4. Electronic Theses and Dissertations (ETDs) - Faculties submissions

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    Implementation of universal health coverage in South Africa: formative effects, perceived quality of healthcare and modelling of health service utilisation indicators in a national health insurance pilot district
    (University of the Witwatersrand, Johannesburg, 2023-01) Mukudu, Hillary; Igumbor, Jude; Otwombe, Kennedy; Fusheini, Adam
    Background: According to the World Health Organisation, member countries should attain universal health coverage by 2030. To achieve this goal, South Africa introduced the National Health Insurance programme in 2012. Since then, the first phase of the pilot programme has been implemented in Tshwane and ten other country districts. Historically, no other health system reform in South Africa has generated more interest than the National Health Insurance. This 15-year preliminary plan and pilot received optimism and criticism depending on several factors. The pilot programme focusing on primary health care was implemented along with several other interventions. The components of the intervention included setting up: ward-based primary healthcare outreach teams, integrated school health programmes, district clinical specialist teams, centralised chronic medicine dispensing and distribution programmes, health patient registration systems, stock visibility systems, and contracting of private non-specialised (general) medical practitioners to provide services in public primary health care facilities. These interventions were envisaged to improve healthcare quality at the primary healthcare level and offset the burden of non-emergency (secondary) care at the hospital outpatient level. However, studies have yet to be done to determine population-level formative effects on primary and non-emergency secondary healthcare indicators, their relationships, and interdependencies. These data are needed to forecast and develop measures to meet the possible increase in health service utilisation. In addition, this information is essential to guide the possible scale-up of South Africa's National Health Insurance mechanism. Such guidance may be in setting benchmarks to monitor policy implementation, determine facility staffing, the package of health services, training needs, budget for medicines and consumables, and other resource allocation. Aim: Therefore, this study first aimed to determine the formative effects of implementing the Medical Practitioners' contracting of the National Health Insurance pilot program on primary healthcare utilisation indicators measured at both primary and non-emergency secondary levels of care. A comparison was made between Tshwane national health insurance pilot district and Ekurhuleni district, which is not a pilot district. Furthermore, the study aimed to determine the relationships between healthcare utilisation indicators and their interdependencies and then provide a forecast for 2025. Methods: This quasi-experimental and ecological study used selected primary health care and outpatient department indicators in the District Health Information System monthly reports between January 2010 and December 2019 for the Tshwane district and Ekurhuleni district. Thus, to determine the formative effects on primary healthcare utilisation indicators, the selected period was from June 2010 to May 2014. A total of 48-time periods (months), with 24 before (June 2010 to May 2012) and 24 after (June 2012 to May 2014) implementation of Medical Practitioners contracting of the National Health Insurance pilot programme. Similarly, June 2012 to May 2014 was the selected period to determine the effects on the perceived quality of care. A total of 24 months, with 12 before (June 2012 to May 2013) and 12 after (June 2013 to May 2014) implementation of the Medical Practitioners' contracting of the National Health Insurance pilot programme. To determine the relationship and interdependence between Primary Health Care and Outpatient Department indicators and forecasts for 2025, 113 time periods (quarters) were selected. There were 28 quarters before and 84 quarters after implementing the National Health Insurance pilot programme. Similar methodological approaches were used to determine the effects of Medical Practitioners contracting in the National Health Insurance pilot programme on Primary Healthcare utilisation indicators and perceived healthcare quality. All study data types used in the thesis were continuous; thus, they were initially evaluated descriptively using means (standard deviations) and medians (interquartile ranges). The range was evaluated using minimum and maximum values. An Independent t-test assuming unequal variances was used to compare the means of Outpatient Department indicators in determining the effect of Medical Practitioners contracting in the National Health Insurance pilot programme on the perceived quality of healthcare. Single- and multiple-group (controlled) interrupted time series analysis was used to determine the effect of the National Health Insurance pilot project implementation on the utilisation of selected primary and non-emergency outpatient department indicators and perceived healthcare quality. A different methodological approach was used to determine the interdependencies and relationships between selected primary healthcare and non-emergency outpatient department indicators and their forecasts for 2025. Initially, data were evaluated descriptively using means (standard deviations) and medians (interquartile ranges) and the range was evaluated using minimum and maximum values. Prior to the development of the vector error correction model, several steps were taken. Firstly, a natural log transformation of all time series data was done to enhance additivity, linearity, and validity. Additionally, the level of lags at which variables were interconnected or endogenously obtained was determined due to the sensitivity of causality. Furthermore, the stationarity of time series data was determined using both graphical means and the Augmented Dick Fuller test to confirm the stability of each time series. Finally, cointegration was determined using the Johansen cointegration test to check for the correlation between two or more nonstationary series. After developing the Vector Error Correction Model, the Granger causality test was done to determine whether one series is helpful for forecasting another. Then the Vector Error Correction Model relationships between variables of selected primary healthcare and non-emergency outpatient department indicators were used to forecast the utilisation of both levels of services by 2025. Results: The findings showed changes in primary healthcare indicators measured at primary and non-emergency secondary levels before and after contracting private medical practitioners of the National Health Insurance pilot programme. The study also confirmed the influence of selected primary health care and outpatient department headcounts on each other by finding four cointegration relationships between the variables. There were differences between single-group and controlled interrupted time series analysis findings for Tshwane district and Ekurhuleni district considered independently and collectively on the utilisation of primary health care services. Thus, the positive impact observed in primary healthcare utilisation post-June 2012 is not attributable to the implementation of the Medical Practitioners' contracting of the National Health Insurance pilot programme. Conversely, there were similarities between single-group and controlled interrupted time series analysis findings for Tshwane district and Ekurhuleni district considered independently and collectively on the perceived quality of primary healthcare. In the interpretation of this finding, the similarities indicated that implementing the Medical Practitioners' contracting of the National Health Insurance pilot programme positively influenced the perception of a better quality of primary healthcare in the Tshwane district. Regarding primary healthcare indicators, there were differences between single-group and controlled interrupted time series analysis. Single-group interrupted time series analysis showed a 65% and 32% increase in the number of adults remaining on anti-retroviral therapy in Tshwane and Ekurhuleni districts, respectively (relative risk [RR]: 1.65; 95% confidence interval [CI]: 1.64–1.66; p < 0.0001 and RR: 1.32; 95% CI: 1.32–1.33; p < 0.0001, respectively). However, controlled interrupted time series analysis did not reveal any differences in any of the post-intervention parameters. Furthermore, single-group interrupted time series analysis showed a 2% and 6% increase in the number of clients seen by a professional nurse in the Tshwane and Ekurhuleni districts, respectively (RR: 1.02; 95% CI: 1.01–1.02; p < 0.0001 and RR: 1.06; 95% CI: 1.05–1.07; p < 0.0001, respectively). However, controlled interrupted time series analysis did not show any differences in any of the post-intervention parameters. In addition, single-group interrupted time series analysis revealed that there was a 2% decrease and 1% increase in the primary healthcare headcounts for clients aged ≥5 years in Tshwane and Ekurhuleni district (RR: 0.98; 95% CI: 0.97–0.98; p < 0.0001 and RR: 1.01; 95% CI: 1.01–1.02; p < 0.0001, respectively). Similarly, there was a 2% decrease and a 5% increase in the total primary healthcare headcounts in the Tshwane district and Ekurhuleni districts, respectively (RR: 0.98; 95% CI: 0.97–0.98; p < 0.001 and RR: 1.05; 95% CI: 1.04–1.06, p < 0.0001, respectively). However, controlled interrupted time-series analysis revealed no difference in all parameters before and after intervention in terms of total primary healthcare headcounts and primary healthcare headcounts for clients aged ≥5 years. Regarding secondary non-emergency outpatient department headcounts, single-group and controlled interrupted time series analyses revealed similar findings. Despite these similarities, single-group interrupted time series analysis showed a disparate increase in the outpatient department not referred headcounts, which were lower in the Tshwane district (3 387 [95%CI 901, 5 873] [p = 0.010]) than in Ekurhuleni district (5 399 [95% CI: 1 889, 8 909] [p = 0.004]). Conversely, while there was no change in outpatient department referred headcounts in the Tshwane district, there was an increase in headcounts in the Ekurhuleni district (21 010 [95% CI: 5 407, 36 611] [p = 0.011]). Regarding the outpatient department not referred rate, there was a decrease in the Tshwane district (-1.7 [95% CI: -2.1 to -1.2] [p < 0.0001]), but not in the Ekurhuleni district. Controlled interrupted time series analysis showed differences in headcounts for outpatient department follow-up (24 382 [95% CI: 14 643, 34 121] [p < 0.0001]), the outpatient department not referred (529 [95% CI: 29, 1 029 [p = 0.038]), and outpatient department not referred rate (-1.8 [95% CI: -2.2 to -1.1] [p < 0.0001]) between Tshwane the reference district and Ekurhuleni district. Four common long-run trends were found in the relationships and dependencies between primary healthcare indicators measured at the primary healthcare level and the non-emergency secondary level of care needed to forecast future utilisation. First, a 10% increase in outpatient departments not referred headcounts resulted in a 42% (95% CI: 28-56, p < 0.0001) increase in new primary healthcare diabetes mellitus clients, 231% (95% CI: 156-307, p < 0.0001) increase in primary healthcare clients seen by a public medical practitioner, 37% (95% CI: 28-46, p < 0.0001) increase in primary healthcare clients on ART, and 615% (95% CI: 486-742, p < 0.0001) increase in primary healthcare clients seen by a professional nurse. Second, a 10% increase in outpatient department referrals resulted in an 8% (95% CI: 3-12, p < 0.0001) increase in new primary healthcare diabetes mellitus clients, a 73% (95% CI: 51-95, p < 0.0001) increase in primary healthcare headcounts for clients seen by a medical professional, a 25% (95% CI: 23-28, p < 0.0001) increase in primary healthcare headcounts for clients on ART, and a 44% (95% CI: 4-71, p = 0.026) increase in primary healthcare headcounts for clients seen by a professional nurse. Third, a 10% increase in outpatient department follow-up headcounts resulted in a 12% (95% CI: 8-16, p < 0.0001) increase in primary healthcare headcounts for new diabetes mellitus, 67% (95% CI: 45-89, p < 0.0001) increase in primary healthcare headcounts for clients seen by public medical practitioners, 22% (95% CI: 19-24, p < 0.0001) increase in primary healthcare headcounts for clients on ART, and 155% (95% CI: 118-192, p < 0.0001) increase in primary healthcare headcounts for clients seen by a professional nurse. Fourth, a 10% increase in headcounts for total primary healthcare clients resulted in a 0.4% (95% CI: 0.1-0.8, p < 0.0001) decrease in primary healthcare headcounts for new diabetes clients. Based on these relationships and dependencies, the outpatient department follow-up headcounts would increase from 337 945 in the fourth quarter of 2019 to 534 412 (95% CI: 327 682–741 142) in the fourth quarter of 2025, while the total primary healthcare headcounts would only marginally decrease from 1 345 360 in the fourth quarter of 2019 to 1 166 619 (95% CI: 633 650–1 699 588) in the fourth quarter of 2025. Conclusion: The study findings suggested that improvements in primary health care indicators in National Health Insurance pilot districts could not be attributed to the implementation of contracting private medical practitioners but were likely a result of other co-interventions and transitions in the district. However, it might have resulted in an improved perception of quality of care at primary health care facilities, evidenced by a reduction in the self-referral rate for non-emergency hospital outpatient departments. The study also confirmed the influence of selected primary healthcare and non-emergency outpatient department headcounts on each other by finding four common long-run trends of relationships. Based on these relationships and trends, outpatient department follow-up headcounts are forecasted to increase by two-thirds. Conversely, the total headcount for primary healthcare clients seen by a professional nurse will marginally decrease. Recommendations: Based on the study findings, the bidirectional referral between primary and non-emergency secondary levels of care in the Tshwane district should be strengthened to offset the burden of care at outpatient departments of district hospitals. Thus, the district health information system should include a down-referral indicator to monitor this activity. With the implementation of National Health Insurance, there is a need to improve the perception of quality of care at the primary healthcare level through appropriate training, recruitment, and placement of medical practitioners. Similarly, professional nurses, the core providers of primary healthcare services, should be supported and capacitated in line with the epidemiological transition.
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    From the onset: Impact of Nutrition and Lifestyle during the Preconception period in Urban South African Young Adults
    (University of the Witwatersrand, Johannesburg, 2023-03) Mukoma, Gudani Goodman; Norris, Shane A.
    Background: In South Africa, 22% of adolescents are overweight or obese, the onset of tobacco smoking is shown to peak between the ages of 15 and 22, 1 in 3 adolescents watch more than 3 hours of television per day, and nearly half of all adults are insufficiently active. Physical inactivity, poor diet, risky alcohol use, illicit drug use are among the behavioural risk factors associated with obesity and mental health problems, all of which have morbidity and mortality implications for adult health. Risks in later life include premature death, long-term disability, childbirth complications, gestational diabetes, diabetes and cardiovascular diseases. However, there is data paucity showing the personal, social, and environmental factors that are determinants of health, especially diet, physical activity (PA), obesity, and associated NCDs in South African adolescents and young adults. Aim: To investigate the individual, household, and environmental factors that influence adolescents' dietary and physical activity habits and to identify ways in which these factors can be leveraged for interventions to better ensure the health of future generations, especially during the crucial preconception years. Methods: This thesis was purposely designed to use a sequential mixed-methods approach that integrates quantitative (Chapter 3 paper 1: cross-sectional and Chapter 6 paper 4: longitudinal) and qualitative (Chapter 4 paper 2: longitudinal and Chapter 5 paper 3: cross-sectional) analyses in order to meet the four specific objectives of my research. The methods selected for this series of investigations were primarily influenced by the substantive research questions that arose, as opposed to methodological and epistemological concerns alone. I utilized three pre-existing data sources, including the "Birth-to-Twenty Cohort," the "Determinants of Type 2 Diabetes Mellitus (T2D)" study, and the "Soweto household enumeration survey." I have gathered new prospective data that is quantitatively and qualitatively longitudinal and cross-sectional. Results: The findings of this thesis in the context of Soweto show that the relationship between dietary patterns and nutritional status (BMI) is independent of socioeconomic status (SES). Adolescents and young adults face a variety of intersecting barriers resulting from personal preferences and their living conditions, which influence their dietary and physical activity habits while occurring at the time; this is important to consider when designing interventions to promote healthy behaviour change. Unexpected stressors, such as the outbreak of the COVID-19 pandemic, contributed to exacerbating adolescents' and young adults' poor health conditions, and as a result, the prevalence of poor nutrition intake, a lack of physical activity, and mental health issues increased. Although the nutrient patterns of adolescents and adults were comparable over time, their associations with BMI were not. The associations with BMI of the "plant-driven nutrient pattern," "fat-driven nutrient pattern," and "animal-driven nutrient pattern" revealed sex differences. Conclusion: Adolescent diet and lifestyle continue to be important research areas in the intent to enhance preconception health and reducing maternal and infant mortality.
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    Exploring the Interplay of Chemokine Receptors CCRS and CXCR6 in Mechanisms of Natural Control in HIV-1-lnfected Black South Africans
    (University of the Witwatersrand, Johannesburg, 2023-06) Koor, Gemma Whitney; Tiemessen, Caroline T.; Paximadis, Maria; Shalekoff, Sharon
    In sub-Saharan Africa, HIV-1 is a significant cause of morbidity and mortality. However, research remains primarily focused on North American and European population groups, who have remarkably different genetic backgrounds to individuals from sub-Saharan Africa. HIV-1 controllers represent a model of HIV-1 functional cure, with some individuals able to control viral replication, and some able to sustain immune function in the presence of high viral loads, both in the absence of antiretroviral therapy (ART). The chemokine receptors CCR5 and CXCR4 are the major coreceptors HIV-1 utilises to enter cells. The use of alternative coreceptors, such as the CXCR6 coreceptor, is thought to contribute to the lower pathogenicity exhibited by the HIV-2 and SIVsmm strains. Building on previous work conducted in our research unit on these two coreceptors in South African populations, this thesis firstly describes CCR5 genetic variants that associate with HIV-1 control or risk of progressive infection in black South Africans, and then explores constitutive expression levels of CCR5 and CXCR6 on various peripheral blood immune cell subsets in the absence of HIV-1 infection in ethnically divergent population groups. The effect of sex, age, and select CCR5 and CXCR6 single nucleotide polymorphisms (SNPs) on expression levels of these two receptors was also investigated. The CCR5 5’UTR and 3’UTR regions were PCR-amplified and sequenced from genomic DNA extracted from 145 ART-naive black South African individuals living with HIV-1 (71 HIV-1 controllers – 23 elite controllers, 37 viraemic controllers, 11 high viral load long-term non-progressors and 74 progressors). Findings confirmed results from other studies in showing that the CCR5 HHE haplotype is deleterious for HIV-1 disease progression, and the HHA haplotype and HHA/HHC genotype associated with protection from HIV-1 disease progression. Novel haplotypes were characterised, both in the 3’UTR and spanning the CCR5 5’UTR and 3’UTR. Overall, findings suggest that two CCR5 promoter SNPs (-2459 G>A and -2135 T>C) and one CCR5 3’UTR SNP (+2919 T>G) may be key functional variants with regards to HIV-1 control in black South Africans. To gain further insight into the constitutive expression of CCR5 and CXCR6 on peripheral blood immune cells and explore the relationship between select genetic variants and expression, immunophenotyping by flow cytometry was conducted using whole blood from age- and sex-matched ethnically distinct South African HIV-uninfected individuals (17 black, 21 white). Expression levels of CCR5 and CXCR6 were assessed on CD4+ and CD8+ T cells, B cells, monocytes and NK cells, and their respective subsets. The effects of age and sex on expression levels of these two receptors was also investigated. Population-specific differences with regards to CCR5 expression on all cell types, except for B cells, were evident. Generally, black South Africans exhibited a lower expression level of CCR5 compared to white South Africans. CXCR6 expression only differed with regards to percentage of CXCR6-expressing cells, not CXCR6 density (numbers of cell surface receptors). Black individuals had a lower percentage of CXCR6-expressing CD8+ T cell subsets (naïve and effector memory) and a higher percentage of CXCR6-expressing CD14+CD16+ monocytes compared to white individuals. Overall, we found significant population-specific differences in expression levels of both CCR5 and CXCR6, multiple associations with cell activation (as measured by HLA-DR expression) and CCR5 and CXCR6 expression, and CCR5 and CXCR6 expression was positively significantly correlated on multiple cell subsets. Furthermore, both sex and age influenced CCR5 and CXCR6 expression, however results varied widely across the two population groups studied. Sex differences were only evident in white individuals; predominantly CXCR6 expression was increased in males compared to females. Age associations with CCR5 and CXCR6 expression were also primarily found in white individuals. Four CCR5-related SNPs that are associated with HIV-1 control in this or other studies (rs553615728 -4223 C>T SNP, rs1799987 −2459 G>A SNP, rs746492 +2919 T>G SNP and rs1015164 G>A SNP) were assessed for their potential association with CCR5 expression levels. The +2919 TG genotype significantly associated with a higher percentage of CCR5-expressing total CD8+ T cells, transitional memory and terminally differentiated CD8+ T cells compared to the GG genotype. The +2919 GG genotype associated with a lower percentage of CCR5-expressing B cells compared to the TT and TG+TT genotypes, however, only in white South Africans. The +2919 TG and TG+TT genotypes associated with significantly higher CCR5 density on all CD8+ T cell subsets, except for naïve CD8+ T cells, when compared to the GG genotype. When evaluating two CXCR6 genetic variants previously associated with HIV-1 viraemic control (rs2234355 G>A and rs2234358 G>T) in relation to CXCR6 expression, possession of the rs2234355 SNP GA genotype associated with lower CXCR6 expression on select CD4+ and CD8+ T cell subsets as well as on B cells, while possession of the rs2234358 SNP TT genotype associated with higher CXCR6 expression on multiple cell types, primarily in white South Africans. Possession of the -358TT/+355GA genotype combination associated with lower CXCR6 expression on select subsets of CD4+ T cells and monocytes. In summary, this study provides information on genetic variation in the CCR5 gene in a South African context, describes genetic variants associating with HIV-1 control in black South Africans, adds novel insight into constitutive CCR5 and CXCR6 expression levels on CD4+ and CD8+ T cells, B cells, monocytes and NK cells in HIV-1-uninfected black and white South Africans, and describes the potential associations of select genetic variants and expression. Black and white individuals differed in their baseline expression levels of CCR5 or CXCR6, which was partly driven by host genetic factors that were explored. This work highlights the importance of considering effects of ethnicity, age, and sex in any studies addressing any immune molecules in relation to differential HIV-1 outcomes of infection susceptibility/protection, disease progression, or HIV-1 virological control on antiretroviral therapy. Although conducted on small numbers of individuals, these variables clearly influenced constitutive expression of CCR5 and CXCR6, and further population-specific studies are warranted to gain further insights. Findings from this study have implications for risk of acquisition of HIV-1 infection and for disease progression in people living with HIV-1. Understanding the role of these molecules is important for informing strategies for both HIV-1 prevention and HIV cure.
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    Nutrition of ageing black South African women and correlates with anthropometry and cardiometabolic outcomes
    (University of the Witwatersrand, Johannesburg, 2023-09) Kankwende, Caroline Belinda Tsitsi; Gradidge, Philippe; Norris, Shane; Chikowore, Tinashe
    Background: Obesity is most prevalent among black women who reside in urban areas in South Africa yet the nutrient patterns of this cohort of women has never been investigated, nor have correlates of body composition indices such as adiposity and body mass index (BMI). These body composition indices are important to analyse as they have been shown to be positively associated with hypertension which is prevalent in this cohort of women. Aim: There were three main goals: 1) To determine the baseline nutrient patterns of middle-aged black South African women residing in Soweto and correlates to body composition indices 2) To evaluate the longitudinal association of nutrient patterns with adiposity in a cohort of middle-aged black South African women over a period of 5.5- years 3) To elucidate the longitudinal associations of nutrient patterns and blood pressure and to explore whether this is an indirect effect mediated by body mass index (BMI) using structural equation modelling Methods: A longitudinal study of children and their families, originally called the Birth to Twenty Plus (Bt20+) cohort and now referred to as the Middle-aged Soweto Cohort (MASC), was used to as the original dataset for this thesis. This study also drew on another embedded study, the Study of Women Entering and in Endocrine Transition (SWEET) study of older women transitioning through menopause. Data on (i) dietary information; (ii) body composition and anthropometry measurements; (iii) blood pressure; (iv) lifestyle behaviours (physical activity, tobacco use, and alcohol use); (v) psychosocial factors; (vi) socioeconomic status; and (vii) educational status were used. A total of 498 Women aged between 40 and 60 years old were included in the study. Principle component analysis (PCA) was applied on the dietary data both at baseline and at 5- years follow-up. This was conducted to extract nutrient patterns from 25 nutrients derived from the food frequency questionnaire (FFQ) and the resulting nutrient patterns are detailed in results chapter 3 (nutrient patterns derived from the baseline FFQ) and results chapter 4 (comparison between both baseline and follow-up nutrient patterns from the FFQ). Simple and complex body composition were recorded for each participant with complex body measurements taken using (DXA). Chapter 3 details the results of the 3 baseline nutrient patterns and correlates with body composition parameters. Using generalized estimating equations, associations between both baseline and 5- years follow-up nutrient patterns and adiposity were evaluated. The results are discussed in results chapter 4. Lastly, the results chapter 5 examined associations between both baseline and follow-up nutrient patterns and blood pressure were examined and furthermore, investigated whether BMI mediates the relationship between repeated measures of nutrient patterns and blood pressure. Results: The majority of the research participants (88%) were classified as individuals having obese status defined by their BMI. The fat mass index (FMI), lean mass index (LMI), gynoid fat, hip and waist circumference, and visceral and subcutaneous adipose tissue (VAT and SAT respectively) measurements were all substantially larger in the group with predominantly individuals having overweight and obese classification compared to woman in the lean group (p <0.001). Protein consumption was greater in the group with individuals having overweight/obese classification, while fat and carbohydrate consumption were matched. At baseline, the "Plant driven nutrient pattern," characterized by higher factor loadings of plant protein, starch, and B vitamins, explained 25% of the total nutritional variance; the "Animal protein driven nutrient pattern," characterized by animal protein and saturated fat, explained 23% of the variance; and the third pattern was the "Vitamin C, sugar and potassium driven nutrient pattern," which had higher factor loadings of vitamin C, sugar and potassium. At baseline, increased consumption of the animal protein driven nutrient pattern resulted in a 1.19 kg/m2 (p = 0.002) increase in BMI, 10.17 cm2 for VAT, 24.43 cm2 for SAT, 0.01 (p = 0.009) increase for VAT/SAT ratio, 0.69 kg/m2 (p = 0.005) increase for FMI, and 0.48 kg/m2 (p = 0.002) increase for LMI. Furthermore at baseline, statistically significant associations were found for the animal protein driven nutrient pattern with all body composition indicators. Subcutaneous adipose tissue increased in the presence of a plant-driven nutrition pattern (p = 0.045). At 5-year follow-up, although the value of the factor loadings of the individual nutrients changed between baseline and follow-up, the nutrients with the highest loadings for each principal component (PC) did not change therefore the overall nutrient patterns remained the same. Only DXA-derived measurements of fat mass, FMI, VAT, and gynoid fat mass (FM) increased with time, while lean mass considerably reduced. Repeated measures of the animal protein driven nutrient pattern was associated with significant increases in FMI, LMI and VAT and repeated measures of the vitamin C, sugar, and potassium driven nutrient pattern was significantly associated with an increase in FMI and LMI. For the purposes of this study, repeated measures of animal-driven nutrient patterns were shown to be significantly related with repeated measures of systolic blood pressure (SBP) only. When structural equation modelling (SEM) was applied, only significant relationships were observed between age and SBP. This relationship was not mediated by BMI but may involve other factors that were not included in this analysis. Conclusions: This thesis explored the nutrient patterns linked to obesity and cardiometabolic complications, namely blood pressure, in a cohort of black middle-aged African females. It has been previously demonstrated that this cohort has been has a high prevalence of obesity. According to literature reviews, programs focusing on nutritional and behavioural changes could aid African women in their fight against the obesity and hypertension epidemic that we are facing today. The animal-driven nutrient pattern was found to be substantially associated with increases in body fat in this cohort at baseline. At 5-year follow-up, the nutrient patterns remained the same and repeated measurements of the vitamin C, sugar, and potassium-driven nutrient pattern were associated with significant increases in FMI and LMI and the animal-driven nutrient pattern remained significantly associated with LMI, FMI and VAT, a measure of visceral obesity which is a major risk factor for cardiometabolic conditions. This is problematic in a population that consists predominantly of individuals that are classified as having an obese and overweight status. As a result of a higher BMI, a greater likelihood of developing cardiometabolic multimorbidity exists which is defined as the co-occurrence of two or three cardiometabolic conditions. This may result in reduced quality of life and an increased burden on the already overstretched healthcare system in South Africa. Furthermore, this study found that only the animal protein driven nutrient pattern had a significant relationship with SBP which was significant. When SEM was applied, BMI did not mediate the relationship between blood pressure and any of the nutrient patterns. No other noteworthy direct relationships between blood pressure and the other nutrient patterns were found. Researchers can apply the findings of this study to improve nutritional policies and guidelines aimed at combating not just obesity, but high blood pressure among black women in Sub-Saharan Africa. It is necessary to conduct further extensive research to verify these findings.
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    Examining the role of affordability, citizen engagement, and social solidarity in determining health insurance coverage in Kenya
    (University of the Witwatersrand, Johannesburg, 2023-08) Maritim, Beryl Chelangat; Goudge, Jane; Koon, Adam
    Rationale: Healthcare costs cause severe financial hardship globally and many low-and middle-income countries (LMIC) are turning to social health insurance to provide financial risk protection and increase population coverage. However social health insurance schemes in LMICs experience significant growth challenges owing to difficulties reaching informal workers through contributory health insurance systems. Kenya has undertaken several health sector reforms and efforts to increase health insurance coverage but has had limited success in capturing the large proportion of informal workers. The broad aim of this study was to describe and assess the reasons for low enrolment in the national insurance scheme among the Kenyan informal worker households in Bunyala sub-County, Busia County, Kenya. It focused on the role of affordability of premiums, citizen engagement and social solidarity in NHIF coverage among the informal worker households. Methods: This study employed an explanatory mixed methods study approach with quantitative and qualitative primary data collection. The quantitative phase included a household survey (n=1,773) from which 36 respondents were purposively identified to participate in in-depth household interviews. The study also conducted 6 focus group discussions (FGD) groups with community stakeholders, and 11 key informant interviews with policymakers and implementers at national and sub-national level. Quantitative data was analyzed using R while qualitative data was analyzed thematically using both manual methods and NVIVO software. Results: Only 12% of households reported having health insurance and NHIF was unaffordable for the majority of households, both insured (60%) and uninsured (80%). Rural households spent a significant proportion (an average of 12%) of their household budget on out of pocket (OOP) expenses on health care, with both insured and uninsured households reporting high OOP spending and similar levels of impoverishment due to OOP I found that there was high awareness of NHIF but low levels of knowledge on services, feedback and accountability mechanisms. Barely half (48%) of the insured were satisfied with the NHIF benefit package. Nearly all of the respondents (93%) were unaware of mechanisms to reach NHIF for feedback or complaints. Respondents expressed desire to know the NHIF performance but expressed high levels of mistrust in the fund owing to negative reports on NHIF performance in the media. This study found high willingness to prepay for healthcare among those without insurance (87.1%) with competing priorities, low incomes, poor access and quality of health services, lack of awareness of flexible payment options cited as barriers to enrolment. More than half of respondents expressed willingness to tolerate risk and income cross-subsidization suggesting strong social solidarity, which increased with socio-economic status. Participants expressed concerns about value of health insurance given its cost, availability and quality of services, and financial protection relative to other social and economic household needs. Households resorted to borrowing, fundraising, taking short term loans and selling family assets to meet healthcare costs. Implications: This study provides a nuanced insight into the challenges of increasing coverage among rural informal worker households with considerations for rolling out mandatory NHIF membership. The findings imply that majority of the informal worker households in rural areas need assistance to afford NHIF. These study findings also highlight the importance of fostering and leveraging existing social solidarity to move away from flat rate contributions and apply more progressive contribution that allow for fairer risk and income cross-subsidization. Finally, the government should rapidly scale up the indigent program to cover most rural informal worker households. There is also need to invest in robust strategies to effectively identify subsidy beneficiaries. Significant reforms of NHIF and health system are required to provide adequate health services and financial risk protection for rural informal households in Kenya. NHIF also needs to evaluate their citizen engagement and accountability frameworks to increase awareness, member satisfaction, improve state accountability to citizens and incorporate citizen voice in their processes.
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    Occupational Exposure to Chrysotile Asbestos in the Chrysotile Asbestos Cement Manufacturing Industry in Zimbabwe
    (University of the Witwatersrand, Johannesburg, 2023-08) Mutetwa, Benjamin; Brouwer, Derk; Moyo, Dingani
    Introduction: Asbestos is a generic term for a group of naturally occurring silicates that principally include serpentine variety (white chrysotile asbestos) and the amphibole variety, consisting of crocidolite (blue asbestos), amosite (brown asbestos), anthophyllite, actinolite and tremolite. Asbestos exposure has drawn much international, regional and national attention as it presents significant public and occupational health concerns. All asbestos types are known to cause asbestos related disease. Objectives: The objectives of this PhD were: 1. To analyse trends in airborne chrysotile asbestos fibre exposure data obtained by the chrysotile asbestos cement manufacturing factories for the period 1996 to about 2016. 2. To establish a job exposure matrix (JEM) to estimate occupational exposure levels in the Zimbabwe chrysotile asbestos industry using available exposure data. 3. To predict asbestos related diseases (ARDs) namely lung cancer, mesothelioma, gastrointestinal cancer and asbestosis in the chrysotile asbestos cement manufacturing industry through exposure levels obtained in the factories. 4. To assess amphibole contaminants in the chrysotile asbestos fibre being used by the factories in the manufacture of asbestos cement (AC) products. 5. To examine approaches for prevention of exposure to chrysotile asbestos fibre and some perspectives on the debate on asbestos ban. Methodology: A retrospective cross-sectional study using the factories personal chrysotile exposure data was designed to evaluate exposure patterns over time. Analysis involved close to 3000 personal exposure measurements extracted from paper records in the two-asbestos cement (AC) manufacturing factories in Harare and Bulawayo, covering the period 1996-2020. Exposure trends were characterised according to three to four time periods and calendar years to gain insight into exposure trends over time. Operational areas for which personal exposure data were available were saw cutting, fettling table, kollergang, moulded goods, ground hard waste, laundry room, and pipe making operations in the case of the Bulawayo factory. The standard method of the Asbestos International Association (AIA) Recommended Technical Membrane Filter Reference Method (AIA, 1982) was reported to be used to collect personal chrysotile asbestos fibre in various operational areas over the years. Quantitative personal exposure chrysotile fibre concentration data collected by the two factories over the considered period were used to construct the JEM. Analysis of amphiboles in locally produced and imported raw chrysotile fibre samples used in the manufacturing processes was done using Scanning Electron Microscopy (SEM) and Energy Dispersive Spectroscopy (SEM). Prediction of asbestos related diseases (ARDs) was done by combining the JEM converted to cumulative exposures, with OSHA’s linear dose effect model in which asbestos related cancers was derived using linear regression equations established for lung cancer, mesothelioma and gastrointestinal cancer by plotting estimates of cancer mortality cases versus respective cumulative exposures. The linear regression equations were applied to establish estimates of possible cancer mortality while for asbestosis, the linear in cumulative dose equation, Ra = m(f)(d), where Ra – predicted incidence of asbestosis, m – slope of linear regression taken as 0.055, f – asbestos fibre concentration and d – duration of exposure, was used to estimate possible asbestosis cases over the respective duration of exposure at 1, 10, 20 and 25 years. To examine arguments for approaches used for prevention of exposure to chrysotile asbestos and examine some perspectives on the debate on asbestos ban, a literature search was conducted. Literature materials that advocated for the complete ban of all forms of asbestos including chrysotile as the only means of control of exposure and that, which argues for the controlled use approach, were reviewed. Search words used in literature search were chrysotile asbestos exposure, asbestos-cement, ban asbestos, controlled use, asbestos related disease, mesothelioma, lung cancer and asbestosis. Data analysis was conducted using IBM SPSS version 26. For analysis, monthly averaged personal exposure levels for the factories were used. Mean personal airborne chrysotile fibre concentrations were analysed per operational area per factory and trends in airborne fibre concentrations over the years were displayed graphically. ANOVA was applied with the aim categories and determine whether there was a statistically significant difference in exposure concentrations between four time-periods for various jobs. Additionally, a Tukey Post Hoc Test (Tukey’s Honest Significance Difference test) was run to find out which specific group means of time periods (compared with each other) were different. Results and Discussion: Trends in airborne chrysotile asbestos fibre concentrations in asbestos cement manufacturing factories in Zimbabwe from 1996 to 2016. Mean personal exposure chrysotile asbestos fibre concentrations generally showed a downward trend over the years in both factories. Exposure data showed that over the observed period 57% and 50% of mean personal exposure chrysotile asbestos fibre concentrations in the Harare and Bulawayo factories, respectively, were above the Zimbabwean OEL of 0.1 f/mL, with overexposure generally being exhibited before 2008. Overall, personal exposure asbestos fibre concentrations in the factories dropped from 0.15 f/mL in 1996 to 0.05–0.06 f/mL in 2016, a decrease of 60–67%. Statistically significant relationships were observed over time between exposure levels and calendar year and time periods (p<0.001) for all occupational categories other than fettling table operations in Harare. The general decline in exposure over time from 1996 to 2016 suggests good occupational safety and health (OSH) framework being implemented by the two factories over the years, with the years after 2008 showing much lower exposure levels below the OEL particularly for the Bulawayo factory. However, for the period 2018 to 2020 exposures in the Harare factory were much higher than the proceeding time period of 2009 to 2016 due to movement of trucks within the factory as they come to load concrete tiles and other products making it possible for residual chrysotile fibre left during manufacture of AC products to become airborne. The company reported no clean-up of asbestos in the factory or wetting of the floors to control dust, hence the possible increased levels of chrysotile asbestos fibre for the period 2009 to 2016. The general decreasing trends in exposure to chrysotile asbestos fibre may also be viewed from the fact that industry was responding to anticipated lowering of chrysotile OEL as a result of increased calls to ban all forms asbestos, triggering the scaling up of exposure controls in the factories. Job Exposure Matrix for chrysotile asbestos fibre in the asbestos cement manufacturing (ACM) industry in Zimbabwe. On average, all jobs/occupations in both factories had annual mean personal exposure concentrations exceeding the OEL of 0.1 f/ml, except for the period 2009 to 2016 in the Harare factory and for the time-periods 2009 to 2020 in the Bulawayo factory. Despite Harare factory having no AC manufacturing activity since 2017, personal exposure concentrations showed elevated levels for the period 2018-2020. Amphiboles were detected in almost all presently collected bulk samples of chrysotile asbestos analysed. The established JEM, which was successfully generated from actual local quantitative exposure measurements, can be used in evaluating historical exposure to chrysotile asbestos fibre, to better understand, inform and predict occurrence of ARDs in future. Prediction of Asbestos Related Diseases (ARDs) and chrysotile asbestos exposure concentrations in asbestos-cement (AC) manufacturing factories in Zimbabwe. The results show that more cancer and asbestosis cases were likely to be experienced among those workers exposed before 2008 as exposure levels (0.11-0.19 f/ml) and subsequently cumulative exposures were generally much higher than those experienced after 2008 (0.04-0.10 f/ml). After a possible working exposure period of 25 years, overall cancer cases, i.e., estimates of possible cancer cases in a factory for each respective duration of exposure, predicted in the Harare factory were 325 cases per 100 000 workers while for the Bulawayo factory 347 cancer cases per 100 000 workers exposed may be experienced. Asbestosis cases likely to be detected after 25-years duration of exposure ranged from 50 to 260 cases per 100 000 workers (0.05 to 0.26% incidence of asbestosis) for various jobs. Possible high numbers of ARDs are likely to be associated with specific tasks/job titles, e.g., saw cutting, kollergang, fettling table, ground hard waste and possibly pipe making operations as cumulative exposures though lower than reported in other studies may present higher risk of health impairment. Examining approaches for prevention of exposure to chrysotile asbestos and some perspectives on the debate on ban of asbestos. Different perspectives on approaches to the prevention of exposure to asbestos have been presented. One position argues that there exist major differences in health risk between amphiboles and chrysotile asbestos, that low exposure and risk experienced under today’s workplace conditions are completely different to high-risk exposures experienced in the past where occupational hygiene conditions were very poor and levels of education, awareness and training in the asbestos industry was low compared to the present situation. It is further argued that there are low levels of exposure below which risk of health impairment becomes insignificant, hence controlled use approach as a measure of exposure control can be successfully applied. However, the other position holds that all forms of asbestos including chrysotile are equipotent, that there is no safe level of exposure, that controlled use is not practical and that there is no merit in continuing use of chrysotile asbestos in light of safer alternatives available today. Both positions appear plausible. Banning as a form of control measure occupies a high level in the hierarchy of controls with potential to eliminate the hazard and risk; nonetheless, the banning of chrysotile may imply substitution with materials that have been reported to carry health risk of cancer and other health impairments. On balance, banning may possibly not be the panacea of elimination of ARDs, in view of the fact that some other forms of mining such as diamond and gold mining have been associated with exposure to amphibole asbestos. The controlled use approach may provide real possibilities of prevention of exposure to levels that presents minimal risk to health if effectively implemented as applied to a range of occupational hazards with success. Conclusion: Not much is known about exposure to airborne chrysotile asbestos fibre exposure in Zimbabwe chrysotile asbestos cement (AC) manufacturing industry. This study may constitute the single largest characterisation of personal exposure chrysotile asbestos fibre concentrations data set in Zimbabwe in which about 3000 airborne personal exposure measurements collected from company records spanning a period of about 25 years, were used in assessing exposure trends over time, building a job exposure matrix, and predicting possible ARDs namely lung cancer, mesothelioma, gastrointestinal cancer and asbestosis in Zimbabwe AC manufacturing industry. The study adds considerably to future epidemiological studies, gives insights into possible magnitude of ARDs that may be observed in AC factories and possibly analysis of exposure response relationships that may be linked to exposure episodes in the distant past. The study also gives some insights into possible amphibole contaminants that may be associated with local and imported chrysotile asbestos that is used in the AC manufacturing processes and thus providing support for a more comprehensive investigation into the presence of amphiboles in chrysotile asbestos in Zimbabwe. The study also provides some perspectives on approaches to prevention of exposure to asbestos and some aspects on the call to ban all forms of asbestos including chrysotile. Personal exposure chrysotile fibre concentration data in the two AC manufacturing factories showed a downward trend over the years, and that overexposure as evaluated against the OEL of 0.1 f/ml were being exhibited largely before 2008. The job categories with high exposure levels were saw cutting, fettling, ground hard waste, laundry room and multi-cutter operator and such jobs are likely to be associated with high risk of ARDs particularly for exposures happening before 2008. Moulded goods operators were associated with low exposures as process is generally a wet process. Despite exposure concentrations being high in the earlier time periods of 1996 to 2008, declines over time particularly for Bulawayo factory which has continued to use chrysotile to date, suggests that controlled use approach may yield exposures that may present minimal risk to health of those exposed to chrysotile asbestos. While banning can still be considered as a way to eliminating ARDs, it may not necessarily be the panacea for prevention of ARDs, as controlled use approach may perhaps still present real possibilities of prevention of exposure to levels that may present minimal risk to health impairment if effectively implemented as applied to a range of hazards with some success. Banning would possibly imply substitution by materials reported to be hazardous to health. These results can be used in future epidemiological studies, and in predicting the occurrence of asbestos-related diseases in Zimbabwe.
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    Effects of Supplemental Zingerone on Cobb 500 Broiler Chicken (Gallus gallus domesticus) Growth Performance, Health and Meat Quality
    (University of the Witwatersrand, Johannesburg, 2023-07) Mdoda, Bayanda; Chivandi, Eliton; Lembede, Busisani Wiseman
    Commercial broiler and pullet chicken producers supplement chicken diets with sub-therapeutic doses of antibiotics such as zinc bacitracin that act as growth promoters to enhance production performance, meat and egg quality. Use of these antibiotics as growth promoters, in addition to causing environmental pollution, causes the public health challenge of antibiotic resistance which compromises poultry and consumer, hence the need to search for environmentally friendly and health-friendly alternatives to antibiotics. Phytochemicals, zingerone included, display biological activities similar to those of antibiotics. This study evaluated zingerone`s potential to replace bacitracin (ZnBcn) as a growth-promoting diet supplement in broiler feed specifically determining its effects on growth performance, meat quality and bird health. One hundred and twenty unsexed 1-day-old Cobb 500 broiler chicks (10 chicks per replicate with 3 replicates per diet) were randomly assigned to four dietary treatments where zingerone replaced ZnBcn at: diet 1 – 0 mg kg-1 (control: 500 mg akg-1 of zinc bacitracin); diet 2 – 40 mg kg-1; diet 3 – 80 mg kg-1 and diet 4 – 120 mg kg-1 in the starter, grower and finisher diets. The broiler chicks were fed ad libitum for 6 weeks: starter (week 1-2), grower (week 3-4), and finisher (week 5-6). Initial and weekly body mass, daily feed intake (FI), and terminal body mass (TBM) were measured. Body mass gain (BMG), average daily gain (ADG), and feed conversion ratio (FCR) were computed. On day 42, the chickens were humanely slaughtered, blood collected and carcasses dressed. The gastrointestinal tract (GIT) and accessory GIT viscera organs were weighed and small and large intestine lengths were measured. Empty carcass masses were measured and the dressing percentages were computed. Viscera macromorphometry, long bone indices and carcass traits, the meat’s physical quality [initial and ultimate pH (pHi and pHu), colour, thawing loss (TL), cooking loss (CL), and tenderness] traits, proximate and amino acid content and fatty acid profiles were measured. Plasma malonaldehyde (MDA) concentration, glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) activities, surrogate markers of liver and kidney function, liver fat content and histology were determined. Across growth phases and overall, dietary zingerone had similar effects (p > 0.05) as ZnBcn on the chicken’s TBM, BMG, ADG, FI, and FCR. It also had similar effects (p > 0.05) as ZnBcn on the chicken’s empty carcass mass, dressing percentage, long bone indices and viscera macromorphometry. Dietary zingerone had similar (p > 0.05) effects as ZnBcn on the broiler chicken meat’s pHi, pHu, CL, TL and tenderness. However, at 40 mg kg-1 of feed (diet 2) it increased the meat’s redness (a*) compared to that of counterparts fed the ZnBcn-fortified control diet. Furthermore, supplemental zingerone had a similar effect to that of ZnBcn on the meat’s crude protein content but it significantly increased the meat’s ash and fat contents (p < 0.01; p < 0.0001). Meat from chickens fed diet 2 (40 mg kg-1 of feed zingerone) had the highest concentration of essential amino acids (p < 0.05) and that from chickens fed diets 3 (80 mg kg-1 of feed zingerone) had the lowest (p > 0.001) total amino acid content. Dietary zingerone had a similar (p > 0.05) effect as ZnBcn on the chicken meat’s total saturated fatty acids, but breast meat from chickens fed diets 3 (80 mg kg-1 of feed zingerone) had significantly increased (p < 0.0001) total monounsaturated fatty acid and oleic acid content. Meat from chicken-fed diet 4 (120 mg kg-1 of feed zingerone) had the highest total polyunsaturated fatty acid and linoleic acid content and a higher PUFA:SFA ratio compared to that from counterparts fed diets 1, 2 and 3. Supplemental zingerone had similar effects (p > 0.05) as ZnBcn on the chickens’ liver masses and fat contents, plasma MDA concentration, GSH-Px, GST, SOD, CAT, alkaline phosphatase, alanine transaminase activities, albumin, total bilirubin, creatinine and urea concentrations. Chickens’ hepatic inflammation and steatosis scores were similar across diets (p > 0.05). At 120 mg kg-1 of feed zingerone, though similar to the control, supplemental zingerone decreased the chickens’ plasma globulin and total protein concentration (p < 0.01; p < 0.05) compared to counterparts supplemented at low and medium dose of zingerone. Zingerone can be used as a growth promoter in place of zinc bacitracin in broiler chicken diets without compromising growth, feed use efficiency, carcass yield, long bone and GIT viscera growth and development, the meat’s pH, CL, TL and tenderness. Furthermore, it can be used without eliciting oxidative stress in the birds and with no risk to kidneys, liver and general health of the birds. Importantly, zingerone, as a dietary supplement, can be used to enhance broiler chicken meat’s redness, positively impacting its acceptability and meat’s total monounsaturated, oleic acid, total polyunsaturated and linoleic acid fatty acid profile; thus improving its nutritional value.
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    Engaging the public in priority setting for health in rural South Africa
    (University of the Witwatersrand, Johannesburg, 2023-10) Tugendhaft, Aviva Chana; Hofman, Karen; Kahn, Kathleen; Christofides, Nicola
    Introduction: The importance of public engagement in health priority setting is widely recognised as a means to promote more inclusive, fair, and legitimate decision-making processes. This is particularly critical in the context of Universal Health Coverage, where there is often an imbalance between the demands for and the available health resources. In South Africa, public engagement is protected in the Constitution and entrenched in policy documents; yet context specific tools and applications to enable this are lacking. Where public engagement initiatives do occur, marginalised voices are frequently excluded, and the process and outcomes of these initiatives are not fully evaluated. This hampers our understanding of public engagement approaches and how to meaningfully include important voices in the priority setting agenda. The aim of this doctoral (PhD) research was to investigate the feasibility and practicality of including the public in resource allocation and priority setting for health in a rural setting in South Africa using an adapted deliberative engagement tool called CHAT (Choosing All Together). Methods: The PhD involved the modification and implementation of the CHAT tool with seven groups in a rural community in South Africa to determine priorities for a health services package. For the modification of CHAT, desktop review of published literature and policy documents was conducted, as well as three focus group discussions, with policy makers and implementers at national and local levels of the health system and the community, and modified Delphi method to identify health topics/issues and related interventions appropriate for a rural setting in South Africa. Cost information was drawn from various national sources and an existing actuarial model used in previous CHAT exercises was employed to create the board. The iterative participatory modification process was documented in detail. The implementation process was analysed in terms of the negotiations that took place within the groups and what types of deliberations and engagement with trade-offs the participants faced when resources were constrained. In terms of the outcomes, the study focused on what priorities were most important to the rural community within a constrained budget and the values driving these priorities, but also how priorities might differ amongst individuals within the same community and the characteristics associated with these choices. Qualitative data were analysed from the seven group deliberations using the engagement tool. Content analysis was conducted, and inductive and deductive coding was used. Descriptive statistics was used to describe the study participants using the data from a demographic questionnaire and to show the group choices from the stickers allocated on the boards from the groups rounds. The investment level (sticker allocation) of all study participants was recorded at each stage of the study. From these the number of stickers allocated to each topic by the participants was calculated by adding up the number of stickers across interventions selected by the participant by topic. The median and interquartile range across study participants was calculated for the topic totals. To examine differences in sticker allocations, Wilcoxon rank sum tests were performed for differences across participant categories and sticker allocations in the final round of CHAT. Findings: Based on the outcomes, seven areas of health need and related interventions specific for a rural community context were identified and costed for inclusion in the CHAT board. These include maternal, new-born and reproductive health; child health; woman and child abuse; HIV/AIDS and TB; lifestyle diseases; quality/access; and malaria. The CHAT SA board reflects both priority options of policymakers/ experts and of community members and demonstrates some of the context specific coverage decisions that will need to be made under NHI. The CHAT implementation shows that the rural communities mostly prioritised curative services over primary prevention due to perceived inefficacy of existing health education and prevention programmes. The exercise fostered strong debates and deliberations. Specifically, the groups engaged deeply with trade-offs between costly treatment for HIV/AIDS and those for non-communicable disease. Barriers to healthcare access were of particular concern and some priorities included investing in more mobile clinic. The individual level priorities were mostly aligned with societal ones, and there were no statistically significant differences between the individual and group choices. However, there were some statistically significant differences between individual priorities based on demographic characteristics such as age. The study demonstrates that giving individuals greater control and agency in designing health services packages can increase their participation in the priority setting process, align individual and community priorities, and enhance the legitimacy and acceptability of the decision-making process. In terms of reconciling plurality in priority setting for health, group deliberative approaches help to identify social values and reconcile some of the differences, but additional individual voices may also need to be considered alongside group processes, especially among the most vulnerable. Conclusion: This research marks the first instance of modifying and implementing a deliberative tool for priority setting in a South African rural context. The findings shed light on the process and some of the outcomes of this approach within a vulnerable community, offering insights into public engagement in priority setting more broadly. The study demonstrates that participatory methods are feasible in modifying public engagement tools such as CHAT and can be adapted to different country contexts, potentially enhancing the priority setting process. Regarding the implementation of CHAT, the study provides an example of how a rural community grappled with resource allocation decisions, considered different perspectives and societal implications, and set priorities together. The research also highlights the priorities of this rural community, the social values driving their choices, and individual characteristics that are important to consider when setting priorities. The work demonstrates that meaningful public engagement includes various factors that interrelate and impact one another and that could inform a dynamic and cyclical approach going forward, as well as the importance of transparency during all stages of the process.
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    Characterising skeletopathy in an animal model of type 2 diabetes
    (University of the Witwatersrand, Johannesburg, 2022-11) Dlamini, Gcwalisile Frances; Ndou, Robert
    Type two diabetes (T2D) is a chronic, progressive heterogonous syndrome with a genetic and environmental origin. It is now recognized as an epidemic with a high morbidity and mortality rate. The endocrinology of type 2 diabetes (T2D) and its predisposing factors have been studied extensively, while diabetic skeletopathy has received negligible research. Previous studies report that fractures in T2D vary with specific sub regions in bones, therefore prompting our study to focus mainly on the femoral head and neck as well as the humerus head. Femoral neck fractures are the commonest, followed by the proximal femur, distal radius and proximal humerus. Susceptibility to fracture is a sequelae of poor bone remodeling. Poor bone remodeling is established at molecular and cellular levels. It depends on the activity of osteoblasts, osteocytes and osteoclasts, which are under the influence of TGF-β1, a pro-osteogenic cytokine, together with BMP3, an anti-osteogenic cytokine. T2D induced bone marrow adipocity and the accumulation of AGEs in cortical bone have also been implicated in increasing susceptibility to fracture. It is still unclear how T2D affects molecular and cellular elements that culminate in weaker bones observed in diabetic patients. In addition, it is debatable if T2D affects the skeleton at disease onset or later in the disease. Therefore, this study aimed to characterize T2D induced skeletopathy and related it to age, in the Zucker Diabetic Sprague Dawley (ZDSD) rat, using the femur and humerus. This study initially confirmed the diabetic state by monitoring animal weights, fasting blood glucose levels, and fasting oral glucose tolerance tests (OGTTs) every fortnight. Then triglyceride levels and quantified serum levels of osteoregulatory hormones such as insulin and osteocalcin were monitored. To assess oxidative stress, Malondialdehyde (MDA) serum levels were also determined by ELISA. Once diabetes was successfully induced, rats were grouped according to strain and age at termination. Termination age was at 20 weeks and 28 weeks . The Sprague Dawley (SD) rats were the controls, while the Zucker Diabetic Sprague Dawley rats (ZDSD) were the experimental groups. These were designated as SD20WK (n=8) and ZDSD20WK (n=7) respectively. Another batch was designated as SD28WK (n=8), and ZDSD (n=15) that were terminated at 28 weeks of age. The latter were further divided into moderate diabetes (ZDSD28WK-MOD) (n=9) and severe diabetes (ZDSD28WK-SVD) groups (n=6). Bilateral humeri and femora were harvested then fixed in 10% buffered formalin. Right proximal femora and humeri were scanned using a 3D-μCT scanner (Nikon XTH 225L) to analyse trabecular morphometric parameters, cortical bone area and medullary canal area. Biomechanical strength was analyzed by three point bending tests using a universal tensile tester. Left proximal femora and humeri were processed for histology. Some sections were stained with Haematoxylin and Eosin (H&E) to assess normal histologic morphology and adipocyte quantification. Remnant sections were immunolabelled using the anti-TRAP and anti-ALP antibodies for osteocyte and osteoblast quantification respectively, to assess osteolysis and osteogenesis. Immunolocalization of AGEs, TGF-β1 and BMP3 was also conducted to investigate their role in diabetic skeletopathy. We found that diabetes affected osteoblastogenesis as measured by ALP positive cells and bone marrow adipocytes. TRAP positive osteocytes numbers were increased in the presence of T2D, suggesting an increased osteolysis. There was reduced TGFB1 expression with increased BMP3 expression. The number of AGEs immuno-positive cells as well as its extracellular expression was increased. Our finding suggest that osteoblast and osteocyte numbers are regulated by TGFβ1 and BMP3 in both bones, under the influence of AGEs. Our findings from osteometry, 3-point bending tests and Micro CT support that diabetes weakens bone. The diabetic effect results in lighter, shorter hollow bones that perform poorly under loading, as well as exhibit unfavourable trabeculae microarchitecture. Our findings confirm that T2D causes increased fragility in the proximal femur and humerus as well the mid-diaphysis. These perturbations occur early and late in the disease, and they are also exacerbated by the presence of hyperglycemia. We conclude that the ZDSD rat can be used as a translational model for diabetic skeletopathy at cellular and molecular level, and it can be extrapolated to humans after consideration of other factors like, basal metabolism, age, sex and skeletal loading patterns. We recommend optimal control of blood glucose levels at all stages of the disease to reduce the incidence of fractures in diabetic patients.
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    The role of the 20-hydroxyecdysone (20E) signaling pathway in modulating Anopheles arabiensis reproduction, gut microbiome and anti-bacterial immunity
    (University of the Witwatersrand, Johannesburg, 2023-05) Ekoka, Elodie; Dahan-Moss, Yael; Koekemoer, Lizette
    The 20-hydroxyecdysone (20E) signaling pathway, which is activated when 20E binds to its ecdysone receptor, EcR, is a promising target to reduce Anopheles mosquitoes’ ability to transmit malaria. The function of this pathway is typically assessed by altering the pathway and assessing how this manipulation affects a phenotype of interest. Two ways to alter this pathway include injecting mosquitoes with 20E or reducing EcR transcript levels with RNA interference (RNAi). Whether the 20E signaling pathway regulates An. arabiensis fecundity, fertility, gut bacteria, and immunity has never been investigated. These questions were addressed in this study by using a South African An. arabiensis strain. First, RNAi was used to investigate whether EcR silencing affects An. arabiensis reproductive output. While EcR depletion did not affect the mosquito fecundity, both vitellogenesis and egg fertility were impaired, as indicated by adecrease in the expression of some yolk genes and the number of eggs that hatched into larvae. Next, a link between the gut bacteria and EcR expression was established, by showing that antibiotic-fed (i.e., with less gut bacteria) mosquitoes displayed fewer EcR transcripts. To investigate whether the relationship between An. arabiensis gut microbiome and EcR expression was mediated by the mosquito innate immune defenses, the expression of ten selected anti-bacterial immune genes was measured in the gut and the whole mosquito after disturbing the 20E signaling pathway. This experiment uncovered that the 20E signaling pathway down-regulates the mosquito anti-bacterial immune defenses, which may favour bacterial proliferation post feeding. Finally, the effect of Gram-negative and Gram-positive bacteria on EcR expression was assessed by injecting mosquitoes with each type of bacteria and quantifying EcR transcripts. The results suggested that only Gram-negative bacteria influenced EcR expression. Altogether, these results demonstrated that An. arabiensis reproduction, gut microbiome, and antimicrobial peptides are regulated by 20E.