Thesis (MPH)--University of Limpopo, 2011. / Background: Tuberculosis is one of the major public health problems in Lesotho. With the occurrence of multi-drug resistant tuberculosis, little is known about the views of health care workers on this disease. The aim of this study was to investigate the knowledge, attitudes, and practices of healthcare professionals about prevention and control of MDR-TB at Botsabelo hospital, situated in Maseru, Lesotho. Methods: This study was conducted by means of a semi-structured, anonymous, and self-administered questionnaire that was sent to health care workers. Returned questionnaires were collected through designated boxes stationed at selected places at the study site from 23rd September to 13th October 2010. The investigator and his assistants collected the returned questionnaires on the 15th October 2010. Results: The results of this study indicate that, overall, less than half (47.3%) of respondents had good level of knowledge about MDR-TB; but the overwhelming majority of them held negative attitude towards patients with MDR-TB. Further analysis showed that the level of knowledge did not affect the attitude towards patients suffering from MDR-TB but it influenced their practices. Having good level of knowledge about MDR-TB was associated with good practices such as the use of protective masks and MDR-TB guidelines and involvement in educating patients about MDR-TB. Moreover, the findings of this study showed also that the attitude of respondents towards patients suffering from MDR-TB did not influence their practices. Conclusion: In conclusion, less than half of respondents had good level of knowledge about MDR-TB, but over 85.5% of them held negative attitude towards patients suffering from MDR-TB. Although the level of knowledge about MDR-TB was found not to have influenced the attitude of respondents towards patients suffering from MDR-TB; and that xi their attitude did not influence practices, good level of knowledge was positively associated with safer practices such as using protective masks, educating patients on MDR-TB, and referring to the MDR-TB guidelines manual. An educational remedial intervention is recommended.

Orientador: José Paes de Almeida Nogueira Pinto / Resumo: O presente trabalho avaliou 250 animais de 25 lotes distintos abatidos em 4 estabelecimentos do estado de São Paulo para a presença de Salmonella nos linfonodos mesentéricos, e caracterizou o perfil de resistência das cepas isoladas aos principais antibióticos. O patógeno estava presente em 36,4% das amostras e 72% dos lotes analisados. Dos 91 isolados, 67 foram sorotipados, e os principais sorovares encontrados foram S. Typhimurium (n=13), S. 1.4,5,12:i:- (n=12) S. Infantis (n=12) e S. Havana (n=11). Os compostos com menor eficácia frente aos isolados foram estreptomicina e tetraciclina (68,1% de resistência) ampicilina e sulfonamidas (62,6%), cloranfenicol (56,0%), trimetoprim-sulfametoxazol (41,8%) e ácido nalidíxico (40,7%). Os mais efetivos foram aztreonam e cefoxitina, (ambos com 3,3% de resistência) e cefepima e ceftriaxona, (ambos com 7,7%). Cepas multidrogas resistentes (MDR) corresponderam a 70,3% dos isolados. Oito cepas foram submetidas ao MLST: quatro S. Typhimurium e uma S. 1.4,5,12:i:- todas pertencentes ao ST 19, duas S. Infantis pertenceram ao ST 32 e uma S. Derby, pertencente ao ST 40. A grande prevalência do patógeno nos animais analisados, com altas taxas de resistência aos antibióticos e pertencentes a grupos genéticos frequentemente associados a surtos e doenças em humanos demonstram que a cadeia produtiva da carne suína é uma fonte de contaminação em potencial nos casos de salmonelose, sendo necessárias medidas preventivas eficazes para o controle do pa... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: This study evaluated 250 animals of 25 different batches processed in four slaughterhouses in São Paulo state - Brazil for the presence of Salmonella in the mesenteric lymph nodes, and characterized the resistance profile for the main antibiotics. The pathogen was present in 36.4% of samples and 72% of the analyzed batches. Of the 91 isolates, 67 were serotyped, and the main serovars found were S. Typhimurium (n = 13), S. 1.4,5,12:i- (n = 12) S. Infantis (n = 12) and S. Havana (n = 11). The compounds with less efficacy were streptomycin and tetracycline (68.1% resistant) ampicillin and sulphonamides (62.6%), chloramphenicol (56.0%), trimethoprim-sulfamethoxazole (41.8%), and nalidixic acid (40.7%). The most effective were cephalothin and aztreonam, (both with 3.3% resistant) and ceftriaxone and cefepime (both with 7.7%). Multidrug-resistant strains (MDR) accounted for 70.3% of the isolates. Eight strains were submitted to MLST: Four S. Typhimurium and one S.1.4,5,12:i:- all belonging to the ST 19, two S. Infantis, belonging to the ST 32 and one S. Derby, belonging to ST 40. The high prevalence of the pathogen in the analyzed animals, with high rates of resistance to antibiotics and belonging to genetic groups that are often associated with outbreaks and disease in humans, shows that the production chain of pork is a potential source of contamination in salmonellosis cases, with the necessity of effective preventive measures for pathogen control and lower the risk of foodborne... (Complete abstract click electronic access below) / Mestre

Submitted by Fabio Sossai Possebon null (fabio.cid@fmvz.unesp.br) on 2016-02-24T18:24:37Z No. of bitstreams: 1 Dissertação Fábio S Possebon - Salmonella em suínos Final.pdf: 1036715 bytes, checksum: 11bc9e5b832c6262c21bfb938afd4b94 (MD5) / Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-02-25T19:42:40Z (GMT) No. of bitstreams: 1 possebon_fs_me_bot.pdf: 1036715 bytes, checksum: 11bc9e5b832c6262c21bfb938afd4b94 (MD5) / Made available in DSpace on 2016-02-25T19:42:40Z (GMT). No. of bitstreams: 1 possebon_fs_me_bot.pdf: 1036715 bytes, checksum: 11bc9e5b832c6262c21bfb938afd4b94 (MD5) Previous issue date: 2016-02-22 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O presente trabalho avaliou 250 animais de 25 lotes distintos abatidos em 4 estabelecimentos do estado de São Paulo para a presença de Salmonella nos linfonodos mesentéricos, e caracterizou o perfil de resistência das cepas isoladas aos principais antibióticos. O patógeno estava presente em 36,4% das amostras e 72% dos lotes analisados. Dos 91 isolados, 67 foram sorotipados, e os principais sorovares encontrados foram S. Typhimurium (n=13), S. 1.4,5,12:i:- (n=12) S. Infantis (n=12) e S. Havana (n=11). Os compostos com menor eficácia frente aos isolados foram estreptomicina e tetraciclina (68,1% de resistência) ampicilina e sulfonamidas (62,6%), cloranfenicol (56,0%), trimetoprim-sulfametoxazol (41,8%) e ácido nalidíxico (40,7%). Os mais efetivos foram aztreonam e cefoxitina, (ambos com 3,3% de resistência) e cefepima e ceftriaxona, (ambos com 7,7%). Cepas multidrogas resistentes (MDR) corresponderam a 70,3% dos isolados. Oito cepas foram submetidas ao MLST: quatro S. Typhimurium e uma S. 1.4,5,12:i:- todas pertencentes ao ST 19, duas S. Infantis pertenceram ao ST 32 e uma S. Derby, pertencente ao ST 40. A grande prevalência do patógeno nos animais analisados, com altas taxas de resistência aos antibióticos e pertencentes a grupos genéticos frequentemente associados a surtos e doenças em humanos demonstram que a cadeia produtiva da carne suína é uma fonte de contaminação em potencial nos casos de salmonelose, sendo necessárias medidas preventivas eficazes para o controle do patógeno e diminuição do risco de veiculação de patógenos por alimentos. / This study evaluated 250 animals of 25 different batches processed in four slaughterhouses in São Paulo state - Brazil for the presence of Salmonella in the mesenteric lymph nodes, and characterized the resistance profile for the main antibiotics. The pathogen was present in 36.4% of samples and 72% of the analyzed batches. Of the 91 isolates, 67 were serotyped, and the main serovars found were S. Typhimurium (n = 13), S. 1.4,5,12:i- (n = 12) S. Infantis (n = 12) and S. Havana (n = 11). The compounds with less efficacy were streptomycin and tetracycline (68.1% resistant) ampicillin and sulphonamides (62.6%), chloramphenicol (56.0%), trimethoprim-sulfamethoxazole (41.8%), and nalidixic acid (40.7%). The most effective were cephalothin and aztreonam, (both with 3.3% resistant) and ceftriaxone and cefepime (both with 7.7%). Multidrug-resistant strains (MDR) accounted for 70.3% of the isolates. Eight strains were submitted to MLST: Four S. Typhimurium and one S.1.4,5,12:i:- all belonging to the ST 19, two S. Infantis, belonging to the ST 32 and one S. Derby, belonging to ST 40. The high prevalence of the pathogen in the analyzed animals, with high rates of resistance to antibiotics and belonging to genetic groups that are often associated with outbreaks and disease in humans, shows that the production chain of pork is a potential source of contamination in salmonellosis cases, with the necessity of effective preventive measures for pathogen control and lower the risk of foodborne diseases transmission.

No description available.

Yes / SETTING: In 2005, in response to the increasing prevalence of rifampicin-resistant tuberculosis (RR-TB) and poor treatment outcomes, Rwanda initiated the programmatic management of RR-TB, including expanded access to systematic rifampicin drug susceptibility testing (DST) and standardised treatment.OBJECTIVE: To describe trends in diagnostic and treatment delays and estimate their effect on RR-TB mortality.DESIGN: Retrospective analysis of individual-level data including 748 (85.4%) of 876 patients diagnosed with RR-TB notified to the World Health Organization between 1 July 2005 and 31 December 2016 in Rwanda. Logistic regression was used to estimate the effect of diagnostic and therapeutic delays on RR-TB mortality.RESULTS: Between 2006 and 2016, the median diagnostic delay significantly decreased from 88 days to 1 day, and the therapeutic delay from 76 days to 3 days. Simultaneously, RR-TB mortality significantly decreased from 30.8% in 2006 to 6.9% in 2016. Total delay in starting multidrug-resistant TB (MDR-TB) treatment of more than 100 days was associated with more than two-fold higher odds for dying. When delays were long, empirical RR-TB treatment initiation was associated with a lower mortality.CONCLUSION: The reduction of diagnostic and treatment delays reduced RR-TB mortality. We anticipate that universal testing for RR-TB, short diagnostic and therapeutic delays and effective standardised MDR-TB treatment will further decrease RR-TB mortality in Rwanda.

No description available.

No description available.

Made available in DSpace on 2016-02-26T13:34:39Z (GMT). No. of bitstreams: 2 melise_silveira_ioc_mest_2014.pdf: 2936486 bytes, checksum: f73183e180b237b1d6dc63c0c0afa155 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2016-02-23 / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil / O surgimento de bactérias Gram-negativas resistentes à drogas tem sido progressivo e alarmante. Entre os patógenos de particular importância está Pseudomonas aeruginosa multirresistentes à drogas (MDR). Um clone epidêmico de P. aeruginosa MDR produtor da metalo-\03B2-lactamase SPM-1, chamado clone SP (ST277), tem sido encontrado em diferentes estados brasileiros. O gene blaSPM-1 foi descrito em uma estrutura genética chamada ISCR4, responsável pela sua mobilização e expressão. Além do gene blaSPM-1, tem sido descrito, neste clone, a presença de um integron de classe I carreando genes de resistência (In163) e um elemento genético ISCR14 carreando uma metilase de RNAr 16S (rmtD), que confere resistência a altas concentrações de aminoglicosídeos. Este tipo de associação resulta em um perfil de resistência extremamente preocupante. Assim, este estudo teve como objetivo investigar a contexto genético dos genes blaSPM-1 e rmtD, além de caracterizar mutações em genes cromossomais associados a multirresistência a antimicrobianos em amostras de P. aeruginosa pertencentes ao clone ST277, através de Sourthen blot e sequenciamento de nova geração. A partir de 50 amostras de P. aeruginosa MDR isoladas entre 2007 e 2010, foram selecionadas 13 amostras pertencentes ao ST277 (através de MLST) que apresentaram positividade para blaSPM-1 e/ou rmtD e In163 (através de PCR), sendo 12 do clone SP (A) e uma de um clone diferente, M, através de PFGE. Através de restrição do DNA com as enzimas de restrição SpeI e XbaI, e posterior hibridação com sondas dos genes alvos (blaSPM-1, rmtD e In163) foi possível observar que os genes alvos encontravam-se em fragmentos distintos e que a amostra do clone M apresentou um perfil de hibridação diferentes das demais amostras demonstrando a ocorrência de vários rearranjos na mesma, indicando uma maior distância evolutiva A partir destes resultados, selecionamos 6 amostras para sequenciamento total do genoma utilizando a plataforma de sequenciamento MiSeq da Illumina. Através de sucessivas análises - que incluíram os contigs gerados na montagem de novo, montagens por referência e alinhamentos par a par- chegamos a uma região de 239.648pb onde estavam contidos o In163 e o ISCR14 carreando rmtD, inseridos em uma ilha genômica incorporada ao cromossomo bacteriano. O gene blaSPM-1 inserido no ISCR4 foi encontrado em uma região de 13.959pb, que incluía genes relacionados a plasmídios e transposons, contudo ainda não sabemos se esse elemento está incorporado ao cromossomo, ou livre em forma de plasmídio. Através da análise das mutações em genes cromossômicos associados a resistência à antimicrobianos, encontramos mutações nos genes oprD, ampD, mexZ, mexS, mexT, gyrA e parC que foram comuns às 6 amostras sequenciadas do ST277. Isso explicaria o fenótipo MDR nas amostras negativas para rmtD e/ou blaSPM-1. Além disso, como estas amostras foram isoladas em estados e anos distintos, acreditamos que essas mutações sejam características do ST277, o que pode ser um dos fatores associados a distribuição epidêmica deste clone no Brasil / The development of antimicrobial resistance among Gram - negative pathogens has been progressive and relentless. A pathogen of particular concern is multidrug - resistant (MDR) Pseudomonas aeruginosa . An epidemic clone of MDR P. aeruginosa producing the metall o - β - lactamase SPM - 1, named SP clone (ST277), has been found in different Brazilian states. The bla SPM - 1 gene has been described in a genetic structure called ISCR4, responsible for its mobilization and expression. Besides the bla SPM - 1 gene, it has been des cribed in this clone, a classe I integron (In163) carrying resistance genes and the genetic element ISCR14 carrying a 16S rRNA metilase ( rmtD ), that confers resistance to high concentrations of aminoglycosides. This kind of association results in an extrem ely worrisome profile of resistance. Thus, this work aimed to investigate the genetic background of bla SPM - 1 and rmtD genes and to characterize mutations in chromosomal genes associated with multidrug resistance in P. aeruginosa isolates belonging to ST277 clone, using Sourthen blot and next - generation sequencing. From 50 MDR P. aeruginosa isolates recovered from 2007 to 2010,there were selected 13 bla SPM - 1 and /or rmtD - positive isolates (by PCR) belonging to ST277 (by MLST), 12 f rom SP (A) clone and one from a different PFGE clone (M). By DNA digestion with Spe I and Xba I restriction enzymes, and subsequent hybridization with probes for target genes ( bla SPM - 1 , rmtD and In163 ), it was observed that the target genes were in separate fragments, and that the M clone isolate showed a different profile compared with the other isolates, indicating various rearrangements, suggesting a greater evolutionary distance. With these results, 6 isolates were selected for whole genome sequencing by Illumina MiSeq platform. Through successive analyzes – which included de novo assembly contigs, map to reference assemblies and pairwise alignments - we came up to a 239648pb region containing the In163 and ISCR14 inserted into a genomic island incorporated into bacterial chromosome. The bla SPM - 1 gene was inserted into ISCR4, found in a 13950pb region, which included genes related to plasmids and transposons, however we do not know whether this element s chromosomal or plasmidial . Through analysis of chromoso mal genes mutations associated with multidrug resistance, we found mutations in oprD, ampD, mexZ, mexS, mexT, gyrA e parC genes, which were common to the 6 ST277 isolates sequenced. This would explain the MDR phenotype in bla SPM - 1 and/or rmtD negative isol ates. Furthermore, since these microorganisms were isolated in different years and states, we believe these mutations are ST277 characteristic, which may be one of the factors associated with the epidemic characteristics of this clone

Abstract Maintenance of the mitochondrial respiratory chain complexes plays crucial role for the aerobic metabolism of the eukaryotes such as unicellular yeasts, for example, Saccharomyces cerevisiae as well as of human being. Mitochondrial respiratory function has been studied using the yeast S. cerevisiae as a model organism. Since yeast cells are also able to grow without respiration by fermentation, identification of the nuclear genes linked to respiratory function is possible by generation of nuclear gene deletions and testing for respiration-deficient phenotype of the yeast deletion strains id est for yeast cells only poorly or not at all growing on the media containing non-fermentable carbon sources. This study reports identification of a novel mitochondrial 2-enoyl thioester reductase from the yeasts Candida tropicalis and S. cerevisiae, Etr1p and Mrf1p, respectively. Examination of the function of these proteins in the respiration-deficient mrf1Δ strain from S. cerevisiae suggests that the reductase is involved in mitochondrial fatty acid synthesis (FAS type II) in the yeast. Site-directed mutagenesis of a conserved tyrosine in the catalytic site of the enzyme indicated that the 2-enoyl thioester reductase activity is critical for mitochondrial respiratory competence. In addition, subcellular localization to mitochondria was required for the complementation of the respiration-deficient phenotype of the yeast reductase deletion strain. The crystal structure for the Etr catalytic site mutant indicated the structural integrity of the mutant supporting the requirement of the tyrosine for the catalysis. Characterization of Etr crystal structures both in apo- and holo-forms containing NADPH established Etr as a member of novel subfamily of enoyl thioester reductases in the superfamily of medium-chain dehydrogenases/reductases (MDR). Two isoforms of Etr with the difference in three amino acids only are encoded by two distinct genes in C. tropicalis, whereas only single gene encodes the reductase functioning in the mitochondria in S. cerevisiae. The presence of two genes in C. tropicalis was taken as an example of genetic redundancy in this yeast, the two genes also shown to be expressed in slightly different ways under various carbon sources available for growth.

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