This dissertation discusses anti-HIV-1 microbicide research. In particular, it concentrates on microbicide formulation and delivery. Microbicides are anti-HIV-1 agents that when applied in the human vagina or rectum may prevent sexual HIV-1 transmission. Although most of the anti-HIV-1 agents being developed as microbicides are active in vitro, they have proved to be ineffective in vivo. A review of microbicide development over the last decade expounds the view that unsatisfactory microbicide failures may be a result of inefficient delivery systems employed. Thus, necessitating a thorough scientific qualitative and quantitative investigation of important aspects involved in HIV-1 transmission as a prerequisite for microbicide development. In this dissertation it is postulated that intravaginal targeting of HIV-1 increases the chances of microbicide success, wherein vaginal micro-environmental factors including pH would be maintained at HIV-1 prohibitive acidic levels to ward off other sexually transmitted diseases which compromise vaginal epithelial barrier properties. Furthermore, targeting early stages of the HIV-1 infection accompanied by computation and delivery of appropriate microbicide quantities could result in an effective microbicide formulation. In an effort to address microbicide formulation challenges, an intravaginal delivery system able to deliver anti-HIV-1 agents (zidovudine and BP36) over 28 days was formulated. This delivery system is a caplet-shaped composite system comprising zidovudine (AZT) and BP36-loaded pectin-mucin-polyethylene glycol submicrospheres embedded within a poly(D,L-lactide), magnesium stearate, polyvinyl acetate/polyvinylpyrolidone (Kollidon® SR) and poly(acrylic acid) based polymeric caplet matrix. The delivery system was tested in vitro and in vivo in the pig model. X-ray imaging illustrated the delivery system swelling and its matrix contrast fading over time as vaginal fluid permeated the matrix’s core. Plasma, vaginal fluid and tissue drug was detected and quantified using ultra performance liquid chromatography-tandem photodiode array detector. AZT plasma and vaginal fluid concentrations measured on days; 3, 7, 14, 21 and 28 decreased gradually with time. Vaginal tissue AZT concentrations (after 28 days) were higher than plasma AZT concentrations and were in the same range as vaginal fluid AZT concentrations. The herbal extract, BP36, was detected in plasma, vaginal fluid and tissue but was only qualitatively analysed due to its lack of standardization. Histopathological analysis of excised vaginal tissue revealed different scores of abnormalities comprising mild to moderate epithelial proliferation and exocytosis, subepithelial leukocyte influx, perivascular cell cuffing and isolated epithelial erosion, stromal fibrosis and isolated tissue necrosis.

Dissertation (Ph.D.)--University of South Florida, 2007. / Title from PDF of title page. Document formatted into pages; contains 107 pages. Includes vita. Includes bibliographical references.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 7 uppsatser.

One-third of American children under the age of 18 years and one in ten Canadian children aged 0-11 years are exposed to environmental tobacco smoke (ETS) predisposing them to multiple health problems. Although several intervention strategies to reduce ETS exposure among children have been tested, to date there is not enough evidence to recommend one strategy over another. The objectives of this study were: (a) to test if parents' participation in an intervention based on an empowerment ideology and participatory experiences decreases the number of cigarettes smoked in homes; and (b) to identify barriers to making homes and vehicles smoke-free, as well as facilitators used by parents to manage these barriers. To enable informed decision-making on how to measure empowerment, a systematic review was conducted to identify questionnaires that best measure health-related empowerment among adults and in families. / In a randomized controlled trial, 36 families were allocated to the intervention (n=17) or control group (n=19). The six week intervention included three, two hour group sessions, followed by three follow-up telephone calls, all at weekly intervals. Data were collected in interviewer-administered questionnaires at baseline and at six months follow-up. / No significant difference was detected between the intervention and control groups in the number of cigarettes smoked in the home daily at six months follow-up. However empowerment increased and the number of cigarettes smoked in the home decreased in both the intervention and control groups from baseline (median=17) to six-month follow-up (median=5). / Parents identified multiple barriers to smoke-free homes and vehicles including personal factors, factors involving others, and factors related to the physical environment. The most commonly identified barriers to smoke-free homes were personal factors, with tobacco addiction cited most often. In describing how to overcome barriers, parents identified facilitators involving other people as most effective, yet they most often relied on themselves. None ofthe parents identified a health provider as a facilitator. The multiple and complex barriers identified in this study suggest that interventions and practice guidelines should incorporate multiple strategies and individualized approaches to assist parents to make their homes and vehicles smoke-free.

No description available.

published_or_final_version / Community Medicine / Master / Master of Public Health

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 Medicine in Diagnostic Radiology Johannesburg, 2013 / Palpable solid breast masses that are circumscribed and not calcified on mammogram or ultrasound are probably benign. There is controversy therefore, whether these deserve tissue diagnosis. More data is required to determine whether short term follow up can replace the need for biopsy. Benign appearing lesions greater than 3cm in diameter on ultrasound continue to undergo biopsy due to fear that a malignancy or phyllodes tumour might be missed. Published research reflects patients from Europe and North America, and no relevant data from Africa exists. AIM: This study aims to determine the histological spectrum of sonographically benign lesions greater than 3cm, which were biopsied, in our local population (majority of black patients) and to determine whether biopsy is indicated based on the local cancer risk. The study also aims to characterise the results by age and population group as well as correlate the histological result with the size of the lesion on ultrasound, the HIV status, family history and the seniority of the examining radiologists. MATERIALS AND METHODS: A retrospective descriptive study of biopsy results of sonographically benign breast masses was undertaken using biopsy procedural recording sheets. . The size of the lesions (continuous variables) mean with standard deviations was determined. The prevalence of lesions was expressed as a percentage. Other categorical variables were summarized as frequency and percentage. The vi histological spectrum of the lesions was determined. The HIV status and family history of the patients as well as the seniority of the reviewing radiologist was assessed. A Krusskal Wallis test and separate logistic regression analysis was used. RESULTS: A total of 68 patients (below 40 years of age) were included from a total of 13112 patients (of all ages) seen between 2007 and the end of 2010. 73 lesions were identified (65 benign and 8 malignant). The prevalence of benign lesions was 89.7%. .The prevalence of malignant lesions was 10.29%.There was little evidence to support lesion size for predicting histology (p value = 0.22) or benignity. There was little evidence that the family history and HIV status were significant. CONCLUSION: There was a high prevalence (10.29%) of malignancies in lesions classified by ultrasound as benign. The size of the lesion did not correlate with histological subtype or whether the lesion was benign or malignant. Training of sonographers, standardization of technique for established users and double reading, may produce a different result, as both junior and senior radiologists mistook malignant lesions for benign ones on ultrasound. Repeating this research using double reading after training may demonstrate whether there is a true higher prevalence of malignancy in ultrasonically benign breast lesions in our community. Until then, routine biopsy of these lesions is recommended.

A research report submitted to the Faculty of Health Sciences, School of Public Health, University of the Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the degree of Master of Public Health: Occupational Hygiene, Johannesburg, 2012 / The aim of the study was to determine if the gold mine under study achieved the 2008 elimination of silicosis occupational hygiene milestones as set out by the South African mining industry in 2003. To identify high risk quartz exposed occupations within the conventional stope and TM³ stope employees of an underground gold mine between July 2008 and June 2010; to describe the personal quartz exposure of conventional stope and TM³ stope employees in an underground gold mine between July 2008 and June 2010; and to compare the time weighted average (TWA) quartz exposures between the conventional stope and TM³ stope to the Department of Mineral Resources-Occupational Exposure Limit (DMR-OEL) of 0.1 mg/m3, the National Institute of Occupational Safety and Health-Recommended Exposure Limit (NIOSH-REL) of 0.05 mg/m3 and the American Conference of Government Industrial Hygienists-Threshold Limit Value (ACGIHTLV) of 0.025 mg/m3.

A research report submitted in partial fulfilment of the requirements for the degree of Master of Science in Epidemiology in the field of Infectious Diseases School of Public Health, University of the Witwatersrand May 2014 / South Africa continues to grapple with the HIV/AIDS epidemic almost 30 years since the disease was first described. South Africa has 6.4 million people living with HIV thereby contributing 17% to the global burden of HIV/AIDs even though it makes up 0.7% of the world population translating to an HIV prevalence of 10.6% in the general population. . Multiple concurrent sexual partnerships (MCP) and inconsistent condom use are notably the major contributors to the spread or transmission of HIV in South Africa. The South African government has allocated massive financial resources to support HIV/AIDS interventions, however, the epidemic continues to amplify in South Africa and there is a growing need for targeted HIV prevention interventions which will address behaviour change. Objectives The objectives of the study were to determine the differences in sexual risk behaviour between self-identified HIV positive and HIV negative men and identify factors associated with sexual risk behaviour. Methodology This was secondary data analysis of a cross sectional design study called "Risk Perceptions of HIV Positive Men" and it was conducted in clinics from Soweto, Cape Town and the Cape Winelands from October 2010 to July 2011. The sample size was 451 and the study population comprised self-identified HIV positive and negative men between ages 18 - 60 years. Proportion of consistent condom use (CCU) and multiple concurrent partnerships (MCP) were calculated and difference between those self-identified HIV positive and negative were determined using Chi-square tests. Factors associated with MCP and CCU between the two groups was determined using univariable and multivariable logistic regression Results We analysed data for 451 men with a mean age of 39 years (std. dev. 11.30). Out of the 451 men 311 (69%) identified themselves as HIV positive and there was a statistical significant difference in baseline characteristics between HIV positive and HIV negative men (age, race, relationship status, employment status, education level, religion, area of residence, age at sexual debut, condom use at first sex, sexual orientation and circumcision status). HIV positive men were four times more likely to have used condoms consistently in the last six months compared to HIV negative men (AOR=3.72, CI: 1.95-7.11), however, HIV positive men were also four times more likely to have had Multiple Concurrent Partnerships in the last 12 months compared to HIV negative men (AOR=4.60, CI: 2.09- 10.12) . Other factors associated with sexual risk behaviour were; relationship status, age group, race, age at sexual debut, alcohol frequency, sexual orientation and perceptions about undetectable viral load reducing HIV transmission risk. Conclusion and recommendation There is a difference in sexual risk behaviour between men who identified themselves as HIV positive and those who identified themselves as HIV negative. Men who identified themselves as HIV negative were less likely to have used condoms consistently in the last six months. Though the HIV positive men are using condoms consistently they have multiple concurrent partners. There is need to strengthen post HIV test counselling coupled with targeted messages for both HIV positive and HIV negative men.

A research report submitted to the School of Public Health, University of the Witwatersrand (Johannesburg, South Africa) in partial fulfilment of the requirements for the degree of Master of Public Health for the year 2014 / Introduction: After 12 years of implementing the national Prevention of Mother-to-Child Transmission of HIV (PMTCT) programme in South Africa, interventions to prevent MTCT of HIV are now offered in more than 95% of public antenatal and maternity facilities country-wide free of charge (MRC, 2010), even though HIV/AIDS-related diseases are said to be a major cause of death in young children (UNICEF, 2011). The context within which women make decisions about PMTCT participation depends on, amongst other things, the level of their knowledge about HIV/AIDS (Leonard et al, 2001; Sematimba et al, 2004). The concept of behavior-based programming is central to a behavior change approach to reducing Mother-to-Child Transmission of HIV. This places behaviours at the centre of the program design process (Moore, 2003). Understanding the providers and users of the PMTCT interventions’ knowledge and experience on HIV and PMTCT is therefore important to ensure appropriate interventions to address beliefs, attitudes, myths and misunderstandings. Methodology: Semi-structured interviews were conducted with users of the PMTCT programme, while structured survey questionnaires were collected with the providers of the PMTCT programme in early 2012. Users of the PMTCT programme were asked questions regarding HIV knowledge, experience of HIV testing in pregnancy, PMTCT knowledge and experience of the PMTCT programme. We also asked questions on infant feeding choices and practices. Forty six interviews were carried out with participants at three ANC Clinics with PMTCT services in Soweto - Gauteng. Thirty were users of PMTCT programme and sixteen were providers of PMTCT service. Results: All participants understood that HIV was a virus that affected the immune system. Results show that there is generally a good understanding of HIV and how it is transmitted. In addition there was a good understanding on methods to prevent acquiring HIV. There was a general feeling that a lot of people were afraid of being tested. Interestingly, most participants believed that people who were pregnant or sick had no choice but to get tested. Most of the participants believed that education should be a tool used to motivate more people to get tested for HIV. Most users in this study disclosed their HIV status and PMTCT programme use. Overwhelmingly the decision to participate was based on the desire not to infect their infants. Women had been informed that mixed feeding increased the risk of transmission by breast feeding. There were a few participants who believed that HIV infected women should not breastfed. It was found that almost two-thirds of the women in this study were formula feeding their infants. Reason cited for formula feeding was that they did not want to infect their infants. As far as PMTCT knowledge was concerned, it was found that almost all health care providers knew that the most common route of HIV acquisition was through heterosexual sexual practices. All the HCWs knew that prolonged breastfeeding increased the risk of transmission. Reassuringly all HCWs knew not to use invasive delivery procedures and that risk of transmission was decreased with low maternal viral load. Only 50% of the HCWs indicated that the first choice of WHO- recommended mother-to-child regimen for antiretroviral prophylaxis in PMTCT was Zidovudine (ZDV) and Nevirapine (NVP) (WHO, 2012). The HCWs understood that infant formula did not provide superior nutritional support or antibody protection. They also knew that formula feeding carried increased risk of diahorrea or bacterial infections. There was confusion regarding the duration of exclusive breast feeding. Only half of the HCWs stated that post-natal infant-feeding counselling and follow-up are required whenever a mother decides to change her feeding practice. HCW participants felt that most patients fail to adhere to their medication requirements. This was cited to be mainly due to the fact that patients may not have disclosed their HIV status to the household members. Baby feeding choices are cited as the strongest barriers to the success of the PMTCT programmes. Mothers who have not disclosed their HIV status to their household members find it difficult to comply with the chosen feeding choices especially bottle feeding; they therefore opt for exclusive breastfeeding –which family members attempt to interrupt with mixed feeding practices for a number of reasons. Conclusion: Contrary to studies cited in the literature review, health systems failure was not a major problem in Soweto and therefore was not a factor that could impact on either the knowledge or the experience of users and providers. Even though disclosure rates were high amongst the users interviewed in this study, participants believed that the biggest barrier to people participating in the PMTCT programme was because of stigma, ignorance, and fear that they may be recognised while accessing services by people they may know. Although women had been provided with information on exclusively breastfeed, most users of the PMTCT programme interviewed were bottlefeeding – not due to stigma, but due to fear of transmission. In terms of barriers – adherence was noted as a major problem by providers. This linked to issues of feeding practices - if mothers bottle-feed they are stigmatised and opt for exclusive feeding, but are then forced by family to supplement with the bottle for various reasons. Mothers do not reveal their status, which jeopardises their success on the programme