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Submitted by Pós Imunologia (ppgimicsufba@gmail.com) on 2017-02-14T16:02:01Z No. of bitstreams: 1 Tese ELISABETE LOPES CONCEIÇÃO.pdf: 1470553 bytes, checksum: a38beb6dfeaae41d703bf5282cabb0a3 (MD5) / Approved for entry into archive by Uillis de Assis Santos (uillis.assis@ufba.br) on 2017-06-20T20:34:44Z (GMT) No. of bitstreams: 1 Tese ELISABETE LOPES CONCEIÇÃO.pdf: 1470553 bytes, checksum: a38beb6dfeaae41d703bf5282cabb0a3 (MD5) / Made available in DSpace on 2017-06-20T20:34:44Z (GMT). No. of bitstreams: 1 Tese ELISABETE LOPES CONCEIÇÃO.pdf: 1470553 bytes, checksum: a38beb6dfeaae41d703bf5282cabb0a3 (MD5) / Capes / O Mycobacterium tuberculosis e o vírus da imunodeficiência humana (HIV) agem em sinergia prejudicando a resposta imune para eliminação de ambos os patógenos. Fatores genéticos dos hospedeiros podem ser determinantes para o risco de progressão da tuberculose (TB) e infecção pelo HIV. Algumas variações genéticas têm sido associadas a diferenças no potencial para indução de apoptose e a alterações na produção de citocinas, tais como os polimorfismos de base única (SNPs) TNF-308G>A, DDX39B -22 G>C e -348C>T. Outra característica que acompanha a evolução da infecção é o estresse oxidativo sistêmico e o aumento da peroxidação. A Heme oxigenase-1 (HO-1) é o principal agente anti-oxidante expresso no tecido pulmonar, uma enzima de resposta ao estresse que degrada moléculas heme para a liberação de íons ferro, monóxido de carbono (CO) e biliverdina (BV). O presente trabalho propôs investigar fatores genéticos e imunológicos relacionados à imunopatogênese da TB e co-infecção TB-HIV. Para a realização do trabalho foram realizados: 1) uma revisão sistemática da literatura sobre os polimorfismos genéticos envolvidos nas vias e morte e associados com TB, 2) um estudo observacional de corte transversal para determinar a frequência de polimorfismos em voluntários monoinfectados com TB latente ou ativa e coinfectados com TB-HIV. Para este último foram recrutados 109 pacientes com tuberculose pulmonar (PTB), 60 pacientes coinfectados com HIV (TB-HIV) e 74 indivíduos com infecção tuberculosa latente (LTBI), e 3) Uma coorte avaliando os níveis de HO-1 e MMP-1 em pacientes com TB. Na revisão sistemática os polimorfismos dos genes do TNF, TNFR, IL-1 e P2RX7 estavam associados com tuberculose. No estudo de corte transversal a frequência do genótipo TNF-308G foi maior para o grupo LTBI comparado com TB e TB-HIV. A produção de TNF foi maior 8 entre os pacientes com PTB portadores do genótipo TNF -308GG. Os níveis de IL- 1α e IL-1β também foram mais elevados entre os pacientes com PTB portadores dos genótipos DDX39B -22CC e DDX39B -348CC. Não houve relação entre a produção de citocinas e a extensão da doença. Na coorte, os pacientes com TB apresentaram uma dicotomia na resposta de HO-1 MMP-1 com dois fenótipos, HO-1hiMMP-1lo e MMP-1 HO-1loMMP-1hi. Nosso estudo sugere que polimorfismos envolvidos na via de morte podem estar associados com susceptibilidade para o desenvolvimento da tuberculose, contudo, a frequência dos alelos e genótipos para os polimorfismos estudados não diferiram na co-infecção pelo HIV. O mecanismo entre o estresse oxidativo e remodelamento do tecido pode ter aplicabilidade clínica nos estágios da progressão da TB. / Mycobacterium tuberculosis and human immunodeficiency virus (HIV) act synergistically damaging immune response to eliminate both pathogens. Genetic factors of the host can be decisive for the risk of progression of tuberculosis (TB) and HIV infection. Some genetic changes have been associated with differences in potential for induction of apoptosis and changes in cytokine production such as single nucleotide polymorphisms (SNPs) TNF-308G> A, DDX39B -22 G> C and -348C> T. Another feature that monitors the infection is systemic oxidative stress and increased peroxidation. The heme oxygenase-1 (HO-1) is the primary anti-oxidant expressed in lung tissue, a response of the enzyme to stress that degrades heme molecules to the release of iron ions, carbon monoxide (CO), and biliverdin (BV) . This study proposed to investigate genetic and immunological factors related to TB immunopathogenesis and co-infection TB-HIV. To carry out the work were performed: 1) a systematic review of the literature on genetic polymorphisms involved in the pathways and death associated with TB, 2) an observational cross-sectional study to determine the frequency of polymorphisms in volunteers monoinfected with latent TB or active and co-infected with TB-HIV. For the latter were recruited 109 patients with pulmonary TB (PTB), 60 patients co-infected with HIV (HIV-TB) and 74 individuals with latent tuberculosis infection (LTBI), and 3) a cohort evaluating the levels of HO-1 and MMP- 1 in patients with TB. In the systematic review of TNF polymorphisms of genes, TNFR, IL-1 and P2RX7 were associated with tuberculosis. In the cross-sectional study the frequency of TNF-308G genotype was higher for LTBI group compared with TB and TB-HIV. The production of TNF was higher among patients with PTB patients TNF -308GG genotype. IL-1α and IL-1β were also higher among patients 10 with genotypes of PTB patients DDX39B -22CC and DDX39B -348CC. No relation between the production of cytokines and the extent of disease. In cohort, patients with TB presented a dichotomy in HO-1 MMP-1 response with two phenotypes, HO- 1hiMMP-1lo HO-1 and MMP-1loMMP-1hi. Our study suggests that polymorphisms involved in the death pathway may be associated with susceptibility to the development of tuberculosis, however, the frequency of alleles and genotypes for the studied polymorphisms did not differ in co-infection with HIV. The mechanism of oxidative stress and remodeling of the tissue may have clinical applicability in the progression of TB staging.

Magister Public Health - MPH / Mycobacterium Tuberculosis (MTB) is an endemic disease in Nigeria. The World Health Organization (WHO) estimates the incidence rate for all forms of Tuberculosis at 322 per 100,000 population in Nigeria in 2014 (WHO, 2015). This figure places Nigeria fourth among the 22-high burden countries in the world after India, Indonesia and China. These 22 countries have been prioritized for intensified Tuberculosis (TB) control at the global level, and together they accounted for over 82% of all estimated forms of Tuberculosis the world over in 2014 (WHO, 2014). The United States Agency for International Development (USAID) estimates the Osun state Tuberculosis Case Notification Rate for all forms of TB to be 54 per 100,000 (USAID, 2014). Osun state also has a total of 30 Local Government Areas (LGAs) with 30 TB and Leprosy Supervisors (TBLS) overseeing TB control at local government level. Osun state TB, Leprosy and Buruli Ulcer programme was established in 1993 and currently comprises of 218 health centres implementing the DOTS (Directly Observed Therapy Short-course) strategy and 55 Acid Fast Bacilli (AFB) diagnostic microscopy centres.

Magister Curationis - MCur / As early as 1993, the World Health Organisation declared Tuberculosis (TB) a global emergency and the South African Department of Health confirmed that TB was a national emergency. The primary cause of the rise in TB cases has been attributed to co-infection with HIV. TB is the leading opportunistic infection worldwide and the primary cause of mortality among people living with Human Immunodeficiency Virus (HIV). TB and HIV are two of the highest health threats globally and in South Africa. Tuberculosis and HIV combined are responsible for the deaths of over 4 million people annually. More than 65% of individuals diagnosed with TB in South Africa are co-infected with HIV. The importance of providing quality health services is a human right and non-negotiable. Better quality of health care is fundamental in improving South Africa's poor health outcomes and in restoring patient and staff confidence in the public and private health system. In 1996, the South African Department of Health introduced the topic of quality to raise its awareness and to make it an inherent part of the health care system. The South African health care consumers (patients) are increasingly becoming aware of their rights as patients and the gap between the actual and ideal health practices. They have broad knowledge and great expectations with regard to available care including effectiveness of service and treatment. Patients have desires for quality services when visiting a health care facility, and these desires are directly linked to the success of the healthcare system. If the desires are not met, they can negatively influence the outcome of healthcare processes such as treatment adherence and retention of patients on the system. This could possibly further escalate the TB/HIV co-infection rate in South Africa. The need to address TB and HIV together in the light of quality care is urgent so as to improve the provision of quality health services rendered to people co-infected with TB and HIV. The Institute of Medicine developed a framework that could guide on healthcare dimensions that need to be met for quality of care to be achieved and it is the underpinning theoretical framework for this study. The patients play a critical role in the healthcare system as they are the customers and therefore, the opinions of the patients need to be recognised to ensure that strategies and programmes that are developed are relevant. The purpose of this research was to explore and describe the perceptions of patients co-infected with TB and HIV regarding the quality of care at the Primary Health Care facilities, in the Chris Hani District. A qualitative, explorative and descriptive design was used which enabled the researcher to understand the perceptions of TB and HIV co-infected patients regarding quality of care. The population studied in this research consisted of TB and HIV co-infected patients attending the Primary Health Care facilities at the Lukhanji Sub-district within the Chris Hani District. Purposive sampling was used to select participants with the assistance of nurses working at the selected facilities. The sample size was determined by data saturation, which was reached after 18 semi-structured interviews were conducted. Data analysis was carried out simultaneously with data collection. In consensus discussions, the researcher and the co-coder reached an agreement on the main theme, sub-theme and sub-categories. From the research findings, two main themes were identified namely; satisfaction with delivered services and impediments to quality of care. These were further divided in sub themes and categories. The conclusion that could be made on the quality of care provided to the TB and HIV co-infected patients in this study is that the nurses in the facilities aim to provide four of the six IOM aims of quality of care to the TB and HIV co-infected patients namely: equitable, effective, efficient and patient-centred domains. Therefore, the quality of care provided to these patients is partial as they are not provided with all the six aims that are needed to achieve quality of care. Recommendations are made for the field of community health nursing practice and nursing research on how to improve quality of care provided to TB and HIV co-infected patients at Primary Health Care facilities.

Nearly 20 studies conducted in the last 40 years indicate that tuberculosis (TB) represents a major health concern among migrant farm worker (MFW) populations, but their role in the transmission of TB within the broader community is poorly understood. To this end an ecological study was undertaken which examined 67 Florida counties between years 2009 through 2013. Its aims were as follows: (1) to describe the demographic, geographic, and temporal distribution of the incidence of active TB, (2) to examine the effect of agriculturally relevant seasonal periods on the incidence of active TB, and (3) to quantify the strength and direction of the association between the incidence of active TB and the quantity of MFWs at the county-level, while adjusting for known ecological risk factors. Secondary data was obtained from a total of eight government resources. Statistical analyses began with univariate and bivariate statistics, and this was followed by choropleth maps, Moran’s I, and hot spot analyses during the geographic analysis. Temporal analyses consisted of graphical methods examining TB incidence on annual, quarterly, monthly, and seasonal bases as well as regression modelling with repeated measures. Multivariate analyses were performed with a series of negative binomial regression models, one for each year of the study time period. The results indicated a lack of any geographic relationship between the clustering of high incidence counties and those with larger MFW populations. Incidence rates in counties with larger MFW populations seemed to follow a cyclic pattern in which increases occurred during the spring and early summer, but this seasonal pattern was neither consistent nor prominent throughout the study time frame. Similarly, multivariate analyses yielded no associations between TB incidence and the quantity of MFWs during the 5-year study period, although relationships were detected between TB incidence and other demographic and socioeconomic variables. Altogether there was insufficient evidence to conclude that MFW populations contribute to TB transmission in the broader communities that they occupy. In the absence of standard, reliable data sources reporting on MFW numbers, future inquiries into this matter would benefit from improved estimation strategies of MFW population sizes. Also, modelling may be enhanced by techniques adapted to spatial autocorrelation, and spatial scales finer than the county-level should be examined.

Magister Public Health - MPH / The aim of the study is to explore the barriers associated with low VCT uptake by the TB patients attending primary health care clinics within the Buffalo City municipality. The study population was drawn from TB patients attending the primary health care facilities in Buffalo city municipality in the Eastern Cape Province. Eight participants were purposively selected to include those who had accepted VCT as well as those who did not.

Magister Public Health - MPH / BACKGROUND: Namibia has generalised Human Immunodeficiency Virus (HIV) and tuberculosis (TB) epidemics. In response to the TB/HIV co-epidemics in Namibia, the Ministry of Health and Social Services approved a policy of TB/HIV collaborative activities at national level and the integration of TB/HIV services at the point of service delivery. The present study explored barriers and facilitators of integration of TB and HIV service delivery in Tsandi District Hospital, which lies in rural northern Namibia. It focused on understanding the perspectives of healthcare workers and service users on integration of TB and HIV services at the health facility. AIMS & OBJECTIVES: The study aimed to describe the barriers, facilitators, and opportunities of integrated TB/HIV service delivery in Tsandi District Hospital. The specific objectives were: to describe the staffing and support systems in place for the integration of TB/HIV care; to describe the perceptions and experiences of integrated TB/HIV care by the health care workers, management and co-infected clients; and to describe the factors that facilitate or hinder the integration of TB/HIV services in the district from the point of view of district hospital managers, health care workers and co-infected clients. METHODS: The study used a descriptive qualitative study design with semi-structured key-informant interviews conducted with five healthcare managers and senior clinicians and focus group discussions with 14 healthcare workers and five TB/HIV co-infected patients, supplemented by non-participant observation in Tsandi district hospital over two weeks between May – June 2011. Sessions were audio-recorded, transcribed, and thematically analysed. RESULTS: Several factors influenced whether and to what degree Tsandi district hospital was able to achieve integration of TB and HIV services. These are: (1) model of care and nature of referral links; (2) the availability and use of human resources and workspace; (3) the system of rotating staff among departments in the hospital; (4) the supply and mode of providing medicines to patients; (5) information systems, recording and reporting arrangements; (6) and the amount of follow-up and supervision of the integrated services. The main suggested barrier factors are: (1) poor communication and weak referrals links between services; (2) inadequate infrastructure to encourage and deliver TB and HIV care; (3) staff shortages and high workload; (4) lack of training and skills among healthcare workers; (5) financial constraints and other socioeconomic challenges; and (6) fragmented recording and reporting systems with limited data use to improve service delivery. The four main facilitating factors are: (1) positive staff attitudes towards TB/HIV integration; (2) common pool of staff managing different programmes; (3) joint planning and review of TB and HIV activities at the ARV Committee; and (4) informal task sharing to alleviate healthcare worker shortages. CONCLUSIONS: This study recommends that the district build on the current facilitators of integration, while the inhibitors should be worked on in order to improve the delivery of TB/HIV services in the district. Simple and practical recommendations have been made to address the some of the barriers at district level. It is hoped that these will inform future planning and review of the current model of care by the District Management Team.

The World Health Organization (WHO) estimated that eight million new cases of tuberculosis (TB) occur every year and that one-third of the world’s population is infected with Mycobacterium tuberculosis (M. tuberculosis). With the increase in HIV/AIDS in the 1980’s, an increase in transmission of TB led to an increase in TB incidence. A study showed that South African adults (ages 15 to 49) will suffer 278 154 deaths between 2008 and 2017 if current control measures are continued. A M. tuberculosis strain that is resistant to isoniazid (INH) and rifampicin (RIF) used in the treatment of TB is known as a multi-drug resistant (MDR-TB) strain. In extensively drugresistant tuberculosis (XDR-TB) the M. tuberculosis strains are not only resistant to INH, RIF and any one of the fluoroquinolones but to at least one of the three injectable second-line drugs such as amikacin or kanamycin. Unfortunately, many people with XDR-TB will die because it is virtually impossible to formulate an effective treatment before the resistance pattern of the M. tuberculosis strain has been identified. Bacteriological culture is considered the diagnostic gold standard and can identify mycobacteria in over 80% of TB cases, with a specificity of over 98%. However, culturing the mycobacteria takes 4 to 6 weeks and makes diagnosis and treatment a prolonged process. In this study 60 patients suspected of TB disease, from the Anti-retroviral (ARV) clinic at the Tshwane District Hospital (TDH) were collected from October 2008 to April 2009. This study evaluated the use of the QuantiFERON-TB GOLD ELISA assay in a high burden setting. Tshwane District Hospital, South Africa. The sensitivity and specificity of the QFT assay in the clinic were 30% (9/30) and 63% (19/30) respectively when compared to the gold standard culture results. Analysis suggested that the sensitivity of the QuantiFERON assay is determined by a limiting patient CD4 value of between 150 and 200. Real-time PCR assays were used for rapid identification of Mycobacterium spp and to determine the presence of isoniazid and rifampicin resistant genes of M. tuberculosis strains. The real-time PCR assay identified 28% (17/60) M. tuberculosis, 2% (1/60) M. kansasii and 70% (42/60) of the isolates Mycobacterium spp negative. No M. avium were detected. The 17 M. tuberculosis positive specimens were further analysed for the presence of INH and RIF resistance genes. All 17 specimens had either no mutation or one or more mutations at the specific gene targets (rpo1, rpo2, katG and inhA). This study showed several possibilities for the use of both an immunological assay as well as molecular methods for the diagnosis of TB. This study suggested that in terms of routine diagnosis of TB in high HIV prevalence settings the QFT test should be used with caution. Realtime PCR for both detection and identification showed useful results and can be used together with culture results to improve turnaround times for TB diagnosis. Copyright / Dissertation (MSc)--University of Pretoria, 2010. / Medical Microbiology / unrestricted

Tuberculosis (TB) remains one of the major public health problems in South Africa. The overall aim of the research project was to evaluate the completeness of TB notification data. A descriptive study design was used. The TB data from the Disease Notification System for the period 1993 to 2003 were analysed to describe 11 year trends by province, sex and population group. The levels of under-reporting of tuberculosis were estimated by comparing the annual numbers and the rates of notified cases and deaths per 100 000 population with the data of registered cases in the electronic TB register and registered TB deaths from the Statistics South Africa’s metadata on causes of deaths in South Africa. A total of 768896 cases and 39052 deaths were recorded in the Disease Notification System for the period 1993 to 2003. The annual case load declined from 42099 cases in 1993 to 36081 in 1996, then peaked to 89111 in 1998. The peak in 1998 resulted mainly from two-fold increases in notified cases in the provinces of Eastern Cape, KwaZulu- Natal and Western Cape. There was also a three-fold increase in Western Cape in 2001 and four-fold increase in Northern Cape in 2002. The lowest numbers of notified cases were for Mpumalanga in the years 1993 to 1996. In Limpopo, a total of 13 cases only were notified between the years 1999 to 2003 inclusively. Nationally and provincially, the annual numbers of notified cases and deaths and rates per 100 000 population were consistently higher among males than females. The Wilcoxon signed rank test comparing the medians between male and female cases showed a p-value of 0.003 indicating that the difference exists between the two medians. Nationally the lowest number of deaths was 1967 notified deaths in 1994 and the highest number of deaths was 6085 notified in 2002. The number of deaths notified varied between the provinces and fluctuated between the years. It was the highest for the years 1993 to 1996 in Western Cape and the highest for the years 1997 to 2003 in Eastern Cape. It was the lowest in Mpumalanga for the years 1993 to 1997 and the lowest in Limpopo for the years 1999 to 2003 and KwaZulu-Natal in the years 2002 to 2003. The Disease Notification System was found to have lesser numbers of notified cases in comparison to registered cases recorded in the TBSYS or electronic TB register. The percent difference between notified and registered cases ranged between 28% in 2001 to 69% in 1996. Comparison of notified and registered TB deaths for the period 1997-2003 showed that the annual numbers and rates of registered deaths in the Statistics South Africa’s metadata were higher for all the years than the notified deaths in the disease surveillance system. It is recommended that the disease surveillance system is evaluated periodically, facility data assessment tools are introduced and capacity for surveillance is strengthened at all levels of the national health systems. Copyright / Dissertation (MSc)--University of Pretoria, 2009. / School of Health Systems and Public Health (SHSPH) / Unrestricted

PhD (Health Sciences) / Department of Advanced Nursing Science