Browsing by Author "Engel, Mark"

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    Clinico-epidemiological profile of cardiac admissions at a district level hospital in South Africa: a cohort study
    (2025) Engelbrecht, Lillian Lize; van der Schyff, Nasief; Engel, Mark
    Background Nineteen percent of all deaths during 2016 in South Africa (SA), were due to cardiovascular disease. Despite this notable burden, research describing cardiac admissions at the district level is limited and thus, area-specific studies are warranted to provide a perspective on SA's unique population of rich genetic, geographic, social, and cultural diversity. The aim of this study was to describe the epidemiological and clinical characteristics, associated risk factors and outcomes of cardiac patients admitted to a district level hospital in SA, in order to fill the void within currently available literature. Methods We conducted a retrospective records review of all patients admitted to Victoria Hospital Wynberg with a primary cardiac diagnosis, between 1 September 2020 to 30 November 2020. Data were transcribed onto a bespoke data collection form and captured into the Victoria Internal Medicine Research Initiative (VIMRI) electronic registry. The study was approved by UCT HREC (048/2022), the Western Cape Government and Victoria Hospital Board. Results Our cohort consisted of 218 patients (52.8% male) with a mean age (SD) of 60 years (±14.6), and an age range from 22 to 95 years. Acute decompensated heart failure, together with acute coronary syndrome, were responsible for 87.4% of all admissions. The mean length (SD) of stay was 4 days (±3.5 days). Most prevalent risk factors among admitted patients included hypertension (76%), cigarette smoking (55%) and diabetes (42.7%). Amongst diabetics, 27.3% were considered to have acceptable diabetic control (HbA1c £7%). Most frequently reported precipitants for hospital admission were prior inadequate therapy, discontinuing chronic medication, uncontrolled hypertension, disease progression, and ongoing substance use. Twenty-one percent of the cohort were transferred to cardiology for further management and specialist intervention. The inpatient mortality rate was 9.2%, and one-year mortality rate was 18.8%. Readmission within six months was reported amongst 30.8% of our cohort. Discussion and Conclusion Our study provides important insight into the clinico-epidemiological profile of cardiac admissions at a public district level hospital in SA. We report notable rates of morbidity, readmission, and mortality together with a high prevalence of well-known cardiovascular risk factors of hypertension, diabetes mellitus and cigarette smoking. While the in-hospital and one-year mortality rates are notable, but not too unexpected when compared to available data, we nevertheless recommend programmes focused on improving adherence to treatment and optimization of heart failure therapy at a primary care level, as means to reduce rates of poor adherence, suboptimal anti-failure therapy and poor glycaemic control observed in our cohort.
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    Clinico-epidemiological profile of cardiac admissions at a district level hospital in South Africa: a cohort study
    (2025) Engelbrecht, Lillian Lize; van der Schyff, Nasief; Engel, Mark
    Background Nineteen percent of all deaths during 2016 in South Africa (SA), were due to cardiovascular disease. Despite this notable burden, research describing cardiac admissions at the district level is limited and thus, area-specific studies are warranted to provide a perspective on SA's unique population of rich genetic, geographic, social, and cultural diversity. The aim of this study was to describe the epidemiological and clinical characteristics, associated risk factors and outcomes of cardiac patients admitted to a district level hospital in SA, in order to fill the void within currently available literature. Methods We conducted a retrospective records review of all patients admitted to Victoria Hospital Wynberg with a primary cardiac diagnosis, between 1 September 2020 to 30 November 2020. Data were transcribed onto a bespoke data collection form and captured into the Victoria Internal Medicine Research Initiative (VIMRI) electronic registry. The study was approved by UCT HREC (048/2022), the Western Cape Government and Victoria Hospital Board. Results Our cohort consisted of 218 patients (52.8% male) with a mean age (SD) of 60 years (±14.6), and an age range from 22 to 95 years. Acute decompensated heart failure, together with acute coronary syndrome, were responsible for 87.4% of all admissions. The mean length (SD) of stay was 4 days (±3.5 days). Most prevalent risk factors among admitted patients included hypertension (76%), cigarette smoking (55%) and diabetes (42.7%). Amongst diabetics, 27.3% were considered to have acceptable diabetic control (HbA1c £7%). Most frequently reported precipitants for hospital admission were prior inadequate therapy, discontinuing chronic medication, uncontrolled hypertension, disease progression, and ongoing substance use. Twenty-one percent of the cohort were transferred to cardiology for further management and specialist intervention. The inpatient mortality rate was 9.2%, and one-year mortality rate was 18.8%. Readmission within six months was reported amongst 30.8% of our cohort. Discussion and Conclusion Our study provides important insight into the clinico-epidemiological profile of cardiac admissions at a public district level hospital in SA. We report notable rates of morbidity, readmission, and mortality together with a high prevalence of well-known cardiovascular risk factors of hypertension, diabetes mellitus and cigarette smoking. While the in-hospital and one-year mortality rates are notable, but not too unexpected when compared to available data, we nevertheless recommend programmes focused on improving adherence to treatment and optimization of heart failure therapy at a primary care level, as means to reduce rates of poor adherence, suboptimal anti-failure therapy and poor glycaemic control observed in our cohort.
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    Narcolepsy associated with Pandemrix influenza vaccine: A systematic review and meta-analysis
    (2021) Lakoma, Leif; Muloiwa, Rudzani; Abdullahi, Leila; Engel, Mark
    This systematic review and meta-analysis forms the mini-dissertation part of the primarily coursework degree of Master of Public Health at the University of Cape Town. The review is divided into three separate parts. The first part constitutes the research protocol which outlines the proposed methods and scope of the review. The second part is a structured literature review further elaborating on the research topic and current knowledge of it. The final third part constitutes the manuscript-ready part of the review. The aim of the review is to systematically explore the current scientific literature regarding the association between narcolepsy and the Pandemrix pandemic influenza vaccine. This particular association has been one of the most studied presumed vaccine adverse effects of the last decade and it has greatly affected the discussion on vaccine safety and vaccine hesitancy still to this date. Despite several studies having been published investigating the association, no systematic review of these studies had been performed prior to the beginning of this this review.
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    Passive surveillance of STI pathogens in Cape Town, South Africa: A six-month molecular epidemiology study
    (2023) Moodley, Clinton; Engel, Mark
    Background: Sexually transmitted infections are among the most commonly occurring globally, with countries in sub-Saharan Africa exhibiting disproportionately higher prevalence rates. Reports indicate the need for accurate detection, epidemiological characterisation, and appropriate management of these infections. This prospective passive surveillance study sought to document local STI prevalence and to evaluate the potential of a molecular assay as a surveillance tool in our setting. Methods: Urogenital swabs, submitted to Groote Schuur Hospital over a period of 6 months, for routine microbiological investigations, were subjected to a commercial multiplex PCR assay to determine the distribution of STI pathogens. Correlations between detected organisms and clinical and demographic information were determined using Stata® software. Results: A total of 148 urogenital swabs were collected and tested, with the majority from women. Up to 83.79% of the samples tested positive for one or more pathogen, with all seven assayed pathogens detected in one or more sample. Ureaplasma parvum was the most prevalent pathogen detected overall, with a 6-month period prevalence of 42.57%, followed by N. gonorrhoeae (37.84%), M. hominis (34.46%), U. urealyticum (23.65%), T. vaginalis (11.49%), C. trachomatis (10.14%), with M. genitalium (1.35%) the least prevalent. There were several different combinations of co-infections with multiple pathogens, with one sample testing positive for five organisms. M. hominis and T. vaginalis were only detected in co-infection with other pathogens. Persons aged 17-30- and 31-40- years old were 51-times and 16-times, respectively, more likely to test PCR-positive for one or more STI pathogen. Samples submitted with non-urogenital specific indications were 11.82 times more likely to test positive for C. trachomatis. There was an association between samples submitted for GBS screening and PCR-positivity for any of the pathogens tested, which were 3.03 times more likely to test positive for U. parvum. Routine microbiological investigations only detected three infections. Conclusions: There is a significantly higher than expected rate and difference in organism distribution of STI prevalence in Cape Town, South Africa as compared with global and regional estimates. The use of molecular testing methods may improve detection, providing rapid results, which may allow for tailored guidelines and interventions to limit spread and resistance.
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    Prevalence, and outcomes of Rheumatic Heart Disease in Ethiopia: a systematic review and meta-analysis
    (2023) Dhodho, Munyaradzi; Engel, Mark
    Background: While eradicated in other parts of the world, Rheumatic Heart Disease, nevertheless, remains one of the most common acquired heart diseases in low- to middle- income countries; in sub-Saharan Africa, there was an estimated prevalence of 10 persons per 1,000 population in 2015. In the Global Burden of Disease estimates 1990-2015, Ethiopia was identified as having one of the highest burdens of RHD with a prevalence of 100-149 persons per 100,000 population. We therefore sought to estimate the prevalence of RHD, and clinical and post-operative outcomes, in Ethiopia. Objectives: We conducted a systematic review of the prevalence and outcomes of RHD according to a priori protocol. Data Sources: Studies included in this review were retrieved from PubMed and Web of Science. In addition, Google Scholar and approaching authors was used to complement the search. Data Extraction: Studies conducted after 2012 were included if the method of RHD diagnosis was echocardiography. A meta-analysis was done to measure the pooled prevalence and outcomes of RHD. Results: A total of nine studies were included in this review, 5 focusing on prevalence and 4 focusing on outcomes of RHD. The overall prevalence of asymptomatic echocardiographic RHD was per 21 per 1000 (95% CI, 12.27;32.03). In hospitalised patients, presentation included congestive heart failure, atrial fibrillation, and stroke. The 30-day mortality and post- operative mortality was 2.5 (95% CI, 0.00;12.81) and 32.8 (95% CI, 11.43;62.82) per 1000 respectively. The 60-day mortality and post-operative mortality was 33.5(95% CI, 0.00;111.38) and 161.7 (95% CI 125.54;201.27) per 1000 respectively. Conclusions And Relevance: The prevalence of asymptomatic RHD in Ethiopia is high while RHD in adults/children is associated with congestive heart failure, atrial fibrillation, and stroke. Mortality was high in patients with RHD-related heart failure; thus, to achieve the World Heart Federation target of a 25% reduction in the mortality due to RHD by 2025 in the under 25- year-olds might prove challenging.
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    The Cape Town Violence and Injury Observatory (VIO) Validity and utility of data sources for a prevention-oriented VIO in urban Cape Town, South Africa
    (2021) Jabar, Ardil; Matzopoulos, Richard; London, Leslie; Engel, Mark; Oni, Tolullah
    Background The Cardiff model purports that the true burden of violence within a community can only be quantified by the addition of violence-related data from health services to violence data reported to the police. This thesis describes the conceptualisation, development and implementation of a violence and injury observatory for the routine collection of violence-related data for the City of Cape Town. The observatory model, which was conceptualised in the early 1990s in Colombia, has gone through various iterations as a municipality-level research tool, to a city-level tool and thereafter as a national and transnational tool. Aims of this thesis The thesis aimed to assess the utility of clinical and non-clinical data sources in constituting a prevention-oriented violence and injury observatory (VIO) in urban Cape Town, South Africa. The specific objectives of each study component were as follows: • To describe the objectives of the pilot VIO, potential violence-related datasets for collection, data analysis and research dissemination plan (Study One) • To assess the validity and utility of VIOs in reducing violence and violencerelated harms in adult populations (Study Two) • To identify the optimal data elements for inclusion in a VIO according to expert consensus (Study Three) • To determine the concordance between violent crimes reported to the police with violence-related injuries presenting at health facilities in Khayelitsha (Study Four). Methods The systematic review method was used to determine whether the introduction of violence and injury observatories was associated with a reduction in violence in adult populations (Study Two). A modified two-round Delphi study (Study Three) determined the optimal data elements (including violence and injury indicators, datasets and research priorities) for inclusion in a pilot violence and injury observatory in Cape Town. The Delphi panel of 21 participants included one Provincial Head of Emergency Medicine, one Provincial Head of Disaster Medicine, several Heads of Department of Emergency Medicine across hospitals in Cape Town, and representatives from relevant data stakeholders, including the Forensic Pathology Services (FPS), South African Police Services (SAPS), Health Systems Trust (HST) and the Violence Prevention through Urban Upgrading (VPUU). This was to ensure that decisions were made by persons in senior posts to facilitate subsequent implementation of the recommendations. Khayelitsha, a peri-urban mixed informal township of Cape Town, was the setting for the final study (Study Four), which included a retrospective analysis of secondary cross-sectional health and police data, from three health facilities and three police stations in the community of Khayelitsha, Cape Town. A case-matching study, using personal identifier matching, was employed to determine the concordance between reports of violent crimes to police stations with reports of injuries arising from interpersonal violence at health facilities within the community of Khayelitsha in Cape Town, South Africa. Results and Discussion Subgroup analyses according to the two types of models implemented in the systematic review (Study Two), namely, the VIO and the injury surveillance system (ISS), provided evidence for an association between the implementation of the VIO model and a reduction in homicide count in high-violence settings (incidence rate ratio [IRR]=0.06; 95% CI 0.02 to 0.19; four studies), while the introduction of ISS showed significant results in reducing assault (IRR=0.80; 95% CI 0.71 to 0.91; three studies). Following expert consultation through a Delphi process (Study Three), this study identified 14 violence and injury indicators and 12 violence-related datasets for inclusion in the pilot VIO. Additionally, research priorities within 16 research themes across five different types of violence were identified including: elder abuse, youth violence, intimate partner violence, sexual violence, and armed violence. Key findings from these thematic priorities included: (1) formal methods to define and measure violence, identification of violence-related risk factors; (2) evaluation of the effectiveness of promising programmes that target violence-related risk factors; and (3) evidence-based recommendations on scaling up programmes that were shown to be effective in reducing interpersonal violence. With regard to the key findings around data sharing, the majority of the panelists (>55%) thought that: (1) violence-related data from health services should be shared with Policing Services; (2) the data model employed should go beyond the Cardiff model (policing and health data) and also include violence-related data from the Fire and Rescue Services (FARS) and the Emergency Medical Services (EMS); and (3) the functions of a local observatory should include a civilian spatial data observatory, an information technology division, a predictive analytics division, a historical data repository and a systematic review repository. The expert-identified violence and injury indicators, datasets and research priorities provide a research framework for interpersonal violence and injury prevention work within South Africa. The findings have theoretical implications and build up evidence-based data for the general field, and they have a practical outcome in recommendations that are both general and specific for implementation in South Africa. They may also serve to guide the development of additional VIOs locally. In the final study (Study Four), with regard to concordance between the datasets, among the 708 patients being treated for violence-related injuries at health facilities, only 104 reported the incident to the police which equates to a matching ratio of 14.7%. Combining health and police data revealed an 81.7% increase in potential total violent crimes over the reporting period. Compared to incidents reported to the police, those not reported were more likely to involve male patients (difference: +47.0%; p< 0.001), and sharp object injuries (difference: +24.7%; p< 0.001) and less likely to report blunt trauma i.e., push/kick/punch injuries (difference: -17.5%; p< 0.001). These findings suggest that the majority of injuries arising from interpersonal violence presenting at health facilities in Khayelitsha are not reported to the police. Conclusion This research provides an evidence-based model for the development and implementation of a VIO, and the Cardiff model, to reduce interpersonal violence. It is supported by the evidence from the systematic review of the effectiveness of VIOs in reducing violence outcomes among adults in high-violence settings. This pilot VIO represents the first attempt to collect contemporary and comprehensive data on violence and injury in the Western Cape Province and South Africa. The implementation of VIOs should be considered in high-violence communities where the collation and integration of violence-related data and violence stakeholders, may guide violence reduction. The Delphi study provided indicators, datasets and research priorities to (1) inform the basic research infrastructure of a VIO, and (2) serve as part of a regional standardised data collection framework to guide the development of other local violence and injury observatories. This is consistent with the aims of the South African National Development Plan 2030 to ‘improve the health information system; to prevent and reduce the disease burden and promote health and to improve quality by using evidence'. Finally, the research further shows a clear benefit in combining data on violence from different settings as demonstrated in our analysis of data in the Cape Town suburb of Khayelitsha, where the overwhelming majority of injuries arising from interpersonal violence presenting at health facilities in Khayelitsha are not reported to the police. This study has broader implications regionally and nationally for the surveillance of injuries arising from interpersonal violence, for the police definition and surveillance of community interpersonal violence, for community policing intelligence development (improving the configuration of violence heat maps on a real time basis) and finally for police resource utilisation and distribution, which should, in turn, impact positively on reducing crime and violence in the community, and reduce the burden on the health services. The Western Cape Safety Plan, a policy document developed by the Western Cape Government, advocates the use of data and technology to understand violent crime patterns to inform the deployment of law enforcement resources and investigators accordingly and furthermore acknowledges research and analysis as an important component of its evidence-based policing (EBP) strategy. The policy document and study findings provide support to the implementation of the Cardiff Model locally.
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    The effectiveness of peer and community health worker-led self-management support programs for improving diabetes health-related outcomes in adults in low- and-middle-income countries: a systematic review
    (2020-06-06) Werfalli, Mahmoud; Raubenheimer, Peter J; Engel, Mark; Musekiwa, Alfred; Bobrow, Kirsten; Peer, Nasheeta; Hoegfeldt, Cecilia; Kalula, Sebastiana; Kengne, Andre P; Levitt, Naomi S
    Objective Community-based peer and community health worker-led diabetes self-management programs (COMP-DSMP) can benefit diabetes care, but the supporting evidence has been inadequately assessed. This systematic review explores the nature of COMP-DSMP in low- and middle-income countries’ (LMIC) primary care settings and evaluates implementation strategies and diabetes-related health outcomes. Methods We searched the Cochrane Library, PubMed-MEDLINE, SCOPUS, CINAHL PsycINFO Database, International Clinical Trials Registry Platform, Clinicaltrials.gov, Pan African Clinical Trials Registry (PACTR), and HINARI (Health InterNetwork Access to Research Initiative) for studies that evaluated a COMP-DSMP in adults with either type 1 or type 2 diabetes in World Bank-defined LMIC from January 2000 to December 2019. Randomised and non-randomised controlled trials with at least 3 months follow-up and reporting on a behavioural, a primary psychological, and/or a clinical outcome were included. Implementation strategies were analysed using the standardised implementation framework by Proctor et al. Heterogeneity in study designs, outcomes, the scale of measurements, and measurement times precluded meta-analysis; thus, a narrative description of studies is provided. Results Of the 702 records identified, eleven studies with 6090 participants were included. COMP-DSMPs were inconsistently associated with improvements in clinical, behavioural, and psychological outcomes. Many of the included studies were evaluated as being of low quality, most had a substantial risk of bias, and there was a significant heterogeneity of the intervention characteristics (for example, peer definition, selection, recruitment, training and type, dose, and duration of delivered intervention), such that generalisation was not possible. Conclusions The level of evidence of this systematic review was considered low according to the GRADE criteria. The existing evidence however does show some improvements in outcomes. We recommend ongoing, but well-designed studies using a framework such as the MRC framework for the development and evaluation of complex interventions to inform the evidence base on the contribution of COMP-DSMP in LMIC.
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    The Epidemiology of Auditory Dysfunction in Type 2 Diabetic Adults in Africa: 4 A Systematic Review and Meta-analysis
    (2022) Fihla, Achuma; Engel, Mark; Petersen, Lucretia; Hohlfeld, Ameer
    Background: There is a growing rate of diabetes related hearing loss (HL) worldwide. However, in under-developed countries, HL is still under-recognised as a complication of type 2 diabetes mellitus (T2DM). Although Africa presents a significant rise in T2DM every year, it is met with limited resources to assist its growing and ageing population. Objectives: This systematic review and meta-analysis brings awareness to diabetes-related HL in the form of reliable medical evidence measuring the prevalence of T2DM-related HL in an African population. Methods: Studies were screened using Rayyan QCRI. STATA software and the random-effects metaanalysis model was used to aggregate prevalence estimates with a 95% confidence interval. The Freeman Tukey Transformation was used to account for between study variability. The study protocol is published in PROSPERO international Register of Systematic Reviews (registration number CRD42021227801). Results: We identified a total of 99 studies, 14 duplicates were removed and 67 were excluded. After full review only five studies were included for quantitative synthesis. All the studied were crosssectional and used purposive sampling as their recruitment method. Conclusions: Findings show most participants with T2DM experienced mild HL and slight delays in objective hearing assessments. Audiometric resources and qualified Audiologists are scarce in Africa. Therefore, the available evidence does not justify the added costs needed for routine audiometric assessments for patients with T2DM. However, it does serve to recommend prioritising further research regarding risk factors associated with developing auditory disorders in people with T2DM.
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    The prevalence of occupational health problems in-flight crews (pilots and flight attendants: A systematic review and meta-analysis
    (2023) Omran, Foad; Engel, Mark
    Background: The International Civil Aviation Organisation (ICAO), a United Nations (UN) body, reports that the “global air transport network” doubles in size, at least, every 15 years. Researchers have become increasingly aware that aircrew members (ACMs) are at high risk for several diseases when compared to the general population. We conducted a systematic review and meta-analysis to estimate the prevalence of occupational health problems in aircrew members (pilots and flight attendants) as compared with the general population. Methods: We identified relevant literature by searching several electronic databases including PubMed, EBSCOhost: CINAHL, PsycINFO, Web of Science, Scopus and Google Scholar and included all observational studies reporting occupational health problems among ACMs. We included published and unpublished cross-sectional studies reporting the prevalence rate of any OHPs among commercial ACMs and/or its risk factors. Articles in any language, irrespective of the date of publication, were taken into consideration. The main outcome was the prevalence of OHPs and its related factors among ACM. Meta-analysis (random-effects model) was employed to derive the summary estimate; subgroup analysis was conducted, given the high heterogeneity. Study quality was assessed using the modified Hoy et al Scale for cross-sectional studies and the National Institutes of Health (NIH) Quality Assessment Tool for Observational Cohort studies. The study protocol was registered in PROSPERO (CRD42020167631). Results: Our search of the literature addressing occupational health among commercial ACMs returned 846 studies, of which 51 articles were included in our systematic review and metaanalysis. The studies were published between (1996 - 2021) and most were cross-sectional in design (n=47) while 4 studies estimated the incidence of occupational health diseases or mortality from different sources. ACMs had various OHPs and workplace accidents and injuries were relatively common. The Pooled Prevalence Rate (PPR) by subgroup analysis showed the second most common OHPs to be Fatigue/Sleep related disorders(FSDs) (diseases or symptoms), which was higher in cockpit crew [PPR=66.64%, 95% confidence interval (CI): 52.65%–79.29%] compared to cabin crew [PPR=44.45%, 95% CI: 31.78%–57.49%]. Cabin crew had higher prevalence rates of respiratory conditions [PPR=24.08%, 95% CI: 14.18%– 36.64%] compared to cockpit crew [PPR=14.61%, 95%l CI: 4.47%–29.20%]. Musculoskeletal disorders (MSDs) were also commonly reported in cockpit crew [PPR=25.78%, 95% CI 10.31– 45.27]), cabin crew [PPR=36.90, 95% CI 25.51–49.08] and increased in ACMs [PPR=72.08%, 95% CI: 67.82%–75.97%]. The PPR of neurological conditions was found to be 13.42%, 95% CI:2.30%–31.55% in cockpit and 22.33% ,95% CI:9.69%–38.34% in cabin crew. The PPR for ENT conditions was 28.28% ,95% CI:25.96%–30.67% in cockpit and 26.8% ,95% CI:19.88%– 34.36% in cabin crew. The PPR for gastrointestinal was 40.14% ,95% CI:24.05%–57.40% in cockpit and 17.29% ,95% CI:16.31%–18.33% in cabin crew. Metabolic disorder prevalence was 19.76% ,95% CI:9.43%–32.72% in cockpit and 37.13% ,95% CI :21.70%–54.04% in cabin crew. The PPR for other conditions were relatively lower and fewer studies reported on these; cardiovascular disease prevalence was 2.42% ,95% CI: 1.99%–2.94 %in cabin crew; ophthalmological disorders 18.93%,95% CI: 18.03%–19.84% in cabin and 2.80%,95% CI: 2.32%–3.38% in cockpit crew; Cancer 0.37% ,95% CI:0.20%–0.69% in cockpit and 17.11% (95% CI:16.12%–18.14%) in cabin crew. PPR for occupational injuries was low at 0.83% ,95% CI:0.69%–0.97% in cockpit and high at 48.14%,95% CI:42.73%–53.48% in cabin crew whilst for sexual harassment it was 24.01% ,95% CI:12.64%–37.65% in cabin crew. Conclusion: There is a high prevalence of work-related illness and injuries among aircrew members supporting the hypothesis that they are at increased risk. This is the first systematic review that addresses the occupational health status of aviation personnel and it found the most prevalent problems in cockpit crew to be FSDs, gastrointestinal disorders, MSDs, ENT disorders and respiratory disorders. For cabin crew the most prevalent conditions were FSDs, occupational injuries, metabolic disorders, MSDs and sexual harassment. Governments, businesses and policy makers should support efforts to improve occupational health and safety measures among this occupational group.
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    Towards Rheumatic Heart Disease vaccine development: Defining host immune responses to Group A Streptococcal infection in Cape Town
    (2023) Salie, Mogamat; Engel, Mark
    Group A streptococcus (GAS) vaccines, as a primary prevention strategy, have the potential to prevent the spread of the bacteria, thus limiting post-sequelae diseases such as acute rheumatic fever (ARF) and rheumatic heart disease (RHD). Due to the limited supply of penicillin, adherence issues and problems associated with the diagnosis of post-sequelae diseases, a vaccine is thought to be the way forward on reducing the morbidity and mortality of ARF and RHD in low-resourced areas across the world. The latest vaccine formulation, a 30-valent M protein-based vaccine, currently in clinical trials is, however, challenged by the sheer volume of emm types (>230). This, along with the fact that significant emm types change over time, results in many gaps in protective efficacy. This body of work sought to contribute much-needed evidence in the quest for GAS vaccine development. This thesis provides a comprehensive understanding of the bacteria and its complexity regarding its emm type epidemiology and underlying immune effects within a population in Cape Town. This information could be used to make added improvements for the early detection and diagnosis of GAS infections, and further inform vaccine formulations, hopefully to ultimately reduce the burden of RHD in high-risk populations. The masters' thesis comprises four linked studies: a systematic review summarising the molecular epidemiology of GAS on the African continent, a longitudinal study, over a 2-year period of the molecular epidemiology of GAS, a systematic review assessing the association of GAS antigens with ARF and, an ELISA-based assessment of the human immune response to common GAS antigens. Chapter 1 provides the background and rationale for undertaking the study. Chapters 2, 3, 4, 5 report the respective studies described above. Finally, Chapter 6 serves to provide a context for the work with recommendations for further research and implications for clinical practice. Study I, published in mSphere 2020, highlights the dearth of epidemiological data found across the African content despite the high burden of GAS infections and post-sequalae diseases. Data, only available from five countries, indicated noticeable gaps in current vaccine formulations; for example, the StrepAnova vaccine, only affords 58.22% protective coverage. Study II serves to update an earlier study undertaken in Cape Town, South Africa, showing a continued significant prevalence of GAS in 256 children presenting with sore throat at community clinics. Among the 83 GAS strains isolated, characterisation through the emm typing procedure, documents a potential vaccine coverage of around 72%. Study III, published in Frontiers in Cardiovascular Medicine 2021, provides evidence confirming that a recent GAS infection is associated with increased levels of antibody titres to GAS antigens, SLO and DNase B in cases of ARF in comparison to controls. The study further indicates caution in the use of the upper limit of normal (ULN) when testing antibody responses and, rather, recommends the use of sequential sampling and testing sera against a panel of GAS antigens. Study IV provided evidence-based support for the utility of GAS-shared antigens and M peptides in documenting the characteristics of human immune responses following GAS infection. This study concludes that the array of GAS-specific antibody responses to GAS infection is broad, individuals demonstrate GAS-specific antibody responses in the absence of symptomatic GAS infection, GASnegative individuals exhibit pre-existing antibody levels and lastly, having a panel consisting of five shared GAS antigens, increased the overall sensitivity of predicting a preceding GAS infection to 73.7%. This thesis, emphasizes the need for population-based studies in Africa, endemic to GAS infection with a high burden of ARF/RHD. Secondly, this study provides empirical support for the value of sequential sampling in ascertaining recent infection, suggesting a panel of at least five antigens in diagnostic assessment. Finally, this work provides valuable epidemiological data and insights into GAS pathobiology, serving to aid in the development of effective, safe and affordable GAS vaccines for global deployment.
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    Treatment of oral fungal infections using antimicrobial photodynamic therapy: A systematic review and meta-analysis
    (2019) Roomaney, Imaan A; Engel, Mark; Holmes Haly
    Part A is a research protocol which describes the background and proposed methodology of this systematic review. This section contains the definitions used for “photodynamic therapy”, “conventional antifungal medication” and “oral fungal infections”. It also provides details of quantitative and qualitative methods used to analyse the effectiveness of photodynamic therapy (PDT) and conventional antifungal medications in the treatment of oral fungal infections. Part B is a literature review which expands on the protocol. It provides an in-depth description of the epidemiology and pathogenesis of oral fungal infections. It also discusses currently available and future treatment strategies and the potential and shortcomings thereof. The importance of this research is highlighted by contextualising PDT as an alternative treatment modality to conventional antifungal medications. Part C presents the research as a journal manuscript according to the Photodiagnosis and Photodynamic Therapy Journal's instructions for authors. The manuscript includes a brief introduction to the research followed by a summary of the methods and presentation of the results which are then discussed.