Este trabalho apresenta o resultado do estudo das causas que interferem na busca passiva de casos de tuberculose pulmonar na população. Entrevistaram-se 350 indivíduos, bacilíferos e não bacilíferos, que procuraram o Centro de Saúde de Pinheiros-SP, durante o ano de 1985. Foram estudadas as informações obtidas referentes ao tempo decorrido desde a percepção de alguma sintomatologia pela população de estudo até a sua chegada ao Centro de Saúde. Os resultados obtidos permitem supor que boa parte da responsabilidade pela demora no atendimento correto da população pode ser atribuída aos profissionais das instâncias anteriores à procura do Centro de Saúde. Outros fatores relacionados à àrea do comportamento humano e a aspectos sócio-econômicos foram identificados como causa provável de demora para a procura de assistência adequada à saúde. Concluiu-se que a população não conhece ou conhece pouco as características da função assistencial do centro de saúde, com exceção da gratuidade dos serviços oferecidos. Este conjunto de fatores resultou num tempo de sintomatologia que variou de menos de 3 semanas até mais de 24 meses, com maior concentração de casos no espaço de tempo compreendido entre 3 semanas ate 12 meses, significando maior risco de disseminação da infecção na comunidade. / This work presents the results of the study of causes that interfere with the passive search of pulmonary tuberculosis cases in the population. Three hundred and fifty infection spreading and non infection spreading subjects who looked up the Pinheiros Public Health Center in the city of São Paulo throughout 1985 were interviewed. Information obtained regarding intervening time between perception of any symptom by the study population and its arrival at the Health Center was studied. The results obtained point ot to the fact that a good deal of responsability for the delay in the provision of correct care lies with the professionals of the anterior instances attended by the population before looking up the Health Center. Other factors related to the area of human behaviour and socio-economic aspects were also identified as probable causes of the delay in obtaining adequate health care. It is concluded that the population has little or no knowledge whatsoever regarding the health care function of the Health Center, save it being free of charge. This group of factors resulted in a symptomatology time span that varied from less than three weeks to twenty-four months with a higher concentration rate comprised between three weeks and twelve months meaning a larger infection spreading risk in the community.

Orientador: Helenice Bosco de Oliveira / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-06T00:26:46Z (GMT). No. of bitstreams: 1 Ferreira_EsterNogueiraWhyteAfonso_M.pdf: 5612471 bytes, checksum: 293938ba956e9881ed4b939f7fca47cd (MD5) Previous issue date: 2005 / Resumo: A distribuição geográfica da tuberculose tem forte relação com os indicadores socioeconômicos das diversas nações. Mesmo com os avanços no conhecimento e com a tecnologia disponível para seu controle, continua sendo grave problema mundial de saúde pública. Objetivo: Analisar a coorte de tratamento dos doentes inscritos no Programa de Controle da Tuberculose (PCT) na cidade de Campinas-SP, em 2003. Métodos: Foram analisados, segundo variáveis demográficas, clínicas e epidemiológicas, 494 doentes de uma coorte de 537 notificados no Sistema de Informação Nacional de Agravos de Notificação. Para determinar as diferenças entre as proporções e calcular as razões de chances (OR) foi utilizado o software Epi 1nfo versão 6. O valor de p foi considerado significativo quando inferior a 0,05. Resultados: Do total de doentes analisados 76,3% eram residentes no município de Campinas. O percentual de casos com a co-morbidade TB/Aids foi de 21,2% para os residentes em Campinas e de 24,8% para os residentes em outros municípios. O risco de adoecer por tuberculose em Campinas foi maior na área com piores níveis socioeconômicos. O sucesso de tratamento do grupo de doentes residentes em Campinas foi de 76,4% entre os que não apresentaram Aids e de apenas 48,8% naqueles com Aids. Os pacientes da forma clínica pulmonar com baciloscopia positiva apresentaram sucesso de 70%. O grupo constituído por pacientes que estavam em retratamento apresentou 2,1 vezes mais insucesso de tratamento comparado aos casos novos (OR = 2,14; IC 1,12 - 4,05). Entre aqueles pacientes com a co-morbidade TB/Aids a chance de insucessotambém foi maior (OR = 3,41; 1C 1,98 - 5,89). A proporção de tratamentos supervisionados foi de 35%. Conclusões: A efetividade do PCT de Campinas apresentou-se abaixo dos 85% proposto pela OMS em todas as estratificações estudadas e a incidência parece estar subdimensionada perante a baixa cobertura de baciloscopias de escarro (43,3%) nos sintomáticos respiratórios, sugerindo problemas na operacionalização do PCT de Campinas. Para melhorar o programa as atividades de busca de casos e as estratégias que asseguram a adesão ao tratamento, incluindo o tratamento supervisionado, devem ser aprimoradas / Abstract: The geographic distribution of tuberculosis has a strong relationship with socioeconomic indicators of different nations. Even with advances in knowledge and available technology for its control, it continues to be a serious worldwide public health problem. Objective: To analyze the treatment cohort of patients enrolled in the Tuberculosis Control Program (TCP) in the city of Campinas, SP, in 2003. Methods: In accordance with demographic, clinical and epidemiological variables, 494 patients IToma 537 cohort, who were notified by the National Disease Reporting Information System, were analyzed. In order to determine the differences among proportions and calculate the odds ratio (aR) the Epi Info version 6 software was used. A p value of less than 0.05 was considered significant. Results: Of the total patients analyzed, 76.3% were resident in the city of Campinas. The percentage of cases with TB/AIDS comorbidity for Campinas residents was 21.2% and for the residents in other cities, 24.8%. The risk for tuberculosis was higher in the areas with worse socioeconomic levels. The successful outcome for the treatment of the group of patients resident in Campinas was 76.4% among those who did not present Aids and only 48.8% for those who presented Aids. Patients with positive baciloscopy presented a success rate of 70%.The group of patients being retreated had a 2.1 times higher rate of unsuccessful treatment when compared to new cases (aR = 2.14; CI = 1.12 - 4.05). Among those patients with the TB/Aids comorbidity the chance of no unsuccessful was also higher (aR = 3.41; IC = 1.98 - 5.89). The proportion of supervised treatment was 35%. Conclusions: The effectiveness of the TCP in Campinas was below the 85% proposed by the WHO in all of the studies strata and the incidence seems to be underdimensioned in face of the low sputum bacilloscopy coverage (43.3%) of those presenting respiratory disease symptoms, which suggests problems in the TCP operation in Campinas. In order to improve the ~program, the activities of case search and supervised treatment should be enhanced. / Mestrado / Saude Coletiva / Mestre em Saude Coletiva

Alan George Miller. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1997. / Includes bibliographical references (p. 204-230). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web.

This research explored several adaptations to tuberculosis among the Indian population of Saskatchewan from 1926 to 1965 in order to demonstrate that this was an era in which disease played an significant role in the lives of the Indians. A broad ecological model' allowed for a variety of interactions to be explored. Within this framework, the study examined: the epidemiology and ecology of tuberculosis in the Saskatchewan Indian population; the development of health services to the Indians and the role of health services in the ecology of disease in this population; and the individual Indians' hospitalization and tuberculosis experience.<P> The epidemic of tuberculosis among the Indians of Saskatchewan began in the early 1880s. Rapidly assuming epidemic proportions, the death rate from tuberculosis among the Qu'Appelle Indians peaked in 1886 at a rate of 9,000 per 100,000. The death rate declined gradually after 1890 through the acquisition of population resistance and the elimination of the non-resistant families. The acute phase of the tuberculosis epidemic, characterized by extra-pulmonary disease in which the majority of cases terminated in a few months, lasted about two decades. Between 1907 and 1926, with gradually improving living conditions, continued acquisition of population resistance, but without application of any specific anti-tuberculosis measures, the death rate fell to 800 per 100,000.<p> Tuberculosis was endemic in the Saskatchewan Indian population by the beginning of the 1930s. Once endemic, the decline of the tuberculosis death rate continued to the end of the 1940s, without application of any specific anti-tuberculosis measures. By the time that specific measures were introduced, the death rate had declined to 417 per 100,000 in 1949. With the introduction of BCG vaccination and antimicrobial drug treatment, by 1959 the death rate declined to 39 per 100,000.<p> By the early 1960s tuberculosis mortality was successfully controlled in Saskatchewan, although death rates remained 15 times higher among the Indians. Tuberculosis morbidity continued to be a problem into the 1980s. In 1984, the incidence of tuberculosis was 21 times greater among the Indians than the corresponding rate in the non-Indian population.<p> Various environmental and cultural factors contributed to the Indian population's experiences with tuberculosis. The most important factor was the absence of population immunity. In addition, concentration of the population on reserves, the occurrence of intercurrent epidemics, sudden and dramatic dietary change, and lifestyle factors such as housing, sanitation and personal hygiene all contributed to incredibly high tuberculosis mortality in this population. The effect of medical care on the epidemiology of tuberculosis in the Saskatchewan Indians was not even considered in the preliminary analysis of the epidemic, because throughout the first several decades of the epidemic, no organized health services existed for the Indians.<p> In Saskatchewan, before World War II, medical services to the Indians were characterized by occasional surveys, the employment of part-time physicians, and health education through the distribution of circulars to Indian agents on health-related issues. Organized anti-tuberculosis programs which were developed in the years following the Second World War, in a large part, account for the dramatic decrease in the tuberculosis death rate in the province through the decade of the 1950s.<p> In the late 1940s, and throughout the 1950s and 1960s, most active Indian tuberculosis cases diagnosed in Saskatchewan were hospitalized for treatment. At least 10% of the Indian population of Saskatchewan received Indian hospital or sanatorium treatment throughout the first decade that those services were available to them.<p> Interviews conducted with fourteen Indian individuals who had been hospitalized for tuberculosis treatment provided two dichotomous perspectives on tuberculosis. Several individuals feared tuberculosis because of their familiarity with it in their families and on their reserves, however, most said that they knew tuberculosis, but they did not fear it. In terms of their knowledge about tuberculosis from a biomedical perspective, most had some idea of its symptomology although its specific etiology was not known. Most of the people interviewed appeared to understand the infectious nature of tuberculosis, however, their concern for their families may have stemmed from observations that tuberculosis was "in" particular families, not necessarily because they thought they could "give" tuberculosis to them. In terms of a perspective on the treatment of tuberculosis, most of the individuals interviewed were aware that hospital treatment was necessary. Archival sources and government annual reports, indicated that many Indians took a very active role in attending to their health needs. None of the individuals who were interviewed refused to go to the sanatorium, except for one woman who ran away several times. Most, however, planned their escape time after time. This suggests that their stay in the sanatorium and hospital may not have been of their own volition.<p> The most common and recurring theme that emerged from the interviews about life in the sanatoria or Indian hospital revolved around the structured, regimented nature of the treatment. Several individuals remembered quite vividly seeing other patients confined in strait jackets and body casts and distinctly remembered how strict the staff was with children.<p> While they were hospitalized, all of the individuals who were interviewed knew several other people who were being treated at the same time who were also their contemporaries from their own or surrounding reserves. All of the individuals also made several lasting friendships with people that they met while in the sanatorium. In addition, all, except for one young boy, were visited frequently by their families and friends. This indicates that the Indian people interviewed were not "isolated" from their families and friends for the duration of their treatment. Hospitalization, for those interviewed, was not a traumatic event because they had an extensive social network which enabled them to cope with the experience. In addition, because of the poor living conditions on many Indian reserves, a trip to the sanatorium or Indian hospital was a relief for some. Indian children in the sanatorium and hospital were given new clothes, toys, and books, and in some cases an education; things they did not get at home. One woman chose to remain in the sanatorium after her treatment regimen ended so that she could complete her education, something she could not do back at home in the north. Only one individual suggested that the experience was instrumental in determining the direction his future took.<p> In demonstrating that this was an era in which disease played a major role in the lives of the Indians, the epidemiology of tuberculosis in this population illustrated the pervasive influence that tuberculosis had on demographic and biological aspects of the population. The history of health services illustrated the role of medical intervention in the ecology of tuberculosis in this population. As a probe for behaviourial adaptations to disease on the individual level, the interviews contributed a human dimension to the study. To complete the picture of the role of disease in the lives of the Indians, the examination of the final component in adaptation, behaviourial adaptation to disease at the cultural level, is recommended.

This research explored several adaptations to tuberculosis among the Indian population of Saskatchewan from 1926 to 1965 in order to demonstrate that this was an era in which disease played an significant role in the lives of the Indians. A broad ecological model' allowed for a variety of interactions to be explored. Within this framework, the study examined: the epidemiology and ecology of tuberculosis in the Saskatchewan Indian population; the development of health services to the Indians and the role of health services in the ecology of disease in this population; and the individual Indians' hospitalization and tuberculosis experience.<P> The epidemic of tuberculosis among the Indians of Saskatchewan began in the early 1880s. Rapidly assuming epidemic proportions, the death rate from tuberculosis among the Qu'Appelle Indians peaked in 1886 at a rate of 9,000 per 100,000. The death rate declined gradually after 1890 through the acquisition of population resistance and the elimination of the non-resistant families. The acute phase of the tuberculosis epidemic, characterized by extra-pulmonary disease in which the majority of cases terminated in a few months, lasted about two decades. Between 1907 and 1926, with gradually improving living conditions, continued acquisition of population resistance, but without application of any specific anti-tuberculosis measures, the death rate fell to 800 per 100,000.<p> Tuberculosis was endemic in the Saskatchewan Indian population by the beginning of the 1930s. Once endemic, the decline of the tuberculosis death rate continued to the end of the 1940s, without application of any specific anti-tuberculosis measures. By the time that specific measures were introduced, the death rate had declined to 417 per 100,000 in 1949. With the introduction of BCG vaccination and antimicrobial drug treatment, by 1959 the death rate declined to 39 per 100,000.<p> By the early 1960s tuberculosis mortality was successfully controlled in Saskatchewan, although death rates remained 15 times higher among the Indians. Tuberculosis morbidity continued to be a problem into the 1980s. In 1984, the incidence of tuberculosis was 21 times greater among the Indians than the corresponding rate in the non-Indian population.<p> Various environmental and cultural factors contributed to the Indian population's experiences with tuberculosis. The most important factor was the absence of population immunity. In addition, concentration of the population on reserves, the occurrence of intercurrent epidemics, sudden and dramatic dietary change, and lifestyle factors such as housing, sanitation and personal hygiene all contributed to incredibly high tuberculosis mortality in this population. The effect of medical care on the epidemiology of tuberculosis in the Saskatchewan Indians was not even considered in the preliminary analysis of the epidemic, because throughout the first several decades of the epidemic, no organized health services existed for the Indians.<p> In Saskatchewan, before World War II, medical services to the Indians were characterized by occasional surveys, the employment of part-time physicians, and health education through the distribution of circulars to Indian agents on health-related issues. Organized anti-tuberculosis programs which were developed in the years following the Second World War, in a large part, account for the dramatic decrease in the tuberculosis death rate in the province through the decade of the 1950s.<p> In the late 1940s, and throughout the 1950s and 1960s, most active Indian tuberculosis cases diagnosed in Saskatchewan were hospitalized for treatment. At least 10% of the Indian population of Saskatchewan received Indian hospital or sanatorium treatment throughout the first decade that those services were available to them.<p> Interviews conducted with fourteen Indian individuals who had been hospitalized for tuberculosis treatment provided two dichotomous perspectives on tuberculosis. Several individuals feared tuberculosis because of their familiarity with it in their families and on their reserves, however, most said that they knew tuberculosis, but they did not fear it. In terms of their knowledge about tuberculosis from a biomedical perspective, most had some idea of its symptomology although its specific etiology was not known. Most of the people interviewed appeared to understand the infectious nature of tuberculosis, however, their concern for their families may have stemmed from observations that tuberculosis was "in" particular families, not necessarily because they thought they could "give" tuberculosis to them. In terms of a perspective on the treatment of tuberculosis, most of the individuals interviewed were aware that hospital treatment was necessary. Archival sources and government annual reports, indicated that many Indians took a very active role in attending to their health needs. None of the individuals who were interviewed refused to go to the sanatorium, except for one woman who ran away several times. Most, however, planned their escape time after time. This suggests that their stay in the sanatorium and hospital may not have been of their own volition.<p> The most common and recurring theme that emerged from the interviews about life in the sanatoria or Indian hospital revolved around the structured, regimented nature of the treatment. Several individuals remembered quite vividly seeing other patients confined in strait jackets and body casts and distinctly remembered how strict the staff was with children.<p> While they were hospitalized, all of the individuals who were interviewed knew several other people who were being treated at the same time who were also their contemporaries from their own or surrounding reserves. All of the individuals also made several lasting friendships with people that they met while in the sanatorium. In addition, all, except for one young boy, were visited frequently by their families and friends. This indicates that the Indian people interviewed were not "isolated" from their families and friends for the duration of their treatment. Hospitalization, for those interviewed, was not a traumatic event because they had an extensive social network which enabled them to cope with the experience. In addition, because of the poor living conditions on many Indian reserves, a trip to the sanatorium or Indian hospital was a relief for some. Indian children in the sanatorium and hospital were given new clothes, toys, and books, and in some cases an education; things they did not get at home. One woman chose to remain in the sanatorium after her treatment regimen ended so that she could complete her education, something she could not do back at home in the north. Only one individual suggested that the experience was instrumental in determining the direction his future took.<p> In demonstrating that this was an era in which disease played a major role in the lives of the Indians, the epidemiology of tuberculosis in this population illustrated the pervasive influence that tuberculosis had on demographic and biological aspects of the population. The history of health services illustrated the role of medical intervention in the ecology of tuberculosis in this population. As a probe for behaviourial adaptations to disease on the individual level, the interviews contributed a human dimension to the study. To complete the picture of the role of disease in the lives of the Indians, the examination of the final component in adaptation, behaviourial adaptation to disease at the cultural level, is recommended.

Submitted by Irene Nascimento (irene.kessia@ufpe.br) on 2016-08-26T18:01:43Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) NILMA MEDTROP VD.pdf: 2060397 bytes, checksum: 801ad4896a8a5f3c544547167d27652d (MD5) / Made available in DSpace on 2016-08-26T18:01:43Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) NILMA MEDTROP VD.pdf: 2060397 bytes, checksum: 801ad4896a8a5f3c544547167d27652d (MD5) Previous issue date: 2015-02-05 / A tuberculose (TB) é a doença mais comum da humanidade. Atualmente, a Organização Mundial de Saúde estimou nove milhões de novos casos e um milhão e meio de mortes decorrentes da doença. A rápida expansão da resistência aos fármacos antituberculose tem prejudicado o controle global da TB, constituindo um grave problema de Saúde Pública. No Brasil, a semelhença de outros países endêmicos, tem-se observado uma variabilidade na prevalência de resistência e no estado da Paraíba (PB) não há dados recentes e concisos. Dessarte, esse estudo objetivou verificar a prevalência de resistência do Mycobacterium tuberculosis aos fármacos do esquema de primeira linha do tratamento da TB utilizados no Brasil e a frequência de fatores de risco - sexo, idade, tratamento prévio e ingesta alcóolica - em pacientes adultos com diagnóstico de TB pulmonar resistente (TBP), atendidos em serviço de referência na PB durante o período de 01 de janeiro de 2003 a 31 de dezembro de 2013. Para obtenção dos dados, utilizou-se formulário padronizado, preenchido, retrospectivamente, a partir das informações contidas nos prontuários dos pacientes atendidos no período do estudo. Foram notificados 69 casos, com prevalência de 0,5%. Evidenciou-se 17,4% de mono, 14,5% de poli e 68,1% de multirresistência. A resistência à isoniazida (INH) mostrou-se importante, tanto isolada, quanto em associações; bem como e, principalmente, a TB multirresistente (TBMR). Perante os fatores de risco, o sexo masculino (73,9%), a faixa etária de 40 a 49 anos (46,4%), a realização de tratamento prévio (98,5%) e a ingesta alcóolica (57,4%) foram os de maior ocorrência. Todavia, não expressaram significância estatística no estudo realizado tendo a PB como cenário. O desfecho foi a cura para 44,9% dos casos; no entanto, o abandono ao tratamento foi considerável, principalmente para a TBP monorresistente (33,3%). As características sociodemográficas compreenderam: a cor da pele parda (68,5%), o estado civil casado (50,9%), o nível de instrução até o fundamental (67,3%) e a procedência do interior da PB (78,2%). Quanto à coinfecção com HIV/AIDS, ocorreu em 14,5%; no entanto, nesse grupo a TBMR, também, foi mais frequente. Desta feita, mais estudos são imprescindíveis no intuito de investigar genotipicamente a resistência da TB no estado da PB, visto que alguns estudos genéticos têm reportado mutações em cepas resistentes à rifampicina (RMP), estando associada a maior transmissibilidade e a resistência à INH tem sido associada com mutações de vários genes. Assim, correlacionando com outros estados e países a fim de colaborar com o enfrentamento da doença na busca do controle e cura extensiva a todos. Por outro lado, há necessidade de fortalecimento das ações do programa de controle da TB, tanto em nível estadual, quanto nos municípios. / Tuberculosis (TB) is the most common disease of humanity. Currently, the World Health Organization estimated nine million new cases and a million and a half deaths from the disease. The rapid spread of resistance to antituberculosis drugs has undermined the global TB control, constituting a serious public health problem. In Brazil, as other endemic countries, it has been observed variability in the prevalence of resistance and the state of Paraíba (PB) no recent and accurate data. Thus, this study aimed to determine the prevalence of resistance of the Mycobacterium tuberculosis to first-line drugs in TB treatment regimen used in the Brazil and frequency of risk factors - gender, age, prior treatment and alcoholic intake - in adults patients diagnosed with resistant pulmonary TB (PTB), treated on reference service in PB during the January 1, 2003 to December 31, 2013. To obtain the data, it used standardized form filled out retrospectively from the information contained in the medical records of patients seen during the study period. Were reported 69 cases, with a prevalence of 0.5%. Revealed a 17.4% to mono, 14.5% to poly and 68.1% to multidrug resistance. The isoniazid (INH) resistance was found to be important, both isolated, as in associations; as well as, and especially multidrug resistant TB (MDR-TB). In view of the risk factors, males (73.9%), the age group 40 -49 years (46.4%), the realization of previous treatment (98.5%) and alcoholic intake (57.4%) were the most frequent. However, did not express statistical significance in the study with the PB as a scenario. The outcome was the cure for 44.9% of cases; however, abandon to treatment was significant, particularly for mono resistant PTB (33.3%). The sociodemographic characteristics included: dark brown skin (68.5%), married status (50.9%), level of education up to primary (67.3%) and the origin from the interior of PB (78.2%). The co-infection with HIV/AIDS occurred in 14.5%; however, this group the MDR-TB also was more frequent. This time, more studies are essential in order to investigate genotypically the TB resistance in the state of PB, as some genetic studies have reported mutations in strains resistant to rifampicin (RMP) and are associated with increased transmissibility and INH resistance has been associated with mutations multiple genes. Thus, correlating with other states and countries to collaborate with coping with the disease in the search of control and extensive cure to all. On the other hand, there is need to strengthen the actions of the TB control program at the state level and in the municipalities.

Pang, Tak Ting Phoebe. / "September 2010." / Thesis (M.Phil.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 153-161). / Abstracts in English and Chinese. / Acknowledgement --- p.I / Abstract --- p.II / 摘要 --- p.IV / List of Figures --- p.V / List of Tables --- p.VII / Abbreviations --- p.VIII / Chapter CHAPTER ONE --- INTRODUCTION --- p.1 / Chapter 1.1 --- Historical perspective of tuberculosis --- p.1 / Chapter 1.1.1 --- Sanatorium care --- p.2 / Chapter 1.1.2 --- Vaccination --- p.2 / Chapter 1.1.3 --- Drug treatment --- p.3 / Chapter 1.1.4 --- Transmission dynamics of tuberculosis --- p.3 / Chapter 1.1.5 --- Resurgence of tuberculosis --- p.4 / Chapter 1.2 --- Current global and local tuberculosis epidemiology --- p.6 / Chapter 1.2.1 --- "Tuberculosis and HIV/AIDS, drug resistance in the world" --- p.6 / Chapter 1.2.2 --- Global epidemiology of tuberculosis --- p.9 / Chapter 1.2.3 --- Local epidemiology of tuberculosis --- p.9 / Chapter 1.2.4 --- "Tuberculosis, HIV/AIDS and drug resistance in Hong Kong" --- p.14 / Chapter 1.2.5 --- Approaches in studying tuberculosis epidemiology --- p.15 / Chapter 1.3 --- Determinants of tuberculosis epidemiology --- p.17 / Chapter 1.3.1 --- TB determinants in the triad of epidemiology --- p.17 / Chapter 1.3.2 --- Rise of spatial epidemiology --- p.18 / Chapter 1.4 --- Recent developments of spatial epidemiology --- p.21 / Chapter 1.4.1 --- Spatial epidemiology and infectious disease --- p.21 / Chapter 1.4.2 --- Disease mapping --- p.22 / Chapter 1.4.3 --- Geographic information system --- p.22 / Chapter 1.4.4 --- Statistics in spatial epidemiology --- p.23 / Chapter CHAPTER TWO --- LITERATURE REVIEW --- p.24 / Chapter 2.1 --- Objective of literature review --- p.24 / Chapter 2.2 --- Literature search --- p.25 / Chapter 2.2.1 --- Strategy for literature search --- p.25 / Chapter 2.2.2 --- Results for literature search --- p.25 / Chapter 2.3 --- Spatial perspective in tuberculosis epidemiology --- p.31 / Chapter 2.3.1 --- Mapping the spatial pattern --- p.32 / Chapter 2.3.2 --- Understanding the spatial pattern --- p.32 / Chapter 2.3.3 --- Modelling the spatial pattern --- p.33 / Chapter 2.4 --- Neighbourhood determinants of tuberculosis --- p.34 / Chapter 2.4.1 --- TB and demographics --- p.35 / Chapter 2.4.2 --- TB and socioeconomic status --- p.36 / Chapter 2.4.3 --- TB and the environment --- p.38 / Chapter 2.4.4 --- TB and care factors --- p.40 / Chapter 2.5 --- Techniques applied in studying tuberculosis epidemiology --- p.41 / Chapter 2.5.1 --- Constructing spatial data --- p.41 / Chapter 2.5.2 --- Disease maps used --- p.45 / Chapter 2.5.3 --- "Integrated approach using spatial statistics, conventional statistics and molecular analysis" --- p.52 / Chapter 2.6 --- Research gap and thesis objectives --- p.55 / Chapter 2.6.1 --- Research gap --- p.55 / Chapter 2.6.2 --- Thesis objective --- p.56 / Chapter CHAPTER THREE --- METHODOLOGY --- p.57 / Chapter 3.1 --- Rationale and approach --- p.57 / Chapter 3.1.1 --- Logical flow of the study --- p.57 / Chapter 3.1.2 --- Methodological flow of the study --- p.60 / Chapter 3.2 --- Choosing spatial units --- p.63 / Chapter 3.3 --- Data collection --- p.69 / Chapter 3.3.1 --- Tuberculosis data --- p.70 / Chapter 3.3.2 --- Spatial data --- p.70 / Chapter 3.3.3 --- Neighbourhood data --- p.70 / Chapter 3.4 --- Data manipulation --- p.73 / Chapter 3.4.1 --- Tuberculosis data --- p.73 / Chapter 3.4.2 --- Spatial data --- p.74 / Chapter 3.4.3 --- Neighbourhood data --- p.74 / Chapter 3.5 --- Centrographic analysis --- p.76 / Chapter 3.5.1 --- Types of centrographic statistics --- p.76 / Chapter 3.6 --- Exploratory spatial data analysis --- p.78 / Chapter 3.6.1 --- Spatial proximity matrix --- p.78 / Chapter 3.6.2 --- Moran's Index --- p.79 / Chapter 3.6.3 --- Local Indicator of Spatial Association --- p.79 / Chapter 3.7 --- Explanatory analysis --- p.81 / Chapter 3.7.1 --- Selecting variables for modelling --- p.82 / Chapter 3.7.2 --- Ordinary linear regression --- p.82 / Chapter 3.7.3 --- Geographically weighted regression --- p.83 / Chapter CHAPTER FOUR --- RESULTS --- p.85 / Chapter 4.1 --- Overview --- p.85 / Chapter 4.1.1 --- Individual level --- p.85 / Chapter 4.1.2 --- Aggregated level --- p.89 / Chapter 4.2 --- Results for centrographic analysis --- p.97 / Chapter 4.3 --- Results for exploratory spatial data analysis --- p.101 / Chapter 4.3.1 --- Results for Moran's Index --- p.101 / Chapter 4.3.2 --- Results for Local Indicator of Spatial Association --- p.103 / Chapter 4.4 --- Results for explanatory analysis --- p.110 / Chapter 4.4.1 --- Correlation analysis and variables selection --- p.110 / Chapter 4.4.2 --- Results for ordinary linear regression --- p.114 / Chapter 4.4.3 --- Results for geographically weighted regression --- p.116 / Chapter CHAPTER FIVE --- DISCUSSION --- p.131 / Chapter 5.1 --- Preamble --- p.131 / Chapter 5.1.1 --- Methods overview --- p.132 / Chapter 5.1.2 --- Results overview --- p.132 / Chapter 5.1.3 --- Layout of this chapter --- p.134 / Chapter 5.2 --- Neighbourhood determinants in relation to TB --- p.135 / Chapter 5.2.1 --- Crowding and tuberculosis --- p.135 / Chapter 5.2.2 --- Poverty and tuberculosis --- p.137 / Chapter 5.2.3 --- Immigrants and tuberculosis --- p.138 / Chapter 5.2.4 --- Marital status and tuberculosis --- p.139 / Chapter 5.2.5 --- Implication of local parameter estimates of association --- p.140 / Chapter 5.3 --- Study design for spatial epidemiology --- p.142 / Chapter 5.3.1 --- Application of spatial dependence in spatial epidemiology --- p.142 / Chapter 5.3.2 --- Choosing spatial units --- p.144 / Chapter 5.4 --- Methodological concern in this study --- p.146 / Chapter 5.4.1 --- Concern over disease mapping --- p.146 / Chapter 5.4.2 --- Application of geographically weighted regression --- p.148 / Chapter 5.5 --- Limitation of the study --- p.150 / Chapter 5.6 --- Conclusion --- p.152 / REFERENCE --- p.153 / APPENDIX --- p.162 / Appendix 1 How to calculate TB SNR? --- p.162 / Appendix 2 How GWR works? --- p.164 / Appendix 3 What is AIC? --- p.165 / Appendix 4 How Monte Carlo test works? --- p.166 / Appendix 5 List of GWR output --- p.167

Doctorat en Sciences médicales / info:eu-repo/semantics/nonPublished

Thesis (MScMedSc)--Stellenbosch University, 2008. / ENGLISH ABSTRACT: Application of molecular fingerprinting highlights transmission as the driving force behind the drug resistant epidemic in South Africa. Different strains dominate within different geographical regions, which is a reflection of micro-epidemics of drug resistance in the different regions. Cluster analysis shows that strains within the same strain family are different. The Beijing drug resistant strain family is the most dominant strain family (31%) in the Western Cape and of particular concern is the highly transmissible Beijing cluster 220 strain in the Western Cape communities. This cluster is widespread in the region and was previously identified in a MDR outbreak in a high school in Cape Town. Results suggest that the spread of Beijing drug resistant cluster 220 in the community was due to a combination of acquisition of drug resistant markers and transmission. This study also indicate that atypical Beijing can acquire drug resistance and become fit amongst HIV infected individuals. This is contrary to believe that atypical Beijing strains are not frequently associated with drug resistance and are attenuated. This implies that HIV levels the playing field for all drug resistant strains. Mechanisms leading to the evolution of MDR-TB and XDR-TB in a mine setting with a wellfunctioning TB control program which exceeds the target for cure rates set by the WHO were investigated. Despite the excellent control program, an alarming increase in the number of drug resistant cases was observed in 2003 and subsequent years. Phylogenetic analysis shows sequential acquisition of resistance to first and second-line anti-TB drugs leading to the development of MDR and XDR-TB. Contact tracing indicate extensive transmission of drug resistant TB in the shafts, hospital and place of residence. This study shows that despite exceeding the WHO cure rate target, it was not possible to control the spread and amplification of drug resistance. In summary, as a top priority, future TB control plans need to address diagnostic delay more vigorously. / AFRIKAANSE OPSOMMING: Molukulêre tegnieke toon transmissie as die hoofrede vir die toename in die anti-tuberkulose middelweerstandigheid epidemie in Suid-Afrika. Die verskillende Mikobakterium tuberkulose rasse wat domineer in verskillende areas is ‘n refleksie van middelweerstandige mikro-epidemies in verskillende gebiede. Analise van identiese rasgroepe demonstreer dat ras families bestaan uit verskillende rasse. Die Beijing middelweerstandige rasfamilie is die mees dominante familie in die Wes-Kaap (31% van monsters van middelweerstandige families) en van spesifieke belang is die hoogs oordraagbare Beijing 220 groep. Hierdie groep is die mees wydverspreide groep in die studie area en was voorheen geïdentifiseer tydens ‘n meervoudige middelweerstandige uitbreking in ‘n hoërskool in Kaapstad. Die resultate dui aan dat die Beijing middelweerstandige groep 220 in die gemeenskap versprei as gevolg van ‘n kombinasie van middelweerstand verwerwing en transmissie. Hierdie studie dui verder aan dat die atipiese Beijing ook middelweerstandigheid kan verwerf en hoogs geskik is vir infeksie veral in MIV geïnfekteerde individue. Hierdie data is in teenstelling met die algemene denke dat atipiese Beijing nie gereeld geassosieer word met middelweerstandigheid nie en dat dit dikwels geattenueer is. Dit beteken dat MIV die hoof faktor is wat alle middelweerstandige rasse kans gee om te versprei. Hierdie studie het die meganisme wat lei tot die evolusie van middelweerstandigheid en “XDRTB” in die myne ondersoek. Die myn besit ‘n goeie funksioneerde tuberkulose kontrole program wat alreeds die Wêreld Gesondheids Organisasie se mikpunt vir tuberkulose genesing oortref. Ten spyte van ‘n uitstekende tuberkulose kontrole program, is daar ‘n bekommerenswaardige toename in die aantal middelweerstandige tuberkulose gevalle waargeneem in 2003 en in die daaropvolgende jare. Filogenetiese analise wys dat opeenvolgende verwerwing van middelweerstandigheid teen eerste en tweede vlak anti-tuberkulose middels gelei het tot die ontwikkeling van meervoudige middelweerstandigheid en “XDR-TB”. Die opsporing van kontakpersone om transmissie te bewys dui aan dat transmissie van middelweerstandige tuberkulose in die werk plek, hospitaal en woon plek plaasvind. Hierdie studie wys dat ongeag die feit dat die Wêreld Gesondheids Organisasie se genesings verwagtinge oortref is, dit steeds onmoontlik was om die verspreiding en amplifisering van middelweerstandigheid te beheer. ‘n Top prioriteit vir tuberkulose kontrole planne in die toekoms behoort die vertraging van diagnose sterk aan te spreek.

Thesis (PhD (Biomedical Sciences. Molecular Biology and Human Genetics))--Stellenbosch University, 2008. / This series of studies includes both methodological analyses, aimed at furthering our understanding of, and improving the tools used in molecular epidemiology, and investigative projects which have used these tools to add to our knowledge of the M. tuberculosis epidemic. Using serial isolates from tuberculosis patients, we have investigated the evolutionary rate of the IS6110 RFLP pattern. In accordance with other studies, we determined a ½-life for this epidemiological marker of 10.69 years, confirming its appropriateness for this purpose. We also identified an initial, much higher apparent rate which we proposed was the result of pre-diagnostic evolution. In support of this, our investigations in the context of household transmission of M. tuberculosis revealed that IS6110-based evolution is closely associated with transmission of the organism, resulting in a strain population rate of change of 2.9% per annum. To accommodate evolution within estimates of transmission, we proposed that calculations incorporate the concept of Nearest Genetic Distance (cases most similar in RFLP pattern and most closely associated in time). We used this to create transmission chains which allowed for limited evolution of the IS6110 marker. As a result, in our study community, the estimated level of disease attributable to ongoing transmission was increased to between 73 and 88% depending on the Genetic Distance allowed. We identified the duration of a study as a further source of under-estimation of transmission. This results from the artefactual abridgement of transmission chains caused by the loss of cases at the temporal boundaries of a study. Using both real and simulated data, we showed that viewing a 12-year study through shorter window periods dramatically lowered estimates of transmission. This effect was negatively correlated with the size of a cluster. Various combinations of MIRU-VNTR loci have been proposed as an alternative epidemiological marker. Our investigations showed that, while this method yielded estimates of transmission similar to those of IS6110, there was discordance between the two markers in the epidemiological linking of cases as a result of their independent evolution. Attempting to compensate for this by allowing for evolution during transmission improved the performance of IS6110, but generally had a deleterious effect of that of MIRU-VNTR. However, this marker remains a valuable tool for higher phylogenetic analysis and we used it to demonstrate a correlation between sublineages of the Beijing clade and the regions in which they are found. We proposed that, either the host population had selected for a particular sublineage, or that specific sublineages had adapted to be more successful in particular human populations. We further explored the dynamics of the epidemic over a 12-year period in terms of the five predominant M. tuberculosis clades. We found that, while four of these clades remained relatively stable, the incidence of cases from the Beijing clade increased exponentially. This growth was attributed to drug-sensitive cases although drug-resistant Beijing cases also appeared to be more successful than their non-Beijing counterparts. Possible factors contributing to this clade’s success were a greater proportion of positive sputum smears and a lower rate of successful treatment.