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

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.

No description available.

Migrant workers in the Deciduous Fruit Industry are part of the marginalised communities in South Africa. They are often voiceless in the communities they find themselves. They are historically displaced, often prone to xenophobia and very vulnerable in terms of HIV. Not only do they have a high infection rate but they also struggle in isolation to carry the burden of HIV and AIDS affection or infection. They will face double jeopardy when a partner becomes ill, in the homeland and they have to continue with employment. The main aim of this research was to reach a holistic understanding through interdisciplinary investigation. The important question that I aim to answer is; “What is the experience of God in the lives of persons affected or infected by HIV and AIDS.” I have looked at Postfoundationalism and the Seven Movements as proposed by Muller to present the research undertaken among migrant workers with HIV and AIDS. The Practical Theology, which I explore, develops out of a very specific praxis, HIV and AIDS. I have also made used of Transversal Rationality as a practical way of doing interdisciplinary work with the stories of my co-researchers affected with HIV AIDS as a case study. I understand that Christian belief has its own integrity, which is exclusive, but if valid, is vital to be able to incorporate the different dimensions of our modern practise to give it the maximum level of meaning and significance. I hope to demonstrate this possibility through my thesis. / Thesis (PhD)--University of Pretoria, 2010. / Practical Theology / unrestricted

No description available.

Thesis ( MPH.) -- University of Limpopo, 2022 / Background Multidrug-resistant tuberculosis (MDR-TB) has recently resulted to be in an emergence state globally and this of constitute a big challenge for TB control and the goals of the World Health Organization’s End TB Strategy. Aminoglycosides (AG) were often used as part of treatment of life-threatening illnesses such as MDR-TB for decades, however their adverse effects are widely described and hearing loss is one of the major side effects. The risk factors for hearing loss in patients treated with AG include the dose and duration of AG, infection with human immunodeficiency virus (HIV), older age and persons exposed to a high level of noise while the damage can be total and permanent. Severe hearing impairment has been reported to occur among patients treated for MDR-TB with injectable drugs, especially among the elderly and patients infected with human immunodeficiency virus, however, Bedaquiline containing regimens have demonstrated improved outcomes over injectable containing regimens in the long-term treatment of MDR-TB. Methods The objective of the current study was to investigate the burden of hearing loss amongst MDR-TB patients on bedaquiline at Zithulele Hospital in Eastern Cape Province. Therefore, the current study followed a quantitative retrospective approach using simple random sampling to select MDR-TB patients treated with bedaquiline and having a baseline audiogram be the initiation of treatment. The data was captured in a Microsoft Excel spreadsheet and then transferred to Statistical Package for Social Sciences (SPSS) Version 20 for data analysis in which categorical variables were presented as percentages and frequencies, while continuous variables was presented as mean, median and standard deviation lastly, comparison of categorical variables was done using a Chi-Squared test, whereas continuous variables were compared using a t-test. P-value of <0.05 will be considered significant. Results The mean age for the participants was 39.2 years with standard deviation of 11.8 and there was no statistical significance difference between the age groups (p value = 0.178). There no was a statistical significance difference between the employment status (p value = 0.794), previous use of injectables (p value = 0.360) and type of hearing of loss (p value = 0.536). Majority of the MDR-TB patients on bedaquiline did not have hearing loss at 67% while those who had gradual hearing loss and sudden hearing loss were 26.8% and 6.2% respectively. There was no statistical significance difference between males and females in both the right and left ears, however, the right ear results appeared to be slightly worse than the left ear results. It was found that both males and females had a high frequency hearing loss in the left ears of 26.8% and 22.2% respectively as compared to the right ears with of 25.9% and 1.6% respectively. The was a statistical significance difference between the age groups in both ears for hearing loss at p-value <0.001. The overall prevalence of hearing loss was found to be 32.9% and hearing loss at 20dB or more loss at any frequency was low at 11.9% while hearing loss at 10B or more loss at any frequency was the highest at 32.9% followed by loss response at 3 consecutive frequencies at 26.2%. Hearing loss was increasing with increasing age from 8.3% in age group and age was significantly associated with hearing loss as older patients were 2.2 times more likely to have a hearing loss at a degree of 20dB and 4.4 times more likely to have a hearing loss at a degree of 10dB. Previous use of injectables was also significantly associated with hearing loss as patients who used injectables previously were 11.5 times more likely to have a hearing loss at degree of 10dB, 5.6 and 11.3 times more likely to have a hearing loss at loss response at 3 consecutive frequencies and overall hearing loss respectively. Conclusion South Africa has a high burden of drug-resistant tuberculosis (DRTB) and until recently, ototoxic aminoglycosides were predominant in treatment regimens. Drug resistant TB treatment with bedaquilines caused clinically and statistically significant deterioration of hearing loss in patients, most prominently at high frequencies. Although public health interventions to prevent hearing loss have been deemed cost effective and have meaningful individual and economic implications, hearing loss and its prevention consistently receive inadequate attention as a global public health priority. Despite the serious impacts of hearing loss, little is known regarding prevalence of ototoxic hearing loss after treatment for DR-TB. Therefore, when the use of injectable ototoxic medications is unavoidable, audiological ototoxicity monitoring is essential to optimise hearing-related outcomes.

As keeping backyard poultry rises, human contact with zoonotic pathogens will increase. One such pathogen that backyard enthusiasts have exposure risks to is Salmonella spp. which may cause a potential public health threat due to its increasing multidrug resistancy. Salmonella spp. were present in 33 of 50 samples collected from 29 sites with backyard poultry coops in San Luis Obispo County during March to May in 2014. Two different Hardy-CHROME™ Salmonella Selective Media plates were used to culture and isolate positive samples of Salmonella spp.. Each positive isolate was tested for antimicrobial sensitivity to 6 standard antibiotics: Ampicillin, Bacitracin, Erythromycin, Gentamicin, Penicillin, and Tetracycline, at the standard disk concentration levels. The Kirby-Bauer antimicrobial sensitivity test determined that 12 different profiles emerged from the Salmonella spp. isolates. All antimicrobial sensitivity profiles showed multidrug resistance in vitro with only high susceptibility to 2 major antibiotics, Gentamicin at 97% and Ampicillin at 51%. All profiles were resistant to 1 or more of the antimicrobials tested, plus the control. One Salmonella isolated was resistant to all 6 antimicrobials and another isolate to 5. The Salmonella spp. isolates proved multidrug resistance between 73%-100% to the other 4 antibiotics tested. The 24 Salmonella spp. positive sites displayed a lack of proper biosecurity and poultry husbandry practices. The criteria developed for accessing the poultry’s environment ranged from dedicated shoes for cleaning, egg handling, access to other animals and wildlife, number of birds and breeds or species in a coop, cleaning routine, over-all biosecurity and human interactions. Human exposure to Salmonella spp. pathogenic strains could increase due to environmental cross contamination and deficiencies in sanitation. The presence of Salmonella spp. with a diversity of antibiotic resistance serotypes is an important source of zoonotic pathogens for animal and human diseases that has public health risk implications.

The continuous emergence of drug-resistance pathogens is a global concern. As a result, substantial effort is being expended to develop new therapeutics and mechanisms for controlling microbial growth to avoid entering a "post-antibiotic" era in which commonly used antibiotics are no longer effective in treating infections. In this work, we investigate the efficacy and application of ceragenins as non-peptide mimics of antimicrobial peptides (AMPs). First, this work examines the susceptibility of drug-resistant Gram-negative bacteria. The susceptibility of colistin-resistant clinical isolates of Klebsiella pneumoniae to ceragenins and AMPs suggests that there is little to no cross-resistance between colistin and ceragenins/AMPs. Furthermore, Lipid A modifications are found in bacteria with modest changes in susceptibility to ceragenins and with high levels of resistance to colistin. Next, we investigated the potential for cross resistance between chlorhexidine, colistin, AMPs and ceragenins as repeated exposure of bacteria to chlorhexidine might result in cross resistance with colistin, AMPs or ceragenins. Furthermore, a proteomics study on the chlorhexidine-resistant strains showed that chlorhexidine resistance is associated with upregulation of proteins involved in the assembly of LPS for outer membrane biogenesis and virulence factors in Pseudomonas aeruginosa.Second, this dissertation describes the antifungal activity of ceragenins against an emerging multidrug-resistant fungus, Candida auris. We found that lead ceragenins displayed activities comparable to known antifungal agents against C. auris isolates. We also found that fungal cell morphology was altered in response to ceragenin treatment, that ceragenins exhibited activity against sessile organisms in biofilms, and that gel and cream formulations including CSA-44 and CSA-131 resulted in a significant log reduction against established fungal infections in ex vivo mucosal tissues. Finally, a hydrogel film containing CSA-131 was generated on endotracheal tubes (ETTs). ETTs provide an abiotic surface on which bacteria and fungi form biofilms that cause serious infections. In this study, the eluting ceragenin prevented fungal and bacterial colonization of coated ETTs for extended periods while uncoated tubes were colonized by bacteria and fungi. Coated tubes were well tolerated in intubated pigs. The ability of ceragenins to eradicate established biofilms make them attractive potential therapeutics for persistent infections in the lung, including those associated with cystic fibrosis. In ex vivo studies, we initially found that this ceragenin, at concentrations necessary to eradicate established biofilms, also causes loss of cilia function. However, by formulating CSA-131 in poloxamer micelles, cilia damage was eliminated and antimicrobial activity was unaffected. These findings suggest that CSA-131, formulated in micelles, may act as a potential therapeutic for polymicrobial and biofilm-related infections in the lung and trachea.