Thesis (PhD)--University of Stellenbosch, 2011. / ENGLISH ABSTRACT: The tuberculosis (TB) incidence has increased in Southern Africa and the situation is worsened by the emergence of drug-resistant Mycobacterium tuberculosis strains. Molecular biological techniques have been used to understand the disease dynamics of TB. In a series of studies we describe the use of these techniques to understand the disease dynamics of TB in Southern Africa. Using spoligotyping and IS6110-restriction fragment length polymorphism (RFLP) to characterize M. tuberculosis strains from TB patients in Zimbabwe, we identified a genotype causing a disproportionate number of TB cases. The genotype belonged to the Latin American Mediterranean (LAM) lineage and we named it the Southern Africa1 (SAF1) family and later renamed it SAF1/RDRio, also reflecting its predominance in South America. To establish if this family of strains was predominant elsewhere in Southern Africa, genotypes were compared to those from Western Cape, South Africa and Zambia. The SAF1/RDRio strains were highly prevalent in Zambia but were only a minor fraction of the strains in South Africa. The geographical distribution of SAF1/RDRio strains was determined in Gweru, Zimbabwe, and was found to be spread in high incidence areas. From these two studies it was hypothesized that certain host and bacterial factors were associated with disease due to SAF1/RDRio. Subsequently potential risk factors and clinical outcomes of disease due to SAF1/RDRio strains were explored. An association was found with smoking and cavitary pulmonary disease suggesting that SAF1/RDRio caused a more severe and highly transmissible formof TB Using IS6110-RFLP, principal genetic grouping, spoligotyping, IS6110 insertion-site mapping and variable-number tandem repeats (VNTR) typing, low IS6110 copy clade (LCC) identified in Zimbabwe were characterized and compared to the strains from Cape Town, South Africa and other regions. The LCC strains from Cape Town, South Africa, were found to have close evolutionary relationship with strains from Zimbabwe and other regions and were widely distributed suggesting they play an important role in the global TB epidemic. Observations from these studies and those from other studies led to the hypothesis that specific genotypes of M. tuberculosis predominate in regions of Southern Africa. To gain an insight on the population structure of M. tuberculosis strains in Southern Africa, spoligotyping and/or IS6110-RFLP data from eight countries were compared. This is the first study to describe the M. tuberculosis population structure in Southern Africa. Distinct genotypes were associated with specific geographic regions. These findings have important implications for TB diagnostics, anti-TB drug and vaccine development. The population structure of multidrug-resistant (MDR), pre-extensively drug-resistant (pre-XDR) and extensively drug-resistant (XDR) M. tuberculosis isolates from provinces in South Africa was also determined. This is again the first study to describe the population structure of drug-resistant M. tuberculosis in South Africa. The results also showed geographic localization of genotypes and an association with resistance class. However, decreasing strain diversity was observed as the isolates evolved from MDR-TB to XDR-TB suggesting selection for the specific genotypes. These findings highlight the importance of identifying genetic markers in drug-resistant strains, to enhance early detection of those at risk of developing XDR-TB. / AFIKAANSE OPSOMMING: Die voorkoms van tuberkulose (TB) in Suider Afrika word vererger deur stamme van Mycobacterium tuberculosis wat weerstandig is teen die beskikbare anti-tuberkulose middels. Molekulêre tegnieke word gebruik om in hierdie reeks studies die dinamika van TB in Suider Afrika te ondersoek Deur spoligotipering en IS6110 restriksie fragment lengte polimorfisme (RFLP) tegnieke te gebruik om M. tuberculosis stamme van pasiente in Zimbabwe te beskryf, het ons ‘n genotipe gevind wat ‘n buitengewone aantal TB gevalle veroorsaak het. Hierdie genotipe is deel van die internasionaal beskryfde Latyns Amerikaase en Meditereense (LAM) stam familie. Ons het dit die Suider Afrikaanse Familie1 (SAF1) genoem, maar later hernoem na SAF1/RDRio, omdat dieselfde genotipe in ook volop is in Suid Amerika. Om vas te stel of hierdie familie ook oorheesend is in die res van Suider Afrika, is dit vergelyk met beskikbare databasisse van die Wes-Kaap, Suid-Afrika en Zambië. Alhoewel SAF1/RDRio in die Wes-Kaap gevind is, dra dit slegs tot ‘n mindere mate by tot die plaaslike TB epidemie. Aan die anderkant kom SAF1/RDRio baie algemeen in Zambië voor. ‘n Verdere studie wys ook dat die SAF1/RDRio familie eweredig en wyd verspreid voorkom in hoë insidensie gebiede in Gweru, Zimbabwe. Vanuit die bevindings van hierdie 2 studies, kan ons aflei dat sekere gasheer- en bakteriële eienskappe geassosieer is met SAF1/RDRio-TB-infeksie. Hierna is potensiële risiko faktore en kliniese uitkomste van siekte as gevolg van infeksie met SAF1/RDRio ondersoek. ‘n Assosiasie met rook en kaviterende pulmonale infeksie is gevind,wat daarop dui dat SAF1/RDRio erger vorm van TB veroorsaak en hoogs oordraagbaar is. Deur gebruik te maak van IS6110- (RFLP), hoof groep groepering, spoligotipering, IS6110 invoegings kaartering en veranderlike getal tandem herhaling (VNTR) tipering kon lae IS6110 invoeginsgetal (LCC) stamme van Kaapstad, Zimbabwe en ander gebiede vergelyk word. Al die LCC stamme in die studie is evolusionêr naby verwant aan mekaar en is wyd verspreid, wat dui op hulle belangrike rol in die wêreldwye TB epidemie. Waarnemings in hierdie asook ander studies het tot die hipotese gely dat spesifieke genotipes van M. tuberculosis dominant is in verskillende gebiede van Suider Afrika. Om meer insig tot die populasie samestelling van M. tuberculosis stamme in Suider Afrika in te win is spoligotipes en RFLP-data van 8 lande vergelyk. Hierdie is die eerste studie om die populasie samestelling van M. tuberculosis in Suider Afrika te beskryf en is belangrike fir toekomstige ontwikkeling van nuwe TB diagnose tegnieke, anti-TB middels en TB entstowwe. Die populasie samestelling van multiweerstandige (MDR), pre-ekstreme weerstandige (pre-XDR) en ekstreme weerstandige (XDR) M. tuberculosis van verskillende provinsies in Suid-Afrika is ook bepaal. Hierdie studie is ook die eerste wat die populasie samestelling van weerstandige M. tuberculosis in Suid-Afrika beskryf. Die resultate wys geografiese lokalisering van genotipes en ‘n assosiasie met weerstandigheidsklas. ‘n Afname in stam diversiteit soos die isolate van MDR-TB tot XDR-TB ontwikkel, dui op seleksie van spesifieke genotipes. Hierdie bevinding lê die klem op die belangrikheid van die identifisering van genetiese merkers in weerstandige stamme om die risiko vir die ontwikkeling van XDR-TB te verminder deur vroë deteksie.

INTRODUÇÃO: A incidência de tuberculose (TB) em Santos (SP) situa-se em 73/100.000 habitantes-ano. A prevalência média de coinfecção TB/HIV é de 16%, taxas de cura e abandono de tratamento, entre casos novos são, respectivamente, 71% e 12%. Tais indicadores sugerem elevado risco para TB multidroga resistente (TBMR) no município, com incidência estimada em 1,9/100.000 habitantes-ano. OBJETIVO: Descrever e analisar o perfil de sensibilidade às drogas (TS) de primeira e segunda linha de tratamento entre pacientes com TB pulmonar (TBP), estimar a incidência de TBMR e a proporção de TB extensivamente resistente (TBXR); analisar aspectos moleculares, epidemiológicos e institucionais dos casos de TBP resistentes em Santos (SP). MÉTODOS: Estudo descritivo de uma coorte de pacientes de TBP, com início de tratamento ou retratamento entre 01 de janeiro de 2011 a 31 de dezembro de 2012. Definiu-se como caso de TBP, indivíduos com 15 anos ou mais, de ambos os sexos, residentes no município de Santos, com manifestações clínicas compatíveis com TBP e confirmação por cultura com isolamento de Mycobacterium tuberculosis. As variáveis de interesse para o estudo foram as características sociodemográficas, história atual e pregressa de TB, aspectos relativos ao tratamento, co-morbidades, ao diagnóstico e resistência a drogas. Para as análises comparativas entre proporções foram usados os testes qui-quadrado de Pearson e o Exato de Fisher e para variáveis contínuas o teste T de Student ou o de Kruskal - Wallis. Os perfis genéticos dos isoladas resistentes a ao menos uma droga foram obtidos pela técnica RLFP e analisados pelo programa Bionumerics versão 5.0 (Applied Maths - Bélgica). A descrição da distribuição espacial da TB resistentes e clusters foram feitas mediante a inserção dos casos no mapa de Santos, por endereço de residência, segundo o índice de vulnerabilidade social. RESULTADOS: Dos 263 casos de TBP selecionados, 68,4% (180/263) eram do sexo masculino, a mediana da idade foi de 38 anos, 8,7% (23/263) eram diabéticos; 20,4% (42/206) dos casos novos apresentavam ao menos um fator de risco para TBMR; destacando-se entre estes casos 10,7% (22/206) de confecção HIV/TB; 47,3% (123/260) tiveram tratamento supervisionado, 14,7% (91/617) dos contatos foram examinados, 18,6% (49/263) foram hospitalizados durante o tratamento, perfazendo uma média de 145,4 dias por paciente. Entre os casos resistentes a ao menos uma droga, a resistência à isoniazida foi 8,4% (22/263) e à rifampicina 3,8% (10/263) dos casos. A TBMR primária foi encontrada em 1,9% (4/206) dos casos e destes 25,0% (1/4) eram TBXR. A incidência média anual de TBMR foi de 0,57/100,000 habitantes. Dos 25 isolados resistentes ao menos uma droga, submetidos à RFLP, 12 (48,0%) foram agrupados em seis grupos genéticos, com dois pacientes em cada grupo. CONCLUSÕES: A elevada proporção TBMR primária, com um caso de TBXR enfatizam a necessidade de universalizar a cultura e TS, ampliar a cobertura do tratamento supervisionado, a investigação rotineira dos contatos e o monitoramento da resistência a drogas. O fortalecimento da vigilância da resistência às drogas é indispensável para o contínuo aperfeiçoamento do Programa de Controle da TB, especialmente em regiões de elevada carga da doença / INTRODUCTION: The incidence of tuberculosis (TB) in Santos (SP) is located around 73 / 100,000-year, approximately double that found on average in the country. The average prevalence of TB / HIV is 16% cure rates and treatment dropout among new cases are, respectively, 71% and 12%. Such indicators suggest high risk for multidrug-resistant TB (MR-TB) in the city, with the incidence estimated at 1.9 / 100,000-year. OBJECTIVE: To describe and analyze the sensitivity to drugs of first and second line treatment of patients with pulmonary TB (PTB) to estimate the incidence of MR-TB and extensively drugresistant TB (TBXR), describe molecular and institutional aspects, spatial distribution, epidemiological PTB resistant cases in the city of Santos (SP). METHODS: A descriptive study of a cohort of patients with PTB residing in the city who started treatment or retreatment in the period January 2011 to December 31, 2012. The case definition PTB individuals 15 years or more, both sexes, living in the city of Santos (SP), who present clinical manifestations compatible with PTB and whose confirmation was made by culture with isolation of M. tuberculosis. The variables of interest for the study were: bacteriological / laboratory socio-demographic characteristics, current and previous history of TB, aspects related to treatment, and comorbidities. For comparative analyzes of proportions the chi-squared tests and Fisher\'s exact were used for continuous variables and the Student t test or the Kruskal - Wallis. The genetic profiles of isolates resistant to at least one drug were obtained by RFLP (length polymorphism restriction fragment) and analyzed using version BioNumerics 5.0 (Applied Maths - Belgium) software. The description of the spatial distribution of resistant TB and the clusters was made by inserting the cases in Santos map, by address of residence, which was according to the index of social vulnerability. RESULTS: Of the 263 cases of PTB selected, 68.4% (180/263) were male, th median age was 38 years, 8.7% (23/263) were diabetes; 20.4% (42/206) of new cases had at least one risk factor for MR-TB, especially 10.7% (22/206) of making HIV / TB; 47.3% (123/260) underwent supervised treatment, 14.7% (91/617) of the contacts were examined, 18.6% (49/263) were hospitalized during treatment, totaling 7127 days of hospitalization with a mean 145.4 days per patient. Among the cases resistant to at least one drug resistance to isoniazid 8.4% (22/263) and rifampin 3.8% (10/263) of the cases was found. The primary MR-TB was found in 1.9% (4/206) of MR-TB cases and of these 25.0% (1/4) were TBXR. The average annual incidence of MDR-TB was 0.57/100,000 inhabitants. Of the 25 isolates resistant least one drug, subjected to molecular characterization of IS6110, 12 (48.0%) were grouped in six clusters, with each group including two isolates. CONCLUSIONS: A high proportion of primary MR-TB, including a case of TBXR emphasizes the need to universalize culture and TS, expand the coverage of supervised treatment, routine investigation of contacts and monitoring of drug resistance. The strengthening of the surveillance of drug resistance is essential for continuous improvement of the TB Control Program, especially in regions of high disease burden

Magister Public Health - MPH (Public Health) / The presence of highly effective medicines has made very little impact in reducing deaths as a result of tuberculosis (TB), a curable condition but when managed inappropriately, may result in Drug Resistant TB. TB accounts for about one in four deaths that occur in HIV positive people and HIV has been found to be a risk factor for complex unfavorable outcomes in MDR TB patients and a very strong predictor for death and default. The relationship between diabetes and TB has also been explored, with some authors identifying diabetes as a risk factor for TB, and with related poor clinical outcomes in both conditions when they co-exist. Exploring the clinical characteristics and treatment outcomes of MDR TB patients in the presence of these risk factors could present an opportunity to provide better care through increased case-detection activities, improved clinical management and better access to care for all these conditions. The aim of the study was to describe the clinical characteristics and treatment outcomes of MDR TB patients initiated on treatment at Nkqubela and Fort Grey Hospitals.

Submitted by Ana Lúcia Torres (bfmhuap@gmail.com) on 2017-10-09T16:06:50Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertação Patricia Costa.pdf: 1100032 bytes, checksum: eb4ab925fc60980c9f75450c5ed034b7 (MD5) / Approved for entry into archive by Ana Lúcia Torres (bfmhuap@gmail.com) on 2017-10-10T11:33:15Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertação Patricia Costa.pdf: 1100032 bytes, checksum: eb4ab925fc60980c9f75450c5ed034b7 (MD5) / Made available in DSpace on 2017-10-10T11:33:15Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertação Patricia Costa.pdf: 1100032 bytes, checksum: eb4ab925fc60980c9f75450c5ed034b7 (MD5) Previous issue date: 2015 / Instituto Estadual de Doenças do Tórax Ary Pareiras / Adesão ao tratamento e o consequente aumento das taxas de cura resultam da interação de fatores relacionados aos serviços de saúde, aos pacientes, à sociedade e à gestão pública. Foi realizado um estudo de caso em uma unidade ambulatorial de referência terciária (UART) para o tratamento da TBMDR no município de Niterói/RJ, utilizando a abordagem quantitativa e qualitativa com o objetivo de conhecer os fatores relacionados à adesão, na perspectiva dos usuários, profissionais e gestores. Foram utilizadas diferentes fontes de evidência na busca de pontos comuns e divergentes e a análise de conteúdo possibilitou a identificação de fatores favoráveis ou não à adesão a partir das categorias adesão, acesso, acolhimento, vínculo, responsabilização. A maioria dos pacientes em tratamento relatou dificuldade de acesso aos benefícios sociais. A ausência de alguns profissionais na equipe comprometeu a abordagem de importantes questões relativas ao perfil dos pacientes, principalmente a vulnerabilidade social, o consumo de álcool e de outras drogas, além do isolamento e preconceito. A oferta gratuita de mediação, a realização de exames na própria UART, a flexibilidade nos agendamentos, a busca de faltosos e o vínculo com a equipe de saúde foram descritos como fatores importantes para a adesão. O conhecimento sobre a doença atual e seu tratamento e seu tratamento associados à vontade do paciente de curar-se foram relatados como aspectos importantes para superar as barreiras encontradas para a realização do tratamento. Os resultados apresentados sugerem que, apesar da existência de fatores desfavoráveis à adesão, as ações de acolhimento, vínculo e responsabilização desenvolvidas pelo serviço foram suficientes para promover a adesão no grupo estudado. Entretanto, recomenda-se a melhoria do acesso aos benefícios assistenciais, a implementação de novas formas de comunicação sobre as formas graves de tuberculose e a articulação com outros segmentos públicos e da sociedade para o enfrentamento da TBMDR

INTRODUÇÃO: A incidência de tuberculose (TB) em Santos (SP) situa-se em 73/100.000 habitantes-ano. A prevalência média de coinfecção TB/HIV é de 16%, taxas de cura e abandono de tratamento, entre casos novos são, respectivamente, 71% e 12%. Tais indicadores sugerem elevado risco para TB multidroga resistente (TBMR) no município, com incidência estimada em 1,9/100.000 habitantes-ano. OBJETIVO: Descrever e analisar o perfil de sensibilidade às drogas (TS) de primeira e segunda linha de tratamento entre pacientes com TB pulmonar (TBP), estimar a incidência de TBMR e a proporção de TB extensivamente resistente (TBXR); analisar aspectos moleculares, epidemiológicos e institucionais dos casos de TBP resistentes em Santos (SP). MÉTODOS: Estudo descritivo de uma coorte de pacientes de TBP, com início de tratamento ou retratamento entre 01 de janeiro de 2011 a 31 de dezembro de 2012. Definiu-se como caso de TBP, indivíduos com 15 anos ou mais, de ambos os sexos, residentes no município de Santos, com manifestações clínicas compatíveis com TBP e confirmação por cultura com isolamento de Mycobacterium tuberculosis. As variáveis de interesse para o estudo foram as características sociodemográficas, história atual e pregressa de TB, aspectos relativos ao tratamento, co-morbidades, ao diagnóstico e resistência a drogas. Para as análises comparativas entre proporções foram usados os testes qui-quadrado de Pearson e o Exato de Fisher e para variáveis contínuas o teste T de Student ou o de Kruskal - Wallis. Os perfis genéticos dos isoladas resistentes a ao menos uma droga foram obtidos pela técnica RLFP e analisados pelo programa Bionumerics versão 5.0 (Applied Maths - Bélgica). A descrição da distribuição espacial da TB resistentes e clusters foram feitas mediante a inserção dos casos no mapa de Santos, por endereço de residência, segundo o índice de vulnerabilidade social. RESULTADOS: Dos 263 casos de TBP selecionados, 68,4% (180/263) eram do sexo masculino, a mediana da idade foi de 38 anos, 8,7% (23/263) eram diabéticos; 20,4% (42/206) dos casos novos apresentavam ao menos um fator de risco para TBMR; destacando-se entre estes casos 10,7% (22/206) de confecção HIV/TB; 47,3% (123/260) tiveram tratamento supervisionado, 14,7% (91/617) dos contatos foram examinados, 18,6% (49/263) foram hospitalizados durante o tratamento, perfazendo uma média de 145,4 dias por paciente. Entre os casos resistentes a ao menos uma droga, a resistência à isoniazida foi 8,4% (22/263) e à rifampicina 3,8% (10/263) dos casos. A TBMR primária foi encontrada em 1,9% (4/206) dos casos e destes 25,0% (1/4) eram TBXR. A incidência média anual de TBMR foi de 0,57/100,000 habitantes. Dos 25 isolados resistentes ao menos uma droga, submetidos à RFLP, 12 (48,0%) foram agrupados em seis grupos genéticos, com dois pacientes em cada grupo. CONCLUSÕES: A elevada proporção TBMR primária, com um caso de TBXR enfatizam a necessidade de universalizar a cultura e TS, ampliar a cobertura do tratamento supervisionado, a investigação rotineira dos contatos e o monitoramento da resistência a drogas. O fortalecimento da vigilância da resistência às drogas é indispensável para o contínuo aperfeiçoamento do Programa de Controle da TB, especialmente em regiões de elevada carga da doença / INTRODUCTION: The incidence of tuberculosis (TB) in Santos (SP) is located around 73 / 100,000-year, approximately double that found on average in the country. The average prevalence of TB / HIV is 16% cure rates and treatment dropout among new cases are, respectively, 71% and 12%. Such indicators suggest high risk for multidrug-resistant TB (MR-TB) in the city, with the incidence estimated at 1.9 / 100,000-year. OBJECTIVE: To describe and analyze the sensitivity to drugs of first and second line treatment of patients with pulmonary TB (PTB) to estimate the incidence of MR-TB and extensively drugresistant TB (TBXR), describe molecular and institutional aspects, spatial distribution, epidemiological PTB resistant cases in the city of Santos (SP). METHODS: A descriptive study of a cohort of patients with PTB residing in the city who started treatment or retreatment in the period January 2011 to December 31, 2012. The case definition PTB individuals 15 years or more, both sexes, living in the city of Santos (SP), who present clinical manifestations compatible with PTB and whose confirmation was made by culture with isolation of M. tuberculosis. The variables of interest for the study were: bacteriological / laboratory socio-demographic characteristics, current and previous history of TB, aspects related to treatment, and comorbidities. For comparative analyzes of proportions the chi-squared tests and Fisher\'s exact were used for continuous variables and the Student t test or the Kruskal - Wallis. The genetic profiles of isolates resistant to at least one drug were obtained by RFLP (length polymorphism restriction fragment) and analyzed using version BioNumerics 5.0 (Applied Maths - Belgium) software. The description of the spatial distribution of resistant TB and the clusters was made by inserting the cases in Santos map, by address of residence, which was according to the index of social vulnerability. RESULTS: Of the 263 cases of PTB selected, 68.4% (180/263) were male, th median age was 38 years, 8.7% (23/263) were diabetes; 20.4% (42/206) of new cases had at least one risk factor for MR-TB, especially 10.7% (22/206) of making HIV / TB; 47.3% (123/260) underwent supervised treatment, 14.7% (91/617) of the contacts were examined, 18.6% (49/263) were hospitalized during treatment, totaling 7127 days of hospitalization with a mean 145.4 days per patient. Among the cases resistant to at least one drug resistance to isoniazid 8.4% (22/263) and rifampin 3.8% (10/263) of the cases was found. The primary MR-TB was found in 1.9% (4/206) of MR-TB cases and of these 25.0% (1/4) were TBXR. The average annual incidence of MDR-TB was 0.57/100,000 inhabitants. Of the 25 isolates resistant least one drug, subjected to molecular characterization of IS6110, 12 (48.0%) were grouped in six clusters, with each group including two isolates. CONCLUSIONS: A high proportion of primary MR-TB, including a case of TBXR emphasizes the need to universalize culture and TS, expand the coverage of supervised treatment, routine investigation of contacts and monitoring of drug resistance. The strengthening of the surveillance of drug resistance is essential for continuous improvement of the TB Control Program, especially in regions of high disease burden

Made available in DSpace on 2015-04-22T22:06:21Z (GMT). No. of bitstreams: 1 eric lima.pdf: 633686 bytes, checksum: 0cc537b946f15fad5d8bce89fbe72b90 (MD5) Previous issue date: 2013-06-04 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Tuberculosis is an endemic disease of great importance to public health since the 1980, has had a significant change in their pattern of incidence and mortality due to advent of the epidemic with HIV. Recently, the increase in reported cases of drug resistance, has also contributed to the worsening of the disease, thus constituting one of the main problems that hinder the control of this disease at present, due to the impact it makes on the duration and cost of treatment. This paper addresses the issue of multidrug resistance in the context of the Amazon, which has the highest incidence rates among all states of the Brazilian federation. The study was developed in three stages corresponding to the goals set resulting papers. The first item corresponds to the product of the analysis of the database Sinan, treating the data Completeness of tuberculosis in Amazonas, in the period 2001-2010, comparing municipalities priority and non-priority. The second article discusses the issue of TB / HIV and its probable influence on the development of drug resistance, through a systematic review of scientific literature nationally and internationally. The third article is a descriptive cross-sectional study, referring to cases of multidrug-resistant tuberculosis reported in the state of Amazonas during the period 2006-2012. / A tuberculose é uma endemia de grande relevância para a saúde pública que, desde a década de 1980, tem apresentado uma alteração significativa no seu padrão de incidência e mortalidade, em decorrência advento da epidemia pelo vírus do HIV. Recentemente, o aumento do registro de casos de resistência aos tuberculostáticos, também tem contribuído para um agravamento do quadro da doença, constituindo assim um dos principais problemas que dificultam o controle deste agravo na atualidade, devido ao impacto que provoca na duração e custos do tratamento. Esta dissertação aborda a questão da multirresistência no contexto do Amazonas, que apresenta uma das maiores taxas de incidência entre todos os estados da federação brasileira. O estudo foi desenvolvido em três etapas correspondentes aos objetivos traçados que resultaram artigos científicos. O primeiro artigo corresponde ao produto da análise do banco de dados Sinan, tratando da Completitude dos dados de tuberculose notificados no Amazonas, no período de 2001 a 2010, comparando municípios prioritários e não prioritários. O segundo artigo discute a temática da coinfecção TB/HIV e sua provável influência no desenvolvimento da resistência aos tuberculostáticos, através de uma Revisão Sistemática da literatura cientifica nacional e internacional. O terceiro artigo trata de um estudo descritivo e transversal, referente aos casos de tuberculose multirresistente notificados no estado do Amazonas durante o período de 2006 a 2012.

Introduction Tuberculosis (TB) is a major cause of death worldwide. Control of Tuberculosis is a serious challenge to global health. A new and potentially devastating threat to TB control is the emergence of multi-drug resistant TB (MDR-TB). South Africa was ranked fourth among the countries with the highest number of confirmed MDR-TB cases. Aim The aim was to investigate the annual MDR-TB prevalence and associated risk factors for MDR-TB from 2001 to 2007 at the Prince Cyril Zulu Communicable Disease Centre. To investigate previous TB treatment duration, previous TB treatment outcome, and duration of previous TB treatment interruption in a subgroup of patients who were previously treated for TB. To determine the average length of time from diagnosis of TB to diagnosis of MDR-TB and commencement of MDR-TB treatment. Methods An observational analytic nested case-control study design was used. All patients who were diagnosed with pulmonary TB and who had a sputum culture performed between 2001 and 2007 were included in the study. The cases were all MDR-TB cases diagnosed on sputum culture between 2001 and 2007. The controls were drug susceptible TB cases which had a sputum culture done at diagnosis, and were diagnosed in the same month as the MDR-TB case Results There were 10 205 sputum cultures performed from 2001 to 2007. MDR-TB was found in 445 patients. An increase in the prevalence of MDR-TB occurred in 2007, due to a significant increase in prevalence among new TB cases. The MDR-TB prevalence was 11.7% among new TB cases and 4.7% among previously treated TB cases in 2007. There was no significant association between demographic characteristics and MDR-TB. Previous TB treatment failure and a duration of previous TB treatment of greater than 32 weeks was found to be significantly associated with MDR-TB. The median time from TB diagnosis to MDR-TB diagnosis was 98 day and from MDR-TB diagnosis to MDR-TB treatment 10 days. Discussion Delays in the diagnosis of MDR-TB, long waiting times before MDR-TB treatment commencement and lack of isolation have contributed to the spread of primary MDR-TB and was most likely responsible for the increase in prevalence of MDR-TB among new TB cases. Recommendations It was suggested that a sputum specimen should be obtained for culture and sensitivity from all new TB patients in areas which have an MDR-TB prevalence of greater than 3% among new TB patients. Ensure patient education on basic infection control measures. Improve MDR-TB diagnosis and reduce waiting times for MDR-TB treatment. / Thesis (M.Med.Sc.)-University of KwaZulu-Natal, Durban, 2011.

Tuberculosis is a disease that has a detrimental effect on the economic growth of South Africa. The country’s TB mortality rate is amongst the highest in the world, and the worst affected industry is mining. Effective environmental controls of tuberculosis in mining areas remain a challenge, mainly because there is a lack of quantitative data to guide the implementation of these controls. No occupational exposure limits exist for bio–aerosols, particularly Mycobacterium tuberculosis. This makes it difficult to distinguish between high– and low risk areas. It is believed that a single inhaled M. tuberculosis particle can cause the tuberculosis disease, and as this disease can deteriorate all major systems of the body, great care should be taken in the classification of an area. Aim: This study aimed to quantify the environmental presence of the M. tuberculosis bacilli in various occupational settings of a platinum mine. Method: The monitored areas are all structures above ground, and include high TB risk areas, such as the hospital TB Ward, and low TB risk areas, such as an office area. Personal monitoring of the staff in high TB risk areas has also been conducted. Monitoring was done via the PTFE filter sampling method and the SKC Bio–Sampler impinger method. The results of these two methods were compared to determine which method is more effective. The environmental variables, such as carbon dioxide and -monoxide levels, temperature (both ambient and wet– bulb), and relative humidity, were also monitored in order to identify any possible correlations between these variables and the levels of ambient TB particles. The effectiveness of the Ultraviolet Germicidal Irradiation (UVGI) system, which is in place in some of the monitored areas, was also indirectly assessed, i.e. to see if there are any M. tuberculosis particles present in an area that makes use of an UVGI system. The PCR analytical method was used to quantify the number of M. tuberculosis bacilli sampled, and the results were statistically analysed. Results: M. tuberculosis was found to be present in the office area, the laundry room, the hospital’s waiting area, the training facility, the dining room, and the mobile clinic. No M. tuberculosis particles were found in the hospital’s TB Ward and the change houses of the mine. The results showed that the PTFE filter method had a greater efficiency than the SKC Bio– Sampler in monitoring environmental M. tuberculosis particles, as the PTFE filter method yielded positive samples where the SKC Bio–Sampler did not. There is a practical significant difference between the two methods. No viable correlations between the environmental variables and M. tuberculosis prevalence were established due to the low number of samples taken. Conclusion: It seems that the effectiveness of a UVGI system is dependent on the number of people crowded into that specific area and the ventilation thereof. A UVGI system is only a precautionary measure and not a solution. There are too many factors that still need better understanding before the risk of contracting environmental TB in high risk areas of a mine can be determined. The high risk areas seem to be occupational settings that have poor ventilation, but accommodate a large number of people. The highest risk of TB infection remains close contact with infected individuals, as the results of the employee monitoring testified. / Thesis (M.Sc. (Occupational Hygiene))--North-West University, Potchefstroom Campus, 2011.

Tuberculosis is a disease that has a detrimental effect on the economic growth of South Africa. The country’s TB mortality rate is amongst the highest in the world, and the worst affected industry is mining. Effective environmental controls of tuberculosis in mining areas remain a challenge, mainly because there is a lack of quantitative data to guide the implementation of these controls. No occupational exposure limits exist for bio–aerosols, particularly Mycobacterium tuberculosis. This makes it difficult to distinguish between high– and low risk areas. It is believed that a single inhaled M. tuberculosis particle can cause the tuberculosis disease, and as this disease can deteriorate all major systems of the body, great care should be taken in the classification of an area. Aim: This study aimed to quantify the environmental presence of the M. tuberculosis bacilli in various occupational settings of a platinum mine. Method: The monitored areas are all structures above ground, and include high TB risk areas, such as the hospital TB Ward, and low TB risk areas, such as an office area. Personal monitoring of the staff in high TB risk areas has also been conducted. Monitoring was done via the PTFE filter sampling method and the SKC Bio–Sampler impinger method. The results of these two methods were compared to determine which method is more effective. The environmental variables, such as carbon dioxide and -monoxide levels, temperature (both ambient and wet– bulb), and relative humidity, were also monitored in order to identify any possible correlations between these variables and the levels of ambient TB particles. The effectiveness of the Ultraviolet Germicidal Irradiation (UVGI) system, which is in place in some of the monitored areas, was also indirectly assessed, i.e. to see if there are any M. tuberculosis particles present in an area that makes use of an UVGI system. The PCR analytical method was used to quantify the number of M. tuberculosis bacilli sampled, and the results were statistically analysed. Results: M. tuberculosis was found to be present in the office area, the laundry room, the hospital’s waiting area, the training facility, the dining room, and the mobile clinic. No M. tuberculosis particles were found in the hospital’s TB Ward and the change houses of the mine. The results showed that the PTFE filter method had a greater efficiency than the SKC Bio– Sampler in monitoring environmental M. tuberculosis particles, as the PTFE filter method yielded positive samples where the SKC Bio–Sampler did not. There is a practical significant difference between the two methods. No viable correlations between the environmental variables and M. tuberculosis prevalence were established due to the low number of samples taken. Conclusion: It seems that the effectiveness of a UVGI system is dependent on the number of people crowded into that specific area and the ventilation thereof. A UVGI system is only a precautionary measure and not a solution. There are too many factors that still need better understanding before the risk of contracting environmental TB in high risk areas of a mine can be determined. The high risk areas seem to be occupational settings that have poor ventilation, but accommodate a large number of people. The highest risk of TB infection remains close contact with infected individuals, as the results of the employee monitoring testified. / Thesis (M.Sc. (Occupational Hygiene))--North-West University, Potchefstroom Campus, 2011.

The purpose of this study was to explore and describe the personal experiences of enrolled nurses while caring for patients infected with multidrug-resistant tuberculosis (MDR-TB) in an urban tuberculosis hospital in KwaZulu-Natal province, South Africa. Generic qualitative research was conducted with a sample of purposively selected enrolled nurses who cared for MDR-TB patients. Data was collected through in-depth individual interviews and analysed using Colaizzi’s (1978) method of data analysis. The research findings revealed six major themes: the working context, fear of contracting the disease, problems that have an impact on the quality of nursing care, nurses' perceptions of the patients, support structures and nurses' expressed needs. The findings of this study indicate that the nurses work in a challenging environment and need to be supported, as they experience more negative than positive feelings while caring for these patients. / Health Studies / (M.A. (Health Studies))