Includes bibliographical references (leaves 236-251). / This thesis develops a methodology for measuring equity in access to health care. The thesis deconstructs the concept of access into dimensions that represent the supply and demand side of health care and tests each of these dimensions by using the example of access to malaria services in the Kassena-Nankana district of northern Ghana. An innovative framework and a disadvantage index are developed herein, and are used to analyse the primary factors of access and to measure inequities in such access. A cross-sectional survey of 1880 household heads, focus group discussions, in-depth and key informant interviews with community members and health providers were used to explore issues in respect of malaria management, health care access and perceptions of poverty. The principal component and factor analysis statistical methods were then applied to estimate access factors and to compile a disadvantaged index of access. The key findings indicate that the dimensions, availability, affordability, information and acceptability primarily determine access to health care. On the availability dimension, physical distance to health care, provision of primary and inpatient are and travel distance are significant factors. The primary factors of affordability are associated more with the socio-economic characteristics of the household than with direct user costs. The information dimension is determined primarily by knowledge to treat levels of severity of malaria and the source of information for treatment. The acceptability of health care is related to methods and services for managing severity of levels of malaria at home as well as using qualified health care providers. The disadvantage index and poverty maps show significant disparities in health care access between geographic areas and socio-economic groups', with areas in the outskirts of the Kassena district being the most disadvantaged in terms of availability, acceptability and information. These areas are however not economically disadvantaged. The poorest households have the lowest accessibility scores across all dimensions.

Includes bibliographical references. / Widespread under-reporting of acute pesticide poisoning (APP) in developing countries, such as Tanzania, leads to under-estimation of the burden from APP. This thesis aimed to characterize the health consequences of APP in rural agricultural areas in Tanzania with a view to developing an effective surveillance system for APP. Several sub-studies comprise this thesis: A household survey of farmers; A hospital data review for APP, both retrospective, covering a 6-year period, and prospective for 12 months;Health care providers' knowledge and practices relating to APP and notification;Pesticide retailers' knowledge, distribution and handling practices; Stakeholder views regarding APP, notification and risk reduction strategies; and an assessment of APP data from sources other than the hospital system. The study found that major agents responsible for poisoning included Organophosphates and highly or moderately hazardous products and the age group 20 - 30 years was most affected. The majority of health care providers lacked skills for diagnosis of APP. The most problematic circumstances of poisoning in hospital data review was suicide but was occupational with pesticide stakeholders and in household surveys. Prospective data collection in the hospital review reduced the amount of missing data, suggesting that with proper training and support, hospital-based reporting can provide better surveillance data. Many farmers and pesticide retailers had unsafe practices likely to result in exposure and risk for poisoning. Modelling suggested that the Incidence Rate for occupational poisoning ranged from 11.3 to 279.8 cases per million people with a medium estimate of 32.4 cases per million people. The study identified a high burden from APP in Tanzania, largely unreported, particularly from occupational poisonings, and proposes an APP surveillance system for Tanzania aimed at addressing both workplace and non-workplace settings. The system is expected to identify poisoning outbreaks, circumstances and outcomes, agents, poisoning patterns by gender, age, population and geographical areas most affected. Data sources for the system will include health care facilities and other government Institutions, media and community members through community self-monitoring. The system is expected to generate rate estimates and trends for pesticide poisoning, identify opportunities for prevention, further research needs and, ultimately, assist in reducing health risks arising from pesticide exposure.

Includes bibliographical references (leaves 184-200). / To effectively support the primary health care transformation of the South African health system, human resource development is needed. Nurses, at the forefront of primary care service delivery, urgently need support and advancement to fulfill their role. This study aimed to investigate the impact of core competency training on primary care nurse competence. To begin this investigation, a framework or core competencies was generated through two reference group meetings. This work was followed by a Delphi study to further define core competence in primary care nursing and how best to measure such competence. Nine core competencies were defined which led to the development and piloting of a core competency evaluation tool including a self-lest and observation tool. This early work was followed by the implementation and evaluation of a novel core-competency training program. This program was implemented within district health systems with working clinic nurses. It involved tour distinct sites in three different provinces. A total of 162 nurses took part in the study, including an intervention and reference group. The goal was to assess the impact of training in a real world setting. Using the self-lest and observation tools, this study showed that competence does improve with this type of training. Additionally, competence is most reliably assessed through observation since test familiarity and possible contamination decrease the usefulness of repeated self-test measures. Further assessment or this novel training program and ref1nement of the measurement tool are recommended. This study can serve to inform health policies, particularly regarding human resource development within emerging district health systems. It provides a practical and effective training approach for increasing nurse performance of primary care core competencies.

Includes bibliographical references (p. 212-244). / [Objectives] There is a paucity of data regarding paediatric adherence in resource-limited settings (RLS) especially among the very young age groups (<7yrs). The study investigated the rates of adherence, the identification of the adherence measurement, amongst four, which best correlates with viral load suppression; as well as correlates of adherence amongst a cohort of children younger than 7 years on antiretroviral HIV treatment. Design: A Prospective cohort study with 6 months follow-up [ Methods ] Measures of adherence used: caregiver self-report (CSR), medicine measure/pill count, pharmacy refill and clinic attendance. Child, caregiver, socio-economic and health service characteristics were assessed for impact on adherence. Bivariate and multivariate analyses were used to determine agreement between measures and viral load outcome and to determine correlates of adherence. [ Results ] Mean age of children enrolled into the study was 27.08 months with a cohort mean adherence rate of 85% and mean viral load suppression of 74% at 6 months. Biological mothers were the majority primary caregivers (85%) and the majority (76%) of caregivers were unemployed with 60% receiving some form of social welfare grant. Results showed that caregiver selfreported adherence (CSR) was significantly correlated with viral load at 6 months (p=0.004). Correlations were found between clinic visits and pharmacy refill (highest values 0.35; p=0.000) and between medicine measure and clinic visits (highest value -0.21; p=0.04) but none of these measures were significantly correlated with viral load. Sensitivity and specificity analysis for CGSR showed that >95% adherence ensured a good viral load outcome. Four factors were significantly associated with adherence in bivariate analyses. These were: access to social welfare grants (OR=2.7; p=0.05); being counselled for initiation of ARV treatment by a counsellor vs. a doctor or nurse (OR 3.2, p=0.03); having another person in the household other than the index child infected with HIV (OR = 0.34, p=0.05) and caregiver depression (OR=0.07, p=0.01). However, in multivariate analyses certain other child, caregiver, socio-economic and health system characteristics as well as the abovementioned variables emerged as significant. [ Conclusion ] Key findings indicate that adherence rates are relatively high in this cohort and CGSR is valid in a resource-poor setting but medicine measure was problematic as a paediatric HAART adherence measure. Certain child, caregiver, socio-economic and health system characteristics have a significant impact on adherence.

Includes abstract. / Includes bibliographical references. / Since 2004, increasing numbers of children in sub-Saharan Africa have commenced antiretroviral therapy (ART). This thesis reviews the outcomes of published studies of paediatric ART cohorts in Africa, describes outcomes for children receiving ART in South Africa and examines determinants of mortality and generalizability across the Southern African region. Temporal trends in characteristics at ART initiation are also examined. The measurement of treatment success in resource-limited settings is reviewed, by examining virological failure, and assessing the diagnostic accuracy of immunological criteria for identifying virological failure.The results chapter is presented in the form of published or submitted papers based on data from the International epidemiologic Databases to Evaluate AIDS-Southern Africa (IeDEASA) collaboration. The first paper reviews paediatric ART studies from Africa published before 2008. Together with the literature review in chapter 1, it provides the background to this thesis. The second paper reports on mortality (8%) and retention in care (81%) by 3 years after ART start for > 6,000 children who initiated ART in South Africa. The generalizable prognostic models in the third paper suggest that mortality during the first year on ART ranges from <2% to >45%, with the majority of children being in the group with the best prognosis. The fourth paper reports that 1 in 5 children meet criteria for confirmed virological failure by 3 years on ART. The risk is greater with triple ART containing nevirapine or unboosted ritonavir (in comparison with lopinavir/ritonavir or efavirenz). The fifth and sixth papers demonstrate that immunological criteria have low sensitivity and positive predictive value for virological failure. Targeted viral load measurement reduces the number of false positive virological failure diagnoses. The final paper shows that increasing numbers of children have initiated ART with a decline in disease severity at therapy start from 2005-2010. However, even in 2010 a substantial number of children started ART with advanced disease. The thesis concludes that access to ART for children has increased, with good outcomes. HIV cohort research is important in evaluating the safety and effectiveness of different models of care, treatment and monitoring strategies.

Includes bibliographical references. / The effectiveness of prevention of mother-to-child of HIV (PMTCT) programmes depends on the successful coverage of a series of interventions through pregnancy, intrapartum and postpartum. Routine monitoring systems based on service data and limited to women on the PMTCT programme may overestimate intervention coverage at multiple points along this cascade. Methods: Cord blood specimens with individually linked anonymous demographic and pregnancy data were collected from three delivery services in the Western Cape Province, South Africa, and screened for HIV. Seropositive specimens were tested for the presence of antiretrovirals.

High intake of sugar has been recognised as a contributing factor to diet-related overweight and obesity, and as a determinant for non-communicable disease (NCD) emergence in LMICs. In 2015, the World Health Organization (WHO) released a guideline giving specific advice on limiting sugar intake in adults and children. Policy guidance has also been provided to promote healthy diets and/or restrict unhealthy eating habits at country-level. The study explored the extent to which global policy recommendations and directives on reducing sugar intake to prevent and control NCDs have found expression in policies issued at the Africa region, South African national or sub-national Western Cape provincial level. A systematic policy document review was conducted to identify policies between 2000 and 2020, at different levels of government using search terms related to sugar, sugar sweetened beverages (SSBs) and NCDs. NVivo 12 software was used to code and thematically analyse the data. A policy transfer conceptual framework was applied for the policy analysis to assess what ideas were transferred, including why and to what extent transfer occurred. Forty-eight policy documents were included in this review. Most were global or national level policies. It was evident that several global policy ideas on unhealthy diets and reduction of sugar intake had found expression in South African health policies, as well in the education and finance sectors. Global recommendations for effectively tackling unhealthy diets and NCDs are to implement a mix of cost-effective policy options employing a multisectoral approach. Local policy action has followed the explicit guidance from international agencies, and ideas on reducing sugar intake have found expression in sectors outside of health, to a limited extent. Together with the adoption of the sugar-sweetened beverages (SSBs) health tax, South Africa's experience offers learnings for other LMICs.

There are insufficient randomized controlled trials to address whether screening for type 2 diabetes mellitus (T2DM) improves health outcomes. This systematic review sought to cast a wider net and synthesise evidence from non-randomised intervention studies to assess the effectiveness of T2DM screening in adults for reducing mortality and T2DM-associated morbidity. We searched PubMed/MEDLINE, Scopus, Web of Science, CINAHL, Academic Search Premier and Health Source Nursing Academic (inception onwards; last search July 2021). We included non-randomised intervention studies that assessed T2DM screening compared to no screening, in adults without known T2DM. Screening was performed independently by two reviewers. Data was abstracted by one reviewer and checked by a second, as was risk of bias (ROBINS-I) and certainty of evidence (GRADE). A narrative summary was performed. We screened 10,892 records, retrieving 67 for full-text screening with one record meeting inclusion criteria. The study was a prospective cohort comparing T2DM screening versus no screening. It included adults, 40 - 65 years, with no known T2DM from a single community practice in Ely, England (N = 4,936) and evaluated outcomes at two time periods. The study was assessed as having moderate risk of bias. There may be little or no difference in mortality between those who were invited to screening versus those who were not invited (1990-1999: adjusted hazard ratio (aHR) 0.79 [95% confidence interval (CI) 0.63 – 1.00], n = 4,936, low certainty evidence and 2000 - 2008: aHR 1.18 [95% CI 0.93 - 1.51], n = 3,002, low certainty evidence). We found only one study reporting the effectiveness of screening for T2DM in adults. Therefore, despite ongoing T2DM screening in clinical care, this review highlights an important research gap in understanding the true health benefits of screening.

Background: HIV incidence amongst adolescents in Southern Africa remains extremely high. The importance of adolescent HIV prevention strategies in tackling the epidemic worldwide is increasingly recognised with a global target from UNICEF to reduce new adolescent HIV infections by 75% by 2020. Adolescent vulnerability to HIV infection is a result of a complex interplay between structural, economic, socio-cultural, and biological factors during a phase when behaviours associated with HIV acquisition and sexual and reproductive health-seeking are initiated. The vulnerability of young people to HIV is particularly manifest in South Africa, where young women aged 15-24 accounted for almost 40% of new HIV infections in 2017. PreExposure Prophylaxis (PrEP) has been demonstrated to be effective for preventing HIV infection in adults but there is little data on its implementation among young people. Given the HIV incidence rates amongst adolescents in Southern Africa, oral PrEP for this group is likely to have an impact on population-level HIV incidence. We designed an open-label demonstration study known as Pluspills, for adolescents aged 15-19 years in South Africa to understand the safety, feasibility, and patterns of use of oral pre-exposure prophylaxis (PrEP) as part of a broad package of interventions, to prevent HIV. Methods: Pluspills was conducted in two distinct peri-urban settings in Johannesburg and Cape Town. The aim was to study the safety and acceptability of oral PrEP (tenofovir disoproxil fumarate/Emtricitabine) in two adolescent populations in South Africa. HIV-negative participants between 15-19 years old participated in an open-label oral PrEP study over 52 weeks. Participants took daily PrEP for the first 12 weeks and were then given the choice to opt-in or opt-out of PrEP use at three-monthly intervals. Serial plasma and DBS tenofovir concentrations were measured at every PrEP refill visit, and results were discussed with participants during adherence counselling sessions. Testing for sexually transmitted infections (STI's) was conducted at baseline, twelve and forty-eight weeks. Findings: Overall 148 participants were enrolled (median age 18 years; 67% female) and initiated PrEP. STI prevalence at the study start was high at 41% (60/148) and remained high throughout the study. The decision to stop using PrEP was made by 26 (18%) participants at 6 the 12-week visit. Cumulative PrEP opt-out at weeks 24 and 36 comprised 41% (60/148) and 43% (63/148) of the total cohort respectively. PrEP was relatively well tolerated with few reported adverse events. Tenofovir diphosphate (TFV-DP) levels as measured in dried blood spot samples were detectable (>16fmol/punch) in 92% (108/118)) of participants who reported PrEP use at week 12, 74% at week 24 (74/100), and 58% (22/37) by the end of the study. One HIV seroconversion occurred during the study (0.76/100 person-years) in a 19-yearold female participant who had chosen to stop taking PrEP, 24 weeks before diagnosis. Interpretation: In this small cohort of South African adolescents at risk of HIV acquisition, PrEP was safe and well-tolerated in those who continued to use it. PrEP use decreased throughout the study as visit frequency declined. The incidence of sexually transmitted infections remained high, despite low HIV incidence. The study confirms that this population needs access to PrEP with particular attention to tailored adherence support. Young people would also possibly benefit from the option for more frequent and flexible visit schedules.

Background: It's been 20 years since the Western Cape (WC) province of South Africa launched its first Prevention of Mother-To-Child-Transmission of HIV(PMTCT) pilot programme in Khayelitsha. The programme evolved alongside the World Health Organization (WHO) guidelines; in 2013 the recommended guidelines in the province was WHO Option B+( life-long antiretroviral therapy (ART) irrespective of CD4 count, and exclusive breastfeeding for the first 6 months of life). Alongside the explanation of the PMTCT programme, the province gradually implemented patient administrative systems in all fixed public health facilities; these systems all shared a unique patient identifier called the folder number. The digitization of folder number lead to the establishment of the Provincial Health Data Centre (PHDC), an African health information exchange (HIE) developed and hosted in the WC Department of Health. The HIE also integrated data from disease management information systems (Three Interlinked Electronic Registers (TIER) and the Electronic Tuberculosis Register (ETR)), allowing the ability to track the cohort of pregnant women living with HIV who attend public health services across the Western Cape. Here we report the latest analysis of vertical HIV transmission in the era of WHO Option B+ with the advantage of a maturing consolidated African HIE. The primary aim of the study was to describe coverage of the PMTCT care cascade, including the implementation of maternal viral load monitoring and early infant diagnosis, among HIV positive women who presented antenatal care, or delivered in the absence of antenatal care, at a public health facility in Khayelitsha subdistrict in 2017; and to quantify MTCT risk factors and outcomes among this cohort up to 12 months post-partum. Methods: Patient-level consolidated PHDC data were used to draw an observational cohort consisting of all live-born and linked mother-infant pairs in which the mother was HIV positive, at any point prior to her first antenatal visit up to 12 months post-partum and attended antenatal care, or in the absence of antenatal care delivered in Khayelitsha in 2017. The PHDC provided a single summative record per pregnancy for each woman (linked to her infant after birth) which enabled the assessment of PMTCT uptake from her first antenatal visit through delivery to infant early infant diagnosis (EID) of HIV-PCR testing and PHDC ascertainment of HIV up to the end of the index period (i.e. 12 months post-partum). iii Using this cohort of HIV-exposed infants, a protocol was designed (Section A: Protocol) to assess the outcomes of the implementation of WHO Option B+(lifelong ART for all HIV positive pregnant women; and periodic re-testing of HIV negative women) under the latest EID guidelines of routine birth HIV-PCR (within 1 week of birth), and repeat testing at 10 weeks (between 2 and 14 weeks of birth) or a first HIV-test at 10 weeks if the infant had not been tested at birth. Continuous variables were converted to categorical variables according to pre-set thresholds, all categorical variables were described using proportions, and frequency tables were used for comparison. Timing of ART initiation was categorized as a binary variable which was assigned 1 if the mother started ART before the first antenatal visits, and 0 of she started ART at the first antenatal visit or anytime during the pregnancy. Viral load was categorised according to coverage and suppression status; virologic suppression was defined as having a viral load of 1000 copies/ml or less after 3 months on ART. Analysis was performed in using R studio; descriptive statistics were used to assess coverage along the PMTCT care cascade, and logistic regression was run to quantify a priori defined risk factors associated with MTCT. Results: The study cohort of 2 576 mother-infant pairs (2548 women living with HIV (WLHIV)) presented in the manuscript was a young cohort with a median age of 30 years (interquartile range of 26 – 34), in which most women delivered vaginally (70.5%), and 78.3% attended at least one antenatal visit before delivery. Most WLHIV (88.3%) presented to their first pregnancy related visit (antenatal care or delivery) already knowing their status, of whom 77.9% were already on ART. 94.5% of women diagnosed prior to birth were initiated on ART prior; 85.0% of these women received a viral load test antenatally, of whom 88.0% were virologically suppressed. Early infant diagnosis coverage was sub-optimal with birth HIV-PCR (within 7 days of birth) coverage of 79.21% among HIV exposed infants (HEI); an even lower proportion (57.9%) of HEI who tested negative at birth had a repeat test around 10-weeks. HIV-PCR ascertained MTCT was 0.8% at 10 weeks, consolidated data from the PHDC suggested an MTCT of 1.8% by the end of the index period (the PHDC HIV episode identified an additional 16 HIVexposed (HEI) infants with HIV who were not detected by laboratory tests). PWLHIV who started ART prior to the first antenatal visit had 50% reduced risk of MTCT compared to those who started ART during the pregnancy. Women who were not suppressed antenatally had a 5- fold (aOR = 5.3, 95% CI: 2.5 – 12.3) increased MTCT risk compared to those were suppressed antenatally. Women who did not attend ANC were at highest risk of transmission (aOR=1.6,95%CI: 0.7 – 3.6). iv Conclusion: Although women most women present to care already knowing their HIV status, ART initiation and uptake of viral load testing is very low at presentation but improved significantly during pregnancy, evidence of maturing PMCT services. National and Provincial MTCT is likely to be underestimated as it relies solely on PCR results; the uptake of the birth PCR among HIV-exposed infants is still not 100% (where it should be) and the uptake of a repeat tests among infants that tested negative is even lower. PHDC data, which consolidates HIV data from multiple sources, revealed a higher MTCT than HIV-PCR testing alone.