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Recent Submissions

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    The Wits Protection of Personal Information Act (POPI) Policy
    (University of the Witwatersrand, Johannesburg, 2021) University of the Witwatersrand, Johannesburg
    The University Processes Personal Information of Persons in accordance with the eight conditions for the lawful processing of Personal Information as contained in the POPIA and these principles guide The University on how Personal Information must be processed. Data Subject consent to process Personal Information is provided voluntarily.
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    The Reported Experiences of Mothers of High-Functioning Cerebral Palsy Adults
    (University of the Witwatersrand, Johannesburg, 2025) Heyman, Alexa Jade
    The experience of raising children is one that is generally considered to be very challenging for mothers. These challenges often arise as a result of the variety of demands and expectations associated with each passing milestone. For mothers of children with high-functioning Cerebral Palsy (CP) these demands are often more intensive due to the extensive interventions required to help their children actualise their potential. The aim of this study was to report on, and interpret the unique nature of experiences confronted by mothers of high-functioning CP adults. In doing so, the study adds to the deficit of literature that demonstrates how societal judgment impacts mothers’ perceptions of their experiences and highlights why it is necessary to cater for high-functioning CP individuals in a mainstream society. Therefore, by providing mothers with the opportunity to articulate their experiences through semi-structured interviews, their lesser-considered voices and subjective perceptions are heard. Participants’ responses to the interview schedule were analysed through the use of an Interpretive Phenomenological framework in order to understand the unique and in-depth nature of mothers’ personal experiences. These responses were dissected into themes through the use of Thematic Analysis. ‘Trauma’ and ‘loneliness and misunderstanding’ were highlighted as prominent emotional responses, and are followed by a discussion of the survival and grief-orientated coping responses mothers reported experiencing. Lastly, mothers’ desires for circumstantial control and worries about their adult CP children’s futures were identified as integral to understanding their experiences. The study was noted to have implications for socialisation studies as it demonstrated how social isolation can affect maternal emotional well-being. Moreover, the study was noted as having implications in resilience and Humanistic studies as the levels of resolve mothers adopted to cope with their circumstances were highlighted. Lack of generalisability and mothers’ inherent biases concerning their children’s functional abilities were noted as potential limitations to the study. The impact of raising a high-functioning CP child on mothers’ journeys as well as the changing worldviews mothers experience as part of their journey were recommended as noteworthy topics for future research
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    A Novel Multi-Component 3D-Printed Scaffold for Targeted Bone Tuberculosis Therapy,
    (University of the Witwatersrand, Johannesburg, 2025) Mphaphuli, Mashudu Theodore; Choonara, Yahya Essop
    Delivering therapeutic agents for the effective treatment of bone tuberculosis (TB) is significantly challenged by inadequate drug penetration into the infected skeletal tissues and limited regeneration of damaged bone. Traditional systemic drug administration often fails to achieve desired therapeutic concentrations locally, leading to increased risk of drug resistance, treatment failure, and systemic toxicity. The aim of this study was to develop a novel, multi- component 3D-printed scaffold incorporating bedaquiline (BQ)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles for localized, sustained release and simultaneous bone regeneration in the targeted management of bone TB. The BQ-loaded PLGA nanoparticles were synthesized using a solvent evaporation technique and optimized through a Box– Behnken design (BBD), focusing on critical quality attributes (CQAs). The optimized nanoparticles exhibited an average particle size of approximately 180 nm, a polydispersity index of less than 0.2, and an encapsulation efficiency (EE) of 78 ± 3%. In-vitro drug release assays demonstrated controlled and sustained release kinetics, achieving approximately 85% cumulative drug release over 21 days. The multi-component scaffold was fabricated using advanced 3D printing technology, integrating natural, synthetic, bioactive, and metallic biomaterials, specifically polycaprolactone (PCL), sodium alginate (NaAlg), bioactive glass (BG), and titanium (Ti). The scaffold exhibited a porosity of nearly 70% and demonstrated optimal mechanical properties with a compressive strength around 3.5 MPa. Comprehensive physicochemical, morphological, and thermal characterizations were conducted using Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), Scanning Electron Microscopy (SEM), and Transmission Electron Microscopy (TEM), confirming the scaffold's desirable structural integrity, thermal stability, and morphological properties. Cytotoxicity assessments performed using the MG-63 osteosarcoma cell line indicated high cell viability exceeding 85% after 72 hours, confirming excellent biocompatibility and suitability for bone tissue engineering applications. An in vivo evaluation in a New Zealand White rabbit femoral defect model provided further evidence of therapeutic efficacy, with histomorphometry analyses revealing bone regeneration at defect sites treated with the scaffold, compared to regeneration in untreated control sites after 4 weeks. Additionally, mechanical testing supported these findings, showing significantly enhanced structural integrity and load-bearing capabilities at the treated sites. The results of this comprehensive study demonstrate that the developed 3D- printed scaffold loaded with BQ-encapsulated nanoparticles effectively addresses the limitations associated with conventional systemic bone TB therapies. The scaffold provides sustained localized drug delivery, reduces systemic side effects, and significantly enhances bone tissue regeneration. This innovative platform holds promise for clinical translation, potentially revolutionizing the management and treatment of bone tuberculosis and similar skeletal conditions requiring targeted therapeutic intervention and robust regenerative support.
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    Understanding Carriage and Transmission of Streptococcus pneumoniae Through a Community Cohort Study in South Africa,
    (University of the Witwatersrand, Johannesburg, 2025) Carrim, Maimuna
    Pneumococcal carriage is shaped by host demographics, human immunodeficiency virus (HIV) status, viral co-infections, and microbial community dynamics, yet the longitudinal interplay of these factors remains underexplored in high HIV prevalence settings. Despite the substantial reductions in disease achieved through widespread pneumococcal conjugate vaccine (PCV) use, colonization and invasive disease continue. Gaps remain in understanding how colonization evolves over time, particularly during respiratory viral infections such as influenza and respiratory syncytial virus (RSV). This study investigates how demographic factors, HIV status, and viral co-infections influence pneumococcal colonization and density over time, and examines nasopharyngeal microbiome changes before, during, and after influenza infections to better understand microbial interactions that may modulate colonization. We analyzed data from a prospective household observational cohort study of influenza, RSV and other respiratory pathogens community burden and transmission dynamics in South Africa (the PHIRST study) of 1684 individuals across 327 randomly selected households conducted in two communities in South Africa from 2016 – 2018. Nasopharyngeal (NP) swabs were collected twice-weekly. Pneumococcal detection and quantification, RSV and influenza virus detection were performed using real-time polymerase chain reaction (qPCR) and nasopharyngeal microbiome were profiled via 16S ribosomal ribonucleic acid (rRNA) gene sequencing (V4 region). Colonization episodes were defined using longitudinal qPCR data and analyzed with Markov models to estimate acquisition and clearance rates, adjusting for age, HIV status, and misclassification. Pneumococcal density was summarized as the median across episodes, with associations assessed via multivariable logistic regression. In viral co- infection analyses, changes in pneumococcal density before, during, and after RSV or influenza infection were evaluated using mixed-effects and linear regression models. For microbiome analyses, samples were selected from before, during, and after influenza episodes. Alpha and beta diversity metrics were compared using mixed-effects and regression models. Changes in dominant Operational Taxonomic Units (OTUs) were analyzed using additive log-ratio transformation and regression adjusted for host factors. Predictor-responder analysis was used to identify directional interactions between ix OTUs. Analyses were conducted using Stata and R/RStudio, with significance set at P<0.05. Pneumococcal colonization was detected in 98% (1,655/1,684) of participants. Younger children (<5 years of age) had higher odds of colonization (adjusted odds ratio (aOR) 14.1; 95% confidence interval (CI) 1.8–111.3) and longer episode durations (median 35.5 days, interquartile range (IQR) 17–88) than individuals aged ≥5 years (median 5.5 days, IQR 4–12). People living with HIV (PLWHIV) also had an increased odds of colonization (aOR 10.1; 95% CI 1.3–77.1). An increase in pneumococcal density was observed during RSV infection compared to the period before (log mean before vs. during: 9.3 vs. 10.2 copies/ml; P<0.01). Influenza infection was not associated with a significant mean increase in pneumococcal density (9.6 vs. 9.9 copies/ml; P=0.2), though high influenza viral load (cycle threshold (Ct) <25) was associated with increased pneumococcal density (coefficient 2.8; 95% CI 1.4–4.2). During RSV infection, underweight individuals were less likely to have an increase in pneumococcal density compared to individuals with a normal body mass index (coefficient -1.8; 95% CI -3.5 to - 0.1; P=0.04). Influenza infection was associated with shifts in nasopharyngeal microbiome composition, particularly post-infection, with greater changes in younger individuals, females, and PLWHIV. Alpha diversity remained largely stable however older individuals showed a decrease before an influenza infection compared to after (coefficient=-1.03, P=0.01). Our results showed that beta diversity changed across all three periods. Streptococcus 5 was more abundant during influenza episodes and showed a temporal patter of medium-high-low relative abundance across the periods. Furthermore, we found that Streptococcus 5 abundance before infection predicted increases in both Streptococcus 5 and Moraxella 1 during infection, while Moraxella 1 increases during infection preceded declines in Streptococcus 5 and Dolosigranulum pigrum 4 after infection. Although PCVs have reduced disease burden, children and PLWHIV remain key reservoirs for pneumococcal transmission. Our findings corroborate previous studies demonstrating that viral co-infections are associated with increased pneumococcal density and alterations in the nasopharyngeal microbiome, supporting the concept of a synergistic effect that may promote progression to invasive disease. These results show that respiratory viral infections, particularly RSV, are associated with increases in x pneumococcal colonization density. This suggests that vaccination against respiratory viruses, such as RSV, could play a role in reducing bacterial disease risk. Furthermore, observed microbiome shifts during viral infections may help explain changes in pneumococcal colonization patterns, offering insights into host-microbe interactions relevant to disease development.
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    Screening and diagnosis of gestational diabetes mellitus in an African population
    (University of the Witwatersrand, Johannesburg, 2025) Khambule, Lungile
    Background: Gestational diabetes mellitus (GDM) is defined as hyperglycaemia that is discovered for the first time during pregnancy and is not overt. The prevalence of GDM in South Africa varies between 9.1% and 25%. Mothers with GDM are at increased risk of preeclampsia, caesarean delivery, and preterm birth. Similarly, babies born to GDM mothers are at increased risk of macrosomia, hypoglycaemia, respiratory distress, hypocalcaemia, hypomagnesaemia and Type 2 diabetes(T2D) later in life. Therefore, efficient screening and diagnosis remain the cornerstone for reducing GDM-related maternal and neonatal morbidity and mortality. The oral glucose tolerance test (OGTT) is the current gold standard for screening for GDM. However, in South Africa, the test is not universally accessible as only pregnant women with GDM-related risk factors are tested. This approach is likely to miss a significant number of women with GDM. Aim: The overall aim of this research is to improve the current screening and diagnostic methods for GDM. Consequently, our first objective was to evaluate the performance of several point-of-care (POC) glucometers against the standard laboratory-based glucose measurements during an OGTT. The second objective was to evaluate the use of glycaemic markers namely, fasting plasma glucose (FPG), glycated albumin (GA) and glycated haemoglobin (HbA1c), for the diagnosis of GDM. The third objective was to determine the associations of various candidate biomarkers with glycaemia in both early and late pregnancy in Black African pregnant women. Methods: This is a prospective cross-sectional study that was carried out at five different health facilities in Johannesburg, South Africa. Pregnant Black African women under 21 weeks of gestation (early pregnancy) and at 24-32 weeks of gestation (late pregnancy) were recruited and stratified into three groups. The women in late pregnancy (groups 1 and 2) were tested for GDM using the 75 g OGTT and classified into GDM and non-GDM following the International Association of Diabetes and Pregnancy Study Group (IADPSG) guidelines. Seven glucometers were compared to laboratory- based glucose measurements for GDM diagnosis using blood samples from the OGTT (Group 1). In the second group of late-pregnancy women (Group 2), candidate biomarkers (TNFα, IL-6, free fatty acids (FFAs), branched-chain amino acids and acylcarnitines) and known markers of glycaemia (FPG, HbA1c and GA) were assessed for their ability to diagnose GDM using the OGTT as the reference. Fasting and random blood samples were taken in women in early pregnancy (group 3), and candidate biomarkers and blood glucose were measured. Univariate correlations and multivariate regression analysis were performed to determine the relationship between glycaemia and ii candidate biomarkers in early and late pregnancy, and their discriminatory power was assessed by receiver-operator characteristic (ROC) curve analysis. Results: A total of 1716 women were recruited: 1076 from pregnancy (group 1), 477 also from late pregnancy (group 2), and 163 from early pregnancy (group 3). For the glucometer study (Group 1), 83 (7.7%) were classified as GDM. The sensitivity of the glucometers for GDM diagnosis ranged from 17.6% to 87.18% and their specificity from 62.7% to 99.8%. The area under the ROC curve (AUC) was between 0.59 and 0.79. However, the laboratory- based FPG showed better performance than the glucometers in terms of sensitivity, specificity, and AUC, with levels of 94.0%, 100%, and 0.98, respectively. Building on the observations from the Group 1 study, which showed potential for diagnosing GDM using a single test i.e. FPG, we subsequently compared the efficacy of FPG, glycated haemoglobin (HbA1c), and glycated albumin (GA), for the diagnosis of GDM in the Group 2 women. Overall, FPG at a 5.1mmol/L cut point performed better than HbA1c and GA, with sensitivity and specificity of 87% and 100% respectively. At the 5.5.% cut-off point, HbA1c had sensitivity and specificity of 54% and 80% respectively and GA, had a sensitivity and specificity of 54% and 83%, respectively at a cut point of 37.6%. Based on the selective screening criteria currently used, all the women in group 2 had one or more risk factors for GDM and as a result, would have qualified for OGTT. If FPG was then used as a second screening test, it would have averted the need for OGTTs in 77% of these women. Thereafter, we sought to identify novel biomarkers for GDM diagnosis. Metabolites and proteins known to be linked to GDM were measured in 163 women below 21 weeks of pregnancy (Group 3) and 477 women between 24-32 weeks of pregnancy (Group 2). Free fatty acids (FFAs), and isoleucine were positively associated with GDM whilst acylcarnitine C2 demonstrated an inverse association. The sensitivity and specificity of these candidate biomarkers for the diagnosis of gestational diabetes mellitus (GDM) were inadequate, and they did not exhibit a significant association with fasting or random plasma glucose levels during early pregnancy, with the exception of valine, which demonstrated a significant correlation with random plasma glucose. (p=0.0029) Conclusions: The current study showed that the performance of laboratory-based FPG measurements for GDM diagnosis is better than HbA1c, GA, and glucometers. Furthermore, we observed that a two-tiered approach utilising FPG would reduce the number of OGTTs required for iii women diagnosed with GDM. In addition, valine has the potential to be used as an early marker of GDM, however, this would need to be validated in longitudinal studies.