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

Introduction: Migrant and mobile seasonal farm workers face multiple challenges in preventing sexual transmission of HIV. They also fall beyond direct reach of district health promotion services and national HIV prevention communication interventions. HIV prevalence rates in rural farming communities are significantly higher than provincial averages. An integrated health promotion intervention was initiated in 2005 on commercial farms in Hoedspruit, Limpopo province, through the International Organization for Migration. In terms of HIV prevention the Hlokomela project’s key innovation was to employ a local process of participatory communication, with and within the farm worker community, in order to create a local context enabling of health promotion and within which efforts to prevent HIV could be more effective. The research sought to explore the social processes and actions related to the on-going process of dialogue at the core of the participatory communication process. The objective was to describe and analyse the role of dialogue during regular purposive face to face interactions with farm worker change agents, in promoting health and addressing vulnerability to HIV. Method: The study population comprised Hlokomela coordinators, farm worker change agents (Nompilos and Gingirikani) and key farm stakeholders from the 59 partner farms. Research was conducted in Hoedspruit, at the Hlokomela Wellness Centre and on a partner farm. A grounded theory approach was used for sampling: participants were selected through purposive sampling for the initial study sample, and theoretical sampling for the balance. Data was gathered monthly, in three stages between August and November 2010, through: 10 semi-structured in-depth individual interviews; 5 focus group discussions, and observation of 2 monthly meetings and a special event organised by the change agents. Data was analysed using a grounded theory approach. Findings: Farm workers perceive and experience the process of on-going dialogue in face to face interactions as being intertwined with other aspects of the intervention, in particular identification and action to enable access to health services. Hlokomela Coordinators guide and support the process as a means to empower a corps of primary farm worker Change Agents (Nompilos). Nompilos, in turn, apply the system to benefit and empower a wider group of farm worker as second level change agents (Gingirikani). Through this system farm workers have found ways to negotiate HIV-related stigma and cultural taboos on speaking about sex, and to address interpersonal tensions and violence, often gender related, on farms. They have come to consider themselves leaders and role models. Individuals have been enabled to define for themselves appropriate HIV-protective behaviours, and new HIV protective social norms which enable protective behaviours, have gained local currency. These norms include placing value on the opportunity and ability to communicate, to learn from each other, to develop different views, and to attain or protect family, physical and spiritual wellness. Discussion: The process of engagement and regular dialogue, nested in processes related to the other elements of the projects, has positively altered the material, experiential and symbolic context on partner farms. It constitutes effective communication for social change, and has enabled health promotion, as described by the Ottawa Charter, to be realised. This demonstrates that an on-going, participatory process of local communication can create an enabling environment for health promotion. A community of communication practice has been developed in the farming community; this constitutes a reservoir of social capital and capacity to communicate and addresses the need for innovative communication in rural settings. A discursive space and public of discourse around wellness and HIV has been created, and new leaders and alternative narratives, which constitute self and collectively defined “AIDS competency” in a marginalised setting, are becoming visible, suggesting pathways for future interventions to enable equivalent responses in similar settings. Conclusion: An opportunity exists to make more effective use of the power of face to face communication in defined local settings, in order to enable disempowered individuals to claim their human and health rights, to protect themselves from HIV, and to help activate and realise synergies in health and development objectives such as the Millennium Development Goals.

This item was digitized as part of the Million Books Project led by Carnegie Mellon University and supported by grants from the National Science Foundation (NSF). Cornell University coordinated the participation of land-grant and agricultural libraries in providing historical agricultural information for the digitization project; the University of Arizona Libraries, the College of Agriculture and Life Sciences, and the Office of Arid Lands Studies collaborated in the selection and provision of material for the digitization project.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the degree of Master of Science in Biology and Control of African Disease Vectors. Johannesburg, February 2012 / In Tanzania both Anopheles funestus and An. gambiae s.l. play a role as major vectors of malaria. Different species exist in the An. funestus group and the An. gambiae complex and play different roles in disease transmission. For malaria vector control programmes knowledge of vector species and their behaviour is key. A recent report on increased exophagy of An. funestus in southern rural Tanzania as a response to increased use of insecticide treated bed nets raised the question of whether there was misidentification of species and/or behavioural insecticide resistance playing a part. The present study used molecular tools to identify the species and determine human biting rates indoors and outdoors along with development and field evaluation of a new tool for sampling malaria vectors which is more effective than human landing catches. The results showed that the majority (96.2%) of the An. funestus group that were collected were An. funestus s.s. by PCR assay. Also, the exophagic proportion (45.9%) of An. funestus was lower than the endophagic proportion (54.1%), similar to other places in Africa, although in this study the difference was insignificant when untreated bed nets and treated bed nets were used. In addition, there was significant outdoor biting activity early in the evening that could lead to the malaria transmission cycle being unaffected by ITNs. The new trap, “Sticky Bucket Trap”, caught considerably fewer mosquitoes (14.2%) than that caught by human landing catches (85.8%), with statistical significance of P>0.05. These results imply that the sticky bucket trap is not a suitable substitute for human landing catches and some modifications are needed to make it more effective. Whereas indoor and outdoor proportions insignificant difference in feeding preference imply that both indoor and outdoor interventions should be used to control this vector.

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.

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.

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.

Diss. (sammanfattning) Uppsala : Univ., 2001. / Härtill 5 uppsatser.