Research Articles (Internal Medicine)

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    Pro-inflammatory interactions of streptolysin O toxin with human neutrophils in vitro
    (Taylor and Francis Group, 2024-12) Joseph, Darren; Theron, Annette J.; Feldman, C.; Anderson, Ronald; Tintinger, Gregory
    The recent global resurgence of severe infections caused by the Group A streptococcus (GAS) pathogen, Streptococcus pyogenes, has focused attention on this microbial pathogen, which produces an array of virulence factors, such as the pore-forming toxin, streptolysin O (SOT). Importantly, the interactions of SOT with human neutrophils (PMN), are not well understood. The current study was designed to investigate the effects of pretreatment of isolated human PMN with purified SOT on several pro-inflammatory activities, including generation of reactive oxygen species (ROS), degranulation (elastase release), influx of extracellular calcium (Ca2þ) and release of extracellular DNA (NETosis), using chemiluminescence, spectrophotometric and fluorimetric procedures, respectively. Exposure of PMN to SOT alone caused modest production of ROS and elastase release, while pretreatment with the toxin caused significant augmentation of chemoattractant (fMLP)-activated ROS generation and release of elastase by activated PMN. These effects of treatment of PMN with SOT were associated with both a marked and sustained elevation of cytosolic Ca2þconcentrations and significant increases in the concentrations of extracellular DNA, indicative of NETosis. The current study has identified a potential role for SOT in augmenting the Ca2þ-dependent pro-inflammatory interactions of PMN, which, if operative in a clinical setting, may contribute to hyper-activation of PMN and GAS-mediated tissue injury.
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    Relationship between glycaemic control and the severity of erectile dysfunction in men with diabetes attending the diabetic clinic at Kalafong Provincial Tertiary Hospital
    (Taylor and Francis, 2024-07) Mathekga, K.H.; Van Zyl, Danie G.; Hanekom, S.
    INTRODUCTION : Erectile dysfunction (ED) is common in men who are in their sixth decade of life and older, particularly those with diabetes. This study aimed to determine whether long-term glycaemic control affects the severity of ED in diabetic male patients attending the diabetic clinic at Kalafong Provincial Tertiary Hospital (KPTH). METHODS : This cross-sectional study used data collected at the KPTH Diabetic Clinic, Gauteng, South Africa. Eighty-one male patients aged over 55 years who attended the diabetic clinic in 2017 were selected to participate in this study. The Sexual Health Inventory for Men (SHIM) questionnaire was used to determine the severity of ED, and the mean glycated haemoglobin A1c (HbA1c) over the preceding two years was used to assess glycaemic control. RESULTS : The SHIM distinguished between ED categories among the participants (Cronbach’s alpha: 0.964). The HbA1c did not differ significantly between SHIM ED categories (p = 0.867). No significant difference was detected between the mean HbA1c in those with ED (8.26%, IQR: 7.2 to 9.4) and those without ED (7.6%, IQR: 6.7 to 8.9) (p = 0.494). Multivariate analyses revealed that a longer duration of diabetes, moderate albuminuria, the presence of any peripheral neuropathy, the number of antihypertensive agents used, and smoking history were associated with ED. However, the mean HbA1c of the preceding two years did not significantly contribute to ED (p = 0.133). CONCLUSION : The SHIM reliably distinguished between ED categories in this population, with high internal consistency; however, glycaemic control, as measured by HbA1c over the preceding two years, did not play a significant role in predicting the presence or severity of ED.
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    Cigarette smoking as a risk factor for Tuberculosis in adults : epidemiology and aspects of disease pathogenesis
    (MDPI, 2024-02) Feldman, Charles; Theron, Annette J.; Cholo, Moloko C.; Anderson, Ronald; ronald.anderson@up.ac.za
    It has been noted by the World Health Organisation that cases of tuberculosis in 2022 globally numbered 10.6 million, resulting in 1.3 million deaths, such that TB is one of the infectious diseases causing the greatest morbidity and mortality worldwide. Since as early as 1918, there has been an ongoing debate as to the relationship between cigarette smoking and TB. However, numerous epidemiological studies, as well as meta-analyses, have indicated that both active and passive smoking are independent risk factors for TB infection, development of reactivation TB, progression of primary TB, increased severity of cavitary disease, and death from TB, among several other considerations. With this considerable body of evidence confirming the association between smoking and TB, it is not surprising that TB control programmes represent a key potential preventative intervention. In addition to coverage of the epidemiology of TB and its compelling causative link with smoking, the current review is also focused on evidence derived from clinical- and laboratory-based studies of disease pathogenesis, most prominently the protective anti-mycobacterial mechanisms of the alveolar macrophage, the primary intracellular refuge of M. tuberculosis. This section of the review is followed by an overview of the major strategies utilised by the pathogen to subvert these antimicrobial mechanisms in the airway, which are intensified by the suppressive effects of smoke inhalation on alveolar macrophage function. Finally, consideration is given to a somewhat underexplored, pro-infective activity of cigarette smoking, namely augmentation of antibiotic resistance due to direct effects of smoke per se on the pathogen. These include biofilm formation, induction of cellular efflux pumps, which eliminate both smoke-derived toxicants and antibiotics, as well as gene modifications that underpin antibiotic resistance.
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    Persistently elevated expression of systemic, soluble co-inhibitory immune checkpoint molecules in people living with HIV before and one year after antiretroviral therapy
    (MDPI, 2024-06) Labuschagne Naidoo, Robyn-Brooke; Steel, Helen C.; Theron, Annette J.; Anderson, Ronald; Tintinger, Gregory Ronald; Rossouw, Theresa M.; theresa.rossouw@up.ac.za
    Please read abstract in article.
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    Who is to blame for the 'problem' of teenage pregnancy? Narratives of blame in two South African communities
    (BMC, 2025-02) Duby, Zoe; Bunce, Brittany; Fowler, Chantal; Bergh, Kate; Jonas, Kim; Slingers, Nevilene; Mathews, Catherine; Abdullah, Fareed
    BACKGROUND : The framing of teenage pregnancy in social discourse influences the way in which adolescent girls and young women (AGYW) are treated, the extent to which they are supported, and to which they are able to engage with services and enact pregnancy prevention behaviours. METHODS : Through the analysis of data from a qualitative study conducted in the South African communities of Newcastle in KwaZulu-Natal and Moretele in the North-West province, we explored narratives of blame for teenage pregnancy. Data derived from seventy-one in-depth interviews conducted with forty AGYW aged between 15 and 24, twenty-four parents/caregivers of AGYW, five service providers, ten school educators, and two other community members. Interpretation of data drew upon blame, attribution and framing theories. FINDINGS : The overall framing of teenage pregnancy was overwhelmingly negative, with participants labelling it immoral and ‘wrong’. Findings were arranged into key thematic areas that emerged in the data relating to blame for teenage pregnancy: the individual centred ‘wrong-girl’ and developmental discourses, in which blame was apportioned to AGYW for being immature, reckless, irresponsible, disobedient and greedy; the ‘wrong-family’ discourse in which blame was attributed to parents of AGYW for poor parenting and failing to adequately care for the adolescents in their responsibility; the ‘wrong-men’ discourse in which blame was attributed to men for luring AGYW into transactional sex, and for perpetrating gender-based violence; and lastly the ‘wrong-society’ discourse which attributed blame to contextual/structural factors such as poverty, a high volume of unregulated drinking establishments, and a lack of youth-friendly services. CONCLUSIONS : Policies, interventions and programmes focusing on adolescents’ sexual and reproductive health need to carefully consider the framing and narratives of blame and responsibility. There is an urgent need to shift away from the individualised moralistic shaming of pregnant AGYW, towards a recognition of a complex interplay of multilevel factors that enable or constrain AGYW’s agency. Policies and programmes should focus on both providing sufficient support to AGYW, while also addressing structural factors and harmful narratives and thus create the conditions necessary to enable AGYW to enact safe, informed, agentic and responsible decisions and behaviours about their own sexual and reproductive health.
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    Sodium, potassium-adenosine triphosphatase as a potential target of the anti-tuberculosis agents, clofazimine and bedaquiline
    (MDPI, 2024-12-04) Mmakola, Khomotso Madimetsa Shelboy; Balmith, Marissa [; Steel, Helen C.; Said, Mohamed; Potjo, Moliehi; Van der Mescht, Mieke Adri; Hlatshwayo, Nomsa; Meyer, Pieter Willem Adriaan; Tintinger, Gregory Ronald; Anderson, Ronald; Cholo, Moloko C.
    Multidrug-resistant tuberculosis (MDR-TB) patients are treated with a standardised, short World Health Organization (WHO) regimen which includes clofazimine (CFZ) and bedaquiline (BDQ) antibiotics. These two antibiotics lead to the development of QT prolongation in patients, inhibiting potassium (K+) uptake by targeting the voltage-gated K+ (Kv)11.1 (hERG) channel of the cardiomyocytes (CMs). However, the involvement of these antibiotics to regulate other K+ transporters of the CMs, as potential mechanisms of QT prolongation, has not been explored. This study determined the effects of CFZ and BDQ on sodium, potassium–adenosine triphosphatase (Na+,K+-ATPase) activity of CMs using rat cardiomyocytes (RCMs). These cells were treated with varying concentrations of CFZ and BDQ individually and in combination (1.25–5 mg/L). Thereafter, Na+,K+-ATPase activity was determined, followed by intracellular adenosine triphosphate (ATP) quantification and cellular viability determination. Furthermore, molecular docking of antibiotics with Na+,K+-ATPase was determined. Both antibiotics demonstrated dose–response inhibition of Na+,K+-ATPase activity of the RCMs. The greatest inhibition was demonstrated by combinations of CFZ and BDQ, followed by BDQ alone and, lastly, CFZ. Neither antibiotic, either individually or in combination, demonstrated cytotoxicity. Molecular docking revealed an interaction of both antibiotics with Na+,K+-ATPase, with BDQ showing higher protein-binding affinity than CFZ. The inhibitory effects of CFZ and BDQ, individually and in combination, on the activity of Na+,K+-ATPase pump of the RCMs highlight the existence of additional mechanisms of QT prolongation by these antibiotics.
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    T-cell phenotypes and systemic cytokine profiles of people living with HIV admitted to hospital with COVID-19
    (MDPI, 2024-11) Van der Mescht, Mieke Adri; Steel, Helen C.; De Beer, Zelda; Masenge, Andries; Abdullah, Fareed; Ueckermann, Veronica; Anderson, Ronald; Rossouw, Theresa M.; theresa.rossouw@up.ac.za
    Whether SARS-CoV-2 infection leads to a higher mortality and morbidity in people living with HIV (PLWH) in Africa remains inconclusive. In this study, we explored the differences in the T-cell phenotypes between people with and without HIV on the day of admission (V1) and ±7 days later (V2), as well as their cytokine/chemokine profiles on V1. Patients admitted with COVID-19 were recruited between May 2020 and December 2021 from the Steve Biko Academic and Tshwane District Hospitals in Pretoria, South Africa. Of 174 patients, 37 (21%) were PLWH. T-cell profiles were determined by flow cytometry, and cytokine levels were determined using a multiplex suspension bead array. PLWH were significantly younger than those without HIV, and were more likely to be female. In an adjusted analysis, PLWH had higher percentages of CD4+ central memory (CM) programmed cell death protein 1 (PD-1)+, CD8+ effector memory (EM)2, and CD8+ EM4 CD57+ cells, as well as higher concentrations of interleukin (IL)-35 at admission. PLWH with CD4+ T-cell counts of >200 cells/mm3 had altered CD4+ and CD8+ T-cell profiles, lower levels of systemic inflammation measured by plasma ferritin and PCT levels, and less severe disease. PLWH with CD4+ T-cell counts of <200 cells/mm3 on admission had higher concentrations of IL-6 and lower levels of IL-29. At V2, the percentages of CD4+ CM PD-1+ T-cells and CD8+ EM4 T-cells co-expressing CD57 and PD-1 remained higher in PLWH, while all other CD8+ EM populations were lower. Fewer CD8+ EM T-cells after ±7 days of admission may be indicative of mechanisms inhibiting EM T-cell survival, as indicated by the higher expression of IL-35 and the T-cell maturation arrest observed in PLWH. This profile was not observed in PLWH with severe immunodeficiency, highlighting the need for differentiated care in the broader PLWH population.
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    Individualized nutritional therapy in a patient with chronic critical illness
    (Elsevier, 2024-12) Ueckermann, Veronica; Francis, Engela; Veronica.ueckermann@up.ac.za
    No abstract available.
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    The evolving science on sudden cardiac death—the marriage of left ventricular hypertrophy and QT-dispersion
    (Wiley, 2024-11) Ker, James A.
    The first description of sudden cardiac death was made by Hippocrates in the 4‘th century BC1. Such cases of sudden collapse and death has intrigued both the public and medical science for centuries and a practical definition is that sudden cardiac death is the unexpected and natural death from a cardiac cause within a short period of time, usually less than 1 hour from the onset of symptoms, in a person without any known prior condition1,2. Sudden cardiac death (SCD) is clearly the end-result of a wide variety of cardiac conditions—both congenital and acquired. However, the most common mechanism for the event of SCD is ventricular fibrillation1. However this is an evolving field of study and the recent study published by Stojanovic et al3 is of great importance as it links two well known risk factors for SCD—left ventricular hypertrophy (LVH) and QT-dispersion4. The finding by Stojanovic et al3 that septal thickness in both athletes and sedentary men are associated with increased QTd is concerning and future studies need to clarify if we need to keep the septum thin at all costs with more exercise for some and less for others.
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    I will find the best method that will work for me : navigating contraceptive journeys amongst South African adolescent girls and young women
    (BioMed Central, 2024-08) Duby, Zoe; Bergh, Kate; Bunce, Brittany; Jonas, Kim; Slingers, Nevilene; Mathews, Catherine; Abdullah, Fareed
    BACKGROUND: Given that South Africa has one of the highest rates of pregnancy amongst adolescent girls and young women (AGYW) globally, the provision of contraceptives to this group has been a key focus in recent years. Pregnancy prevention involves an on-going continuum of decision-making around contraceptive method choice, uptake, use, experience, continuation, and discontinuation. METHODS: This paper presents analysis of data from a cross-sectional survey with 2376 AGYW, as well as qualitative in-depth interviews (IDIs) with 54 AGYW, inclusive of contraceptive journey narratives. We examine the preferences, valued characteristics, choices, beliefs, understandings and experiences of choosing and using contraceptives amongst AGYW in two South African communities characterised by high rates of pregnancy. RESULTS: These findings shed light on the preferences towards, beliefs about, and experiences of choosing, using and discontinuing contraceptive methods amongst this population, with survey data suggesting that the most popular methods were the injection, followed by the implant, and then the oral pill. Findings illustrate the complexity and dynamic nature of contraceptive decision-making and the varied embodied and lived experiences of contraceptive use, and how these are impacted by contraception service provision. CONCLUSIONS: Our findings show that contraception experiences of each individual are cumulative, and comprise a continuum of method initiation, use, discontinuation, method switching and on-going circular decision-making influenced by multiple social, structural, contextual and interpersonal factors, combined with shifting preferences, values and needs. To maximise the use of contraceptives amongst South African AGYW, it is necessary to provide responsive contraception service provision to reflect the changing contexts and preferences of users, in order to ensure that pregnancy prevention needs are catered for throughout their reproductive life course.
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    Mystical myositis : a case series from Kalafong Provincial Tertiary Hospital, Pretoria, South Africa
    (Wiley, 2024-08) Myburgh, Michael; michael.myburgh@up.ac.za
    Idiopathic inflammatory myositis (IIM) is an expanding field in rheumatology as more myositis-specific antibodies (MSAs) and myositis-associated antibodies (MAAs) become available for testing. Clinical signs and specific clinical phenotypes are found in the MSA group, with as high as 70% of IIM patients having a positive myositis-specific antibody. Although IIM remains a heterogenous disease, assigning a phenotype to these patients will prove to be critical as we learn which cases require more aggressive therapy and what complications to search for as the disease progresses. The IIM patients for the last 5 years were reviewed and profiled using recently available myositis profile testing at our National Health Laboratory Services. Patients from our rheumatology clinic were categorized according to this antibody profile. Three cases diagnosed with dermatomyositis (DM) were selected for discussion in this article which include a patient with each of the following: anti-transcriptional intermediary factor 1-y (TIF1y) DM, anti-melanoma differentiation-associated protein 5 (MDA 5) DM, and anti-signal recognition particle (SRP) DM.
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    Angiogenesis and pancreatic cancer : novel approaches to overcome treatment resistance
    (Bentham Science Publishers, 2024-01) Grobbelaar, C.W. (Craig); Kgomo, Mpho K.; Mabeta, Peaceful Lucy; peace.mabeta@up.ac.za
    Pancreatic cancer (PCa) is acknowledged as a significant contributor to global cancer- related mortality and is widely recognized as one of the most challenging malignant diseases to treat. Pancreatic ductal adenocarcinoma (PDAC), which is the most common type of PCa, is highly aggressive and is mostly incurable. The poor prognosis of this neoplasm is exacerbated by the prevalence of angiogenic molecules, which contribute to stromal stiffness and immune escape. PDAC overexpresses various proangiogenic proteins, including vascular endothelial growth factor (VEGF)-A, and the levels of these molecules correlate with poor prognosis and treatment resistance. Moreover, VEGF-targeting anti-angiogenesis treatments are associated with the onset of resistance due to the development of hypoxia, which in turn induces the production of angiogenic molecules. Furthermore, excessive angiogenesis is one of the hallmarks of the second most common form of PCa, namely, pancreatic neuroendocrine tumor (PNET). In this review, the role of angiogenesis regulators in promoting disease progression in PCa, and the impact of these molecules on resistance to gemcitabine and various therapies against PCa are discussed. Finally, the use of anti-angiogenic agents in combination with chemotherapy and other targeted therapeutic molecules is discussed as a novel solution to overcome current treatment limitations in PCa.
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    Anti-melanoma differentiation associated gene 5 (MDA 5) dermatomyositis complicated by spontaneous pneumomediastinum : a case report from South Africa
    (Wiley, 2024-11) Myburgh, Michael; michael.myburgh@up.ac.za
    Spontaneous pneumomediastinum is a rare complication in anti–melanoma differentiation associated gene 5 (MDA 5) dermatomyositis (DM). In this case, it occurred relatively early in the course of this patient's illness before established interstitial lung disease was present; hence, it should be investigated in any anti-MDA 5 DM patient with dyspnea or chest pain.
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    Landscape of esophageal cancer in Northern Kenya : experience from Garissa Regional Cancer Center
    (eCancer Global Foundation, 2024-04) Abdihamid, Omar; Abdourahman, Houda; Ibrahim, Abdulsadiq; Kareu, Thinwa; Hadi, Abdullahi; Omar, Abeid; Mutebi, Miriam
    INTRODUCTION : Esophageal cancer (EC) is the ninth most common cancer and the sixth leading cause of cancer deaths worldwide. More than 80% of cases and deaths from EC occur within developing countries. In Kenya, cancer is the second leading cause of non-communicable disease deaths, and the trend of cancer deaths is projected to increase as per the 2020 GLOBOCAN report showing 42,116 new cases annually with a mortality of 27,092 cases. EC is the leading cancer in men and the third most common in women in Kenya. The Garissa Regional Cancer Center (GRCC) is one of the three regional cancer centres in Kenya. Despite the rising EC incidence in the region, there is limited data about the clinicopathological features and treatment outcomes of EC, therefore, this is the first study to look at the landscape of EC in the northern Kenya region. METHODS : This was a retrospective study involving patients’ file review of confirmed EC cases diagnosed or treated at the GRCC from 2019 to 2023. Data collected from each patient’s chart included age, sex, risk factors, family history of EC, histological type, stage at diagnosis, treatment type and survival outcomes. For patients who were no longer in contact with the staff through clinic visits, the patients or their next of kin were contacted through phone calls for patients’ survival status. Data were collected and stored using the STATA software. RESULTS : Over the study period, 124 esophageal cases were identified, 64 (51.4%) were males and 60 (48.4%) were females with a mean age of 57.56 years. In terms of risk factors, hot beverage consumption was the highest (47 cases, 37.9%), followed by history of peptic ulcer disease (27 cases, 21.8%), smoking (8.9%) and gastresophageal reflux disease (2 cases, 1.6%). Stage of diagnosis at presentation was stage 1 (1 case, 0.8%), stage 2 (22 cases, 17.8%), stage 3 (25 cases, 20.2%), stage 4 (50 cases, 40.3%), not staged (26 cases, 21%). The majority had squamous cell carcinoma (SCC) (105 cases, 84.7%), followed by adenocarcinoma (5 cases, 4%), anaplastic (5 cases, 4%), SCC+ adenocarcinoma (1 case, 0.8%), unknown histology (8 cases, 3.2%). Nearly all patients had triple assessment (Endoscopy, histology and staging scans) accounting for 92 cases (74.2%), 24 cases (20%) had endoscopy+ histology only, and 8 cases (3.2%) had only imaging scans. In terms of family history of EC, 20 cases (16.1%) had a family history of EC. Most of the patients were of ethnic Kenyan-Somali background (108 cases, Kenyan Somali, 87.1%) and majority were from Garissa County 96 cases (77.4%), 12 cases (9.7%) Wajir County, 12 cases (9.7%) from Tana River County and 4 cases (3.2%) from other counties. Many patients lacked health insurance (27 cases, 25.8%), while the majority paid out of pocket (92 cases,74.1%). Only 21% (26 cases) received chemotherapy alone, 5 cases (4%) got radiotherapy alone, 12.9% (16 cases) got chemoradiotherapy and a significant number of patients (77 cases, 62.1%) did not receive hospital-based cancer treatment. CONCLUSION : This study is the first esophageal study at the GRCC and in northern Kenya in general. Our study confirmed the clinicopathological features of one of the most common cancers in Kenya and more so among Kenyan-Somalis. The study also validates the predominance of histological subtypes of esophageal SCC with the late presentation, short survival and significant loss of follow-up. We recommend future EC studies employing a large prospective design with a large sample size to determine the impact of the new GRCC on the outcomes of EC patients and the local community.
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    Feasibility of provision and vaccine hesitancy at a central hospital COVID-19 vaccination site in South Africa after four waves of the pandemic
    (MDPI, 2024-06) Nair, Shanal; Tshabalala, Khanyisile; Slingers, Nevilene; Vanleeuw, Lieve; Basu, Debashis; Abdullah, Fareed; shanal.nair@up.ac.za
    BACKGROUND : As mortality declined significantly during the fourth and fifth waves compared to previous waves, the question of the future role of COVID-19 vaccination arose among both experts and the public in South Africa. Turning attention away from the general public, now considered to be at very low risk of severe COVID-19 disease, a commonly held view was that the vaccination campaign should focus only on those who remain highly vulnerable to severe disease and death from COVID-19. Primary amongst this group are patients with common chronic diseases attending hospital outpatient departments. We hypothesized that providing COVID-19 vaccinations on-site at a central hospital will increase uptake for the patients with co-morbid chronic conditions who need them most in the Omicron phase of the pandemic. AIM : Evaluate the acceptability, need, and uptake of a hospital-based vaccination site for patients attending the medical hospital outpatient departments. OBJECTIVES : To assess vaccination uptake, coverage, and hesitancy in people attending a central hospital, to determine factors associated with and influencing vaccination uptake, and to document implementation and assess acceptability of the vaccination project among staff and persons attending the hospital. METHODS : Mixed-methods study using quantitative and qualitative methods. RESULTS : Of the 317 participants enrolled in the study, 229 (72%) had already received at least one dose of the COVID-19 vaccine. A total of 296 participants were eligible for a first vaccination, additional vaccination, or booster vaccination according to the South African Department of Health guidelines. Of those previously vaccinated, 65% opted for an additional dose on the day it was offered (same day). Only 13 previously unvaccinated participants (15% of vaccine naïve participants) opted for vaccination, increasing vaccine coverage with at least one dose from 72% to 76%. Approximately 24% (n = 75) of all participants refused vaccination (vaccine hesitant). Variables tested for an association with vaccination status demonstrated that age reached statistical significance. Emerging themes in the qualitative analysis included perceptions of vulnerability, vaccine safety and efficacy concerns, information gaps regarding vaccinations, the value of convenience in the decision to vaccinate, and the role of health promoters. CONCLUSIONS : This study has shown that it is logistically acceptable to provide a vaccination site at a large hospital targeting patients attending outpatient services for chronic medical conditions. This service also benefits accompanying persons and hospital staff. Access and convenience of the vaccination site influence decision-making, increasing the opportunity to vaccinate. However, vaccine hesitancy is widespread with just under one-quarter of all those offered vaccinations remaining unvaccinated. Strengthening health education and patient–clinician engagement about the benefits of vaccination is essential to reach highly vulnerable populations routinely attending hospital outpatient departments with an appropriate vaccination program.
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    The association of smoking and alcohol in colorectal cancer in black patients - case-control study
    (AOSIS, 2024-10) Kgomo, Mpho K.; Zingoni, Ratidzo L.; Becker, Piet J.; mpho.kgomo@up.ac.za
    BACKGROUND : Studies have focused on smoking and alcohol as risk factors for colorectal cancer (CRC). Caucasians and other populations have been studied worldwide, and both smoking and alcohol have been validated as causes of CRC. However, there are limited data on the black population; studies that have been performed in Africa have not specifically focused on these two risk factors but rather in combination with other risks. AIM : To determine how smoking and alcohol affect the incidence of CRC in the African black population. SETTING : Steve Biko Academic Hospital’s gastrointestinal clinic. METHODS : Subjects used for the study included black African patients above 18 years who had undergone a colonoscopy for suspected CRC between 2016 and 2018. Cases used were confirmed CRC on histology; controls were negative on histology. A minimum of 68 cases and 136 controls were needed for this study according to sample calculation. Hundred and ten cases and 220 controls were obtained in the final analysis. Data were collected between June 2019 and March 2020. RESULTS : Smoking (odds ratio [OR] = 1.795, p = 0.049) was a significant risk factor for CRC among black patients who presented at the gastrointestinal clinic. Age > 50 years (OR = 3.742, p < 0.001), family history (OR = 12.457, p < 0.001), and the combination of smoking and alcohol (OR = 5.927, p = 0.008) were significant risk factors. Interestingly, alcohol alone was protective (OR = 0.205, p < 0.001). CONCLUSION : Both smoking and a combination of alcohol and smoking are significant risk factors in the development of CRC in the black African population. Contribution: Smoking, as in most population groups, is a risk factor for CRC. The observed protective role of alcohol needs to be confirmed in larger studies representing the African population.
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    Cannabinoid hyperemesis syndrome
    (BMJ Publishing Group, 2024-04) Elnagar, Ali; Kgomo, Mpho K.; Mokone, Modise; Yousif, Badreldin
    Cannabis use is legalised in many countries. We present a patient in their 40s who complained of recurrent abdominal pain and associated nausea and vomiting. The patient was previously seen in various hospitals, treated symptomatically, and discharged with a diagnosis of non-specific abdominal pain. The patient had a chronic history of smoking cannabis and nicotine and drinking alcohol. Abdominal examination revealed no masses, and abdominal X-ray was normal. Blood tests and gastroduodenoscopy revealed no obvious aetiology. Intravenous fluids, together with antiemetics and proton pump inhibitors, were administered. The patient also received counselling and was advised to stop cannabis use. At discharge, the patient was well and asked to come back for review in 2 weeks, and, thereafter monthly for a period of 6 months after stopping cannabis use. The patient reported no recurrent symptoms despite continued cigarette and alcohol use. A suspected cannabinoid hyperemesis syndrome (CHS) became a consideration. Awareness of cannabis-related disorders such as CHS may assist in avoiding costly hospital workups.
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    Epidemiology and aetiology of moderate to severe diarrhoea in hospitalised patients ≥5 years old living with HIV in South Africa, 2018- 2021 : a case-control analysis
    (Public Library of Science, 2023-09-08) Johnstone, Siobhan; Erasmus, Linda; Thomas, Juno; Groome, Michelle J.; Du Plessis, Nicolette Marie; Avenant, Theunis Johannes; De Villiers, Maryke; Page, N.A. (Nicola)
    Diarrhoea is a recognised complication of HIV-infection, yet there are limited local aetiological data in this high-risk group. These data are important for informing public health interventions and updating diagnostic and treatment guidelines. This study aimed to determine the pathogenic causes of diarrhoeal admissions in people living with HIV (PLHIV) compared to hospital controls between July 2018 and November 2021. Admitted diarrhoeal cases (n = 243) and non-diarrhoeal hospital controls (n = 101) 5 years of age were enrolled at Kalafong, Mapulaneng and Matikwana hospitals. Stool specimens/rectal swabs were collected and pathogen screening was performed on multiple platforms. Differences in pathogen detections between cases and controls, stratified by HIV status, were investigated. The majority (n = 164, 67.5%) of enrolled diarrhoeal cases with known HIV status were HIVinfected. Pathogens could be detected in 66.3% (n = 228) of specimens, with significantly higher detection in cases compared to controls (72.8% versus 50.5%, p0.001). Amongst PLHIV, prevalence of Cystoisospora spp. was significantly higher in cases than controls (17.7% versus 0.0%, p = 0.028), while Schistosoma was detected more often in controls than cases (17.4% versus 2.4%, p = 0.009). Amongst the HIV-uninfected participants, prevalence of Shigella spp., Salmonella spp. and Helicobacter pylori was significantly higher in cases compared to controls (36.7% versus 12.0%, p = 0.002; 11.4% versus 0.0%, p = 0.012; 10.1% versus 0.0%, p = 0.023). Diarrhoeal aetiology differed by HIV status, with Shigella spp. (36.7%) and Salmonella spp. (11.4%) having the highest prevalence amongst HIV-uninfected cases and Shigella spp. (18.3%), Cystoisospora (17.7%), and Cryptosporidium spp. (15.9%) having the highest prevalence in cases amongst PLHIV. These differences should be considered for the development of diagnostic and treatment guidelines.
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    Adults living with type 2 diabetes experiences of a randomised adapted diabetes nutrition education programme : a qualitative process evaluation
    (NISC (Pty) Ltd and Informa UK Limited (trading as the Taylor & Francis Group), 2024) Muchiri, Jane Wanjiku; Gericke, Gerda J.; Rheeder, Paul; jane.muchiri@up.ac.za
    AIM : The purpose of this study was to investigate how a randomised controlled trial (RCT) of an adapted diabetes nutrition education programme (NEP) was received by adults with sub-optimally controlled (HbA1c of ≥ 8%) type 2 diabetes in a tertiary setting. This could aid in understanding the small effect of NEP on HbA1c and other outcomes and the high attrition rate. METHODS : This qualitative study was done alongside the year-long RCT. In the RCT, intervention participants received four NEP components, and both intervention and control group participants received education materials (fridge/wall poster). Five focus-group discussions were held with the intervention group participants at two time periods: after they completed the NEP curriculum (7th month) (n = 26; 67% of randomised participants [RP]( and at the end of the study (12 months) [n = 24; 61.5% RP). Nineteen (50% RP) control group participants were individually interviewed at the end of the study. Data were analysed using a thematic framework. RESULTS : All participants (control and intervention) reported high satisfaction with the NEP. Participants emphasised the value of the fridge/wall poster for themselves and their families. Participants (control and intervention) reported various benefits of the NEP: improved diabetes knowledge, skills in dietary self-care, family support for self-care, better health and motivation for appropriate self-care. Some participants also reported positive changes to their diet and physical activity behaviours. The perceived benefits were the main reason for completing the study. CONCLUSIONS : Irrespective of the arm of participation, the NEP was well received, and perceived benefits inspired participation. The limited NEP impact and the sub-optimal programme participation do not appear to be related to participants’ perceptions of the adapted NEP.
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    SARS-CoV-2 BA.4/5 infection triggers more cross-reactive FcγRIIIa signaling and neutralization than BA.1, in the context of hybrid immunity
    (American Society for Microbiology, 2024-07) Richardson, Simone I.; Mzindle, Nonkululeko; Motlou, Thopisang; Manamela, Nelia; Van der Mescht, Mieke Adri; Lambson, Bronwen E.; Everatt, Josie; Amoako, Daniel Gyamfi; Balla, Sashkia; Von Gottberg, Anne; Wolter, Nicole; De Beer, Zelda; De Villiers, Talita Roma; Bodenstein, Annie; Van den Berg, Gretha; Abdullah, Fareed; Rossouw, Theresa M.; Boswell, M.T.; Ueckermann, Veronica; Bhiman, Jinal N.; Moore, Penny L.
    SARS-CoV-2 variants of concern (VOCs) differentially trigger neutralizing and antibody-dependent cellular cytotoxic (ADCC) antibodies with variable cross-reactivity. Omicron BA.4/5 was approved for inclusion in bivalent vaccination boosters, and therefore the antigenic profile of antibodies elicited by this variant is critical to understand. Here, we investigate the ability of BA.4/5-elicited antibodies following the first documented (primary) infection (n = 13) or breakthrough infection after vaccination (n = 9) to mediate neutralization and FcγRIIIa signaling across multiple SARS-CoV-2 variants including XBB.1.5 and BQ.1. Using a pseudovirus neutralization assay and a FcγRIIIa crosslinking assay to measure ADCC potential, we show that unlike SARS-CoV-2 Omicron BA.1, BA.4/5 infection triggers highly cross-reactive functional antibodies. Cross-reactivity was observed both in the absence of prior vaccination and in breakthrough infections following vaccination. However, BQ.1 and XBB.1.5 neutralization and FcγRIIIa signaling were significantly compromised compared to other VOCs, regardless of prior vaccination status. BA.4/5 triggered FcγRIIIa signaling was significantly more resilient against VOCs (<10-fold decrease in magnitude) compared to neutralization (10- to 100-fold decrease). Overall, this study shows that BA.4/5 triggered antibodies are highly cross-reactive compared to those triggered by other variants. Although this is consistent with enhanced neutralization and FcγRIIIa signaling breadth of BA.4/5 vaccine boosters, the reduced activity against XBB.1.5 supports the need to update vaccines with XBB sublineage immunogens to provide adequate coverage of these highly antibody evasive variants. IMPORTANCE : The continued evolution of SARS-CoV-2 has resulted in a number of variants of concern. Of these, the Omicron sublineage is the most immune evasive. Within Omicron, the BA.4/5 sublineage drove the fifth wave of infection in South Africa prior to becoming the dominant variant globally. As a result this spike sequence was approved as part of a bivalent vaccine booster, and rolled out worldwide. We aimed to understand the cross-reactivity of neutralizing and Fc mediated cytotoxic functions elicited by BA.4/5 infection following infection or breakthrough infection. We find that, in contrast to BA.1 which triggered fairly strain-specific antibodies, BA.4/5 triggered antibodies that are highly cross-reactive for neutralization and antibody-dependent cellular cytotoxicity potential. Despite this cross-reactivity, these antibodies are compromised against highly resistant variants such as XBB.1.5 and BQ.1. This suggests that next-generation vaccines will require XBB sublineage immunogens in order to protect against these evasive variants.