La presente investigación tuvo como objetivo, comparar los niveles de depresión en pacientes con tuberculosis, según los tipos de tratamientos de la red urbana del Minsa Chiclayo, 2012, el diseño utilizado fue comparativo de tipo no experimental. El grupo de trabajo fue conformado por 120 pacientes diagnosticados con tuberculosis. El instrumento utilizado fue el inventario de depresión de Aaron Beck, el cual mide los niveles de depresión, leve, moderada y severa. Dentro de los resultados más resaltantes, se halló que la depresión difiere por tipos de tratamiento, encontrándose que los pacientes que recibieron el tratamiento esquema 1, presentan bajos niveles de depresión leve a moderada; a diferencia de los que reciben el tipo de tratamiento multiresistente, quienes demuestran altos niveles de depresión moderada a severa. / Tesis

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Tuberculosis (TB) and an infectious disease caused by Mycobacterium tuberculosis that afflicted mankind since antiquity with reports of up to about 5,000 BC Despite the high efficiency of treatment, TB remains a major health problem. In 2011, an estimated 8.7 million incident cases of TB worldwide. Among the main measures for tuberculosis control are early diagnosis and proper treatment of the disease. Thus, the active search should be performed continuously for all healthcare services (primary, secondary and tertiary). The study aimed to evaluate the benefits of automated methodology for the diagnosis of tuberculosis in different clinical specimens in relation to the methodology manual. This is a descriptive study and experimental evaluation of two diagnostic tests (manual and automated) for which several samples were analyzed. The survey was conducted from July to September 2011. The samples were provided by patients of 15 health units of the State, which needed to confirm or culture tuberculosis control. In the 1520 samples, smear, 188 (12.37%) samples were positive and 1,332 (87.63%) negative. In cultures on solid media (LJ), a manual methodology, 254 (16.71%) samples were positive, 1.156 (76.05%) and 110 negative (7.24%) were contaminated. In automated methodology (MGIT), the result was 258 (16.97%) positive, 1,149 (75.59%) and 113 negative contaminated (7.43%). The median time to positivity in the manual method was 31.95 days, with a mean deviation of 15.01 and automated methodology was 16.53 days, with a standard deviation of 12.39. It was possible to demonstrate concordance between the methods and various advantages that automated methodology presents compared to manual in the laboratory routine. Among them is the decreased time to detection of the disease, representing a breakthrough in the initial treatment of patients, which, in the case of TB, may mean to decrease the number of cases, since people no longer be bacillary patients. / A tuberculose (TB) e uma doenÃa infectocontagiosa causada pelo Mycobacterium tuberculosis que aflige a humanidade desde a antiguidade com relatos de ate cerca de 5.000 a.C. Apesar da alta eficiÃncia do tratamento, a TB continua como um grande problema de saÃde. Em 2011, estimou-se 8,7 milhÃes de casos incidentes de TB no mundo todo. Dentre as principais medidas para o controle da tuberculose estÃo o diagnÃstico precoce e o correto tratamento da doenÃa. Desta forma, a busca ativa deve ser realizada permanentemente por todos os serviÃos de saÃde (nÃveis primÃrio, secundÃrio e terciÃrio). O estudo teve como objetivo geral avaliar os benefÃcios da metodologia automatizada no diagnÃstico da tuberculose em diferentes amostras clÃnicas em relaÃÃo à metodologia manual. Trata-se de um estudo descritivo e experimental para avaliaÃÃo de dois testes diagnÃsticos (manual e automatizado) pelos quais diversas amostras foram analisadas. A pesquisa foi realizada no perÃodo de julho a setembro de 2011. As amostras foram fornecidas por pacientes, de 15 Unidades de SaÃde do Estado, que necessitavam de cultura para confirmaÃÃo ou controle da tuberculose. Em 1.520 amostras, na baciloscopia, 188 (12,37%) amostras apresentaram-se positivas e 1.332 (87,63%) negativas. Nas culturas em meio sÃlido (LJ), por metodologia manual, 254 (16,71%) amostras foram positivas, 1.156 (76,05%) negativas e 110 (7,24%) apresentaram contaminaÃÃo. Na metodologia automatizada (MGIT), o resultado foi de 258 (16,97%) positivas, 1.149 (75,59%) negativas e 113 contaminadas (7,43%). A mediana do tempo necessÃrio para positivaÃÃo no mÃtodo manual foi de 31,95 dias, com desvio mÃdio de 15,01 e na metodologia automatizada foi de 16,53 dias, com desvio padrÃo de 12,39. Foi possÃvel demonstrar concordÃncia entre os mÃtodos e diversas vantagens que a metodologia automatizada apresenta em comparaÃÃo a manual na rotina do laboratÃrio. Dentre elas està a diminuiÃÃo do tempo de detecÃÃo da doenÃa, representando um grande avanÃo no inÃcio do tratamento dos pacientes, o que, no caso da TB, pode significar a diminuiÃÃo do nÃmero de casos, jà que pessoas doentes deixariam de ser bacilÃferas

O presente trabalho baseia-se no estudo de 1.678 casos de pacientes inscritos no Setor de Quimioprofilaxia da Tuberculose do Centro de Saúde \"Geraldo de Paula Souza\" da Faculdade de Saúde Pública, USP,no período de 1959-76. Os pacientes foram analisados sob as variáveis de sexo, idade, medida da enduração tuberculínica no início e no final da quimioprofilaxia, tempo de viragem tuberculínica antes do início do tratamento, da condição de ser ou não comunicante de casos de tuberculose, de ter sido ou nao vacinado, pelo BCG oral, de residir ou não na área de atendimento da Unidade Sanitária, do adoecimento durante e até 5 anos após o término da quimioprofilaxia, da intolerância medicamentosa, dos esquemas terapêuticos e da permanência ou abandono do tratamento. Os resultados identificam as variáveis que influíram no êxito e no fracasso da quimioprofilaxia da tuberculose. / The present paper is based on the study of 1.678 cases of patients attending the Setor de Quimioprofilaxia da Tuberculose do Centro de Saúde \"Geraldo de Paula Souza\", Faculdade de Saúde Pública, USP, during the 1959-1976 period. The patients were analysed according to the variables of sex, age, measure of the tuberculinic induration at the start and at the end of the chemoprophylaxis, time of tuberculinic turnover before institution of the treatment, instance of being or not a transmitter of tuberculosis cases, of being or not vaccinated by oral BCG, of residing or not in the area attended by the Sanitary Unit, of being taken ill during and up to 5 years after completion of the chemoprophylaxis, of the drug intolerance, of the therapeutic schedules, and of the adherence to or abandonment of treatment. The results identify the variables that have influenced in the success and in the failure of the tuberculosis chemoprophylaxis.

Foram estudados 375 óbitos ocorridos no município de São Paulo, de pessoas de 15 anos ou mais residentes nessa cidade e em cujo atestado de óbito constava a tuberculose como causa básica ou associada. Desses 375 óbitos, foram localizadas 245 famílias dos falecidos e realizadas entrevistas domiciliárias. Houve 287 pacientes que faleceram em hospitais, e em dois desses casos não foi conseguido realizar a entrevista institucional. Dessas entrevistas, pôde ser concluído que os possíveis fatores que influíram nesses óbitos foram o baixo nível sócio-econômico e o alcoolismo; não influíram nestes óbitos a migração e o tabagismo. Foi observado que estes doentes entraram tardiamente no sistema de saúde e a maioria dos que chegaram a ser internados faleceram nos primeiros dias de internação. Foi observado também, que a maioria dos casos não estava notificada, nem como caso nem como óbito, e a Secretaria da Saúde tinha conhecimento de apenas 119 casos. Analisando esses atestados, notou-se que a tuberculose foi causa básica em 88,4 por cento deles e, após a revisão dos mesmos com base nas entrevistas domiciliárias e institucionais, a tuberculose passou a ser causa básica em 92,8 por cento , havendo uma concordância de 95,6 por cento entre o atestado original e o revisto. / Three-hundred and seventy-five deaths of persons aged 15 years or more, which ocurred in São Paulo city, have been studied taking into account the death certificates in which tuberculosis had been appointed as the basic or associate cause of death. From these 375 deaths, 245 families of the deceased have been located and then submitted to domiciliary interviews: it was found out that two-hundred and eighty-seven patients had died in hospitals; in two of the cases it was not possible to make an institutional interview. From these data, some factors which could possibly have influenced the deaths were the low-socioeconomic status and alcoholism; it was found out that neither migration nor tabaccoism had influenced the deaths. It was also noticed that these patients had entered the health system very late and the majority of those who had been duly hospitalized died within the first days of hospitalization. It was also observed that most of the cases had not been reported either, neither as a case nor as a death, being that the State Health Department only had knowledge of 119 cases. Analysing these certificates, it was observed that tuberculosis was the basic cause of death in 88.4 per cent of them, and that after reviewing them on the basis of domiciliary and institutionas interviews, tuberculosis came out to be the basic cause of death in 92.8 per cent 06 the causes, having been reached an agreement of 95.6 per cent between the original certificates and the reviewed ones.

結核病是由結核桿菌感染而引起的慢性傳染病，它是危害人類健康的主要殺手。根據世界衛生組織的報導，目前在全球範圍內有三分之一的人口感染了結核桿菌，每年約有915 萬人口被確診患有結核病。耐藥結核病尤其是對最有效的一線抗結核藥物異煙阱和利福平產生抗藥的耐多藥結核病的出現，令有效的控制結核病更加棘手。 / 在本研究中，我們首先用利福平誘導得到五株伴有明顯生長緩慢的高水平利褔卒耐藥的恥垢分支桿菌。通過比較基因組學研究發現，在編碼區有四個突變，其中兩個位於中rpoB 基因(N484T and 1488F) ，一個位於MSMEG_0436 (V49M) ,一個位於MSMEG_6872 (V181L)。rpoB 基因突變是該恥垢分支桿菌利福平耐藥的主要原因。而生長緩慢主要源於MSMEG_6872基因的影響。更為有趣的是，我們發現一個與MSMEG_6872具有相同的蛋白模序的結核分支桿菌蛋白質Rv1367 在不間的結核分支桿菌菌株之間存在I193V 多態性。193V 主要存在于北京株或者在耐藥的非北京株上。進一步的研究發現，過量表達MSMEG_6872或者Rv1367c 的恥垢分支桿菌形態上呈現為細長棒狀，而他們的親代則為短棒狀。 / 為獲得耐藥性，以及在高濃度的抗生素環境下生存，細菌必須付出一定的生物學代價。本研究中，恥垢分支桿菌以生長缺陷為代價獲得了對利褔平的耐藥，而這個代價可能是由於MSMEG_6872 基因的突變或者過量表達打破了細胞壁延長和分裂的平衡引起。 / Mycobacterium tuberculosis (MTB), which is the pathogen of tuberculosis (TB), remains a major human public health problem throughout the world. According to the report from the World Health Organization, currently about one third of the world's population was infected by MTB and there is globally 9.15 million recorded cases of TB annually. The occurrence of resistance to drugs used to combat TB, particularly multi-drug resistant TB (MDR-TB), defined as resistance to at least isoniazid and rifampin (RIF), has become a significant public health problem in a number of countries and an obstacle to effective global TB control. / In this project, we firstly obtained high level RIF resistant Mycobacterium smegmatis (MSM) strains with obviously growth retardation by repeated drug selection. Comparative analysis of genomic sequences revealed 4 mutations in coding sequences, including two in rpoB (N484T and I488F), one in MSMEG 0436 (y 49M), and one in MSMEG 6872 (y181L). Characterization of these four mutations showed that the two mutations in rpoB were correlated to RIF resistance. The one in MSMEG_6872 can render obviously growth retardation when MSMEG_6872 is over-expressed. Interestingly, we found an MTB protein, Rv1367c, which has the same motif with MSMEG_6872, had an I193V polymorphism in different MTB strains. The 193V variant was mainly found in Beijing/W or drug resistant non-Beijing/W family strains. The transformants, no matter MSMEG_6872 or Rv 1367 c, all exhibited slim and long rod shape compared to stocky and short rod appearance of the parental strain. / Mycobacterial cells must pay biological cost in order to obtain RIF resistance and survive in the high concentration of RIF. In our case, the growth arrest may be due to the mutation of MSMEG_6872 which disrupts the balance of cell wall elongation and cell division. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Guan, Bing. / "November 2011." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 139-143). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / Acknowledgements --- p.I / Abstract --- p.II / Abstract in Chinese --- p.IV / List of Abbreviations --- p.V / List of Tables --- p.VI / List of Figures --- p.VII / Contents --- p.IX / Chapter CHAPTER 1 --- INTRODUCTION / Chapter 1.1 --- Overview of Tuberculosis --- p.1 / Chapter 1.1.1 --- Pathogens --- p.2 / Chapter 1.1.2 --- Syndromes --- p.2 / Chapter 1.1.3 --- Transmission --- p.3 / Chapter 1.1.4 --- Diagnosis --- p.4 / Chapter 1.1.5 --- Epidemiology --- p.6 / Chapter 1.1.6 --- Mortality --- p.8 / Chapter 1.2 --- The Anti-TB Strategies --- p.8 / Chapter 1.2.1 --- Chemotherapy Treatment for MTB --- p.8 / Chapter 1.2.2 --- Vaccine Development for MTB --- p.9 / Chapter 1.3 --- Genome Sequencing of MTB Isolates --- p.9 / Chapter 1.4 --- Drug Resistance of MTB --- p.13 / Chapter 1.4.1 --- MDR-TB and XDR-TB --- p.15 / Chapter 1.4.2 --- Mechanism of Drug Resistance --- p.18 / Chapter 1.4.2.1 --- Intrinsic Resistance of Mycobacterium Species --- p.20 / Chapter 1.4.2.2 --- Acquired Resistance of Mycobacterium Species --- p.22 / Chapter 1.4.3 --- RIF Resistant MTB --- p.24 / Chapter 1.5 --- Useful tool for MTB Research --- p.26 / Chapter 1.6 --- The Biological Cost of Antibiotic Resistance in MTB --- p.27 / Chapter 1.6.1 --- The meaning of Biological Cost --- p.27 / Chapter 1.6.2 --- Factors Involved in Biological Cost of Mycobacterium Species --- p.29 / Chapter 1.17 --- Objectives of the Project and Experimental Strategies --- p.30 / Chapter CHAPTER 2 --- MATERIALS AND METHODS / Chapter 2.1 --- Selection of RIF Resistant MSM mc²155 Strains --- p.31 / Chapter 2.1.1 --- Bacterial Strains, Media, and Growth Conditions --- p.31 / Chapter 2.1.2 --- Selection of RIF Resistant Strain --- p.31 / Chapter 2.2 --- Minimum-Inhibitory-Concentration (MIC) Assay --- p.34 / Chapter 2.3 --- Detection of Mutations in the rpoB Gene of RIF Resistance Strains --- p.36 / Chapter 2.3.1 --- Primers Design --- p.36 / Chapter 2.3.2 --- PCR and Direct Sequencing --- p.36 / Chapter 2.4 --- Characterization of the RpoB Gene --- p.38 / Chapter 2.4.1 --- Construction of Recombinant Clones --- p.38 / Chapter 2.4.2 --- Preparation of MSM competent cell. --- p.38 / Chapter 2.4.3 --- Electroporation of plasmid into MSM competent cells --- p.39 / Chapter 2.4.4 --- Site-directed Mutagenesis of the RpoB Clone --- p.39 / Chapter 2.5 --- Whole Genome Sequencing of Parental and Drug --- p.43 / Chapter 2.5.1 --- MSM Genomic DNA Extraction --- p.43 / Chapter 2.5.2 --- Genomic Sequencing --- p.44 / Chapter 2.5.3 --- Data Analysis and SNPs Identification --- p.45 / Chapter 2.6 --- Validation of Mutations by PCR and Direct Sequencing --- p.46 / Chapter 2.6.1 --- PCR Primers Design --- p.46 / Chapter 2.6.2 --- PCR and Direct Sequencing --- p.46 / Chapter 2.7 --- Characterization of MSMEG 0436 and MSMEG 6872 --- p.47 / Chapter 2.7.1 --- Construction of the recombinant clones --- p.47 / Chapter 2.8 --- Assay of Ethidium Bromide in Intact Cells --- p.48 / Chapter 2.9 --- Quantitative Real-time PCR to Expression of the Measure the ATP-binding Cassette (ABC) Superfamily Efflux Pumps --- p.49 / Chapter 2.9.1 --- RNA Extraction --- p.49 / Chapter 2.9.2 --- Synthesis of Double-stranded cDNA from Total RNA --- p.49 / Chapter 2.9.3 --- Real-time PCR to Quantify the Efflux Pump Gene Expression Level --- p.49 / Chapter 2.10 --- The construction of the Growth Curve --- p.53 / Chapter 2.11 --- Generation of ΔMSMEG_6872 Mutant Strain --- p.54 / Chapter 2.11.1 --- Preparation of Recombination Strain Stocks --- p.54 / Chapter 2.11.2 --- Preparation of the Electrocompetent Cells of the Recombination Strain --- p.54 / Chapter 2.11.3 --- Preparation of Allelic Exchange Substrate (AES) for Generating Gene Replacement Mutants --- p.55 / Chapter 2.12 --- Validation of Rv1367c (MT1414) in MTB --- p.60 / Chapter 2.12.1 --- Primer Design --- p.60 / Chapter 2.12.2 --- Strain Selection --- p.60 / Chapter 2.12.3 --- PCR and Direct Sequencing --- p.60 / Chapter 2.12.4 --- Alignment the Gene Sequence of Rv1367c of Different MTB Strains --- p.61 / Chapter 2.13 --- Model building of the RpoB protein --- p.62 / Chapter 2.14 --- MSM staining method --- p.63 / Chapter CHAPTER 3 --- RESULTS / Chapter 3.1 --- dentification of RIF Resistant Related-genes Using Induced RIF Resistant MSM Model --- p.64 / Chapter 3.1.1 --- Emergence ofRIF Resistant Strains after the Prolonged Drug Exposure --- p.64 / Chapter 3.1.2 --- Induced RIF Resistance Were Stable In the Absence of Selection --- p.66 / Chapter 3.1.3 --- The Growth State of 5 RIF Resistance MSM mc²155 Strain --- p.68 / Chapter 3.1.4 --- Involvement of RpoB in the Mechanisms of the Emergence of RIF Resistance in MSM --- p.71 / Chapter 3.1.4.1 --- Mutations in the RpoB Gene --- p.71 / Chapter 3.1.4.2 --- Identical Mutations of RpoB Gene in Different RIF Resistance Isolates from Different Generation --- p.74 / Chapter 3.1.4.3 --- Characterization of RpoB in MSM strains --- p.76 / Chapter 3.1.4.4 --- Rifampin-Binding Pockets of RpoB Protein Model --- p.80 / Chapter 3.1.5 --- Other Genetic Alternations possibly Involved in RIF Resistance --- p.83 / Chapter 3.1.5.1 --- Whole Genome Sequencing of the Patental and P5 MSM mc²155 Strains --- p.83 / Chapter 3.1.5.2 --- Validation of the 32 Selected Alterations --- p.88 / Chapter 3.1.5.3 --- Characterization of MSMEG_0436 and MSMEG_6872 in RIF Resistance --- p.91 / Chapter 3.1.5.4 --- Characterization of MSMEG_0436 in the Growth Rate of MSM --- p.93 / Chapter 3.1.5.5 --- Characterization of MSMEG_6872 in the Growth Rate of MSM --- p.95 / Chapter 3.1.5.6 --- MSMEG_6872 Knock-out Strain Exhibited Normal Phenotype as its Parent --- p.98 / Chapter 3.1.5.7 --- Identification of Mutations in the Beta-Iactamase Gene of Mycobacterium Tuberculosis (MTB) --- p.101 / Chapter 3.1.5.8 --- Characterization of Rv 1367 c in Mycobacterium Growth Rate --- p.108 / Chapter 3.1.5.9 --- Morphology Changes of the Rv1367c and MSMEG_6872 Transformants --- p.110 / Chapter 3.2 --- Genetic Alterations in Non-coding Sequence --- p.112 / Chapter 3.2.1 --- ATP-binding Cassette (ABC) Superfamily Efflux Pumps Up-regulated in Drug Resistant M Smegmatis Strain --- p.112 / Chapter 3.2.2 --- RIF Resistant M smegmatis mc²155 Strain exhibited Low Level Cross-drug Resistance to INH --- p.115 / Chapter 3.2.3 --- RIF Resistant M smegmatis mc²155 Strain Showed Low level Accumulation of Ethidium Bromide --- p.117 / Chapter CHAPTER 4 --- DISCUSSION / Chapter 4.1 --- The Protocol for the Preparation RIF Resistant Strains --- p.121 / Chapter 4.2 --- RIF Induced Stable Chromosomal Mutations in RIF Resistant MSM Strains --- p.123 / Chapter 4.3 --- MIC Levels of the RIF Resistant Strains --- p.125 / Chapter 4.4 --- Factors May involved in RIF Resistant MSM Strains --- p.128 / Chapter 4.5 --- Cell Shape and Growth Regulation --- p.129 / Chapter 4.6 --- MSMEG _6872 and Twin-Arginine Translocase (TAT) Secretion System --- p.135 / Chapter 4.7 --- Conclusion --- p.137 / Chapter 4.8 --- Future Perspectives --- p.138 / REFERENCES --- p.139

O objetivo desta investigação foi analisar a percepção do doente de tuberculose sob tratamento supervisionado em uma Unidade Distrital de Saúde do município de Ribeirão Preto-SP. Optou-se pela pesquisa de natureza qualitativa. A população do estudo constituiu-se 6 doentes de tuberculose inscritos no Programa de Controle de Tuberculose sob o regime de tratamento supervisionado (TS). Para a coleta de dados utilizou-se o prontuário do doente e a Ficha Epidemiológica de Notificação da doença e a entrevista semi-estruturada como tendo como questões orientadoras "o significado da tuberculose" e "o tratamento supervisionado na vida do doente". Para a análise dos dados utilizou-se a técnica de análise de Conteúdo, modalidade Temática. A unidade temática central é o tratamento supervisionado na tuberculose: a percepção do doente foi conformada a partir dos seguintes núcleos de sentido: Enfoque da ação terapêutica no Tratamento Supervisionado (A ingestão medicamentosa e Fortalezas e Debilidades do Tratamento Supervisionado ); e Singularidades do doente sob tratamento supervisionado, (Percepção sobre a doença, Convivência com a doença, As repercussões do tratamento supervisionado na vida do doente). As fortalezas percebidas no processo da doença e no tratamento: medicação gratuita; a cesta básica, o vale transporte; a supervisão através da visita domiciliária permite o vínculo entre os trabalhadores de saúde e os doentes e suas famílias. As debilidades do TS percebidas foram: a fiscalização na tomada da medicação; a dependência do horário da visita para ingerir a medicação. A família e a equipe de saúde (na figura da visitadora) são reconhecidos como fator de adesão ao tratamento. / This study aimed to analyze the perception of tuberculosis patients under supervised treatment (ST) in a District Health Unit in the City of Ribeirão Preto - SP. A qualitative analysis was selected as the methodological approach. The study population consisted of 7 tuberculosis patients participating in the Tuberculosis Control Program under the a regimen of supervised treatment. The patients' medical records, the Epidemiological Form of Disease Notification and semi-structured interviews were used as instruments for data collection. The following were used as guiding questions: "the significance of tuberculosis" and "the supervised treatment in the patient's life". The Content Analysis technique - Thematic Modality - was used for data analysis. The main thematic unit "Supervised treatment in tuberculosis: the patient’s perception" was found from the following meaning units: the focus of ST as a therapeutic action (medication ingestion and the weaknesses and strengths of ST); and the Singularities of patients under supervised treatment (The perception of the disease, Living with the disease, The consequences of ST on the patient's life). The following were perceived by patients as strengths in the disease and treatment process: the provision of free medication; the availability of other forms of incentive such as the basic food basket and transportation vouchers; supervision through home visits allowed the link between health workers, the patients and their families. The weaknesses of ST were perceived as: the surveillance of medication ingestion and the dependence on the visiting hours for medication ingestion. The social actors involved in the treatment, such as the family and the health care team (in the visiting figure), were recognized as a factor of adherence to the treatment.

South Africa (SA) is burdened with one of the highest tuberculosis (TB) infection rates worldwide. The dual epidemic of HIV and MDR- and extensively drug-resistant (XDR) -TB outbreaks prompted the World Health Organisation to call for a new rapid molecular diagnostics tool(s). To curb the spread of drug-resistant TB, SA introduced genotypic Hain MTBDRplus line probe assays (Hain LPA) for the routine rapid diagnosis of MDR-TB. This study aimed to determine the frequency, geographic distribution and genetic basis for phenotypic and genotypic drug susceptibility testing (DST) discordant findings. The cultures used in this study were isolated during the period June 2007- July 2008 from Western Cape, Gauteng, KwaZulu-Natal, and Northern Cape. A total of 118 comparable MGIT and Hain LPA DST were obtained with 41 isolates verified to be discordant. The predominant families were the LAM, T, X and, S. Hain LPA failed to identify INH resistance (R) in 46.3% (19/41) of isolates with MIC‟s supporting the phenotypic resistance. Genotypic RIF-R was shown in 31.7% (13/41) of isolates which was not expressed phenotypically but interestingly the MIC‟s favour the LPA resistance. Sequencing analysis of the rpoB gene region identified new mutations; Leu458Pro, Leu436Pro, and Asp441Gly, associated with missing wildtypes. For INH, the katG and inhA gene regions were sequenced. Mutations at codon Gly213Val, Pro232Lys, Lys254Asn, and Ser259Asn were detected in katG and a variety found in inhA. These mutations have not been previously reported neither are they incorporated on the Hain LPA strips. Detailed knowledge of the frequency distribution of resistance-linked mutations and associated MICs in different regions of SA, could facilitate understanding of the limitations of current molecular tests and inform testing algorithms. These findings impact on the use of new molecular diagnostics as well as epidemiological monitoring of drug-resistant strains.

El presente trabajo se ha desarrollado con el objetivo de optimizar el uso de los recursos asignados a la Prevención y Control de Tuberculosis en el marco de la modernización de la gestión pública hacia una gestión para resultado, orientado a las necesidades del ciudadano, a través de uso racional de los recursos con un estándar de calidad adecuado y en las cantidades óptimas que maximicen el bienestar social.

Publicación a texto completo no autorizada por el autor / Refiere que la hepatitis inducida por drogas antituberculosis (HID) es una reacción adversa frecuente de los fármacos empleados en el tratamiento de la tuberculosis (RAFA). La ausencia de un reto con drogas antituberculosis establecido con un régimen adaptado a nuestra realidad, que incluya 4 drogas, y que no sea muy prolongado para evitar la transmisibilidad de la tuberculosis, hace necesaria la investigación de regímenes cortos, con alto valor predictivo, y con margen de seguridad aceptable, y que ya se han venido efectuando. Se realizó un estudio descriptivo retrospectivo longitudinal de todos los casos presentados en el Hospital Rebagliati entre 2000 y el 2011 a quienes fueron retados luego de haber presentado hepatitis inducida por drogas antituberculosis, una vez remitida. Se identificaron 30 casos de HID secundaria a esquema 1, en 17 hombres y 13 mujeres, entre las edades de 14 a 91 años. En el 60% de casos solo con compromiso hepático y en 40% con compromiso sistémico. Se aplicaron varias modalidades de retos, encontrándose una mayor proporción de identificación de droga injuriante, así como una subsecuente menor recurrencia de la RAFA cuando se retó con las 4 drogas de primera línea. Otros factores relacionados a recurrencia fueron alteraciones clínicas y laboratoriales desestimadas durante los retos; y perfil hepático anormal al final de los retos. Hubo 2 casos mortales que estuvieron relacionados a edad avanzada y desnutrición. / Trabajo académico

archives@tulane.edu / Mycobacterium tuberculosis (Mtb) remains the single largest infectious disease killer of man worldwide. The non-human primate (NHP) model, including the Indian Rhesus macaque, is particularly valuable for the study of this disease because they fully recapitulate the pathological and immunological responses, can be co-infected with Simian Immunodeficiency Virus to model lentivirus synergism, and provide ideal candidates to study novel vaccine and drug development. However, while much has been elucidated over the past centuries in regards to host immunity, bacterial responses, and granuloma formation, little remains known about histomorphologic differences between active tuberculosis (ATBI) and latent tuberculosis (ATBI) disease states. Differentiation between these disease states, in humans or in NHPs, is based on clinical parameters, and there are currently no established methods for detecting morphologic differences between these conditions at the microscopic level. The aim of this study was to develop and validate a novel approach for assessment of pulmonary pathology in Rhesus macaques experimentally-infected with M. tuberculosis alone or in the setting of SIV co-infection. Archival lung samples from experimentally-infected macaques were assessed by blinded pathologists to determine differences in a series of pathological parameters based on previous experiments. Interobserver agreement and repeatability was good between pathologists. Significant differences were observed in several pathology categories, with ATBI animals having a greater likelihood of increased alveolar macropahges, type II pneumocyte hyperplasia, perivasculitis, vasculitis/lymphangitis, and consolidation in comparison to LTBI animals. SIV co-infection increased the likelihood of perivasculitis and lymphangitis/vasculitis in both ATBI and LTBI animals. SIV co-infection also increased alveolar macrophages and type II pneumocyte hyperplasia in LTBI animals. Immunofluorescence was used to confirm the presence of Mtb bacilli within the perivascular inflammation. A similar grading system approach was used in 2 additional studies examining reactivation of ATBI in the setting of SIV coinfection unrelated to CD4+ T cell depletion and to evaluate pulmonary pathology changes in the setting of the use of an attenuated vaccine in SIV co-infected animals with similarly significant results. This grading scheme provides a valuable and desperately needed adjunctive assessment tool for evaluation of pulmonary pathology changes in the NHP model of pulmonary tuberculosis. / 1 / Denae N. LoBato