Magister Scientiae (Occupational Therapy) - MSc(OT) / TB is a multi- faceted public health problem spurred on by the biological progression of the disease as well as the social issues associated with it. The treatment of TB is however primarily driven by the medical model where the focus is on the disease and not on a holistic view of the patient. Occupational therapy is a profession concerned with the use of occupation in the promotion of health and well being through the facilitation of the process of occupational adaptation. There is however a paucity of literature pertaining to the role that occupational therapy could play within the TB context. The aim of this study was to explore how adults with MDR- TB who undergo long-term hospitalisation at a hospital in the Western Cape experience occupational adaptation. The objectives of the study were to explore how the participants perceive their occupational identity, to explore the meaning and purpose the participants assign to their occupational engagement and to explore the how the participants perceive their occupational competence. The interpretive research paradigm employing a phenomenological qualitative research approach was utilized in this study. Purposive sampling was used to select four participants based on specific selection criteria. The data gathering methods utilized included diaries, semistructured interviews, participant observation and a focus group. Photographs taken by the researcher for the purpose of participant observation were used to elicit a rich, in depth response from the participants during the focus group discussion. All data was analysed through thematic content analysis. The study findings highlighted that the participants viewed themselves as occupational beings and that they valued the role that occupational engagement played in facilitating their occupational competence and ultimately their ability to adapt to long- term hospitalisation. The environmental demands and constraints that they experienced however infringed their engagement in meaningful occupation and hampered their ability to achieve occupational competence. It was recommended that the hospital adopt an integrative intervention approach to the management of MDR- TB patients that include principles of psychosocial rehabilitation and occupational enrichment to address occupational risk factors and institutionalisation.

Background: There is a dearth of information regarding prevalence of extensively drugresistant tuberculosis (XDR-TB) in Africa. Although countries in Africa conduct national tuberculosis surveys on a regular basis, this information has not been systematically reviewed to ascertain the overall prevalence of XDR-TB in Africa. Methods: The study aimed to perform a systematic review and meta-analysis of the prevalence and factors associated with prevalence of pulmonary XDR-TB among adults in Africa. Eligible studies, published between 2006 and 2018, were sourced from various electronic databases including PubMed, Scopus, and Web of Science. Meta-analysis was performed using STATA (version 14.2) statistical software. The protocol of this review was registered with PROSPERO, reg No CRD42018117037. Result: A total of 6242 records were retrieved. Forty-eight studies were screened for eligibility and seven, which varied in terms of country setting and study design, were included. The prevalence of XDR-TB is 4% (95%CI 2-7) among participants tested for second-line anti-TB drug resistance, and 3% (95%1-6) among participants with drug resistant TB. The prevalence of XDR-TB was 7% (95%CI 1-18) among participants with MDR-TB. A few studies reported on the factors associated with the prevalence of XDR-TB. Discussion: The reported prevalence of XDR-TB among participants tested for second-line anti-TB drug resistance is low compared to WHO estimates. The systematic review underscores a dearth of studies depicting the reality regarding the prevalence of XDR-TB in Africa. Policymakers and stakeholders interested in drug-resistant TB should apply prudence when considering XDR-TB prevalence reported for Africa.

Magister Public Health - MPH / Background: Multidrug resistant tuberculosis (MDR TB) is a growing threat globally. The large increase in the incidence and prevalence of MDR TB in South Africa in recent years has impacted on the way in which MDR TB is managed within the health services. It became logistically difficult to manage MDR TB by treating all patients as in-patients in a specialized tuberculosis (TB) hospital. The clinics, which are run by nurses and/or general medical officers, are then required to manage this more complex form of TB, with limited resources, less experience and assumingly with less MDR TB knowledge. Of particular concern is that shifting of the patient management from specialized TB hospitals to Primary Health Care clinics which might worsen the already poor MDR TB treatment outcomes. There has been minimal assessment of the management of MDR TB at clinic level and hence the comparison of treatment outcomes for those patients initiated on treatment in clinics compared to in-patients in specialized TB hospitals is urgently needed. Aim: To compare the treatment outcomes and the effectiveness of medication regimens provided to MDR TB patients initiated on treatment in specialized TB hospitals as inpatients, to that of MDR TB patients initiated on treatment as outpatients at community clinics within the Western Cape Province, South Africa. Methodology Study Design: A retrospective cohort study was undertaken, as the length of treatment for a MDR TB patient can be for 24 months or longer and this study was based on treatment outcome data. Study Population and sample: The study population was uncomplicated MDR TB patients initiated on treatment in hospitals and clinics from January 2010 to December 2012. The sample comprised of 568 participants that were laboratory confirmed to have MDR TB and had the outcomes of their treatment recorded in an electronic database or a paper register. Data Collection: The researcher collected MDR TB information from standardized MDR TB registers as well as an electronic MDR TB database. Analysis: Data was analyzed comparing the exposed (clinic initiated) and unexposed (hospital initiated) cohorts incidence of 4 key treatment outcomes, namely: successfully treated, failed treatment, died and defaulted treatment. Bivariate analysis (relative and absolute) was done to determine the cumulative incidence ratio and cumulative incidence difference and multivariate logistic regression analysis for the adjusted odds ratio to control for confounders and effect modifiers. Ethics: Permission to conduct this research was obtained from the relevant authorities. The confidentiality of the participants as per the Department of Health policy and in adherence to general ethical guidelines was strictly maintained. The study proposal received ethical clearance and approval from the University of the Western Cape Research Committee. Results: All participants within this study received the appropriate treatment as per the MDR TB guidelines. The incidence rate for the main outcomes of this study indicated that successfully treated for the clinic initiated participants was 41% and 31% for the hospital initiated participants. ‘Defaulted’ treatment was 39% and 41%, ‘failed’ treatment 7% and 13% and ‘died’ was 14% and 16%, respectively. The clinic initiated participants appeared to have better treatment outcomes on bivariate analysis, however on multivariate analysis, there was no difference in the treatment outcomes of the clinic initiated participants compared to the hospital initiated participants, and therefore the clinic initiated treatment is seen as effective. The time to treatment initiation for clinic and hospital initiated participants is excessively long for both cohorts, with a median of 29 days, and 37 days respectively. The key findings of note in the multivariate analysis is that the Human Immunodeficiency Virus positive (HIV+) participants provided with antiretrovirals therapy (ART) were, based on adjusted cumulative incidence ratios, 6.6 times more likely to have a successfully treated outcome (95% CI 1.48-29.84), and were 0.2 times less likely to die (95% CI 0.08-0.53). Having a previous cured history of TB and no previous history of TB were 2.9 times more likely to have a successfully treated outcome (95% CI 1.48-5.56) and were 0.1 times (0.04-0.38) less likely to fail treatment. An interesting finding was that participants living in the rural districts were 2.6 times more likely to die. Conclusion: Clinic initiated treatment for uncomplicated MDR TB is as effective as hospital initiated treatment. Also, those provided with ART and those without previous TB or who had a previous bout of TB cured, had better outcomes. Main Recommendations: The Western Cape health department should continue with the decentralization of MDR TB services to the clinics and could safely consider expanding the decentralization to include uncomplicated Preextensively drug-resistant TB and Extensively drug-resistant TB patients. Offering ART to HIV+ patients should be mandatory. The delays in the time to treatment initiation of MDR TB need to be further investigated.

Thesis (M.Cur) --University of Limpopo, 2011 / The aim of this study was to determine the factors that contribute to the increase in the number of tuberculosis (TB) patients in Mpumalanga Province, and to develop guidelines and recommendations to address the challenges of this health issue. The design of the study was qualitative phenomenological. The population consisted of all TB patients who were receiving treatment either at the intensive or the continuation phase. The sampling method was purposive and the sample size comprised 20 participants, of whom 10 were drawn from Shatale clinic at Bushbuckridge, and 10 from Mashishing clinic at Thabachweu municipalities in the Ehlanzeni district of Mpumalanga Province. The data was gathered by means of semi-structured interviews. Data analysis was performed, from which themes and categories were derived. This study revealed several factors that contributed to the increase in the number of TB patients at the study sites. The factors considered most important in this study were the general lack of knowledge of TB among participants, despite their various levels of education, poverty, overcrowding, poor ventilation in the shacks and Reconstruction and Development Program (RDP) houses, unemployment, lack of support while taking treatment, religious and ritual beliefs, and the influence of traditional healers who dispense herbal medicines with the dictum that participants have been possessed by evil spirits and witches. The majority of patients developed TB as a secondary opportunistic infection because of their HIV-positive status, and lack of capacity to practice personal hygiene and proper infection control. Guidelines, strategies and recommendations were formulated to address these public health challenges in the context nursing education, research, administration and practice

BACKGROUND: Multi drug resistant Tuberculosis (MDR-TB) is a serious public health concern in many parts of the world. As per the WHO- 2010 global report on Surveillance and response 3.6% of all incident TB cases globally are multidrug resistant. In this regard, there is an increasing demand for timely, reliable and comprehensive drug susceptibility testing (DST) as MDR-TB surveillance is being geared up. The intent of this analysis is to determine whether there is a need to continue routine confirmatory DST testing at CDC in addition to just sending the isolates for genotyping. Analysis is done by measuring the discordance between the results of laboratory DST at CDC and the local labs drug type, drug testing concentrations, and study sites. METHODS: The data for this analysis was provided by the Tuberculosis Trials Consortium (TBTC), CDC. Data for this analysis was collected over nearly two decades (1993-2011), gathered from 7 clinical trials. Discordance between the local and CDC lab DST results was measured using Kappa statistic. Sensitivity and specificity analysis was done by taking the CDC DST lab results as the gold standard. Discordance levels were calculated by local sites and baseline drug resistance for each antibiotic in each study was measured. RESULTS: Average Kappa values for inter rater agreement for all the studies was 0.6444 whereas the overall level of discordance across all studies is 7.786%. Drug resistance at baseline was highest for Isoniazid and Streptomycin (except Study 23 and 22). CONCLUSION: Though the current results show few DST result discordances between local and CDC labs, it is better to continue to send isolates to the centralized lab (CDC) in view of the worldwide threat of drug resistant TB epidemic, the recommendations of the current literature and the benefits of reliable confirmatory testing services and availability of other molecular diagnostic methods.

Emerging multidrug-resistant tuberculosis (MDR/XDR-TB) has become a major public health problem, placing millions at risk. Further, nosocomial transmission of MDR/XDR-TB places both patients and healthcare workers at an even higher risk. Effective tuberculosis (TB) infection prevention and control (IPC) policies in high-risk settings must use evidence-based science and should be customized to the setting. However, the growing incidence of MDR/XDR-TB in some global settings raises questions about whether adequate healthcare-related TB IPC policies are in place and whether they are implemented effectively. The purpose of this systematic literature review was to catalogue healthcare-related TB IPC policy research conducted in high-prevalence settings and draw a picture of existing evidence-based TB IPC policies and their implementation, with a focus on preventing and controlling nosocomial transmission of MDR/XDR-TB. Two databases (PubMed and Embase) were searched from 1990 – 2013 and outputs were categorized by region/country, income, MDR/XDR-TB incidence, level of IC intervention, and time period. None of the 20 captured research studies were conducted in TB high-prevalence, low-income settings. Most (12/20) were implemented within the Pan American Health Organization region, followed by the African (4/20) and European (4, 20%) regions. Most studies reviewed (70%) were undertaken because of an outbreak and most (70%) were published between 1990 – 2000. This systematic literature review showed a gap in research on TB IPC policies addressing nosocomial transmission of MDR/XDR-TB in high-prevalence, low-income settings. TB IPC policy development and implementation should be routinely undertaken as a part of effective and efficient public health practice. Development of TB IPC global best practices should be guaranteed and a concerted effort to promote, distribute, train, and implement these TB IPC best practices in low-resource countries would help mitigate the growing incidence of MDR/XDR-TB worldwide.

Submitted by Irene Nascimento (irene.kessia@ufpe.br) on 2016-08-26T18:01:43Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) NILMA MEDTROP VD.pdf: 2060397 bytes, checksum: 801ad4896a8a5f3c544547167d27652d (MD5) / Made available in DSpace on 2016-08-26T18:01:43Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) NILMA MEDTROP VD.pdf: 2060397 bytes, checksum: 801ad4896a8a5f3c544547167d27652d (MD5) Previous issue date: 2015-02-05 / A tuberculose (TB) é a doença mais comum da humanidade. Atualmente, a Organização Mundial de Saúde estimou nove milhões de novos casos e um milhão e meio de mortes decorrentes da doença. A rápida expansão da resistência aos fármacos antituberculose tem prejudicado o controle global da TB, constituindo um grave problema de Saúde Pública. No Brasil, a semelhença de outros países endêmicos, tem-se observado uma variabilidade na prevalência de resistência e no estado da Paraíba (PB) não há dados recentes e concisos. Dessarte, esse estudo objetivou verificar a prevalência de resistência do Mycobacterium tuberculosis aos fármacos do esquema de primeira linha do tratamento da TB utilizados no Brasil e a frequência de fatores de risco - sexo, idade, tratamento prévio e ingesta alcóolica - em pacientes adultos com diagnóstico de TB pulmonar resistente (TBP), atendidos em serviço de referência na PB durante o período de 01 de janeiro de 2003 a 31 de dezembro de 2013. Para obtenção dos dados, utilizou-se formulário padronizado, preenchido, retrospectivamente, a partir das informações contidas nos prontuários dos pacientes atendidos no período do estudo. Foram notificados 69 casos, com prevalência de 0,5%. Evidenciou-se 17,4% de mono, 14,5% de poli e 68,1% de multirresistência. A resistência à isoniazida (INH) mostrou-se importante, tanto isolada, quanto em associações; bem como e, principalmente, a TB multirresistente (TBMR). Perante os fatores de risco, o sexo masculino (73,9%), a faixa etária de 40 a 49 anos (46,4%), a realização de tratamento prévio (98,5%) e a ingesta alcóolica (57,4%) foram os de maior ocorrência. Todavia, não expressaram significância estatística no estudo realizado tendo a PB como cenário. O desfecho foi a cura para 44,9% dos casos; no entanto, o abandono ao tratamento foi considerável, principalmente para a TBP monorresistente (33,3%). As características sociodemográficas compreenderam: a cor da pele parda (68,5%), o estado civil casado (50,9%), o nível de instrução até o fundamental (67,3%) e a procedência do interior da PB (78,2%). Quanto à coinfecção com HIV/AIDS, ocorreu em 14,5%; no entanto, nesse grupo a TBMR, também, foi mais frequente. Desta feita, mais estudos são imprescindíveis no intuito de investigar genotipicamente a resistência da TB no estado da PB, visto que alguns estudos genéticos têm reportado mutações em cepas resistentes à rifampicina (RMP), estando associada a maior transmissibilidade e a resistência à INH tem sido associada com mutações de vários genes. Assim, correlacionando com outros estados e países a fim de colaborar com o enfrentamento da doença na busca do controle e cura extensiva a todos. Por outro lado, há necessidade de fortalecimento das ações do programa de controle da TB, tanto em nível estadual, quanto nos municípios. / Tuberculosis (TB) is the most common disease of humanity. Currently, the World Health Organization estimated nine million new cases and a million and a half deaths from the disease. The rapid spread of resistance to antituberculosis drugs has undermined the global TB control, constituting a serious public health problem. In Brazil, as other endemic countries, it has been observed variability in the prevalence of resistance and the state of Paraíba (PB) no recent and accurate data. Thus, this study aimed to determine the prevalence of resistance of the Mycobacterium tuberculosis to first-line drugs in TB treatment regimen used in the Brazil and frequency of risk factors - gender, age, prior treatment and alcoholic intake - in adults patients diagnosed with resistant pulmonary TB (PTB), treated on reference service in PB during the January 1, 2003 to December 31, 2013. To obtain the data, it used standardized form filled out retrospectively from the information contained in the medical records of patients seen during the study period. Were reported 69 cases, with a prevalence of 0.5%. Revealed a 17.4% to mono, 14.5% to poly and 68.1% to multidrug resistance. The isoniazid (INH) resistance was found to be important, both isolated, as in associations; as well as, and especially multidrug resistant TB (MDR-TB). In view of the risk factors, males (73.9%), the age group 40 -49 years (46.4%), the realization of previous treatment (98.5%) and alcoholic intake (57.4%) were the most frequent. However, did not express statistical significance in the study with the PB as a scenario. The outcome was the cure for 44.9% of cases; however, abandon to treatment was significant, particularly for mono resistant PTB (33.3%). The sociodemographic characteristics included: dark brown skin (68.5%), married status (50.9%), level of education up to primary (67.3%) and the origin from the interior of PB (78.2%). The co-infection with HIV/AIDS occurred in 14.5%; however, this group the MDR-TB also was more frequent. This time, more studies are essential in order to investigate genotypically the TB resistance in the state of PB, as some genetic studies have reported mutations in strains resistant to rifampicin (RMP) and are associated with increased transmissibility and INH resistance has been associated with mutations multiple genes. Thus, correlating with other states and countries to collaborate with coping with the disease in the search of control and extensive cure to all. On the other hand, there is need to strengthen the actions of the TB control program at the state level and in the municipalities.

Magister Pharmaceuticae - MPharm / Tuberculosis and HIV are arguably South Africa’s largest and most important health issues. With drug-resistant strains of tuberculosis on the increase and little research on new drugs, there is an urgent need for research around the drugs presently available to ensure their optimal use and to minimise their sometimes serious and significant side effects. Treatment of drug-resistant tuberculosis is expensive and lengthy, and is complicated by a limited choice of drugs with lower efficacies and higher toxicities. Treatment is further complicated in patients with HIV due to several factors including drug interactions. While some authors suggest that HIV and malabsorption might be associated with poor clinical outcomes, other researchers have found no link. Patients may benefit from Therapeutic Drug Monitoring in order to ensure that their doses of antituberculosis drugs are reaching the required minimum effective concentrations, without attaining toxic levels in the plasma which may cause unpleasant side effects. There is little research concerning drug levels in HIV patients with TB in South Africa, let alone in patients with drug-resistant forms of tuberculosis, and there are no studies in this country that use Liquid Chromatography-Mass Spectrometry to investigate the plasma levels of pyrazinamide in patients with MDR-TB. This study aimed to investigate whether or not there is a difference in the pharmacokinetics of PZA in MDR-TB patients with HIV, and those without HIV infection. It also aimed to establish whether LC-MS could be used to study the levels of pyrazinamide in the plasma of patients with multidrug-resistant tuberculosis with and without concurrent HIV infection. The plasma levels of pyrazinamide in 32 MDR-TB patients (23 HIV negative and 9 HIV positive), were successfully 2 analysed using LC-MS, and the pharmacokinetics of PZA in these 2 populations was described. It was established that the Tmax of pyrazinamide was significantly higher in HIV-negative patients than in HIV-positive patients. Although there was a difference between the Ka in the two populations, this difference did not quite reach statistical significance. There were no statistically significant differences between HIV-negative and HIV-positive patients with regards to the other pharmacokinetic parameters investigated. Our findings established that there was little evidence to suggest that there is a difference between the pharmacokinetics of the antimycobacterial drug pyrazinamide in HIV-positive patients and that in HIV-negative patients. We were also able to successfully develop and validate an assay for the analysis of PZA in plasma using LC-MS, and this finding could be very valuable for further studies. Although our study failed to prove this, the possibility still exists that HIV-positive patients could exhibit altered kinetics of antiTB drugs and this has not been fully investigated in South Africa. The clinical impact of low plasma levels of antimycobacterial drugs is still largely unexplored and further research with larger sample sizes should be done in order to establish which factors may contribute to low plasma levels of anti-tuberculosis drugs in MDR-TB patients, and whether or not these low levels are increasing the risk of treatment failure or other poor clinical outcomes.

Thesis (MSc. (Medical Sciences)) -- University of Limpopo, 2015 / Introduction: Multidrug-resistant tuberculosis (MDR-TB) caused by resistance to at least rifampicin (RIF) and isoniazid (INH) drugs is a growing public health concern in South Africa. The detection of MDR-TB still relies on culture despite advancement in molecular diagnostic technology. Currently MTBDRplus and GeneXpert are the only available assays used in rapid diagnosis of MDR-TB using chromosomal mutations in drug target regions. Some strains are missed by these assays due to their limitation in mutational detection profile. Novel Seegene Anyplex assays simultaneously detect TB and resistance to RIF and INH using fifteen and six mutational probes, respectively within 3 hours. Limpopo Province has limited information on the circulating strains of TB. Aim: To determine drug-resistant Mycobacterium tuberculosis (M. tuberculosis) mutations using Anyplex™ MTB/NTM/MDR-TB real time assay and characterise the drug-resistant strains. Methods: We prospectively collected 204 clinical samples at Modimolle MDR-TB unit and retrospectively used 104 culture isolates from MRC laboratory in Pretoria. The MTBDRplus assay was used to screen for M. tuberculosis and drug resistant mutations to RIF and INH drugs. Anyplex™ MTB/NTM/MDR-TB assay was used for rapid detection of M. tuberculosis and drug resistance to RIF and INH within 3 hours. The discordance between phenotypic and genotypic assays was resolved by sequencing and the Anyplex™ resistant profiles were spoligotyped. Diagnostic data was collected from NHLS and MRC databases and analysed using the Microsoft excel and Epi Info version 3.5. Descriptive statistics (percentages and frequencies) were used to explain proportions. Results: The Anyplex™ MTB/NTM assay detected M. tuberculosis in 69/111(62%) and 100/104 (96%) of clinical and culture samples respectively. The sensitivities, specificity, PPV and NPV obtained for both RIF and INH resistance by Anyplex™ MDR-TB assay were 67%, 59%, 67%, 55% and 15%, 100%, 100% and 17%, respectively. Anyplex™ MTB/NTM/MDR-TB resolved 23/45 (51%) of discordant vi samples. Sequencing of remaining discordant isolates revealed L511P, L533P and D516Y mutations within rpoB gene. A novel R385W mutation within katG was also detected. Spoligotyping of Anyplex™ MDR-TB resistant clinical isolates revealed Euro American clade with 20% followed by 15% Manu2, 5% East African Indian, 5% H37Rv, 5% atypical and 50% were orphans. Conclusion: The novel Anyplex™ MTB/NTM/MDR-TB assay is a rapid and valid technique for detecting M. tuberculosis and most common mutations conferring resistance to RIF and INH. However further investigations are required, as the assay has a lower sensitivity as compared to already endorsed techniques. / National Research Foundation (NRF) and University of Limpopo TB Grant

Philosophiae Doctor - PhD / Although TB is a curable communicable disease, poor adherence to TB treatment is a major barrier to TB control in South Africa as it increases the risks of morbidity, mortality and drug resistance at individual and community level. As a result, multi-drug-resistant TB (MDR-TB) has become a serious public health issue. Underpinning this study was the assumption that a client-centred approach to treatment of MDR-TB clients, with a hospital programme which adopts an integrated multidisciplinary approach that is client-centred and is not purely biomedically driven, would improve treatment outcomes of MDR-TB clients.