Thesis (PhD)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: Please refer to full text for abstract / AFRIKAANSE OPSOMMING: Sien volteks vir opsomming

An estimated 9 to 14 million persons in the United States have latent tuberculosis infection (LTBI) and are therefore at risk for progression to active disease. Diagnosis and treatment for LTBI has been identified by the Centers for Disease Control and Prevention (CDC) and the Institute of Medicine as a major strategy for elimination of tuberculosis (TB) in the U.S. Approximately 200,000 - 300,000 Americans are treated for LTBI each year. This dissertation investigates patient characteristics that are associated with LTBI treatment completion and assesses the impact of a peer-based experimental intervention on adherence to, and completion of, LTBI treatment. A review of the literature (Chapter 2) demonstrates that LTBI treatment completion rates in the U.S. and Canada generally fall below established targets and have been reported to range from 20 to 65% for a 6-month course of self-administered treatment. Associations between patient factors, clinic facilities, or treatment characteristics and adherence to LTBI treatment were found to be inconsistent across studies. Additionally, adherence interventions have been developed but no single intervention has shown consistent effectiveness. This suggests that a 'one-size-fits-all' approach to LTBI treatment adherence is not likely to succeed across all settings. The remainder of the dissertation focuses on predictors of LTBI treatment completion and the impact of a peer-based experimental intervention on adherence to, and completion of, LTBI treatment in two separate randomized controlled trials. Data for these analyses are drawn from two sequential randomized controlled trials designed to compare a peer-based intervention to usual care for ensuring completion of treatment for LTBI in an urban clinic setting: the Pathways to Completion Study (recruitment from 1996 through 2000) as well as from the Tuberculosis Adherence Partnership Alliance Study (TAPAS ) (recruitment from 2002 through 2005). Chapter 3 describes the change in demographic, social, and behavioral characteristics between the two study populations. The first analysis (Chapter 4) examines predictors of LTBI treatment completion in this population. Our results suggest that foreign birth, homelessness, marriage, and alcohol or drug use all influence completion of TLTBI through complex interactions. Overall, married persons had better completion rates, but married foreign-born patients were substantially more likely to complete therapy than unmarried foreign-born patients. Similarly, alcohol users were less likely to complete therapy, but homeless alcohol users were more likely to complete treatment than other homeless patients. The latter is probably an artifact of our clinic population, which includes patients from alcohol and substance abuse rehabilitation programs. Residence in such programs may have a positive effect on treatment completion. Race/ethnicity did not appear to be associated with treatment completion, although the differences between the two study populations made this difficult to assess. Following from this, an analysis of the effectiveness of a peer-based experimental intervention on adherence to, and completion of, LTBI treatment in two separate randomized controlled trials (Chapter 5) finds peer support experimental intervention to be very effective in the Pathways population but not in the TAPAS population where completion rates increased substantially for both the intervention and control groups. The power for detecting an intervention effect in TAPAS was reduced by the higher than expected completion rates in both groups; however, the effect of the TAPAS intervention is statistically significant in the adherence model. Adherence analysis in TAPAS suggests that it is important to intervene early in the treatment as the first two months of treatment present a danger period where patients tend to default treatment. The most common reasons reported for not adhering to treatment were forgot, ran out of medications, and other priorities. Identifying reasons for missing medications can suggest possible foci for interventions in the early months, such as weekly reminders to take the medications and ensuring that prescriptions are refilled on schedule. Taken together, the findings of this research have significant implications for improving adherence to and completion of LTBI treatment. Currently, the primary intervention for improving LTBI adherence consists of educational programs to increase knowledge and modify attitudes. Our findings suggest that tangible assistance would be more effective in encouraging treatment completion. Additionally, adherence analysis in TAPAS suggests that it is important to intervene early in the treatment. Close follow-up of patients during the first two months of treatment, with prompt intervention to encourage completion among those stopping treatment, may yield better outcomes and reduce costs over the long term.

Whole genome sequencing (WGS) is an attractive approach for mycobacteria diagnosis and epidemiological studies. It provides the potential for a rapid method that produces detailed information and could theoretically be used as a routine tool in clinical settings. This thesis focuses on the benefits and challenges involved in transforming molecular approaches into practical clinical mycobacteriology in general, and in particular WGS, as well as examining how it might be implemented. We first set out to improve the quantification of viable mycobacteria cells in vitro and make the molecular bacterial load assay (MBLA) sensitive enough to use in future clinical trials that monitor treatment response. The results showed the assay is rapid and accurate in its detection and count of viable bacteria. WGS was tested with different types of mycobacteria species to address different epidemiological questions. WGS not only provides a higher resolution result than traditional epidemiological methods but it can rapidly identify an outbreak, thus simplifying the investigation and reducing the cost. WGS accurately identified the sources of TB recurrence and could therefore have a potential role in determining the endpoints for clinical trials. Rapid genotyping of species in this way has been demonstrated in our studies. In addition, WGS has the ability to, in most circumstances, predict TB drug resistance. This could also prove very beneficial from a clinical standpoint. We used different approaches in our studies; for example, single nucleotide polymorphism threshold methods and the creation of a putative outbreak reference genome, which can be used in future outbreak investigations. WGS is a cost-effective, high-resolution method with a short turnaround. This makes it potentially usable as a routine tool in clinical settings and reference laboratories. Future studies are needed to improve the mycobacterial genome sequencing procedure, analysis and bioinformatics in order to implement WGS in clinical practice.

KwaZulu-Natal province records the highest number of tuberculosis cases diagnosed in the country, but less than 50% of these were cured in 2008, and fewer in those from rural areas and informal settlements where inadequate health care continues. HIV and AIDS associated tuberculosis frequently require labour-intensive methods of monitoring and combating for any success to be achieved. The socio-economic context wherein these diseases occur further limit their control. The low proportion of tuberculosis patients currently with successful treatment outcomes in Umgungundlovu Health District makes essential an in-depth investigation to establish the factors that are associated with these poor outcomes. This study investigates the factors affecting the current poor treatment outcomes in new patients with tuberculosis in a high disease burden district of KwaZulu-Natal in 2011. Methods A retrospective case-control study was conducted comprising 300 adult cases of tuberculosis who failed to complete 6 months of ambulant therapy and 300 frequency matched controls who completed therapy. A random sample of 15 primary health care clinics was selected from where consecutive cases and controls were selected with probability proportional to the number of tuberculosis patients seen at the clinic. Data was extracted from patient records and interviews. Processed data was analysed to identify risk associations using multivariate logistic regression. Results After adjusting for confounding statistically significant risk factors associated with poor tuberculosis treatment outcomes were unemployment (Odds Ratio (OR) 16.0; 95% CI: 6.7 to 37.8); living in a rural area (OR 14.3; 95% CI: 1.1 to 18), distance from home to clinic (OR 1.4; 95% CI: 1.3 to 1.6), living with HIV (OR 2.3; 95% CI: 1.1 to 4.7) and being very ill (OR -5.0; 95% CI: 2.1 to 11.9). Discussion The principal findings are that non-adherence to TB treatment is significantly associated with a number of non-health systems issues. Determinants of poor TB treatment outcomes in patients receiving six-month ambulatory care are diverse and multifactorial. After adjusting for confounding variables, unemployment, distance from patient home to the clinic, living with HIV and being very ill during TB therapy remained significantly associated with a poor TB treatment outcome. Conclusions Although determinants of poor tuberculosis treatment outcomes in patients receiving six-month ambulatory care are diverse and multifactorial, poor tuberculosis treatment outcomes are significantly associated with identifiable factors independent of the health system. Rigorous intervention strategies should prioritize at least these five major risk factors. Recommendations The TB control programme should go beyond the health systems issues to include inter-sectoral collaboration to address socio-economic and other non-health system barriers to adherence to TB treatment. Further research is recommended in this field. / Thesis (M.Med.Sc.)-University of KwaZulu-Natal, Durban, 2012.

Orientador: Helenice Bosco de Oliveira / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-06T00:26:46Z (GMT). No. of bitstreams: 1 Ferreira_EsterNogueiraWhyteAfonso_M.pdf: 5612471 bytes, checksum: 293938ba956e9881ed4b939f7fca47cd (MD5) Previous issue date: 2005 / Resumo: A distribuição geográfica da tuberculose tem forte relação com os indicadores socioeconômicos das diversas nações. Mesmo com os avanços no conhecimento e com a tecnologia disponível para seu controle, continua sendo grave problema mundial de saúde pública. Objetivo: Analisar a coorte de tratamento dos doentes inscritos no Programa de Controle da Tuberculose (PCT) na cidade de Campinas-SP, em 2003. Métodos: Foram analisados, segundo variáveis demográficas, clínicas e epidemiológicas, 494 doentes de uma coorte de 537 notificados no Sistema de Informação Nacional de Agravos de Notificação. Para determinar as diferenças entre as proporções e calcular as razões de chances (OR) foi utilizado o software Epi 1nfo versão 6. O valor de p foi considerado significativo quando inferior a 0,05. Resultados: Do total de doentes analisados 76,3% eram residentes no município de Campinas. O percentual de casos com a co-morbidade TB/Aids foi de 21,2% para os residentes em Campinas e de 24,8% para os residentes em outros municípios. O risco de adoecer por tuberculose em Campinas foi maior na área com piores níveis socioeconômicos. O sucesso de tratamento do grupo de doentes residentes em Campinas foi de 76,4% entre os que não apresentaram Aids e de apenas 48,8% naqueles com Aids. Os pacientes da forma clínica pulmonar com baciloscopia positiva apresentaram sucesso de 70%. O grupo constituído por pacientes que estavam em retratamento apresentou 2,1 vezes mais insucesso de tratamento comparado aos casos novos (OR = 2,14; IC 1,12 - 4,05). Entre aqueles pacientes com a co-morbidade TB/Aids a chance de insucessotambém foi maior (OR = 3,41; 1C 1,98 - 5,89). A proporção de tratamentos supervisionados foi de 35%. Conclusões: A efetividade do PCT de Campinas apresentou-se abaixo dos 85% proposto pela OMS em todas as estratificações estudadas e a incidência parece estar subdimensionada perante a baixa cobertura de baciloscopias de escarro (43,3%) nos sintomáticos respiratórios, sugerindo problemas na operacionalização do PCT de Campinas. Para melhorar o programa as atividades de busca de casos e as estratégias que asseguram a adesão ao tratamento, incluindo o tratamento supervisionado, devem ser aprimoradas / Abstract: The geographic distribution of tuberculosis has a strong relationship with socioeconomic indicators of different nations. Even with advances in knowledge and available technology for its control, it continues to be a serious worldwide public health problem. Objective: To analyze the treatment cohort of patients enrolled in the Tuberculosis Control Program (TCP) in the city of Campinas, SP, in 2003. Methods: In accordance with demographic, clinical and epidemiological variables, 494 patients IToma 537 cohort, who were notified by the National Disease Reporting Information System, were analyzed. In order to determine the differences among proportions and calculate the odds ratio (aR) the Epi Info version 6 software was used. A p value of less than 0.05 was considered significant. Results: Of the total patients analyzed, 76.3% were resident in the city of Campinas. The percentage of cases with TB/AIDS comorbidity for Campinas residents was 21.2% and for the residents in other cities, 24.8%. The risk for tuberculosis was higher in the areas with worse socioeconomic levels. The successful outcome for the treatment of the group of patients resident in Campinas was 76.4% among those who did not present Aids and only 48.8% for those who presented Aids. Patients with positive baciloscopy presented a success rate of 70%.The group of patients being retreated had a 2.1 times higher rate of unsuccessful treatment when compared to new cases (aR = 2.14; CI = 1.12 - 4.05). Among those patients with the TB/Aids comorbidity the chance of no unsuccessful was also higher (aR = 3.41; IC = 1.98 - 5.89). The proportion of supervised treatment was 35%. Conclusions: The effectiveness of the TCP in Campinas was below the 85% proposed by the WHO in all of the studies strata and the incidence seems to be underdimensioned in face of the low sputum bacilloscopy coverage (43.3%) of those presenting respiratory disease symptoms, which suggests problems in the TCP operation in Campinas. In order to improve the ~program, the activities of case search and supervised treatment should be enhanced. / Mestrado / Saude Coletiva / Mestre em Saude Coletiva

Magister Public Health - MPH / Background: Tuberculosis (TB) in the majority of cases is a curable disease requiring prolonged treatment of six months. The World Health Organisation (WHO) recommends the Direct Observation Treatment Short course (DOTS) strategy as the approach to control TB. Despite such interventions, defaulting from TB treatment is still a major problem among TB patients at Botšabelo Clinic in Maseru. This research aimed to describe knowledge, attitudes and perceptions to TB as a disease and its treatment among non-adherent and adherent at Botšabelo Clinic in the Maseru district of Lesotho, in order to identify contributing factors related to defaulting treatment. Study design: A cross-sectional descriptive study was conducted. Population and sampling: TB non-adherent and adherent registered at Botšabelo Clinic in 2007 were included in the study. Simple random sampling was used to select both non-adherent and adherent. Data collection: Data were collected by means of a structured questionnaire. Data analysis: Epi-Info Version 3.4.3 was used for data analysis. Descriptive statistics were calculated using frequencies, means and percentages for socio-demographic information, knowledge, attitudes and perceptions. A p-value of less than 0.05 was accepted as being statistically significant in all statistical tests. Results: The total number of respondents who were interviewed in this study was 283. 131(46%) were non-adherent and 152 (54%) were adherent. Non-adherent and adherent showed good knowledge of symptoms, prevention and transmission of TB. They were also knowledgeable about duration of treatment. 98% non-adherent and 100% adherent knew that TB is curable. 93% non-adherent and 93% adherent visited a health facility when TB symptoms occurred. Less than half of the respondents (47% non-adherent and 47% adherent) smoked. 47% non-adherent 43% adherent drank alcohol. Many non-adherent and adherent experienced support from the community. A large number mentioned that TB did not affect their marriage negatively. Conclusion: Non-adherent and adherent showed good knowledge of symptoms, prevention, disease transmission and definition of TB. Even though many could define TB, there were misconceptions that TB is caused by poison. Therefore, there is a need to strengthen health education on TB among communities. They were also knowledgeable that TB is curable and many could define DOT. Their attitudes and perceptions towards TB as a disease were positive. Many (93%) of those who were diagnosed with TB went to a health facility for treatment, while others sought it from traditional healers. Less than half of non-adherent and adherent delayed seeking treatment. A considerable number of non-adherent and adherent were heavy smokers. Alcohol intake was moderate among both groups. Media was reported as the main source of TB information in this study. Side effects to medication were the most reported deterrent to treatment among non-adherent. The side effect with the highest frequency was vomiting. It was followed by nausea and skin rash. Socio-economic factors that determined treatment were access to health services, long distance to the clinic, lack of transport and lack of funds and personal habits like smoking and alcohol abuse. Delay in seeking treatment was found to be a problem in this study. There was no difference found between knowledge attitude and perceptions of non-adherents and adherents.

Thesis (MPH.) -- University of Limpopo, 2022 / Background: Tuberculosis(TB) and Human Immunodeficiency virus(HIV) continues to be a public health concern globally. There is no data on TB outcomes on HIV programme outcome in Lebowakgomo hospital of Limpopo Province. The main objective of this study was to determine the TB treatment outcomes in TB/HIV co-infected people at Lebowakgomo hospital in Limpopo Province. Methodology: A quantitative retrospective design was used in the study in which a sample size of 180 patients’s files who are 18 years and above and TB/HIV co-infected were reviewed. A self-designed data collection tool was used to collect data. The tool covered variables such as age, gender, HIV status, CD4 cell count, type TB, duration on TB treatment and the outcome. Data was analysed using the STATA statistical software version 12 for Windows (STATA Corporation, College Station, Texas). Results: The majority of records were age group 35-44 years at 32%. There was a statistical significance differences (p˂0.001) between males and females in relation to age groups. TB treatment success rate was 68.9% and mortality 16.9%. Females were more likely to complete TB treatment successfully than males. Overall age, gender, previous TB infections, TB type, duration on ART and CD4 Count were not significantly associated with treatment outcomes amongst TB/HIV co-infected people. Conclusion: This study has revealed that TB treatment success rate in HIV co-infected is lower (68.3%) than the WHO target of 85%.

Thesis (MScMedSc)--University of Stellenbosch, 2011. / ENGLISH ABSTRACT: Isoniazid forms part of the first line anti-tuberculosis therapy and it is generally used to treat latent Mycobacterium tuberculosis infection. Isoniazid inhibits synthesis of long chain mycolic acids found in cell wall of Mycobacterium tuberculosis, which have proven vital for the survival of the bacterium. Mycolic acids are primarily synthesized by the fatty acid synthase enzyme (FAS) system found in mycobacteria as the FAS-I and FAS-II complex. Isoniazid kills the bacteria by blocking the FAS-II complex, required for extension of mycolates. It does this by entering the tubercle bacilli as a prodrug where isoniazid becomes activated by catalase peroxidase encoded by katG gene. The activated isoniazid then forms a complex with NAD+ which targets InhA (NADH-dependent enoyl-acyl carrier protein reductase) located in the FAS-II complex. Loss of catalase peroxidase, due to gene mutations or a complete katG gene deletion is one of the primary mechanisms conferring resistance to INH in Mycobacterium tuberculosis. In addition, four other genes (inhA, KasA, ndh and ahpC) are also associated with INH resistance. Nonetheless, mutations in these five genes are present in only 70-80% of INH resistant clinical isolates, implying that other mechanisms are involved in resistance of Mycobacterium tuberculosis to isoniazid. This study aims to quantify the expression level of genes induced by isoniazid in the mycolic acid pathway and drug transport in two closely related Mycobacterium tuberculosis Beijing cluster 208 isolates. These are the fully susceptible (K636) and isoniazid mono-resistance strains (R55), with minimum inhibitory concentrations of 0.1 and 4 µg/ml, respectively. Both these isolate had no isoniazid gene associated mutations. The isolates were cultured in the presence and absence of 0.1µg/ml isoniazid for 24 hours after which RNA was extracted followed by QRT-PCR analysis to identify differentially expressed genes. This result has shown that various genes were differentially expressed in response to low level INH exposure. The most significant up-regulation was observed in genes (acpM, fabD, Accd6 and fbpC) encoding the FAS-II complex and genes (efpA, iniA, iniB, and mmpl7) involved in drug transport. In addition, two genes (ndh and fbpC) were significantly down-regulated in the isoniazid mono-resistant isolate. Based on these findings, we propose a model whereby isoniazid exposure in the susceptible isolate inhibits FAS-II complex and with its associated accumulation in mycolates kills the bacterium. In contrast, we propose that in the resistance isolate the bacterium acquires additional resistance by the activation of efflux pumps in combination with disruption in INH-NAD+ complex formation that protect inhibition of InhA located in FAS-II complex. / AFRIKAANSE OPSOMMING: Isoniasied vorm deel van die eerste linie van behandeling teen tuberkulose en word algemeen gebruik om latente Mycobacterium tuberculosis infeksie te behandel. Isoniasied inhibeer die sintese van langketting mikolitiese sure wat in die selwand van Mycobacterium tuberculosis voorkom. Dit is bewys dat hierdie sure essensieel is vir die oorlewing van die bakterie. Mikolitiese sure word hoofsaaklik gesintetiseer deur die vetsuur sintase ensiem (FAS) sisteem wat in mikobakteriee voorkom as die FAS-I en FAS-II komplekse. Isoniasied dood die bakteriee deur die FAS-II kompleks, wat nodig is om die verlenging van mikoliete, te blokkeer. Dit word bewerkstellig deurdat 'n pro-vorm van die middel die tuberkulose bacilli binnedring, waarna isoniasied geaktiveer word deur katalase peroksidase, wat deur die katG geen geenkodeer word. Die geaktiveerde isoniasied vorm 'n kompleks met NAD+, wat InhA (NADH-afhanklike eno.asiel draer prote.enreduktase), gelee in die FAS-II kompleks teiken. Een van die primere meganismes wat weerstandigheid teen isoniasied bewerkstellig, is die verlies van katalase peroksidase weens geenmutasies of algehele delesie van die katG geen. 'n verdere vier gene (inhA, kasA, ndh en ahpC) word ook verbind met isoniasied weerstandigheid. Nietemin is mutasies in hierdie vyf gene teenwoordig in slegs 70-80% van isoniasied weerstandige kliniese isolate, wat impliseer dat ander meganismes ook betrokke is in die weerstandigheid van Mycobacterium tuberculosis teen isoniasied. Die doel van hierdie studie is om die vlak van uitdrukking van gene wat deur isoniasied in die mikolitiese suur biochemiese pad geïnduseer word, asook middel transport te kwantifiseer in twee naby verwante Mycobacterium tuberculosis isolate van Beijing groep 208. Die twee isolate is die volledig sensitiewe (K636) en isoniasied monoweerstandige (R55), met minimum inhiberende konsentrasies van onderskeidelik 0.1 en 4µg/ml. Mutasies wat geassosieer word met isoniasied weerstandigheid was afwesig in beide die isolate. Kulture is van die isolate gemaak met en sonder 0.1µg/ml isoniasied vir 24 uur, waarna RNA geekstraeer is deur middel van QRT-PCR analise om gene te identifiseer wat verskillend uitgedruk word. Die resultate toon dat verskeie gene verskillend uitgedruk is in reaksie op laevlak isoniasied blootstelling. Die mees prominente opregulering is waargeneem in die gene (acpM, fabD, accd6 en fbpC) wat die FAS-II kompleks enkodeer, asook die gene (efpA, iniA, iniB en mmpl7) wat betrokke is in middel transport. Beduidende afregulering van 'n verdere twee gene in die isoniasied monoweerstandige isolate, naamlik ndh en fbpC is waargeneem. Op grond van hierdie waarnemings, stel ons 'n model voor waarvolgens isoniasied blootstelling in die sensitiewe isolaat die FAS-II kompleks inhibeer, en met die gevolglike akkumulasie van mikoliete, dood dit die bakterium. In teenstelling stel ons voor dat addisionele weerstandigheid bekom word in die weerstandige isolaat deur die aktivering van uitvloeipompe, in kombinasie met die ontwrigting van die INH-NAD+ kompleksvorming wat die inhibisie van InhA binne die FAS-II kompleks beskerm.

The study seeks to identify factors affecting compliance to TB treatment and determine those that make some patients complete TB treatment in Andara district, Kavango region in Namibia. The self-efficacy model by Shortridge-Baggett and Van der Bijl (1996) was the conceptual framework which guided this study. A quantitative, cross-sectional, descriptive and comparative study design was used. Data was collected using a structured questionnaire administered by a registered nurse. A total of 49 respondents were interviewed: (23 compliant and 26 non-compliant). Informed consent was obtained from each respondent prior to data collection. SPSS and MS Excel were used to analyse data and describe differences between the two groups. Respondents (N=26) gave „feeling better‟ 7 (27%), „distance‟ 8 (31%), „lack of family support‟ 4 (15%), no food 2 (8%), side effects 2 (8%), other reasons 2 (8%) and medicines not working 1 (4%), as their reasons for not completing treatment. However, long waiting times at the clinic, non availability of food and lack of knowledge of TB or treatment are the significant factors contributing to non-compliance. / Health Studies / M.A. (Public Health)

Submitted in fulfilment of the requirements of the Degree of Master of Technology: Environmental Health, Durban University of Technology, 2011. / Worldwide Tuberculosis (TB) is a major public health concern. The Directly Observed Treatment Strategy (DOTS) has been used widely internationally and in South Africa (SA) to control the disease yet defaulting on treatment has still not achieved its World Health Organization (WHO) guideline of 5.0%. The eThekwini Municipality reported a defaulter rate of 18.9% in 2007 even with the adoption of DOTS in 1996. This study aimed to investigate the predictors of default amongst informal dwellers of eThekwini and to evaluate the implementation and the efficiency of the DOTS programme within the eThekwini Municipality, KwaZulu-Natal (KZN), and SA. The study population comprised of 102 defaulters from informal settlement, 16 nurses and 5 health personnel that are involved in TB management and control. The study was a mixed method cross sectional descriptive study that generated both quantitative and qualitative data. The Cyril Zulu Communicable Disease Centre (CDC) Electronic TB Register was used to trace the defaulters from the informal settlements that were interviewed. Non-defaulters were matched from the CDC Electronic TB Register but could not be traced due to accessibility and financial issues. Due to the low response from nurses 16(53%), semi structured qualitative interviews were conducted with health personnel. The three sets of data generated were analysed using descriptive statistics and content analysis. Multivariate logistic regression models found smoking, drinking and having a family member with TB as statistical significant predictors of default. Based on the multivariate model with a 95% confidence interval (CI), smoking (OR: 11.23, CI: 5.79, 21.78; p<0.005), alcohol consumption (OR: 15.22; CI: 7.66, 30.25; p<0.005) and had family member with TB (OR: 4.60, CI: 2.34, 9.04; p<0.005) were all significantly associated with defaulting. It was apparent that DOTS implementation was partly implemented due to lack of human resources. Tracing of defaulters, DOTS supporters, DOTS sites and incentives to patients and volunteers were major challenges hindering the iv effective implementation of the DOTS programme in eThekwini. Defaulting occurs as a result of an association between patient and health care characteristics. This study provides useful information specific to predictors of default amongst informal dwellers and the implementation and efficiency of the DOTS programme specific to informal settlements. The results from this study could be used to improve TB control and management specifically in informal settlements addressing factors that predict default and tracing and supporting patients to ensure adherence to TB treatment. / DUT Finance