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Diagnostic tests are widely used in medicine and epidemiology. Most diagnostic tests areimperfect at distinguishing subjects with and without the condition of interest, and manythat provide results on a continuous scale have overlapping densities from diseased andnon-diseased subjects. For the se continuous tests, most statistical techniques developed todate assume a parametric (e.g. normal) family for the distribution of the continuousoutcomes within groups, an often unverifiable but convenient distributional assumption.In addition, evaluating the properties of these tests typically requires or assumes a perfectgold standard test is available. [...] / Les tests diagnostiques sont abondamment utilisés en médecine et en épidémiologie. Laplupart d'entre eux ne distinguent pas parfaitement les sujets qui ont ou non la conditiond'intérêt, et ceux qui fournissent des résultats sur une échelle continue ont souvent desdensités des résultats des sujets malades et non-malades qui se chevauchent. Pour cestests continus, la plupart des techniques statistiques développées jusqu'à présentprésument une famille de distributions paramétriques des résultats dans les 2 groupes, unehypothèse pratique mais souvent non vérifiable. De plus, l'évaluation de leurs propriétésrequiert typiquement qu'un test étalon d'or soit disponible. [...]

The increasing prevalence of type 2 diabetes mellitus (T2DM) poses a major threat to the health and well-being of South Africans. Effective interventions to inform health planning and policy are hampered by the paucity of accurate national epidemiological data. Although several prevalence studies have been conducted, these estimates are not representative of the South African population or are sub-optimal due to the diagnostic methods employed. To address the lack of accurate and representative prevalence data, the aim of this dissertation is to use robust systematic review methods to collate, synthesise and summarise all T2DM prevalence data in South Africa. The dissertation comprises of four parts. Part A contains the study protocol that was published in BMJ Open in 2018. The protocol outlines the problem statement, motivation and rationale, aim, search strategy and robust systematic methods that were used to conduct the study. Part B provides an overview of T2DM enabling a broader understanding of the disease, with a focus on South Africa and the challenges of obtaining accurate T2DM prevalence estimates. We also describe prevention and management strategies for T2DM, and point to priority actions and approaches to achieve such prevention and management of T2DM. Part C consists of a manuscript that has been formatted for submission to BMJ Open and Part D is an Appendix with supporting information. This part addresses the aim of the dissertation and presents the systematic review "The prevalence of type 2 diabetes in South Africa: A systematic review". The manuscript outlines the rationale and methodologies, together with presenting and discussing the results of the systematic review. Our literature search, which included PubMed, Scopus, Web of Science and African Index Medicus, grey literature and references of included studies identified 1782 articles published in South Africa between January 1997 and May 2019. Of these, 15 met the inclusion criteria and were included in the systematic review. Heterogeneity across studies did not allow for a meta-analysis and a pooled estimate, thus results are described narratively. Some studies failed to report key methodological elements, which limited our ability to accurately appraise study quality. In conclusion, the systematic review highlights the high prevalence of glucose intolerance in South Africa and confirms the paucity of accurate and representative T2DM prevalence data. There is a need for well-designed epidemiological studies that use best-practice, uniform diagnostic methods to assess prevalence. Collaboration between public health scientists, diabetes specialists and policy makers is recommended to enable the collection of reliable national epidemiological data which can guide policy and planning towards effective diabetes prevention and management strategies.

Staphylococcus aureus is a major human pathogen found worldwide, causing a wide variety of clinical infections. This ranges from skin and soft tissue infections to lifethreatening invasive disease, such as S. aureus bacteraemia (SAB). Despite being a common cause of both community-acquired and hospital-acquired infections, limited evidence exists on the management and outcomes of Staphylococcus aureus bacteraemia (SAB) in resource-limited settings. The aim of this study was to describe a cohort of South African patients with SAB, and explore the factors associated with complicated infection and death. A prospective observational study was performed of patients over the age of 13 years admitted to a South African referral hospital with SAB. Data were analysed using Kaplan Meier survival models and linear regression models. One hundred consecutive SAB infection episodes in 98 patients were included. SAB was healthcare-associated in 68.4%, with 57.6% of these linked to drip site infection; 24.0% of all cases were caused by methicillin-resistant S. aureus (MRSA). Ninety-day mortality was 47.0%, with 83.3% of deaths attributable to SAB. Predictors of 90-day mortality were MRSA (odds ratio (OR) 1.28; 95% confidence interval (CI) 1.0 to 15.1) and the presence of co-morbidities (OR 4.1; 95% CI 1.0 to 21.6). The risk of complicated infection was higher with suboptimal antibiotic therapy (OR 8.5; 95% CI 1.8 to 52.4), female sex (OR 3.8; 95% CI 1.1 to 16.3) and community-acquired infection (OR 7.4; 95% CI 2.0 to 33.1). Definitive antibiotic therapy was suboptimal in 22.6% of all cases. Overall, SAB-related mortality was high. A large proportion of SAB episodes may be preventable, and there is a need for improved antibiotic management in this setting. Part A. The study protocol, as submitted for departmental and ethical approval, is presented here. It includes the background, rationale and methodology of the research done for this mini-dissertation. Part B. A structured literature review is presented of articles pertaining to SAB epidemiology and treatment, with the aim to place this research study in context and identify gaps in research. Part C. A journal-ready manuscript according to the requirements of the International Journal of Infectious Diseases. Appendix. All additional documentation necessary as addendums in the presentation of this mini-dissertation.

Background: The increase in access and coverage of ART, including through prevention of mother-to-child transmission (PMTCT) programmes in Africa, has resulted in the reduction of vertical transmission, which has led to >95% of infants born to women living with HIV (WLHIV) in South Africa being born HIV uninfected. Concerns have however been raised regarding the health and development of HIV exposed and uninfected (HEU) infants. WLHIV in South Africa are more likely to have an unintended pregnancy compared HIV negative women. Unintended pregnancies continue to be a challenge towards the on-going strides and achievement of PMTCT goals. There is however a paucity of data on the investigations in research for the effect of unplanned pregnancy and early child development in South Africa. This research study focused on early infant development health outcomes of HIV exposed but uninfected (HEU).The aim of the study was to investigate the association between the intention of pregnancy among pregnant WLHIV, and the subsequent early child development of their HEU infants in Gugulethu, South Africa. Methods: This study used data from the “Long-term Adherence and Care Engagement” study (LACE; May 2017-Apr 2018), which provided long-term data from women who had initiated antiretroviral therapy (ART) during pregnancy. During pregnancy, the London Measure of Unplanned Pregnancy was used to assess pregnancy intentions. At 36-60 months postpartum, child development was assessed across six developmental domains using the Ages & Stages questionnaire (ASQ). Multivariate Linear regression models were used to examine the association between pregnancy intentions and subsequent child development, with results reported as regression coefficients (β) with 95% confidence intervals (CI). Results: A total of 250 mother-infant pairs completed assessments and were included in analysis. At enrolment, the median age for the women was 28.3 years, and 38% were married and/or cohabiting. Overall, based on the women's responses 58% of pregnancies were categorised as unplanned. Upon analysis, no associations were observed between pregnancy intention and all early child development domains p>0.05. Overall, infants with evidence of early developmental delay that scored below threshold (ASQ-3) were 8% for the gross motor domain, 19% for fine motor, 4% for communication, 15% for problem solving, and 7% for personal social domain. Whilst for the social emotional domain (ASQ: SE-2), two percent of infants scored above threshold and hence, had evidence of early developmental delay. Conclusions: Among women initiating ART during pregnancy, we observed no significant association between pregnancy intention and the early child development of their HEU infants. The findings of this research accentuate the need for targeted strategies towards psychosocial issues, and educational interventions for WLHIV and, for informed fertility decisions. Furthermore, the need for exploration of interventions to encourage infant-parent attachment and interaction for development, as well as the impact of pregnancy intentions on parenting behaviours.