Magister Pharmaceuticae - MPharm / Many studies have investigated the pharmacokinetics of anti-tuberculosis drugs in patients infected with tuberculosis. However, little is known about the pharmacokinetics of the drugs that are used in the treatment of multi-drug resistant tuberculosis (MDRTB).Therefore, the objective of the present study was to investigate the steady state concentrations and the pharmacokinetics of ofloxacin, one of the drugs used in the treatment of MDR-TB in patients infected with MDR-TB and patients with MDR-TB co-infected with HIV Plasma samples were drawn at different times over 24 hours after ofloxacin oral administration. For the determination of ofloxacin plasma concentrations, the liquid chromatography coupled with mass spectrometry analysis method was used.The method was validated over a concentration range of 0.1-10 μg/ml. The lower limit of ofloxacin detection was 0.05μg/ml, while the lower limit of quantification was 0.1μg/ml. The response was linear over the range used with a mean recovery of 97.6%. Ofloxacin peak was well separated at a retention time of 9.6 minutes.The pharmacokinetic parameters obtained were presented as mean ± standard deviation(SD). The peak concentration of ofloxacin (Cmax) was 4.71± 2.27 μg/ml occurred at Tmax 3±1.29 hours after ofloxacin oral administration. The mean (±SD) for the area under the concentration-time curve (AUC0-24) and the area under the concentration-time curve(AUC0-∞) were 68.8±42.61 μg/ml.hr and 91.93±76.86 μg/ml.hr, respectively. Ofloxacin distributed widely with a mean (±SD) volume of distribution (Vd) 2.77±1.16 L/kg and it was eliminated with a mean (±SD) total clearance rate of 0.27±0.25 L/hr/kg. Ofloxacin mean (±SD) half-life was 9.55± 4.69 hours and mean (±SD) of the mean residence time (MRT) was 1512± 6.59 hours.In summary, compared with the previous findings in the literature, ofloxacin pharmacokinetic was altered in MDR-TB patients with or without HIV co-infection.The AUC and Cmax were reduced, while the half-life and the time to reach the peak concentration were prolonged. This suggests that, both the rate and the extent of ofloxacin absorption were decreased. Furthermore, ofloxacin was highly eliminated in patients, which may be related to the altered liver function in this group of patients.Further studies investigating the effect of HIV, liver and kidney dysfunctions on ofloxacin pharmacokinetics are recommended in large number of patients infected with MDR-TB.in addition to the therapeutic drug monitoring to maintain the desired concentration of ofloxacin in the patients.

The purpose of the study was to develop best practice guidelines to prevent permanent hearing loss associated with the management of multi-drug resistant tuberculosis (MDR-TB) through raised awareness and monitoring. The Human Immunodeficiency Virus (HIV) and MDR-TB are global public health problems requiring urgent scale-up of treatment services. Irreversible sensorineural hearing loss (SNHL) is one of the adverse drug reactions of the current World Health Organization (WHO) recommended MDR-TB chemotherapy fuelling another public health problem, that disabling hearing loss, which is the second highest contributor of Years Lived with Disability (YLD) according to the World Health Report (2003). Expansion of MDR-TB treatment threatens to increase incidence of SNHL unless there is urgent implementation of intervention towards preservation of hearing for patients on treatment. This empirical study determined and documented the incidence of SNHL in HIV positive and HIV negative patients on MDR-TB treatment, the risk factors for SNHL, from the time treatment initiation to SNHL. Based on the findings, developed and improved the understanding of best practice guidelines for monitoring and prevention of MDR-TB treatment-related SNHL. The empirical study recruited a cohort of 173 patients with normal hearing status, after diagnosis with MDR-TB and enrolled on MDR-TB therapy over thirteen month period. Patients in the cohort received monthly hearing sensitivity testing during the intensive MDR-TB therapy when injectable aminoglycoside antibiotics are part of the treatment regimen. The three study endpoints included completion of the eight-month intensive treatment phase without developing hearing loss, development incident hearing loss or loss to follow up. Data was analysed using STATA statistical software and summarised using frequencies, means, proportions, and rates. The study documented incidence of SNHL, time to hearing loss and risk factors for hearing loss. Recommendations to prevent and monitor hearing loss are made based on the the study findings. / Health Studies / D. Litt. et Phil. (Health Studies)

Philosophiae Doctor - PhD / Tuberculosis is a bacterial infection which is a major cause of death worldwide. TB is a curable disease, however the bacterium can become resistant to the first line treatment against the disease. This leads to a disease called drug resistant TB that is difficult and expensive to treat. It is well-known that TB disease thrives in communities in overcrowded environments with poor ventilation, weak nutrition, inadequate or inaccessible medical care, etc, such as in some prisons or some refugee camps. In particular, the World Health Organization discovered that a number of prisoners come from socio-economic disadvantaged population where the burden of TB disease may be already high and access to medical care may be limited. In this dissertation we propose compartmental models of systems of differential equations to describe the population dynamics of TB disease under conditions of crowding. Such models can be used to make quantitative projections of TB prevalence and to measure the effect of interventions. Indeed we apply these models to specific regions and for specific purposes. The models are more widely applicable, however in this dissertation we calibrate and apply the models to prison populations.

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