In this thesis, we explore the benefits of microencapsulating isoniazid and pyrazinamide within sporopollenin exine capsules derived from Lycopodium clavatum. Sporopollenin is a natural biopolymer, which is extracted from the outer shell of pollen grains. These hollow microcapsules can encapsulate and release drug actives in a controlled manner and possess many other advantages such as homogeneity in morphology and size, resilience to both strong acids and bases, they have antioxidant properties as well as UV protection to protect the material inside the microcapsule. Compared to artificial microcapsules, sporopollenin’s muco-adhesion to intestinal tissues contributes greatly to the extended contact of the sporopollenin with the intestines leading to an increased efficiency of delivery of drugs. The hollow microcapsules can be easily filled with a solution of the active or active in a liquid form by simply mixing both together. The drug actives are released in the human body depending on pH factors. Active release can otherwise have controlled by adding a coating on the shell, or co-encapsulation with the active inside the shell so that high drug concentrations are delivered to the site of infection. Encapsulation of the drug active will possibly improve therapeutic abilities of the drugs; simplify the treatment of TB-HIV coinfections by eliminating troublesome drug-drug interactions and drastically reduce or eliminates side effects. The SECs were loaded using a passive filling method. The drug active (0.1 g) was dissolved in a solvent and mixed with the SECs (0.1 g) for 10 minutes. After mixing for 10 minutes, the solvent was removed by a rotary evaporator and dried to a constant mass. The surface of the sporopollenin exines were analysed on a FTIR to observe if there are any drug deposits on the surface of the SECs. The loading efficiency and drug release percentage was determined by using calibrations curves and analysed on a UV-vis spectrophotometer. Further work has been proposed in which to characterize the SECs further and producing coated tablets from loaded SECs.

M.Sc. / The induction of heat shock proteins (HSPs) in human monocytes during a pathogen challenge is a sophisticated selective response and plays an important role in cytoprotection from inflammation-related stress, including oxidative injury. We investigated the accumulation of the inducible isoform of the 70 kDa HSP, Hsp70, in peripheral blood monocytes from 12 healthy donors in response to Mycobacterium tuberculosis (M.tb) using flow cytometry, biometabolic labeling or Western blot analysis. Cells from each donor, prepared on two different occasions, were exposed to virulent (H37Rv) and attenuated (H37Ra) strains of M.tb at two bacterium : monocyte ratios (1:1 and 10:1) for 3 h and allowed to recover for an additional 2 h or 24 h. In spite of a prominent inter-individual variation, H37Ra (1:1, 2 h) significantly induced the mean Hsp70 accumulation (p<0.05) compared to normal cells, while H37Rv (10:1, 24 h) significantly suppressed the mean Hsp70 levels (p<0.001) in monocyte compared to normal monocytes or monocytes exposed to H37Ra. Survival of H37Rv-infected monocytes showed a significant correlation with Hsp70 levels. These results suggest a protective role of Hsp70 in host defense against mycobacterial infection. Cell death due to insufficient endogenous levels of Hsp70 implies a novel pathogenic strategy for virulence of M. tuberculosis.

M.A. (Political Science) / Although an effective cure for tuberculosis exists, the incidence and mortality rate for TB in South Africa remain exceptionally high. The reason for this is both medical as well as sociopolitical. The purpose of this dissertation is to examine the inter-action of various differential variables which influence the control of TB in this country. TB whilst caused by a germ, is adversely affected by socioeconomic deprivation, which in turn has distinct political connotations in South Africa. The dissertation therefore examines the inter-play of the historical and present influences of sociopolitical factors on the TB situation at present. Another important aspect of TB control is the State's efforts to control TB through the TB Control Programme (TBCP). This dissertation discusses the objectives of the TBCP and meaSures its effectivity against the socio-political context in which it functions. This is followed by a series of suggestions including an examination of the financial implications of these. A non-governmental organisation (NGO), SANTA ( The South African National TB Association) is a further actor in the control of TB. As specified delegates of the State for TB health education, it is essential that their role be examined both in terms of the TBCP as well as in terms of their own stated objectives for TB control. This includes an examination of the role of NGOs in complimenting the activities of the State and their believability in the community they claim to serve. Further proposals are put forward with regard to ways in which SANTA can improve their believability, relevance and effectivity within TB control in South Africa. Further influencing factors are the impact of AIDS and political violence on TB and the ability of the various actors to control TB. These two aspects are discussed briefly and constitute areas for further research. In addition it would be relevant for some form of cost-benefit analysis to be conducted, in order to extend the scope of the policy analysis conducted here.

Thesis (PhD)--Stellenbosch University, 2012. / Includes bibliography / ENGLISH ABSTRACT: Tuberculosis (TB) has been declared a global health emergency by the World Health Organisation, and consequently there is an urgency to develop improved methods of diagnosis and treatment. Despite the current TB epidemic, the disease can be treated effectively using isoniazid (INH) in combination with other antibiotics. However, INH is inactivated in the body by certain drug metabolising enzymes, which may reduce the efficacy of TB treatment. The activity of these drug metabolising enzymes, called NAT, are in turn reduced by nucleotide changes (SNPs) in the gene. These genetic variants (alleles) have been correlated with the rapid- (FA), intermediate- (IA), and slow acetylation (SA) enzymatic activity, and one is therefore able to investigate potential phenotypic effects via genotypic analyses. We investigated these genetic changes in the NAT1 and NAT2 genes in individuals from the local Coloured community (SAC) since this group has one of the highest TB incidences in the country. NAT2 is primarily responsible for the inactivation of INH, whilst NAT1 metabolises para-aminosalicyclic acid (PAS) which is used in the treatment of drug resistant TB. The NAT2 results indicated that the NAT2 alleles were not equally represented in three local ethnic groups studied, and subsequently the rapid, intermediate and slow acetylation activity reflected these differences. However, the relative frequency of these variants in the SAC and Caucasian groups were relatively low. These differences require further investigation to determine their overall relevance to the NAT2 activity differences between groups. In the case of the NAT1 analysis we also observed differences in the relative frequency of various NAT1 alleles between Caucasian and SAC individuals. However, many of these NAT1 SNPs and alleles have not as yet been characterised, so effects of these variants are currently unknown. Interestingly, the NAT1*4 and NAT1*10 alleles were the most prevalent NAT1 alleles in both Caucasians and SAC. The NAT1*4 allele exhibits the rapid NAT1 activity, whilst the activity of the NAT1*10 allele is currently subject to ongoing debate. In this respect, the analysis of NAT1 continues to be a topic for ongoing research. These results, observed for the NAT genes, underscore the importance of doing genetic analyses in local ethnic groups, since these differences may vary significantly between the groups. / AFRIKAANSE OPSOMMING: Tuberkulose (TB) is deur die Wêreldgesondheidsorganisasie (WGO) tot 'n globale gesondheidsnood verklaar en derhalwe is dit noodsaaklik dat nuwe, verbeterde diagnostiese metodes ontwikkel word, wat tot meer effektiewe behandeling kan lei. Ten spyte van die huidige TB-epidemie, kan die siekte doeltreffend behandel word deur middel van isoniasied (INH), in kombinasie te met ander antibiotika. INH kan egter geïnaktiveer word deur sekere ensieme in die liggaam, met die gevolg dat INH nie meer effektief is nie in die behandeling van TB. Die aktiwiteit van hierdie ensiem, die sogenaamde NAT2 (Arielamien N-asetieltransferase 2) ensiem, word op sy beurt beïnvloed deur sekere nukleotied veranderings (SNPs) in die geen. Hierdie genetiese veranderings gekorreleer met ensiemaktiwiteitsveranderings (geklassifiseer as vinnig (FA) Intermediêr (IA) en stadig (SA)), wat mens in staat stel om potensiële fenotipiese effekte te ondersoek deur middel van genotipiese analise. Ons het hierdie genetiese veranderings ondersoek in die NAT1 en NAT2 gene in individue van die Kleurling-gemeenskap (SAC) omdat díe bevolkingsgroep die hoogste voorkoms van TB in die land het. NAT2 is primêr verantwoordelik vir die inaktivering van INH, terwyl NAT1 para-amienosalisilaat (PAS) inaktiveer, wat gebruik word in die behandeling van midel-weerstandige TB. Die NAT2 resultate dui daarop dat die allele van die NAT2 geen nie eweredig verteenwoordig wasin die drie etniese groepe nie en derhalwe word die vinnige (FA), intermediêre (IA) en stadige (SA) ensiemaktiwiteite deur hierdie verskille weerspieël. Hoewel die teenwoordigheid van hierdie variante relatief laag was in die SAC en Koukasiër gemeenskappe, is verdere studies nodig om die omvang van hierdie verskille te bepaal ten onsigte van NAT2 aktiwiteit tussen groepe. In die geval van die NAT1 analise het ons verskille waargeneem in die voorkoms van verskeie NAT1 allele tussen Koukasiese en SAC individue. Baie van hierdie NAT1 SNPs is egter nog nie gekarakteriseer nie, en derhalwe is die effek van hierdie NAT1 variante onbekend. Die NAT1*4 en NAT1*10 allele was die prominentste NAT1 alleel in beide Koukasiërs en SAC. Die NAT1*4 is betrokke by vinnige NAT1 aktiwiteit, terwyl die effek van die NAT1*10 alleel nog onderhewig is aan aktiefwe debat. In hierdie verband, is die studie van NAT1 steeds 'n onderwerp vir toekomstige navorsing. Hierdie resultate, wat vir die NAT gene waargeneem is, beklemtoon die belangrikheid van verdere genetiese analises in plaaslike etniese groepe, aangesien hierdie verskille beduidend kan wees tussen die verskillende groepe.

Text in English with Abstracts in English and Afrikaans / Health promotion is an educational tool that can be used to educate and create awareness of health issues through various media forms. The purpose of this study was to explore the use of TB Proof South Africa‘s Facebook page in creating TB awareness. The literature on TB, social media, health promotional campaigns and health promotional models was reviewed to contextualise this study. A qualitative case study approach was used to collect data from TB Proof South Africa‘s Facebook page. Data was collected using three data collection methods; namely, online ethnographic observation, textual analysis and visual analysis. The findings indicate that TB Proof South Africa‘s Facebook page creates awareness of TB. Results from this study also suggested collaboration between South African healthcare professionals and traditional health practitioners in the fight against tuberculosis. The study advocates the need for comparative studies to explore the use of other health-related Facebook pages. / Gesondheidsbevordering is ʼn opvoedkundige werktuig wat gebruik kan word om op te voed en bewustheid van gesondheidskwessies deur middel van verskeie mediavorme te skep. Die doel van hierdie studie was om die gebruik van TB Proof South Africa se Facebook-blad in die skepping van TB-bewustheid te verken. Leesstof oor TB, sosiale media, gesondheidsbevorderingsveldtogte en gesondheidsbevorderingsmodelle is beoordeel om hierdie studie te kontekstualiseer. ‘n Kwalitatiewe gevallestudiebenadering is gebruik om data van TB Proof South Africa se Facebook-blad in te samel. Data is ingesamel deur gebruikmaking van drie data-insamelingsmetodes, naamlik aanlyn etnografiese waarneming, teksontleding en visuele ontleding. Die bevindings dui daarop dat TB Proof South Africa se Facebook-blad bewustheid van TB skep. Resultate van hierdie studie beveel ook samewerking tussen Suid-Afrikaanse gesondheidsorgberoepslui en tradisionele gesondheidspraktisyns in die stryd teen tuberkulose aan. Die studie bepleit die behoefte aan vergelykende studies om die gebruik van ander gesondheidsverwante Facebook-blaaie te verken. / Communication Science / M.A. (Communication)