School of Public Health (ETDs)

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    A comparative assessment of the legislative and regulatory frameworks for local manufacture of vaccines in South Africa and Egypt
    (University of the Witwatersrand, Johannesburg, 2024) Naidoo, Thevendran
    Healthcare systems in low-and middle-income countries in Africa are highly dependent on immunisation programmes and the availability of vaccines to manage infectious disease outbreaks and, together with clean water and access to health care, serve as the cornerstone of prevention. A dependable supply of quality vaccines is crucial in maintaining a country’s health care needs. Local manufacture of vaccines in Africa is vastly inadequate to meet the healthcare needs of the continent. South Africa, like most low-and middle-income countries, is highly reliant on external supplies of vaccines to meet its healthcare needs. This makes the health care system extremely vulnerable during public health emergencies and pandemics. A well-developed policy, legislative and regulatory framework is crucial in supporting local vaccine manufacturing activities. The study investigated the framework that currently exists for local vaccine manufacturing in South Africa in comparison to Egypt as a similar middle- income country with a rapidly advancing local vaccine manufacturing industry. The comparative analysis enabled the formulation of strategies and recommendations to overcome barriers to local manufacturing of vaccines in South Africa. A qualitative study utilising comparative content analysis, was used to compare the policy, legislative and regulatory frameworks in South Africa with that of Egypt. The study found that South Africa and Egypt have adopted vaccine policies of the African Union. South African legislation is well developed with the relevant regulations to support local vaccine manufacturing. Detailed guidelines for vaccine manufacturing activities are present in South Africa and Egypt that are aligned with international regulatory bodies. The South African Health Products Regulatory Authority has established itself as the frontrunner for regulatory harmonisation in Africa. Strong collaboration between national regulators and vaccine manufacturers is needed. National Regulatory Authority harmonisation on the African continent is the cornerstone for supporting the local vaccine manufacturing industry.
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    A Cost Comparison study of the electronic tick register with a paper based tick register in clinics within the Ekurhuleni District
    (University of the Witwatersrand, Johannesburg, 2023-08) Khoza, Courage Macduff; Thomas, Leena Susan
    Introduction & Background: A paper-based register is used to capture routine health information from Primary Health Care (PHC) clinics into the District Health Information System (DHIS) in South Africa. However, DHIS data was reportedly unreliable and inaccurate, as the paper-based system was error-prone. To address this, the Ekurhuleni Health District in the Gauteng Department of Health (GDOH) developed and piloted an electronic (E-tick) PHC register in three of its facilities. Upon completing the pilot in 2019, the implementation of this system was halted as it was not incorporated into the GDOH budget, partly due to inadequate information on its costs compared to the paper-based system. Aim: This study aims to cost and compare the expenditure of the electronic tick register and the paper-based tick register systems and determine provider views on their use in the Ekurhuleni Health District. Methods: Two methods were used: a) a descriptive cost-comparison study of the paper-based tick and the E-tick registers from November 2017 to December 2019 and b) a descriptive cross-sectional study using interviewer-administered questionnaires about health worker experiences using both registers during the stated period. Results: The study found that the E-tick register was less costly than the paper-based register. The year 2018/19, which was the only complete financial year in the study period is used for comparison. The paper-based register cost the district R42.4 per patient, while the E-tick cost R29.9 (29.5% cheaper). Of ten study theme areas explored in the interviews, the E-tick was advantageous in eight, these were: Convenience, easy accesses, quick recording time, safe information storage, immediate data capturing, ability to add more elements, fewer errors and good font size and legibility. The paper-based register was found to be advantageous in just four study themes which were: Convenience, easy accesses, independence from electricity supply and sufficient writing space. Conclusions: The E-tick register was found to be preferred over the paper-based register as it was quicker, cheaper, and acceptable to most of the health workers who used it. These are important findings for the health district as the study generates local evidence that the Ekurhuleni Health District and the Gauteng Department of Health can use to justify investments in scaling up and sustaining locally developed innovative digital solutions such as the E-tick register. This further enables the health district to improve recording times and compliance with record management legislation.
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    A nexus of student food (in)security, common mental disorders, and academic success in the midst of the covid-19 pandemic
    (University of the Witwatersrand, Johannesburg, 2024) Wagner, Fezile
    Background: South African Higher Education Institutions (HEIs), akin to their global counterparts, grapple with the challenge of low throughput and dropout rates, as students often extend beyond the minimum required duration to complete their academic programmes. Research has identified the first year of study as the period carrying the highest risk for student failure and attrition. Factors such as prior academic performance, family background, and the student's ability to integrate into various aspects of university life emerge as significant determinants of academic success. Notably absent from these determinants are considerations pertaining to student wellbeing, encompassing mental health and food security status. These aspects assumed heightened awareness during the coronavirus disease of 2019 (COVID-19) pandemic, which posed threats to social, economic physical, and psychological wellbeing. For university students, the pandemic necessitated a swift adoption of a new pedagogical approach - Emergency Remote Teaching and Learning (ERTL) – along with most students being forced to relocate home, while simultaneously facing the harsh realities of mass job loss, illness, and grief brought on by the pandemic. Objective: This PhD aims to measure the impact of the COVID-19 pandemic on first time, first year university students’ food insecurity and mental health status (specifically, the common mental disorders (CMDs): anxiety, depression and mental distress symptoms), as well as to understand the implications of this on academic success. Methods: Taking place at a large, urban South African university, this research made use of a concurrent triangulation research design. Two cross-sectional surveys were administered in the years 2019 (before the pandemic) and 2020 (during the COVID-19 pandemic). Included in the surveys were validated tools used to measure depression (Patient Health Questionnaire 9-item (PHQ 9)), anxiety (Generalized Anxiety Disorder 7-item (GAD-7)), and mental distress symptoms. The Household Food Insecurity Access Scale (HFIAS) was also included in the two cross-sectional surveys to measure food insecurity levels. This tool was validated before being administered. Academic success was evaluated through two distinct approaches: i) the first method involved scrutinizing student failure rates and progress; ii) the second method focused on assessing retention and dropout rates. Qualitative data collection took place in 2020 and took the form of in-depth interviews (IDIs) and focus group discussions (FGDs). ii Results: Due to the lockdown directive, students living at home during studies increased from 29% in 2019 to 88% in 2020. In terms of the student failure rate, a reduction was noted from 23.4% (95% CI: 20.7- 26.3) in 2019 to 14.6% (95% CI: 12.0- 17.7) in 2020. Teaching staff acknowledged that students seemed to have a better grasp of complex content during ERTL, and feedback from students themselves indicated the benefits of being able to access and replay lecture recordings as well as the flexibility introduced by ERTL. Increased dropout levels were found - increasing from 5.5% (95% CI 4.2- 7.2) in 2020 to 10.5% (95% CI 8.2- 13.2) in 2021. Moderate food insecurity status (OR= 2.50; 95% CI: 1.12- 5.55; p=0.025), and severe mental distress symptoms (OR= 7.08; 95% CI: 2.67- 18.81; p<0.001) increased the odds of student dropout. The adjusted prevalence of food security was found to be better during the later time point - 30.3% (95% CI: 27.4- 33.4) in 2019 before the COVID-19 pandemic, to 37.9% (95% CI: 34.1- 41.9) 2020 during the COVID-19 pandemic. While the prevalence of CMD symptoms worsened over time; the prevalence of severe anxiety symptoms increased from 17.5% (95% CI: 15.2- 20.1) in 2019 to 25.4% (95% CI: 22.0- 29.1) in 2020. Conclusions: The study found an increase in student dropout and a decrease in failure rates during the pandemic, findings corroborated by other studies. Analyses suggest mental distress symptoms and food insecurity were important drivers of student dropout during the pandemic. Findings highlighted a clear decline of food insecurity when compared to figures before the pandemic. Literature highlighted how food and eating practices change when students are at home; this may have reduced food insecurity levels. A significant increase in the prevalence of CMD symptoms during the COVID-19 pandemic was observed and is believed to have been influenced by various intricate factors including grief, job loss and confinement. These findings provide important insights to HEIs in the event of future disruptions and as they embrace hybrid teaching and learning approaches post COVID-19. Although the reduction in failure rates may have been possibly due to changing the delivery of content (ERTL), HEIs must consider economic, social and mental health factors that may exclude certain groups of students when designing these approaches. It is crucial to explore ways to facilitate remote learning for students that address epistemological access challenges while maintaining inclusivity and connectedness as this is likely to contribute positively to academic success.
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    A Qualitative Study of the Nurses' Perceptions of their Practice Environments in two Selected Hospitals in Gauteng Province
    (University of the Witwatersrand, Johannesburg, 2024) Moyo, Promise; Ditlopo, Prudence
    BACKGROUND South Africa, similar to many low- and middle-income countries (LMICs), faces significant human resources for health (HRH) challenges, including an aging workforce, heavy workloads, inadequate staffing, insufficient equipment, and unequal distribution of health professionals between the public and private sectors, as well as between urban and rural areas. While the causes of this crisis are complex, unhealthy work environments are a significant contributing factor. Improving nursing practice environments is essential for addressing these challenges, as healthy environments correlate with increased job satisfaction, retention, and patient care quality. However, research on nurses' practice environments in LMICs, particularly South Africa, is limited, especially qualitative studies utilising the domains of the Practice Environment Scale of the Nursing Work Index (PES-NWI) to gauge nurses' perceptions. METHODOLOGY Therefore, this study explored nurses’ perceptions of their practice environments in both public and private hospitals in Gauteng province. An exploratory qualitative study design was used, and data was collected from April to June 2023. A multi-stage sampling strategy was used to select all categories of nurses from the two selected hospitals in Gauteng to participate in the study. Face-to-face in-depth interviews were conducted with eighteen participants using a semi-structured interview guide. Thematic analysis was done using MAXQDA Plus 2022 software. RESULTS Eighteen nurses were interviewed, exploring eight domains related to their practice environments: participation in hospital affairs, managerial support, foundations for quality care, staffing adequacy, resource availability, team collaboration, staff development, and safety. Contradictory views emerged, with some nurses expressing positive perceptions while others reported negative experiences, particularly regarding involvement in decision-making and managerial support. Participants identified a lack of adequate staffing and resources, with differing views on team collaboration and communication. Facilitators for a positive practice vii environment included in-service training opportunities, resource provision, and supportive management. Barriers included limited professional growth opportunities, excessive workloads, and inadequate resources. To enhance practice environments, participants suggested strategies such as adequate staffing, resource provision, professional development opportunities, recognition, and improved managerial support. CONCLUSION This study highlights the critical need for addressing barriers to create healthier work environments for nurses, ultimately improving patient care quality and workforce stability. Moreover, nurses had solutions for the improvement of their work environments which could be detrimental to the nurse managers and policy makers to improve the nurse work environments as perceived by the people on the ground. Therefore, nurse managers and policy makers should adopt and implement fair and transparent policies for workload distribution and scheduling, ensuring that nurses have a manageable workload and a healthy work-life balance. This could include the involvement of nurses in decision-making pertaining to hospital affairs. Nurses could be given opportunities to be part of the policy formulation where surveys can be distributed to have their views as their involvement would improve the work environment.
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    A retrospective study of isokinetic dynamometry parameters in patients diagnosed with unilateral Achilles tendinopathy
    (University of the Witwatersrand, Johannesburg, 2024) Lloyd, Rohan; Gradidge , Philippe; Constantinou, Demitri
    Introduction: The Achilles tendon, the strongest tendon in the human body, is vital for locomotive activities like walking and running. Despite its strength, it is prone to Achilles tendinopathy (AT), a debilitating condition characterised by pain, swelling, and decreased performance. As a common foot and ankle disorder, AT’s prevalence spans across athletes, recreational exercisers, and the sedentary population, with incidences up to 52% in former elite athletes with a lifetime incidence of six percent in the general population. The aetiology of AT involves both extrinsic- and intrinsic risk factors, including overuse, biomechanical irregularities, and muscular dysfunction, particularly in the gastrocnemius-soleus muscles. Research indicates that plantar flexor weakness often occurs before Achilles tendon pain develops. Weakness in the plantar flexor muscles is a key modifiable risk factor for AT issues. Conventional research on AT has primarily focused on peak torque (PT) derived from isokinetic dynamometry evaluations, leaving a gap in understanding the full spectrum of muscle performance affected by AT. Isokinetic dynamometry, with its versatile protocols and advanced software, can comprehensively evaluate muscle performance from both strength and endurance perspectives, addressing this gap. Aim of study: This study aimed to investigate the effects of unilateral AT on various isokinetic dynamometry parameters, including torque, position, and time, in individuals diagnosed with this condition. The objectives were to determine the extent of dysfunction and weakness in the gastrocnemius-soleus muscles and to compare these parameters between symptomatic and asymptomatic extremities, thus enhancing the understanding of AT's unilateral nature. By expanding the analysis beyond PT, the study addresses the gap in current research, exploring a more comprehensive scope of muscle performance in AT. Method: This retrospective study investigated the impact of unilateral AT on isokinetic dynamometry parameters. Participants were males and females, aged 18 years or older, diagnosed with unilateral AT. Initial isokinetic dynamometry evaluation reports from 2015 to 2022 were collected from a private biokinetics practice in South Africa. Although data on 54 participants initially met the inclusion criteria, the exclusion criteria, which required evaluations to be performed at an angular velocity of 60 degrees per second, reduced the number of suitable reports. Consequently, only the evaluations of n=21 participants (n=18 males and n=3 females, with a total sample mean age of 53.1 years) were included in the study. Isokinetic dynamometry evaluation, conducted by registered biokineticists, followed standardised protocols with the Humac Norm Cybex Testing and Rehabilitation System. Parameters analysed included torque, position, and time measures. Statistical analysis 4 involved paired t-Tests and Wilcoxon tests for normally and non-normally distributed data, respectively, with a significance level set at p<0.05. Results: The analysis of PT between symptomatic- and asymptomatic extremities revealed no statistically significant difference, with symptomatic extremities demonstrating a mean PT of 38.81 foot-pounds (SD: ±10.97) compared to 40.91 foot-pounds (SD: ±11.48) for asymptomatic extremities (p = 0.24). However, a significant difference was noted in the joint angle at PT (JAPT), as determined by the Wilcoxon signed-rank test. Symptomatic extremities exhibited a lower mean joint angle of 1.8 degrees (SD: ±5.11) compared to 2.24 degrees (SD: ±3.89) in asymptomatic extremities (p = 0.0001). Time to PT (TPT) did not differ significantly between symptomatic- (0.20 seconds; SD: ±0.13) and asymptomatic (0.21 seconds; SD: ±0.11) extremities (p = 0.16). Similarly, time PT held (TPTH) showed no significant difference between symptomatic- (0.36 seconds; SD: ±0.33) and asymptomatic (0.34 seconds; SD: ±0.39) extremities (p = 0.49). The analysis of work per repetition (WPR) revealed marginal differences between symptomatic- (17.57 foot-pounds; SD: ±5.48) and asymptomatic (18.91 foot-pounds; SD: ±5.90) extremities, but these differences did not reach statistical significance (p = 0.16). The average power per repetition (APR) differed between symptomatic- (35.48 watts; SD: ±11.71) and asymptomatic (39.05 watts; SD: ±13.14) extremities, with a paired t-Test indicating a trend toward statistical significance (p = 0.06), though this did not meet the conventional threshold for significance in this sample. Conclusion: The study provides an understanding of unilateral AT's impact on isokinetic dynamometry parameters. The study highlighted bilateral muscle dysfunction and weakness in individuals with unilateral AT. This was evidenced through the comparative analysis of PT, PT percentage body weight (PT%BW) and PT ratio (PTR) parameters against established norms. Achilles tendinopathy does not significantly affect the speed of muscle contraction or endurance in maintaining PT. This questions the notion of unilateral impairment in AT and highlights the necessity of a comprehensive approach in rehabilitation, focusing on strength, endurance, and biomechanics. The findings also suggest the need for further research with larger cohorts and varied isokinetic dynamometry parameters to validate these conclusions and enhance rehabilitation protocols in AT.
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    A survey of the professional quality of life of pharmacists and rehabilitation therapists at three public sector hospitals in Gauteng, South Africa
    (2024) Moyo, Nonkazimulo
    Background- The global goal of Universal Health Coverage (UHC) cannot be achieved without a wellmotivated and productive health workforce. Central to their motivation and productivity is the notion of professional quality of life (ProQOL) that captures both the positive and negative emotions of caring work. However, there is a dearth of empirical studies on the ProQOL of pharmacists and rehabilitation therapists, especially in an African setting. Study aim -The aim of the study was to examine the self-reported ProQOL of pharmacists and rehabilitation therapists at three public sector hospitals in the Gauteng Province of South Africa. Methodology- During 2021, a cross-sectional analytical study was conducted at three public sector hospitals in the Gauteng Province of South Africa. Following informed consent, all eligible pharmacists, pharmacist assistants, occupational therapists, physiotherapists and speech therapists and audiologists completed a self-administered questionnaire electronically. In addition to sociodemographic information, the questionnaire obtained information on compassion satisfaction, burnout, and secondary traumatic stress using the ProQOL scale (version 5) and work-related experiences during the COVID-19 pandemic. STATA® 17 was used for descriptive and multivariate analysis of the survey data. Results- A total of 118 pharmacists and rehabilitation therapists completed the survey. The majority were female (83.00%), single (63.46%), with mean age 30.77 years (SD=9.08). The results revealed moderate mean scores for compassion satisfaction (39.62; SD=5.48), burnout (24.26; SD=5.12) and secondary traumatic stress (23.03; SD=6.31). The predictors of compassion satisfaction were moderate positive COVID-19 experiences score (β=+2.61;95% CI 0.54; 4.68; p=0.014) and high positive COVID-19 experiences score (β =+ 2.68; 95%CI 0.40; 4.96; p=0.021); moderate overall job satisfaction score (β =+ 3.17; 95% CI 0.16; 6.18; p=0.039) and high overall job satisfaction score (β =+ 7.26; 95% CI 4.06; 10.47; p<0.001). The predictors of burnout were being single (β=+2.02 95% CI 0.07; 3.97; p=0.042), full professional registration (β=+4.23; 95% CI 1.79; 6.67; p=0.001), direct involvement in patient care (β=+3.24; 95% CI 0.22; 6.26; p=0.036) and reporting a heavy workload (β=+ 2.61; 95% CI 0.75; 4.48; p=0.007). The predictors of secondary traumatic stress were being male (β=+ 3.26; 95% CI 0.36; 6.15; p=0.028), and full registration (β=+ 5.72; 95% CI 2.41; 9.03; p<0.001). Conclusion- The ProQOL of pharmacists and rehabilitation therapists is influenced by a combination of individual, workplace, and health system factors, suggesting the need for a multifaceted approach to optimise their contribution to the achievement of UHC. Such approach should include provincial health, hospital management, and peer support as well as self-care activities.
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    A visual analytics approach to characterising disease progression among adults with chronic diseases in rural Agincourt northeast South Africa
    (University of the Witwatersrand, Johannesburg, 2024) Nhlapho, Mapule Dorcus; Kabudula, Chodziwadziwa
    Chronic diseases pose a significant challenge to the healthcare systems in South Africa, calling for innovative approaches for comprehensive understanding and management. This research study utilizes the Agincourt HDSS-Clinic dataset to design and implement a visual analytics system using the R Shiny web application framework. Focused on adults with chronic diseases, the tool employs dynamic visualizations to show patterns of healthcare utilization and disease progression. Through the R Shiny platform, the system provides a user-friendly interface for exploring and interpreting complex data, offering valuable insights into patient healthcare behaviours and the dynamics of chronic illnesses. The study used data from a total of 26 426 patients consisting of 19 265 (73%) females and 7 161 (27%) males. The study revealed previously unrecognized associations between specific chronic conditions including the existence of a substantial intersection between HIV, Hypertension, and Diabetes with 101 patients experiencing the coexistence of all the three conditions. Notably, the visual analytics system facilitated the identification of distinct healthcare utilization patterns across different demographic groups highlighting the most frequently visited health facility accounted for 5 912 patient visits overall while the least visited health facility accounted for 1 447 patient visits. The findings underscore the effectiveness of visual analytics in uncovering trends within complex datasets. The implications of these findings extend beyond the immediate research scope, influencing healthcare strategies and contributing to the ongoing discussions on innovative solutions for chronic disease management. This study contributes to the evolving field of visual analytics in healthcare, demonstrating the potential for such tools to inform decision-making and enhance patient outcomes
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    Acceptability of HPV vaccine among adolescent girls and young women in Sub-Saharan Africa: A Systematic review
    (University of the Witwatersrand, Johannesburg, 2024) Motlatsi, Mokete; Ojifinni , Oludoyinmola
    Background: Human papillomavirus (HPV) is a common sexually transmitted infection and a precursor of cervical cancer in women. It is a significant public health concern globally, particularly in Sub-Saharan Africa where cervical cancer incidence rates are among the highest in the world. HPV vaccination has emerged as a key preventive strategy to reduce the burden of HPV-related diseases, including cervical cancer. Therefore, understanding the acceptability of the HPV vaccine among adolescent girls and young women in Sub-Saharan Africa is crucial for a successful vaccination program. Aim: The aim of this review was to synthesise existing qualitative research on factors associated with HPV vaccine acceptability among adolescent girls and young women (AGYW) to highlight programmatic gaps for successful scale-up and penetration of the vaccine in sub- Saharan Africa. Methods: The review was conducted in line with the Joanna Briggs Institute (JBI) methodology for qualitative reviews and meta-aggregation. The key search terms used the operator “or” to combine the synonyms and the operator “and” to filter the results which contained the desired terms. The keywords used were HPV vaccine, acceptability, adolescent girls, young women, Sub-Saharan Africa. The databases searched included EBSCO-host, ProQuest, and MEDLINE/PubMed, Web of Science and Google Scholar. Results: There were 19 findings derived from the included studies which were further analysed through meta-aggregation from four SSA countries. Data collection was mainly through focus group discussion of AGYW. Aggregated quotes were narrated through a synthesis of findings which identified a range of motivators, deterrents and agency problem influencing vaccine acceptability. Motivators included knowledge, awareness, and peer influence, while deterrents included safety concerns and agency problem included autonomy to decision making among adolescents and female caregivers. Conclusion: There is a complex interplay of factors influencing HPV vaccine acceptance, which underscores the importance of targeted interventions to address misconceptions, improve access to vaccination services, and promote informed consent on HPV vaccination among adolescent girls and young women in Sub-Saharan Africa. Further research is needed to explore the effectiveness of interventions aimed at increasing HPV vaccine acceptability and coverage in Sub-Saharan Africa.
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    Activity and time spend patterns of residents in low-income settlements in the City of Johannesburg, South Africa
    (2024) Bhuda, Hope Prudence Boipelo
    Background: Human health risk assessment is concern about estimating the population exposure (HHRA) for environmental pollutants or contaminants. Exposure assessment for population-level require time-activity pattern distributions in association to microenvironments where individuals reside and spend their time. Time-activity patterns in South Africa have not been adequately explored, which may lead to wrong dose estimation for health risk assessment. No in-depth and systematic analyses of time-activity patterns in low-income communities have been done to date in South African context. Aim: The aim of this study was to describe variations on time-activity patterns based on age, sex and socioeconomic status amongst residents of low-income communities in South African township (Matholesville informal settlement). Methodology: A cross-sectional study design was adopted to assess time-activity patterns amongst lowincome residents in South African townships. One Hundred and Thirty (130) households were selected randomly to participate in the study. A questionnaire survey comprising of key questions including demographics, type of household, type of activities conducting indoor, time spent on activities indoor and outdoor in a microenvironment, preferred season of the year and mode of transport commuting to different areas was administered to the study participants. In addition, diaries were used to get information on daily activity time pattern for seven (7) days. Completion of questionnaire were based on interviews with the study participants while diaries were self-administered by the participants daily over seven days. Results In this study, a total of 130 participants aged 18-35 and 36-75 years were included. Approximately 33% and 67% of the respondents were < 35 years and >35 years, respectively. This suggests that most of the households are headed by adults outside the youth age category. About 30 houses were found to be erected using bricks while 100 houses were made of corrugated iron. About 75%, 14%, 8% and 2% of the study respondents were found to fall into the following race, black, coloured, Indian and white. Approximately (83% brick, 71% shacks) of the study respondents attained secondary education the remainder of the respondents attained primary education. The most performed activities inside brick type dwellings are sleeping (100%), cooking (77%), cleaning (70%) and watching television (TV) (60%). While most performed activities indoors for shack dwellings are cleaning (87%), cooking (70%), sleeping (68%) and TV (37%). There is a high prevalence of none employed household heads at 53% for the brick dwelling and 63% for the shack dwellers. The average monthly income was found to be R4 304 and R3 650, for brick and shack type dwellings, respectively. Females were found to perform a larger proportion of indoor household activities than males. A total of 36% was spend on cooking and cleaning followed by 29% of the time watching TV in the brick type dwellings. For the brick dwellers spend 67% indoors and 33% outdoor while for the shack dwellers about 31% of the time is spend indoor. Conclusion: The study had hypothesised that females above 18 years old residing in low-income communities are likely to spend most of their time at home carrying out domestic duties compared to their male counterparts, who are expected to spend most of the time outside the residential spaces. Therefore, the hypothesis for this study is partially confirmed, meaning that women spend most of their time indoor performing household chores than males. It was also found that the time spent indoor is relatively lower than what is globally reported as known to be >80% of the time, people are said to be indoors. This implies that the variation on the socio-economic status and sub-population including country’s dynamic might be the biggest influencer of time-activity pattern. Data obtained from this study can be used to account variability in human health risk assessments and reduce uncertainty in the derived exposure dosage where time spent pattern is considered an important variable. Recommendations: ✓ Future studies may be carried out covering a larger population density to gain more detailed time activity patterns. ✓ This study focused on a low-income settlement which has different characteristics to semi-formal, rural, high tax yield settlements in South Africa. Therefore, a larger study focusing on different socio-economic classes need to be carried out to have a comprehensive time activity pattern dataset for South African population. ✓ The current project focused only on adult age group without considering vulnerable groups (toddlers, and elderly person) time activity pattern. An additional study focusing on children time activity pattern is required in order to gain an understanding on what activities children spend most time.
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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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    Adoption of managed care by medical aid societies in Zimbabwe
    (University of the Witwatersrand, Johannesburg, 2024) Gukushu, Silence Tendayi; Blaauw, Duane
    Background: Globally healthcare costs have increased, and a significant proportion of this growth is attributable to moral hazard. Managed care tools are therefore widely used as healthcare cost containment strategies that attempt to moderate classical, provider and patient moral hazard. There is, however, no data on the extent of implementation of managed care tools by private health insurance organisations in Zimbabwe. Aim: We investigated the adoption of managed care tools by medical aid societies in Zimbabwe and explored their perceptions of how managed care tools have affected their healthcare expenditure. Methods: We used a cross-sectional study design and a sequential explanatory mixed method approach. Total population sampling was done for the quantitative component of this study, and six medical aid societies were purposively sampled for the qualitative component. Quantitative data were collected through a REDCap self-administered online survey and qualitative data were collected through online and telephonic in-depth interviews of medical aid society managers. The numerical data of the medical aid societies’ key operational factors were summarised using medians and inter-quartile ranges. Proportions of the adoption of manged care and the types of managed care tools implemented by medical aid societies were calculated. We also calculated the proportions of agreement by the medical aid societies managers to the factors affecting managed care tools adoption. A six-step inductive thematic analysis was used to analyse the qualitative data of the perspectives of medical aid societies on the effects of managed care tools on healthcare expenditure. Results: Our quantitative results show that 77.8% of medical aid societies have adopted managed care tools, with an average usage of 3.33±1.80 managed care tools. The adoption of specific managed care tools was 90.5% for preauthorisation, 57.1% for gatekeeping, 52.4% PPN, 42.9% capitation, 38.1% disease management, 28.6% discounted FFS and 23.8% for formulary by the study medical aid societies. Based on our qualitative data analysis, all the participants highlighted improved cost control as one of the effects of implementing managed care tools. iv Conclusion: Medical aid societies in Zimbabwe are adopting managed care tools into their operations. However, the use of some managed care tools is still low.
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    An audit of the Speech Therapy and Audiology Department at a district hospital in Gauteng
    (University of the Witwatersrand, Johannesburg, 2024) Graca, Lucie Berthe Lynda; Bezuidenhout, Jacqueline Kim
    Background. Children require speech and language to communicate adequately and to participate in daily activities and in society. Speech and language delays may have far- reaching consequences on a child’s development. Objectives. To audit the referrals of children less than six years of age referred to a speech therapy and audiology department at a district-level hospital in Gauteng, South Africa. Methods. A retrospective audit of children aged below six years referred to the outpatient Speech Therapy and Audiology (STA) Department from 01st January 2021 to 30th June 2022 was conducted. Mean and standard deviation (SD) were used for normally distributed continuous variables and median and interquartile range (IQR) for skewed variables. Categorical data were analysed using the Chi-squared and Fishers exact test. Results. One hundred and fifty outpatient referrals were reviewed, of which 94 (62.7%) were males. Speech delay was the most common reason for referral (38%). Of the children seen by the speech therapists and audiologists, 24 (20.3%) children were discharged and 58 (49.2%) defaulted follow-up. One hundred and two children had auditory screening and three children (2.5%) were identified with hearing loss. Twenty-eight children (23.7%) were referred for neurodevelopmental assessments. Conclusions. This audit provided insight into the disease profile of children referred to a STA department at a district level one hospital. It highlighted the demographics of children referred to a district hospital, further emphasising the importance of early identification, referral and intervention of children with speech and language delay and hearing loss. The high number of children lost to follow-up motivates for more research be done to identify the reasons for these findings.
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    An Economic Evaluation of the Establishment of a Paediatric Dialysis Unit at Pietersburg Hospital, Polokwane, Limpopo
    (University of the Witwatersrand, Johannesburg, 2024) Levy, Cecil Steven
    Introduction: Many children who develop end stage kidney disease in South Africa are denied therapy due to their distance from the hospital. Decentralising paediatric nephrology services would go a long way to relieving the burden on these children and their families. Pietersburg Hospital, Polokwane, has the potential to house a paediatric satellite dialysis unit, but some understanding of the costs and benefits of such a program is needed before it is implemented. Methods: A cost utility analysis was performed using Markov modelling techniques to analyse the expected costs and benefits of such a program from both the societal and the healthcare payer perspectives. The cost effectiveness was evaluated by analysing incremental cost effectiveness ratios (ICER) and incremental net monetary benefits generated by the analysis. All cost data was obtained from a cohort of children receiving chronic kidney replacement therapy (dialysis and/or kidney transplant) at the Nelson Mandela Children’s Hospital (NMCH) between 1 April 2019 and 31 March 2022. The comparator was represented by data from children whose home address was more than 150 km from NMCH, and from a group of “Unstable Kidney Transplant” patients, while the intervention was the theoretical establishment of a satellite paediatric dialysis unit at Pietersburg Hospital, Polokwane, represented by data from children whose home address was less than 150 km from NMCH, and from a group of “Stable kidney transplant” patients. Results: The deterministic sensitivity analysis predicted that the intervention would be cost effective from both the societal and the healthcare payer perspectives and showed that length of stay resulted in the largest change in the ICER. The probabilistic sensitivity analysis also predicted that the intervention would be cost effective from both the societal and the healthcare payer perspectives. The cost effectiveness acceptability curves demonstrated that the intervention was likely to be cost effective more than 50% of the time for a willingness to pay threshold of ZAR 112 000 (or one times the average gross domestic product per capita for South Africa in 2022). Conclusion: Our findings are in conformity with data from the literature which show that satellite dialysis units can be cost effective. Establishing a satellite unit at Pietersburg Hospital, Polokwane for the treatment of children with end stage kidney disease in the area would not vi only improve access and quality of life for these children, but it is also likely to be cost effective, from both the societal and the healthcare payer perspectives. We hope that these findings will encourage the introduction of, at least, a pilot program at Pietersburg Hospital, Polokwane to establish the validity of our results. Success with this model could then be used as a template to roll out similar projects across the region.
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    An evaluation of the integration of oral pre-exposure prophylaxis (prep) as standard of care for HIV prevention in clinical trials in South Africa
    (University of the Witwatersrand, Johannesburg, 2023) Beesham, Ivana; Mansoor, Leila E; Beksinska,Mags
    Background: Oral tenofovir-based pre-exposure prophylaxis (PrEP) is an effective biomedical HIV prevention option. In 2015, the World Health Organization (WHO) recommended oral PrEP for those at substantial risk of HIV infection, and several countries have since adopted oral PrEP into their national guidelines. In the context of trials, HIV endpoint-driven trials frequently enrol individuals who are at elevated risk of acquiring HIV. Ethical guidelines recommend that study sponsors and investigators should provide access to a package of HIV prevention methods to trial participants, as recommended by WHO, including adding new prevention methods as these are validated. In 2017, the South African Medical Research Council recommended that oral PrEP be provided in HIV prevention trials. The Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial was ongoing at the time and incorporated oral PrEP into the trial’s HIV prevention package, including the onsite provision of oral PrEP at the South African trial sites during the last eight months of the trial. The ECHO Trial, conducted from 2015 to 2018, enrolled women aged 16-35 years, from 12 research sites in four African countries, and assessed the effect of three contraceptives on HIV incidence. In 2019, when this PhD project was conceptualised, there was a lack of data on the integration of oral PrEP as part of the HIV prevention package in HIV endpoint-driven trials. To address this gap, I evaluated the integration of oral PrEP as standard of care for HIV prevention in clinical trials in South Africa. Objectives: 1. To describe the process of implementing oral PrEP provision, the uptake of oral PrEP and the characteristics of women who initiated (versus those who did not initiate) oral PrEP during the ECHO Trial. 2. To evaluate oral PrEP adherence and factors associated with adherence by conducting plasma tenofovir (TFV) drug level testing using stored blood samples among a subset of women from South Africa who reported current oral PrEP use at the final ECHO Trial visit. 3. To describe the experiences of women who initiated oral PrEP at the Durban, South Africa, ECHO Trial site. 4. To explore post-trial access to oral PrEP, and barriers and enablers to post-trial oral PrEP access, among a subset of women from the Durban, South Africa, ECHO Trial site. 5. To review the current status of oral PrEP as standard of care for HIV prevention in clinical trials in South Africa. Methods: This was a mixed methodology study, conducted from 2019 to 2022, and both qualitative and quantitative methods were utilized. I describe the process undertaken by the ECHO Trial team to incorporate oral PrEP delivery into the trial’s HIV prevention package, including the onsite provision of oral PrEP by ECHO Trial staff at the South African trial sites. Characteristics between women who ever initiated oral PrEP versus those who had access to but did not initiate oral PrEP, were assessed using Chi-squared/Fisher’s exact tests for categorical variables and t-tests for continuous variables. HIV seroincidence comparisons between participants who never versus ever initiated oral PrEP were modelled using exact Poisson regression. To objectively measure adherence to oral PrEP, plasma samples collected at the final ECHO Trial visit, from a subset of women enrolled at the South African ECHO Trial sites, who reported ongoing PrEP use, were tested for TFV. Bivariate logistical regression was used to evaluate participant characteristics associated with quantifiable TFV at the final ECHO Trial visit. 10 | P a g e To understand experiences of women who used oral PrEP and patterns of oral PrEP use, we conducted questionnaires with women who initiated oral PrEP onsite at the Durban, South Africa, ECHO Trial site. Face-to-face questionnaires were conducted approximately three months following oral PrEP initiation, and explored reasons for using and discontinuing oral PrEP, side effects experienced, oral PrEP adherence and disclosure of oral PrEP use. I also evaluated factors associated with oral PrEP continuation at the final ECHO Trial visit using univariate and multivariate logistical regression. Among women continuing oral PrEP at ECHO Trial exit, telephonic follow-up was conducted 4-6 months later, to briefly explore oral PrEP access and ongoing use following study exit. Additional face-to-face, participant in-depth interviews were conducted in 2021 with a subset of women from the Durban, South Africa, ECHO Trial site, who reported ongoing oral PrEP use at ECHO Trial exit and who were given a 3-month PrEP supply at study exit. The interviews explored barriers and enablers to post-trial oral PrEP access. Finally, telephonic in-depth interviews were held with key stakeholders from research sites across South Africa known to conduct HIV endpoint-driven clinical trials to explore their perspectives on providing oral PrEP as HIV prevention standard of care in clinical trials in South Africa. Participant and stakeholder interviews were audio-recorded and transcribed, and thematic analysis was facilitated using NVivo. Results: Our key findings indicate that it was feasible to integrate oral PrEP as standard of care for HIV prevention in the ECHO Trial. PrEP uptake was 17.2% (622/3626) among those eligible for oral PrEP when it became available. Women who initiated oral PrEP were more likely to be unmarried, not living with their partner, having multiple partners; and less likely to be earning their own income and receiving financial support from partners (all p<0.05). There were 37 HIV seroconversions among women who had access to oral PrEP but did not initiate oral PrEP, and 2 seroconversions among women who initiated oral PrEP (HIV incidence 2.4 versus 1.0 per 100 person-years; Incidence Risk Ratio = 0.35; 95% confidence interval (CI) = 0.04 to 1.38). Among the 260 plasma samples from the eight South African ECHO Trial sites that were available for TFV testing, plasma TFV was quantified in 36% of samples (94/260). Women >24 years old had twice the odds of having TFV quantified compared to younger women (Odds Ratio (OR) = 2.12; 95% CI = 1.27 to 3.56). Women who reported inconsistent/no use of condoms had lower odds of TFV quantification (age-adjusted OR = 0.47; 95% CI = 0.26 to 0.83). The ancillary study conducted at the Durban, South Africa ECHO Trial site found that onsite oral PrEP uptake was high (43%, 138/324). Almost all women who initiated oral PrEP at the trial site agreed to participate in the ancillary study (96%, 132/138). Of these, 88% reported feeling at risk of acquiring HIV. Most women (>90%) heard of oral PrEP for the first time from trial staff. Oral PrEP continuation via self- report was 87% at month-1, 80% at month-3, and 75% elected to continue using oral PrEP at trial exit and were referred to off-site facilities for ongoing access. Disclosure of oral PrEP use was associated with five-fold increased odds of continuing oral PrEP at trial exit (adjusted OR = 4.98; 95% CI = 1.45 to 17.13; p=0.01). At telephonic follow-up 4-6 months after women exited the ECHO Trial, >50% reported discontinuing PrEP. Qualitative interviews conducted with a subset of women from the Durban, South Africa ECHO Trial site identified several barriers to post-trial oral PrEP access at facilities such as long queues, facilities being located far from women’s homes, unsuitable clinic operating hours, negative attitudes from providers, and oral PrEP being unavailable at some clinics. Interviews with key stakeholders from research sites in South Africa found that most stakeholders reported incorporating oral PrEP provision as part of the HIV prevention package offered to participants in HIV endpoint-driven trials. Stakeholders identified barriers to oral PrEP 11 | P a g e uptake, adherence, persistence, and post-trial access. Demand creation, and education and counselling about oral PrEP were reported as factors that facilitated uptake. Conclusion: The ECHO Trial provides evidence that it was feasible to successfully integrate oral PrEP provision as part of the trial’s HIV prevention package offered to study participants. Other HIV endpoint-driven trials can utilize our findings as a model to integrate oral PrEP provision into the HIV prevention package offered in a trial. The ancillary study findings on PrEP uptake, adherence and persistence can be utilized to guide oral PrEP trials and implementation programs. While post-trial oral PrEP access was concerning and several barriers were identified, it is possible that with the scale-up of oral PrEP in the public sector in South Africa after the ECHO Trial was completed, participants exiting trials and desiring to continue oral PrEP could have better access
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    An Exploratory Investigation into Institutional and Staff Performance: Evidence from Public Hospitals in Gauteng
    (University of the Witwatersrand, Johannesburg, 2024) Punwasi, Jayshina; Blaauw, Duane
    There are various challenges facing the South African health system, especially in Gauteng, the most densely populated province in South Africa with the largest public sector hospital network. This research was undertaken to understand how hospital performance and staff performance is measured in Gauteng public hospitals and to determine if there is a correlation between hospital performance and staff performance. Panel data from 2 administrative datasets for 34 hospitals was analysed over an 8- year period from 2013/14 to 2020/21. Hospitals were classified according to level of care into 5 categories (central, tertiary, regional, district and specialised) and data for 11 hospital performance indicators and 5 staff category indicators were analysed. Trend analysis was conducted for hospital and staff performance, PCA was used to explore the relationship between hospital performance indicators and investigate the construction of a composite index of hospital performance, and regression analysis was used to investigate the relationship between hospital performance and staff performance. Overall, capacity within the Gauteng hospitals has not increased and output only slightly increased over the 8-year period. Trends suggest that the majority of inpatient and outpatient care were provided by central hospitals where the costs of care were the highest. Regional hospitals followed closely on most indicators except emergency headcount and expenditure per PDE. Emergency care was provided more by regional and district hospitals, but it costed more to treat a patient at a district hospital than a regional hospital. Specialised hospitals tended to be outliers on most of the indicators assessed. Staff performance had consistent scores for all 5 staff categories with doctors being scored lower than other staff categories. PCA analysis determined that patient day equivalent, bed utilisation rate, average length of stay and inpatient crude death rate could form a composite indicator of hospital performance. However, it is not straightforward to capture hospital performance in a single indicator as each of these indicators captures a different element of performance. iv The key finding of this research was that there was no correlation between hospital performance and staff performance over the 8-year period based on both individual indicators and principal components. This emphasises the need for staff performance to be linked to hospital performance indicators from an output, process, quality and outcome perspective in order for Gauteng hospitals and staff to provide health care in an effective and efficient way.
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    An Ubuntu-based Account of the Moral Obligation to Provide Gender-Affirming Medical Treatment to Transgender Adolescents, aged 12-17, in South Africa
    (University of the Witwatersrand, Johannesburg, 2024) Bellingan, Kelsay Grace; Behrens, Kevin
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    Analysis of Progestin-Based Injectable Contraception and the Risk of Curable Sexually Transmitted Infections in a Prospective Cohort of Adolescent Girls and Young Women in Johannesburg, South Africa
    (University of the Witwatersrand, Johannesburg, 2024) Rundogo, Juliet Vimbai
    Introduction: Several studies have shown an increased risk for sexually transmitted infections (STIs) in women using hormonal contraception. We explored this association in a cohort of adolescent girls and young women (AGYW) in Johannesburg, South Africa. Methods: CHOICES was a prospective observational study that investigated the association between progestin-based injectable contraception (IC) and Neisseria gonorrhoea (GC), Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), and Trichomonas vaginalis (TV) in Human-Immuno-Deficiency Virus (HIV) uninfected AGYW aged 16-24 years. We used logistic regression to explore the associations between IC compared to non-HC use for each STI. Results: Of 736 AGYW screened, 611(83%) were eligible, and 577 included in this analysis. Median age was 21 years (IQR 19-22 years). Overall, 183/577 (32%) had a curable STI, with 130/577 (23%) having CT, 37/577 (6%) MG, 24/577(4%) NG and 19/577 (3%) TV at baseline. In both bivariate and after adjusting for sexual behavioural factors, there were no statistically significant associations between IC use and having an STI. Conclusion: Although there was a trend, there was no statistically significant association between IC and any STIs were observed in this cohort with a high STI burden.
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    Antibacterial resistance patterns found in urine samples obtained from the elderly in Gauteng
    (University of the Witwatersrand, Johannesburg, 2024) Labuschagne, Olivia; Leigh-De Rapper, Stephanie; Williams, Christopher David
    Background: Elderly are frequent users of healthcare services and may have complex needs related to frailty and multimorbidity. Urinary tract infection (UTI) is often diagnosed in this cohort (often based on non-specific or atypical symptoms) leading to antimicrobial therapy, often chosen empirically. This presents a poorly understood risk of antimicrobial resistance. More accurate data on antimicrobial resistance (AMR) of urinary pathogens in older people, including LTCF residents, is needed. This study aims to determine if samples obtained from LTCF-dwelling individuals show different rates of in vitro AMR compared to samples obtained from community dwelling older people (aged 60 years). Methodology: The study used computerised microbiology laboratory records of urinary samples analysed by Ampath Laboratories in South Africa. 𝜒2 analyses were used to detect differences in resistance patterns between LTCF and community-dwelling individuals. Sub-group analyses and multivariable logistic regression were undertaken for gender, age, in-patient and out-patient samples, and year of collection. Results: Microbiological results from urine samples in Gauteng where analysed (n=50,704). Three cultured bacteria (Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis) showed significant differences in AMR between the two study cohorts. The adjusted odd ratios for Escherichia coli and Proteus mirabilis indicated increased AMR amongst LTCF residents. Conclusion: Urine samples from LTCF-dwelling people have higher rates of in vitro resistance to common antimicrobials used to treat UTI. Greater focus on antimicrobial stewardship in LTCFs is recommended extending to diagnostic approach, empirical antibiotic choice and bacteriological confirmation of antimicrobial choice.
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    Assessing the potential interaction between CBD and TBR1 CBD and T-box domain
    (University of the Witwatersrand, Johannesburg, 2024) Blignaut, Chanel; Sylvia, Fanucchi; Adeyemi, Samson
    In 2020, Cannabidiol (CBD) emerged as the most commonly used recreational substance among pregnant women and was perceived as a natural and safer option for alleviating pregnancy- related symptoms, yet its potential effects on foetal neurodevelopment remain uncertain. With varied results from existing literature on the association between prenatal cannabis use and Autism Spectrum Disorder (ASD) development, this study focuses on filling these knowledge gaps. It investigates the potential interaction of CBD with the T-box domain of TBR1, a transcription factor implicated in ASD. CBD may cross the placenta and distribute throughout the developing foetal organs, including the brain, where it may interact with TBR1. This study's objective is to lay the groundwork for future research into the impact of CBD binding on TBR1 functionality, whose dysregulation is implicated in ASD. The study aims to use in vitro and in silico methods to identify and characterise the interaction between CBD and TBR1 T-box Domain. Initially, predictive models were utilised to determine the structure of the TBR1 T-box domain and its binding domains. Subsequently, the ADMET properties of CBD are assessed to determine its potential interaction with TBR1 T-box domain within the body. Through the optimisation of the TBR1 T-box domain and CBD structures, induced fit docking and molecular dynamics simulations, the study aims to predict the potential interaction sites, dynamics and stability of this interaction. The study confirms the computational results using in vitro methodologies. After expressing and purifying the TBR1 T-box domain, a pull-down assay (PDA), thermal shift assay (TSA) and Time-resolved Fourier-transformed infrared spectroscopy (TR-FTIR) are used to evaluate the potential binding, stability and physiochemical properties of the interaction. Computational analysis, using Maestro Schrödinger Induced Fit Protocol, predicts that CBD binds stably within a hydrophobic pocket of TBR1 T-box domain, away from its DNA-interacting residues. Pose 2 and 3 from molecular docking shows the highest binding affinity and molecular dynamics simulations, using Maestro Schrödinger Desmond Molecular Dynamics System, reveal that the TBR1 T-box domain stabilises upon interaction with CBD. Specifically, the interaction is facilitated by hydrophobic interactions and hydrogen bond formation with residues Ser238, Pro335, Thr360, Glu363 and Asn240. Experimental validation through PDA and TSA provided inconclusive results, but TR-FTIR confirmed the dynamic nature of the CBD-TBR1 interaction, characterised by time-dependent spectral changes. While the results do not directly indicate an impact of CBD on TBR1 functionality, further DNA binding studies are necessary for confirmation. This study suggests caution in using CBD during pregnancy due to its complex and largely unexplored interaction with TBR1, underscoring the need for more comprehensive research to conclusively understand its influence on neurodevelopmental disorders and its therapeutic potential
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    Association between serum zinc level and dynamics of Group B Streptococcus colonisation among pregnant women in South Africa
    (University of the Witwatersrand, Johannesburg, 2024) Dhar, Nisha; Madhi, Shabir A
    Background Maternal colonisation by Group B Streptococcus (GBS) is a major risk factor for early onset invasive GBS disease among newborns. Zinc micronutrient plays a critical role in several biological processes that are essential to prevent bacterial colonisation and/or invasion. The aim of this study was to investigate the association of serum zinc levels with GBS rectovaginal new acquisition and clearance from 20 to 37+ weeks gestation in pregnant women. Methods Vaginal and rectal GBS colonisation was determined at 20–25 weeks (visit-1), followed by 3 subsequent visits at 5–6 weeks intervals, until 37–40 weeks gestation (visit-4). Serum was collected at visit-1 and visit-4 and serum zinc was estimated by inductively coupled plasma mass spectrometry. “New acquisition” group was defined as participants for whom GBS culture was negative at visit-1 and acquired GBS in one of the subsequent visits. Participants not colonised with GBS at any visits were categorized as GBS “persistently uncolonised”. Participants who remained colonised throughout all study visits were defined as “persistently colonised” group. GBS “clearance group” included participants who were colonised at enrolment (visit-1) and in whom GBS colonisation cleared by last visit (visit-4). Results Participants in persistently un-colonised group had significantly higher zinc geometric mean concentration (GMC) at visit-1 compared with those who had new acquisition (20.18 µmol/L; 95%CI 17.99-22.64 vs 13.68 µmol/L; 95%CI 12.59-14.87, p=0.03). Higher zinc concentration in the persistently un-colonised group when compared with new acquisition group was significantly associated with lower odds of GBS rectovaginal acquisition [Odds ratio (OR) 0.15, p=0.001]. The lowest zinc threshold significantly associated with 45% lower odds of new acquisition was ≥15 umol/L (27.2% in new acquisition vs 40.5% in persistently un-colonised; OR 0.55; 95%CI 0.31- 0.96; p=0.03). Furthermore, zinc concentration was higher among women in clearance group compared with those in persistently colonised group (20.03 µmol/L; 95%CI 16.54-24.27 vs 16.45 µmol/L; 95%CI 13.32-20.31, p=0.04). Conclusion There was an inverse association between serum zinc levels in pregnant women and odds of GBS acquisition in those not initially colonised. Zinc supplementation in early pregnancy could reduce risk of invasive GBS disease in their newborns