<p><font face="Times New Roman" size="3"><font face="Times New Roman" size="3"> <p align="left">The aim of the study is to explore the barriers associated with low VCT uptake by the TB patients attending primary health care clinics within the Buffalo City municipality. <font face="Times New Roman" size="3"><font face="Times New Roman" size="3">The study population was drawn from TB patients attending the primary health care facilities in Buffalo city municipality in the Eastern Cape Province. Eight participants were purposively selected to include those who had accepted VCT as well as those who did not.</font></font></p> </font></font></p>

Tese (doutorado)—Universidade de Brasília, Faculdade de Medicina, 2008. / Submitted by Jaqueline Oliveira (jaqueoliveiram@gmail.com) on 2008-12-11T18:15:49Z No. of bitstreams: 1 TESE_2008_JuanJCEscalante.pdf: 4789546 bytes, checksum: 592c90d5f7b6e9da19c34782bde221bf (MD5) / Approved for entry into archive by Georgia Fernandes(georgia@bce.unb.br) on 2009-02-19T15:32:57Z (GMT) No. of bitstreams: 1 TESE_2008_JuanJCEscalante.pdf: 4789546 bytes, checksum: 592c90d5f7b6e9da19c34782bde221bf (MD5) / Made available in DSpace on 2009-02-19T15:32:57Z (GMT). No. of bitstreams: 1 TESE_2008_JuanJCEscalante.pdf: 4789546 bytes, checksum: 592c90d5f7b6e9da19c34782bde221bf (MD5) / Antecedentes: a tuberculose (TB) tem causado importante morbidade e mortalidade durante séculos. Embora a incidência e letalidade diminuíram marcadamente no decurso do século XX, o surgimento da infecção pelo vírus da imunodeficiência humana (HIV) no final desse século mudou significativamente estas tendências. Objetivo: identificar características associadas à TB ativa nos pacientes com HIV/Aids, atendidos nos estabelecimentos de saúde especializados do Distrito Federal e desenhar um escore clínico‐epidemiológico para fins de predição. Método: Foi realizado um estudo de caso – controle em pacientes com 18 anos ou mais com diagnóstico de HIV/Aids, comparando os que desenvolveram TB ativa com os que não desenvolveram a doença entre os anos 2000 a 2004. Os pacientes foram identificados nas bases de dados da Secretaria de Saúde do Distrito Federal (DF), isto é no Sistema de Informação de Agravos de Notificação (SINAN) de TB e Aids, de HIV e do Sistema de Informações sobre Mortalidade (SIM), complementada com os dados dos laboratórios de TB e HIV do LACEN – DF. A identificação dos fatores de risco foi realizada utilizando regressão logística para análises uni e multivariada. Com esses fatores se desenvolveu um modelo de predição de TB ativa nos pacientes com HIV/Aids. O modelo foi avaliado no mesmo grupo de pacientes que o gerou, mediante análise de sensibilidade, especificidade, valores preditivos positivos e negativos, razões de verossimilhança, acurácia, curva ROC e a área sob esta curva, assim como o cálculo de probabilidade pós‐teste. Resultados: foram identificados 222 pacientes co‐infectados, dos quais, 206 apresentaram critérios de seleção adequados. Desses, 64 foram identificados como óbitos e 51 não foram encontrados. Foram incluídos na investigação 91 casos e 91 controles. A prevalência estimada de TB nos pacientes com HIV/Aids em 2000 e 2004 foi 0,55 e 0,43%, respectivamente. Na população geral, a prevalência da co‐infecção foi 2,62 casos por 100.000 habitantes. Dentre as características associadas à TB, sete permaneceram significativas após a análise multivariada: ter menos de 8 anos de estudos completos (OR ‐ ajustado = 4,6; IC 95% = 1,5 a 13,8), renda mensal menor que R$ 600,00 (US$ 300,00) (OR ‐ ajustado = 4,8; IC 95% = 1,5 a 14,8), mais de uma família morando no domicílio (OR ‐ ajustado = 48,7; IC 95% = 3,5 a 672,3), existência de doente com TB na família (OR ‐ ajustado = 13,6; IC 95% = 2,4 a 78,3), ter apresentado toxoplasmose cerebral nos últimos dois anos (OR ‐ ajustado = 7,2; IC 95% = 1,5 a 33,8), linfócitos T CD4+ inferior a 200 células/ μl no mesmo período (OR ‐ ajustado = 6,5; IC 95% = 2,1 a 20,1) e o não uso de um mesmo esquema HAART nos últimos 6 meses (OR ‐ ajustado = 27,2; IC 95% = 7,8 a 95,1). Estas sete características constituíram o modelo de predição recebendo escores de 1, 1, 3, 2, 1, 1 e 2, respectivamente. Na avaliação do modelo encontrou‐se 100% de sensibilidade quando o ponto de corte foi zero, 100% de especificidade quando foi igual ou maior que seis pontos, a maior razão de verossimilhança positiva (69) com seis pontos e a maior acurácia (90,1%) com quatro pontos. Com a prevalência de TB nos pacientes com HIV/Aids de 0,43% a maior probabilidade pós‐teste (23%) foi obtida com o ponto de corte 6. Conclusão: foi possível identificar características associadas à TB nos pacientes com HIV/Aids, que definem a co‐infecção no Distrito Federal e com estas características foi desenvolvido um modelo de predição clínica. _______________________________________________________________________________________ ABSTRACT / Antecedents: Tuberculosis (TB) has been causing important morbidity and mortality for centuries. Although, incidence and case fatality rates decreased remarkably in 20th century, the emergence of human immunodeficiency virus infection (HIV) at the end of that century changed these tendencies, significantly. Objectives: to identify active TB prognostic factors in HIV/AIDS patients looked after by specialized health‐care services in Brazilian Federal District (DF) and to develop a clinicalepidemiologic score. Method: a case‐control study were conducted in HIV/AIDS adult patients (> 18 years‐old) with active TB co‐infection, developed among 2000 to 2004, and the ones without active TB. The patients' identification took place in the databases of Federal District Health Department; they were: TB and AIDS Information System on Notification Diseases (SINAN‐TB and SINANAIDS), HIV database and Mortality Information System (SIM); it was complemented with TB and AIDS laboratories data of LACEN ‐ DF. Univariate and multivariate logistic regression were performed to indentify risk factors and to develop a prediction model of active TB in HIV/AIDS patients. Training group was used as the validation group. Results of the validation procedure were described by sensitivity, specificity, the positive and negative predictive value, the likelihood ratio, accuracy, the area under the receiver operating characteristic (ROC) curve and pos‐test probability. Results: Two hundred six co‐infected patients were identified with all the selection approaches. From this group of patients, 64 were died and 51 were not found. Therefore, 91 cases were included in this study, together with 91 controls. The estimated prevalence of TB in HIV/AIDS patients in 2000 and 2004 was 0.55% and 0.43%, respectively. In the general population, the prevalence of co‐infection was 2.62 cases for 100000 inhabitants. Seven characteristics were associated to active TB: a) less than 8 years of schooling (adjusted OR = 4.6; 95% CI = 1.5 to 13.8), monthly income less than R$ 600.00 (US$ 300.00) (adjusted OR = 4.8; 95% CI = 1.5 to 14.8), household with more than one family (adjusted OR = 48.7; 95% CI = 3.5 to 672.3), any relative with TB (adjusted OR = 13.6; 95% CI = 2.4 to 78.3), cerebral toxoplasmosis in the last two years (adjusted OR = 7.2; 95% CI = 1.5 to 33.8), lymphocytes T CD4+ count lower than 200 cells/μl in the last two years (adjusted OR = 6.5; 95% CI = 2.1 to 20.1) and non‐use the same HAART regimen in the last 6 months (adjusted OR = 27.2; 95% CI = 7.8 to 95.1). The prediction model was developed with these features with the following scores: 1, 1, 3, 2, 1, 1 and 2, respectively. In the evaluation model, sensibility was 100% (cutoff point = 0), specificity 100% (cut‐off point > 6), the higher positive likelihood ratio of 69 (cut‐off point = 6) and the higher accuracy of 90.1% (cut‐off point = 4). The higher pos‐test probability was 23% (cut‐off point = 6), it was estimated from 0.43% of TB prevalence in HIV/AIDS. Conclusion: It was possible to identify prognostic factors of TB in HIV/AIDS patients in the Federal District and to develop a clinical prediction model.

Submitted by Heitor Rapela Medeiros (heitor.rapela@ufpe.br) on 2015-03-06T12:37:03Z No. of bitstreams: 2 Dissertacao_Final_13_08-14_Fabio_queiroga.pdf: 1835518 bytes, checksum: 4868aed1cb91d21043f2bb5266455b63 (MD5) license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) / Made available in DSpace on 2015-03-06T12:37:03Z (GMT). No. of bitstreams: 2 Dissertacao_Final_13_08-14_Fabio_queiroga.pdf: 1835518 bytes, checksum: 4868aed1cb91d21043f2bb5266455b63 (MD5) license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Previous issue date: 2012-03-27 / A tuberculose (TB) em associação à infecção pelo HIV tem apresentações clínicas diferentes do habitual. Isso também acontece com imagens radiológicas que correspondem às lesões pulmonares atípicas em relação ao encontrado em indivíduos soronegativos com TB pulmonar. Este estudo teve, como objeto de investigação, indivíduos infectados pelo HIV que iniciaram tratamento para tuberculose pulmonar em um serviço de referência para HIV/AIDS, em Pernambuco (Hospital Correia Picanço), no período de 2007 a 2010. O principal objetivo foi verificar a associação entre a presença e o tipo de lesão pulmonar na radiografia de tórax, bem como os níveis de linfócitos CD4. Trata-se de um estudo observacional do tipo corte seccional com um componente analítico. Inicialmente, foram incluídos no estudo 182 pacientes que iniciaram tratamento para tuberculose, dos quais 64 foram excluídos da análise. A contagem mediana de células T CD4 dos pacientes analisados foi de 147,5 células/mm3. Entre os pacientes com CD4<200 células/mm3, as apresentações radiológicas mais encontradas foram: consolidação segmentar ou lobar, infiltrado difuso, infiltrado focal, derrame pleural, infiltrado miliar e linfonodomegalia. Não houve ocorrência de cavidades simples nos pacientes com CD4 abaixo de 200 células/mm3. Não se encontrou associação estatística significativa de nenhum acometimento pulmonar com nível de CD4, mesmo após o ajuste realizado. Os resultados sugerem que nenhuma alteração radiológica está associada aos níveis de linfócitos CD4 na população de indivíduos coinfectados pelo TB/HIV.

Submitted by Daniella Sodre (daniella.sodre@ufpe.br) on 2015-04-15T15:11:48Z No. of bitstreams: 2 TESE Gabriela Guedes.pdf: 1658990 bytes, checksum: d74ac5823949c1e44d7efd506322f238 (MD5) license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) / Made available in DSpace on 2015-04-15T15:11:48Z (GMT). No. of bitstreams: 2 TESE Gabriela Guedes.pdf: 1658990 bytes, checksum: d74ac5823949c1e44d7efd506322f238 (MD5) license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Previous issue date: 2013 / A imunossupressão, causada por diversos fatores tais como desnutrição, doença auto-imune, infecção pelo HIV ou uso de drogas imunossupressoras tem contribuído com o aumento da incidência da tuberculose (TB) no mundo. O requisito essencial para o controle da TB é a identificação rápida e precisa dos indivíduos infectados. Os métodos convencionais (baciloscopia, cultura, histopatológico, radiografia de tórax e teste tuberculínico-TT) para diagnóstico da TB têm as suas limitações de especificidade, rapidez e sensibilidade. Ainda é uma tarefa desafiadora diferenciar pacientes com tuberculose ativa daqueles com lesões quiescentes, vacinação prévia com BCG ou outras doenças com sintomas semelhantes ao da TB. Portanto, o trabalho teve como objetivo principal avaliar o desempenho dos testes QuantiFERON®-TB Gold (QFT-GIT) e PCR único tubo (STNPCR) no diagnóstico da TB em pacientes imunodeprimidos. Foram selecionados 100 pacientes, que foram divididos em dois grupos: imunodeprimidos (n = 88) e controle (n = 12). As amostras biológicas (sangue, urina, LCR e escarro) de todos os indivíduos envolvidos foram submetidas aos testes QFT-GIT e STNPCR. A sensibilidade e especificidade do QFT-GIT, da STNPCR e do TT foram 57,4% e 95,3%; 64,3% e 91,4%; 69,2% e 98,1%, respectivamente. Os testes QFT-GIT e TT demonstraram uma concordância moderada (κ = 0,41). Dez pacientes apresentaram resultado indeterminado ao QFT-GIT e apenas 1 foi reagente ao TT. A maior frequência de TT reatores ocorreu nos indivíduos com contagem de T CD4+ >350 céls/μL. Entre os pacientes com TT reator, 60% possuíam vacina BCG, confirmada através da cicatriz vacinal e 46,7% relataram história prévia de TB. Apenas 20% dos pacientes com TB confirmada apresentaram cultura bacteriana positiva nas amostras (urina, LCR ou escarro). Os testes QFT-GIT e STNPCR não demonstraram utilidade na rotina dignóstica em pacientes imunodeprimidos. Portanto, o TT deverá continuar a ser usado para a triagem inicial de pacientes imunodeprimidos com suspeita de TB.

M.Tech. (Biomedical Technology) / TB continues to be one of the major causes of morbidity and mortality in developed and developing countries, (Mauch, 1993), despite the development of drugs and vaccines. Today, TB is one of the most serious health problems not only in South Africa, but worldwide. The transmission rate for TB for the population of Cape Town is 3% per year, while the transmission rate in gold mineworkers is estimated at 10% per year (Churchyard and Corbett, 2001). Tubercle bacilli have the ability of evading the immune system by entering a dormant phase while in the human host, and are able to reactivate at a later stage. Little is known about the mechanisms of this reactivation. TB remains a global emergency because of our lack of understanding of the details of its pathogenesis (Rook and Zumla, 2001). Since radioactive minerals are found in mines, it was postulated that radioactivity may be the reason for pulmonary cancers, a fact which is now well established. The biologic effects of radiation have been shown to produce irreparable deoxyribonucleic acid double-strand breaks or singlestrand breaks, or create structural changes by damaging the nucleus. Although no studies have shown toxic effects resulting from long-term, low-dose radiation exposure, risks are still assumed, (Herscovici and Sanders, 2000), and research concerning the mutagenic affects of lowdose radiation exposure is necessary. All the risk factors for pulmonary tuberculosis (PTB) in mineworkers are not known, although many have been identified, such as age and mining occupation. This study aimed to determine if long-term, low-dose exposure to ionizing radiation has an effect on the reactivation of dormant tubercle....

Magister Public Health - MPH / Background: Botswana has one of the highest TB incidence rates in the world. Tuberculosis in those without HIV infection accounts for 13% of adult mortality and in those living with TB and HIV in Botswana account for 40% of annual adult mortality. Francistown is a health district with TB mortality rates in excess of 5% of diagnosed TB patients yearly. The aim of this study was to assess patient related factors and early warning signs (predictors) of death among TB patients on treatment in Francistown clinics in order to identify possible interventions. Methodology: A retrospective case-control study design was used in this study. The records of all patients treated for TB from January 2010 to November 2015 who met the study inclusion criteria were extracted from the district electronic register (ETR). Socio-demographic variables, clinical variables and treatment outcome were collected and analysed. Univariate and multivariate logistic regression techniques were used to assess the predictors of death and the Kaplan Meier plot to determine time to death while on treatment. Result: A total of 1718 participants were included in the study. The median age of the study population was 35 years (IQR: 29, 42). Of the study population, 56% were male. Most of the participants had pulmonary TB (78%). There was a very high HIV prevalence among the study population (74%). About 44% of participants had smear results at the start and at the completion of TB treatment. Of the 1718 participants 161 (95% CI 8.0-10.8) died during the course of TB treatment. Univariate analysis showed HIV status, extra-pulmonary TB and a history of TB treatment default to be associated with earlier death. Multivariate analysis of selected variables showed that being older (≥ 55 years old), HIV-positive, having a history of TB and extra-pulmonary TB are independent predictors of death while on TB treatment. The overall median time to death was 52 days. Lack of HIV-related intervention during TB treatment was a significant independent predictor of time to death (adjusted HR = 1.79; 95% CI 1.03 – 3.1; p = 0.037). Conclusion: Of the 1718 adult patients treated for TB in Francistown clinics from January 2010 to November 2016, 161 (9%) died while on treatment. The predictors of death identified in the study include, prior history of TB infection, Extra-Pulmonary TB, HIV status, HIV-related intervention and over 55 years of age. Gender was not a predictor of death in this study. Their overall median time to death in the study was 52 days. Patients on treatment for the first time with no previous history of TB lived on average 150 days on TB treatment. All TB patients with HIV co-infection that did not receive Antiretroviral Therapy (ART) and or Cotrimoxazole Preventive Therapy (CPT) died during the intensive phase of TB treatment. More than half of all deaths recorded in this study occurred during the intensive phase of TB treatment. After adjusting for gender, age, treatment classification, treatment group and HIV status and the lack of HIV-related interventions during TB treatment was the significant predictor of earlier death among patients with TB/HIV co-infection in this study.

Read abstract on the attached document. / Dissertation (MSc)--University of Pretoria, 2014. / lk2014 / School of Health Systems and Public Health (SHSPH) / MSc / Unrestricted

The serious threat of tuberculosis, especially XDR-TB, is a reality in Southern Africa particularly in individuals with HIV/AIDS. Therefore the importance of development of new or improved anti-TB treatment must now be emphasized more than ever. In this study, a model was created to target isoniazid (toxophore) specifically to a cholesterol rich environment where mycobacteria reside in macrophages, by making use of a sterol binding drug, Amphotericin B (haptophore). Isoniazid was covalently linked to Amphotericin B via a Schiff base to a linker molecule, terephthalaldehyde. Although this molecule showed a loss of biological activity, a discovery was made by serendipity that could have great impact in understanding how Mycobacterium tuberculosis enters and survives in the host macrophage. During the testing of the compound, it was discovered that Amphotericin B bound to mycolic acids at least as well as it binds to cholesterol, its natural ligand. This could provide proof of the structural similarity between mycolic acids and cholesterol but many more controls need to be investigated. As cholesterol was previously shown in literature to be critical for entry and survival of Mycobacterium tuberculosis in macrophages, the indication of a structural mimicry between the cell wall mycolic acids and cholesterol and the attraction of these two chemical entities to one another seems to be highly relevant. This characteristic can now be further explored to improve the understanding of the process of entry and survival of Mycobacterium tuberculosis in the macrophage host. Copyright 2006, University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. Please cite as follows: Benadie, Y 2006, Amphotericin B as a mycolic acid specific targeting agent in tuberculosis, MSc dissertation, University of Pretoria, Pretoria, viewed yymmdd < http://upetd.up.ac.za/thesis/available/etd-04212008-151642 / > / Dissertation (MSc (Biochemistry))--University of Pretoria, 2008. / Biochemistry / unrestricted

Tuberculosis has become one of the world’s most devastating diseases, with more than two million deaths and eight million new cases occurring annually due to the development of drug-resistant strains of Mycobacterium tuberculosis, the breakdown of the immune system of its host by HIV, lapses in public health programmes and the fact that diagnosis of TB is not 100% reliable. Early, affordable, unsophisticated and accurate diagnosis of TB to facilitate timely and proper treatment has become of highest priority to public health. Mycolic acid (MA) is the major lipid cell wall component of Mycobacterium tuberculosis and is unique to mycobacteria and closely aligned genera. Mycolic acids have been shown to be unique antigens for TB diagnosis and have been utilized in standard serodiagnostic techniques, but sensitivity and specificity was found to be unsatisfactory. Two vastly different techniques were investigated in this study – one making use of antibodies and MA, the other, just MA and its unique physical properties of interaction with other MA using fluorescently labelled MA. In the first approach, Sepharose protein-A was employed to trap patient IgG antibodies. The anti-MA antibodies were then quantified by probing with liposomes containing fluorescently labelled MA. Although it generally worked well, a few false –positive and –negative results were obtained. This assay appeared to be more accurate than the standard ELISA immunoassay but it is more labour intensive and not even remotely as amenable to large-scale screening and automation as ELISA. The second approach is based on the release of fluorescent MA from immobilized liposomes on glass by means of the specific attraction that MA in test liposomes or TB patient serum was perceived to have on the immobilized MA. The end-point measured was the remaining fluorescent MA on the surface. Differences were observed between the control and patients’ sera at a very high dilution but not between the HIV negative, TB positive and HIV positive, TB positive patients. This was merely an exploratory investigation and more work still needs to be done before the test is ready for validation with large numbers of serum samples. If subsequent studies confirm these findings, then this concept may be converted into a simple, rapid and affordable TB diagnostic test or be used in combination with the IAsys affinity biosensor to provide a more thorough diagnosis / Dissertation (MSc (Biochemistry))--University of Pretoria, 2009. / Biochemistry / unrestricted

BACKGROUND: The incidence of tuberculosis (TB) in the United States has declined following a logarithmic pattern, with few exceptions. One exception was during the acquired immunodeficiency syndrome (AIDS) epidemic, which was thought to have caused the deviation. However, since then, alternative explanations have been proposed, including the increased burden of chronic diseases, immigration, and the increase in the use of immune suppressant medications.CONCLUSIONS: The HIV/AIDS epidemic likely played a significant role in the 1979-1985 deviation, but not subsequently. Furthermore, EPTB as a proportion of total TB cases has remained high. Further studies to delineate the etiologies of these findings are needed.METHODS : Epidemiological data of the Center for Disease Control and Prevention (CDC) and the Bureau of the Census were analyzed regarding TB incidence, human immunodeficiency virus (HIV) infection, immigration status, and age for the period 1953-2011.RESULTS : Data analysis identified a deviation from the logarithmic decline in TB cases that started in the mid- 2000s. This divergence did not appear to be related to HIV status. The overall decline in TB cases since 1953 has been almost exclusively due to a reduction in pulmonary TB (PTB) and not to extra-pulmonary TB (EPTB).