Background: Disabling hearing loss is a global burden. This burden is worsened by the emergence of multi-drug resistant tuberculosis (MDR-TB). Some of the medications used to treat MDR-TB are damaging to the cochlea and auditory nerve (ototoxic) and can lead to permanent hearing loss and/or balance disorders. Ototoxicity monitoring aims to reduce this burden by preventing or minimising the damage caused by ototoxic treatment as it can progress and worsen speech perception difficulties. However, the proposed test battery for ototoxicity monitoring is lengthy and demands active participation which is not ideal for ill patients (such as those on MDR-TB treatment). The Sensitive Range of Ototoxicity (SRO) technique is recommended to shorten the test time. The SRO consists of seven consecutive relatively high frequencies determined from the highest frequency the participant responded to. The SRO technique is time efficient. Although the SRO technique provides the prospect of a shortened test battery, there is still a global lack of audiologists. Automated audiometry is a vital application for testing especially when audiologists are not available to physically do the test. Automated audiometry has been previously validated. Clinically, automated audiometry is objective and allows for standardisation. Even though automated audiometry helps improve access to monitoring more patients, patient preference is an important factor when using automated audiometry to ensure patient-centred care is not compromised. Aims and Objectives: This study aimed to investigate the specificity and sensitivity of the SRO technique with automated audiometry compared to the gold standard (manual audiometry). This comparison was made by firstly, determining the testing time efficiency and the correlation of thresholds obtained with the different test methods and, secondly, testing the diagnostic value of automated audiometry using the SRO technique. The incidence of an ototoxicity-induced hearing loss was described by determining the time interval between starting ototoxic MDR-TB treatment and the onset of a significant threshold shift (STS) according to ASHA's criteria. Lastly, the test method preference of the participants with MDR-TB was described and compared using a short exit survey. Study Design: A prospective repeated-measures study design was used. Participants were chosen based on a risk factor (i.e. exposure to ototoxic medication) for an outcome of interest (i.e. the presence or absence of an STS). With a repeated measures study, multiple tests using different test methods can be compared with the same sample. Participants: Twenty-seven in-patients at Brooklyn Chest Hospital and DP Marais TB Hospital with normal hearing and on MDR-TB medication were included in the study. Their age range was from 19 to 51 years old with an average age of 33 years old. Non-probability convenience sampling was used as it was cost-effective, reduced data collection time and was relatively easy to execute. Data collection materials and procedures: The procedure for data collection included weekly follow-up testing for a maximum of four weeks. The test battery was as follows: an auditory symptom questionnaire, otoscopy examination, and manual and automated audiometry using the SRO technique with a fifteen-minute break in between. Participants were tested with the KUDUwave ™ in a non-sound treated room. The frequency range was determined with the SRO technique. If an STS was obtained, the patient was discharged from the study after completing an exit survey. Statistics: Analysis included descriptive statistics and inferential statistics. A Bonferroni corrected p-value (initially p ≤ 0.05) was used. Manual and automated audiometry thresholds were compared using the Pearson's Correlation Coefficient test. Manual and automated audiometry testing time and threshold means were compared using paired sample's t-tests. The diagnostic value of automated audiometry with the SRO technique was assessed with Receiver Operating Characteristics (ROC) Curves. Results: Manual audiometry was statistically more time-efficient compared to automated audiometry by an average of one minute and ten seconds (t (94) = -5.44; p< 0.003). There was a strong positive correlation for both left and right ears between the thresholds' obtained from manual and automated audiometry at 8kHz to 16 kHz (df> 28 = r > 0.70, p< 0.003). Automated audiometry was found to be a fair diagnostic test (area under the curve was 0.75; p= 0.002). Also, the ROC curve revealed that automated audiometry had a sensitivity of 61% and specificity of 90% when compared to manual audiometry (gold standard). Only participants that started data collection within 31 days after starting their MDR-TB treatment were included in the analysis of determining the incidence of an ototoxicity-induced hearing loss (n= 24 ears). This study found that 41.67% of ears (n= 10) had an ototoxicity-induced hearing loss. A box and whisker plot revealed that data was skewed to the right (i.e. more variation in data between the median and the maximum values) and that the median number of days for an ototoxicity-induced hearing loss to appear was 33 days. Secondly, 55.55% of participants (n=15 out of 27) reported auditory symptoms before data collection commencement. Aural fullness was the most reported symptom (n= eight out of 15). Ten out of 15 (66.66%) participants that reported auditory symptoms obtained an ototoxicity-induced hearing loss. Lastly, most participants (i.e. 13 out of 19; 68.42%) that completed the exit survey had no preference between manual or automated audiometry. The common rationale among these participants was “No difference noted.” Conclusion: This research study has revealed that manual audiometry was more time-efficient compared to automated audiometry in patients with MDR-TB. Also, automated audiometry was a fair diagnostic test. It may aid in reducing the disproportionate audiologist to patient ratio, especially in a developing country. However, manual audiometry (with the SRO technique) is more clinically appropriate in patients that are difficult-to-test. Secondly, audiometric settings can be changed to accommodate testing frequencies in 1/6 octaves so that the SRO technique can be clinically adopted. An ototoxicity-induced hearing loss seems to appear 33 days after ototoxic MDR-TB treatment commencement. Aural fullness was a commonly reported symptom among participants with MDRTB. Aural fullness is omnipresent in peripheral auditory pathologies. Therefore, auditory symptoms reported by patients' needs a comprehensive audiological investigation. Lastly, more research is needed on how patients (and clinicians) experience the advances in technology innovation especially in audiology where technology innovation is continuously evolving.

Over time, “superbugs,” or bacteria that have become resistant to antibiotics, have become a great concern in modern medicine. Viable alternates are currently being looked into as effective and safe ways to prevent or treat infections caused by these superbugs. One such method is through the utilization of the second messenger molecule cyclic-di-GMP (c-di-GMP) that has been shown to regulate phenotypes within other bacteria that may control surface colonization in Acinetobacter baumannii. Through a series of experiments, the active enzymes that create c-di-GMP - diguanylate cyclases - and break down c-di- GMP - phosphodiesterases - have been inactivated in mutants to test phenotypes including biofilm formation, motility, antibiotic resistance, and desiccation survival. The research’s objective is to show that manipulation of c-di-GMP within the multi-drug resistant strain of Acinetobacter baumannii may serve as a means to control this bacteria.

No description available.

<p>Insects are continually exposed to potentially toxic endogenous compounds and xenobiotics that require rapid elimination from the body. Xenobiotic resistance in insects has evolved predominantly by increasing the activity of detoxification enzymes and/or by increasing toxin excretion via the Malpighian (renal) tubules. The tubules have long been known to transport organic anions at high rates. This thesis examines the mechanisms of excretion and detoxification of the organic anion methotrexate (MTX) by isolated tissues of the fruit fly <em>Drosophila melanogaster</em>. A radioisotope tracer technique and the Ramsay assay were used to measure MTX secretion. Quantitative PCR (qPCR) was used to evaluate the expression of the genes for putative organic anion transporters. My results show that MTX transport across the Malpighian tubule epithelium is active, saturable, Na⁺-independent and inhibited by a wide range of organic anions including MK-571, probenecid and Texas Red. Pharmacological studies and qPCR analyses suggest multiple transporters are involved in the movement of MTX across the Malpighian tubules. Moreover, chronic exposure of larvae to dietary MTX or salicylate dramatically increases the transepithelial transport of MTX by isolated Malpighian tubules, suggesting that excretion of MTX is upregulated by exposure to these organic anions in the diet. In addition, treatments known to increase expression of specific detoxification enzymes, such as the P450 monoxygenases (P450s) and the glutathione-S-transferases (GSTs), also led to an increase in expression levels of multidrug efflux transporter (MET), multidrug resistance like protein 1 (dMRP) as well as to increased secretion of MTX by the tubules. This latter finding suggests a coordinated response to toxin exposure, so that when detoxification pathways are increased, there is a corresponding increase in the capacity for elimination of the products of P450 and GST enzymes. Finally, the last section of this thesis has shown that RNAi knockdown of a single organic anion transporter gene in the principal cells of <em>D. melanogaster</em> Malpighian tubules is associated with reductions in the expression of multiple, functionally-related genes. Importantly, these results indicate that dMRP andMET are not the dominantMTX transporters in the tubules when flies are reared onMTX-enriched diets. However, reductions in the expression of organic anion transporting polypeptide (OATP) are associated with reduced secretion of the organic anionsMTX, fluorescein and Texas Red. Taken together, these results suggest that OATP and at least one additional transporter, as yet unidentified, are required forMTX secretion. In conclusion, the results of my research contribute to our understanding of the mechanisms of organic anion detoxification and excretion in flies exposed to dietary toxins.</p> / Doctor of Science (PhD)

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.

No description available.

M. Tech. (Chemistry, Department of Chemistry), Vaal University of Technology / Infectious diseases, a group of illnesses caused by specific pathogens or its toxins is a leading cause of death globally. Treatment with antibiotics is a key intervention in the control and management of many infectious disease. However, the increasing incidence of antibiotics failure, due to the emergence of drug resistant pathogens, is rendering the use of antibiotics chemotherapy ineffective. A possible solution is to synthesize new compounds with broad spectrum characteristics and superior drug performances as alternative to conventional antibiotics. Schiff Bases are biologically active ligands. They form metal complexes with superior biological activities. This research aims to synthesize some Schiff Base metal complexes and investigate their biological effects on Staphylococcus aureus and Enterococcus faecalis. Metal acetylacetonates of Vanadium, Copper, Cobalt, Zinc, Magnesium, Manganese, Cadmium, Nickel and Iron were synthesized and characterized by Fourier transform infrared spectroscopy. Four Schiff bases, LI, L2, L3 and L4 were also synthesized by the condensation of 4- (diethylamino)-2-hydroxybenzaldehyde with 4-nitrobenzohydrazide and 4-methoxybenzohydrazide to form L1 and L2. 4-(dimethylamino) benzaldehyde was reacted with 4-nitrobenzohydrazide and 4-methoxybenzohydrazide to form L3 and L4 respectively. The Schiff base ligands were then reacted with synthesized Vanadium, manganese, cobalt and magnesium acetylacetonates to form Schiff base complexes (SBC 1A to 4D). Schiff bases ligands and complexes were characterized by FT-IR, 1H-NMR, 13C-NMR, TGA and DTA. Fourier Transform infrared spectroscopy (FTIR) of the acetylacetonates showed the formation of metal acetylacetonates as characterized by the absence of the carbonyl stretching n(C=O) vibration in metal acetylacetonate spectra as compared to pure acetylacetone. Metal acetylacetonates also showed the presence of metal oxygen vibration frequency, n(M-O-C), in the spectra obtained. Thermogravimetric analysis (TGA) and Derivative or Differential Thermogravimetric analysis (DTA) of the Schiff base ligands showed the presence of a single decomposition product in L1, L2, L3 and L4 indicating the formation of a single reaction product while those of Schiff base complexes showed the formation of several decomposition products. Proton and carbon thirteen Nuclear Magnetic Resonance (1H- and 13C-NMR) spectroscopy of the Schiff base ligands indicated the presence of hydrogen and carbon-13 in different environments. The chemical shifts of the hydrogens and carbon-13 provided evidence that Schiff base ligands were formed. The strongest evidence is the presence of the azomethine hydrogen and carbon in the spectra of the Schiff base ligands. The presence of aromatic hydrogens and carbon at chemical shift environments found in literature also confirmed the formation of Schiff base ligand. The NMR spectra of Schiff base complexes showed the presence of azomethine (HC=N) and aromatic hydrogens at expected chemical shifts. The synthesized Schiff bases and their corresponding metal complexes were screened for their invitro antibacterial activities against two Gram-positive (Staphylococcus aureues and Enterococcus feacalis) bacterial strains by the Agar-well diffusion methods.The ligands and complexes were tested against confirmed S. aureus and E. faecalis strains and only 4 exhibited antimicrobial activities. The ligands and complexes were effective against the S. aureusand E. faecalis isolates. / VUT

Parmi les patients souffrant d'épilepsie, particulièrement du lobe temporal (ELT), 30% restent résistants aux médicaments malgré l'administration optimale des traitements pharmacologiques. Le caractère imprédictible des crises est l’un des aspects les plus invalidants de la maladie. De plus, les troubles dépressifs et anxieux sont des comorbidités psychiatriques fréquemment associées à l’épilepsie et impactent encore plus négativement la qualité de vie que les crises. Les approches par biofeedback, ont démontré leur efficacité dans le contrôle des crises. Une thérapie par biofeedback sur la conductance cutanée (GSR biofeedback) a montré son efficacité sur les symptômes psychiatriques. Cependant, les mécanismes sous-tendant l’efficacité sur ces symptômes restent peu connus. L’objectif de cette thèse est de mieux comprendre ces mécanismes. Deux pistes sont explorées : une physiologique dans laquelle il existerait un effet direct du GSR biofeedback sur la régulation physiologique des émotions ; une attentionnelle, dans laquelle il y aurait un effet indirect de l’entraînement sur le contrôle de l’attention. Les études menées ont permis de montrer que les patients avec ELT présentent des réponses électrodermales aux émotions plus faibles que des témoins, mais qu'elles ne sont pas plus élevées après des séances de GSR biofeedback. En revanche, l’amélioration des symptômes anxieux et dépressifs est liée à des modifications du traitement attentionnel des informations menaçantes. Le GSR biofeedback en améliorant le contrôle attentionnel induirait une diminution de la vigilance face à la menace, conduisant à une réduction de la vulnérabilité émotionnelle chez ces patients. / Among patients with epilepsy, particularly temporal lobe epilepsy (TLE), 30% remain drug-resistant despite optimal administration of pharmacological treatments. The unpredictability of seizures is one of the most disabling aspects of the disease. In addition, depressive and anxiety disorders are psychiatric comorbidities frequently associated with epilepsy and have a greater negative impact on quality of life than seizures. Biofeedback approaches have been shown to be effective in controlling seizures. A biofeedback therapy on skin conductance (GSR biofeedback) has shown its efficacy on psychiatric symptoms. However, the mechanisms underlying this efficacy remain poorly understood. The objective of this thesis is to better understand these mechanisms. Two tracks are explored: a physiological one in which there is a direct effect of GSR biofeedback on the physiological regulation of emotions; an attentional one, in which there would be an indirect effect of the training on the control of attention. The studies presented have shown that TLE patients have weaker electrodermal responses than controls but that they are not higher after GSR biofeedback sessions. In contrast, the improvement of anxiety and depressive symptoms is related to changes in the attentional processing of threatening information. GSR biofeedback by improving attentional control would lead to a decrease in alertness to threat, leading to a reduction in emotional vulnerability in these patients.

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

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