Submitted by lariza Maza (lariza.maza@hotmail.com) on 2018-04-16T14:40:41Z No. of bitstreams: 1 Dissertação Final Mestrado Lariza Maza pdf.pdf: 2708028 bytes, checksum: d776645b08f3ecce08017c07afc27ae3 (MD5) / Approved for entry into archive by ROSANGELA APARECIDA LOBO null (rosangelalobo@btu.unesp.br) on 2018-04-17T13:47:03Z (GMT) No. of bitstreams: 1 maza_l_me_bot.pdf: 2708028 bytes, checksum: d776645b08f3ecce08017c07afc27ae3 (MD5) / Made available in DSpace on 2018-04-17T13:47:03Z (GMT). No. of bitstreams: 1 maza_l_me_bot.pdf: 2708028 bytes, checksum: d776645b08f3ecce08017c07afc27ae3 (MD5) Previous issue date: 2018-02-26 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Introdução. A Paracoccidioidomicose (PCM) é micose sistêmica causada por fungos termo dimórficos do gênero Paracocidioides. A associação sulfametoxazol trimetoprim, também denominada Cotrimoxazol (CMX), é uma das principais opções terapêuticas. No atual tratamento da PCM, o CMX é utilizado na dose de 2400 mg de sulfametoxazol, o que corresponde a seis comprimidos, divididos em duas tomadas diárias, fato que tem levado a menor adesão do paciente à terapia antifúngica. Estudos experimentais têm observado que a dose única diária pode ser suficiente para tratar a PCM. Objetivo. Este estudo teve como objetivo avaliar a eficácia do tratamento da PCM Murina com CMX administrado em uma e duas doses diárias. Material e métodos. Utilizou-se camundongos machos, isogênicos da linhagem Balb/c e o isolado Pb 326, de uma paciente atendida no Hospital das Clínicas da Faculdade de Medicina de Botucatu em 2012 com a forma aguda e subaguda. Este estudo apresentou três experimentos. No experimento I, 100 animais foram sorteados em 4 grupos: controle saudável (G1), controle infectado (G2) e os grupos infectados que receberam CMX uma vez (G3) e duas vezes ao dia (G4). Após 28 dias da infecção, iniciou-se o tratamento, com avaliação da recuperação fúngica em pulmão e baço, exame histopatológico dos pulmões e pesquisa de anticorpos séricos específicos anti P. brasiliensis, pela imunodifusão dupla em gel de ágar (IDD) nas semanas 8, 12, 16 e 20 após a infecção. No experimento II, os mesmos animais foram avaliados quanto a sobrevida cumulativa em 140 dias. No experimento III, 40 camundongos infectados e tratados por 10 dias com dose única diária e com duas tomadas ao dia foram avaliados quanto ao perfil sérico de sulfametoxazol em quatro medidas durante o dia e foi determinado a concentração inibitória mínima deste isolado utilizado no estudo. Os testes de Kruskal-Wallis e Mann-Whitney foram utilizados para comparação de medianas, regressão linear para analisar os parâmetros nos sucessivos momentos de sacrifício e Kaplan-Meier para a avaliação de sobrevida. Foi considerado significativo os valores de p menores que 0,05. Resultados. Os dois grupos tratados com CMX (G3 e G4) apresentaram resposta ao tratamento, caracterizada pela melhora do aspecto e do comportamento do animal, queda dos níveis de anticorpos séricos pela IDD (G3: p=0,005; G4: p=0,01), redução da carga fúngica pulmonar, analisada pelo exame histopatológico, na 16ª e 20ª se- manas comparadas com a 8ª e 12ª (p<0,01) e menor porcentagem de fibras colágenas por área peribronquiolar na 20ª semana comparados com a 12ª semana (p<0,05). Não houve diferença na recuperação fúngica em pulmões e baço, na carga fúngica contada pelo exame histopatológico de pulmão e nem na porcentagem de fibra colágena por área peribronquiolar entre G3 e G4 nas semanas 8, 12, 16 e 20. No entanto, os níveis de IDD tenderam a ser mais baixos no G4 do que no G3 na 8ª semana de tratamento (1:4 vs 1:16, p = 0,08). O grupo G4 apresentou menor recuperação fúngica dos pulmões na 8ª e 12ª semanas e no baço nas semanas 16 e 20 quando comparado ao controle infectado. Não houve diferença na mortalidade cumulativa entre G3 e G4 (0,0% vs 4,0%). Conclusões. Esses achados demonstram eficácia em ambos os esquemas de tratamento da PCM Murina com CMX. Embora não se observou diferenças diretas entre os dois esquemas de tratamento com CMX, o grupo que recebeu duas doses ao dia apresentou maior resposta quando comparado com o controle infectado, fato que não ocorreu com o grupo tratado com dose única diária. Isto sugere que diferenças podem existir entre os dois esquemas e que estudo futuros são necessários para se conhecer melhor a eficácia destes esquemas terapêuticos. / Introduction. Paracoccidioidomycosis (PCM) is systemic mycosis caused by termodimorphic fungi of the genus Paracoccidioides. The association of sulfamethoxazole-trimethoprim, also called cotrimoxazole (CMX), is one of the main therapeutic options. In the current treatment of PCM, CMX is used in the dose of 2,400 mg of sulfamethoxazole, which corresponds to six tablets divided into two daily doses, a fact that has led to the patient's lesser adherence to anti-fungal therapy. Experimental studies have observed that the single daily dose may be suffi-cient to treat PCM. Goal. This study aimed to evaluate the efficacy of murine PCM treatment with CMX administered in one and two daily doses. Material and methods. Male, isogenic mice of the Balb / c gem line and Pb 326 isolate were collected from a patient attended at the Hospital das Clínicas of the Faculty of Medicine of Botucatu in 2012 with the acute and sub-acute form. This study presented three experiments. In the experiment I, 100 animals were randomly assigned to 4 groups: healthy control (G1), infected control (G2) and infected groups receiving CMX once (G3) and twice daily (G4). After 28 days of infection, treatment with the evaluation of fungal recovery in the lung and spleen, histopathological examination of the lungs and the detection of specific serum antibodies to P. brasiliensis by double agar gel immunodiffusion (IDD) in the weeks 8, 12, 16 and 20 after infection. In Experiment II, the same animals were evaluated for cumulative survival at 140 days. In Experiment III, 40 mice infected and treated for 10 days with single daily dose and with two intakes per day were evaluated for the serum sulfamethoxazole profile in four measures during the day and the minimum inbred concentration of this isolate used in the study. The Kruskal-Wallis and Mann-Whitney tests were used for comparison of medians, linear regression to analyze the parame-ters in the successive moments of sacrifice and Kaplan-Meier for the evaluation of survival. P value of less than 0.05 was considered significant. Results. The two groups treated with CMX (G3 and G4) presented a response to treatment, characterized by an improvement in the ap-pearance and behavior of the animal, a decrease in serum antibody levels by IDD (G3: p = 0.005, G4: p = 0.01), reduction of lung fungal load, analyzed by histopathological examination, at the 16th and 20th week periods compared with the 8th and 12th days (p <0.01), and a low-er percentage of collagen fibers by peribronchiolar area at week 20 compared to at week 12 (p <0.05). There was no difference in fungal recovery in the lungs and spleen, in the fungal load counted by histopathological examination of the lung, nor in the percentage of collagen fiber per peri-brachial area between G3 and G4 at weeks 8, 12, 16 and 20. However, levels of IDD tended to be lower in G4 than in G3 at week 8 of treatment (1: 4 vs. 1:16, p = 0.08). The G4 group presented lower fungal recovery of the lungs at the 8th and 12th weeks and in the spleen at weeks 16 and 20 when compared to the infected control. There was no difference in cumulative mortality between G3 and G4 (0.0% vs 4.0%). Con-clusions. These findings demonstrate efficacy in both murine PCM treatment regimens with CMX. Although there were no direct differences between the two treatment regimens with CMX, the group receiving two doses per day presented a higher response when compared to the infected control, a fact that did not occur with the single daily dose group. This suggests that differences may exist between the two schemes and that future studies are needed to better understand the efficacy of these therapeutic regimens

Orientador: Ricardo de Souza Cavalcante / Resumo: Introdução. A Paracoccidioidomicose (PCM) é micose sistêmica causada por fungos termo dimórficos do gênero Paracocidioides. A associação sulfametoxazol trimetoprim, também denominada Cotrimoxazol (CMX), é uma das principais opções terapêuticas. No atual tratamento da PCM, o CMX é utilizado na dose de 2400 mg de sulfametoxazol, o que corresponde a seis comprimidos, divididos em duas tomadas diárias, fato que tem levado a menor adesão do paciente à terapia antifúngica. Estudos experimentais têm observado que a dose única diária pode ser suficiente para tratar a PCM. Objetivo. Este estudo teve como objetivo avaliar a eficácia do tratamento da PCM Murina com CMX administrado em uma e duas doses diárias. Material e métodos. Utilizou-se camundongos machos, isogênicos da linhagem Balb/c e o isolado Pb 326, de uma paciente atendida no Hospital das Clínicas da Faculdade de Medicina de Botucatu em 2012 com a forma aguda e subaguda. Este estudo apresentou três experimentos. No experimento I, 100 animais foram sorteados em 4 grupos: controle saudável (G1), controle infectado (G2) e os grupos infectados que receberam CMX uma vez (G3) e duas vezes ao dia (G4). Após 28 dias da infecção, iniciou-se o tratamento, com avaliação da recuperação fúngica em pulmão e baço, exame histopatológico dos pulmões e pesquisa de anticorpos séricos específicos anti P. brasiliensis, pela imunodifusão dupla em gel de ágar (IDD) nas semanas 8, 12, 16 e 20 após a infecção. No experimento II, os mesmos animais fo... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction. Paracoccidioidomycosis (PCM) is systemic mycosis caused by termodimorphic fungi of the genus Paracoccidioides. The association of sulfamethoxazole-trimethoprim, also called cotrimoxazole (CMX), is one of the main therapeutic options. In the current treatment of PCM, CMX is used in the dose of 2,400 mg of sulfamethoxazole, which corresponds to six tablets divided into two daily doses, a fact that has led to the patient's lesser adherence to anti-fungal therapy. Experimental studies have observed that the single daily dose may be suffi-cient to treat PCM. Goal. This study aimed to evaluate the efficacy of murine PCM treatment with CMX administered in one and two daily doses. Material and methods. Male, isogenic mice of the Balb / c gem line and Pb 326 isolate were collected from a patient attended at the Hospital das Clínicas of the Faculty of Medicine of Botucatu in 2012 with the acute and sub-acute form. This study presented three experiments. In the experiment I, 100 animals were randomly assigned to 4 groups: healthy control (G1), infected control (G2) and infected groups receiving CMX once (G3) and twice daily (G4). After 28 days of infection, treatment with the evaluation of fungal recovery in the lung and spleen, histopathological examination of the lungs and the detection of specific serum antibodies to P. brasiliensis by double agar gel immunodiffusion (IDD) in the weeks 8, 12, 16 and 20 after infection. In Experiment II, the same animals were evaluated f... (Complete abstract click electronic access below) / Mestre

The purpose of the study was to identify factors associated with the HIV transmission rate in 18 to 24 month-old children enrolled in the PMTCT programme at two selected City of Tshwane clinics. Mother-to-child transmission of HIV during labour and breastfeeding accounts for 40% of all HIV infection in children. The prevention of mother-to-child transmission of HIV programme is one effective strategy to reduce the rate of HIV infection in children. The HIV transmission rate was low at six weeks of age but increases at 18 to 24 months of age due to several factors. The researcher selected a descriptive retrospective correlational research design. A structured questionnaire was used to collect data from 60 mothers of children aged 18 to 24 months on the PMTCT programme and a data-collection form to collect data from 152 clinic records of children of the same age on the programme. The study found that the PMTCT guidelines were not properly adhered to by the nurses and the respondents. Prophylactic treatment was not provided as required and mixed feeding was prominent. The uptake of HIV test at 18 to 24 months was low compared to at 6 weeks. The transmission rate was high at 18 to 24 months compared to at 6 weeks. No factors were associated with the transmission rate / Health Studies / M.A. (Public Health)

Opportunistic infections (OIs) have been identified as a leading cause of poor outcomes in the ARV therapy (ART) programme. In order to reduce OIs, the Malawi, MoH introduced routine prescription of cotrimoxazole preventive therapy (CPT) in 2005. The MoH also started scaling up a point-of-care electronic medical record (EMR) system in 2007 to improve monitoring and evaluation. This study had the following objectives: i) to quantify prescription of CPT before and after implementing EMR; ii) to compare the difference in CPT prescription before and after implementing EMR. A historically controlled study design was used to compare CPT prescriptions one year before, and one year after implementation of the EMR at two health facilities. The data indicated that there was a significant (P <0.001) decrease in CPT prescribing at one health facility and a significant increase in CPT prescription at another. / Health Studies / M.A. (Public Health)

The purpose of the study was to identify factors associated with the HIV transmission rate in 18 to 24 month-old children enrolled in the PMTCT programme at two selected City of Tshwane clinics. Mother-to-child transmission of HIV during labour and breastfeeding accounts for 40% of all HIV infection in children. The prevention of mother-to-child transmission of HIV programme is one effective strategy to reduce the rate of HIV infection in children. The HIV transmission rate was low at six weeks of age but increases at 18 to 24 months of age due to several factors. The researcher selected a descriptive retrospective correlational research design. A structured questionnaire was used to collect data from 60 mothers of children aged 18 to 24 months on the PMTCT programme and a data-collection form to collect data from 152 clinic records of children of the same age on the programme. The study found that the PMTCT guidelines were not properly adhered to by the nurses and the respondents. Prophylactic treatment was not provided as required and mixed feeding was prominent. The uptake of HIV test at 18 to 24 months was low compared to at 6 weeks. The transmission rate was high at 18 to 24 months compared to at 6 weeks. No factors were associated with the transmission rate / Health Studies / M.A. (Public Health)

Opportunistic infections (OIs) have been identified as a leading cause of poor outcomes in the ARV therapy (ART) programme. In order to reduce OIs, the Malawi, MoH introduced routine prescription of cotrimoxazole preventive therapy (CPT) in 2005. The MoH also started scaling up a point-of-care electronic medical record (EMR) system in 2007 to improve monitoring and evaluation. This study had the following objectives: i) to quantify prescription of CPT before and after implementing EMR; ii) to compare the difference in CPT prescription before and after implementing EMR. A historically controlled study design was used to compare CPT prescriptions one year before, and one year after implementation of the EMR at two health facilities. The data indicated that there was a significant (P <0.001) decrease in CPT prescribing at one health facility and a significant increase in CPT prescription at another. / Health Studies / M.A. (Public Health)