Electronic Theses and Dissertations (PhDs)

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    Salient beliefs, preferences and intention to use HIV pre- exposure prophylaxis among pregnant and breastfeeding women in Zambia
    (University of the Witwatersrand, Johannesburg, 2024) Hamoonga, Twaambo Euphemia
    Pregnant and breastfeeding women living in sub-Saharan Africa are at substantial risk for HIV infection, and maternal seroconversion may affect the quality of life for the mother, and is a risk for vertical transmission of HIV. Despite the adoption of PrEP into national guidelines for HIV prevention, its uptake in antenatal and postnatal settings in Zambia remains low. We used an exploratory sequential mixed methods design to explore facilitators and barriers to uptake of PrEP among pregnant and breastfeeding women (18 years or older) not living with HIV in Zambia. We purposively recruited 24 women for the qualitative component and conveniently selected 389 women for the quantitative component of the study at Chipata Level 1 Hospital in Lusaka. For qualitative data, Nvivo was used for data management and data was analysed using thematic analysis. Quantitative data was analysed using chi-square test, pearson correlation coefficient (r) and logistic regression analysis using Stata v.16. Findings from our qualitative study showed that women had positive attitudes and favourable intentions to use PrEP. Most women felt that people who are important to them, especially their male partners, would not support PrEP use during pregnancy and breastfeeding. The anticipated disapproval from partners made women believe that PrEP use would not entirely be under their control, with some reporting that they would not use PrEP if their partners disapproved. Women also cited rude health care provider attitude as a potential barrier to uptake. Some women preferred receiving PrEP from a health facility for fear of stigma in the community while others preferred community-based delivery as an avenue for creating PrEP awareness. This paper was published in Frontiers in Reproductive Health In our second paper, we determined intention to use PrEP during pregnancy and breastfeeding and also identified salient beliefs associated with it. Participants had positive attitude and favourable intention to use PrEP during pregnancy and breastfeeding (mean = 6.65, SD = 0.71 and mean = 6.01, SD = 1.36), respectively. They felt that people who are important to them would approve of their use of PrEP (mean = 6.09, SD = 1.51) and also believed that they would be able to use PrEP if they desired (mean = 6.52, SD = 1.09). All salient beliefs positively and significantly predicted intention to use PrEP during pregnancy and breastfeeding: attitude (β = 0.24, p<0.01); subjective norms (β = 0.55, p<0.01); and perceived behavioural control (β = 0.22, p < 0.01). This paper was published in Global Public Health. The third paper discusses findings from a discrete choice experiment (DCE) on preferences for PrEP service delivery among pregnant and breastfeeding women. In this study, waiting time, travel time, health care provider attitude and amount of PrEP supply at each refill were important considerations likely to influence PrEP use during pregnancy and breastfeeding (all p<0.01). Women expressed strong preference for 3-month’s supply of PrEP compared to other attribute levels (β= 1.69, p<0.01). They were willing to wait for 5 hours at the facility, walk for more than an hour to a facility dispensing PrEP, encounter a health care provider with a negative attitude as long as they received PrEP enough for 3 months. This paper is under review in Frontiers in Reproductive Health. The overall contribution of this PhD research to the body of knowledge on HIV prevention strategies is the ability to identify beliefs about PrEP and how each salient belief influences intention to use PrEP during pregnancy and breastfeeding. It is also one of the first to estimate the benefit (value or satisfaction) that women derive from different attributes of PrEP service delivery for pregnant and breastfeeding populations interested in using PrEP. This information could provide guidance on specific beliefs and service delivery attributes of PrEP that women prefer the most and therefore need to be prioritized if PrEP uptake is to improve in antenatal and postnatal settings
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    Adolescent health in rural South Africa: building an evidence-base to inform a health promotion intervention supporting healthier lifestyles
    (University of the Witwatersrand, Johannesburg, 2024) Seabi, Tshegofatso Martha; Kahn, Kathleen; Wagner, Ryan G
    Background Low- and middle-income countries (LMICs), including South Africa, face the persisting double burden of malnutrition, with undernutrition and overnutrition coexisting within the population. This issue is particularly pronounced among rural adolescents, who experience limited access to healthcare services, inadequate infrastructure, poverty, and a scarcity of nutritious foods. Addressing this double burden of malnutrition is essential for improving the health outcomes of rural adolescents and breaking the intergenerational cycle of malnutrition. Community health worker-led interventions have shown promise in promoting healthier lifestyles in this population, making it crucial to understand the feasibility and acceptability of such interventions. Aim This thesis aims to provide context-specific information on the changing distribution of Body Mass Index (BMI) and views on obesity among rural South African adolescents to inform the development of a targeted behaviour change intervention. Furthermore, it seeks to determine the feasibility, acceptability, and overall experience of implementing a complex intervention aimed at promoting healthier lifestyles in this population. Methods Using a mixed methods approach focusing on adolescents 12-20 years of age living in rural South Africa. This work is nested within the MRC/Wits rural public health and health transitions research unit (Agincourt) Health and Demographic Surveillance System, which is where the sample was drawn and provided explanatory variables such as SES. This work includes data from two studies with comparable measures, conducted in 2007 (n= 1309) and in 2018 (n=518), this study analysed comprehensive data on the prevalence and trends of BMI, including both undernutrition and overweight/obesity, among rural adolescents in 2007 and 2018. This was done through weight and height measures. Growth z-scores were used to determine stunting, underweight and overweight and overweight/obesity was generated using the 2007 WHO growth standards for adolescents aged up to 17 years and adult cut-offs of BMI of <=18.5 for underweight and =>30 kg/m2 for overweight and obese respectively for adolescents 18 to 20 years. Qualitative data was collected in the form of focus group discussions and in-depth interviews. Pre-intervention, three focus group discussions were held with male (n = 16) and female adolescents (n = 15) focusing on obesity to capture views, attitudes and perceptions surrounding obesity. Post-interventions, six focus group discussions were held with male and female adolescents. In-depth interviews were conducted with adolescents (n=20), parents (n=5) and CHWs (n=3), focusing on the feasibility and acceptability of the health promotion intervention. All qualitative data were analysed using inductive thematic analysis. Results This study found that there is a persistent double burden of malnutrition amongst rural adolescents. The pattern of underweight and overweight/obesity remains similar between 2007 and 2018, with an increase in overweight and obesity, and a decrease in underweight observed across different age and gender groups throughout this period. The prevalence of stunting and underweight, particularly in males in both 2007 and 2018 was substantial although lower in the later year. Adolescents expressed conflicting views of obesity, highlighting their knowledge of the cause and long-term consequences of obesity. In regard to the intervention, participants expressed support for the CHWs and the community-based intervention guided by them. The findings demonstrated the feasibility of providing the intervention to adolescents in a rural context, with modifications needed to ensure participant uptake, such as changes to the time and location. Responses from participants show how the intervention, which included dietary and quantity modifications, was acceptable to adolescents. The gathered information in this study serves as a foundation for developing a health promotion intervention tailored to the specific needs and circumstances of rural adolescents, considering both undernutrition and overweight and obesity. Conclusion This research provides valuable context-specific insights into the burden of malnutrition and perceptions of obesity among rural South African adolescents, considering the complexities of the double burden of malnutrition. The findings contribute to the development of tailored health promotion interventions that address both undernutrition and overweight/obesity in this population. Understanding the feasibility and acceptability of such interventions is vital for successful implementation and sustainability in rural communities.
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    Attrition in the dental therapy profession: an exploration of the contributing factors
    (University of the Witwatersrand, Johannesburg, 2024) Sodo, Pumla Pamella; Jewett, Sara
    Background: A new type of oral health profession called dental therapy was introduced to address the growing need for affordable and accessible oral healthcare services, especially among marginalised communities. Extensive global research has demonstrated that dental therapists provide cost-effective and high-quality services, effectively addressing the issue of limited access to basic oral health services. The introduction of dental therapy into the South African healthcare system took place in 1977, however, disparities in accessing basic oral healthcare persist, particularly among some population groups where the highest prevalence of oral diseases has been reported. Despite being established over four decades ago, the number of registered dental therapists remains low, and there have been reports of attrition within this professional group. This PhD aimed to explore the factors contributing to attrition in the dental therapy profession. The first objective was to determine South African dental therapists' attrition rate and demographic profile over 42 years (1977-2019). The second objective explored factors contributing to attrition, while the third objective explored the applicability of the Hertzberg Two-Factor Theory in the context of dental therapy attrition in South Africa. Methods: This was a concurrent mixed methods study, involving registered graduate dental therapists, former dental therapists, and key stakeholders. The conceptual framework that guided the study was derived from Hertzberg's Two-Factor Theory. Data sources included the HPCSA registry and primary data collected using a quantitative survey investigating job satisfaction and intention to leave among registered graduate dental therapists and qualitative in-depth interviews with former dental therapists and key stakeholders to gain insights into their perspectives on attrition in the dental therapy profession. The attrition rate was determined by using the formula (Attrition Rate = Number of dental therapists who left the profession divided by the total number of dental therapists registered during the period of interest, multiplied by 100). Quantitative data was analysed in STATA version 15 using descriptive and inferential statistics, and qualitative data was analysed using thematic analysis. Findings: A total of 1232 dental therapists were registered with HPCSA over 42 years, with only 714 registered in 2019, two-thirds of whom were Africans. The attrition rate over the 42 years was 40%, while it reduced to 9% during the 10 years from 2010 to 2019. Of the 200 registered dental therapists who took part in the survey, 74.5% being Africans, approximately 51.5% expressed their intention to leave the profession and a notable 69.5% reported job dissatisfaction. In logistic regression analysis, job satisfaction correlated positively with several factors, including qualification from UKZN (AOR= 2.28, CI: 1.06-4.91), post-graduation job availability (AOR=3.87, CI: 1.73-8.69), awareness of postgraduate opportunities (AOR=2.28, CI: 1.05-4.96), and feeling valued (AOR= 6.91, CI: 1.45-26.36). Conversely, job satisfaction was negatively associated with becoming aware of the scope of work only after enrolment (AOR= 0.31, CI: 0.21-0.81). Job satisfaction was inversely correlated with the intention to leave; satisfied individuals had significantly lower odds of intending to leave (AOR= 0.25, CI: 0.11-0.57). In-depth interviews with 14 former dental therapists identified diverse reasons for enrolling in dental therapy and a shared enthusiasm for the dental therapy profession. Most reasons they cited for attrition, such as inadequate remuneration, job scarcity, poor working conditions, lack of career advancement opportunities, and policy implementation gaps aligned with Herzberg's Two-Factor Theory. One novel factor contributing to attrition not covered by the theory was a lack of professional identity. The 12 key stakeholders who were interviewed echoed similar factors contributing to the attrition of dental therapists. To address limitations in moving from a description of factors to recommendations on how to address system-level challenges, I adapted a framework that is a combination of Herzberg's Two-Factor Theory and the Human Resources for Health System Development framework. This new framework addresses multifaceted issues affecting dental therapists, covering production, deployment, and retention. Conclusion: This study sheds light on challenges within South Africa's dental therapy profession, highlighting their profound implications for both the profession and the broader healthcare system. Despite comparable attrition rates to other mid-level health professionals, there were alarmingly high job dissatisfaction levels and intentions to leave the profession, demanding immediate attention and intervention. Identifying key factors contributing to attrition and the novel insight into the lack of professional identity collectively highlight the multifaceted nature of the issue. To address these challenges, embracing a comprehensive human resource retention framework is imperative. This study emphasizes the urgent need for proactive measures to ensure the sustainability and contentment of dental therapists, ultimately benefiting the healthcare system and the communities it serves. Addressing these factors will lead to increased retention rates and improved access to basic oral health services nationwide
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    Exploring the relationship between orphanhood status, living arrangements and sexual and reproductive health outcomes among female adolescents in Southern Africa
    (University of the Witwatersrand, Johannesburg, 2024) Shoko, Mercy; Kahn, Kathleen; Ginsburg, Carren
    Adolescent Sexual and Reproductive Health (ASRH) is high on the global development agenda. Among the respective research conducted is the various social contexts that may contribute to adverse SRH outcomes, including the overlapping issues of orphanhood and living arrangements. These are crucial given that the presence or absence of parents emerges as critical for the sexual and reproductive well-being of adolescents. While orphanhood, particularly in the context of the HIV epidemic in Southern Africa, receives considerable attention, this study highlights a noteworthy gap in the literature – the limited focus on living arrangements and its influence on ASRH, often overshadowed by orphanhood. This research is important given the evidence suggesting that the African traditional kinship care systems offer support for orphans. However, recent research also highlights the crucial role of biological parents in providing effective care and support for adolescents. The study aims to contribute by exploring the relationship between orphanhood status, living arrangements, and ASRH in Southern Africa. Utilising cross-sectional Demographic and Health Survey (DHS) data, the analysis delves into key dimensions of SRH, including sexual debut, HIV knowledge, and adolescent fertility, which are all critical links to HIV risk. The findings underscore a significant association between non-coresidency with parents, whether due to orphanhood or separate living arrangements, and a heightened risk of adverse SRH outcomes. This suggests that interventions aimed at addressing adolescent SRH in Southern Africa should encompass a holistic understanding of parental presence or absence. The study emphasises the complex interplay between orphanhood, parental absence, and various individual, household, and geographic factors that collectively contribute to the vulnerability of female adolescents in the context of ASRH. Despite that the results suggest that the data on orphanhood and living arrangements may be of acceptable quality, the study recognises the potential for detailed insights through future research employing longitudinal data. Such an approach could offer a more nuanced and comprehensive understanding of ASRH over time, subsequently informing targeted policies and interventions in the unique socio-cultural context of Southern Africa
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    The development of a competency-based programme for management of disease outbreaks
    (University of the Witwatersrand, Johannesburg, 2024) Engelbrecht, Linette
    Purpose: The purpose of this study was to develop, a competency-based programme for the management of disease outbreaks. Method: The study utilized an exploratory sequential mixed method approach, using both qualitative and quantitative methods to develop a competency-based program. This study was conducted in South Africa, Gauteng, whilst the country was experiencing the third COVID-19 wave (May 2021 – October 2021), the fourth COVID-19 wave (December 2021– April 2022), and the fifth (May 2022 – July 2022), as well as the post-pandemic phase. The study was conducted in three phases namely: Phase One: Exploratory phase, Phase Two- Development of the programme Phase Three- Validation of the programme. In phase one, a scoping review on the existing literature was conducted using the Joanna Briggs Institute methodological approach. Following this were individual in-depth interviews with purposively sampled healthcare professionals as well as professional nurses. Through reflexive thematic analysis themes were identified for inclusion in the Delphi-survey in the next phase. For the second phase, a Delphi-survey was developed based on the data from phase one. The Delphi-survey consisted of two rounds whereby categories were identified to be included in the competency-based curriculum. A curriculum, consisting of ten modules was developed using the Backward design. In phase three the curriculum matrix was validated by experts. Results: A total of 62 publications were included in this study. Three categories and eight sub-categories were identified as needs of nurses during disease outbreaks. In-depth interviews with healthcare professionals resulted in the development of eight themes and 21 sub themes (challenges) of nurses. The in-depth interviews with nurses resulted in the development of 11 themes (challenges) of nurses. The results of the scoping review and in- depth interviews were used to develop a Delphi-survey. Experts in this two-round Delphi survey validated the domains and statements. The results of the Delphi-survey was used to develop a curriculum matrix consisting of ten modules, which was validated by three experts. Conclusion: A competency- based curriculum was developed based on the challenges nurses experienced working through the COVID-19 pandemic. This program could contribute to the development of disease outbreak competent nurses
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    Community-orientated primary health care: Exploring the interface between community health workers, the healthcare system and communities in South Africa
    (University of the Witwatersrand, Johannesburg, 2024) Malatji, Hlologelo; Goudge, Jane; Griffiths, Frances
    Background: To achieve universal health coverage, low and middle income countries (LMICs) are extending primary health care (PHC) services using community health worker (CHW) programmes. However, CHWs are marginalized within the healthcare system. Community-orientated primary health care (COPC) and supportive supervision are two interventions being used to strengthen CHW programmes. Primary aim: To understand whether and how the COPC and supportive supervision approaches strengthen CHW programmes in South Africa. Methods: Data was collected between 2016 and 2019 using qualitative methods in nine PHC facilities in rural and semi-urban areas of Mpumalanga and Gauteng provinces, South Africa. Purposive and snowball sampling techniques were used to recruit participants. The participants included: CHWs, supervisors, facility staff members and community members. Data was collected using focus group discussions, individual interviews and observations, and was analysed thematically. Findings: In line with the COPC approach, there were efforts to engage communities in the implementation of the CHW programmes but community members prioritised other challenges such as lack of housing and running water. In some facilities, in-service training increased CHWs knowledge and skills but challenges such as lack of supervision, lack of resources and outsourced employment without benefits demotivated the CHWs (Paper 1 / Objective 1, Published). In response to challenges, in the semi-urban sites, CHWs unionised to present their grievances to government. This resulted in an increase in stipend but not permanent government employment. During the height of the COVID-19 pandemic, when decision- makers recognised the essential role of CHWs higher remuneration was secured. CHWs in rural areas were not active in demanding permanent employment (Paper 2 / Objective 2, Published). Supportive supervision provided by a nurse mentor over 14 months, (1) trained CHWs and their supervisors resulting in increased knowledge and new skills, (2) addressed their fears of learning and failing and (3) established operational systems to address inefficiencies in CHW core activities (household registration and medication delivery). The intervention was disrupted by union activities. The communities’ demonstrated little interest in the functioning of CHW programmes (Paper/ Objective 3, Published). Conclusion: Both the COPC approach and supportive supervision can reduce marginalisation of CHW within the health system
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    Characterisation of emission and exposure to diesel engine exhaust from trackless mobile machinery in underground South African Platinum Mines: Evaluating strategies to prevent and control exposure
    (University of the Witwatersrand, Johannesburg, 2024) Manyike-Modau, Amukelani Portia; Brouwer, Derk
    Background: Mining remains one of the major economic drivers in South Africa, as is evident through continued focus on long-term investments in mining and the mechanisation of mining operations. Mechanisation uses diesel-powered machinery; such machinery offers greater versatility than electric and battery-operated vehicles due to their ability to cover greater distances and move between different working sections (1). Diesel powered machines are most preferred because of their high energy efficiency and low carbon monoxide and carbon dioxide emissions compared to gasoline equipment (2). Using diesel-powered machines in mechanised mining has introduced a new risk to mine workers working in confined spaces underground. Diesel engine exhaust (DEE) can increase significantly due to wear or breakdown of the engine components and after-treatment systems. The impact on emissions varies depending on the engine type, age, and state of wear and tear (3). Significant evidence demonstrates a correlation between DEE exposure and respiratory outcomes in mine workers. DEE is a known carcinogen. In 2012, the International Agency for Research on Cancer (IARC) classified DEE as being carcinogenic to humans (class I) when inhaled, based on sufficient evidence that exposure is associated with an increased risk for lung cancer (4). There has been an incredible drive to manage diesel Particulate matter (DPM) in the South African mining industry (SAMI). The approach, however, has been focused on monitoring personal exposure to DPM rather than a multifaceted approach that includes eliminating or reducing the pollutant at the source. Efforts should be made to ensure that management plans for engineered solutions and risk-based approaches are in place when monitoring DPM (5). As a result, research in the mining domain has focused on developing integrated control strategies/solutions to prevent exposure to diesel engine exhaust. South Africa shares the same concern with other countries regarding the DPM challenges in mining operations. The South African legal framework requires the employer to conduct a risk assessment and implement measures to prevent employees from overexposure to harmful airborne pollutants (MHSA 1996). Therefore, without local guidelines and regulations, SAMI can use the available scientific knowledge to control the exposure of DPM to employees and to ensure continuous monitoring of employees while working at the mines. Currently, no specific systems guide sets standards or limits for personal or occupational exposure or tailpipe emissions of DPM (6,7). Further, even though enough knowledge is The Occupational Cancer Research Centre Report published in 2017 presented different control strategies for DPM following the hierarchy of control principles (8). These ranged from the proactive (most effective) to reactive (less effective) controls and included the following controls: elimination using alternative energy such as electric or battery-powered machines, substitution such as replacing, repowering, or engine rebuilds, and this would typically include retrofitting the engines with engine after-treatment systems; Engineering controls which may include retrofitting the engines with after-treatment technologies, improving general ventilation systems, idling technologies, installation of protective cabs; Administrative controls which may include preventative maintenance, idling policies, operator training and planned schedule for the site such as planning the number of machines required to operate in a working place; and lastly the use of personal protective equipment such as respirators. These controlscan be implemented in a multifaceted approach to reduce or prevent employees from being overly exposed (3,8,9). Diesel emission is a complex mixture and may require multiple control strategies to minimise employee exposure. In the study conducted by Bugarski et al, 2009, they highlighted different monitoring and control strategies ranging from emissions monitoring, including undiluted emissions measurements, i.e., Both ‘tailpipe output’ and ‘engine out’ (upstream of after- treatment systems), and the installation of after-treatment strategies and higher tier standard engine emissions. The control strategies can help identify and distinguish between engine maintenance issues and emission control device failures and assist in estimating ventilation requirements (10). In addition, in a study by Hines in 2019, significant improvements were achieved in reducing tailpipe emissions (reduction at source) by implementing an emission- based maintenance (EBM) program. This has resulted in a reduction of Carbon Monoxide (CO) by more than 80% and DPM by more than 47% on personal exposure, showing the direct impact the EBM has on reducing exposure of DPM to employees working underground. The study successfully reduced tailpipe emissions by introducing the EBM program at the mines. Further, fuel usage was also reduced by 7-20%, showing that when machines are well maintained, there are improvements in efficiencies and even utilisation and availability of machines for production (11). Objective: The overarching aim of the research project was to determine the characteristics of diesel engine exhaust emissions at the source (aerodynamic size fractions) and evaluate how maintenance, maintenance plus installation of diesel particulate filters (DPF), and ventilation will impact the levels of DEE at the source and in the workplace. Methods: A quantitative, quasi-experimental study, designed with an intervention component, was conducted in two Platinum underground mines in South Africa. DEE was measured at the source, and DPM was personally exposed to employees. DPM dispersion modelling was conducted underground, and different control strategies were evaluated to determine their role in reducing the pollutant underground. Results: The concentration of median particles significantly decreased post the interventions, achieving an efficacy of 90-96% and 20-40% (p-value=0.001) for the machines that underwent maintenance plus installation of the DPF and machines that underwent maintenance only, respectively. Most particles emitted were in the ultrafine aerodynamic range, with a diameter between ≥0.01<0.1μm and an aerodynamic fine size of ≥0.1<1μm. Conclusion: A combination of control strategies (maintenance, retrofitting of machines with DPF, and ventilation) has shown great potential to reduce DEE in underground mines. Therefore, focused effort is required to implement integrated strategies to prevent or minimise exposure to DEE. Future studies to link dispersion models with real-time monitors are recommended to improve DEE's risk-based management
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    Trend of Pre-antiretroviral Therapy HIV-1 Drug Resistance in Kilombero and Ulanga Antiretroviral Cohort, South-Western Tanzania, for over 15 years (2005-2020)
    (University of the Witwatersrand, Johannesburg, 2024) Ntamatungiro, Alex; Kagura, Juliana
    Introduction Pre-treatment HIV drug-resistance (PDR) may result in increased risk of virological failure and subsequently acquisition of new HIV drug resistant mutations. With recent increase in antiretroviral therapy (ART) coverage and periodic modifications of the guidelines for HIV treatment, monitoring changes in levels of PDR is critical, particularly in under-sampled areas, such as rural Tanzania. This PhD project aimed to determine the trend and patterns of PDR in the Kilombero and Ulanga antiretroviral cohort (KIULARCO), analyse the impact of recent HIV-1 infection, and dolutegravir rollout in rural Tanzania. Methods The study comprised a systematic review and meta-analysis of primary studies about prevalence of PDR among ART-naive people living with HIV (PLHIV) (³15 years old), published between 2017 and 2022. The data had to be in one or several of the countries of Eastern Africa, namely, Ethiopia, Kenya, Malawi, Rwanda, Mozambique, Tanzania, and Uganda. Thereafter, cross- sectional analyses of data on newly HIV-1-diagnosed ART-naïve adults (aged ≥ 15 years), enrolled in the on-going prospective clinic-based observational rural antiretroviral cohort- KIULARCO focusing on various aspects of PDR. Multivariate logistic regressions were used to determine the factors associated with recent HIV-1 infection, and viral suppression at 12-months in patients initiating dolutegravir-based ART in the KIULARCO. Results Overall, the pooled prevalence estimate of any PDR was 10.0% (95% CI: 7.9%–12.0%, I2 =88.9%) among 22 studies in the general adults’ population, which was higher than the previously reported prevalence of 8.7% using data available until 2016 in the Eastern Africa region. PDR was mainly driven by non-nucleoside reverse transcriptase inhibitors (NNRTI); whereas the pooled prevalence of PDR to nucleoside reverse transcriptase inhibitors (NRTI) was 2.6% (95% CI: 1.8%–3.4%, I2=69.2%). Remarkably, PDR to NRTIs in a sub-population of recently HIV-1 infected PLHIV in the KIULARCO was high at 12.5%. Also, there was a notable tendency to an increasing prevalence of PDR to NRTI, with the overall prevalence of 2.1% in the first five-year period (2005-2009) of the ART program in Tanzania, and 3.4 % in the most recent period (2019-2022). Moreover, there was no PDR to the dolutegravir co-administered NRTI in those with viremia ≥50 copies/mL, at one year, in patients initiating dolutegravir-based ART in the KIULARCO 2 years after dolutegravir roll. Notably, dolutegravir-based ART was associated with >2 times the odds of viral suppression compared to NNRTI-based ART with an adjusted odds ratio (aOR) of 2.10 (95% CI 1.12-3.94). Conclusions There is notable level of PDR to NRTI among general adults’ population in Eastern Africa region, that was high among recently HIV-1 infected PLHIV in a representative rural Sub-Saharan Africa setting. Hence, routine surveillance of pre-existing resistance to the DTG co-administered NRTI remains particularly important, in resource-limited settings, to prevent risk of failure of newer antiretroviral agents such as dolutegravir, which would be detrimental to Tanzania and other low- and middle-income countries for the aim to “end AIDS by 2030”. Our results underline the benefit of programmatic uptake of dolutegravir -based ART in low- and middle-income countries.
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    Surveillance of gastrointestinal infections in individuals over the age of 5 years in South Africa
    (2024) Johnstone, Siobhan Lindsay
    Gastrointestinal infections cause significant mortality and morbidity, especially in Africa. While children ≤5 years of age bear the brunt of diarrhoeal disease, there is a significant burden in older age groups. Limited data on aetiology in these older age groups limits appropriate interventions. Diarrhoeal surveillance is important for monitoring disease trends in a population and should inform testing and treatment guidelines, and interventions. This body of work evaluated the epidemiology of diarrhoea at each level of the surveillance pyramid to assist in interpretation of routine health data and identify gaps in surveillance. A household survey was conducted in Soweto to estimate community diarrhoeal prevalence, associated risk factors and healthcare seeking behaviors. An analysis of diagnostic testing practices for diarrhoeal diseases was done, using a doctors’ survey, at three public hospitals in South Africa. Routine diagnostic data and enhanced surveillance data were compared to evaluate patient-related factors associated with requests for diagnostic investigation, type of diagnostic testing offered and the efficiency of available tests. A hospital surveillance study investigated the infectious causes of diarrhoea in hospitalised patients >5 years. Results indicated a high diarrhoeal burden across all age groups in South Africa (5.3% of respondents reported an episode in the preceding 2 weeks). While the majority of infections were mild, 40% required healthcare. Many of those requiring healthcare (34%), specifically adults, were unable to access the required care. Those that did access healthcare were treated empirically and seldom had stool samples collected for diagnostic investigations (approximately 10% of admitted cases). Available diagnostics in public health laboratories detected pathogens in only 13.7% of these submitted stools due to pre-analytical and analytical issues including not testing for all relevant pathogens. Diarrhoeal prevalence was particularly high among HIV-infected patients (67.5% of patients >5 years admitted for diarrhoea were HIV-infected) and these patients presented with a unique aetiology. This research highlights the need for diarrhoeal testing and treatment guidelines based on local epidemiological data with a focus on HIV-infected patients. Current diagnostics require optimisation including specimen collection, standardisation, pathogens included in routine testing panels, turnaround time and methods of detection. This will guide decisions on future public health interventions including vaccines.
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    Estimating and predicting HIV risk using statistical and machine learning methods: a case study using the 2005 to 2015 Zimbabwe demographic health survey data
    (2024) Makota, Rutendo Beauty Birri
    Background: The 90–90–90 targets were launched by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and partners with the aim to diagnose 90% of all HIV-positive persons, provide antiretroviral therapy (ART) for 90% of those diagnosed, and achieve viral suppression for 90% of those treated by 2020. In Zimbabwe, a population-based survey in 2016 reported that 74.2% of people living with HIV (PLHIV) aged 15–64 years knew their HIV status. Among the PLHIV who knew their status, 86.8% self-reported current use of Antiretroviral treatment (ART), with 86.5% of those who self-reported being virally suppressed. For these 90–90–90 targets to be met, prevalence and incidence rate estimates are crucial in understanding the current status of the HIV epidemic and determining whether the trends are improving to achieve the 2030 target. Ultimately, this will contribute to the achievement of Sustainable Development Goals 3 (SDG 3) and the broader goal of promoting sustainable development and eradicating poverty worldwide by 2030. Using data from household surveys, this thesis provides a unique statistical approach for estimating the incidence and prevalence of the Human Immunodeficiency Virus (HIV). To properly assess the efficacy of focused public health interventions and to appropriately forecast the HIV-related burden placed on healthcare systems, a comprehensive assessment of HIV incidence is essential. Targeting certain age groups with a high risk of infection is necessary to increase the effectiveness of public health interventions. To jointly estimate age-and-timedependent HIV incidence and diagnosis rates, the methodological focus of this thesis was on developing a comprehensive statistical framework for age-dependent HIV incidence estimates. Additionally, the risk of HIV infection was also evaluated using interval censoring methods and machine learning. Finally, geospatial modelling techniques were also utilised to determine the spatial patterns of HIV incidence at district levels and identify hot spots for HIV risk to guide policy. The main aim of this thesis was to estimate and predict HIV risk using statistical and machine learning methods. Study objectives: The study objectives of this thesis were: 1. To determine the effect of several drivers/factors of HIV infection on survival time over a decade in Zimbabwe, using current status data. 2. To determine common risk factors of HIV positivity in Zimbabwe and the prediction capability of machine learning models. 3. To estimate HIV incidence using the catalytic and Farrington models and to test the validity of these estimates at the national and sub-national levels. 4. To estimate the age- and time-dependent prevalence and HIV Force-of-infection (FOI) using current status data by comparing parametric, semi-parametric and non-parametric models; and determining which models best fit the data. 5. To investigate the HIV incidence hotspots in Zimbabwe by using geographicallyweighted regression. Methods: We performed secondary data analysis on cross-sectional data collected from the Zimbabwe Demographic Health Survey (ZDHS) from 2005 to 2015. Datasets from three Zimbabwe Demographic Health Survey HIV test results and adult interviews were merged, and records without an HIV test result were excluded from the analysis. The outcome variable was HIV status. Survey and cluster-adjusted logistic regression were used to determine variables for use in survival analysis with HIV status as the outcome variable. Covariates found significant in the logistic regression were used in survival analysis to determine the factors associated with HIV infection over the ten years. The data for the survival analysis was modelled assuming age at survey imputation (Model 1) and interval-censoring (Model 2). To determine the risk of HIV infection using machine learning methods, the prediction model was fit by adopting 80% of the data for learning/training and 20% for testing/prediction. Resampling was done using the stratified 5-fold cross-validation procedure repeatedly. The best algorithm was the one with the highest F1 score, which was then used to identify individuals with a higher likelihood of HIV infection. Considering that the proportion of those HIV negative and positive was imbalance with a ratio of 4.2:1, we applied resampling methods to handle the class imbalance. We performed the Synthetic Minority Over-sampling Technique (SMOTE) to balance the classes. We evaluated two alternative methods for predicting HIV incidence in Zimbabwe between 2005 and 2015. We estimated HIV incidence from seroprevalence data using the catalytic and Farrington-2-parameter models. These models were validated at the micro and macro levels using community-based cohort incidence and empirical estimates from UNAIDS EPP/SPECTRUM, respectively. To ascertain the age-time effects of HIV risk, we estimated the age- and time-dependent HIV FOI using current status data. Five generalised additive models were explored, ranging from linear, semi-parametric, non-parametric and nonproportional hazards additive models. The Akaike Information Criteria was used to select the best model. The best model was then used to estimate the age- and time-dependent HIV prevalence and force-of-infection. The OLS model was fitted for each survey year to determine the global relationship between HIV incidence and the significant covariates. The Moran's I spatial autocorrelation method was used to assess the spatial independence of residuals. The Getis-Ord Gi* statistic was used for Hotspot Analysis, which identifies statistically significant hot and cold spots using a set of weighted features. Interpolation maps of HIV incidence were created using Empirical Bayesian Kriging to produce smooth surfaces of HIV incidence for visualisation and data generation at the district level. The Multiscale Geographically Weighted Regression method was used to see if the relationship between HIV incidence and covariates varied by district. The software used in the thesis analysis included R software, STATA, Python, ArcGIS and WinBugs. Results: Model goodness of fit test based on the Cox-Snell residuals against the cumulative hazard indicated that the model with interval censoring was the best. On the contrary, the Akaike Information Criterion (AIC) indicated that the normal survival model was the best. Factors associated with a high risk of HIV infection were being female, the number of sexual partners, and having had an STI in the past year prior to the survey. The machine learning model indicated that the XGBoost model had better performance compared to the other 5 models for both the original data and SMOTE processed data. Identical variablesfor both sexes throughout the three survey years for predicting HIV status were: total lifetime number of sex partners, cohabitation duration (grouped), number of household members, age of household head, times away from home in last 12 months, beating justified and religion. The two most influential variable for both males and females were total lifetime number of sex partners and cohabitation duration (grouped). According to these findings, the catalytic model estimated a higher HIV incidence rate than the Farrington model. Compared to cohort estimates, the estimates were within the observed 95% confidence interval, with 88% and 75% agreement for the catalytic and Farrington models, respectively. The limits of agreement observed in the Bland-Altman plot were narrow for all plots, indicating that our model estimates were comparable to cohort estimates. Compared to UNAIDS estimates, the catalytic model predicted a progressive increase in HIV incidence for males throughout all survey years. Without a doubt, HIV incidence declined with each subsequent survey year for all models. Based on birth year cohort-specific prevalence, the female HIV prevalence peaks at approximately 29 years of age and then declines. Between 15 and 30 years, males have a lower cohort-specific prevalence than females. Male cohort-specific prevalence decreases marginally between ages 33 and 39, then peaks at age 40. In all age categories, the cohort-specific FOI is greater in females than males. Moreover, the cohortspecific HIV FOI peaked at age 22 for females and age 40 for males. A 18-year age gap between the male and female HIV FOI peaks was observed. Throughout the decade covered by this study, the Tsholotsho district remained a 99 % confidence hotspot. The impact of STI, condom use and being married on HIV incidence has been strong in the Eastern parts of Zimbabwe with Mashonaland Central, Mashonaland East and Manicaland provinces. From our findings from the Multiscale Geographically Weighted Regression (MGWR), we observed that Matabeleland North’s HIV incidence rates are driven by wealth index, multiple sex partners, STI and females with older partners. Conclusions: The difference between the results from the Cox-Snell residuals graphical method and the model estimates and AIC value may be due to inadequate methods to test the goodness-of-fit of interval-censored data. We concluded that Model 2 with interval-censoring gave better estimates due to its consistency with the published results from the literature. Even though we consider the interval-censoring model as the superior model with regard to our specific data, the method had its own set of limitations. Programmes targeted at HIV testing could use the machine learning approach to identify high-risk individuals. In addition to other risk reduction techniques, machine learning may aid in identifying those who might require Pre-exposure prophylaxis. Based on our results, older men and younger women resembled patterns of higher HIV prevalence and force-of-infection than younger men and older women. This could be an indication of age-disparate sexual relationships. Therefore, HIV prevention programmes should be targeted more at younger females and older males. Lastly, to improve programmatic and policy decisions in the national HIV response, we recommend the triangulation of multiple methods for incidence estimation and interpretation of results. Multiple estimating approaches should be considered to reduce uncertainty in the estimations from various models. The study spread the message that various factors differ from district to district and over time. The study's findings could be useful to policymakersin terms of resource allocation in the context of public health programs. The findings of this study also highlight the importance of focusing on districts like Tsholotsho, which have consistently had a high HIV burden over time. The main strength of this study is dependent on the quality of the data obtained from the surveys. These data were derived from population-based surveys, which provide more reliable and robust data. Another strength of this study was that we did not restrict our analysis to one method; however, we had the opportunity to determine the risk and incidence of HIV by exploring different methodologies. However, the limited number of variables accessible to us for this study constituted one of its drawbacks. We could not determine the impact of variables including viral load, health care spending, HIV- risk groups, and other HIV-related interventions. Additionally, there were missing values in the data, which required making assumptions about their unpredictability and utilising imputation methods that are inherently flawed. Last but not least, a number of the variables were self-reported and, as a result, were vulnerable to recall bias and social desirability bias.