3. Electronic Theses and Dissertations (ETDs) - All submissions
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Item Risk factors associated with TB incidence in an adult population from poorly resourced South African urban communities with a high TB prevalence(2011-03-10) Ncayiyana, Jabulani RonnieIntroduction: Tuberculosis (TB) persists as a serious global public heath problem of a magnitude requiring urgent attention. The increase in new cases of TB in African countries where the prevalence of HIV is relatively low has been associated with other host and environmental factors. There is little or no comparable data on the association between host and environmental related factors and TB incidence in low HIV prevalence regions of South Africa. Objectives: This study aims to investigate host and environmental factors associated with incident TB in one region of South Africa. Methods: 3493 TB-free participants were recruited, and baseline data collected at the beginning of 2003 in the Lung Health Study in Ravensmead and Uitsig, Cape Town, South Africa. The TB register was used to identify new cases among the 3493 participants between 2003 and 2007. Results: Of the 3493 study participants, 109 developed TB; i.e. 57 males and 52 females. The incidence of TB in the Ravensmead and Uitsig study population was 632 per 100 000. Cohabiting, OR= 2.09 (95% CI= 1.05 - 4.17), smoking, OR= 2.19 (95% CI= 1.48 - 4.14), and history of imprisonment OR= 1.88 (95% CI= 1.09 - 3.23) were all statistically associated with TB incidence in multiple logistic regression models. The summary population attributable fraction for these three factors was 53.2%. Conclusions: TB incidence was high in this community. Cigarette smoking was one of the most important predictors of TB incidence, and the proportion of smokers in this population was relatively high. TB control and prevention strategies need to focus on interventions which will reduce or limit the impact of TB risk factors.Item Tuberculosis (TB) treatment outcomes in adult TB patients attending a rural HIV cllinic in South Africa (Bushbuckridge).(2010-04-14T12:00:47Z) Mashimbye, LawrenceSouth Africa is ranked fourth on the list of 22 high-burden TB countries in the world. Intensifying the prevalence of TB in South Africa is the high TB/HIV co-infection rate, with 44% of new TB patients testing positive for HIV. This burden is intense for rural communities due to poverty and return of people with TB/HIV co-infection who previously migrated for employment. In rural South Africa, TB is the leading cause of mortality in HIV-infected persons, but limited information is available about predictors of death. This study measures TB treatment outcomes in Rixile clinic and assesses predictors of TB mortality. Rixile HIV clinic is based in Tintswalo hospital, Acornhoek, Bushbuckridge, Mpumalanga province. This current study uses secondary data collected through a prospective cohort study conducted by PHRU and RADAR from March 2003 to March 2008 on 3 to 6 monthly intervals. Chi-square and logistic regression statistical tests were used to assess predictors of TB Mortality. TB mortality among study participants was 62.5% during the pre-ARV rollout period (March 2003- October 2005), and treatment completion was 31.7%. Some 5.8% participants interrupted treatment during the pre-ARV rollout period as compared to 4.5% during the ARV rollout period (November 2005- March 2008). TB mortality among study participants was 7.5% during ARV rollout and treatment completion increased to 84.4%. Factors associated with TB mortality were age (p=0.006), sex (p=0.017), BMI (p< 0.001), marital status (p=0.004), education (p=0.03), alcoholic beverages consumption (p=0.04), and ARV treatment (p<0.001). However, only age, sex, and ARV treatment were found to predict TB mortality. The proportion of TB treatment completion was higher and TB mortality was lower during ARV roll-out compared to pre-ARV roll-out. Being at the age of 40 to 75 years, not being on ARV treatment and male sex predicts TB mortality in this population. There is a need to expand ARV treatment and intensify TB care services for older people, particularly males living with HIV in this rural community.Item Outcome of HAART in patients with tuberculosis in the Themba Lethu clinical cohort(2009-05-21T13:07:51Z) Akiy, Zeh ZacheausIntroduction: The burden of disease due to HIV/AIDS and tuberculosis remains great for many countries around the world. Continuing attention must be devoted to these epidemics if we ever hope to one day contain their devastating effects on humankind. The objective of this study is to; to evaluate and compare cohort treatment outcomes of HIV infected TB patients and HIV infected non-TB patients treated with HAART at the Themba Lethu Clinic between 1st April 2004 and 1st April 2007. To measure outcomes in CD4, viral load, hemoglobin, liver function tests, weight, BMI, loss to follow up and death and to compare this outcomes between HIV patients who have had TB and HIV patients who have never had TB. Materials and Methods: information collected of patients for three years shall be used to carry out analysis. A total of 5818 patients were included in the cohort sample. 19.23% (1,048) of the patients had been diagnosed with TB at some point in time while 80.77% (4,770) had never been diagnosed with TB. Mean baseline CD4 cell counts were 113.47cells/mm3 for non TB patients and 88.85cells/mm3 for those who have ever had TB. This baseline CD4 counts are considered 2 months prior to ARV start and 1 month post the start of ARV. Baseline means for weight, BMI, AST and ALT were also taken into consideration by the two patient groups. Clinical out come was assessed and evaluated by comparing incidence of designated end points either as survival or failures. Incidence of deaths and loss to follow up was also compared in the two groups of patients. Results: Among HIV non TB patients, incidence rate of them having CD4 counts greater than 200 was at 36.47 persons per 10000 person days while for the patients who had been diagnosed with TB incidence of CD4 rising to above x 200 was lower at 34.19persons per 10000 person days. A rate ratio of 0.94 (95% CI 0.85 - 1.03) showed no true difference in the two groups. When looking at deaths in the two groups of patients, incidence in those who had TB was 3.84 deaths per 100 patient years and 4.16 deaths per 100 patient years for the non TB group with RR 0.93 and CI 0.66 - 1.28. Differences in incidence and outcomes were noticed in Hb gain, weight and BMI change, Liver function test changes over time and loss to follow up “defaulters”. Survival curves were modeled to show trend of change and log rank test were used to ascertain equality of survival curves. Where log rank p. values < 0.05 were noticed among survival curves of weight, BMI, AST, ALT, Hb and Loss to follow up. This again showed differences in weight, BMI, hemoglobin, AST, ALT and loss to follow up while no statistical differences were recognized between the two groups of patients when considering changes in CD4, deaths and Viral load over time as log rank test failed to reject the null hypothesis of similar curves. Conclusion: Data indicated that similarity and differences between HIV TB patients and HIV non TB patients could vary along certain outcomes. But one sure point is both groups of patients had an equal chance of staying alive when properly treated with ARV/HAART.Item Adrenal function in hospitalised patients with pulmonary tuberculosis treated with rifampicin(2009-02-13T08:49:51Z) Venter, Willem Daniel FrancoisAbstract Introduction: Tuberculosis carries a high mortality in the days immediately after treatment. It is also the commonest cause of adrenal insufficiency in the developing world. Rifampicin is a potent hepatic enzyme inducer, and may contribute to adrenal insufficiency by accelerating cortisol breakdown. The aim of the study was to determine whether rifampicin induced accelerated catabolism of corticosteroids. Methods: A prospective, randomised study comparing adrenal function in 20 patients with pulmonary tuberculosis in the first five days treated with two different antituberculosis regimens, one containing rifampicin, and the other ciprofloxacin. Results: Demographic, clinical and laboratory results were similar in both groups. Both groups showed a statistically significant and similar decrease in morning cortisol, with similar responses to ACTH stimulation at both 30 and 60 minutes before and after four days of treatment. In the entire cohort, 40% demonstrated an incremental cortisol rise of <250nmol/l after ACTH stimulation on day 1. Mean basal cortisol concentrations were substantially elevated and DHEA-S levels were consistently subnormal, resulting in a high cortisol:DHEA-S ratio. No patient demonstrated overt adrenal insufficiency. There were no significant differences between the two groups before or during therapy for any electrolytes, hormones or calculated serum osmolality. Conclusions: Rifampicin did not additionally impair adrenocortical function during the initial period of therapy.Item Analysis of secondary data from Mycobacterium vaccae tuberculosis clinical trial(2008-11-04T12:13:27Z) Mapingure, Munyaradzi PaulBackground: Sputum culture conversion at two months is an important indicator for the effectiveness of treatment and the infectivity of a patient with pulmonary TB. This study aimed at investigating factors that are associated with tuberculosis culture conversion at two months as well as investigating whether sputum culture conversion at two months is a reliable predictor of relapse. Methods: The study makes use of data obtained from 347 newly diagnosed tuberculosis patients who participated in a randomized placebo controlled immunotherapy trial at King George V hospital in Durban. Above objectives were met by carrying out statistical analysis of the secondary data. Chi-square tests for categorical explanatory variables such as HIV status and smoking status and (b) t-tests for continuous variables such as age were used for investigating factors associated with 2-month culture conversion. Multivariate models were used to find the most important variables for predicting 2-month culture conversion. Kaplan Meier curves were used for investigating whether culture conversion at two months is a reliable predictor of relapse. Findings: Of the 347 tuberculosis patients, 34 % were HIV sero-positive. Age, body mass index (BMI), smoking status and gender were found to be important variables that affect sputum culture conversion at two months. At 5 % significance level there was no evidence that those who culture convert at two months were less likely to relapse than those who had not culture converted at two months (p=0.1165). However the trend shown is striking to report as it may be of clinical significance. Among those who had not culture converted at two months, more people (40) than expected (34) relapsed an among those who had culture converted at to months, less people (19) than expected (24) relapsed. Interpretation and recommendations: Some behavioral and biological factors affect two month tuberculosis culture conversion therefore successful tuberculosis management need to take into account the effect of these factors. This study did not show that the sterilizing potential of an anti-tuberculosis regimen can be obtained by evaluation of the culture conversion rates at two months and this may be due to small sample size.Item Tuberculosis treatment experience at Hillbrow Health Centre(2008-11-04T11:55:45Z) Makhetha, Motseng MalehloaTuberculosis remains a communicable disease of major public health importance in South Africa. The purpose of this study is to search for trends in management of tuberculosis at Hillbrow Health Centre from 2000 to 2002. Furthermore, to assess completeness of routine records, compare performance of tuberculosis control in this clinic with others in region 8 during 2002 and identify residential areas with high volumes of tuberculosis patients. Data was obtained from tuberculosis documents at the facility. Information provided by the district office was compared with research findings and used to evaluate performance of Hillbrow Health Centre against the other four clinics in the region. The main findings from the study conducted at Hillbrow Health Centre were the large number of patients diagnosed with tuberculosis annually and cure rates below 40% during the study period. In 2002, the clinic reported the highest proportion of TB patients and the lowest cure rate compared to the other four clinics reporting tuberculosis in region 8. “Hot spots” for the disease were identified in Hillbrow and Joubert Park suburbs and this is where Esselen, Hillbrow and Urban Health Clinics are situated. There is room for improvement of tuberculosis control. More research needs to be done to determine factors contributing to the high incidence of TB in Hillbrow and Joubert Park Suburbs.Item The study of TB and MDR-TB in Kwa-Thema township from 2000-2004(2008-10-06T10:53:34Z) Rembuluwani, AzwinakiAbstract will not copy to DSpaceItem Do tuberculosis treatment supporters influence patients treatment outcome? A study in the southern service delivery region, Ekurhuleni Metropolitan Municipality, Gauteng Province, South Africa(2008-09-30T07:40:53Z) Oduor, Peter AggreyAbstract This study aimed to investigate the role played by treatment supporters in promoting patients’ treatment outcomes in six TB clinics of Ekurhuleni Metropolitan Municipality, Gauteng. A descriptive research design was used to study TB patients who were registered in the clinics in April and May 2006. Interviews were conducted on 216 new adult patients six months after their registration at clinics, all 30 treatment supporters of those who had supporters and the staff responsible for TB at the six clinics at which the patients were registered. The patients were grouped into those who had supporters 53% (n=115) and those who did not 47% (n=101). Patients’ response rate was 97%. Treatment outcomes were compared between these two groups. Results showed that significantly more supported patients achieved successful outcomes than patients who did not have supporters. The results did not change when transfers and deaths were excluded from the measurement. Successful treatment outcomes were significantly associated with treatment supporters having fewer than 10 patients, patients living with someone, patients of age 40 or more years, male patients, those whose highest education levels were tertiary and secondary. Patients and clinic staff said that supporters were useful in checking on patients’ treatment, giving medicine, counselling and advising patients on medication and in practical help. Conclusion: Treatment supporters had a significant role in promoting patients’ treatment outcomes. It is recommended that TB treatment programme staff should consider using treatment supporters in their programmes.Item Study of vitamin C levels in relationship to stress hormone response and acute phase reaction in patients with newly diagnosed pulmonary tuberculosis(2008-09-29T13:29:18Z) Opolot, John OjilongINTRODUCTION Tuberculosis remains a major public health threat globally and the Human Immunodeficiency Virus (HIV) pandemic afflicting developing and developed countries has resulted in enormous increases in tuberculosis infections worldwide. Researchers have previously documented very low plasma vitamin C levels in patients with active pulmonary tuberculosis. This was attributed to a number of factors including: accelerated turnover of vitamin C, shifts in plasma concentrations, increased collagen formation and tissue repair and decreased vitamin C intake. Vitamin C appears to have a role in steroid-genesis and catecholamine synthesis. Decreased plasma vitamin C levels may therefore impact on the stress hormone response and acute phase reaction of patients with active tuberculosis. AIM The primary aims of the study were to measure plasma vitamin C levels, as well as stress hormone levels and acute phase reaction in patients with newly diagnosed active pulmonary tuberculosis and control patients (without tuberculosis), to determine if there was any relationship between vitamin C levels and the levels of these other variables. METHODS AND MATERIALS This was a prospective study of seventy one (71) consecutive patients admitted to Helen Joseph Hospital (between March and October 2002) with newly diagnosed active pulmonary tuberculosis and eighty nine (89) control patients with medical conditions other than tuberculosis. Demographic, clinical and laboratory data were captured and analyzed using SPSS 7.5 soft-ware. Continuous variables were analyzed using students t-test. Categorical data were analyzed by non parametric analysis and Pearsons linear regression model was used to determine the correlation between vitamin C and the other variables in the two groups. RESULTS There were no differences in race, gender, age, suburb of residence and occupational distributions in the study group with tuberculosis compared to the control group. There were more smokers and consumers of alcohol in the control group (54 and 62 patients respectively) than in the study group (28 and 31 patients respectively). The study patients had lower blood pressure (average 90/40 mmHg versus 100/60 mmHg of controls), higher mean pulse rate (101.87 ± 15.14 beats/minute versus 82.92 ± 8.88 beats/minute, p< 0.01), higher mean temperature (38.66 ± 0.67oC versus 37.14 ± 0.44oC, p< 0.01), and lower body mass index (18.29 ± 3.80 Kg/ M2 versus 23.20 ± 5.35 Kg/ M2, p< 0.01). Laboratory data comparing study group and controls also showed marked differences as follows: White cell count (WCC) 8.68×106 / L ± 5.44 versus 11.00×106 / L ± 4.94, p = 0.01; Haemoglobin 9.56gm / dl ± 1.93 versus 12.92gm / dl ± 2.34, p < 0.01 and platelet count 369.21× 106/L ± 190.71 versus 295.94×106 / L ± 94.64, p = 0.01. White cell vitamin C levels (normal range – 20-40 μg/108 leucocytes) were low in half of the patients in both groups (study patients mean 29.85 ± 28.70μg/108 leucocytes versus controls 31.39 ± 30.24μg/108 leucocytes, p = NS). Plasma vitamin C levels were reduced (normal range 10-20 mg/ml) in both groups but more so in the controls (mean 3.87 ± 2.82 mg/ml versus 4.81 ± 3.21 mg / ml in study patients, p= 0.053). Mean cortisol levels were slightly higher in the study patients (448.11 ± 197.41ηmol/L) than controls (392.70 ± 191.25ηmol/L, p = NS). Norepinephrine levels were slightly higher in the study patients than controls (study patients mean 2531.61 ± 2043.60 ρmol/L versus 2178.98 ± 1719.98 ρmol/L of controls, p = NS). Dopamine levels were higher in the study patients than in the controls (468.42 ± 377.57 ρmol/L in study patients versus 293.37 ± 355.84 ρmol/L in controls, p = 0.01). Epinephrine levels were higher in the controls (control patients mean 680.64 ± 743.78 ρmol/L versus 449.41 ± 380.04 ρmol/L of the study patients, p = 0.03). Ferritin levels were much higher in the study patients compared with controls (study patients mean 3005.87 ± 5023.26 μg/L versus 466.51 ± 1774.76 μg/L of the controls, p<0.01) as were CRP levels (125.91 ± 54.77 mg/L in the study patients versus 77.22 ± 81.17 mg/L in the controls, p=0.01). Mean urine cotinine levels were 16.42 ± 24.26μM/L for controls and 9.28 ± 11.59 μM / L for the study patients (p=0.027). Correlation studies did not show any significant differences between the different variables. There was an inverse correlation between CRP levels and urine cotinine levels in the control group (R squared=0.058 and p= 0.024). DISCUSSION There were no differences in the demographic profile of the two groups. Smoking and alcohol consumption were more common in the control group than in the study patients. Over 90 % of patients in both groups had low plasma vitamin C levels, while half of the patients in each group had low white cell vitamin C levels. The low levels of vitamin C could be due to some of the reasons given above or possibly due to the fact that generally there are low levels in Africans for reasons that are not apparent. The control group had increased mean urine cotinine levels suggesting a possible influence of cigarette smoking on vitamin C homeostasis in these patients. In both groups, the majority of patients had normal cortisol levels as well as normal to high catecholamine levels. Also, Ferritin and CRP levels were much higher in the study group than in the controls. The low levels of vitamin C did not, however, have any relationship with stress hormone levels and acute phase reactants. CONCLUSION This study has reaffirmed low plasma and white cell vitamin C levels in patients with new onset pulmonary tuberculosis but has also found low levels in control patients with diseases other than pulmonary tuberculosis. The study demonstrates adequate stress hormone responses in tuberculosis patients, which was not different from non- tuberculosis patients. Acute phase responses were found to be of higher magnitude in tuberculosis patients than in the controls. There were, however, no correlations between plasma vitamin C and stress hormones or acute phase reactants.Item Expression and function of the mutator DNA polymerasencoding umuC-like genes in mycobacteria(2006-11-17T09:04:27Z) Brackin, RobynMycobacterium tuberculosis is an important human pathogen, claiming more lives per annum than any other single infectious organism. The host environment of M. tuberculosis contains DNA-damaging agents that pose a constant threat to the M. tuberculosis genome, and as a result, the ability to repair damaged DNA is likely to play an important role in bacterial survival. Y-family polymerases perform translesional synthesis and replicate DNA in an error-prone manner. By characterising the Y-family polymerases in mycobacteria, a better understanding the organism’s adaptive mutagenesis may be established. Through gene expression studies, it was found that UV irradiation of Mycobacterium smegmatis resulted in the up-regulation of dinP3, which was determined to be a Y-family polymerase by sequence analysis. DinP3 expression was found to be under control of the SOS response and is the first example of a Y-family polymerase in mycobacteria forming part of the SOS regulon. However, loss of DinP3 did not change the ability of M. smegmatis to tolerate UV irradiation. Mutagenesis studies revealed a complex interaction between the different Y-family polymerases in M. smegmatis. It was shown that spontaneous mutagenesis was increased in the absence of DinP3, whereas UV-targeted mutagenesis was increased in the absence of DinP, another Y-family polymerase. In conclusion, these results reflect the differences in control and in the mutational profiles of the Y-family polymerases in M. smegmatis. Moreover, these polymerases exhibit distinctive features from other bacterial Y-family polymerases, highlighting the different way in which bacteria have adapted to deal with lesions in their genetic material.