Masters Degrees (Medical Science)

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Tissue and systemic dipeptidyl peptidase 4 and glucose homeostatic responses in a dietinduced prediabetic rat model.
(2025) Shange, Anele.; Khathi, Andile.; Mzimela, Nomusa Christina.
Background Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycaemia, resulting from impaired insulin action, insulin secretion, or both. Type-2-diabetes mellitus (T2DM) is the most common occurring form of DM accounting for 90% of all cases. Various enzymes including dipeptidyl peptidase-4 (DPP-4), an enzyme found in various tissues including plasma (sDPP-4) that primarily degrades incretin hormones such as GLP-1 and GIP that stimulate insulin secretion and inhibit glucagon release and are dysregulated during T2DM. The onset of T2DM is often preceded by a condition called prediabetes whereby blood glucose levels are elevated but not high enough to be diagnosed as T2DM. However, there is a lack of studies that have documented DPP-4 expression in tissues as well as sDPP-4 concentrations during the prediabetic state and how these may influence glucose homeostasis. Therefore, this study investigated the changes in tissue and plasma DPP-4 expression in a diet-induced prediabetic rat model and examined how these changes influence glucose homeostasis. Materials and Methods Twelve male Sprague Dawley rats were randomly allocated into two equal groups (n=6 each). Experimental prediabetes was induced in the animals using a previously reported protocol. The first group (A) was fed a standard rat chow and supplied with tap water. The second group (B), group was fed high-fat high-carbohydrate (HFHC) diet supplemented with 15% fructose for 20 weeks to induce prediabetes. At the end of the 20-week induction period, the American Diabetes Association (ADA) criteria were used to confirm prediabetes. At the end of the induction period, the animals were then sacrificed, and ELISA was used to measure plasma sDPP-4, insulin, GLP-1, ghrelin and leptin in both groups. Furthermore, quantitative PCR was used to measure DPP-4 gene expression in tissues including the kidney, lungs and liver. Fold change in gene expression was calculated using the 2-ΔΔCt method. Results and Discussion The induction of prediabetes in the HFHC-diet fed group resulted in increased blood glucose and HbA1c levels by comparison to the non-prediabetic group. This was accompanied by increased plasma sDPP-4, insulin, ghrelin and leptin levels in the PD group by comparison to the NPD group. There was also decreased plasma GLP-1 in the PD group by comparison to the NPD group. The increased insulin, glucose and HbA1c levels reflect insulin resistance and disrupted glucose regulation. The elevated sDPP-4 and decreased plasma GLP-1 levels indicate impaired incretin signalling. Additionally, the rise in ghrelin and leptin suggest hormonal imbalance contributing to metabolic dysregulation. Furthermore, the results showed increased DPP-4 expression in the kidney, whereas reduced expression was observed in the liver and lungs. These findings suggest that DPP-4 is regulated in a tissue-specific manner during the prediabetic state. The upregulation in the kidney may indicate a compensatory or pathological role in renal glucose handling or inflammation, while the downregulation in the liver and lungs could reflect altered metabolic or immune responses. Overall, this differential expression pattern points to a complex, tissue-dependent role of DPP-4 in the early stages of metabolic dysregulation. Conclusion Taken together, the results of the present study suggest a complex disruption of glucose homeostasis and hormonal signalling. The reduced plasma GLP-1 levels in the presence of elevated sDPP-4 suggest enhanced incretin degradation, which may impair insulin secretion and contribute to hyperglycaemia. Furthermore, the results suggest that DPP-4 expression varies between tissues and is differently regulated during the prediabetic state. Increased expression in the kidney, along with decreased levels in the liver and lungs, indicates that DPP-4 may have distinct, tissue-dependent roles in metabolic regulation and disease development. The observed metabolic and hormonal disturbances highlight the role of DPP-4 in impairing glucose homeostasis during the prediabetic state.
Role of c-reactive protein response to antibiotic therapy in children with a ventriculo-peritoneal shunt infection.
(2026) Rampershad, Kiara.; Msibi, Zama Ndlondlo Princess.; Enicker, Basil Claude.
Hydrocephalus is a common neurosurgical condition in children, with a higher incidence in low and middle-income countries (LMIC). Ventriculoperitoneal (VP) shunt insertion remains the primary treatment, but postoperative infections are a major source of morbidity, leading to repeated surgeries and increased mortality. C-reactive protein (CRP) is a rapid, sensitive marker of inflammation that rises within hours of infection and declines quickly with effective treatment and correlates with bacterial burden. This makes it a practical, low-cost tool for monitoring VP shunt infections and determining the appropriate duration of antibiotic therapy in children. This study aims to evaluate whether CRP trends correlate with clinical improvement and can inform decisions regarding antibiotic treatment length. A total of 147 patients diagnosed with meningitis secondary to a VP shunt infection, from January 2018 to December 2024, were included in this retrospective study conducted at Inkosi Albert Luthuli Central Hospital (IALCH). Clinical presentation, serology results, and culture results were obtained and analysed. Of the 147 children included, more than half were infants (51.7%), presenting with the lowest mean CRP on admission (34.7 mg/L) and congenital hydrocephalus (48.3%). CRP levels were elevated at admission (mean 48.6 mg/L), peaked by day 3-5, and declined gradually to 29.4 mg/L by day 30, with a significant reduction from admission (p = 0.02). Staphylococcus epidermidis (25.9%) and Staphylococcus aureus (21.1%) were the most common organisms, with 58.6% showing antimicrobial resistance. Vancomycin (n = 41; 27.9%) was the most frequently used antibiotic, and mean treatment duration was 27 days, which aligned with a decrease in CRP at day 30. Persistent CRP elevation with no clear infection resolutions was associated with resistant organisms and a complicated infection. CRP is a valuable marker for monitoring treatment response in paediatric VP shunt infections, showcasing a decline with clinical improvement. However, its variability, particularly in infants and resistant infections, limits its use as the sole guide for antibiotic duration. The integration of CRP with clinical indicators, microbiological data, and shunt-related decision-making enhances therapy and supports better paediatric outcomes.
Repositioning FDA-approved drugs to identify potential mycobacterial FadD23 inhibitors.
(2025) Pillay, Chitra Dipika.; Mhlongo, Ndumiso Nhlakanipho.
Tuberculosis (TB) is a respiratory disease caused by Mycobacterium tuberculosis (M. tuberculosis). The high transmission and mortality rates show that the medical and scientific community need new strategies to combat the TB burden. One strategy would be repurposing drugs which have already been Food and Drug Administration (FDA)-approved to aid in discovery of potential inhibitors against novel TB drug targets. This project aimed to identify a potential inhibitor of FadD23 through in silico screening of FDA-approved drugs against the FadD23 protein structure. Ligand structures were retrieved from the ZINC database and docked into FadD23 using AutoDock Vina. Simeprevir had the highest docking score (-10.5 kcal/mol), and was further subjected to 600 ns molecular dynamics (MD) simulations using Amber 18, with Phosphoaminophosphonic acid-adenylate (ANP) used as a control ligand. Post-MD analysis namely root mean square deviation (RMSD), root mean square fluctuations (RMSF), hydrogen bond (Hbond), radius of gyration (Rg), dynamic secondary structure elements (SSE), and distances were calculated using a CPPTRAJ module. Binding affinities of ligands were calculated using MM/GBSA module. The results of RMSD showed that Simeprevir (2.23 Å) was stable during simulations, where its bulky hydrophobic conformation governed complex stability. This was also supported by the compact conformation of FadD23 structure induced by Simeprevir. Simeprevir also had a higher binding affinity (-33.87 kcal/mol) compared to ANP (-17.95 kcal/mol), where its binding affinity was driven by electrostatic and van der Waals forces. Energy contributions from Thr177, Thr176, Arg555, Ala179, Lys553, and Arg460 notably influenced Simeprevir’s binding affinity. RMSF suggested that Simeprevir made contact with both the N- and C-terminal domains of FadD23, where it suppressed residue displacement in the N-terminal domain and induced notable residue displacement in the C-terminal domain. SSE analysis showed that Simeprevir potentially arrests FadD23 function by altering native secondary structure elements. At present, there’s no reported drug that has been approved by the FDA against FadD23, nor existence of records showing clinical studies of potential inhibitors of FadD23. Compound 5’-O-[N-(11-phenoxyundecanoyl) sulfamoyl] adenosine (Phu-Ams) was reported to be a general inhibitor of FadD enzymes; however, its interaction with FadD23 did not involve the C-terminal domain. This differs from Simeprevir, where it was noted to form interactions with residues in the C-terminal domain, a domain that is responsible for substrate catalysis. The analysis based on molecular docking, MD simulations and subsequent post-MD trajectory analysis suggest that Simeprevir may be able to serve as a potential inhibitor of FadD23, thus potentially interferes with SL-1 production in M. tuberculosis.
The impact of low-dose aspirin on haemoglobin levels during pregnancy.
(2026) Ngcobo, Nokwethemba Monica.; Dorsamy, Vinogrin.; Bagwandeen, Chauntelle Ingrid.
Background: Low-dose aspirin, initiated between 12 and 28 weeks of gestation, is recommended for the prevention of preeclampsia, a major hypertensive complication of pregnancy. However, its influence on maternal haemoglobin levels—and its possible role in modifying anaemia risk, remains unclear. Anaemia continues to pose a significant burden in maternal health, contributing to increased morbidity and mortality. Aim: This study investigated the effect of low-dose aspirin on maternal haemoglobin levels and explored the association between haemoglobin changes and hypertensive disorders of pregnancy. Methods: This secondary analysis included 249 pregnant women selected from a larger randomised controlled trial, in which participants were randomised to receive 162 mg low-dose aspirin daily or standard care. Haemoglobin levels at enrolment were retrieved from trial records, while haemoglobin measurements at birth were extracted retrospectively from hospital maternity charts and the National Health Laboratory Service. Maternal outcomes, including hypertensive disorders of pregnancy, were analysed in relation to haemoglobin changes. Result: Of the total participants, 111 showed a decline in haemoglobin levels from enrolment to birth, while 138 demonstrated an increase. Repeated measures analysis of variance revealed a significant group-by-time interaction (p = 0.002, η² = 0.088) amongst those with declining haemoglobin. Participants in the low-dose aspirin group experienced a smaller decrease in haemoglobin (ΔHb = -0.902 g/dL) compared to the control group (ΔHb = -1.405 g/dL). Furthermore, a decline in haemoglobin was associated with higher odds of developing hypertensive disorders of pregnancy (odds ratio = 2.21 vs 0.45, p = 0.021). Within this subgroup, those receiving low-dose aspirin had a 76% lower risk of hypertensive disorders of pregnancy (relative risk = 0.24, 95% confidence interval [0.11–0.53], p < 0.001). Conclusion: Low-dose aspirin attenuated the decline in maternal haemoglobin levels, suggesting a novel haematological benefit beyond preeclampsia prevention. This therapeutic agent may offer value for integration into public health strategies aimed at improving maternal and fetal outcomes—particularly in low to middle-income countries, where anaemia is prevalent. A reduction in haemoglobin levels may also serve as an early predictor of hypertensive disorders of pregnancy.
The Effect of the 14:10-Hour Time-Restricted Feeding Regimen on Selected Markers of Glucose Homeostasis in Diet-Induced Prediabetic Male Sprague Dawley Rats.
(2025) Msane, Sthembiso Snegugu.; Khathi, Andile.; Sosibo, Aubrey Mbulelo.
Background Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by persistent high blood glucose levels due to either impaired insulin secretion, reduced insulin sensitivity, or a combination of both. It is strongly linked to insulin resistance, leptin resistance, obesity, elevated fasting glucose levels, and glucose intolerance. The global incidence of T2DM is increasing rapidly, currently affecting approximately 500 million people worldwide. Projections indicate a 25% rise by 2030 and a 51% increase by 2045. Management of T2DM typically involves pharmacological interventions, such as metformin, combined with lifestyle changes, including enhanced physical activity and dietary modifications. However, poor patient adherence to these approaches often compromises their effectiveness, underscoring the need for alternative treatment options. Recently, intermittent fasting (IF) has garnered interest as a potential management strategy for T2DM. The IF protocols alternate between periods of eating and fasting, which may involve caloric restriction or complete fasting during the fasting phases. The duration and structure of fasting and eating windows differ across various IF regimens, including the 5:2 diet, alternate-day fasting, and time-restricted feeding (TRF). In TRF, individuals typically fast for 14 hours followed by a 10-hour eating window (14:10) or a 16-hour fasting period with an 8-hour eating window (16:8). Studies have demonstrated that the 14:10 TRF regimen effectively reduces body weight, leptin resistance, glucose intolerance, insulin resistance, and blood glucose levels in individuals with T2DM. While the positive effects of 14:10 TRF on T2DM are well-established, its impact on glycemic control during the prediabetic stage remains to be studied. Materials and Methods Twenty-four male (120g to 180g) Sprague Dawley rats were obtained and randomly divided into two dietary groups: Group 1 (n=6) received a standard diet and water. In contrast, group 2 (n=18) was provided a high-fat, high-carbohydrate (HFHC) diet supplemented with 15% fructose for 20 weeks to induce prediabetes. After confirming prediabetes, an additional 12 weeks of treatment took place during which an intermittent fasting (IF) regimen was assigned to the rats while also having untreated and metformin-treated prediabetic rats serving as controls. The IF regimen assigned in this study is TRF where Sprague Dawley rats were exposed to fasting for 14 hours, then had a 10-hour window to eat (14:10). Every 4 weeks during the treatment period, body weight, calorie intake, oral glucose response, and fasting glucose were measured for all groups. Following study termination after 12 weeks of treatment, organs such as the skeletal muscle and the liver were harvested from the animals along with blood. Glycogen concentrations were measured in the liver and skeletal muscle tissues. Additionally, the expression levels of insulin receptor substrate 1 (IRS1), insulin receptor substrate 2 (IRS2), protein kinase A (Akt), Phosphoinositide 3-Kinase (PI3K), and Mechanistic Target of Rapamycin Complex 1 (mTORC1) were assessed in liver tissue, while glucose transporter 4 (GLUT4). Moreover, plasma was extracted to assess fasting insulin and leptin concentrations and computed as well as determined Homeostatic Model Assessment of Insulin Resistance (HOMA-IR).
The effects of Zingiber officinale (ginger) extract on inflammation, innate immune system, haematological factors and cardiovascular diseases in diet-induced prediabetic rats.
(2025) Langa, Bonakele.; Mabuza-Mashaba, Lindokuhle Patience.; Khathi, Andile.
Prediabetes, characterized by intermediate hyperglycemia, is frequently accompanied by chronic inflammation, disrupted haematological profiles, and an elevated risk of progressing to type 2 diabetes mellitus (T2DM) and cardiovascular disease. This study examines the effects of Zingiber officinale (ginger) extract on inflammation, innate immune system, haematological parameters and cardiovascular complications in diet-induced prediabetic rats. Thirty-six (36) male Sprague Dawley rats were divided into six groups (n=6 per group) and were induced with prediabetes using high carbohydrate for a period of 20 weeks. After induction, the groups were treated as follows for a period of 12 weeks: a prediabetic (PD) control; a dietary intervention (DI) control; Zingiber officinale treatment groups in the presence (ZO+DI) and absence [ZO+HFHC] of DI; as well as metformin in the presence (MT+DI) and absence (MT+HFHC) of DI. An additional six animals were kept on a standard diet and served as a non-prediabetic control (NPD). At the end of the treatment period, parameters measured included homeostatic model assessment index (HOMA-IR), body weight, anti-inflammatory cytokine (adiponectin), pro-inflammatory cytokines (TNF α, IL-6 and CRP), neutrophils cell count, MDA levels, nuclear factor erythroid 2-related factor 2 (NFE2L2). As well as fasting blood glucose (FBG), oral glucose tolerance test (OGTT), glycated haemoglobin (HbA1c), triglycerides (TG), heart-to-body weight ratio, RBC and platelet indices, as well as mTOR and erythropoietin (EPO) expression. Treatment with Zingiber officinale significantly improved glucose tolerance and decreased HbA1c and triglyceride levels. It normalized RBC and platelet counts, aligning with previous findings where ginger ameliorated haematological disturbances in diabetic rats. Expression of mTOR and EPO was modulated, suggesting reduced inflammation and attenuated cardiovascular risk. Zingiber officinale also demonstrated cardioprotective benefits, echoing earlier studies showing structural recovery and improvement in cardiac biomarkers in prediabetic rat models. Zingiber officinale extract enhances glycaemic control, restores normal haematological function, and mitigates early cardiovascular complications in diet-induced prediabetic rats. These findings support its potential as a nutraceutical therapeutic to prevent progression from prediabetes to T2DM and related cardiovascular conditions.
Investigating antimicrobial resistance patterns in Gardnerella vaginalis isolates.
(2024) Durga, Thasmika.; Abbai, Nathlee Samantha.; Ngobese, Bongekile N.
Background: Bacterial vaginosis (BV) is gaining interest due to its problematic outcomes in women of reproductive age. Common symptoms are abnormal grey discharge that has a fishy odour accompanied by itchiness and pain. BV is characterized by the overall decrease in Lactobacilli and an increase in anaerobic facultative bacteria such as Gardnerella vaginalis. G. vaginalis is said to be the main species of bacteria involved in BV and is responsible for its pathogenicity. G. vaginalis has many virulence factors (formation of biofilms, mucus degrading sialidase and the production of the protein toxin, vaginolysin) that influence its pathogenicity, aiding in establishing infection. Treatment of BV includes the use of broad spectrum antibiotics such as metronidazole and clindamycin, which can be administered orally or in the form of an ointment. However, in clinical settings, antimicrobial resistance has increased due to resistant bacteria left behind after initial treatment, resulting in recurrent BV. The aim of the current study was to determine the susceptibility patterns of isolates of G. vaginalis to various antibiotics. This study also investigated the genetic diversity of isolates and linked genetic data with antimicrobial resistance patterns. attending care at the antenatal clinic at the King Edward VIII hospital in Durban, KwaZulu-Natal, South Africa. A total of 150 pregnant women, 18 years and older, who were willing to provide written informed consent and willing to provide two self-collected vaginal swabs were enrolled in this study. Following sample collection, the first swab was placed in Amies transport media (Copan, Brescia, Italy) for the cultivation of G. vaginalis. The second swab was rolled onto a glass slide to diagnose BV by Nugent scoring on gram-stained vaginal smears. The genetic diversity assessments of the isolates were based on genetic differences in the tuf gene using clade specific primers on a quantitative polymerase chain reaction (PCR) platform. The antimicrobial susceptibility profiles were generated using the Sensititre™ Anaerobe MIC Plate (Thermo Fischer Scientific, United States). Results: Sixteen isolates of G. vaginalis were cultured from pregnant women. Of the 16 isolates, five isolates were obtained from BV positive women, nine from BV intermediate women, and two were from BV negative women. The 16S rRNA gene specific to G. vaginalis was amplified in all isolates, confirming the identity of the isolates. The genotyping/clade PCR revealed the presence of three clades. The frequencies for each clade were as follows; 100% for clade 1, 37.5% for clade 2 and 43.75% for clade 4. Multiple clades were found in 56.25% of the isolates. For antimicrobial susceptibility testing, only 14 isolates were viable for analysis. Of the 14 isolates that were successfully cultured and tested, 8/14 (57.1%) were susceptible to metronidazole (MIC of ≤8μg/ml) and 6/14 (42.9%) were resistant to metronidazole (MIC of ≥32μg/ml). Of the G. vaginalis isolates (n=5) cultured from BV positive women, 60% (3/5) of the isolates were susceptible to metronidazole whilst 40% (2/5) were resistant. There was no link between resistant patterns and infection symptoms, since one isolate was from an asymptomatic woman and the other isolate from a symptomatic woman. Of the G. vaginalis isolates (n=7) cultured from intermediate BV women, 43% (3/7) of the isolates were resistant to metronidazole while 57% (4/7) were susceptible. For intermediate women, there was a link between resistant patterns and infection symptoms, since all resistant isolates were cultured from symptomatic women. The G. vaginalis isolate cultured from the BV-negative women was susceptible to metronidazole and the woman was asymptomatic. Of the six resistant isolates, five isolates (83%) were assigned to clade 1 alone. The remaining resistant isolate was a mixed clade, it was assigned clade 1 and 4. The eight susceptible isolates belonged to mixed clades such as 1 and 2, 1, 2 and 4 and 1 and 4. The resistant isolates were more homogeneous in terms of the clades to which they belonged. However, it cannot be suggested that a particular clade is driving resistance since the clades were distributed among susceptible and resistant isolates. Conclusion: The current study provided information on the resistance patterns of clinical isolates of G. vaginalis. In this study a high level of resistance to metronidazole was observed. Approaches to approve the administration of clindamycin and vancomycin should be taken into consideration for the future treatment of BV in our current setting.
Investigation of sexual dimorphism, morphology, and morphometry of the cribriform plate in the KwaZulu-Natal population: Osteological and radiological assessment.
(2024) Hlatshwayo, Nondumiso Ngiphiwe.; Naidu, Edwin Coleridge Stephen.; Olojede, Samuel Oluwaseun.; Rennie, Carmen Olivia.; Azu, Onyemaechi Okpara.
Introduction: The cribriform plate is a fragile anatomical structure of the ethmoid bone. It is situated in the anterior cranial fossa between the brain and nasal cavity and serves as a channel for olfactory nerves to pass through to the brain. Despite its importance, there is a paucity of information in the literature on the morphology and sexual dimorphism of the cribriform plate, particularly in African populations. So, understanding the anatomical variations of the cribriform plate, particularly in relation to sex and laterality, is crucial as these differences may influence olfactory function, surgical approaches in the anterior cranial fossa, and the overall understanding of craniofacial anatomy in the selected KwaZulu-Natal (KZN) population. This study intended to observe and measure the shape, forms, and variations in the dimensions of the cribriform plate in relation to sex and laterality on both the bones and for computed tomography (CT) scans of a selected KZN population. Materials and methods: Fifty-five (55) CT scans of the cribriform plate were assessed from the axial and coronal views and fifty-eight (58) dried skulls without the calvaria were investigated bilaterally in this study. Morphology of the cribriform plate was recorded based on the Kawahara method, morphometry and related structures of the cribriform plate were investigated to identify any sexual dimorphism in KZN population. Result: In CT scans, the Type IV shape of the cribriform plate was the most prevalent in males, and the Type I cribriform plate shape was the most common in females. All morphometric parameters in comparison to sex were not statistically significant (p > 0.05) and they were observed to be slightly higher in males on both sides (males width on the right side was 4.78±1.30 mm and females width on the right side was 4.19±1.05 mm; males width on the left side was 4.33 mm (median) and females width on the left side was 4.18±0.97 mm; males length on the left side was 20.1±4.34 mm and females length on the left side was 20.0±3.84 mm; males depth on the left side was 5.15±1.65 mm and females depth on the left side was 4.94±1.40 mm) except for the length on the right side of females which was 20.6±3.73 mm. The teardrop type of the crista galli was the most common type with 53.3% on males and 64.0% on females. Keros classification type II was the most prevalent on sexes and Keros type III was the least identified within the population. On the right and left sides of the cribriform plate in both sexes, the anterior ethmoidal artery was commonly located below the skull base. Male Black South Africans had a right side of the cribriform plate that was longer (20.6 mm), whereas White South African males had a right side of the cribriform plate that was slightly smaller (19.7 mm). Compared to White females, Black South African females have a longer right side of the cribriform plate (20.7 mm). Cribriform plates’ width and depth in Black South African females had lower means (width on the right side was 4.00±1.05 mm and on the left side it was 4.17±1.06 mm; depth on the right side was 4.74±1.56 mm and on the left side it was 4.81±1.26 mm) than White South African females on both sides.
Modulation of Tenofovir by Probenecid: Impact on Drug, Interleukin-1β, and Dopamine Concentration in the Prefrontal Cortex and Cerebellum.
(2023) Shabalala, Ntombifikile Euphemia Shabalala.; Mabandla, Musa Vuyisile.
Abstract available in a PDF.
Evolution of Anti-Tat Antibodies and its role in developing prophylactic and therapeutic HIV-1 vaccine.
(2024) Kubheka, Thandeka Innocentia.; Mkhwanazi, Nompumelelo Prudence.
Abstract available in PDF.
Waist circumference, waist-to height ratio, or body mass index: which is the better predictor of hypertension in patients living with diabetes mellitus in low-to-middle-income countries?
(2022) Konar, Kylie Divashnee.; Pillay, Somasundram.
Background Hypertension (HPT) in low and middle-income countries (LMICs) remains a leading preventable factor for death and disability. Approximately 20-60% of patients living with diabetes (PLWD) have HPT which doubles the mortality risk and accelerates the progression of complications. Obesity is a well-known preventable risk factor for HPT. Despite this, countries in Sub-Saharan Africa (SSA) faces an increasing challenge of obesity. Current evidence on anthropometric indices as a predictor for HPT in PLWD remain unclear. Methods A scoping review was performed to determine the association between anthropometry and HPT in PLWD in LMICs in SSA, by using PubMed, Google, Scopus and Cochrane between 2011- 2021. A total of 4590 records were identified. The associations between body mass index (BMI), waist circumference (WC) or waist-to-height ratio (WTHR) in PLWD and HPT in LMICs in SSA were assessed. Results We analyzed 21 studies with 11 057 patients included in this review. BMI was the most common anthropometric index used with more than 80% of studies suggesting a positive association with HPT. Varying associations between other anthropometric indices and HPT were found. Conclusions Our scoping review highlighted a positive association between HPT and anthropometry in most studies. Limited data was available comparing the different anthropometric indices. We found that additional studies are warranted to evaluate anthropometric indices in PLWD.
Molecular epidemiology of Antibiotic-Resistant Escherichia coli from companion animals attending veterinary practices in Durban, KwaZulu-Natal, South Africa.
(2023) Ntuli, Nondumiso Lungile.; Essack, Sabiha Yusuf.; Mbanga, Joshua.; Abia Akebe, Luther King.
Background: Companion animals are globally documented to harbour antibiotic-resistant E. coli. This study aimed to investigate the molecular epidemiology of antibiotic-resistant E. coli from companion animals presenting at veterinary practices in Durban, KwaZulu-Natal, South Africa. Methods: E. coli were isolated on selective media from rectal swabs sampled from dogs and cats attending veterinary practices in Durban, KwaZulu-Natal, South Africa. All isolates were confirmed using real-time polymerase chain reaction (PCR) of the uidA gene. Antibiotic susceptibility testing was done against 20 antibiotics using the Kirby-Bauer disk diffusion method. Selected antibiotic-resistance genes (ARGs) that confer resistance to third-generation cephalosporins (blaTEM, blaSHV, and blaCTX-M), tetracycline (tetA, and tetB), and tigecycline (tetX/X2, tetX3, and tetX4), were detected using conventional PCR. PCR amplicons were confirmed by DNA sequencing and bioinformatics analysis. Enterobacterial Repetitive Intergenic Consensus Polymerase Chain Reaction (ERIC-PCR) was carried out to determine the clonality of E. coli (101) isolates that showed resistance to at least one antibiotic. Results: A total of 330 E. coli isolates from dogs (234) and cats (96) formed the study sample. Overall resistance was high in tetracycline (24.2%), ampicillin (18.8%), trimethoprim-sulfamethoxazole (14%), cephalexin (11.2%) and nalidixic acid (9.7%). Whilst lower resistance was observed in amikacin (0.3%), ceftazidime (0.3%), and piperacillin-tazobactam (0.6%). Third-generation cephalosporin-resistant E. coli retrieved from cats (26%) was more prevalent compared to dogs (9.8%). E. coli from dogs (2.1%) and cats (2%) were resistant to forth-generational cephalosporins. E. coli (3%) retrieved from dogs was resistant to tigecycline, which is regarded as a medically important antimicrobial (MIA) in human medicine. No resistance was observed against carbapenems. Thirty-five (10.6%) E. coli were multidrug-resistant (MDR) and exhibited twenty-two different phenotypic patterns. Amongst the E. coli that were not susceptible to third-generation cephalosporin, and tetracycline, it was observed that the blaCTX-M-15 (8%), and tetA (24%) were the most prevalent resistance genes. Thirty-one (9.3%) isolates were non-susceptible to third-generation cephalosporins and had the corresponding extended-spectrum beta-lactamase (ESBL) genes. The blaCTX-M-15 type gene was prevalent in all 25 E. coli isolates that tested positive for the blaCTX-M. The blaTEM-1 (17) was the second most prevalent β-lactamase gene. A total of 80/330 (24%) isolates were phenotypically not susceptible to tetracycline and carried either one, or both of tetA and tetB resistance genes. Only one tetracycline-resistant E. coli isolate did not harbour either tetA, or tetB genes. The blaSHV, tetX/X2, tetX3, and tetX4 were not detected in all the isolates. Using a 75% similarity cut-off, forty-eight clusters with isolates from both dogs and cats were identified. The ERIC-PCR types depicted a variety of clusters within veterinary practices in Durban, indicating that a high diversity of E. coli is in circulation in Durban, South Africa. Conclusion: Companion animals are reservoirs of antibiotic-resistant E. coli and ARGs. However, there was no evidence of transmission of antibiotic-resistant E. coli in Durban, South Africa. Resistance of E. coli from companion animals to MIA for humans is of particular concern and requires measures to control the spread of antibiotic-resistant bacteria, and ARGs between companion animals, veterinary practice personnel, and owners.
Type I, II, and III interferon responses in the female genital tract.
(2024) Ngubane, Slindile Brilliant Lyzeth.; Sivro, Aida.
Abstract available in PDF.
Anti-HIV and Immunomodulatory properties of the fractionated crude extracts isolated from Alternaria alternate.
(2024) Kubheka, Mbali Xolile.; Mkhwanazi, Nompumelelo Prudence.; Ndlovu, Sizwe Innocent.
Abstract available in PDF.
An exploration of binge drinking and coping behaviour during covid-19 among students in a major tertiary institution in KwaZulu-Natal.
(2023) Faborode, Joy Adebowale.; Kathree, Tasneem.
Background: The COVID-19 pandemic has profoundly impacted human lives. At the emergence of the novel disease, several restrictive measures, including lockdowns, were implemented to mitigate the spread of COVID-19. These measures created stressful challenges that affected people’s mental wellbeing, including that of tertiary students. There is a dearth of information on the strategies students use to cope with COVID-19-related stress. This study aimed to understand how students experienced and coped with changes attributed to the lockdowns in South Africa, including factors that influenced alcohol use among students at a major tertiary institution in KwaZulu Natal during the COVID-19 lockdown. Method: A qualitative approach was used. Twenty students were recruited from two campuses at the University of KwaZulu-Natal (UKZN), Durban, South Africa, using purposive sampling. Individual indepth interviews were conducted using a semi-structured interview guide comprising open-ended questions. The NVivo software program was used for analysis. Results: The majority (60%) of participants were male and ranged from 20 to 36 years old. The results of this study indicate drinking patterns among the study sample. Results indicate that despite implementing an alcohol sale ban during the COVID-19 lockdowns, alcohol use was not eliminated, but there was some reduction in the intake of alcohol. Apart from alcohol restrictions, some factors influencing drinking included drinking location and people with whom participants consumed alcohol. Many participants also indicated that they preferred to consume alcohol with friends because it helped them to bond with their friends and improved their social interactions. In addition, over 50% of the students stated that they drank alcohol because they felt happy, socialized with others, had fun, and that they enjoyed the taste. In contrast, only a few (four) reported drinking as a coping mechanism. Respondents were also aware of the negative consequences of drinking alcohol, especially when it is in large quantities. Results also indicate that half of the participants felt stressed, depressed, anxious and sad during the lock down. In addition, they also experienced problems related to eating and sleeping. The study highlighted the various coping mechanisms participants used to deal with stress. These included emotion-based coping strategies such as social support, sleeping, exercise, reading, watching television, listening to music, and maintaining a positive attitude, problem-based coping strategies (e.g., positive thinking and planning), as well as avoidance forms of coping (such as ignoring the situation). Conclusion: This study found that alcohol misuse was common in this sample of university students prior to the onset of COVID-19, and they experienced some distress during the COVID-19 lockdown. Factors that influenced alcohol use were also identified in this study sample which provided insight into how they experienced and coped with changes directly caused by the lockdowns in South Africa. 11 Despite these findings, sampling students from only one tertiary institution in KwaZulu Natal and being unable to interview students in their home language or the language of fluency if this was not English are identified as limitations. This study recommends that health promotion and education on alcohol use and coping strategies should be encouraged at tertiary institutions to curb alcohol misuse and improve students’ wellbeing.
Mortality trends during the first three waves of the covid- 19 pandemic at an urban district hospital in KwaZulu-Natal.
(2023) Hirachund, Omishka.; Naidoo, Mergan.
Introduction Severe Acute Respiratory Syndrome Corona Virus 2 (SARS COV 2) is the virus responsible for the COVID -19 (C19) pandemic. South Africa (SA) experienced multiple periods of increased transmission during which tertiary, regional and central hospitals were overwhelmed, resulting in a low acceptance rate of referrals from district hospitals (DHs). Thus, many severely ill, complex patients were managed at DHs while awaiting an Intensive Care Unit (ICU) bed. This study aims to describe mortality trends in a comparative analysis of the first three C19 waves at Wentworth Hospital (WWH). Literature Review Known risk factors for mortality are older age; male sex; Black African, Coloured and Indian compared to white race; admission in the public sector; comorbid diseases and obesity. Waves 2 and 3 had higher mortality rates compared to wave 1. Methods The study is a single-centre retrospective analysis of WWH’s clinical records and included all patients infected with C19 (based on clinical, biochemical or radiological features suggestive of infection) who were admitted and subsequently demised in-hospital during the defined waves. Data was collected using a pre-piloted data extraction tool. Demographic and presenting features of the patients along with investigations and management strategies were compared by the primary investigator across the three waves. Results Wave one, two and three yielded case fatality rates of 14.5%, 27.6% and 6.3%, respectively, and crude fatality rates of 16.7%, 33.0% and 12.2%, respectively. Black Africans were less likely to demise during the third wave (odds ratio (OR) 0.54; 95% confidence interval (CI) 0.31 to 0.94). Obesity was most prevalent in the second wave (OR 1.87; CI 1.01 to 3.46). Patients in the second wave had clinical frailty scores of less than five (OR 2.51; CI 1.56 to 4.03). Severe ground glass appearance on chest radiographs was most common during the second wave (OR 2.37; CI 1.49 to 3.77). Conclusion The beta variant dominated the second wave and was the most virulent, as highlighted by the highest case- and crude fatality rates. This study identified the need to understand if case fatality 2 rates and mortality trends at a DH were significantly higher than those at regional or tertiary hospitals. It is hoped that this study will provide clinical and hospital managers, and provincial and national healthcare policy makers with insight into challenges faced in the health system in the public health sector and allow implementation of improved public health and planning strategies for future pandemics.
Prevalence of pulmonary tuberculosis among correctional services staff in KwaZulu-Natal prisons.
(2022) Fawole, Adefolarin Ayotunde.; Rajen, Naidoo.
Abstract available in a PDF
Genotyping of Chlamydia trachomatis detected in South African pregnant women.
(2022) Ramnarain, Caitlin.; Abbai, Nathlee Samantha.; Mabaso, Nonkululeko.
Background Chlamydia trachomatis (C. trachomatis) is a common cause of bacterial sexually transmitted infections (STIs). The genetic characterisation of C. trachomatis serovars reveals significant genetic diversity in this organism. Untreated C. trachomatis infection in pregnant women has been linked to miscarriage, low birth weight babies, premature rupture of membranes, postpartum endometritis, and transmission to the new-born babies. Currently, there is limited data and analyses on the serovars of C. trachomatis circulating in South African pregnant women. In this study, the prevalence of C. trachomatis infection was determined, and the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) of the outer membrane protein gene (omp1) was performed in order to identify the different serovars circulating in the population of pregnant women. Methods In this study, 385 vaginal swab samples were analysed for the presence of C. trachomatis. The swabs were collected from human immunodeficiency virus (HIV)-positive pregnant women at the King Edward VIII hospital in Durban, South Africa. Chlamydia trachomatis was detected using commercial primers and probes (TaqMan Assay, assay ID Ba04646249_s1) which targets the gene encoding the translocated actin-recruiting phosphoprotein of C. trachomatis. Genotyping of C. trachomatis positive samples was performed by an omp1 semi-nested polymerase chain reaction (PCR) assay followed by restriction fragment length polymorphism (RFLP) analysis. The omp1 from C. trachomatis was amplified with gene-specific primers in the first round PCR to yield a 1033 base pair (bp) fragment. Following the first round PCR, 1 μL of the first-round PCR product was used for the semi-nested PCR, amplifying a 978 bp fragment. The 978 bp omp1 amplicons were digested with AluI, DdeI and HinfI, and the banding patterns were compared across the three digests for assignment of serovars. Associations between categorical variables was assessed using chi square (𝑥2) tests. All statistical analysis was conducted using RStudio, version 3.6.3. All p-values were considered significant at < 0.05. Results The actin-recruiting phosphoprotein of C. trachomatis was detected in 47/385 swab samples using the TaqMan Assay. The prevalence of C. trachomatis in the study population was 12.2%. All negative no-template controls did not produce any amplification. Factors associated with testing positive for C. trachomatis included, having a low level of education, being unemployed, being unmarried, not cohabitating with sex partner, early age of first sex, high number of lifetime sex partners, partner having other partners, lack of condom use, lacking symptoms of STIs, lacking treatment for STIs and women having a perceived risk of getting STIs. Serovar E (20/43) - 46.5% was the most frequent serovar in our study population, followed by serovar F (9/43) - 20.9%, G (6/43) - 14.0%, D (5/43) - 11.6%, and the least frequent serovar I (2/43) - 4.7% which was detected in two samples. From the five women that carried serovar D, 20.0% (1/5) reported past treatment of STIs. From the 20 women that carried serovar E, 20.0% (4/20) reported having abnormal vaginal discharge. Of the women with serovar E, 20.0% (4/20) reported past treatment of STIs. From the nine women that carried serovar F, 11.1% (1/9) reported having abnormal vaginal discharge and 22.2% (2/9) reported past treatment of STIs. From the six women that carried serovar G, 16.7% (1/6) reported past treatment of STIs. From the two women that carried serovar I, 50.0% (1/2) reported having abnormal vaginal discharge. Conclusion This study detected an overall 12.2% prevalence rate for C. trachomatis in the pregnant women. The identification of factors associated with infection provided evidence on the importance of antenatal clinics to screen women during their routine check-ups for vaginal infections and provide continuous risk reduction counselling to this vulnerable population. Five different serovars were observed in the studied population with serovars E and F being the most prevalent. The observed diversity of serovars reported within specific populations can be challenging for future vaccine design and development for chlamydia. However, many of the South African serovars detected correlated with serovars found in studies conducted throughout the world. This suggests the possibility of conserved C. trachomatis strains from various geographical areas, which may offer some hope for future vaccine development and diagnostic research aimed at the entire C. trachomatis population.
Characterization of Candida isolates from South African pregnant and non-pregnant women.
(2023) Sukali, Gloria.; Abbai, Nathlee Samantha.; Mabaso, Nonkululeko.
Candida infections are a serious health threat to women. Characterization of Candida isolates has become the gold standard method used in determining antimicrobial susceptibility profiles and resistance mechanisms in vaginal Candida infections. However, there is a lack of data on the antimicrobial susceptibility profiles of South African Candida isolates to amphotericin B. This study investigated antimicrobial resistance profiles and genotypes of Candida isolated from South African pregnant and non-pregnant women. This study was a sub-study of a larger study which involved the diagnosis of vaginitis and vaginosis pathogens in women. For the parent study, n=150 women were recruited from the King Edward VIII hospital in Durban, KwaZulu-Natal, South Africa. The women enrolled in the parent study were; 18 years and older, were willing to provide written informed consent and were willing to provide self-collected vaginal swabs. A total of 72 Candida isolates were obtained by culture. Of the 72 isolates, 31 isolates were obtained from pregnant women and 41 isolates were from non-pregnant women. The isolates were typed using the ABC genotyping method. Susceptibility testing was performed using the broth microdilution assay to measure the minimal inhibitory concentrations (MICs) for clinical isolates to amphotericin B. The Candida albicans ATCC 10231 strain was used as a control strain, and untreated cultures of the respective isolates were used as growth controls. Descriptive characteristics of the study participants according to Candida status were presented as frequencies and percentages. Comparisons by Candida status in the descriptive characteristics were performed using Chi square tests with a 5% significance level. P-values ≤0.05 were considered significant. All analyses were conducted using STATA. The prevalence of Candida in the study population was 48.0% (72/150). All the isolates (100%) were confirmed to be C. albicans as per the germ tube test and quantitative polymerase chain reaction (PCR) using primers and probes specific for C. albicans. All 72 isolates (100%) produced positive PCR results for C. albicans. The majority of the isolates (45/72; 62.5%) yielded a 450bp band which was assigned Genotype A. Of the 72 isolates, 19 isolates (26.4%) yielded a band size of 840bp and was assigned Genotype B. A total of 11.1% (8/72) of the isolates yielded band sizes of 450bp and 840bp which was Genotype C. Of the 72 isolates tested, 79.2% (57/72) of the isolates were resistant to amphotericin B (MIC >1ug/ml) and 20.8% (15/72) of the isolates were susceptible to amphotericin B (MIC ≤ 1 ug/ml). When linking MIC patterns to distribution of genotypes, it was observed that the majority (80%) of the isolates which were assigned genotype A were resistant to amphotericin B. When linking clinical symptoms with the distribution of genotypes, it was observed that the majority (58.8%) of women who reported having current symptoms of abnormal vaginal discharge carried genotype A. Genotype A was most prevalent in women who had been treated for vaginal infections in the past and in women who were HIV positive with prevalence of 64.1% and 60.8%, respectively. genotype A was most prevalent in the non-pregnant women with a prevalence of 63.4%. Genotype A was prevalent (61.3%) amongst the pregnant women and the majority (66.7%) of the HIV negative women had Candida infections which belonged to genotype A. The prevalence of Candida was shown to be high in both pregnant and non-pregnant women in this study. This study also found a high level of resistance to the antifungal amphotericin B. Currently in our local setting, resistance patterns to the commonly used antifungals to treat Candida infections are not being monitored. There is a need for antifungal resistance monitoring in order to reduce the risk of future persistent and untreatable infections.
The role of mir-29a, mir-181a, and mir-222 in preeclamptic and gestational hypertensive patients.
(2017) Khaliq, Olive Pearl.; Mackraj, Irene.
Backgrounds Hypertensive disorders of pregnancy, a major cause of maternal and neonatal morbidity worldwide are characterized by widespread maternal endothelial dysfunction and metabolic disorders (blood pressure and insulin resistance). Dysregulation in proteins (AKT and PI3K) involved in the insulin signaling pathway lead to insulin resistance, which is a common feature in the second half of most pregnancies complicated by preeclampsia and gestational hypertension. The objective of this study was to quantify microRNAs in serum and placental tissue of women with gestational hypertension (GH) and preeclampsia (PE). Methods This study is a prospective cross-sectional study involving 32 normotensive pregnant women (control), 32 women with preeclampsia (PE) and 28 with gestational hypertension (GH). The patients were recruited from a regional hospital in Durban, KwaZulu-Natal Province, South Africa. Serum and placental microRNA were quantified using RT-qPCR to compare levels of expression in the control, PE, and GH. In addition, a western blot analysis was carried out to investigate the levels of protein expression (AKT and PI3K) in the insulin signaling pathway. Results Serum, miRNA-222 quantitative real-time PCR expression levels were significantly lower in PE compared to normotensives (p=0.0186). miR-29 expression levels were significantly higher in PE (p<0.0001) and GH (p<0.0001) groups compared to normotensives. miR-181a serum expression levels of GH were significantly higher compared to normotensives (p=0.0070). Placental tissue expression showed significantly higher expression levels of miR-181a in PE (p=0.0344) and GH (p=0.0344) groups compared to normal controls. Western blot analysis of proteins showed a lower expression of AKT-serine and threonine in the PE (p=0.0001) compared to the normal control groups and significantly higher expression in the GH (p=0.0001) groups compared to the normal controls. Furthermore, the expression of the phosphatidyl-inositol-3 kinase (PI3K) was statistically lower in PE (p=0.0001) and GH (p=0.0001) compared to the normal controls. Discussion/Conclusion MicroRNAs may be used as potential biomarkers for PE and GH. The results of this study showed a correlation between the expression levels of miRNAs with AKT/PI3K in the insulin signaling pathway, reinforcing the existence of metabolic dysregulation in PE and GH

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