Masters Degrees (Medical Science)

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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
The role of endoplasmic reticulum stress in shedding of syncytiotrophoblast microparticles in pregnant black South African women.
(2016) Verma, Sonal Raj.; Mackraj, Irene.
Background and aim: Preeclampsia, accounts for the majority of maternal deaths emanating from hypertension in pregnancy. Although its exact aetiology is unclear, endoplasmic reticulum (ER) stress and trophoblast apoptosis are implicated. The placental microenvironment in preeclampsia is hypoxic and induces the expression of Hypoxia inducible factor-1 alpha (HIF-1 α) and CHOP (C/EBP homologous protein) which are activated due to ER stress. Hypoxia-induced oxidative and endoplasmic reticulum stress initiate a cascade of apoptotic events with the consequential shedding of microparticles which mediate the peripheral maternal syndrome of preeclampsia. The main aim of the study was to immuno-localise the expression of HIF-1 α and CHOP in placental tissues and concomitantly characterise and quantify the syncytiotrophoblast microparticles in the maternal circulation. Materials and Methods: Plasma and placental tissue were obtained from normotensive and pre-eclamptic pregnant women. The expression of HIF-1α and CHOP was analysed using immunohistochemistry. Microvesicles in maternal circulation were isolated and their size distribution was determined using nanoparticle tracking analysis. The relative concentration of syncytiotrophoblast microvesicles (STBMs) from isolated microvesicles was determined using Placental Alkaline Phosphatase ELISA. Results: This study demonstrated an increased immuno-expression of HIF-1 α and CHOPS in preeclampsia compared to the controls (p < 0.05). Additionally, a significant increase in the mean syncytiotrophoblast microparticles concentration was observed in PE, compared to the controls (p < 0.05). Further analysis showed a positive correlation between the immunohistochemical expression of HIF-1 α and CHOP and the STBMs concentration. Conclusion: This study demonstrates increased placental-expression of HIF-1α and CHOP in preeclampsia compared to normotensive pregnancies which directly relate to the increase syncytiotrophoblast microvesicles concentration in maternal circulation. These findings indicate that placental hypoxia and ER stress are contributory factors to the pathogenesis of PE and may be a key contributory factor in placental cell apoptosis and the consequent release of placental derived debris into the maternal circulation. Key words: HIF-1α; CHOP; Syncytiotrophoblast Microvesicles; Pre- eclampsia; Endoplasmic Reticulum Stress; Hypoxia
The relationship between age and diabetes control in patients living with diabetes mellitus in low-to-middle income countries.
(2021) Chetty, Rushern Ruvashin.; Pillay, Somasundram.
Diabetes Mellitus (DM) is a chronic, metabolic disease characterised by raised blood glucose levels. In 2019, there were an estimated 463 million adult patients living with diabetes (PLWD), with this figure expected to reach around the 700 million mark by 2045. Patients living in low-income and middle-income countries comprise approximately 79% of global adult PLWD figures, with approximately 20% of these PLWD being older than 65 years. This illustrates that the burden of DM rests on the younger working-age population in low-to-middle-income (LMIC) countries. These patients living with type 1 and type 2 diabetes have reduced life expectancies of approximately 20 and 10 years, respectively. Unfortunately, this compounds the problem of further decreasing the life expectancy of the population of LMIC countries which are already being affected by communicable diseases like HIV infection. South Africa has the highest prevalence of human immuno-deficiency virus (HIV) in the world at 13% with many PLWD also being HIV-infected. With the effective roll-out of anti-retroviral treatment (ART), patients are also able to live longer and can develop diabetes mellitus as a result of longevity, ART and the HIV-infection itself. With the prevalence of both these conditions and the numbers of DM expected to rise, determining relationships in PLWD in an HIV-endemic area would offer better knowledge and allow for better strategies to be implemented to effectively manage a significant proportion of patients in our setting. A scoping review was conducted globally to identify associations between ‘age’ and ‘glycaemic control’ in HIV-infected PLWD. The review concluded that “varying data exists on the associations between glycaemic control and age in PLWD in the context of HIV infection (PLWDH). Further studies are recommended to determine associations in this regard, especially in LMIC where HIV and DM have a higher prevalence.” The lack of conclusive associations identified from the scoping review suggested that another study was warranted in an HIV-endemic region. A retrospective study was conducted among 957 PLWD of whom 146 patients were HIV-infected from the Edendale Hospital Diabetes Clinic, Pietermaritzburg, South Africa from 1 January 2019 to 31 December 2019. Statistical analysis was performed with a p value<0.05 being considered statistically significant. Our study showed that younger PLWD had poorer glycaemic control and were likely to develop diabetes-related complications later in life. Of note, older age was associated with improved mean glycated haemoglobin (HbA1c) levels after adjusting for glomerular filtration rate (GFR) [r=-0.141, p<0.001; (before adjustment: r=-0.108; p=0.001)]. In addition to this, PLWD with an HIV-infection who had a mean HbA1c>7% were significantly younger than those with HbA1c≤7% (47.38 years vs. 52.77 years, p=0.013). viii From this study, we evaluated associations between age and glycaemic control in PLWD has served to highlight that “more emphasis, in terms of diabetes education and management, needs to be placed in the younger age category of both PLWD and PLWDH”. This study, as well as future prospective studies, will assist with providing patients, healthcare workers and government with improved knowledge, thereby managing patients more effectively at any given age. Some of our recommendations from this study include: screening all patients for DM and implementing strategies to optimise glycaemic control and prevent complications; healthy diet to be implemented by patients of all ages; exercise as well as optimal pharmacological management and self-monitoring of glucose levels.
The prevalence and risk factors for genital mycmoplasmas in Human immunodeficiency virus infected pregnant women from King Edward Vlll hospital.
(2021) Nundlall, Nikita.; Abbai, Nathlee Samantha.; Singh, Ravesh.
Background: Genital mycoplasmas can be found amongst the normal human flora mostly in the respiratory, reproductive and urinary tracts as commensal or pathogenic organisms. These bacteria are sexually transmitted and can be linked to sexually transmitted diseases and other conditions. There are a limited number of studies conducted in South African pregnant women especially from KwaZulu-Natal which have assessed the prevalence, co-infection rates and risk factors for genital mycoplasmas. In this study, the prevalence, co-infection rates and risk factors for Mycoplasma genitalium, M. hominis, Ureaplasma urealyticum and U. parvum were investigated in a cohort of Human immunodeficiency virus (HIV) infected pregnant women. The data generated in this study, therefore adds to the growing body of knowledge on these pathogens. Methods: This study included 264 HIV infected pregnant women attending the King Edward VIII antenatal clinic in eThekwini, South Africa. The women were recruited between October 2020 and April 2021. Each enrolled women provided self-collected vaginal swabs (dry swabs) for detection of the vaginal infections. The consenting women had also completed a questionnaire on socio-demographic, behavioural and clinical factors. DNA was extracted from the vaginal samples using the PureLink Microbiome kit. The individual pathogens were detected using the TaqMan Real-time PCR assays using commercially available primers and probes on a QuantStudio 5 Real-time polymerase chain reaction (PCR) platform. The statistical data analysis was conducted in a freely available Statistical Computing Environment, R software, version 3.6.3 using the RStudio platform. Results: The most prevalent infection in the study population was U. urealyticum, 236/264 (89.4%), followed by M. hominis, 215/264 (81.4%), U. parvum, 203/264 (76.9%) and lastly M. genitalium, 7/264 (2.70%). A total of five women (1.90%) were coinfected with all four microorganisms. Within the group of women who tested positive for Mycoplasma genitalium (M. genitalium), partner having other partners was the only significant behavioral factor in relation with being positive, p=0.031. However, a smaller proportion of positive women reported that their partner had other partners (28.6%) when compared to 57.1% who reported that their partner did not have other partners and 14.3% who did not know if their partner had other partners. Within the group of women who tested positive for Mycoplasma hominis (M. hominis), partner having STI symptoms was a significant clinical factor in relation with being positive, p=0.027. Women that experienced current symptoms of STIs was significantly associated with being positive, p<0.001. In addition, of the M. hominis positive women, a higher proportion, 80.5% tested positive for U. parvum infection compared to 19.5% who tested negative and this was significant, p=0.004. Partner being circumcised was a significant clinical factor in relation with being positive for Ureaplasma urealyticum (U. urealyticum), p=0.028. In addition, partner having symptoms of STIs was a significant clinical factor in relation with being positive, p=0.027. The majority of the positive women were in the third trimester of pregnancy and trimester of pregnancy was significantly associated with being positive for infection, p=0.040. Of the women who tested positive for U. urealyticum, a higher proportion of women also tested positive for M. hominis and this association was significant, p=0.051. Within the group of women who tested positive for Ureaplasma parvum (U. parvum), partners HIV status was significant in relation with being positive, p=0.049. Lifetime number of sex partners was significantly associated with being positive, p=0.012. Partner having other partners was also a significant factor in relation with being positive, p=0.023. Of the U. parvum positive women, a higher proportion of women (85.2%) tested positive for M. hominis. This association was significant, p=0.004. In the adjusted analysis, being employed increased the risk of getting infected with M. hominis p=0.012. In the adjusted analysis, current STI symptoms increased the risk for M. hominis by 95.27 fold, p<0.001. Being U. parvum positive increased the risk for M. hominis by 8.19 fold, p=0.001. Being U. urealyticum positive also increased the risk for M. hominis, p=0.039. In the adjusted analysis, having >4 lifetime sex partners increased the risk of infection with U. parvum by 88.02 fold. This factor was significant, p<0.001. Partner having other partners increased the risk of infection with U. parvum, p=0.008. In the adjusted analysis, being M. hominis positive increased the risk for U. parvum by 4.33 fold, p=0.008. Conclusion: The present study provides information on the risk factors associated with genital mycoplasma infections. The identification of risk factors provides the foundation for the development of prevention interventions. In this study, clinical and behavioral factors were shown to be significantly associated with the risk for infection. Based on this finding, it is evident that a single prevention strategy will not be sufficient, what will be needed is a combination prevention strategy for this vulnerable population.
Renal and metabolic effects of tulbaghia violacea harv. and captopril in fructose-fed streptozotocin induced diabetic rats.
(2017) Joseph, Kimane Megan.; Mackraj, Irene.; Moodley, Kogilambal.
Background: Diabetes mellitus has rapidly emerged as a worldwide epidemic resulting in significant morbidity and mortality. The incidence of type 2 diabetes mellitus, induced by a high carbohydrate diet, a sedentary lifestyle as well as obesity, is increasing rapidly. Despite the availability of current conventional drugs, the complications of diabetes mellitus continue to progress. Therefore the search for alternate therapies that are antidiabetic in nature and elicit minimal side effects is essential. This study investigated the effects of the medicinal plant Tulbaghia violacea. Harv and angiotensin converting enzyme inhibitor, Captopril in a fructose-fed streptozotocin induced diabetic rat model. Methods: Thirty-six, male Sprague-Dawley rats (six-week old) were randomly divided into six groups’ namely non-diabetic control, diabetic control, diabetic treated with Tulbaghia violacea Harv. (60 mg/kg bw), diabetic treated with captopril (50 mg/kg bw), diabetic treated with metformin (250 mg/kg bw) and diabetic treated with glibenclamide (10 mg/kg bw). Diabetes was induced by fructose feeding for 1 week followed by a single intraperitoneal injection of 40 mg/kg.bw streptozotocin. Animals with a fasting blood glucose concentration >25mmol/L were considered diabetic and included in the study. Thereafter, respective doses of Tulbaghia violacea and conventional drugs were daily administered to the diabetic groups by oral gavage for seven weeks. At week six, an oral glucose tolerance test was performed. At the end of week 7, the animals were euthanized by halothane overdose. Blood was collected and organs were harvested for further biochemical analyses. Results: Tulbaghia violacea treatment significantly increased plasma insulin and liver glycogen content. Tulbaghia violacea treatment also reduced liver thiobarbituric acid reactive substances levels, increased liver superoxide dismutase concentration and increased plasma nitric oxide levels. Furthermore, Tulbaghia violacea administration reduced serum triglycerides, total cholesterol, VLDL cholesterol, LDL cholesterol and increased HDL cholesterol. The plant treated group showed increased pancreatic islet counts as well as improved glomerular morphology. The angiotensin converting enzyme inhibitor captopril showed a significant increase in angiotensin converting enzymeactivity as well as increased angiotensin type 1 receptor expression compared to the diabetic controls and Tulbaghia violacea. Conclusion: Tulbaghia violacea did not decrease fasting blood glucose levels or improve glucose tolerance. However, in this study, the data obtained demonstrated the ability of Tulbaghia violacea to elicit antioxidant and hypolipidemic effects, augment plasma insulin levels, improve pancreatic and glomerular morphology and positively impact β- cell function in a fructose-fed streptozotocin induced diabetic rat model.
“Sugars”: the chemical characterization of a prevalent illicit drug cocktail in South Africa.
(2016) Chetty, Yvette Yolanda.; Nadar, Anand.
ABSTRACT Introduction “Sugars” is an illicit drug cocktail that is thought to be a mixture of heroin, cocaine and other substances in order to add bulk to the final product. Since its emergence in a local KwaZulu-Natal community known as Chatsworth in 2006, the use of the drug has spread to other provinces in South Africa and has currently become a popular drug amongst the youth. The affordability of the cocktail has allowed it to become rampant in low income communities and this coupled with its accessibility further reinforces “Sugars” as the preferred drug of choice. The use of the drug allows the user to experience euphoria, however once the effects wear off, the pain of the resulting withdrawal or “roster” drives the individual to continue using the drug. The withdrawal symptoms range from common cold and flu-like symptoms to extreme bone pain, stomach cramps, constipation and nausea. There have been attempts at rehabilitating “Sugars” addicts however, due to the lack of knowledge of a precise chemical composition of the cocktail, it is difficult to effectively maintain therapeutic interventions. Aim The aim of this study was therefore to chemically characterize the composition of “Sugars”, thereby allowing for the development of targeted treatment options for rehabilitation centres. Method Batches of samples of the mixture were sourced from 3 independent suppliers in the Durban South area of KwaZulu-Natal, South Africa. Chromatographic techniques were used to separate the individual constituents of the mixture and determine molecular weights of these compounds. Nuclear magnetic imaging was used to identify the compounds. Results and discussion The tests confirmed the presence of heroin, papaverine and noscapine in the “Sugars” samples analysed. However, there was variance noted in the composition between the different sources of the drug. We hypothesize that “Sugars” was therefore not heroin that is bulked up with other substances, but may be the waste product of the final purification process in the illicit heroin manufacturing process. Conclusion It was concluded that “Sugars” contained heroin, noscapine and papaverine. The variance in composition of heroin in the samples suggests independence between suppliers. The presence of papaverine and noscapine, which are impurities that are usually removed during the final purification of heroin, supports the hypothesis that “Sugars” is the waste product of the manufacture of heroin. Noscapine and papaverine are costly pharmaceutical products and we therefore speculate that it would not be economically viable to bulk up a cheap low grade drug cocktail with these compounds.
Anatomic study of the morphologic relationship between the proximal left and right coronary arteries.
(2016) Singh, Sadhna.; Satyapal, Kapil Sewsaran.; Lazarus, Lelika.; Ajayi, Nasirudeen Oladipupo.
Arising from the aorta, the right (RCA) and left (LCA) coronary arteries provide the arterial supply to the heart. An extensive literature review revealed that most studies have either evaluated the morphology of the RCA or the LCA independently. This study aimed to document the relationship between the morphology of the RCA and LCA using coronary angiograms and fetal dissections. In addition, variations such as split or double RCA and absence of the LCA was documented. A review of 500 coronary angiograms and a fetal dissection of 41 heart specimens was conducted. The RCA and LCA were classified according to their branching patterns and arterial dominance. The embryologic relationship between the RCA and the LCA was also documented including their lengths and diameters. The angiographic review showed that the most prevalent branching pattern of the LCA was bifurcation in 65.8%, while trifurcation and quadrifurcation occurred in 20.4% and 1.6%, respectively. The splitting of the RCA and absence of the LCA occurred in 4.2% and 11.8%, respectively. A significant correlation was found between the split RCA and absent LCA showing that the split RCA was more prevalent in the absence of the LCA. The dissection of the fetal heart specimens (age range 13.13 - 26.95 weeks) found that the RCA arose from the right aortic sinus and provided arterial dominance in all the specimens. The LCA was classified into types according to their branching pattern. The bifurcation, trifurcation and quadrifurcation of the LCA occurred in 68.3%, 29.3% and 2.4% of hearts, respectively. The mean lengths of the RCA and LCA were 0.98 ± 0.54mm and 1.83 ± 0.77mm, respectively. The mean diameters of the RCA and LCA were 0.38 ± 0.12mm and 0.49 ± 0.17mm, respectively. A significant correlation was found between the RCA and LCA length and the fetal age indicating changes in the development of the coronary vasculature with fetal development. A knowledge of the distribution of the RCA and LCA assists in providing information on the area of the myocardium supplied. With the advent of coronary angiography, a comprehensive understanding of coronary arterial anatomy and their variations is necessary.
Evaluation of teixobactin derivatives as potential antimicrobial agents.
(2017) Ramchuran, Estelle Juanita.; Bester, Linda Antionette.
Methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant Enterococcus (VRE) are on the World Health Organization (WHO) high priority list of pathogens that require serious attention. Therefore, the need for novel class of compounds is vital in overcoming this problem. Teixobactin is a new class of antibiotic that has exhibited antimicrobial activity against resistant bacteria. In this study we are expanding the investigation of teixobactin derivatives against clinically relevant bacterial isolates from South African patients. The minimum inhibitory concentration (MIC), the minimal bactericidal concentration (MBC), the serum effect on the MIC’s and the time kill kinetics studies of three of our synthesized teixobactin derivatives 3, 4 and 5 were ascertained by broth microdilution according to the CLSI 2017 guidelines. Haemolysis on red blood cells (RBCs) and cytotoxicity on peripheral blood mononuclear cells (PBMCs) were performed to investigate the safety of these derivatives. MIC’s of the teixobactin derivatives against ATCC reference strains were between 4-64 µg/ml (3), 2-64 µg/ml (4) and 0.5-64 µg/ml (5). The MIC’s for MRSA were 32 µg/ml for (3), 2-4 µg/ml for (4) and 2-4 µg/ml for (5) whilst the MIC’s obtained for VRE’s were 8-16 μg/ml for (3), 4 μg/ml for (4) and 2-16 μg/ml for (5). 50% human serum had no effect on the MIC’s. All these derivatives did not show any effect on cell viability at their effective concentration. Teixobactin derivatives (3, 4 and 5) were capable of inhibiting bacterial growth in drug resistant bacteria and thus serve as potential antimicrobial agents.

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