published_or_final_version / Community Medicine / Doctoral / Doctor of Philosophy

published_or_final_version / Politics and Public Administration / Doctoral / Doctor of Philosophy

Approved for public release, distribution is unlimited / Extreme examples like the Spanish Flu pandemic of 1918 make clear the devastating impact that communicable diseases can have on military readiness. It is highly desirable to have models and tools that can be used to evaluate the course of a disease over time. These tools can help assess the effectiveness of strategies employed to contain the outbreak such as constraining movement, wearing protective gloves or masks, closing high traffic areas, etc. Armed with these tools, a medical practitioner can better assess the right course of action in a time critical situation. The primary difficulty with creating models and simulations for this purpose is that disease spread depends upon the details of human behavior and environmental variables which are not accounted for in current mathematical models. The likelihood that a particular individual will catch a given disease depends upon such specifics as where he works, whom he interacts with, where he sleeps, what he eats, his habits of personal hygiene, etc. It is hypothesized that a software disease simulation can combine agents that mimic human behavior, a ship specific environment, and disease specific attributes to more accurately model the spread of disease aboard ship than a mathematical model. / Outstanding Thesis / Lieutenant, United States Navy

Philosophiae Doctor - PhD / Background: Non-communicable diseases (NCDs) continue to rise in South Africa, accounting for 43% of total deaths in 2012. Smoking and a diet high in salt are among the major modifiable risk factors for NCDs that can be addressed through cost-effective policy interventions in the form of regulation or legislation and active multisectoral engagement. Population-based prevalence and mortality data are necessary for monitoring and evaluation such interventions. South Africa has developed a National Strategic Plan for NCDs but there is limited evaluation of NCD policies. Furthermore, there is a need to explore the availability of population-based data and the role that it can play to monitor interventions. Aim: The overall aim of the thesis is to assess the implementation of policies for reducing risk factors for chronic NCDs in South Africa, and to explore the role of population-based data in supporting environmental and policy approaches to prevent NCDs. The thesis will also examine whether there are differences in urban and rural settings in the implementation of tobacco control and salt reduction regulation as well as the barriers to implement the National Strategic Plan for prevention of NCDs. Methods: Multiple methods of data collection were used. A desk review of policies to address NCDs in South Africa was undertaken and semi-structured interviews with the NCD policymakers and managers in two provinces (the Eastern Cape and Western Cape) were undertaken, to explore challenges and successes of implementation of the NSP. The Cross-sectional baseline questionnaire and quantified food frequency data from the PURE study were used to determine the prevalence of smoking and the intakes of sodium and potassium in a selected urban and a rural community. Data collected using a validated community audit tool was used to assess the physical environment related to tobacco as well as questionnaire data from face-to-face interviews about perceptions about tobacco use in the urban and rural communities. Trends in mortality from tobacco related and high salt consumption related conditions together with prevalence data from national health surveys were reviewed to assess the health impact.

Philosophiae Doctor - PhD / Non-communicable diseases (NCD) continue to be a public health concern globally and contribute to the burden of disease. The formal health system in developing countries lacks the capacity to deal with these NCD as it is overburdened by communicable diseases. Thus, community health workers (CHWs) have been suggested as a solution for alleviating the burden for primary health facilities, by extending NCD care to the community. This thesis aims to develop an integrated model of care for CHWs working with patients with non-communicable diseases by describing and exploring current CHW roles, knowledge and practices in relation to community-based NCD care. The specific objectives for this study included 1) the exploration of the NCD roles of generalist CHWs in the context of a limited resource urban setting; 2) determining the NCD-related knowledge of CHWs, and factors influencing this in a limited resource urban setting and 3) a comparison of actual and envisaged roles in the management and prevention of NCD using the integrated chronic diseases management model (ICDM) as a benchmark, and propose key competencies and systems support for NCD functions of CHWs in South Africa Mixed methods were used to achieve the objectives of this study. First, a qualitative enquiry was conducted using observations to respond to the first objective. A quantitative cross-sectional design was then used to achieve the second objective, and a questionnaire was used to interview CHWs. A comparison of findings from both the quantitative and qualitative studies with policy guidelines was undertaken to address the third objective.

Magister Artium (Sport, Recreation and Exercise Science) - MA(SRES) / The prevalence of non-communicable diseases (NCDs) are the rising cause of mortality globally. Physical inactivity, unhealthy diet, tobacco use, and excessive alcohol consumption are common NCDs risk factors contributing to premature death, related to NCDs worldwide. Youth’s lack of knowledge and misconception on physical activity (PA) and NCDs risk factors, aids the growing burden of NCDs globally. Thus, the purpose of this study is to explore the knowledge and perception of youth in a low-resourced community in the Western Cape Province. A qualitative methodological approach was adopted for data collection, using a qualitative exploratory study design. Convenience sampling was used to select the female youth participants, aged 18-35 years old from, Vrygrond in the Western Cape Province. Focus group discussions were steered by means of a semi-structured interview plan to guide the discussion about perceptions and knowledge of PA and NCDs risks factor. Trustworthiness was used to review information and to assess accuracy of findings. The discussions were analysed using Atlas.Ti8. Results indicated that the female youth were reasonably knowledgeable about the term PA. However, they lacked sufficient knowledge with regards to NCDs, indicating that participants are uninformed about NCDs and their risk factors in their community and local healthcare centres. Female youth’s socio-economic environment had an influence impact on their perceptions and decisions made with regards to PA and preventing them from engaging in NCDs risk factors. Furthermore, there were various barriers hindering the female youth from participating in PA and preventing them from engaging in NCDs risk factors. Results of this study will inform policy at the provincial, and national level, to provide cost effective and sustainable educative intervention programmes that address the youth misconception on physical activity and NCDs risks factor. Creation of awareness can positively influence beliefs and promote healthier practices, therefore making it crucial to understand NCDs risks factor implications on health, in lieu to combating the onset of NCDs.

A dissertation submitted to the Faculty of Science under the School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Master in Science. Johannesburg, June 2017. / In South Africa, the anti-HIV-1 activity of various indigenous plants has not been studied extensively. Most of the phytochemical screening work has focused on anti-cancer activity with less attention given to infectious diseases. A large proportion of South Africans (70-80%) still rely on traditional medicines for treatment of various ailments. And, therefore, there is a need to evaluate and validate the effectiveness of the traditional medicines. The aim of this study was to identify, screen, phytochemically characterize and isolate bioactive compounds from a South African herbal extract that exhibit the best anti-HIV-1 activity. Three extracts were prepared: an ethanol extract, a dereplicated ethanol extract and an aqueous extract from a herbal concoction comprised of a mixture of six plants. These herbal concoctions were investigated for anti-HIV-1 subtype C activity. Phytochemical profiling of the ethanol- and dereplicated ethanol- extracts from the herbal concoctions showed the presence of intermediate polar compounds (flavonoids, alkaloids, sugars and terpenes) for both extracts, while the aqueous extract contained predominantly highly polar compounds. Anti-HIV-1 screening of the three extracts showed that the ethanol and dereplicated ethanol herbal- extracts had the best anti-reverse transcriptase activity. The ethanol extract had mean IC50 values of 56.53, 53.96 and 55.39 μg/ml against MJ4, Du179 and CM9 HIV-1 subtypes C isolates, respectively. The dereplicated ethanol extract had mean IC50 values of 51.87, 47.56 and 52.81 μg/ml against MJ4, Du179 and CM9 HIV-1 isolates, respectively. The aqueous extract was inactive against HIV-1 activity. Moreover, both the ethanol- and dereplicated ethanol- extracts showed activity against HIV neutralization. The ethanol- and dereplicated ethanol- extracts had mean IC50 values of 36.33 and 32.06 μg/ml, respectively. Furthermore, they also potently neutralized Vesicular stomatitis virus (VSV) yielding mean IC50 values of 24.91 and 20.82 μg/ml for ethanol- and dereplicated ethanol- extracts, respectively. All extracts were inactive against Murine leukemia virus (MLV). The isolation and phytochemical characterization of the bioactive compound(s) was done by utilizing various chromatographic and spectroscopic methods. Four homoisoflavanoids were isolated and tested for anti-HIV-1 subtype C activity. Three compounds (1, 3a and 3b) were inactive while compound 2 was found to be bioactive against HIV-1 reverse transcriptase (RT) and yielded mean IC50 values of 7.23 ± 1.88, 12.83 ± 0.41 & 12.81 ± 0.10 μg/ml for MJ4, CM9 and Du179 HIV-1 subtype C isolates, respectively. Compound 2 had a mean CC50 value of 23.08 ± 0.1981 μg/ml against HEK293T cells. Overall, the data suggested that ethanol- and dereplicated ethanol- herbal extracts possess direct and indirect anti-HIV-1 activity. They possess a cocktail of phytochemicals that can inhibit HIV-1 RT, HIV-1 entry. Furthermore, these extracts possess phytochemicals that can lower the activation of inflammatory responses during an infection and, hence, reduction in the number new cells infected during the course of HIV-1 infection. Moreover, they possess phytochemicals that have antioxidant activity which, in relation to HIV infection, results in a boosted immune system response in order to ward off the virus. / MT 2017

Introdução - Considerada um grave problema de saúde pública mundial em regiões de clima tropical e subtropical, a dengue foi a única dentre as doenças tropicais negligenciadas a apresentar tendência de aumento na mortalidade nos últimos anos. Fatores relacionados ao ciclo de vida do principal vetor, fêmeas do mosquito Aedes aegypti, influenciam a distribuição espacial e o caráter sazonal da doença. A incidência de casos de dengue é dependente de uma complexa rede de relações entre vetor, vírus e hospedeiro, assim como a ocorrência de casos graves e de óbito. Desde a introdução do vírus, o estado de São Paulo vem apresentado epidemias envolvendo número cada vez maior de municípios, de incidência de casos e de óbitos por dengue. Objetivo - Avaliar a distribuição espacial, temporal e espaço-temporal dos óbitos por dengue no estado de São Paulo. Métodos - Trata-se de estudo ecológico, com componentes espacial e temporal, a partir da notificação de óbitos por dengue no SINAN, tendo como unidades de análise os municípios e as microrregiões do estado de São Paulo, no período de 1998 a 2017. Os óbitos por dengue no estado de São Paulo foram descritos segundo sexo e idade. As taxas de mortalidade bruta, padronizada por sexo e idade e suavizada pelo método bayesiano empírico local foram estimadas e mapeadas segundo município de residência. Os sorotipos detectados pelo Instituto Adolfo Lutz foram mapeados segundo microrregião. Estimou-se as tendências temporais da mortalidade. Aglomerados de alto risco espacial e espaço-temporal e de variação espacial na tendência temporal foram detectados e mapeados. O risco relativo espacial da mortalidade por dengue ajustado pelo tempo e covariáveis consideradas foi estimado por modelos Bayesianos Gaussianos Latentes com abordagem INLA (2007 - 2016). Foi aprovado pelo Comitê de Ética em Pesquisa da Faculdade de Saúde Pública da Universidade de São Paulo sob parecer de número 1.687.650. Resultados - Foram identificados 1.121 óbitos por dengue com confirmação laboratorial e residentes no estado de São Paulo entre 1998 e 2017. A mediana de idade foi de 57 anos. A média anual da mortalidade bruta por dengue no estado de São Paulo na série histórica foi de 0,14 óbitos por 100.000 habitantes. Houve tendência de elevação da mortalidade para todos os sexos e idades no período, sendo o crescimento mais proeminente nos adultos com >= 50 anos, e de aumento do percentual de municípios com casos e óbitos ao longo dos anos estudados. Houve associação positiva entre as regiões com maior quantidade de sorotipos e taxas de mortalidade mais elevadas. Aglomerados de alto risco foram identificados nas áreas com alta taxa de mortalidade. O grau de urbanização, número de anos com casos e a introdução de novo sorotipo associaram-se a um maior risco relativo para a mortalidade por dengue. Tanto as taxas de mortalidade mais elevadas, quanto os maiores riscos relativos para o óbito foram observados nas regiões norte, noroeste, oeste, sudeste e litoral do estado de São Paulo. Conclusão - a mortalidade por dengue no estado de São Paulo apresentou padrão cíclico e sazonal, com tendência de elevação principalmente nas faixas etárias mais avançadas. Houve identificação de agregados de área de alto risco, com associação do grau de urbanização, do número de anos com casos e da introdução de novo sorotipo a maior risco de mortalidade por dengue. / Introduction - Considered a major global public health problem in tropical and subtropical regions, dengue was the only one among neglected tropical diseases to show an increase in mortality in recent years. Factors related to the life cycle of the main vector, females of Aedes aegypti mosquito, influence the spatial distribution and the seasonal nature of the disease. The incidence of dengue cases is dependent on a complex network of relationships between vector, virus and host, as well as the occurrence of severe cases and death. Since the introduction of the virus, the state of São Paulo has been presenting epidemics involving an increasing number of municipalities, incidence of cases and deaths due to dengue. Objective - To evaluate the spatial, temporal and spatial-temporal distribution of dengue deaths in the state of São Paulo. Methods - This is an ecological study, with spatial and temporal components, based on the notification of dengue deaths at SINAN, with the municipalities and microregions of the state of São Paulo as analysis units from 1998 to 2017. Deaths from dengue in the State of São Paulo were described according to sex and age. The crude mortality rates standardized by sex and age and smoothed by the local empirical Bayesian method were estimated and mapped according to the municipality of residence. The serotypes detected by the Adolfo Lutz Institute were mapped according to microregion. The temporal trends of mortality were estimated. High-risk space and space-time clusters and spatial variation in time trend were detected and mapped. The spatial relative risk of dengue mortality adjusted by time and covariables considered was estimated by Latent Gaussian Bayesian models with INLA approach (2007 - 2016). It was approved by the Research Ethics Committee of the School of Public Health of the University of São Paulo under opinion number 1,687,650. Results - A total of 1,121 dengue deaths with laboratory confirmation were identified and residents of the State of São Paulo between 1998 and 2017. The median age was 57 years. The annual average of the gross mortality from dengue in State of São Paulo in the historical series was 0.14 deaths per 100,000 inhabitants. There was a trend of increased mortality for all sexes and ages in the period, with the most prominent growth in adults aged >= 50 years, and an increase in the percentage of municipalities with cases and deaths over the years studied. There was positive association between the regions with the highest number of serotypes and the highest mortality rates. High-risk clusters were identified in areas with high mortality rates. The degree of urbanization, number of years with cases and the introduction of a new serotype were associated with a higher relative risk for dengue mortality. Both the highest mortality rates and the highest relative risks for death were observed in the north, northwest, west, southeast and coastal regions of the State of São Paulo. Conclusion - dengue mortality in the state of São Paulo presented a cyclical and seasonal pattern, with a tendency to increase mainly in the more advanced age groups. There was identification of high risk area clusters, with association of the degree of urbanization, number of years with cases and the introduction of a new serotype at greater risk of dengue mortality.

International norms are central to international relations because they constitute key instruments to influence state behaviour (Finnemore and Sikkink, 1998; Risse and Sikkink, 1999; Acharya, 2004). The process by which international norms, principles and procedures diffuse into national systems is called norm diffusion (Krook and True, 2010; Towns, 2012; Brown, 2014). This thesis contributes to our understanding of the complexities of norm diffusion processes by undertaking the first in-depth analysis of the role that community-based organizations (CBOs) play in such processes. Focusing on the area of global health norms regarding HIV/AIDS, and based on extensive field research undertaken in Honduras, Ukraine, Uganda, and El Salvador, the thesis presents evidence of the CBOs analysed playing various essential roles in the diffusion of international norms domestically. First, they may act as implementers of such norms ensuring their appropriation among the populations they represent and generating local practice, on occasion even bypassing their own governments when these have rejected such norms. Second, CBOs may also be able to influence their governments and other relevant state actors at the later stages of norm diffusion, when states are deemed to implement international norms through their integration into national practice, even to the point of making states change their stated positions on certain international norms. Thirdly, through the simultaneous interaction with and entanglement in multiple norm diffusion processes, CBOs may also be able to alter such processes by tactically interlinking them and affecting their respective outcomes.

Submitted by Natalia Vieira (natalia.vieira@famerp.br) on 2016-05-20T18:39:11Z No. of bitstreams: 1 gismarmonteirocastrorodrigues_dissert.pdf: 1476033 bytes, checksum: 1656cd496debef44e68dd36fe6a5966c (MD5) / Made available in DSpace on 2016-05-20T18:39:11Z (GMT). No. of bitstreams: 1 gismarmonteirocastrorodrigues_dissert.pdf: 1476033 bytes, checksum: 1656cd496debef44e68dd36fe6a5966c (MD5) Previous issue date: 2007-09-13 / Fundação de Amparo à Pesquisa do Estado de São Paulo - FAPESP / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Introduction: Candida albicans is as a human oral cavity colonizer. However, for the human immunodeficiency virus (HIV) serum-positive individuals and/or acquired immunodeficiency syndrome (AIDS) patients, it assumes opportunistic profile causing, amongst other clinical manifestations, oropharyngeal candidiasis. In the population, it is also isolated a group of species named Candida “non-albicans”, whose response in the presence of antifungical drugs can diverge. Objective: To study Candida sp. oral colonization in HIV-1 carriers/AIDS patients and their respective group, and describe its antifungal susceptibility profile. Methodology: Oral cavity samples, collected from 52 patients and respective controls were submitted micromorphological analysis of the strains. The antifungal susceptibility profile was evaluated by disc diffusion and by broth microdilution, for the following drugs: anfotericin-B, ketoconazole, itraconazole and fluconazole. Results: Candida sp. colonization/infection index was higher in the HIV/AIDS patients compared to their controls (p<0.05), and C. albicans was the most isolated species. Candida “non-albicans” frequency was similar for both studied groups, including C. dubliniensis absence. Single and mixed species colonization/infection rates were superior among HIV/AIDS dental prosthesis users in relation to those without such apparatus (P <0.05). the strains of the C. albicans isolated from the group patient regarding the isolated in the control group, showed higherthe fluconazole minimum inhibitory concentration (CIM) (P<0,01), smaller percentages of dose-dependent susceptibility (SDD) to ketoconazole (P<0,1) and greater ones for itraconazole (P<0,06). Higher percentages of SDDs to the same drugs were provided by Candida “non-albicans” isolated from healthy individuals. None of the isolated strains displayed resistant phenotype to fluconazole whereas they were all sensitive to anfotericin-B. Conclusions: The HIV/AIDS group, compared to the HIV serum-negative individuals, is more often colonized by Candida sp., without changes in the albicans x “non-albicans” ratio, and also with equivalent antifungal susceptibility profiles. C. dubliniensis does not colonize/infects the oral cavities of HIV infected subjects/AIDS patients, or their healthy controls, from São Paulo State Northwest region. HIV carriers/AIDS personnel who make use of dental prosthesis have higher Candida sp. oral cavity colonization/infection rates, needing, therefore, closest attention to their oral health. / Introdução: Candida albicans é colonizadora da cavidade bucal humana sendo que em pacientes soropositivos para o vírus da imunodeficiência humana (HIV)/doentes com a síndrome da imunodeficiência adquirida (AIDS), assume perfil oportunista causando, dentre outras manifestações, a candidíase orofaríngea. Nesses indivíduos, são também isoladas as espécies “não albicans”, cuja resposta aos antifúngicos pode variar. Objetivo: Avaliar Candida sp. isolada a partir da microbiota oral de pacientes soropositivos para o HIV-1/doentes de AIDS e do respectivo grupo controle e descrever seu perfil de sensibilidade aos antifúngicos. Metodologia: As amostras obtidas a partir da mucosa oral de 52 pacientes e respectivos controles foram submetidas às análises micro-morfológicas das cepas. Para a pesquisa molecular de C. dubliniensis foi utilizada a reação em cadeia de polimerase. O perfil de sensibilidade antifúngica foi avaliado por difusão em disco e por microdiluição, frente à anfotericina B, cetoconazol, itraconazol e fluconazol... Resultados: O índice de colonização/infecção por Candida sp. foi maior no grupo HIV/AIDS comparado ao grupo controle (p<0,05), sendo C. albicans a espécie mais isolada. A freqüência de espécies “não albicans” foi similar em ambos os grupos, sem detecção de C. dubliniensis. O índice de colonização (única e mista) foi superior entre os pacientes HIV/AIDS usuários de próteses em relação aos não usuários (P <0,05). As cepas de C. albicans isoladas do grupo paciente em relação às isoladas do grupo controle apresentaram maior concentração inibitória mínima (CIM) frente ao fluconazol (P<0,01), menor percentual de sensibilidade dependente da dose (SDD) frente ao cetoconazol (P<0,1) e maior SDD para o itraconazol (P<0,06). Já Candida “não albicans”, isolada a partir de pessoas saudáveis, mostrou porcentagens maiores de SDD frente às mesmas drogas. Nenhuma levedura mostrou resistência às drogas avaliadas sendo unânime também a sensibilidade à anfotericina B. Conclusões: O grupo HIV/AIDS é mais colonizado por Candida sp. que os soronegativos para esse vírus, sem mudanças na proporção Candida albicans x “não albicans”, sendo que as cepas obtidas a partir de ambos grupos apresentam perfil de sensibilidade equivalente aos antifúngicos testados. C. dubliniensis não coloniza/infecta a mucosa oral dos portadores do HIV/doentes com AIDS ou de controles saudáveis da região Noroeste paulista. Portadores do HIV/doentes com AIDS que fazem uso de prótese dentária têm maiores chances de colonização/infecção da mucosa oral por tais levedu ras, necessitando, portanto, de maior atenção à saúde bucal.