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    Human health risks of exposure to fine particles (PM2.5) from the gold mine tailings in the community of eMbalenhle, South Africa
    (University of the Witwatersrand, Johannesburg, 2025) Thabethe, Nomsa Duduzile Lina; Brouwer, Derk
    South Africa is home to some of the world’s largest gold mines and contributes significantly to global gold production. However, gold mining activities generate waste in the form of soil, which is stored as Tailing Storage Facilities (TSFs). Gold mine TSFs are a source of ambient PM2.5. PM2.5 is particulate matter with a diameter of 2.5 micrometers or smaller. Epidemiological studies have found that exposure to fine particulate matter (PM2.5) poses potential human health risks. The human health risks posed by exposure to PM2.5 include respiratory, cardiovascular and cerebrovascular diseases. PM2.5 and heavy metals are transported from their sources to receptors. Mining activities are also a source of heavy metals in nearby soils. The most common heavy metals found in soil are Lead (Pb), Mercury (Hg), Cadmium (Cd), Manganese (Mn), Nickel (Ni), Zinc (Zn) and Arsenic (As). The heavy metals find their way to the ground, thus contaminating the soil. This study aimed to assess the potential human health risks associated with exposure to PM2.5 in the community of eMbalenhle which is near gold mine TSFs. The study was divided into four objectives, 1) to assess the PM2.5 spatial and temporal variations at the source (TSFs) and receptor (community), 2) to determine the atmospheric dispersion of PM2.5 emissions from gold mine TSFs to nearby communities, 3) to determine the concentrations of heavy metals in the soils collected within the mining area and identifying their sources, 4) to assess the potential human health risks associated with exposure to PM2.5 in the community of eMbalenhle. Ambient PM2.5 concentrations were monitored over a year (07 February 2022 to 07 February 2023) using Clarity Node-S Low-Cost Monitors (LCMs). Meteorological data (wind speed, wind direction, solar radiation, atmospheric radiation, rain, relative humidity, and temperature) for the same period were sourced from the South African Air Quality Information System (SAAQIS). Statistical analyses were performed using the Openair packages in R Studio (version 4.0.2) and Stata software (version 18). The American Meteorological Society Environmental Protection Agency Regulatory Model (AERMOD), coupled with meteorological information from the Weather Research Forecasting (WRF) model, was applied to predict the ground-level concentrations of PM2.5. The Inductively Coupled Plasma Mass Spectrometry (ICP-MS) method was used to analyze the heavy metals in the soil samples. The samples were prepared in a 1% Nitric Acid (HNO3) matrix. About 0.5% Hydrochloric acid (HCl) was routinely added to soil samples to ensure the iii stability of the heavy metals. The Absolute Principal Components Score - Multiple Linear Regression (APCS-MLR) Model was used to calculate the contribution rate of the heavy metals at each sampling point. The Enrichment Factor (EF) and Contamination Factor (CF) were calculated to determine whether the heavy metals in the soil samples originated from natural sources or were influenced by anthropogenic activities. The Upper Earth’s Crust (UEC) values were used as the soil background values of heavy metals. Mn was chosen as the reference element. The Probabilistic Human Health Risk Assessment (PHHRA) was applied to estimate cancer risks in four population subgroups (toddlers, children, adults and elderly). The results showed that PM2.5 concentrations were higher in Winter and lower in Summer at both the community site and gold mine TSFs. The average daily (24-hour) PM2.5 concentrations at the community site and gold mine TSFs were 19.24 and 9.70 μg/m³, respectively. The daily PM2.5 concentrations at the community site exceeded the South African National Ambient Air Quality Standard (NAAQS) of 40 μg/m3 twenty-six (26) times and the World Health Organisation (WHO) guidelines of 15 μg/m3 hundred and eighty-one times (181) times. The daily (24-hour) NAAQS was not exceeded at the gold mine TSFs; however, the WHO guideline was exceeded 85 times. Although the higher PM2.5 concentrations were recorded in the community compared to the gold mine TSFs, local PM2.5 sources could have contributed to the elevated concentrations. The dispersion model indicated a maximum PM2.5 24-hour average concentration of 11ug/m3 and; maximum annual average of 3.4 ug/m3 at the 99th percentile (worst-case scenario). The predicted concentrations were below both the national, Environmental Protection Agency (EPA) NAAQS and World Health Organization (WHO) guidelines. The mean Cr, As, Pb, U, and Au concentrations were higher in TSFs (89.2±58.8, 22.9±25.7, 10±10, 5.72±4.78, and 0.53±0.54 mg/kg) compared to residential sites (79.7±24.6, 2.6±1,33, 8.98±5.05,1.55±1.42, and 0.08 ±0.07 mg/kg), respectively. There were a significant difference in Mn concentrations (rrb = 0.833, p = 0.038) between the residential sites and TSFs. Results of the APCS-MLR of the heavy metals concentrations at the TSFs sites indicated that Au (92.7%), As (93.3%), U (93.3%) and Cr (88.3%) mainly originated from mining activities. The study findings confirmed that TSFs are basically waste soil and may have affected the surroundings. The PHHRA results indicated that the Hazard Quotient (HQ) was highest at the 95th percentile for all subgroups. Using the SA NAAQS, the HQ was estimated to be 0.9 for all subgroups, iv indicating safe levels. When utilizing the EPA NAAQS, a value of 2.5 was reported, while the WHO guidelines recorded the highest HQ of 3.5, indicating unsafe levels. This demonstrated that the South African NAAQS underestimated exposure to PM2.5. For both male and female elders, the Cancer Risk (CR) was approximately 1 in 10, meaning that about 100,000 out of 1,000,000 exposed elders were at an increased risk of developing cancer over their lifetime. The study had four (4) recommendations based on each objective, 1) revising the current NAAQS to adopt more stringent measures and align them to international benchmarks to safeguard the public from adverse health effects due to PM2.5 exposure, 2) future studies should focus on the dispersion and source apportionment of PM2.5 to quantify the contribution of various sources in eMbalenhle, 3) integrating other methods alongside bulk sampling and APCS-MLR in future studies to capture heterogeneity within the soil matrix and improve source apportionment resolution 4) carry out an elemental characterization of soil particles and estimate the health risks associated with chronic exposures in these communities
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    Nano-Embedded Bioplatform for Ocular Delivery of Genetic Material
    (University of the Witwatersrand, Johannesburg, 2025) Sikhosana, Nombeko
    This thesis explores gene therapy as a promising strategy for treating retinal degenerative diseases, with a particular focus on the development and future of gene delivery vectors. Effective gene delivery systems must be biocompatible and versatile, capable of encapsulating and delivering various nucleic acid payloads. However, current vectors often face limitations such as immunogenicity, low payload capacity, non-specific tropism, and suboptimal transfection efficiency. Numerous studies over the past decade highlight that the limited success of gene therapy is largely due to the inefficiencies of these delivery systems. To address this, the thesis proposes a biocompatible, cationic gene delivery nanosystem targeting CD44 receptors on retinal pigment epithelium (RPE) cells. This targeted approach enhances tissue specificity and supports nucleic acid encapsulation and delivery. A dual delivery system was developed comprising a thermoresponsive hydrogel designed to encapsulate the nanosystem and support ocular cell proliferation for tissue regeneration. The gene delivery vehicle referred to as the nano-polyplex was constructed using hyaluronic acid (HA) conjugated to 2-aminobenzimidazole and oleylamine, forming an amphiphilic, cationic structure. Upon loading with the plasmid pcDNA6.2-EmGFP (pEmGFP), the nano-polyplex exhibited spherical morphology, with particle sizes ranging from 75 nm (unloaded) to 150 nm–3.6 μm (loaded), and zeta potentials ranging from 2.5 mV to 27 mV, depending on the nitrogen-to-phosphate (N:P) ratio. Encapsulation efficiencies exceeded 90% for most N:P ratios, except for N:P 5, which achieved 19.5%. The formulations effectively protected pEmGFP from nuclease degradation and enabled sustained release over 96 hours. Cell viability remained above 90% across all tested formulations. Transfection efficiency, evaluated via GFP expression and fluorescence microscopy, was highest for the N:P 15 formulation. In Phase II, the nano-polyplex was embedded in a pluronic-chitosan hydrogel to form the Gen-I system, a "Trojan horse" platform enabling sustained gene delivery and promoting cell viability. The Gen-I system supported cell survival and proliferation over 36 hours in vitro. A seven-day pilot in vivo study demonstrated the system’s safety and the sustained presence of pEmGFP following intravitreal administration, with only moderate inflammation observed. Collectively, this work presents a novel, biocompatible gene delivery platform with targeted tropism and regenerative potential for retinal gene therapy applications.
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    Understanding the Genetic Basis of extreme levels of High and Low LDL- Cholesterol in African Populations
    (University of the Witwatersrand, Johannesburg, 2025) Smyth, Natalie
    Cardiovascular diseases (CVDs) are a growing public health concern across Africa, with dyslipidaemia, particularly elevated low-density lipoprotein cholesterol (LDL-C), being a key modifiable risk factor. However, the genetics of lipid metabolism in African populations remain poorly understood due to limited representation in genomic studies. This thesis investigates both monogenic and polygenic contributions to extreme LDL-C levels in Sub- Saharan African populations, leveraging the Africa Wits-INDEPTH Partnership for Genomic Studies (AWI-Gen) cohort. To explore monogenic dyslipidaemia, we performed targeted next-generation sequencing (NGS) on 191 individuals with extreme high and low LDL-C levels from West, East, and South Africa, focusing on 16 genes implicated in LDL-C regulation, including LDLR, APOB, and PCSK9. This analysis identified 356 unique variants, including known pathogenic mutations and novel variants predicted to be functionally disruptive. While 28 variants were previously associated with phenotypic outcomes in ClinVar or HGMD, most were classified as variants of uncertain significance (VUS). Interpretation was complicated by the presence of multiple variants per individual, epistatic effects, and the absence of family-based cascade screening. Nevertheless, the findings highlight the complex genetic architecture associated with LDL-C levels in African populations and reinforce the need for functional studies and better population-specific variant classification. In the polygenic arm of the study, we evaluated the predictive performance of four published polygenic scores (PGS) for LDL-C, developed from European, African-American, and multi- ancestry cohorts, across 10,603 participants from the AWI-Gen study. The variance explained (R²) by each PGS ranged from 0.03 to 0.205, with the Graham and Zhang scores that were both developed in African–ancestry cohorts achieving the highest overall accuracy. Notably, regional differences in performance were observed, with PGS trained on African-American datasets performing better in South and East Africa than in West Africa, despite African- American having predominantly West African ancestral admixture. These results suggest that current PGS have limited and uneven predictive power in African populations, highlighting the need for ancestry-diverse discovery cohorts and region-specific calibration. v Together, these findings emphasize the importance of incorporating African genetic diversity into both monogenic and polygenic frameworks to improve CVD risk stratification and enable more equitable implementation of precision medicine on the continent.
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    An Assessment of Oral Health Care Delivery to Children with Special Needs at Dental Schools in South Africa
    (University of the Witwatersrand, Johannesburg, 2025) Njoroge, Nancy Wanjiru
    Background: Children with special healthcare needs (CSHCN) including adolescents may experience disproportionately poorer oral health and greater access barriers to dental care than those with no special care need (NSHCN). There is limited knowledge pertaining to the oral health status and delivery of dental care to CSHCN in South Africa (SA). Objective: The aim of the study was to assess oral healthcare delivery to CSHCN at academic dental hospitals (ADHs) in SA. The specific objectives were to: - compare the dental treatment provided to CSHCN and NSHCN at ADHs, describe the dental care services provided for CSHCN at ADHs, explore the perceptions of oral health professionals (OHPs) towards provision of dental care to CSHCN at ADHs and identify factors influencing the delivery of oral healthcare to CSHCN at ADHs in SA from the perspectives of OHPs. Methods: A sequential mixed methods study design was utilised. The inter-related methodological components to answer the research objectives included the quantitative phase of a narrative of literature review (2002-2023) on the oral health status of CSHCN in SA; a record review (2017-2023) of dental treatment provided under general anaesthetic (GA) to CSHCN and NSHCN aged 1-16 years at ADHs; a cross-sectional online survey conducted among OHPs at ADHs to assess their perceptions towards provision of dental care for CSHCN. The qualitative arm involved in depth interviews with clinical heads in Paediatric Dentistry at ADHs and a focus group discussion with OHPs from some respondents of the survey. Quantitative data was presented using frequencies and percentages. The Chi-square test and Fischer exact test were used for statistical analyses, and all tests were done at 95% confidence level. Thematic framework analyses were used to assess the qualitative data. Results: Twenty-six articles were retrieved for the narrative literature review and six studies that met the eligibility criteria were analysed. A total of 2,402 CSHCN were included in the review, 59.7% (n=1,433) of whom were male and 40.3% (n=969) were female. The age of the children ranged between 0 and 20 years. The types of CSHCN varied across the studies, and included, inter alia, intellectual/mental disability, cerebral palsy, learning disabilities, autism spectrum disorders, hearing impaired, physical disabilities, Down Syndrome, epilepsy, ‘complex/multiple disabilities’ and other health disorders. The prevalence of dental caries ranged from 22.5% to 85.2% and 68%-100% of the caries was untreated. v Four hundred records were retrieved from the ADHs for the record review study. Of the children treated under GA, 29% were CSHCN and 71% were NSHCN. The median age at assessment was 5 years (IQR: 3-6.5). The medical conditions of CSHCN who presented for dental treatment under GA included inter alia, cerebral palsy, various chronic medical conditions, craniofacial anomalies and other developmental disorders. The CSHCN were older than NSHCN, (p< 0.001). More CSHCN (52.6%) compared to NSHCN (25.4%) were referred from primary health care centres (PHC), (p<0.001). Caries was the main dental diagnosis. Overall, both groups received mainly extractions (43.5%), while 20% had restorative care and <10% had preventative care. Fifty OHPs completed the survey, and eight participated in the interviews. The majority of the OHPs were female (n=36; 72%), above 35 years (n=40; 80%) and two-thirds had more than 10 years of clinical experience (n=33;66%). Furthermore, the dental services provided to CSHCN comprised mainly of basic tooth extractions, restorative care, fissure sealants and oral prophylaxis. Oral surgery and orthodontics were the limited specialty services for children with cleft lip and palate. Four themes emerged from the perceptions of OHPs towards provision of dental care for CSHCN: - service provision, resource constraints, patient affordability and organisational factors. Other challenges experienced by OHPs at ADHs included inadequate infrastructure, theatre and sedation facilities, inadequate resources such as time, dental assistants, limited inter-disciplinary collaborations, and challenges with the children’s medical/behavioural problems. However, the OHPs felt positive and found their work fulfilling. They suggested proposals to alleviate the challenges they faced. Conclusions: The study findings revealed that CSHCN in SA were a diverse and heterogenous group. Poor oral health and high unmet treatment needs were prevalent among these children from the limited data available. Patients who received dental treatment under GA at ADHs in SA were CSHCN or NSHCN typically under the age of 6 years, presenting with extensive caries. The treatment provided consisted mainly of extractions with little restorative and preventative treatment. The OHPs at ADHs experienced challenges related to service provision, resource constraints, low patient affordability and organisational factors that in turn affected the availability of quality dental services for CSHCN. These challenges can be addressed by advocating for enhanced multi-disciplinary collaborations, creation of more public-private partnerships, increasing training opportunities for OHPs especially in PHC settings, properly vi equipping the PHC facilities to be able to provide basic dental services for CSHCN; thus, the travelling costs of patients and referral load to ADHs would be alleviated. Recognition of paediatric dentistry as a specialty in SA is long overdue so that the specialists can support the general dentists in the dental management of CSHCN and hence improve access to dental care.
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    Evaluation of the Implementation Outcomes of the Framework and Strategy for Disability and Rehabilitation for South Africa: An Explanatory Mixed-Methods Study
    (University of the Witwatersrand, Johannesburg, 2025) Reis, Naeema Ahmad Ramadan
    Background Disability remains a global challenge, affecting 15% of the population worldwide and 7.5% in South Africa. The increase in disability poses significant implications for the healthcare system, exacerbated by a quadruple burden of disease and systemic inequalities. To address these challenges, South Africa introduced the Framework and Strategy for Disability and Rehabilitation (FSDR) (2015–2020, extended to 2023) to align with international disability rights frameworks, such as the United Nations Convention on the Rights of Persons with Disabilities (UNCRPD). The FSDR has not been evaluated to assess its implementation outcomes, limiting opportunities to inform future policy. Aim This study evaluated the implementation outcomes of the Framework and Strategy for Disability and Rehabilitation (FSDR) in Gauteng Province by assessing provincial processes, exploring stakeholder perceptions, and mapping influencing factors. This study aimed to develop evidence-based strategies to enhance the implementation of future disability and rehabilitation policies in South Africa. Methods The study employed an explanatory mixed-methods design that integrated quantitative and qualitative approaches. A document review analysed provincial reports on FSDR implementation, while semi-structured interviews and focus group discussions captured the experiences of key stakeholders, including rehabilitation professionals, policymakers, and community representatives. Data was analysed thematically and categorised using Proctor’s Model, the Consolidated Framework for Implementation Research (CFIR), the Exploration, Preparation, Implementation, and Sustainment (EPIS) framework and the ERIC Framework. Key Findings The evaluation revealed a mixed picture of the successes and challenges of implementing the FSDR. Key barriers include inadequate funding, limited rehabilitation resources, paucity of skilled personnel, and systemic inefficiencies in referral systems. Stakeholders also cited poor inter-sectoral collaboration and lack of standardised training as critical issues. However, the study also identified enabling factors, such as the involvement of disability advocacy organisations, the alignment of the FSDR with global disability rights goals, and the role of community-based rehabilitation initiatives. The study proposed implementation strategies to improve disability and rehabilitation policies, including optimising resource allocation, enhancing capacity-building for healthcare professionals, vi and promoting inter-sectoral collaboration. It also emphasised the need for thorough monitoring and evaluation mechanisms to ensure effective implementation and track progress. Conclusion This study highlights the critical importance of evaluating health policy implementation to ensure its alignment with stakeholder needs and global standards. By addressing the barriers identified in FSDR implementation, South Africa can strengthen its commitment to inclusive healthcare and advance the rights and well-being of persons with disabilities. Implications The findings of this study contribute to the growing body of knowledge regarding the implementation of science and disability policy. Evidence-based recommendations offer a roadmap for policymakers to improve rehabilitation services and address systemic barriers to equitable healthcare. These strategies aim to uphold the rights of persons with disabilities, reduce health disparities, and enhance the integration of rehabilitation services into South Africa’s health care system.