<p>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. </p>

<p>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. </p>

No description available.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1969. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliography.

Background: Even with newer and repurposed anti-TB drugs almost a third of patients with XDR-TB have unfavourable outcomes. In patients with localised disease and adequate pulmonary reserve, surgery is an important adjunctive treatment. However, there are no outcome data from TB endemic countries, and the prognostic significance of pre-operative PET-CT findings remains unknown. Objectives: To report outcomes for resectional surgery in our setting, and to study whether PET activity outside of the resection influences treatment outcomes. Methods: A retrospective study of all XDR-TB patients undergoing surgery at Groote Schuur Hospital (GSH) between July 2010 and December 2016 was performed. PET-CT was performed in a subgroup. Patients were followed up to determine treatment outcomes at 24-months post- surgery. Treatment success and failure, including all-cause mortality, was determined. Results: In total, 35 patients underwent surgery. The mean age was 36, 49% were male and 26% were HIV-infected. Pneumonectomy was the most common procedure (57%). Three patients (9%) were lost to follow up by 24 months. Total all-cause mortality was 34%. Treatment success was achieved in 15/35 (43%). In patients who underwent pre-operative PET-CT, there were no overall radiological features or PET parameters that were found to be prognostic for treatment failure. Conclusion: Resectional surgery for DR-TB in combination with chemotherapy resulted in cure in less than half of patients. Our data do not support the use of PET-CT to preselect patients or prognosticate about their outcome. These data inform clinical practice and underscore the need to support antibiotic stewardship strategies in TB-endemic settings.

This anthropological research began with curiosity about human relationships with microbes. Inside the contained environment of a Biosafety Level 3 laboratory at a South African university-based tuberculosis research division, the fieldwork focused on the relationships between scientists and Mycobacterium tuberculosis − the pathogenic bacterium that causes the disease tuberculosis (TB). These deadly bacteria were cared for and nurtured by women scientists. This care extended to the cells and various species with which they worked. Moreover, this care moved beyond the scope of their immediate scientific research projects and well beyond the laboratory. Care was also central to how the participants conducted their scientific research and themselves in the world. This long-term, qualitative ethnographic research weaves together many layers of care in biomedical scientific research, highlighting that scientific research is a deeply personal, caring and subjective practice. The natural and the social are not − and can never be − mutually exclusive. Boundaries between mind/body, subject/object, human/nonhuman, researcher/researched, subjectivity/objectivity and science/society are porous. Acutely aware of the socio-political moment in which this research was embedded, these findings are put into conversation with South African student calls to decolonise science that emerged alongside the #RhodesMustFall student movement. In particular, the focus is on a 2016 meeting about decolonising science at the University of Cape Town where students argued for connection between the university and the community, science and society and the world of academia and the world of Africans. Implicit was the need for science to be relevant to Africans and deeply complex African social formations and problems. The care by women scientists that was observed inside the laboratory and beyond it speaks volumes to cultivating a more caring science and caring institutions of science that connect the laboratory to the world in which it exists in meaningful, relevant and impactful ways. I demonstrate how the participants embodied a decolonised science, and that what they cared about and how they acted upon those cares could serve as important guides for decolonising science and scientific institutions. This research provides important contributions to the field of science and technology studies (STS), to anthropological research on TB and to the conversation on decolonising science in South Africa.

Transmission between hosts is crucial for the success and survival of the obligate human pathogen and aetiological agent of tuberculosis (TB), Mycobacterium tuberculosis (Mtb). Despite this, little is known about how and when Mtb is aerosolized nor the key metabolic and morphological determinants driving successful transmission. To address these knowledge gaps, my doctoral research sought to develop a microscopic method for the detection of aerosolized Mtb following liquidcapture within the respiratory aerosol sampling chamber (RASC). This was achieved through the combination of the mycobacterial cell wall probe, 4-N,Ndimethylamino-1,8-naphthalimide-trehalose (DMN-tre), with the arraying of bioaerosol samples on bespoke nanowell devices amenable to fluorescence microscopy. With this method, a median of 14 live Mtb bacilli (range 0-36) were detected in 90% of confirmed TB patients following 60 minutes of bioaerosol sampling. Three distinct DMN-tre staining patterns were identified among aerosolized Mtb, strongly suggestive of metabolic heterogeneity. Moreover, a low proportion of patients produced Mtb in small clumps. These observations highlight the advantages of using microscopy over conventional culture- or molecular-based techniques for probing the metabolic and morphological characteristics of aerosolized Mtb. Applying this method in a second study, we sought to understand how and when Mtb is aerosolized. To this end, we aimed to compare the aerosolization of Mtb and total particulate matter from patients with TB during three respiratory manoeuvres: tidal breathing (TiBr), forced vital capacity (FVC), and cough. Although total particle counts were 4.8-fold greater in cough samples than either TiBr or FVC, all three manoeuvres returned similar rates of positivity for Mtb. No correlation was observed between total particle production and Mtb count. Instead, for total Mtb counts, the variability between individuals was greater than the variability between sampling manoeuvres. Finally, when modelled using 24-hour breath and cough frequencies, our data indicate that TiBr might contribute more than 90% of the daily aerosolized Mtb among symptomatic TB patients. Assuming the number of viable Mtb organisms detected provides a proxy measure of patient infectiousness, this method suggests that TiBr is a significant contributor to TB transmission. In developing a novel platform for the detection of aerosolized Mtb, this work has suggested the need to re-examine old assumptions about Mtb transmission.

Les traitements simultanés des antituberculeux et de thérapie antirétrovirale (ARV) chez les patients co-infectés par le VIH et la tuberculose (TB) peut être compliqué en raison de la survenue du syndrome inflammatoire de reconstitution immunitaire associé à la TB (TB-IRIS) dont le diagnostic est basé sur les manifestations cliniques. La compréhension de l’immunopathologie de TB-IRIS est cruciale pour améliorer le diagnostic et la prise en charge des patients. L'immunité innée semble de plus en plus jouer un rôle dans le TB-IRIS. Dans la présente thèse de doctorat, j'ai étudié le rôle de l'immunité innée cellulaire, notamment des cellules NKT et γδ t, ainsi que l'implication des marqueurs soluble plasmatique : IL-1Ra, sCD14 et sCD163 liés à l’activation des monocytes/macrophages dans la survenue de l’iris chez les patients co-infectés par le VIH et TB au Cambodge.Les résultats ont montré que : 1/. Le TB-IRIS est associé a une forte activation des cellules γδ T et des sous populations γδ2+ avant l’initiation des ARV, 2/. Aucun des marqueurs IL-1Ra, sCD14 et sCD163 n’était prédictif de la survenue de l’iris. L'analyse longitudinale des taux plasmatiques d’ IL-1Ra pourrait être utile pour le diagnostic de l’iris et l’évaluation de la réponse au traitement antituberculeux. En conclusion, nos résultats révèlent l’association entre une activation importante de l’immunité innée et l’émergence de TB-IRIS dans la physiopathologie. De plus, nos données apportent des nouveaux éléments de l'iris et des marqueurs pour évaluer l'efficacité du traitement antituberculeux. / Simultaneous anti-tuberculosis and antiretroviral (ARY) therapy in HIV and tuberculosis (TB) co-infected patients can be complicated due to the occurrence of TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). The diagnosis test of TB-IRIS is not yet available and mainly based on clinical data. A better understanding of TB-IRIS immunopathology is crucial to improve diagnostic test and patients’ clinical outcomes. Innate immunity seems increasingly play a role in TB-IRIS. In the present doctoral thesis, is studied the role of cellular innate immunity, including NKT and γδ t cells, and as well as the implication of IL-1Ra, sCD14 and sCD163 plasma soluble markers related to the activation of monocytes/macrophages in the development of iris in HIV and TB co-infected patients in Cambodia. The results have shown that 1/. TB-IRIS is associated with a strong activation of γδ t cells and γδ2+ subset before initiation of ARY, 2/. None of IL-1Ra, sCD14 and sCD163 markers was predictive of the onset of iris. Longitudinal analysis of IL-1Ra plasma level could be useful for the diagnosis of the iris occurrence and for the evaluation of response to TB-IRIS In conclusion, our results reveal the association between important activation of innate immunity and the emergence of TB-IRIS in the physiopathology. In addition, our data provides new element of TB-IRIS and markers for evaluation of TB treatment efficacy.

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.

Magister Public Health - MPH / 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 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, 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 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 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 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 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 participants were purposively selected. A thematic content analysis of transcribed data was conducted where themes related to patient’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 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 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 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 study are made. / South Africa