Thesis (M.D.)--University of the Witwatersrand, Faculty of Medicine, 1947.

Thesis (MSc (Community Health))--University of Stellenbosch. 1995. / Please refer to full text for abstract

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.

The emergence and spread of multi-drug resistant (MDR-TB) and extensively drugresistant tuberculosis (XDR-TB) are a major medical and public problem threatening the global health. The objectives of this study were to (i) determine the prevalence of MDR-TB and XDR-TB in the Eastern Cape; (ii) analyze patterns of gene mutations in MDR-TB and (iii) identify gene mutations associated with resistance to second line injectable drugs in XDR-TB isolates. A total of 1520 routine sputum specimens sequentially received within a period of 12 months i.e. February 2012 to February 2013 from all MDR-TB and XDR-TB patients treated by Hospitals and clinics in the Eastern Cape were included in this study, of which 1004 had interpretable results. Samples were analyzed with the Genotype MTBDRplus VER 2.0 assay kit (Hain Lifescience) for detection of resistance to Rifampicin and Isoniazid while solid and liquid culture drug susceptibility tests were used for ethambutol, streptomycin, ethionamide, ofloxacin, capreomycin and amikacin. PCR and sequence analysis of short regions of target genes gyrA, (encode subunit of DNA topoisomerase gyrase), rrs (16S rRNA) and tlyA (encodes a 2’-O-methyltransferase) were performed on 20 XDR-TB isolates. MTBDRplus kit results and drug susceptibility tests identified 462 MDR-TB, 284 pre-XDR and 258 XDR-TB isolates from 267 clinics and 25 hospitals in the Eastern Cape. There was a high frequency of resistance to streptomycin, ethionamide, amikacin, ofloxacin and capreomycin. Mutation patterns indicated differences between the health districts as well as differences between the facilities within the health districts. The most common mutation patterns observed were: (i) ΔWT3, ΔWT4, MUT1 [D516V+del515] (rpoB), ΔWT, MUT1 [S315T1] (katG), ΔWT1 [C15T] (inhA) [39 MDR, 204 XDR-TB and 214 pre XDR-TB isolates], (ii) ΔWT8, MUT3 [L533P+S531L] (rpoB), ΔWT, MUT1 [S315T1] [145 MDR, 18 pre-XDR and 3 XDR-TB solates] and (iii) ΔWT3, WT4 [D516Y+del515] (rpoB), ΔWT, MUT1 [S315T1] (katG) [75 MDR, 1 pre-XDR and 7 XDR-TB isolates]. Mutations in inhA promoter regions were strongly associated with XDR-TB isolates. Two thirds (66.6 percent (669/1004) of the isolates had inhA mutations present with 25.4 percent (170/669) found among the MDR isolates, 39.2 percent (262/669) among the pre-XDR isolates and 35.4 percent (237/669) among the XDR-TB isolates, which implies that these resistant isolates are being spread by transmission within the community and circulating in the province. There was good correlation between XDR-TB drug susceptibility test results and sequence analyses of the gyrA and rrs genes. The majority of XDR-TB isolates contained mutations at positions C269T (6/20) and 1401G (18/20) in gyrA and rrs genes respectively. Sequence analysis of short regions of gyrA and rrs genes may be useful for detection of fluoroquinolone and amikacin/ kanamycin resistance in XDR-TB isolates but the tlyA gene is not a sensitive genetic marker for capreomycin resistance. This study highlighted the urgent need for the development of rapid diagnostics for XDR-TB and raised serious concerns regarding ineffective patientmanagement resulting in ongoing transmission of extremely resistant strains of XDRTB in the Eastern Cape suggesting that the Eastern Cape could be fast becoming the epicenter for the development of Totally Drug-resistant Tuberculosis (TDR-TB) in South Africa.

The aim of this study was to assess community members’ knowledge levels regarding Drug Resistant TB and HIV and AIDS. The study was conducted at ward 40 in Green bushes area in Nelson Mandela Metropolitan Municipality (NMMM). A quantitative research method was used in this study. Random sampling is the type of probability sampling method that was used in this study. The sample consisted of 100 respondents above 18 years who were randomly selected from the beneficiary list of for the RDP houses in Green bushes area in the Nelson Mandela Metropolitan Municipality. Data for this study were collected using close ended questions which were administered by the researcher to the selected participants. Data was analysed using bivariate and descriptive statistics according to the identified themes. The study revealed that community members had high knowledge levels regarding Drug Resistant TB and HIV and AIDS prevention, transmission modes and diagnosis and treatment methods. The findings revealed that community members were highly knowledgeable and aware of the fact that abstaining and practising safe sex were means of preventing the spread of HIV and AIDS as it was spread through unprotected sex, while opening of windows and minimisation of close contact with HIV positive people and children with people infected with Drug Resistant TB are infection control measures or methods of preventing the spread of the disease. Additionally, the study indicated that female respondents were more aware and knowledgeable about prevention, transmission modes and diagnosis and treatment of Drug Resistant TB and HIV and AIDS than male respondents. Furthermore, the findings revealed that the respondents were highly knowledgeable and aware about transmission of Drug Resistant TB and HIV and AIDS; knowledgeable about prevention and less knowledgeable about diagnosis and treatment. A high percentage of female respondents knew that there was no vaccine to neither prevent nor cure HIV and AIDS and that antiretroviral drug were used to manage it. The study also showed that female respondents knew that all people irrespective of race and economic class can be infected with Drug Resistant TB and HIV and AIDS. It is important to note that the respondents between 41-60 years possessed more knowledge regarding Drug Resistant TB and HIV and AIDS than the respondents who were between 18-40 years. Lastly, the study showed that there were significant differences in gender and knowledge and no significant differences in age and knowledge of the respondents regarding Drug Resistant TB and HIV and AIDS. It is recommended that in future, research regarding knowledge levels about Drug Resistant TB and HIV and AIDS be extended to other wards in the Nelson Mandela Metropolitan Municipality (NMMM). Accurate knowledge should be provided by ensuring that educational materials that are developed, are appropriate for the various levels of literacy, and that more appropriate and relevant information regarding these diseases is made more accessible to community members in their home languages. The researcher further recommends that during training interventions and educational campaigns more emphasis should be put on prevention, diagnosis and treatment of Drug Resistant TB and HIV and AIDS.

This thesis focuses on the attitudes and policies which shaped the history of pulmonary tuberculosis in the Cape from 1870 to 1920 and culminated in the passing of the Public Health Act, Act 36 of 1919. It was this act which formed the basis of public health legislation in South Africa until the 1970s. The thesis is a contribution to the history of medicine and to the history of legislation. Topics explored include pulmonary tuberculosis and its early global history. When the practice of sufferers visiting places with particular climates became fashionable, towns in the Karoo became a popular destination. Their journey to the colony, together with their experience in Cradock is the subject of a chapter. Once the disease spread to the local population, the focus shifted to the attitudes and policies of the local authorities and their failure to address its spread. In contrast, in Cape Town the city council and its medical officer of health took up the challenge, but with limited success. The fight against tuberculosis was assisted by a number of dedicated individuals such as Dr Neil Macvicar who was the founder of the Native Health Society. The Society for the Prevention of Consumption, which was officially launched in Cape Town in June 1904, also contributed to educating the public about the disease. Once the Cape Colony entered into political Union in 1910 there was the added dimension of tuberculosis on the mines and the reluctance of mine officials to take care of workers suffering from the disease. This became an issue during the proceedings of the Tuberculosis Commission. The attitudes and prejudices towards the local population became formalised in the Public Health Act, Act 36 of 1919 because the act was drafted with the health of the white population in mind. By providing a skeleton budget for local authorities to deal with tuberculosis, the legislature ensured that the healthcare of the majority of the population, especially those who were most vulnerable to the disease, was not addressed. The legacy of that decision continues to haunt South Africa to the present day. / History / D.Litt.et Phil. (History)

Thesis (MTech (Biomedical Technology))--Cape Peninsula University of Technology, 2007. . / Non-tuberculous mycobacteria (NTM) are often isolated from Human Immunodeficiency Virus (HIV) infected individuals, but there is very little information documented about the prevalence of NTM in community settings. An increase in NTM infection is also noted in HIV-negative people. Although it is as yet unknown whether the organisms cause desease in HIV-negative individuals or whether they are merely commensal organisms, their affect on HIV-positive individuals is unquestionable.

Tuberculosis (TB) is acknowledged as an epidemic in South Africa. Health care professionals (HCPs), including dieticians, are at an increased risk for TB-infection compared to the general population. Implementation of the World Health Organization (WHO) TB infection control measures can protect HCPs from contracting TB; however, many studies have shown poor adherence to guidelines by HCPs. The aim of the study was to determine dieticians’ knowledge, attitudes and experiences in relation to TB at the workplace. A descriptive quantitative, cross-sectional research design was employed. Convenience sampling was applied. The online survey was conducted between August 2014 and March 2015. Data analysis included descriptive and inferential statistics. Ethical principles were adhered to. The sample consisted of 102 registered dieticians in South Africa. Good knowledge was displayed as two-thirds of dieticians correctly identified the National TB Management Guidelines and the main signs and symptoms of TB. However, a critical knowledge gap regarding TB transmission was identified, as only 42% of dieticians knew that TB could spread by talking. Favourable attitudes towards TB and infection control measures were present, except towards inadequate staffing levels and being worried about TB. The respondents reported that the fear of contracting TB affected patient interaction. Poor adherence to infection control measures was found. Only 45% of dieticians reported having a written TB infection control plan at their workplace, and only 23% were trained on TB infection control measures. Coughing patients were not always triaged and education material was not always available for TB patients. The availability of N-95 respirators was reported by 76% of dieticians. Training on TB infection control measures could influence dieticians’ adherence to infection control measures, ultimately protecting them from contracting TB at the workplace.

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.

MPH / Department of Public Health