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.

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M.Tech. (Biomedical Technology) / TB continues to be one of the major causes of morbidity and mortality in developed and developing countries, (Mauch, 1993), despite the development of drugs and vaccines. Today, TB is one of the most serious health problems not only in South Africa, but worldwide. The transmission rate for TB for the population of Cape Town is 3% per year, while the transmission rate in gold mineworkers is estimated at 10% per year (Churchyard and Corbett, 2001). Tubercle bacilli have the ability of evading the immune system by entering a dormant phase while in the human host, and are able to reactivate at a later stage. Little is known about the mechanisms of this reactivation. TB remains a global emergency because of our lack of understanding of the details of its pathogenesis (Rook and Zumla, 2001). Since radioactive minerals are found in mines, it was postulated that radioactivity may be the reason for pulmonary cancers, a fact which is now well established. The biologic effects of radiation have been shown to produce irreparable deoxyribonucleic acid double-strand breaks or singlestrand breaks, or create structural changes by damaging the nucleus. Although no studies have shown toxic effects resulting from long-term, low-dose radiation exposure, risks are still assumed, (Herscovici and Sanders, 2000), and research concerning the mutagenic affects of lowdose radiation exposure is necessary. All the risk factors for pulmonary tuberculosis (PTB) in mineworkers are not known, although many have been identified, such as age and mining occupation. This study aimed to determine if long-term, low-dose exposure to ionizing radiation has an effect on the reactivation of dormant tubercle....

The serious threat of tuberculosis, especially XDR-TB, is a reality in Southern Africa particularly in individuals with HIV/AIDS. Therefore the importance of development of new or improved anti-TB treatment must now be emphasized more than ever. In this study, a model was created to target isoniazid (toxophore) specifically to a cholesterol rich environment where mycobacteria reside in macrophages, by making use of a sterol binding drug, Amphotericin B (haptophore). Isoniazid was covalently linked to Amphotericin B via a Schiff base to a linker molecule, terephthalaldehyde. Although this molecule showed a loss of biological activity, a discovery was made by serendipity that could have great impact in understanding how Mycobacterium tuberculosis enters and survives in the host macrophage. During the testing of the compound, it was discovered that Amphotericin B bound to mycolic acids at least as well as it binds to cholesterol, its natural ligand. This could provide proof of the structural similarity between mycolic acids and cholesterol but many more controls need to be investigated. As cholesterol was previously shown in literature to be critical for entry and survival of Mycobacterium tuberculosis in macrophages, the indication of a structural mimicry between the cell wall mycolic acids and cholesterol and the attraction of these two chemical entities to one another seems to be highly relevant. This characteristic can now be further explored to improve the understanding of the process of entry and survival of Mycobacterium tuberculosis in the macrophage host. Copyright 2006, University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. Please cite as follows: Benadie, Y 2006, Amphotericin B as a mycolic acid specific targeting agent in tuberculosis, MSc dissertation, University of Pretoria, Pretoria, viewed yymmdd < http://upetd.up.ac.za/thesis/available/etd-04212008-151642 / > / Dissertation (MSc (Biochemistry))--University of Pretoria, 2008. / Biochemistry / unrestricted

This thesis aimed to investigate, first, the potentially traumatic effects of AIDS-related bereavement on HIV/AIDS aid workers in South Africa; second, the resources that aid workers utilise in order to cope with their work; and third, differences in the experiences of local versus international aid workers. HIV/AIDS work is associated with various stresses and burnout is commonly observed among HIV/AIDS caregivers. Care of HIV/AIDS aid workers, however, has been largely overlooked; research has typically focused on the experiences of professional health workers, and often outside of an African setting. This present study, therefore, addressed these limitations with the use of participant observation ethnography and ethnographic interviewing. A period of one year was spent with an organisation in South Africa that provides care for vulnerable children in need and affected by HIV/AIDS. Openended semi-structured interviews were conducted with 63 male and female local and international staff and volunteers. The interviews were analysed using discourse analysis (DA), a methodology novel within HIV/AIDS and trauma research and particularly suitable for investigating language, social context and interaction, and identities, which are factors found to be important in HIV/AIDS work. Participants’ discourses were analysed to identify how they construct their identities, concepts such as HIV/AIDS and tuberculosis, events they experienced, and how they made sense of these phenomena. The main finding of this study was that contemporary HIV/AIDS aid work involves new challenges that have surpassed AIDS-related bereavement as the most prominent concern. The main challenges reported by participants involved the inability to control HIV/AIDS treatment and consequently inability to prevent, or control, AIDS-related death as a result of patient non-compliance. Participants further constructed HIV contraction as controllable and, therefore, avoidable, and used this micro discourse on control to counter HIV-related stigma, particularly stigma they experienced as HIV/AIDS aid workers. This rhetorical technique, however, rather maintains the macro discourse on HIV-related stigma by maintaining the blame component of the disease. Two identity constructions emerged in participants’ discourses. First, the characteristics inherent in the child identity suggested that loss is not merely a matter of death but also sadness for and on behalf of children for their various losses. Second, the caregiver identity prescribed how ‘proper’ and ‘genuine’ HIV/AIDS caregivers are expected to behave. The prescriptive nature of this identity can explain burnout among HIV/AIDS caregivers. The rewards of caregiving, however, can act as a buffer against difficult or traumatic experiences inherent in HIV/AIDS work. Managerial support and global belief systems that allow finding meaning were further identified as important coping resources for HIV/AIDS aid workers. Finally, differences between local and international participants, in terms of how they conceptualise phenomena and consequently have different needs, emphasise the role of culture in the experiences of HIV/AIDS aid workers. In the thesis I further discuss these findings in light of theories of social psychology, such as the Just World hypothesis, Cognitive Dissonance, and Identity Control Theory and Self-Categorization Theory. I conclude that although AIDS-related death no longer is a prominent issue, care of HIV/AIDS aid workers should not be overlooked. Contemporary HIV/AIDS work simply involves new challenges and traumas, and it is important that such work is continuously researched to identify evolving needs.

Master of Public Health - MPH / Adequate levels of adherence to treatment for tuberculosis (TB) and HIV at the same time poses a problem for public health in South Africa. TB/HIV co-infected patients face many potential barriers to adherence to treatment for both conditions. There is a need for more knowledge about factors influencing treatment adherence in co-infected patients on concomitant treatment. The aim of this study was to explore the barriers and facilitators to treatment adherence among people co-infected with TB/HIV living in the Alfred Nzo District, Eastern Cape, in order to identify the barriers and facilitators to adherence.

Philosophiae Doctor - PhD / This thesis was informed by what I perceived to be a tense relationship between Western biomedical science and, for example, “traditional” or “indigenous” ways of producing knowledge about medicinal plants used to manage a pervasive condition like Tuberculosis (TB) in South Africa. Hoping to reimagine this relationship and its possibilities, I follow medicinal plants collected from Genadendal through three research spaces with disparate but intertwined knowledge heritages to investigate these tensions but also to tease out how knowledge about locally used medicinal plants is generated and “done” in practice. The first space was at the South African Herbal Science and Medicines Institute (SAHMI) as part of an experiential science project led by scientists who were interested in studying medicinal plants which could potentially provide new sources of safe, affordable, and sustainable medicine for communicable conditions such as TB.

Magister Scientiae - MSc (Chemistry) / Tuberculosis (TB) is one of the major infectious diseases that affect the health of people all over the world. South Africa is one of the countries that account for most of the TB cases; it is the leading cause of death in South Africa and is known to be lethal when combined with HIV in patients. Various tests have been used to diagnose tuberculosis infected patients, but some of these tests give false positive results. Studies have shown that tuberculosis-related cytokines can serve as biological markers for the diagnosis of TB. Cytokines are signalling proteins secreted by immune cells and one such cytokine is interferon-gamma (IFN-?). Interferon-gamma is secreted by immune cells in response to various pathogens and has many physiological roles in the immune system and inflammatory stimuli. IFN-? was first detected using antibody-based immunosensing techniques but this approach is expensive, time consuming and has low stability, it is therefore vital that an alternative detection method for IFN-? be developed.

Thesis (PhD (Molecular Biology and Human Genetics))--University of Stellenbosch, 2005. / 157 leaves single sided printed, preliminary pages i-xvii and numbered pages 1-141. Includes bibliography, and abbreviations and a list of figures. / ENGLISH ABSTRACT: A gene coding for Arylaminie N-acetyltransferase (NAT) has been found in Mycobacterium tuberculosis, the casual agent of tuberculosis (TB). N-acetyltransferase acetylates and inactivates isoniazid (INH), which is a front line drug used in TB therapy. A guanine to adenine SNP at basepair 619 (G619A) has previously been identified in this gene, which results in a glycine to arginine change at amino acid 207 (G207R) (Upton et al. 2001). In this study the nat gene was further characterised. The frequency of the G619A SNP was analysed in 37 M tuberculosis strain families found in the Western Cape Province of South Africa, and it was found that the G619A SNP is conserved in two strain families (strain family 3 and strain family 28). Further sequence analysis identified a new thymine to cytosine SNP at base-pair 529 (T529C) resulting in a tyrosine to histidine change at amino acid 177 (Yl77H). This SNP was found only in isolates from strain family 3. These results imply that these SNPs may be used in epidemiology studies to classify isolates into these strain families. Using Real Time PCR, the expression of nat in M bovis BCG and M tuberculosis (reference strain H37Rv) was determined over a 7 and 28 day growth cycle, respectively. Using 16S rRNA as an endogenous control, the nat gene was shown to be expressed early during the growth curve and reach its maximum expression level at approximately mid-log phase. The expression of nat was induced in drug susceptible M tuberculosis isolates (reference strain H37Rv and isolate 1430 containing both SNPs) exposed to INH at a concentration of O.Oll-lg/ml, but minimal change in expression was observed in resistant isolates (isolate 816) exposed to INH at the same concentration. Mycobacterium bovis BCG cultures exposed to INH, at a final concentration of 0.28I-lg/ml, showed an increase in protein production. The increase of nat mRNA and NAT protein in M tuberculosis and M bovis BCG, respectively, implies that INH affects the expression of NAT. The NAT protein was localised to all fractions of the cell in Mycobacterium smegmatis, M bovis BCG and M tuberculosis, using the Western blot technique. However, protein fractions from the cell envelope region showed a protein (detected with specific NAT antibodies) that ran at a higher molecular weight (MW). This implies that the cytosolic hydrophilic NAT undergoes some type of post-translational process that may make it hydrophobic, and enable it to pass into the cell envelope region. These results show for the first time how nat is expressed during the entire growth cycle of M tuberculosis and M. bovis BeG. It was shown that nat is expressed early during the growth cycle of the bacterium reaching maximum expression levels at mid-log phase. These results are in concordance with those obtained using M. smegmatis nat mutants, which taken together, show that early expression of nat is important for early growth and development of mycobacteria. The results in this study also showed that NAT appeared to be translocated into the cell envelope of the bacterium, implying that NAT may be involved in one of the pathways needed for complete formation of the cell envelope. These results suggest that NAT may be an important target for drug development, as inhibitors of NAT could result in hindered growth and hence spread of the bacterium within its host. Inhibitors may also result in the incomplete development of the cell wall, enabling the host to combat the disease using its own immune system.

Background: A post-exposure regrowth model utilizing the well-tried Bactec radiometric system, which would simulate in vivo situations at the site of invasive disease, was developed to measure drug activity against multiplying Mycobacterium tuberculosis. Aims: The aims of this dissertation were to (a) construct a radiometric model simulating drug efficacy relating to the combined bactericidal activity and delays in regrowth due to the action of anti¬tuberculosis (TB) agents, (b) compare the killing kinetics of drugs singly and in combinations by the time-kill curve method, with the radiometrically-determined regrowth model, and (c) assess whether the Bactec radiometric regrowth model could predict likely bactericidal activities of drugs. Design and methods: Drug concentrations in the time-kill curve method were in a range of achievable drug concentrations at the site of infection and in multiples of the minimal inhibitory concentration (MIC), (1x, 2x or 3x, and 8x). Exposure times of 6h, 24h, 48h and 72h were used and these were based on pharmacokinetic data reflecting likely periods of in vivo exposure in TB lesions. Standardized inocula of approximately 106CFU/mi of actively multiplying M. tuberculosis strains were used. The same concentrations, exposure times and bacterial concentrations were used for the assessment of radiometrically-determined post-exposure regrowth times of M. tuberculosis. Growth times were recorded as the number of days required to reach a predetermined growth index (GI) level in the Bactec system, and were expressed as T400 readings in days. Simple linear regression and a mathematical logistic model were used to assess whether the radiometric post-exposure regrowth model could predict the bactericidal activity of the drugs. For drug combination studies, 1MIC of isoniazid (INH) and rifampicin (RMP) were used singly and in combination while 2MIC of ethambutol (EMB), streptomycin (SM), ofloxacin (OFL) and amikacin (AMK) were used in combinations studies. Colony counts at Oh and following 24h exposures were performed and regrowth patterns were determined using the T400 method. M. tuberculosis H37Rv was tested and subsequently resistant strains. Results: INH and RMP were highly bactericidal while EMS showed moderate activity in the time-kill curve method. The three drugs produced the best curves, showing longer regrowth times and markedly depressed rates of regrowth in the Sactec post-exposure regrowth model. Using simple linear regression, a linear relationship between bacterial survivors and the radiometric regrowth times, T400, was achieved for all drugs tested. Even better agreement was found when control-related regrowth times, (T-C) 400, were used in the analysis. Conditions compromising the linear relationsbip in the radiometric regrowth model, for OFL and less markedly EMS and AMK, were likely postantibiotic effects (PAEs) brought on by the short exposure time (6h), and drug carry-over effects due to concentrations ≥ 8 MIC for INH, RMP and 8M (10x and 20x MICs). The mathematical logistic model showed good correlation between bactericidal activity and regrowth for INH and RMP but not for EMB, SM, OFL and AMK. Drug combination effects in the two techniques depended on the criteria used to describe synergy. Generally, it was found in drug combination experiments that the drugs did not influence each other to a meaningful extent. Discussion and conclusions: For prediction of bactericidal activity, interpretation of the radiometrically-determined regrowth model needs to accommodate PAEs and the effect of subinhibitory concentrations. The validity of the mathematical logistic model is not clear. Technical aspects of future studies such as better organism dispersal, need to be improved to achieve a more reliable evaluation based on the logistic model. For drug combination studies, the radiometric regrowth model yielded findings that were difficult to interpret in relation to published data, reinforcing the need for the use of internationally standardized techniques which would give statistically reliable data. The radiometrically-determined regrowth model showed good discrimination between the standard activities of anti- TB agents, correlating with clinical efficacy. It is simple to perform and could prove to be useful for the screening of candidate anti- TB drugs. Improved technical stringency and the evaluation of poorly active control drugs, are however needed before proof of validity of the model can be established. / Dissertation (MSc (Medical Microbiology))--University of Pretoria, 2007. / Medical Microbiology / unrestricted