Background: IPT is an effective, safe and feasible disease prevention scheme that should be administered for all PLHIV living in areas with high latent TB prevalence. Objective: To assess the impact of isoniazid in the incidence of tuberculosis among HIV infected individuals in Addis Ababa. Methods: A case control study design was undertaken among 489 HIV and TB infected patients in Addis Ababa from January 2008 to December 2010. Results: Tuberculosis incidence rate among those who developed TB after completing 6-9 month isoniazid preventative therapy was17.14 PYO compared to 10.28 PYO among those who were not. Isonizide reduced the chance of developing tuberculosis among HIV infected patients (OR= 0.072; 95% CI 0.044, 0.12). Age (AOR= 0.14; 95% CI 0.03, 0.97) and sex (AOR= 1.86; 95% CI 1.02, 2.23) of the patient, CD4 count at HIV diagnosis (AOR= 0.21; 95% CI 0.13, 0.31), clinical stage of HIV illness (AOR= 1.22; 95% CI 1.09, 1.84) and past tuberculosis history (AOR = 1.97; 95% CI 1.24, 3.67) were major factors associated with tuberculosis incidence. Conclusions: INH prophylaxis was associated with lower incidence of tuberculosis among PLHIV. / Health Studies / M. Public Health

Background: IPT is an effective, safe and feasible disease prevention scheme that should be administered for all PLHIV living in areas with high latent TB prevalence. Objective: To assess the impact of isoniazid in the incidence of tuberculosis among HIV infected individuals in Addis Ababa. Methods: A case control study design was undertaken among 489 HIV and TB infected patients in Addis Ababa from January 2008 to December 2010. Results: Tuberculosis incidence rate among those who developed TB after completing 6-9 month isoniazid preventative therapy was17.14 PYO compared to 10.28 PYO among those who were not. Isonizide reduced the chance of developing tuberculosis among HIV infected patients (OR= 0.072; 95% CI 0.044, 0.12). Age (AOR= 0.14; 95% CI 0.03, 0.97) and sex (AOR= 1.86; 95% CI 1.02, 2.23) of the patient, CD4 count at HIV diagnosis (AOR= 0.21; 95% CI 0.13, 0.31), clinical stage of HIV illness (AOR= 1.22; 95% CI 1.09, 1.84) and past tuberculosis history (AOR = 1.97; 95% CI 1.24, 3.67) were major factors associated with tuberculosis incidence. Conclusions: INH prophylaxis was associated with lower incidence of tuberculosis among PLHIV. / Health Studies / M. Public Health

PURPOSE: The purpose of this study was to assess factors associated with the development of drug resistant tuberculosis in Ethiopia. DESIGN: A quantitative case-control study was conducted to determine if there were any significant differences in prevalence of pre-defined factors between cases and controls. METHODS: Cases were patients with drug resistant tuberculosis who had a confirmed diagnosis by culture drug-susceptibility or gene expert tests. Successfully treated, tuberculosis symptom free patients who had been on first-line tuberculosis treatment and who were registered as cured or treatment completed were taken as controls. An equal number of cases (N=181) and controls (N=181) was selected using a systematic random sampling method and was used in the study. A structured questionnaire developed by the researcher was used to collect data. Odds ratio and multiple logistic regression were used to quantify the strength of association between dependent and independent variables. RESULTS: The development of drug resistant tuberculosis was significantly associated with two or more previous episodes of tuberculosis illness (adjusted odds ratio (AOR): 14.84; 95% CI 8.90 –24.75), previous first-line tuberculosis treatment not directly observed by a health worker for 7 to 8 weeks (AOR: 13.41; 95% CI 8.06 – 22.29) and previous first-line tuberculosis treatment outcome of failure (AOR: 39.19; 95% CI 12.05 -127.46). Interruption of first-line tuberculosis treatment for one day or more (AOR = 4.28; 95% CI 2.76 – 6.64) and history of treatment in the first-line tuberculosis treatment category for previously treated patients (AOR: 3.70; 95% CI 2.40 – 5.72) were also significantly associated with the development of drug resistant tuberculosis in the current study. CONCLUSION: Patients with a history of previous first-line tuberculosis treatment, patients who interrupted previous first-line tuberculosis treatment and patients with previous first-line tuberculosis treatment outcome of failure were at high risk of developing drug resistant tuberculosis. Therefore, the full course of first-line tuberculosis treatment should be given, following the Directly Observed Treatment (DOT) guide. Patients with recurrent tuberculosis and unfavourable first-line tuberculosis treatment outcome should be tested for drug susceptibility. / Health Studies / D. Litt. et Phil. (Health Studies)

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)

This study assessed implementation status of collaborative TB/HIV services in Addis Ababa City Administration aiming to promote better implementation strategies. The study employed mixed research methods and was descriptive. The study design used both quantitative and qualitative data using structured questionnaires and semi-structured interview guides, respectively. The study population for the quantitative design included 1,683 TB/HIV patients from 10 conveniently selected health facilities: Zewditu and Menelik Hospitals, health centres of Lideta, Yeka, Kazanchis, NifaSilk-Lafto-No1, Woreda-7, Kality, Bole and Gulele. All the patients who were on their follow-up cares during the data collection period were interviewed. Participants for qualitative design were 1,650 TB/HIV patients for short answered questions; 8 FGDs among patients; interview of 10 TB/HIV care facility coordinators/health workers and one regional TB/HIV care coordinator, all purposively selected. Quantitative data was analysed using SPSS 15.0, while qualitative data were thematically analysed manually. Majority of HIV patients (92.8%) self-reported that they had been screened for TB; of which, 11.2% were diagnosed for active TB during their follow-up cares. Whereas, 87.1% of TB patients had been offered for HIV test; 79.8% tested; 20.2% tested positive. Knowledge on TB and HIV diseases, transmission and prevention was found to be low. However, participants appreciated the support of the healthcare delivery system in improving their health. Collaborative TB/HIV activities brought additional on-the-job training for healthcare workers; improved flow of logistics and re-arrangement of infrastructures of facilities. The study revealed that, implementation of collaborative TB/HIV activities in Addis Ababa need boosting. The study recommends the need for coordinated efforts of all stakeholders for improving implementation of collaborative TB/HIV care services, as identified by this study. The contribution of this study developed pocket-guide for healthcare workers on collaborative TB/HIV care services, which provides guidance in promoting better TB/HIV care / Health Studies / D. Litt. et Phil. (Health Studies)

This quantitative, descriptive study investigated risk factors for MDR-TB in Addis Ababa, Ethiopia. A total of 439 medical records belonging to MDR-TB and non MDR-TB patients managed in public health centres from January 2008 to December 2011 were analysed. Data were transcribed from each TB patient‟s medical records using a specifically designed checklist. The findings revealed that male gender, previous history of TB treatment, poor treatment adherence, an outcome of failure after TB re-treatment, previous category of failure, pulmonary involvement of TB infection and HIV infection were associated with MDR-TB. The findings illustrate that efforts should be made to prioritise the development and implementation of effective MDR TB screening and treatment protocols for these high risk groups to improve treatment outcome and minimize the emergence of XDR TB. / Health Studies / M. Public Health

This quantitative, descriptive study investigated risk factors for MDR-TB in Addis Ababa, Ethiopia. A total of 439 medical records belonging to MDR-TB and non MDR-TB patients managed in public health centres from January 2008 to December 2011 were analysed. Data were transcribed from each TB patient‟s medical records using a specifically designed checklist. The findings revealed that male gender, previous history of TB treatment, poor treatment adherence, an outcome of failure after TB re-treatment, previous category of failure, pulmonary involvement of TB infection and HIV infection were associated with MDR-TB. The findings illustrate that efforts should be made to prioritise the development and implementation of effective MDR TB screening and treatment protocols for these high risk groups to improve treatment outcome and minimize the emergence of XDR TB. / Health Studies / M.A. (Public Health)

Purpose: The purpose of this study is to assess risk factors associated with TB co-infection in HIV/AIDS patients taking antiretroviral therapy (ART). Methodology: An observational, analytic, case-control and quantitative study was conducted on a randomly selected 367 HIV and AIDS patients of whom 92 of them were TB co-infected. Data collection was done by using self-structured questionnaire. Result: In this study, educational status, waste disposal system, monthly income, contact history with a patient of active tuberculosis or presence of a family member with active tuberculosis, drug adherence, knowledge on tuberculosis prevention and history of exposure to substance were factors independently associated with the occurrence of active tuberculosis among HIV and Aids patients taking ART. Conclusion: The findings highlight the need for on-going educational, informational and other interventions to address the risk factors of tuberculosis in HIV and Aids patients in order to decrease the rate of TB co-infection / 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).

Purpose: The purpose of this study is to assess risk factors associated with TB co-infection in HIV/AIDS patients taking antiretroviral therapy (ART). Methodology: An observational, analytic, case-control and quantitative study was conducted on a randomly selected 367 HIV and AIDS patients of whom 92 of them were TB co-infected. Data collection was done by using self-structured questionnaire. Result: In this study, educational status, waste disposal system, monthly income, contact history with a patient of active tuberculosis or presence of a family member with active tuberculosis, drug adherence, knowledge on tuberculosis prevention and history of exposure to substance were factors independently associated with the occurrence of active tuberculosis among HIV and Aids patients taking ART. Conclusion: The findings highlight the need for on-going educational, informational and other interventions to address the risk factors of tuberculosis in HIV and Aids patients in order to decrease the rate of TB co-infection / Health Studies / M.A. Public Health