M.Cur. / Tuberculosis is regarded as a global health problem as accelerated by the impact of the HIV/AIDS epidemic. In South Africa it is regarded as a top national health priority. Taking treatment regularly prevents multi-drug resistance TB. The introduction of Directly Observed Treatment Short-course (DOTS) ensures that treatment supporters observe TB patients swallow tablets under direct supervision. In the area of research, treatment supporters are trained by South African National Tuberculosis Association trainers to supervise treatment. It happened on a regular basis that patients complain about various aspects of the observational progress, resulting in change of treatment supporters, some preferred to be supervised from the clinic. The researcher developed interest to find out about the shortcomings in the observation of TB patients by treatment supporters, so as to address those shortcomings. A qualitative, exploratory, descriptive and contextual research study was conducted to identify the experience of treatment supporters in observing tuberculosis patients on TB treatment and also, the experience of TB patients as observed by treatment supporters. Permission was obtained from both treatment supporters and TB patients. A pilot phenomenological interview was conducted from one TB patient and one treatment supporter supervising TB treatment, who met the selection criteria. The phenomenological interviews were conducted in Northern Sotho (Pedi), Shangaan, Tswana, Xhosa, Zulu, Southern Sotho and Northern Sotho (Tlokwa) from both treatment supporters and TB patients. The samples comprises of 14 TB patients and 14 treatment supporters supervising those TB patients. Steps were taken to ensure trustworthiness. Tesch’s method of data-analysis was followed to analyze the data. Results indicated that there are interfering factors relating to the working relationship between the TB patients and the treatment supporter. From the findings, facilitative factors are used as proposals to promote the observation of TB patients by treatment supporters. Strategies are described from the rationale, which explain how the proposal can be reached. The strategies were based on the study findings and the literature reviewed.

Thesis (PhD)--Stellenbosch University, 2008. / ENGLISH ABSTRACT: Setting Study conducted in Tygerberg, Cape Town in South Africa. Hypothesis Host biomarkers associated with the antimycobacterial immune response during active infection with M. tuberculosis and during anti-tuberculosis chemotherapy are indicative of bacterial killing in the host and can be used in models to predict eventual treatment outcome. Objectives 1. To investigate immune parameters that were selected in a biological context as biomarkers of the extent of disease and early response to anti-tuberculosis treatment. 2. To use selected immune parameters to characterise fast and slow responders to anti-tuberculosis therapy. Findings Evaluation of cytokine multiplex fluorescent bead-based immunoassays as a screening tool in the search for biomarkers The data showed that cytokine multiplex fluorescent bead-based immunoassays achieved acceptable recoveries to detect antigen-specific IFN- responses in whole blood supernatant making it attractive for biomarker screening. However, proper optimisation needs to be done and proper controls included when using these kits. Markers of extent of disease High levels of CRP at diagnosis were found to be associated with the presence of multiple cavities on chest X-rays. A high level of suPAR and sICAM-1 at diagnosis were associated with the extent of alveolar disease. Also significant were the associations between the level of granzyme B, LAG-3 at diagnosis and the size of the cavities. No significant associations were observed between sTNFRs or DR5 with the chest X-ray grading of tuberculosis disease. Early classification of fast and slow responders to anti-tuberculosis treatment After cross-validation classification, discriminant analysis (DA) and support vector machine (SVM) analysis of selected immune parameters (sICAM-1 CRP, granzyme B, suPAR, sTNFRs, LAG-3 and CD3dim/CD56+ (% of CD45+) resulted in a 75% to 100% correct classification of the fast responders and a 82% to 100% correct classification of the slow responders when using DA. For SVM, the correct classification of the fast responders ranged from 88% to 100%, and that for the slow responders ranged from 95% to 100%. Differential gene expression in fast and slow responders to treatment Direct comparison of fast and slow responders showed that IL-4 transcripts were significantly higher in the fast responders at week one after initiation of treatment when compared to slow responders. IL-42 was also differentially expressed. Although IL- was significantly up-regulated in both fast and slow responders after one week of treatment compared to diagnosis, IL- expression was more than two folds higher in slow responders than in fast responders. No significant differences between the fast and slow responders were observed in the expression of TGF-, TGF-RII, Foxp3 and GATA-3. Conclusion Predictive models for differential anti-tuberculous treatment responses combining host proteins are promising and should be included in larger prospective studies to find the optimal markers for inclusion into clinical trials of new drugs and for implementation into clinical practice. / AFRIKAANSE OPSOMMING: Ligging Studie onderneem in Tygerberg, Kaapstad, Suid-Afrika. Hipotese Gasheerbiomerkers wat verband hou met die antimikobakteriële immuunrespons tydens aktiewe infeksie deur M. tuberculosis en tydens teentuberkulose chemoterapie dui op bakteriële doding in die gasheer en kan in modelle gebruik word om die uiteindelike uitkoms van die behandeling te voorspel. Doelwitte 1. Om gekose immuunparameters in ’n biologiese konteks as biomerkers van die omvang van siekte en vroeë reaksie op behandeling te ondersoek. 2. Om gekose immuunparameters te gebruik om vinnige en stadige reageerders op teentuberkulosebehandeling te karakteriseer. Bevindings Evaluering van die sitokien veelvuldige fluoresseer-pêrelbaseerde immuuntoets (cytokine multiplex fluorescent bead-based immunoassays) as ’n siftingsinstrument in die soeke na biomerkers Die data het getoon dat die sitokien veelvuldige fluoresseer-pêrelgebaseerde immuuntoets in staat was om antigeenspesifieke IFN--respons te meet wat dit aanloklik maak vir biomerkersifting. Sorgvuldige optimering moet egter gedoen word en behoorlike beheer moet ingesluit word wanneer hierdie stelle gebruik word. Merkers van omvang van siekte Hoë vlakke van CRP by diagnose is getoon om verband te hou met die teenwoordigheid van veelvoudige holtes op die pasiënte se borskas x-strale. Hoë vlakke van suPAR en sICAM-1 by diagnose was assosieer met die omvang van alveolêre siekte. Die assosiasie tussen die vlakke van granzyme B, LAG-3 by diagnose en die grootte van die holtes was ook betekenisvol. Daar was geen betekenisvolle assosiasies toe sTNFRs of DR5 en die borskas x-straalgradering van tuberkulosesiekte nie. Vroeë klassifikasie van vinnige en stadige reageerders op teentuberkulosebehandeling Ná klassifikasie op grond van kruisstawing het diskriminant-analise (DA) en ondersteuningsvektormasjiene (SVM) van geselekteerde immuunparameters (sICAM-1 CRP, gransiem B, suPAR, sTNFRs, LAG-3 en CD3dim/CD56+ (% van CD45+)) gelei tot ’n 75% tot 100% korrekte klassifikasie van die vinnige reageerders met DA en ’n 82% tot 100% korrekte klassifikasie van stadige reageerders. Vir SVM het die korrekte klassifikasie van vinnige reageerders gewissel van 88% tot 100%, en vir stadige reageerders het dit gewissel van 95% tot 100%. Differensiële geenuitdrukking in vinnige en stadige reageerders op behandeling In vergelyking met die vlak by diagnose is die uitdrukkingsvlak van IL-4 in die vinnige reageerders betekenisvol opgereguleer met ’n faktor van 9.2 teen die eerste week ná die aanvang van behandeling, in kontras met die stadige reageerders. Daar was geen verskille tussen die vinnige en die stadige reageerders met betrekking tot die uitdrukking van TGF-, TGF-RII, Foxp3 en GATA-3 nie. Gevolgtrekking Voorspellende modelle vir differensiële tuberkulose behandelingsresponse wat gasheerproteïene kombineer, hou belofte in en behoort in groter prospektiewe studies ingesluit te word om die mees geskikte merkers te vind vir insluiting in kliniese proewe van nuwe middels en vir implementasie in kliniese praktyk.

The purpose of the study was to investigate the factors associated with the interruption of tuberculosis treatment in the Swakopmund district of Namibia. A descriptive cross-sectional survey was conducted. Data was collected using a structured questionnaire administered by interviewers. The population consisted of both treatment interrupters and non-interrupters. The total sample was 143 respondents. The findings revealed that three factors were significantly associated with TB treatment interruption, namely a lack of formal education (p = 0.032), lack of access to media (p = 0.017), and clinic opening times (p = 0.000). Recommendations made include improving the support given to TB patients, increasing their understanding of TB and adopting new research and technology. / Health Studies / M.A. (Public Health)

Text in English / Aim: The aims of this study were to investigate the treatment outcomes of patients with MDRTB and its determinants at referral hospitals in Ethiopia. The study also aims to develop a conceptual model for enhancing treatment of patients with MDR-TB in Ethiopia. Design and methods: A concurrent mixed methods design with quantitative dominance was used to investigate treatment outcomes of patients with MDR-TB and its determinants. Results: A total of 136 (n=136) patients with MDR-TB participated in the study, 74 (54%) were male and 62 (46%) were female. Forty-one (31%) of the patients had some co-morbidity with MDR-TB at baseline, and 64% had body mass index less than 18.5kg/m2. Eight (6%) of the patients were diagnosed among household contacts. At 24 months, 76/110 (69%) of the patients had successfully completed treatment, but 30/110 (27%) were died of MDR-TB. Multivariable logistic regression revealed that the odds of unfavourable treatment outcomes were significantly higher among patients with low body mass index (BMI <18.5kg/m2) (AOR=2.734, 95% CI: 1.01-7.395; P<0.048); and those with some co-morbidity with MDR-TB at the baseline (AOR=4.260, 95%CI: 1.607-11.29; p<0.004). The majority of the patients were satisfied with the clinical care they received at hospitals. But as no doctor was exclusively dedicated for the MDR-TB centre, patients could not receive timely medical attention and this was especially the case with those with emergency medical conditions. The caring practice of caregivers at the hospitals was supportive and empathic but it was desperate and alienating at treatment follow up centres. Patients were dissatisfied with the quality and adequacy of the socio-economic support they got from the programme. Despite the high MDR-TB and HIV/AIDS co-infection rate, services for both diseases was not available under one roof. Conclusions: Low body mass index and the presence of any co-morbidity with MDR-TB at the baseline are independent predictors of death among patients with MDR-TB. Poor communication between patients and their caregivers and inadequate socio-economic support were found to determine patients’ perceived quality of care and patients’ satisfaction with care given for MDR-TB. / Health Studies / D. Litt et Phil. (Health Studies)

The purpose of the study was to investigate the factors associated with the interruption of tuberculosis treatment in the Swakopmund district of Namibia. A descriptive cross-sectional survey was conducted. Data was collected using a structured questionnaire administered by interviewers. The population consisted of both treatment interrupters and non-interrupters. The total sample was 143 respondents. The findings revealed that three factors were significantly associated with TB treatment interruption, namely a lack of formal education (p = 0.032), lack of access to media (p = 0.017), and clinic opening times (p = 0.000). Recommendations made include improving the support given to TB patients, increasing their understanding of TB and adopting new research and technology. / Health Studies / M.A. (Public Health)

Thesis (PhD)--Stellenbosch University, 2013. / ENGLISH ABSTRACT: The immune response against M. tuberculosis is multifactorial, involving a network of innate and adaptive immune responses. Characterization of the immune response, a clear understanding of the dynamics and interplay of different arms of the immune response and the identification of infection-stage specific biomarkers are critical to allow the development of better tools for combating tuberculosis. In an attempt to identify such biomarkers, we studied pulmonary tuberculosis patients and their contacts in Addis Ababa, Ethiopia as part of EDCTP and BMGF funded tuberculosis projects by using multiplex techniques. We analysed 45 genes using the Multiplex Ligation Dependent Probe Amplification (MLPA) technique and the expression of IL-4δ2, BLR1, MARCO, CCL-19, IL7R, Bcl2, FcyR1A, MMP9, and LTF genes discriminate TB cases from their healthy contacts. FoxP3, TGFß1 and CCL-19 discriminate latently infected from uninfected contacts. Single genes predict with an area under the Receiver Operating Characteristic (ROC) curve of 0.68 to 0.85 while a combination of genes identified up to 95% of the different groups. Similarly, the multiplex analysis of cytokines and chemokines also showed that single or combinations of plasma cytokines and chemokines discriminate between different clinical groups accurately. The median plasma level of EGF, fractalkine, IFN-y, IL-4, MCP-3 and IP-10 is significantly different (p<0.05) in active tuberculosis and non active tuberculosis infection and the median plasma levels of IFN-y, IL-4, MCP-3, MIP-1ß and IP-10 were significantly different (p<0.05) before and after treatment. We also found a significant difference (p<0.05) in plasma levels of cytokines of patients infected with the different lineages and different families of the modern lineage. The plasma level of IL-4 was significantly higher in patients infected with lineage 3 (p<0.05) as compared to lineage 4 and the CAS familyinfected patients had a higher plasma level of IL-4 (P<0.05) as compared to patients infected with H and T families but there was no difference between H and T families. We identified genes and cytokines which had been reported from other studies in different settings and we believe that these molecules are very promising biomarkers for classifying active tuberculosis, latent infection, absence of infection and treated infection. These markers may be suitable for the development of clinically useful tools but require further validation and qualification in different populations and in larger studies. / AFRIKAANSE OPSOMMING: Die immuunrespons teen M. tuberculosis is multifaktoriaal en betrek ‘n netwerk van niespesifieke and spesifieke immuunresponse. Karakterisering van die immuunrespons, ‘n duidelike insig in die dinamika en tussenspel deur die verskillende arms van die immuunrespons en die identifikasie van spesifieke biomerkers is krities belangrik om die ontwikkeling van nuwe hulpmiddels teen tuberkulose te bevorder. In ‘n poging om sulke biomerkers te identifiseer het ons pulmonale tuberkulose pasiënte en hulle kontakte in Addis Ababa, Etiopië, as deel van die EDCTP en BMGF befondste tuberkulose projekte bestudeer met multipleks tegnieke. Ons het 45 gene analiseer met ‘Multiplex Ligation Dependent Probe Amplification (MLPA)’ en gevind dat die geenuitdrukking van IL-4•2, BLR1, MARCO, CCL-19, IL7R, Bcl2, Fc•R1A, MMP9, en LTF TB pasiënte van hulle kontakte onderskei. FoxP3, TGF•1 en CCL-19 onderskei tussen latent infekteerde en ongeïnfekteerde kontakte. Enkele gene voorspel met ‘n area onder die ‘Receiver Operating Characteristic (ROC)’ kurwe van 0.68 tot 0.85 terwyl die kombinasie van gene 95% van die verskillende groepe identifiseer. Soortgelyk het multipleks analise van sitokiene en chemokiene verskillende kliniese groepe akkuraat van mekaar onderskei. Die mediane plasmavlakke van EGF, fractalkine, IFN-•, IL-4, MCP-3 en IP-10 is beduidend verskillend (p<0.05) in aktiewe tuberkulose en nie-aktiewe tuberkulose infeksie en die mediane plasmavlak van IFN-•, IL-4, MCP-3, MIP-1• en IP-10 was beduidend verskillend voor en na behandeling. Ons het ook beduidende verskille (p<0.05) in plasmavlakke van sitokiene in pasiënte gevind wat infekteer is met verskillende stamme and verskillende families van die moderne stamme. Die plasmavlak van IL-4 was beduidend hoër in pasiënte wat infekteer is met stam 3 (p<0.05) teenoor stam 4 en die CAS familie-infekteerde pasiënte het ‘n hoër plasmavlak van IL-4 (p<0.05) teenoor pasiënte met H en T familie infeksie hoewel daar geen versikke was tussen die H en T families nie. Ons het gene en sitokiene identifiseer wat deur ander werkers onder verskillende omstandighede ook beskryf is en ons glo dat hierdie molekules baie belowende biomerkers is om aktiewe tuberkulose, latent tuberkulose, die afwesigheid van infeksie en behandelde infeksie van mekaar te onderskei. Hierdie merkers mag toepaslik wees vir die ontwikkeling van bruikbare kliniese hulpmiddele maar benodig verdere validasie en kwalifikasie in verskillende populasiegroepe en in groter studies. / Bill and Melinda Gates Foundation (BMGF) / European and Developing Countries Clinical Trials Partnership (EDCTP) / African European Tuberculosis Consortium (AE TBC).