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)

Thesis (M.P.H.)--University of Texas Health Science Center at Houston, School of Public Health, 2008. / Source: Masters Abstracts International, Volume: 46-05, page: 2665. Adviser: Tommy C. Douglas. Includes bibliographical references.

Magister Pharmaceuticae - Mpharm / Many studies have investigated the pharmacokinetics (PK) of anti-tuberculosis drugs in tuberculosis patients. However, currently in South Africa, no studies have been done on ethionamide (ETH) PK in adult MDR-TB patients that are infected with HIV and those without HIV infection. Therefore, the objective of this current study was firstly, to find out ethionamide plasma concentration using the LC-MS method; secondly, to evaluate and compare the pharmacokinetics of ethionamide in MDR-TB patients infected with and without HIV infection; thirdly, to examine the effects of ARVs and kidney impairment on the PK of ethionamide and fourthly, to find out the consequence of sex and age on ETH PK parameters.

nÃo hà / Baixos nÃveis sangÃÃneos de drogas antituberculose podem ser causa de resistÃncia do Mycobacterium tuberculosis. Este estudo objetivou avaliar a absorÃÃo intestinal transcelular e paracelular e verificar possÃvel repercussÃo nas concentra-ÃÃes sÃricas de de rifampicina (RMP) e isoniazida (INH) em pacientes com tuberculose multirresistente (TBMR). Realizou-se estudo caso-controle no AmbulatÃrio de Tisiologia do Hospital de Messejana, em Fortaleza-CearÃ, entre agosto de 2006 e abril de 2007. TBMR foi definida como o caso de portador de bacilo resistente a pelo menos RMP+INH, de acordo com o teste de sensibilidade realizado pelo mÃtodo das proporÃÃes. Foram formados dois grupos para controle, o dos portadores de tuberculose sensÃvel (TBS) e o dos voluntÃrios sÃos (VS). Realizaram-se exames hematolÃgicos e bioquÃmicos, o teste da lactulose / manitol (L/M) (para avaliar a absorÃÃo intestinal) e coleta de dados clÃnicos e sociais de todos os voluntÃrios. Para a avaliaÃÃo das concentraÃÃes sÃricas foi coletado sangue duas e seis horas apÃs a ingestÃo observada da RMP+INH. A tÃcnica utilizada para a quantificaÃÃo da L e M na urina e dosagem sÃrica de RMP e INH foi a cromatografia lÃquida de alta pressÃo. O total de componentes dos grupos com TBMR, TBS e de sadios foi, respectivamente, 41, 33 e 41, emparelhados por gÃnero e idade. Na anÃlise univariada, encontrou-se mediana / variaÃÃo do percentual de excreÃÃo urinÃria da L e M menor no grupo com TBMR em relaÃÃo aos sadios (p<0,05). Ao se corrigir para a associaÃÃo alcoolismo + tabagismo ou Ãndice de massa corporal (IMC), desapareceu a significÃncia da menor excreÃÃo de lactulose nos portadores de TBMR. ApÃs a anÃlise multivariada, a mÃdiaÂdesvio-padrÃo (dv) do percentual de excreÃÃo urinÃria do M foi menor no grupo com TBMR em relaÃÃo ao grupo de VS (p=0,0291) e em relaÃÃo ao de TBS (p=0,0369). A relaÃÃo L/M foi semelhante entre os grupos (p=0,4747). A concentraÃÃo sÃrica mÃxima de INH (CHX) mÃdiaÂdesvio-padrÃo foi maior no grupo com TBMR (3,82Â1,18) em relaÃÃo ao VS (2,79Â1,19), p<0,01, nÃo havendo diferenÃa entre TBS e VS nem entre TBMR e TBS. ApÃs a anÃlise multivariada, a CHX aumentou no grupo VS (3,07Â0,24), mas continuou a ser maior no grupo com TBMR e, agora, com diferenÃa significante em relaÃÃo apenas à TBS. Houve CHX < 3 Âg/ml em 18,8% (6/32) dos casos e 56,7% (17/30) dos sadios (p<0,05), nÃo havendo diferenÃa entre TBS, 39,3% (11/28) e sadios. ApÃs a anÃlise multivariada, a mediaÂdp da concentraÃÃo sÃrica mÃxima de RMP (CRX) foi menor no grupo com TBMR do que nos sadios (p<0,05) e no grupo com TBS do que nos sadios (p<0,001), nÃo havendo diferenÃa entre TBMR e TBS. Houve (CRX) < 8 Âg/ml em 90,6% (29/32) dos portadores de TBMR e 66,7% (20/30) dos sadios (p<0,05) e em 82,1% (23/28) do grupo com TBS (em relaÃÃo aos sadios, p<0,05). Em conclusÃo, observou-se reduÃÃo na absorÃÃo transcelular intestinal em pacientes com TBMR versus TBS ou sadios, e os dados sugerem significante participaÃÃo do alcoolismo+tabagismo e IMC na reduÃÃo do transporte paracelular em portadores de TBMR. A CRX foi mais baixa em portadores de TBMR e TBS do que em sadios, com altas proporÃÃes de nÃveis subterapÃuticos de RMP e INH nos trÃs grupos, principalmente para CRX, mas, tambÃm preocupante para CHX. / Reduced antituberculosis drugs concentrations are associated with Mycobacterium tuberculosis resistance. This study aims to evaluate intestinal permeability and serum concentrations of rifampin (RIF) and isoniazid (INH) in patients with multidrug-resistant tuberculosis (MDR-TB). A case-control was conducted with outpatients who attended Messejanaâs Hospital in Fortaleza-Cearà from August 2006 to April 2007. MDR-TB (case) was defined as resistance to at least RIF+INH according to the susceptibility test by the proportion method. Two control groups were formed. The drug sensible TB (DS-TB) group defined so when the isolate was sensible to RIF, INHH, streptomycin and ethambutol and the healthy control group (HC). The final MDR-TB, DS-TB and health control groups composition was 41, 33 and 41 respectively, matched by sex and age. Biochemical and haematological examinatios, lactulose:mannitol (L/M) test (to access intestinal absorption) were performed as well as social and clinical interview in all volunteers. To access the serum concentrations two blood samples were collect at two and six hours after RIF and INH ingestion in 32 MDR-TB and 28 DS-TB patients and 30 HC. The drug serum concentrations and L/M test in urine were performed by HPLC. After univariate analysis the median/range of the L and M urinary excretion percentage was significantly lower in MDR-TB patients comparing to HC (p<0.05). Adjusting for alcoholism+tabagism association or Body Mass Index (BMI), this difference disappeared for lactulose. After multivariate analysis the mean  standard (sd) deviation M urinary excretion percentage was lower in MDR-TB than in HC (p=0.0291) group or DS-TB (p=0.0369) group. The L:M ratio did not differ between the groups (p=0.4747). The meanÂsd of the INH maximum serum concentration (HCmax) was higher in MDR-TB (3.82Â1.18) than in HC (2.79Â1.19) group, p<0.01 and there was no difference between DS-TB and HC nor between MDR-TB and DS-TB groups. After multivariate analysis the HCmax increased in HC (3.07Â0.24), but, remained to be higher in MDR-TB group, and now, significantly higher only than DS-TB group. There was HCmax < 3 Âg/ml in 18.8% (6/32) of the cases and 56.7% (17/30) of the HC (p<0.05) and no difference between DS-TB (39.3%, 11/28) and HC. After multivariate analysis the meanÂsd RIF maximum serum concentration (RCmax) was lower in MDR-TB than in HC(p,0.05) and in DS-TB than in HC (p<0.001), with no difference between MDR-TB and DS-TB groups. The RCmax was < 8 Âg/ml in 90.6% (29/32) of the cases and 66.7% (20/30) of HC (p<0.05) and in 82.1% (23/28) of the DS-TB patients (comparing to HC, p<0.05). In conclusion there was reduction in transcellular intestinal absorption in MDR-TB versus DS-TB or HC and the data suggest that alcoholism+tabagism association and BMI have an important role in the reduction of paracellular transport in MDR-TB patients. The RCmax was low in MDR-TB and DS-TB patients with high proportions of subtherapeutic levels in theses groups, mainly for RCmax, but also worrying for HCmax.

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)

The purpose of this study was to explore and describe the personal experiences of enrolled nurses while caring for patients infected with multidrug-resistant tuberculosis (MDR-TB) in an urban tuberculosis hospital in KwaZulu-Natal province, South Africa. Generic qualitative research was conducted with a sample of purposively selected enrolled nurses who cared for MDR-TB patients. Data was collected through in-depth individual interviews and analysed using Colaizzi’s (1978) method of data analysis. The research findings revealed six major themes: the working context, fear of contracting the disease, problems that have an impact on the quality of nursing care, nurses' perceptions of the patients, support structures and nurses' expressed needs. The findings of this study indicate that the nurses work in a challenging environment and need to be supported, as they experience more negative than positive feelings while caring for these patients. / Health Studies / (M.A. (Health Studies))

Magister Public Health - MPH (Public Health) / The presence of highly effective medicines has made very little impact in reducing deaths as a result of tuberculosis (TB), a curable condition but when managed inappropriately, may result in Drug Resistant TB. TB accounts for about one in four deaths that occur in HIV positive people and HIV has been found to be a risk factor for complex unfavorable outcomes in MDR TB patients and a very strong predictor for death and default. The relationship between diabetes and TB has also been explored, with some authors identifying diabetes as a risk factor for TB, and with related poor clinical outcomes in both conditions when they co-exist. Exploring the clinical characteristics and treatment outcomes of MDR TB patients in the presence of these risk factors could present an opportunity to provide better care through increased case-detection activities, improved clinical management and better access to care for all these conditions. The aim of the study was to describe the clinical characteristics and treatment outcomes of MDR TB patients initiated on treatment at Nkqubela and Fort Grey Hospitals.

Introduction Tuberculosis (TB) is a major cause of death worldwide. Control of Tuberculosis is a serious challenge to global health. A new and potentially devastating threat to TB control is the emergence of multi-drug resistant TB (MDR-TB). South Africa was ranked fourth among the countries with the highest number of confirmed MDR-TB cases. Aim The aim was to investigate the annual MDR-TB prevalence and associated risk factors for MDR-TB from 2001 to 2007 at the Prince Cyril Zulu Communicable Disease Centre. To investigate previous TB treatment duration, previous TB treatment outcome, and duration of previous TB treatment interruption in a subgroup of patients who were previously treated for TB. To determine the average length of time from diagnosis of TB to diagnosis of MDR-TB and commencement of MDR-TB treatment. Methods An observational analytic nested case-control study design was used. All patients who were diagnosed with pulmonary TB and who had a sputum culture performed between 2001 and 2007 were included in the study. The cases were all MDR-TB cases diagnosed on sputum culture between 2001 and 2007. The controls were drug susceptible TB cases which had a sputum culture done at diagnosis, and were diagnosed in the same month as the MDR-TB case Results There were 10 205 sputum cultures performed from 2001 to 2007. MDR-TB was found in 445 patients. An increase in the prevalence of MDR-TB occurred in 2007, due to a significant increase in prevalence among new TB cases. The MDR-TB prevalence was 11.7% among new TB cases and 4.7% among previously treated TB cases in 2007. There was no significant association between demographic characteristics and MDR-TB. Previous TB treatment failure and a duration of previous TB treatment of greater than 32 weeks was found to be significantly associated with MDR-TB. The median time from TB diagnosis to MDR-TB diagnosis was 98 day and from MDR-TB diagnosis to MDR-TB treatment 10 days. Discussion Delays in the diagnosis of MDR-TB, long waiting times before MDR-TB treatment commencement and lack of isolation have contributed to the spread of primary MDR-TB and was most likely responsible for the increase in prevalence of MDR-TB among new TB cases. Recommendations It was suggested that a sputum specimen should be obtained for culture and sensitivity from all new TB patients in areas which have an MDR-TB prevalence of greater than 3% among new TB patients. Ensure patient education on basic infection control measures. Improve MDR-TB diagnosis and reduce waiting times for MDR-TB treatment. / Thesis (M.Med.Sc.)-University of KwaZulu-Natal, Durban, 2011.

The purpose of this study was to explore and describe the personal experiences of enrolled nurses while caring for patients infected with multidrug-resistant tuberculosis (MDR-TB) in an urban tuberculosis hospital in KwaZulu-Natal province, South Africa. Generic qualitative research was conducted with a sample of purposively selected enrolled nurses who cared for MDR-TB patients. Data was collected through in-depth individual interviews and analysed using Colaizzi’s (1978) method of data analysis. The research findings revealed six major themes: the working context, fear of contracting the disease, problems that have an impact on the quality of nursing care, nurses' perceptions of the patients, support structures and nurses' expressed needs. The findings of this study indicate that the nurses work in a challenging environment and need to be supported, as they experience more negative than positive feelings while caring for these patients. / Health Studies / (M.A. (Health Studies))

Thesis ( MPH.) -- University of Limpopo, 2022 / Background Multidrug-resistant tuberculosis (MDR-TB) has recently resulted to be in an emergence state globally and this of constitute a big challenge for TB control and the goals of the World Health Organization’s End TB Strategy. Aminoglycosides (AG) were often used as part of treatment of life-threatening illnesses such as MDR-TB for decades, however their adverse effects are widely described and hearing loss is one of the major side effects. The risk factors for hearing loss in patients treated with AG include the dose and duration of AG, infection with human immunodeficiency virus (HIV), older age and persons exposed to a high level of noise while the damage can be total and permanent. Severe hearing impairment has been reported to occur among patients treated for MDR-TB with injectable drugs, especially among the elderly and patients infected with human immunodeficiency virus, however, Bedaquiline containing regimens have demonstrated improved outcomes over injectable containing regimens in the long-term treatment of MDR-TB. Methods The objective of the current study was to investigate the burden of hearing loss amongst MDR-TB patients on bedaquiline at Zithulele Hospital in Eastern Cape Province. Therefore, the current study followed a quantitative retrospective approach using simple random sampling to select MDR-TB patients treated with bedaquiline and having a baseline audiogram be the initiation of treatment. The data was captured in a Microsoft Excel spreadsheet and then transferred to Statistical Package for Social Sciences (SPSS) Version 20 for data analysis in which categorical variables were presented as percentages and frequencies, while continuous variables was presented as mean, median and standard deviation lastly, comparison of categorical variables was done using a Chi-Squared test, whereas continuous variables were compared using a t-test. P-value of <0.05 will be considered significant. Results The mean age for the participants was 39.2 years with standard deviation of 11.8 and there was no statistical significance difference between the age groups (p value = 0.178). There no was a statistical significance difference between the employment status (p value = 0.794), previous use of injectables (p value = 0.360) and type of hearing of loss (p value = 0.536). Majority of the MDR-TB patients on bedaquiline did not have hearing loss at 67% while those who had gradual hearing loss and sudden hearing loss were 26.8% and 6.2% respectively. There was no statistical significance difference between males and females in both the right and left ears, however, the right ear results appeared to be slightly worse than the left ear results. It was found that both males and females had a high frequency hearing loss in the left ears of 26.8% and 22.2% respectively as compared to the right ears with of 25.9% and 1.6% respectively. The was a statistical significance difference between the age groups in both ears for hearing loss at p-value <0.001. The overall prevalence of hearing loss was found to be 32.9% and hearing loss at 20dB or more loss at any frequency was low at 11.9% while hearing loss at 10B or more loss at any frequency was the highest at 32.9% followed by loss response at 3 consecutive frequencies at 26.2%. Hearing loss was increasing with increasing age from 8.3% in age group and age was significantly associated with hearing loss as older patients were 2.2 times more likely to have a hearing loss at a degree of 20dB and 4.4 times more likely to have a hearing loss at a degree of 10dB. Previous use of injectables was also significantly associated with hearing loss as patients who used injectables previously were 11.5 times more likely to have a hearing loss at degree of 10dB, 5.6 and 11.3 times more likely to have a hearing loss at loss response at 3 consecutive frequencies and overall hearing loss respectively. Conclusion South Africa has a high burden of drug-resistant tuberculosis (DRTB) and until recently, ototoxic aminoglycosides were predominant in treatment regimens. Drug resistant TB treatment with bedaquilines caused clinically and statistically significant deterioration of hearing loss in patients, most prominently at high frequencies. Although public health interventions to prevent hearing loss have been deemed cost effective and have meaningful individual and economic implications, hearing loss and its prevention consistently receive inadequate attention as a global public health priority. Despite the serious impacts of hearing loss, little is known regarding prevalence of ototoxic hearing loss after treatment for DR-TB. Therefore, when the use of injectable ototoxic medications is unavoidable, audiological ototoxicity monitoring is essential to optimise hearing-related outcomes.