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.

Thesis (PhD)--Stellenbosch University, 2013. / ENGLISH ABSTRACT: This thesis focused on the provision of economic support to improve the outcomes of patients on TB treatment. Although the association between poverty and tuberculosis is generally acknowledged, there is little evidence to guide the use of economic interventions to improve tuberculosis control. In South Africa, a high burden country with extensive poverty, such evidence is particularly important. The first part of this thesis is a Cochrane systematic review of evidence from randomized controlled trials regarding the effectiveness of economic support among patients with tuberculosis. Eleven trials were included: ten conducted among marginalised groups in the United States on economic support for people on prophylactic treatment for latent TB; and one from Timor-Leste on economic support for patients with active TB. The review found that the use of economic interventions in patients with latent TB may increase the return rate for reading tuberculin skin test results, probably improves clinic re-attendance for initiation or continuation of prophylaxis and may improve completion of prophylaxis, compared to normal care. However, it is uncertain if economic support improves treatment completion in patients with active TB (low quality evidence). The second part of the thesis reports the findings of a pragmatic, cluster randomized controlled trial to evaluate the feasibility and effectiveness of delivering economic support to patients on treatment for active TB in South Africa. Patients with drug sensitive pulmonary TB were offered a monthly voucher valued at ZAR120 until completion of treatment or a maximum of eight months. Patients in control clinics received usual TB care. A parallel process evaluation provided contextual information to explain the trial findings. The qualitative component of this evaluation consisted of in-depth interviews with a sample of trial participants, including patients, nurses and health managers, to assess responses to the voucher and its administration. The quantitative component included a survey of patients’ household expenditure to assess patients’ levels of poverty and the effects of the voucher on these, and an analysis of the goods on which patients spent their vouchers. 4091 patients were included in the trial: 1984 in the control arm (10 clinics) and 2107 in the intervention arm (10 clinics). Intention to treat analysis showed a small but non-significant improvement in treatment success rates in intervention clinics (intervention 76.2%; control 70.7%; risk difference 5.6% (-1.2; 12.3%), p = 0.107). Fidelity to the intervention was low, partly because nurses preferred to issue vouchers based on perceived financial need, rather than on eligibility. Logistical difficulties in delivering vouchers to clinics also undermined fidelity. The vouchers did not significantly increase patients’ household expenditure, but were experienced by patients as helpful, especially in providing more food with which to take their tablets. Factors related to the administration of economic support may undermine its effectiveness in improving TB treatment outcomes. Further research is needed to explore how best to deliver such economic support to those eligible to receive it, particularly in low and middle income countries where the burden of tuberculosis is highest. / AFRIKAANSE OPSOMMING: Hierdie tesis was toegespits op die verlening van ekonomiese steun om die uitkomste van pasiënte op tuberkulose- (TB-) behandeling te verbeter. Hoewel die verband tussen armoede en TB in die algemeen erken word, is daar nie veel bewyse om die gebruik van ekonomiese intervensies ter verbetering van TB-beheer te staaf nie. In Suid-Afrika – ’n land met ’n hoë TB-las en wydverspreide armoede – is sulke bewyse veral belangrik. Die eerste deel van hierdie tesis behels ’n sistematiese Cochrane-oorweging van bewysmateriaal afkomstig van verewekansigde, gekontroleerde proewe oor die doeltreffendheid van ekonomiese steun aan pasiënte met tuberkulose. Altesame 11 proewe is ingesluit: Tien is gedoen onder gemarginaliseerde groepe in die Verenigde State met die fokus op ekonomiese ondersteuning aan mense wat profilaktiese behandeling vir latente TB ontvang het. Een, van Timor-Leste, was gefokus op ekonomiese ondersteuning aan pasiënte met aktiewe tuberkulose. Die ondersoek het aan die lig gebring dat, vergeleke met normale sorg, die gebruik van ekonomiese intervensies by pasiënte met latente tuberkulose tog die omdraaikoers vir die lees van tuberkulien-veltoetsresultate kan verhoog, waarskynlik hertoelating tot klinieke vir die inisiëring of voortsetting van profilakse verbeter, en die voltooiing van profilakse kan verbeter. Die tweede gedeelte van die tesis behels ’n verslag oor die bevindings van ’n pragmatiese, trosverewekansigde gekontroleerde proef, om te bepaal hoe doenlik en doeltreffend dit sou wees om ekonomiese steun te verleen aan pasiënte wat in Suid-Afrika vir aktiewe tuberkulose behandel word. Pasiënte met middelsensitiewe pulmonêre tuberkulose het tot en met die voltooiing van hul behandeling, of tot ’n maksimum van agt maande, ’n maandelikse koopbewys ter waarde van ZAR120 ontvang. Pasiënte in kontroleklinieke het die gewone TB-sorg ontvang. ’n Parallelle prosesevaluering het kontekstuele inligting voorsien ter verklaring van die bevindinge van die proef. Die kwalitatiewe komponent van hierdie evaluering het bestaan uit diepte-onderhoude met ’n steekproef van alle deelnemers aan die proefneming, insluitend pasiënte, verpleegpersoneel en gesondheidsbestuurders, om hul reaksies te bepaal op die koopbewys self sowel as op die administrasie daarvan. Die kwantitatiewe komponent het ’n opname oor pasiënte se huishoudelike besteding ingesluit, ter vasstelling van hul armoedevlak en die moontlike uitwerking van die koopbewys daarop, asook ’n ontleding van die goedere waarop pasiënte hul koopbewyse bestee het. Altesame 4 091 pasiënte is by die proef ingesluit – 1 984 in die kontrole-afdeling (10 klinieke) en 2 107 in die intervensie-afdeling (10 klinieke). ’n Voorneme-om-te-behandel- (ITT-) ontleding toon ’n klein dog nie-betekenisvolle verbetering in behandelingsuksessyfers in intervensieklinieke (intervensie 76,2%; kontrole 70,7%; risikoverskil 5,6% (-1,2; 12,3%), p = 0.107). Getrouheid aan die intervensie was laag – deels omdat verpleegkundiges verkies het om die koopbewyse op grond van veronderstelde finansiële behoeftigheid eerder as volgens die studiekriteria uit te deel. Die koopbewyse het nie pasiënte se huishoudelike besteding beduidend verhoog nie, maar pasiënte het dit wél as nuttig ervaar, veral omdat hulle daarmee meer kos kon koop om saam met hul pille in te neem. Faktore wat verband hou met die administrasie van ekonomiese ondersteuning kan die doeltreffendheid van sodanige steun in die verbetering van TB-behandelingsuitkomste ondermyn. Verdere navorsing word vereis om te verken wat die beste manier sou wees om sodanige ekonomiese steun te bied aan diegene wat daarvoor in aanmerking kom, veral in lae- en middel-inkomstelande, waar die TB-las die hoogste is.

Text in English with questionnaire in Amharic / Purpose: The purpose of the study was to evaluate the effectiveness of the tuberculosis directly observed treatment, short-course (DOTS) strategy with respect to patient centeredness and satisfaction, and propose a model in support of the DOTS strategy in Addis Ababa, Ethiopia. Method: The study was conducted in Addis Ababa, Ethiopia using a mixed-method approach. An interviewer-administered questionnaire was used to collect quantitative data from 601 randomly selected TB patients who were on TB treatment followup in 30 health facilities.Three focus group discussions were conducted with 23 TB experts purposefully selected from 10 sub-city health offices and health bureau. Moreover, telephonic interviews were conducted with 25 defaulted TB patients who had been attending TB treatment in the health facilities. The quantitative data were described using mean, median, percentage and frequencies. Logistic regression and exploratory factor analysis were used to extract associated factors using SPSS version 21 software. Thematic analysis was used for qualitative data analysis. Deductive and inductive reasoning was used to propose a descriptive model with substantiating literatures. Findings: Of the 601 TB patients included, 40% of them perceived they had not received a patient-centred TB care (PC-TB care) with DOTS strategy. Gender (AOR=0.45, 95%CI 0.3, 0.7), good communication (AOR=3.2, 95%CI 1.6, 6.1), treatment supporter (AOR=3.4, 95%CI 2.1, 5.5) were associated with the perceived PC-TB care. Thirty-seven percent of TB patients were following their TB treatment with feeling of dissatisfaction with DOTS strategy. Gender (AOR=2.2; 95%CI 1.3, 3.57), place of residence (AOR=3.4; 95%CI 1.6, 7.6), presence of symptoms (AOR=0.6, 95%CI 0.40, 0.94) and treatment-supporter (AOR=4.3, 95%CI 2.7, 6.8) were associated with satisfaction of TB patients. TB experts and defaulted TB patients pointed out that DOTS strategy is not providing comprehensive PC-TB care except the provision of facility choice where to follow during initiation of the treatment. DOTS delivery system inflexibility, loose integration, HCPs’ characteristic, communication skill and motivation and the community awareness were explored factor with patient centeredness of DOTS. DOTS delivery system, incompatible of diagnosis and patient beliefs were the identified categories to default. The proposed PC-TB care model core constructs are patient, community, health care providers, health care organisation and TB care delivery system. The core constructs are directed by policy and monitoring and evaluation components. Conclusion: DOTS strategy is limited to provide fully integrated PC-TB care and did not provide full satisfaction to TB patients. Therefore, a support that makes the TB care patient-centred are important and the proposed PC-TB care model needs to be tested, practiced and evaluated for its performance toward increments of patient centeredness of TB care. / Health Studies / D.Litt. et Phil. (Health Studies)