Submitted to the Department of Epidemiology and Biostatistics, School of Public Health, University of Witwatersrand, in partial fulfillment of the requirements for the degree of Master of Science Epidemiology and Biostatistics, 2012 / TB is a high burden disease (prevalence: 940/100,000 in 2006) with high morbidity and mortality in South Africa and the primary health care facilities are well position to provide primary TB care in accordance to the national TB control guidelines and achieve desired treatment outcome targets. This study followed the TB management at Thandukukhanya clinic from 2000-2005 and found among others that the number of TB cases tripled, the TB cure rate progressively declined and DOTS support dwindle over the six years. The study was motivated by 26% decline in TB cure rate at Mkhondo sub-district from 2003 – 2005 and 76% increase in TB default in the same period. The TB cure rate in 2005 was 37% compared to 85% national target. The poor treatment outcome prevails despite availability of DOTS support in the program. In addition, the number of drug resistant TB has increased in the past years and extremely drug resistant TB emerged in the past three years in South Africa

D.Cur. / Although tuberculosis is regarded as a curable disease, it still remains a health problem. The World Health Organization declared tuberculosis as a global emergency in 1993, and a global failure of health service providers to deal with the burden of tuberculosis in 1997. One of the factors that has a detrimental effect on the struggle against tuberculosis, is the fact that certain patients suffering from tuberculosis interrupt and/or stop taking their treatment before the scheduled period, thus, not adhering to their treatment. This non-compliance contributes to the increasing problem of chronic “halfcured and half-ill” patients with an increase of resistance against some of the first-linemedication. The problem with resistance is that second-line-medication must then be used. These medications are more toxic, the treatment is more expensive and takes longer, and, at the most, only half of the patients are cured. There are however other patients who comply with their treatment and complete it successfully. As a result of the above-mentioned problem the researcher has researched treatment compliance of tuberculosis within the context of the North West Province’s Southern District with the following objectives: ? to explore and describe the reasons why certain patients suffering from tuberculosis interrupt or prematurely stop their treatment; ? to explore and describe the reasons why certain patients suffering from tuberculosis comply with their treatment and complete it successfully; ? to develop and validate strategies in order to facilitate treatment compliance of the patient suffering from tuberculosis. Unstructured interviews were conducted with six patients who complied with their treatment, 11 patients who did not comply with their treatment (or defaulters), eight family members of non-compliant patients, and nine community health nurses. The following questions were asked in each respective group of participants: ? The treatment compliant patients and the defaulters were asked: “Tell me about your TB and treatment”. ? The family members were asked: “Tell me how his TB and treatment was for him”. ? The nurses were asked: “Why do you think some TB patients comply with their treatment and others are defaulters?” Interviews were recorded on tape and transcribed verbatim. Tesch’s (in Creswell, 1994:155) eight-step method of data-analysis was used in collaboration with an independent encoder to analyse the data. This research has proven that the treatment compliant patient is motivated and ready to comply with his treatment. Although the defaulter is also motivated he is not ready to comply with his treatment, because he does not accept tuberculosis as his problem nor the treatment thereof. This non-acceptance contributes to his misconceptions regarding tuberculosis and its treatment, and a negative attitude also develops towards the medicine, which becomes evident in the termination or adjustment of his treatment. The compliant patient on the other hand, within the same situation, when experiencing side effects, for example, still adheres to his treatment. Factors that contribute to the treatment compliance of the patient are: his motivation; his stage of behavioural change; the application of specific processes that will enable the patient to move from a nonready to a ready mode, where treatment compliance can be maintained; a patientcentred approach in the nurse-patient-relationship, where effective interpersonal skills are applied, where the patient is actively involved and where a member of his family is involved in the interaction process; and where cultural beliefs, stigmatisation and misconceptions with regard to tuberculosis and treatment are addressed. Strategies have been developed and validated that may enable the nurse to facilitate the patient’s treatment compliance. These strategies address the following aspects in order to promote the nurse’s knowledge and skills concerning: tuberculosis as problem and the treatment thereof; interpersonal skills within a patient-centred nursing approach; assessment of patient’s readiness to accept behavioural change within the patient’s cultural context; facilitation of the patient’s treatment compliance; facilitation of the community’s behavioural change in order to promote social support of the patient while cultural beliefs, stigmas and misconceptions are addressed.

Objective The consistent emerging of multidrug-resistant tuberculosis (MDR-TB) cases are increasingly becoming a major threat and challenge in global TB control, especially in some resource-limited settings like India, China, South Africa. Currently there is no widely acknowledged treatment strategy for MDR-TB. Effectiveness and of current DOTS-Plus strategy is remaining controversial. This systematic review aims to investigate treatment outcomes for MDR-TB under DOTS-Plus and potential factors associated with poor outcome (death, default and failure). Methodology The literatures were searched in Pubmed, Medline, the Cochrane library, Essential Evidence Plus, EMBASE and CNKI. Some manual search articles were also added and 164 literatures in total were founded related to treatment outcomes for multidrug resistant patients under DOTS-Plus. After basically screening and carefully full-text reading, nine studies meeting the inclusion criteria were included. A total of 3358 participants from 8 high MDR-TB countries were investigated. Result Baseline characters were varied across these nine studies, including HIV prevalence (0-1.6%), MDR-TB prevalence (0-4.7%), previous treatment history (without TB treatment, with TB treatment but not under directly observed therapy, short courses (DOTS) and with TB treatment under DOTS), and male/female ratio (54%-86.5%). All studies reported a successful outcome rate (cure and complete) higher than 60 percent, and three of the studies reported higher than 70 percent, which are comparatively high in MDR-TB treatment. Factors associated with poor outcomes that reported by these studies were including alcohol use/ abuse, homelessness, unemployment, imprisonment, BMI, cavitary and bilateral disease, missing doses, and resistant to some second-line drugs. Conclusion In sum, the overall treatment outcomes from these nine studies under DOTS-Plus were acceptable, and most of them were satisfactory. Nevertheless, in consideration of potential bias arising from these cohort analyses, conclusions should be drawn carefully. Several major challenges restrict low- and middle- income countries from implementing DOTS-Plus, which put high command on TB infrastructure, policy commitment, human resources and financial support. Further effort could be put on systematical review and meta-analysis on cost-effectiveness of DOTS-Plus programs. In China, policy makers should pay attention to arrive at national and provincial guidelines of MDR-TB treatment under DOTS-Plus. / published_or_final_version / Public Health / Master / Master of Public Health

Background: Optimal tuberculosis (TB) treatment remains the backbone of effective TB control programmes. However, TB drugs are often associated with adverse drug reactions (ADR) that affect treatment adherence and cure. Cutaneous adverse drug reactions (CADR) are more commonly associated with Human Immunodeficiency Virus (HIV)/TB co-infection, occurring in up to 7% of patients. If severe, CADR require treatment interruption and hospitalisation. There are no standardised guidelines for managing CADR to TB therapy. Current practice in South Africa involves drug rechallenge, a process, which aims to identify the offending drug and modify the treatment regimen. This practice can carry significant risks that need to be weighed against the benefits. Despite significant resources required to manage CADR, there is no available data regarding their economic impact. Alternate strategies to manage TB therapyassociated CADRs and their cost have never been evaluated. The purpose of this study is to evaluate the economic impact of TB therapy-associated CADRs in South Africa and compare the cost of drug rechallenge with alternative strategies. Methods: Data was obtained from 97 patients, admitted to the Groote Schuur Hospital dermatology ward with TB therapy-associated CADR. Clinical data pertaining to hospitalisation, diagnostic/monitoring tests and drug prescriptions was extracted from patient medical records. Healthcare and patient-related costs were obtained from financial department records, interviews and hospital admission records. Alternative drug regimens for CADR management were derived from literature and expert clinical advice. Costs were estimated using an ingredient's approach in 2016 US dollars. A cost-comparative analysis was performed comparing the cost of the current practice with alternative options. Univariate sensitivity analysis was used to investigate the uncertainties around cost components. Results: The cost of managing a TB therapy-associated CADR was $6,525 per patient. Within this population the average cost of managing a CADR in a patient with DS-TB was $5,831 (95% CI: 8438; 10727). The main contributor of CADR costs was hospitalisation amounting to $3,638/patient (62% of total cost). Alternative CADR management strategies using outpatient-initiated second-line regimens containing rifabutin, bedaquiline and delamanid cost 44-55% less than drug rechallenge depending on the drug regimen used ($2,651/patient to $3,276/patient). Sensitivity analyses indicated that drug rechallenge was most sensitive to hospitalisation costs, whereas second-line treatment strategies were sensitive to TB drug costs. The average total loss experienced by patients as a result of the CADR was $530 (25% of their annual income), as compared to an estimated loss in the alternate regimens of $154 (10% of their annual income). Societal costs with alternate regimens were also lower at 46-66% that of current cost of $6,134. Conclusion: CADR to TB treatment represent a significant economic burden to the healthcare system and affected patient. The alternate strategy of outpatient-initiated second-line therapy provides an economically feasible option by implementing an ambulatory practice of care despite using more expensive drugs. Shorter hospitalisation reduces patient and healthcare costs. This data should inform policy makers on optimal resource use within the healthcare system. Once the effectiveness and risk of drugresistance of these strategies has been determined, further research should estimate their cost-effectiveness.

Thesis (M.Dev.) --University of Limpopo (Turfloop Campus), 2005 / The aim of this study was to investigate the socio-economic impact of interrupting TB treatment to the families of the TB sufferers and the reasons for patients interrupting treatment. The study was conducted at Mashishimale Village, Ba- Phalaborwa Municipality, Mopani District, Limpopo Province in South Africa. A sample of 35 tuberculosis patients and their family members was drawn from the Mashishimale population. The sample comprised of 17 (49%) males and 18 (51%) females. Self-administered questionnaires were distributed to the participants to complete. The questionnaire elicited demographic information; knowledge about TB, its causes, signs and symptoms, transmission, the reasons for interrupting treatment, and the patients’ coping and support structures. The findings of the study reported that 50% of TB patients are conversant with the signs, symptoms and mode of the spread of TB. However, 43% of the TB patients reported that there was a perception that TB patients are also HIV positive. A further 29% mentioned that there is stigma attached to TB disease. The lack of a Directly Observed Treatment Supporter, poverty and poor nutrition, side-effects of drugs, loss of disability grants, long clinic queues, and traditional healing were some of the reasons cited for the interruption of TB treatment. The interruption of TB treatment had an impact on the socio-economic situation of the family as they often relied on assistance from social grants, other family members and churches.

M.Cur. / In 1995, the South African Department of Health described tuberculosis (TB) as South Africa's number one health problem. The Directly Observed Treatment Short-course (DOTS) strategy was thereafter implemented as a way of managing TB patients. One of its key elements is a network of trained treatment supporters who are able to support and observe TB patients swallow their treatment. In Alexandra Township a group of treatment supporters was trained in 1998 and another in 2002 but have subsequently I left the community based DOTS programme. ,..~ Why do treatment supporters leave the community based DOTS programme? What can be done to make treatment supporters stay on the community based DOTS programme? An exploratory, descriptive, qualitative contextual study was undertaken to determine the factors: • that interfere with the retention of treatment supporters within the community based DOTS programme in Alexandra Township; • that can facilitate the retention of treatment supporters on the community based DOTS programme; and • to formulate strategies that can be used to promote the retention of treatment supporters within the community based DOTS programme in Alexandra Township. Community nurses, treatment supporters and members of the Anti-TB Association were selected for the study. Focus group interviews were conducted with all three sample groups. The following questions comprised the focus group discussions with all respondents: • What do you think makes treatment supporters leave the community based DOTS programme in Alexandra Township?; and • What do you think should be done to make treatment supporters stay within the community based DOTS programme in Alexandra Towns hip? iii Under.,the following categories factors that interfere as well as factors that can facilitate the retention of treatment supporters were identified: • factors relating to the working relationship between community nurses and treatment supporters; • factors relating to the training of treatment supporters; • factors relating to the management of the community based DOTS programme in Alexandra township. I Data was analysed by using Kerlinger's (1986:477-483) method of content analysis. Strategies for the retention of treatment supporters within the community based DOTS programme in Alexandra Township were formulated. These were based on the study findings and the reviewed literature.

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.

The tuberculosis epidemic is escalating in South Africa as well as globally. This escalation is exacerbated by the increasing prevalence of multidrug-resistant tuberculosis (MDRTB), which is defined by the World Health Organisation (WHO) as resistance of Mycobacteria to at least isoniazid and rifampicin. Multi-drug resistant tuberculosis is estimated to occur in 1-2% of newly diagnosed tuberculosis (TB) patients and in 4-8% of previously treated patients. MDRTB is both difficult and expensive to treat, costing up to 126 times that of drug-sensitive TB. Resource constrained countries such as South Africa often lack both the money and the infrastructure to treat this disease. The aim of this project was to determine whether the performance of a systematic review with subsequent economic modelling could influence the decision making process for policy makers. Data was gathered and an economic evaluation of MDRTB treatment was performed from the perspective of the South African Department of Health. Three treatment alternatives were identified: a protocol regimen of second line anti-tuberculosis agents, as recommended in the South African guidelines for MDRTB, an appropriate regimen designed for each patient according to the results of culture and drug susceptibility tests, and non-drug management. A decision-analysis model using DATA 3.0 by Treeage® was developed to estimate the costs of each alternative. Outcomes were measured in terms of cost alone as well as the ‘number of cases cured’ and the number of ‘years of life saved’ for patients dying, being cured or failing treatment. Drug, hospital and laboratory costs incurred using each alternative were included in the analysis. A sensitivity analysis was performed on all variables in order to identify threshold values that would change the outcome of the evaluation. Results of the decision analysis indicate that the individualised regimen was both the cheaper and more cost-effective regimen of the two active treatment options, and was estimated to cost R50 661 per case cured and R2 070 per year of life saved. The protocol regimen was estimated to cost R73 609 per case cured and R2 741 per year of life saved. The outcome of the decision analysis was sensitive to changes in some of the variables used to model the disease, particularly the daily cost of drugs, the length of time spent in hospital and the length of treatment received by those patients dying or failing treatment. This modelling exercise highlighted significant deficiencies in the quality of evidence on MDRTB management available to policy makers. Pragmatic choices based on operational and other logistic concerns may need to be reviewed when further information becomes available. A case can be made for the establishment of a national database of costing and efficacy information to guide future policy revisions of the South African MDRTB treatment programme, which is resource intensive and of only moderate efficacy. However, due to the widely disparate range of studies on which this evaluation was based, the outcome of the study may not be credible. In this case, the use of a systematic review with subsequent economic modelling could not validly influence policy-makers to change the decision that they made on the basis of drug availability.

Magister Artium - MA (Anthropology/Sociology) / Biomedicine positively maintains that tuberculosis transmission occurs due to close contact with a diseased individual (Coovadia and Benatar, 1991). Consequently, this refers to a direct mode of transmission where individuals are at direct risk of becoming infected. It is often taken for granted that when one speaks of contact within the context of tuberculosis, one is necessarily referring to contact or interactions among tuberculosis patients and people in the community with whom they have contact of any nature. It is then assumed that tuberculosis is transmitted in this manner. However, there are also indirect modes of transmission which are often neglected to be explored, but have an equally serious effect on transmission in high incidence areas. This paper also addresses other contact patterns that are also role-players in the tuberculosis epidemic.

Introduction Tuberculosis (TB) causes approximately 2 million deaths every year. The problem is escalating explosively in sub-Saharan Africa and is directly related to the increase in the prevalence ofHuman Immunodeficiency Virus infection. South Africa was ranked as having the fourth highest global incidence of TB in 2006. In 1993, the World Health Organization introduced the Directly Observed Treatment Short-Course strategy to increase efficiency of national TB programmes. The Direct Observation of TB therapy element of the strategy has been contentious. An ideal method of direct observation remains elusive and its role in improving adherence is questionable. Aim The purpose ofthis research is to detennine the most effective directly observed method for pulmonary TB offered in an urban area of South Africa. Methods A retrospective cohort analysis was conducted at the Prince Cyril Zulu Communicable Diseases Centre in Durban, KwaZulu-Natal. The study population consisted of adult patients who commenced a course of TB therapy between July 2005 and June 2006. The effect of clinic based, family member, community health worker, lay community health volunteer and workplace based direct observation on TB treatment outcomes, and frequency of recurrence was detennined. A sub analysis was perfonned of the effect of the different methods ofdirect observation in employed patients. Results Workplace based direct observation resulted in a higher frequency of successful treatment outcomes than the other methods of Direct Observation. Being a re treatment patient was the only significant factor associated with recurrence, both for the entire study population and for those who were employed. Discussion The findings of this study are generalizable to other developing countries where challenges in implementation ofan effective TB programme such as poverty, high burden of HIV infection, a migrant population with strong rural ties and reliance on traditional practices to cure illness play a major role. Recommendations There is often no best treatment observer. Every case has to be individually evaluated and the most acceptable and accessible treatment observer chosen. The findings ofthis study strongly suggest that workplace Direct Obse ation can have a significant impact in improving TB treatment outcomes. / Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2008.