Biotène® products have been developed with the intention of preventing tooth decay, plaque accumulation and oral infections in individuals with xerostomia (dry mouth). Not much is known about the effect of Biotène® chewing gums. Biotène® chewing gum contains host proteins. Due to these contents the manufacturer claims that Biotène® chewing gum is an “enzyme gum” that “boosts and strengthens the mouths natural defences”. The aim of this study was to investigate the effect of Biotène® chewing gum on saliva flow rates, saliva buffering capacity, plaque index, as well as salivary Streptococcus mutans and Lactobacilli counts, in healthy subjects with hyposalivation. One hundred and nine subjects with an age range of 18 to 23 years were screened for hyposalivation. Hyposalivation is a reduced salivary flow rate in a subject based on examination of the subject. Thirteen healthy subjects, who initially presented with hyposalivation, were included in the study. A baseline laboratory analysis of saliva was performed. Saliva was collected at rest and with masticatory stimulation, and measured. Resting saliva is saliva produced without any stimulation and can be obtained by allowing the subject to passively drool into a sputum jar. Stimulated saliva is produced as a result of stimulation of the salivary glands and may be obtained by allowing subject to chew inert rubber tubing while expectorating into a sputum jar. Buffering capacity was performed on both the saliva samples. Plaque index and DMFT was measured. Bacterial counts such as S. mutans and Lactobacilli counts were performed on the stimulated saliva. Subjects were given rubber tubing, xylitol chewing gum or Biotène® chewing gum to use for 2 weeks. A rubber tubing phase was introduced into the study to eliminate the effect of masticatory stimulation, which any chewing gum can provide. A xylitol-containing chewing gum (xylitol) phase was also introduced into the study in order to eliminate the effect of xylitol, as Biotène® chewing gum contains xylitol. A second laboratory analysis of saliva was performed. After a two weeks wash out period the second test product was given and the same procedure was repeated with the third product. The results showed that two weeks use of Biotène® chewing gum had no significant effect on the resting and stimulated saliva flows. It did not increase the buffering capacity of either the resting or stimulated saliva samples. Although it did not reduce the plaque index and S. mutans counts, it significantly reduced the Lactobacilli counts. Xylitol chewing gum, which was used as a control to eliminate the xylitol effect from the Biotène® chewing gum, significantly increased the stimulated saliva, reduced the plaque index and the salivary Lactobacilli count. Biotène® chewing gum which contains host proteins has no beneficial effects regarding saliva flow rate or against dental plaque and therefore against dental caries.

PhD, Faculty of Law, Commerce and Management, University of the Witwatersrand, 2009. / The global health revolution of the last 50 years has generated significant health gains in terms of increased life expectancy and reduced maternal mortality. South Africa, an upper middle income country, has performed poorly along the same development indicators. Development gains for women and children won over two decades are now being reversed, largely due to HIV/AIDS. This is in spite of the evidence that lifesaving antiretroviral medication can prolong life and enhance quality of life. Using a joint capabilities and health equity lens, this thesis seeks to understand a critical development problem in South Africa – premature mortality in pregnant women and children attributed to HIV – an infectious disease that is both preventable and treatable. The research identifies key barriers faced by pregnant and postnatal women with HIV who seek (freely available) access to PMTCT (prevention of mother to child HIV transmission) and ART (antiretroviral therapy) programmes in the public health sector. The study considers whether disparities in, and missed opportunities for, preventing and treating HIV in these population groups comprise avoidable, systematic and unfair health inequities. The implications for the capabilities of women and children with HIV in this country are also explored. Qualitative research methods are employed to investigate the research concern. Semi-structured interviews with 83 women comprise the mainstay of the field research. Interviews with 37 caregivers of children with HIV, together with patient files and interviews with key informants, supplement the data collection. Research was undertaken in two sites in two provinces: Eastern Cape and Gauteng. Each site constitutes a bounded case study. A rural-urban perspective is put forward – with attention to equity considerations in access to maternal-child HIV services. The study evinces a host of avoidable factors in the operational delivery of ART/PMTCT, along a range of intervention points in the continuum of care: including the antenatal, labour, postnatal and pediatric wards. While some of these factors are influenced by individual behaviour, the vast majority are directly linked to the health system – illuminating the ways in which the health system serves as a social determinant of health (SDH), and often restricting, constraining, and ironically, preventing people from obtaining the interventions and information they need to improve their health. iii By connecting the empirical findings related to ART/PMTCT within the health system to the capabilities and health equity literatures, an understanding of disparities in access to, and delivery of, such services – and their importance in shaping health, development and health outcomes of these population groups – becomes clearer. As a consequence, strengthening the public health system is a necessary first step to ensuring at least some of the minimum conditions that allow people to be healthy. As an entry point, there is great scope for systems’ interventions that would address the shortfall in health for black South Africans and deprivations in their health capability. At the same time, the research reveals that – owing to the contribution of social determinants of health (e.g., factors that impact on health such as living and working conditions, but lie outside the realm of healthcare) to health status: good health is not achieved solely by access to and provision of good healthcare. This reality underscores the importance of health as a central capability; and good health as a normative social goal. In the capability view, the moral concern for state and society is the reduced capability of individuals due to health inequities that are socially-constructed, and in turn, changeable. Recommendations to address modifiable factors related to effective ART/PMTCT provision in these facilities are put forward, with a set of suggestions for future research in maternal, child and women’s health in South Africa.

Hepatitis B virus (HBV) is hyperendemic to southern Africa and parts of Asia where it is a major cause of serious liver disease. Licensed antivirals for chronically infected individuals are only partially effective and approximately one million deaths occur annually as a result ofpersistent infection with the virus. Although RNA interference (RNAi) based gene silencingof HBV has been successfully demonstrated, difficulties with delivery of anti-HBV RNAieffectors remains an obstacle to their clinical use. Recombinant adenoviruses (Ads), amongst the most efficient hepatotropic gene vectors following systemic administration, have been successfully used to deliver expressed anti-HBV RNAi sequences. However, a drawback of Ad vectors is diminished efficacy and toxicity that results from stimulation of innate andadaptive immunity.To attenuate these effects we used polyethylene glycol (PEG) to modify first generation recombinant Ad (FG Ad) vectors that express an anti-HBV short hairpin (shRNA) sequence. Efficient hepatocyte transduction occurred and expressed shRNAs were processed to generate intended HBV-targeting guides. Inhibition of HBV replication was achieved after intravenous administration of PEGylated or native recombinant first generation Ads (FG Ads) to HBV transgenic mice. Circulating HBV viral particle equivalents (VPEs) remained low for 3 weeks and began to increase after 5 weeks. A second dose of PEGylated anti-HBV Ad caused a less sustained decrease in circulating VPEs, but no silencing after a second dose was observed in animals treated with unmodified vector. Release of inflammatory cytokines was elevated in animals receiving unmodified vectors and only a modest increase in monocyte chemotactic protein-1 (MCP-1) was observed in mice that received a second dose of PEG Abstract Ads. Also, polymer-conjugated vectors induced a weaker adaptive immune response and were less hepatotoxic than their unmodified counterparts. To address concerns about the transient nature of transgene expression by FG Ads resulting from immunostimulation, third generation helper-dependent (HD Ad) were utilised to delivered anti-HBV RNAi effectors. Seven days after intravenous administration of infectious HD Ads to HBV transgenic mice, 80-90% of hepatocytes were transduced and markers of HBV replication were decreased by approximately 95% which was sustained for 8 weeks. HD Ad-induced release of proinflammatory cytokines was minimal in preparations that were enriched with infectious particles. PEGylated HD Ad vectors caused similar anti- HBV effects and may be useful to evade interaction with vector-sequestrating receptors and further attenuate immunostimulation. Collectively these observations indicate that PEG modification of Ads and the use of HD Ads may have utility for delivery of therapeutic HBVsilencing sequences. Future work will focus on improving strategies to avoid immune detection and utilisation of HD Ad vectors for other HBV targeting sequences.

Thesis (M.Med.(Orthopaedic Surgery))--University of the Witwatersrand, Faculty of Health Sciences, 2013.

HIV-1 integrase is an essential enzyme in the HIV replication cycle and is a validated target for antiretroviral drugs. Due to the inevitable emergence of drug resistance of HIV-1 strains to all currently approved FDA antiretroviral drugs, antivirals with new mechanisms of action are continuously investigated. As such, this study aimed to reposition existing drugs as HIV-1 integrase inhibitors by screening the NIH Clinical Collection compound library comprising 727 compounds. Recombinant integrase was expressed in bacterial cells, purified by nickel affinity chromatography, and used to set up a Scintillation Proximity Assay (SPA). The SPA was subsequently amended to an automated system to allow for rapid screening of compounds. The complete compound library was successfully screened using the newly established automated SPA. Overall, only two compounds were identified as HIV-1 IN inhibitors: cefixime trihydrate and a previously identified HIV integrase inhibitor, epigallocatechin gallate. These compounds exerted IC50 values < 10μM in the automated SPA. Cefixime trihydrate was not toxic to mammalian cells (CC50 > 200μM) while no appreciable antiretroviral activity was observed in in vitro phenotypic inhibition assays (23% inhibition of viral replication), thus concluding that this compound was non-selective. By contrast, epigallocatechin gallate was toxic to mammalian cells at the evaluated ranges (CC50 = 23 + 1μM) and therefore could not be validated as an integrase inhibitor in in vitro phenotypic inhibition assays. Overall, this study resulted in the establishment of an automated SPA, the successful screening of 727 compounds, and the availability of a platform to expedite the future screening of potential HIV-1 integrase inhibitors.

M.Sc (Med.), Faculty of Health Sciences, University of the Witwatersrand, 2009 / Background: Bacterial vaginosis (BV) results from a shift in normal vaginal flora and predisposes women to sexually transmitted infections (STI) including HIV. Risk factors for BV are not well understood. This analysis seeks to determine the disease frequency of BV, assess determinants of BV and quantify time to first BV episode in HIV negative women. Methods: Baseline and follow-up data from 1066 women was analysed in STATA10. Logistic regression was used to determine baseline factors associated with BV and Kaplan Meier survival analysis to estimate time to BV episode. Results: BV prevalence and incidence was estimated at 48.42% and 81 cases per 100 women years respectively. Controlling for age and education, women with Trichomonas vaginalis, Chlamydia trachomatis, Herpes Simplex Virus2 and lower socio-economic status were 67%- 380%, 31%-472%, 20%-220% and 4%-91% more likely to present with BV respectively. Consistent condom use and being a housewife or student was significantly (p<0.05) associated with lower prevalent BV, with a significant interaction between age and education (p<0.05). The median time to first BV episode was 9.7 months. Conclusion: The analysis identifies modifiable risk factors like condom use, injectable contraceptives and treatment of STIs which could potentially decrease the high BV disease burden.

In order to employ the Sterile Insect Technique (SIT), biologically fit mosquitoes able to compete with their wild counterparts, suitable field sites for mass release of sterilized male mosquitoes, and appropriate methods of rearing genetic sex-separation (GSS) mosquito strains are required. The life history traits and biological fitness of four laboratory-reared, southern African Anopheles arabiensis strains were investigated. Despite being colonized at different times, the four strains demonstrated comparable levels of biological fitness. Three sites in the Kruger National Park were assessed as possible SIT field sites. Mosquito collections were conducted at each site during three summer months. Anopheles arabiensis was predominant at Malahlapanga during each collection period, establishing Malahlapanga as the most appropriate site for SIT field trials. A standard larval diet was shown to be appropriate for rearing An. arabiensis GSS. This work formed the laboratory basis for the evaluation of a SIT strategy for South Africa.

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This thesis explores the use of universal, prevention programmes in primary schools. A systematic literature review examined the effectiveness of universally targeted, schoolbased body-image programmes in children under 12. The review highlighted that approximately half of programmes were successful in reducing body dissatisfaction or improving body satisfaction. Improvements in other associated risk factors were also found. Not all results were maintained at follow-up and the longer-term impact of such programmes was not clear. There were also several methodological concerns that must be considered. An empirical study investigated the use of a bullying programme, KiVa, in Welsh primary schools and the school-level factors that predict outcomes. A mixed-methods approach was used with analysis of pupil survey data and interviews with school staff. KiVa was found to have a positive impact on bullying behaviour which continued as years progressed. School level free-school meal percentage as a proxy for socio-economic deprivation and additional learning needs were found to be predictive of KiVa outcome. Teachers also discussed several within school-factors that they felt affected implementation. The final chapter discusses the implication of the findings for future research and clinical application in relation to other research. Recommendations are made for how schoolbased programmes may be successful implemented within primary schools. Finally, a personal reflection of the research process is considered.