambos os grupos foram mortos e seus órgãos retirados para contagem da radioatividade em cintilador gama. Os resultados não mostraram diferença estatisticamente significativa na captação da -E.coli entre os dois grupos (p 0,05). Porém a análise das interações grupo x órgão mostrou diferença entre os grupos ictérico e controle para os órgãos: fígado e pulmão. Os dados disponíveis permitem concluir que em ratos ictéricos por ligadura do colédoco ocorreu translocação de bactérias detectáveis por exame microbiológico. Não ocorreu translocação de bactérias com 99mTc no modelo proposto. This study was designed to evaluate the bacterial translocation (TB) from the gastrointestinal tract to visceral organs in rats submitted to laparotomy and common bile duct ligation (CBDL). Four groups of rats were studied: group I (n = 10) CBDL; group II (n=10) control or “sham operation”; group III (n= 12) CBDL and 99mTc-E.coli and group IV (n=5) control or “sham operation” e 99mTc-E.coli. All the animals were operated with aseptic technic under intraperitoneal anesthesia with pentobarbital sodium (200mg/Kg). On 7th postoperative day the animals of groups I and II were killed with a letal dosis of anesthetic and the liver, spleen, mesenteric lynfonodes and lungs were ressecated to microbiological (Agar-blood and Agar-Mac Conkey) and histological examination (H.E. and Masson Trichromic) through morphometric analysis. On 7th postoperative day the animals of III and IV groups were submitted to 99mTc-E.coli gavage and after 24 hr they were killed and their organs were ressected. After that, the bacterial radioactivity was mensured through an Automatic count of Gama Radioative – model ANSR (Abott Laboratories). The bilirrubin levels of the jaundiced rats were elevated compared with the control groups. The incidence of bacterial translocation was higher in group I compared with control group (p 0,05). The results showed no significant differences among the jaundiced and control groups to the liver and lungs. The data allow to conclude that in jaundiced rat with ligated bile duct occurred bacterial translocation through microbiological analyses. The model proposed showed no bacterial translocation by the labeled 99mTc technic.

APA, Harvard, Vancouver, ISO, and other styles

40

Lucca, Maria Elvira Santos de. "Análise epidemiológica da tuberculose e co-infecção HIV/TB, em Ribeirão Preto-SP, de 1998-2006." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/17/17139/tde-01042008-151419/.

Full text

Abstract:

A pesquisa teve como objetivo analisar o Programa de Controle da Tuberculose (PCT) no município de Ribeirão Preto -São Paulo, no período de 1998 a 2006. Utilizou-se para este propósito indicadores epidemiológicos e de desempenho construídos a partir de dados das fichas de notificação de tuberculose (TB) armazenadas no sistema de informação o EPI-Tb, da Secretaria municipal de saúde deste município e os dados populacionais de estimativas do DATASUS, do período de estudo. Selecionaram-se para o estudo casos novos de TB notificados e residentes no município, por ano de diagnóstico, excluindo-se casos atendidos em outros municípios e presidiários. No período compreendido entre 1998 a 2006 foram notificados no EPI-Tb da SMS/Ribeirão Preto 1623 casos novos de tuberculose, sendo que houve queda no número absoluto de casos e no coeficiente de incidência de 47,8% (50,01- 26,08) dos casos no período ou 5,3% ao ano. O risco de ser um caso novo de TB foi 2,4 vezes maior para homens que para as mulheres. Apesar do número de casos notificados serem maiores na faixa etária de 15 a 49 anos, o risco de adoecer por TB foi maior na faixa etária acima de 50 anos, a partir de 2001. O percentual de co-infecção HIV/TB ficou em 27,1% (prevalência mínima), mas a prevalência máxima foi de 32,7%. A forma clínica mais freqüente para os casos novos foi a pulmonar com 85%, enquanto para os casos co-infectados esta forma esteve presente em 58,3% deles e a extra pulmonar em 27,8%. O local de descoberta dos casos de TB foi 51% em ambulatórios (públicos e privados), 39% em hospitais (universitários, público e privados) e 10% outras formas. Uma das fragilidades observadas foi a baixa detecção de casos de TB no município que nos últimos anos ficou próxima de 45% e que as unidades básicas de saúde e PCTs realizam apenas um quinto das baciloscopias de escarro para diagnóstico que deveriam realizar (segundo estimativas do MS). No entanto uma das fortalezas foi a implantação do tratamento supervisionado no município, que iniciou efetivamente em 1998, e foi aumentando gradativamente, chegando em 2006 a supervisionar 76% dos casos. Houve melhora nas taxas de cura, ficando próximo à 72% e 50,5%, para os casos novos sem co-infecção e com co-infecção HIV/TB, respectivamente. A taxa de mortalidade por TB no município apresentou ligeira tendência de queda no período. Apesar da baixa letalidade no período, 50,8% dos óbitos por TB só foram diagnosticados e notificados após o óbito; indicando dificuldade de acesso ao diagnóstico e tratamento da TB nestes casos. Conclui-se que para melhorar a detecção de casos de TB no município serão necessárias mudanças na forma de acolher os indivíduos suspeitos de TB na atenção básica de saúde, facilitando seu acesso a essas unidades, além de investigar mais sintomáticos respiratórios na comunidade. Algumas ações de controle da doença poderiam ser descentralizas, como o tratamento supervisionado e controle de comunicantes. Para os pacientes co-infectados HIV/TB apenas o tratamento supervisionado não está sendo suficiente para alcançarem sucesso no tratamento. The objective of the present investigation was to analyze the Program of Tuberculosis Control (PTC) in the municipality of Ribeirão Preto- São Paulo, during the period from 1998 to 2006. Epidemiological and performance indicators were used for this purpose, constructed from data of the charts of tuberculosis (TB) notification stored in the information system of EPI-Tb, of the municipal health Secretariat of this municipality and from estimate population data of DATASUS regarding the study period. New TB cases notified regarding patients residing in the municipality were selected according to year of diagnosis, with cases attended in other municipalities and prisoners being excluded. A total of 1623 new cases of TB were notified to EPI-Tb of the SMS/Ribeirão Preto during the period from 1998 to 2006, with a fall in the absolute number of cases and a 47.8% (50,01-26,08) reduction of the coefficient of incidence being observed during this period, corresponding to 5.3% per year. The risk of being a new TB case was 2.4 times higher for men than for women. Although the number of notified cases was higher for the 15 to 49 year age range, starting in 2001 the risk of becoming ill with TB was higher in the age range above 50 years. The percentage of HIV/TB co-infection was 27.1% (minimum prevalence), but the maximum prevalence was 32,7%. The most frequent clinical form for the new cases was the pulmonary one (85%), while this form was present in 58.3% of co-infected cases and the extrapulmonary form in 27.8%. The site of detection of TB cases was public and private outpatient clinics in 51% of cases, university, public and private hospitals in 38%, and other sites in 10%. One of the fragilities observed was the low detection of TB cases in the municipality, which remained close to 45% over the last few years and the fact that the basic health units and PTCs perform only one fifth of the sputum bacilloscopies they should perform for diagnosis (according to Health Ministry estimates). However, one of the strong points was the implantation of supervised treatment in the municipality, which was effectively started in 1998 and increased gradually, with 76% of cases being supervised in 2006. There was an improvement in cure rates, that reached 72% and 50.5% for non-co-infected new cases and HIV/TB co-infected cases, respectively. The TB mortality rate in the municipality showed a slight tendency to a fall during the period. Despite the low lethality observed, 50.8% of the TB deaths were only diagnosed and notified after death, indicating a difficulty in access to diagnosis and treatment of TB in these cases. We conclude that, in order to improve the detection of TB cases in the municipality, changes are needed in the reception of individuals suspected to have TB at basic health units, facilitating their access to these units, in addition to the investigation of more persons with respiratory symptoms in the community. Some actions for the control of the disease such as supervised treatment and the control of communicants could be decentralized. Supervised treatment alone is not sufficient for HIV/TB-co-infected patients to achieve successful treatment.

APA, Harvard, Vancouver, ISO, and other styles

41

Tsuro, Urgent. "Modelling the impact of risk factors affecting TB treatment." Thesis, University of Fort Hare, 2013. http://hdl.handle.net/10353/d1019782.

Full text

Abstract:

The Tuberculosis infection rate has been generally escalating due to poor health conditions in the Gweru district of Zimbabwe. The study therefore seeks to identify the risk factors that affect TB treatment in the Gweru district. A cross sectional study was carried out in which a questionnaire was employed for data collection on 113 respondents. A binary logistic regression model was employed for data analysis. A total of 98 TB patients were interviewed: [50 respondents (44.0%) had Multi-drug resistant Tuberculosis and 63 respondents (56.0%) had general Tuberculosis). Before being enrolled into the study, an informed consent form was given to each of the participants. The data was then put into excel and later transferred to SPSS for analysis. Out of the 14 potential risk factors of TB treatment, only 6 variables (side effects, gender, alcohol use, HIV status, smoking during the treatment period and having been pre-exposed to TB drugs) were statistically significant in their association with treatment failure.

APA, Harvard, Vancouver, ISO, and other styles

42

Visser, Hanri. "Mechanisms of resistance to new generation anti-TB drugs." Thesis, Stellenbosch : Stellenbosch University, 2015. http://hdl.handle.net/10019.1/96863.

Full text

Abstract:

Thesis (MScMedSc)--Stellenbosch University, 2015. ENGLISH ABSTRACT: Drug resistance in Mycobacterium tuberculosis is an increasing global problem. Drug resistance is mostly caused by single nucleotide polymorphisms (SNPs) within the bacterial genome. This observed increase in global incidence of drug resistant tuberculosis (TB) has sparked the search for new anti-TB drugs and the repurposing of drugs that are currently used against other organisms or species of mycobacteria. One such repurposed drug, clofazimine (CFZ), is currently used for the treatment of leprosy, caused by Mycobacterium leprae. The mechanism of action of CFZ is not clear, but it is hypothesized that CFZ is reduced by a mycobacterial type II NADH oxidoreductase (NDH-2). The reduction of CFZ drives the production of reactive oxygen species (ROS) which is toxic to the pathogen. The aim of this study was to elucidate the mechanism of CFZ resistance. Towards this aim, spontaneous in vitro CFZ resistant mutants were selected, characterized and whole genome was used identify SNPs which may cause CFZ resistance. Mutations were identified in a transcriptional regulator encoded by Rv0678, fatty-acid-AMP ligase, or FadD28 (Rv2941) and glycerol kinase or GlpK (Rv3696c). Mutations in Rv0678 have previously been shown to play a role in both CFZ resistance and bedaquiline (BDQ) cross-resistance, while no link has been found between CFZ resistance and mutations in fadD28 and glpK. The novel, non-synonymous SNP identified in Rv0678 resulted in the replacement of an alanine residue with threonine at codon 84, which is located in the DNA binding domain. Virtual modelling of the mutated Rv0678 protein showed that the A84T mutation may influence DNA binding, possibly due to its proximity to the DNA binding domain. This mutation caused a change in hydrophobicity, which may influence binding to DNA. Previous studies showed that mutations in Rv0678 resulted in the upregulation of mmpL5, a putative efflux pump. However, the mechanism whereby CFZ resistance occurs via increased abundance of this efflux pump in the cell wall is not clear and needs further investigation. The cross-resistance between CFZ and BDQ, caused by mutations in Rv0678, is of concern and may influence the planning of anti-TB drug regimens for the future. The roles of the other two mutations identified in this study in CFZ resistance is also not clear and requires further investigation. Finally, the findings of this study support the role of Rv0678 in CFZ resistance thereby suggesting that this gene could be useful as a diagnostic marker to test for CFZ resistance in clinical isolates. AFRIKAANSE OPSOMMING: Middelweerstandigheid in Mycobacterium tuberculosis is 'n wêreldwye toenemende probleem. Middelweerstandigheid word meestal veroorsaak deur enkel nukleotied polimorfismes (SNPs) in die bakteriële genoom. Hierdie toename in middelweerstandige tuberkulose (TB) het gelei tot die soektog na nuwe anti-TB-middels en die alternatiewe aanwending van middels wat tans teen ander organismes of spesies van mikobakterieë gebruik word. Een so 'n alternatiewe middel, clofazimine (CFZ), word tans gebruik vir die behandeling van melaatsheid wat veroorsaak word deur Mycobacterium leprae. CFZ se meganisme van werking is nie duidelik nie, maar dit word vermoed dat CFZ gereduseer word deur 'n mikobakteriële tipe II NADH oksidoreduktase (NDH-2). Die reduksie van CFZ dryf die produksie van reaktiewe suurstof spesies wat giftig is vir die patogeen. Die doel van hierdie studie was om die meganisme van CFZ weerstandigheid te ondersoek. Om hierdie doel te bereik was spontane in vitro CFZ weerstandige mutante gekies, gekarakteriseer en heel genoom volgorde bepaling is gebruik om SNPs te identifiseer wat CFZ weerstandigheid veroorsaak. Mutasies in Rv0678, 'n transkripsie reguleerder, vetsuur-AMP ligase, of FadD28 (Rv2941) en gliserol kinase of GlpK (Rv3696c) geïdentifiseer. Dit is al voorheen gevind dat mutasies in Rv0678 ‘n rol speel in beide CFZ weerstandigheid en bedaquiline (BDQ) kruis-weerstandigheid, terwyl geen verband gevind is tussen CFZ weerstandigheid en mutasies in fadD28 en glpK nie. Die nuwe, nie-sinonieme SNP, geïdentifiseer in Rv0678 het gelei to die vervanging van 'n alanien aminosuur met treonien by kodon 84, wat geleë is in die DNS bindings domein. Virtuele modellering van die gemuteerde Rv0678 proteïen het getoon dat die A84T mutasie DNS binding moontlik kan beïnvloed, as gevolg van sy nabyheid aan die DNS bindings domein. Hierdie mutasie veroorsaak 'n verandering in die hidrofobiese natuur, wat DNS binding kan beïnvloed. Vorige studies het getoon dat mutasies in Rv0678 lei tot die opregulering van mmpL5, 'n waarskynlike uitvloei pomp. Die meganisme waardeur CFZ weerstandigheid veroorsaak, deur ‘n groot aantal van hierdie uitvloei pompe in die selwand, is nie duidelik nie en moet verder ondersoek word. Die kruis-weerstandigheid tussen CFZ en BDQ, wat veroorsaak word deur mutasies in Rv0678, is van belang en kan die beplanning van anti-TB middel behandeling vir die toekoms beïnvloed. Die rolle van die ander twee mutasies, wat in hierdie studie geïdentifiseer is, in CFZ weerstandigheid is ook nie duidelik nie en vereis verdere ondersoek. Ten slotte, die bevindinge van hierdie studie steun die rol van Rv0678 in CFZ weerstandigheid en dit dui daarop dat hierdie geen gebruik kan word as 'n diagnostiese merker om vir CFZ weerstandigheid te toets in kliniese isolate.

APA, Harvard, Vancouver, ISO, and other styles

43

Medina, Nilberto Heder. "Momentos magnéticos de estados nucleares do \'ANTPOT.159 Tb\'." Universidade de São Paulo, 1992. http://www.teses.usp.br/teses/disponiveis/43/43131/tde-04102012-153339/.

Full text

Abstract:

Foram medidos os momentos magnéticos dos estados da banda rotacional do estado fundamental do ANTPOT 159 Tb, através da técnica da distribuição angular perturbada, utilizando-se o campo magnético transiente. Os estados do ANTPOT. 159 Tb foram populados via excitação coulombiana com feixe de ANTPOT. 35 Cl a 88 Me V, sendo os raios -y, emitidos na desexcitação dos estados, observados em coincidência com as partículas retroespalhadas do feixe. Os momentos magnéticos medidos neste trabalho, foram comparados com as previsões de modelos híbridos (rotor+partícula e rotor triaxial+quase-partícula), nos quais a hamiltoniana do núcleo é separada em uma parte fenomenológica que descreve o caroço e uma parte microscópica que leva em conta o movimento da partícula desemparelhada. Os resultados experimentais também foram interpretados com um cálculo puramente microscópico, baseado no modelo de camadas com projeção de momento angular. Os níveis de energia da banda do estado fundamental são bem descritos pelos modelos, embora o staggering em energia previsto pelo modelo rotor triaxial+quase-partícula apresente uma fase de oscilação oposta à observada. Os momentos magnéticos experimentais são bem reproduzidos pelos modelos, nos quais a inclusão de outras configurações sugere uma pequena oscilação, observada nos resultados experimentais. As probabilidades de transição magnéticas B(M1) não são bem descritas por nenhum dos modelos, nos quais a inclusão de várias configurações atenua os valores calculados. Magnetic moments of the levels in the ground state rotational band of 159Tb were measured using the transient magnetic field perturbed angular distribution technique. The levels in 159Tb were populated by Coulomb excitation with an 88 MeV beam and the deexciting rays were observed in coincidence with backscattered projectiles. The magnetic moments measured in this work were compared with hybrid models (rotor+particle and triaxial rotor+quasiparticle) in which the Hamiltonian of the nucleus is separated in a phenomenological part describing the core and a rnicroscopic part which takes into acconnt the movement of the unpaired particle. The experimental results were also interpreted with a purely microscopic calculation based on the angular momentum projection shell model. The energy levels in the ground state band are well described by the models, although the energy staggering predicted in the triaxial rotor+quasi-particle calculation has a phase opposite to the observed one. The experimental magnetic moments are well reproduced by the models, with the band miring suggesting a slight oscillation as observed in the experimental data. The magnetic transition probabilities B(M1) are not well described by the models, in which the band mixing attenuates the calculated values.

APA, Harvard, Vancouver, ISO, and other styles

44

Giannopoulos, Mihail. "Tunable bandwidth quantum well infrared photo detector (TB-QWIP)." Thesis, Monterey, Calif. : Springfield, Va. : Naval Postgraduate School ; Available from National Technical Information Service, 2003. http://library.nps.navy.mil/uhtbin/hyperion-image/03Dec%5FGiannopoulos.pdf.

Full text

Abstract:

Thesis (M.S. in Applied Physics)--Naval Postgraduate School, December 2003. Thesis advisor(s): Gamani Karunasiri, James Luscombe. Includes bibliographical references (p. 59-61). Also available online.

APA, Harvard, Vancouver, ISO, and other styles

45

Ansa, Gloria Akosua. "Integration of tuberculosis (TB) and HIV services in Ghana." Thesis, University of Leeds, 2011. http://etheses.whiterose.ac.uk/2419/.

Full text

Abstract:

Integration of health services involves managing services to enhance quality for patient needs that cut across multiple services, providers and settings. The rapid growth of human immunodeficiency virus (HIV) has increased tuberculosis (TB) cases, and TB/HIV integration offers a unified strategy for control. This study evaluated TB/HIV integration in Ghana. The three sites evaluated applied varying degrees of integration. A mixed methods approach comprised an uncontrolled before-and-after study involving 1330 TB cases, and qualitative interviews with 29 providers and patients. TB treatment success was 51% before and 69% after integration [p<0.01; OR(95% CI)=2.17 (1.72 to 2.74)]. Treatment success increased in all sites after integration: 43% to 53% at the one-stop shop (OSS), 69% to 78% at the partially integrated site (PIS), and 46% to 78% at the referral site (RS). The change was significant only at the RS [(Χ2=64.54; p<0.01; OR(95% CI)=4.28 (2.97 to 6.18)]. HIV screening was highest (99%) at the OSS (Χ2=68.26; p<0.01), HIV-positive cases on CPT were highest (93.8%) at the RS (Χ2=9.29; p<0.01), and the PIS had the highest number (59.5%) on ART (Χ2=95.00; p<0.01). TB/HIV integration may improve TB treatment outcomes but effectiveness is difficult to ascertain due to study design limitations. TB treatment success and TB mortality might be more informative indicators for TB/HIV activities. TB/HIV outputs seemed unrelated to greater integration when compared across sites. This was probably due to existing barriers to integration including missed opportunities, provider fear of loss of influence, financial burden of illness, and stigma. Patient-provider interactions offered privacy and counselling but patients’ illness experiences were not explored, and there was lack of decision-sharing. Patients were also unaware of their right to dignity and respect, or their role in disease management. Facilitators of integration included direct supervision, mutual adjustment and standardisation. Recommendations include conducting more rigorous evaluation studies, including TB mortality in TB/HIV monitoring, prioritising health system strengthening instead of increasing degrees of integration, and improving patient-centred care through provider communication and patient empowerment.

APA, Harvard, Vancouver, ISO, and other styles

46

Patel, Ravikumar. "Rapid PCR TB Testing Results in 66% Reduction in Total Isolation Days in Smear Positive Patients." Thesis, The University of Arizona, 2018. http://hdl.handle.net/10150/626867.

Full text

APA, Harvard, Vancouver, ISO, and other styles

47

Yang, Christine K. "Using age of infection models to derive an explicit expression for Ro." Thesis, University of British Columbia, 2007. http://hdl.handle.net/2429/447.

Full text

Abstract:

Using a multiple stage age of infection model, we derive an expression for the basic reproduction number, Ro. We apply this method to find Ro in analogous treatment models. We find, in the model without treatment, Ro depends only on the mean infective period, and not on the infective distribution. In treatment models, Ro depends on the mean infective and mean treatment period, as well as the distribution of the infective period, but not on the distribution of the treatment period. With an explicit formula for Ro and the final size relation, we provide a practical alternative to evaluating the effect of treatment and other control measures. We compare our models to previous models of SARS and TB.

APA, Harvard, Vancouver, ISO, and other styles

48

Cervino, Alessandra C. L. "Genetic susceptibility to tuberculosis : an analytical and experimental analysis." Thesis, University of Oxford, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.326112.

Full text

APA, Harvard, Vancouver, ISO, and other styles

49

Raphela, Mabule Lucas. "Targeted depletion of RibF, a putative bifunctional FAD synthetase/ flavokinase in Mycobacterium smegmatis using CRISPR interference." Master's thesis, Faculty of Health Sciences, 2020. http://hdl.handle.net/11427/32943.

Full text

Abstract:

Tuberculosis (TB) is the leading killer globally owing to an infectious disease. There is consequently an urgent need to develop novel TB drugs and shorter regimens to treat the causative agent, Mycobacterium tuberculosis, an imperative which demands the identification of new drug targets in essential mycobacterial pathways. To that end, the work presented in this dissertation aimed to functionally characterize ribF, an essential gene in the mycobacterial riboflavin (RF; vitamin B2) biosynthetic pathway. Given the role of RF as a core component of the essential flavin cofactors, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), it was hypothesized that silencing ribF would disrupt the biosynthesis of all flavoproteins, crippling numerous (essential) processes within the organism. Moreover, based on previous observations in Bacillus subtilis, it was predicted that the mycobacterial ribF homolog might play a role in regulating the rib operon (comprising a cluster of RF pathway genes) – either directly by binding to the FMN riboswitch, or indirectly through the production of FMN from RF, in turn enabling riboswitch-mediated repression of downstream genes. CRISPR interference (CRISPRi) technology was used to generate an anhydrotetracycline (ATc)-inducible ribF hypomorph of M. smegmatis, a widely exploited mycobacterial model. Consistent with other organisms, ribF was shown to be essential for in vitro growth of M. smegmatis: CRISPRi-mediated depletion of ribF was bacteriostatic, resulting in a 10-fold growth inhibition in liquid media and corresponding to no reduction (0 log-fold change) in colony forming units (CFU). Moreover, targeted metabolomic analyses revealed that ribF depletion was associated with accumulation of 6,7-Dimethylribityllumazine (DMRL), suggesting that the disruption of RibF function blocked conversion of RF to the essential cofactors, FMN and FAD, in turn inhibiting cell growth. Notably, the lethality of ribF depletion could not be complemented chemically by exogenous supplementation of growth media with RF, FMN or FAD. Downregulation of ribF also caused enhanced susceptibility to the known cell wall-targeting agent, vancomycin, but not to the putative RibF domain inhibitor, thonzonium bromide, suggesting an alternative mechanism of action or impaired bacillary permeation. In summary, these data support the inferred essentiality of ribF in mycobacteria, in turn supporting future work which aims to target this enzyme for new TB drug discovery.

APA, Harvard, Vancouver, ISO, and other styles

50

Motamen, Seyedehsara. "Synthesis of a new compound class of anti-tuberculosis natural products." Thesis, Griffith University, 2021. http://hdl.handle.net/10072/408500.

Full text

Abstract:

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. It usually affects the lungs (pulmonary TB) but can also affect other parts of the body (extrapulmonary TB). According to the World Health Organisation (WHO) report in 2020, TB is one of the top ten leading causes of death worldwide and the main cause of death from infectious disease, ranked above HIV/AIDS. TB treatment is challenging and requires early diagnosis, effective chemotherapy regimens, and drug-resistance screening. Therefore, development of shorter and simpler drug regimens that are safe, suitable for joint tuberculosis/HIV treatment, and well tolerated is essential. Fragment-based drug discovery (FBDD) that screens small molecules with molecular masses of < 250 Da, has become a reliable approach for early stage drug development. It includes the elaboration of small molecules to produce potent ligands. In this project, the physiochemical properties of 39 TB drugs (both marketed and drugs in the development pipeline) and 1271 synthetic compounds reported in 40 publications from 2006 to early 2020 were analysed. A new TB space of physiochemical properties was proposed in this thesis that may provide more appropriate guidelines for design of anti-TB drugs. The putative TB space includes limited ranges for three physiochemical properties: MW ≤ 700, -4 ≤ cLog P ≤ 3, and 30 ≤ PSA ≤ 140 Å. This guideline was consequently used to analyse compounds synthesised in this project. One desirable fragment was selected for further elaboration based on the result of a previous screening of a fragment library against TB proteins by Native Mass Spectrometry. Different analogues of the desired fragments were synthesised with moderate to good yields and screened against two tuberculosis proteins (BirA and Rv3267) by Native Mass Spectrometry. The method is based on the observation and evaluation of protein-ligand complexes to a target protein. The hits were categorised as weak, medium, and strong binders according to the ratio of the protein-ligand peak to the total protein in the mass spectrum. SAR analysis revealed that variation of the substitutions affects the binding affinity. Activity of the hits were also tested in vitro against Mycobacterium smegmatis (M. smegmatis) strain. Screening of a library of 600 compounds against a TB protein (phenylalanyl t-RNA synthetase) was performed by Native Mass Spectrometry and hits were identified. For a specific target, observation of the peaks corresponding to one ligand bound to the protein indicates binding to the same site (competitive), while observation of the ternary complex peak shows that two ligands could bind to different sites of the protein simultaneously (non-competitive). In this screening, some ternary complexes were detected in the mass spectra where two compounds could bind to different binding sites of the protein at the same time. One hit (RQ202049) showed 100% activity in four concentrations of 25, 50, 100 and 300 μM in vitro against M. smegmatis that makes it a possible lead compound. In addition, a library of 1630 compounds (with molecular weight of more than 250 Da) and 330 fragments (with molecular weight of less than 250 Da) were screened against a cancer protein (DnaJ fusion of Protein Kinase A) and hits were identified. In some mass spectra, ternary complexes were also detected which means two compounds could bind to different binding sites (or domains) of the protein. Thesis (PhD Doctorate) Doctor of Philosophy (PhD) School of Environment and Sc Science, Environment, Engineering and Technology Full Text

APA, Harvard, Vancouver, ISO, and other styles

Dissertations / Theses on the topic 'Tb'

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles