Motivation In South Africa, various transitional changes parallel detrimental modifications in lifestyle behaviour of especially the lower socio-economic communities. We are currently double-burdened by a high prevalence of communicable and noncommunicable diseases such as diabetes, chronic respiratory and cardiovascular diseases, which is accompanied by a high cardiovascular mortality rate. Healthcare and treatment resources are limited and low-cost intervention strategies to lower this burden are urgently needed. Unhealthy lifestyle behaviours, such as excessive alcohol consumption and tobacco use, are known to augment inflammation as reflected by inflammatory markers such as C-reactive protein and interleukin-6, which are well-known risk factors for cardiovascular disease and mortality. Several studies showed the prognostic value of soluble urokinase plasminogen activator receptor (suPAR) in advanced disease states and that suPAR associates with different types of cancers, infectious diseases, diabetes, coronary artery disease and all-cause mortality. Since the discovery of suPAR in 1991, the role of this less known inflammatory marker in various diseases has been under debate. It was further reported that black individuals have higher suPAR levels than whites. However, whether an unhealthy lifestyle and cardiometabolic risk factors are related to suPAR, whether suPAR plays a role in the development of cardiovascular disease such as hypertension, and whether suPAR could predict all-cause and cardiovascular mortality, especially among the understudied black South African population, remain to be established. Aim The central aim of this thesis was to determine if suPAR associates with cardiovascular disease development in a black South African population. We therefore explored whether suPAR relates to lifestyle and cardiometabolic risk factors, associates with the development of hypertension and has prognostic value for cardiovascular and all-cause mortality over five years. Methodology This five-year prospective sub-study, which is embedded in the international Prospective Urban and Rural Epidemiology study, included black South African volunteers of ages older than 35 years from the North West province, South Africa. Baseline data collection took place in 2005 during which 2 010 men and women from urban and rural areas were examined. A total of 1 292 participants returned for examination and were followed-up for the first time in 2010. Of these participants, 214 were newly identified as being infected with the human immunodeficiency virus (HIV), while 233 died during the five year period. Standardised methods were used to capture all data and included health questionnaires (lifestyle factors, medication use, disease status and history, mortality outcome), cardiovascular and anthropometric measurements, as well as biochemical analyses of inflammatory markers (suPAR, C-reactive protein, interleukin-6), HIV status and relevant metabolic markers. In preparation for statistical analyses, non-Gaussian variables were logarithmically transformed. We compared means and proportions with independent t-tests, analysis of variance, analysis of covariance (for adjustments) and Chi-square tests, while dependent t-tests and McNemar tests were used for analysis of longitudinal data within individual groups. We determined relationships between variables with Pearson’s correlation coefficients. Independent relationships were determined with logistic regression, forward stepwise multiple regression and proportional Cox-regression analyses. Mortality rates were calculated using Kaplan-Meier survival function estimates and log-rank tests. In all cases, p≤0.05 were used to indicate statistical significance. Results and conclusions of each manuscript Three manuscripts were written in order to achieve the aim of this thesis. In the first manuscript we explored the cross-sectional relationships of suPAR with lifestyle and cardiometabolic risk factors in a black South African population. We showed that suPAR was independently associated with lifestyle behaviours, including alcohol consumption, as indicated by gamma-glutamyltransferase levels (β=0.24; p<0.001), tobacco use (β=0.13; p<0.001) and unemployment (β=0.07; p=0.039), despite no direct links with cardiometabolic factors such as blood pressure, dyslipidaemia, glycaemia or adiposity. These findings emphasise the important need to address lifestyle behaviours in order to limit the detrimental effect of modifiable risk factors on the health and mortality rate of this population. Secondly, we determined whether suPAR was associated with the development of hypertension over five years. We found that suPAR was higher and increased more prominently (14.2% vs. 6.94%; p=0.007) in participants that developed hypertensio than in those that remained normotensive. Change in systolic blood pressure was independently associated with baseline suPAR (β=0.14; p=0.043), while becoming hypertensive was associated with an increase in suPAR (odds ratio=1.41; p=0.015). Whether inflammation leads to the development of hypertension or vice versa, remains unclear. Our findings emphasise the need to acknowledge the role of inflammation in hypertension and may permit further investigation of the use of suPAR as a potential marker for early risk identification and intervention. The third manuscript investigated the prognostic value of suPAR, compared to other inflammatory markers C-reactive protein and interleukin-6, in all-cause and cardiovascular mortality. We showed for the first time in a black population that suPAR predicted both all-cause (hazard ratio=1.27; p=0.003) and cardiovascular mortality (hazard ratio=1.40; p=0.026), independent of interleukin-6. Future research is needed to clarify the mechanisms behind the association of suPAR with cardiovascular mortality and to explore the possibility of a suPAR cut-off value for early identification of those with increased risk for cardiovascular morbidity and mortality in this population. General conclusion In this thesis we showed for the first time that suPAR has potential as a marker of cardiovascular disease development in black South Africans. SuPAR associated with hypertension and independently predicted all-cause and cardiovascular mortality over five years. Our findings, that suPAR is independently associated with adverse health behaviours such as alcohol and tobacco use, lend support for the use of suPAR as a novel approach for early risk identification and intervention strategies, which may be effective in combatting the high cardiovascular disease burden among the black South African community. / PhD (Physiology), North-West University, Potchefstroom Campus, 2015

Purpose of the study - Identify predictors of mortality and develop a related care plan for patients who are on antiretroviral therapy (ART) in Gondar, Ethiopia. Design - A quantitative, retrospective cohort study was conducted analysing medical records of HIV patients who presented to Gondar University Hospital (GUH), Gondar, and started ART between 1 January 2007 and 30 June 2010. Results - In defining the predictors of mortality, the findings in bivariate analysis revealed: female sex, CD4 cell count ≤ 50/μl, CD4 cell count 51-199/μl, a haemoglobin concentration ≤8g/dl, a history of oral candidiasis, tuberculosis and Cryptococcus meningitis were all statistically significant. A female sex, CD4 cell count ≤ 50/μl and CD4 cell count 51-199/μl maintain their significance level in the multivariate analysis. Conclusions - The study therefore recommends that clinicians and case managers be vigilant of these predictors of mortality while managing HIV patients who are on ART. Key Concepts- ART, AIDS, HIV, predictors of mortality / Health Studies / (M.A. (Public Health))

Objectif : To determine the frequency and the nature of complications and sequelae of serogroup B and serogroup C meningococcal disease, during a recrudescence caused by a virulent clone of serogroup C, serotype 2a Neisseria meningitidis. To evaluate the quality of life of survivors. Methods. The study population included all cases of culture-proven serogroup B and C meningococcal disease reported in the province of Quebec, Canada, between 1 January 1990 and 31 December 1994. Complications and sequelae were assessed by review of medical files, postal questionnaires, and telephone interviews. Results. There were 167 cases of serogroup B and 304 cases of serogroup C infection. The largest number of cases was observed in the under 1 year age group for serogroup B and in the 10-19 year age group for serogroup C. Fatality rates were 7% for serogroup B and 14% for serogroup C. %). Only 3% of survivors of serogroup B cases had physical sequelae. 15% of survivors of serogroup C infection had one or more significant physical sequelae (skin scars 12%, amputations 5%, significant sensorineural hearing loss 2%, renal failure 1%, other sequelae 4%. Among cases without identified physical sequelae who completed the questionnaire, 19% reported a reduction in their quality of life attributable to the disease. Conclusions. These results confirm the gravity of disease caused by serogroup C, serotype 2a Neisseria meningitidis and support vaccination for control of outbreaks and epidemics of disease caused by this particular strain.

Eradication of polio outbreaks and tetanus neonatorum mortality, as well as lowering Egyptian infant mortality to less than 50 per 1000 live births, were specific goals to be achieved by the year 2000. National television immunization campaigns were launched to persuade mothers to change their attitude and vaccinate their children against the killer diseases. This study investigates the effects of these campaigns on mothers' knowledge, attitude, and behaviour regarding immunization in Egypt. A comparative study was conducted among three groups of mothers who have a child three to twelve months of age. A total of 158 mothers were selected, by systematic random sample technique (1:2), from the part of Kolosna village, in Upper Egypt, which is supplied with electricity, to constitute the viewer group. From the other part of the same village, which is not yet supplied with electricity, all mothers (98) were selected, representing the non viewer group. Another 76 mothers were selected from two prestigious social clubs in Cairo, to represent a second control group of known social class and educational level. Through comparing mothers' knowledge, attitude, and behaviour between the viewer and the non viewer groups, the effect of television immunization messages can be illustrated. Similarly, comparing the village viewer with the Cairo viewer group determines the effects of some intervening factors such as educational level, health professionals, or experience With a structured interview, mothers in the viewer group showed a significant positive and stable attitude and behaviour towards immunization, as well as more correct knowledge when compared with the non viewer group, demonstrating the positive role of television in child health promotion. Television enhances mothers' efficiency to use the available health services and promotes their perceived control over children's health. Health professionals, experience, and social support can potentiate the television's positive role. Educational level, occupation, baby's sex, or mothers' age are insignificant factors in changing mothers' attitude and behaviour.

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For life insurance and annuity products whose payoffs depend on the future mortality rates, there is a risk that realized mortality rates will be different from the anticipated rates accounted for in their pricing and reserving calculations. This is termed as mortality risk. Since mortality risk is difficult to diversify and has significant financial impacts on insurance policies and pension plans, it is now a well-accepted fact that stochastic approaches shall be adopted to model the mortality risk and to evaluate the mortality-linked securities. The objective of this thesis is to propose the use of a time-changed Markov process to describe stochastic mortality dynamics for pricing and risk management purposes. Analytical and empirical properties of this dynamics have been investigated using a matrix-analytic methodology. Applications of the proposed model in the evaluation of fair values for mortality linked securities have also been explored. To be more specific, we consider a finite-state Markov process with one absorbing state. This Markov process is related to an underlying aging mechanism and the survival time is viewed as the time until absorption. The resulting distribution for the survival time is a so-called phase-type distribution. This approach is different from the traditional curve fitting mortality models in the sense that the survival probabilities are now linked with an underlying Markov aging process. Markov mathematical and phase-type distribution theories therefore provide us a flexible and tractable framework to model the mortality dynamics. And the time-changed Markov process allows us to incorporate the uncertainties embedded in the future mortality evolution. The proposed model has been applied to price the EIB/BNP Longevity Bonds and other mortality derivatives under the independent assumption of interest rate and mortality rate. A calibrating method for the model is suggested so that it can utilize both the market price information involving the relevant mortality risk and the latest mortality projection. The proposed model has also been fitted to various type of population mortality data for empirical study. The fitting results show that our model can interpret the stylized mortality patterns very well.