Faculty of Health Sciences (Research Outputs)
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Item A histopathological snapshot of bladder cancer: a Johannesburg experience of 1480 histopathology reports(Springer, 2025-03) Jonosky, Jaclyn; Adam, AhmedPurpose To evaluate the histopathological characteristics of bladder cancer in patients presenting to Johannesburg hospitals over a 13-year period (2010–2023). Methods Following ethical clearance, a retrospective observational, descriptive review of histopathological reports over 13 years was conducted in Johannesburg. Inclusion criteria was bladder biopsies, TURBT specimens, and radical cystectomy (RC) specimens positive for bladder cancer. Exclusion criteria was non-primary bladder cancers (prostate, cervical, colon) and urothelial carcinoma of upper tract origin (N=970). Of the initial specimens (N=2450), 1480 met the inclusion criteria, representing 858 patients, owing to multiple transurethral resections of bladder tumours (TURBT). Categorical variables were summarised as counts and percentages, while numerical variables were reported as means with standard deviations or medians with interquartile ranges, depending on data distribution and tested via the Shapiro‒Wilk test. Statistical compari sons were performed using Fisher’s exact test (sex), one-way ANOVA, or the Kruskal‒Wallis test (age). Statistical signifi cance was set at p<0.05. Results Urothelial carcinoma accounted for 88.8% of bladder cancer, squamous cell carcinoma (7.7%), adenocarcinoma (1.5%), and other malignancies (2%). High-grade urothelial carcinoma was predominant at 75%. Non-muscle invasive disease accounted for 72% of these cases, while 28% were muscle invasive. Data from radical cystectomies showed a high proportion of aggressive and advanced disease. Conclusions The study highlights the predominance of high-grade non-muscle invasive bladder cancer in Johannesburg, consistent with global trends. The findings suggest a shift in bladder cancer trends in Johannesburg away from assumed squamous cell carcinoma towards urothelial carcinoma.Item Resistance mutations that distinguish HIV-1 envelopes with discordant VRC01 phenotypes from multi-lineage infections in the HVTN703/HPTN081 trial: implications for cross-resistance(Elsevier, 2025-02) Cohen, Paula; Lambson, Bronwen E.; Mkhize, Nonhlanhla N.; Morris, Lynn; Moore, Penny L.; Moodley, Chivonne; Yssel, Anna E. J.; Moyo-Gwete, Thandeka; York, Talita; Gwashu-Nyangiwe, Asanda; Ndabambi, Nonkululeko; Thebus, Ruwayhida; Williamson, CarolynThe Antibody Mediated Prevention (AMP) trials showed that passively infused VRC01, a broadly neutralizing antibody (bNAb) targeting the CD4 binding site (CD4bs) on the HIV-1 envelope protein (Env), protected against neutralization-sensitive viruses. We identified six individuals from the VRC01 treatment arm with multi-lineage breakthrough HIV-1 infections from HVTN703, where one variant was sensitive to VRC01 (IC50 < 25 ug/mL) but another was resistant. By comparing Env sequences of resistant and sensitive clones from each participant, we identified sites predicted to affect VRC01 neutralization and assessed the effect of their reversion in the VRC01-resistant clone on neutralization sensitivity. In four pairs, a single mutation restored partial or full sensitiv ity to VRC01, whereas in the fifth participant, transfer of the entire β23-V5 loop was required. No VRC01 resistance mutations could be identified in the sixth participant, with the discordant clones differing by >100 amino acids. Mutations responsible for the differential neutralization phenotypes occurred at distinct sites across Env, including residues in loop D, the CD4-binding loop, and between the β23 and V5 loops. Analysis of deep sequencing env data showed that VRC01 resistance was likely the property of the acquired virus, rather than occurring through post-acquisition evolution. Although VRC01-resistant parental clones generally retained sensitivity to other CD4-binding site bNAbs, they were less potently neutralized than the VRC01-sensitive clones. In conclu sion, VRC01 resistance mutations occurred through multiple mutational pathways, but sensitivity to second-generation CD4bs bNAbs was retained even in VRC01-resistant transmitted viruses, confirming the potential of these bNAbs for HIV-1 prevention studies.Item Genetic therapies for movement disorders ‑ current status(Springer, 2025-02) Waddington, S. N.; Sartorelli, J.; Ng, J.; Rahim, A. A.; Kurian, M. A.Movement disorders are a group of heterogeneous neurological conditions associated with alterations of tone, posture and voluntary movement. They may either occur in isolation or as part of a multisystemic condition. More recently, the advent of next generation sequencing technologies has facilitated better understanding of the underlying causative genes and molecular pathways, thereby identifying targets for genetic therapy. In this review, we summarize the advances in genetic therapy approaches for both hyperkinetic and hypokinetic movement disorders, including Parkinson’s Disease, Huntington’s Disease and rarer monogenic conditions of childhood onset. While there have been significant advances in the field, multiple challenges remain, related to safety, toxicity, efficacy and brain biodistribution, which will need to be addressed by the next generation of genetic therapies.Item Prevalence and factors associated with caesarean section among Tanzanian women of reproductive age: evidence from the 2022 Tanzania demographic and health survey data(BioMed Central, 2025-02) Olorunfemi, Gbenga; Nahayo, Bonfils; Ndayishimye, Samuel; Nsanzabera, CharlesBackground: Caesarean Section (CS) is one of the commonest surgical procedures worldwide. It is an important medical intervention for reducing the risk of poor perinatal outcomes. However, there was increased trends in CS in sub-Saharan Africa as maternal and neonatal mortality and morbidity remains high. This study aims to determine the prevalence and factors associated with CS rates in Tanzania. Methodology: This was a secondary data analysis of 4,768 women of reproductive age (15–49) in Tanzania. The data utilized was from the Tanzania Demographic Health and Survey (TDHS) 2022. The factors associated with CS were identified using multivariable binary logistic regression. Results: Out of 4,768 women of reproductive age in Tanzania, 497 (10.4%) had CS. Attaining primary (Adjusted Odds Ratio (aOR): 1.79,95% CI 1.23–2.60), secondary (aOR:2.07,95% CI 1.36–3.14) and higher education (aOR: 2.35, 95% CI 1.08–5.12); having a husband/partner with higher education; being in richest household wealth quintile (aOR:1.98,95% CI (1.31-3.00), having a job (aOR:1.29, 95% CI: 1.05–1.58 and having attended more than 4 antenatal care (ANC) visits (aOR: 1.36, 95% CI: 1.11–1.67) were associated with a higher odds of undergoing CS compared to their respective counterparts. However, living in rural areas (aOR: 0.74, 95% CI:0.58–0.94), being multiparous women with 2–4 births (aOR: 0.67, 95% CI: 0.53–0.84) and 5 or more births (aOR: 0.44, 95% CI: 0.32–0.60) were associated with lower odds of CS. Conclusion: The overall prevalence of CS among women of reproductive age in Tanzania was 10.4%. The highest educational level, husband/partner’s educational attainment, household wealth quintile, type of residence, employment status, increased ANC number, and high parity were associated with CS. The CS prevalence is at the lower limit of the recommendation of the World Health Organisation of 10–15%. Further researches are necessary to highlight other barriers, facilitators and outcome of CSs in Tanzania to advise policy stakeholders.Item Group-based trajectory modeling to describe the geographical distribution of tuberculosis notifcations(Springer Nature, 2025-02) Martinson, Neil A.; Lebina, Limakatso; Dagnew, Alemnew F.; Hanrahan, Colleen F.; Dowdy, David W.; Nonyane, Bareng A. S.Background Tuberculosis (TB) is a major public health problem, and understanding the geographic distribution of the disease is critical in planning and evaluating intervention strategies. This manuscript illustrates the application of Group-Based Trajectory Modeling (GBTM), a statistical method that analyzes the evolution of an outcome over time to identify groups with similar trajectories. Specifically, we apply GBTM to identify the evolution of the number of TB notifications over time across various geographic locations, aiming to identify groups of locations with similar trajectories. Locations sharing the same trajectory may be considered geographic TB clusters, indicating areas with similar TB notifications. We used data abstracted from clinic records in Limpopo province, South Africa, treating the clinics as a proxy for the spatial location of their respective catchment areas. Methods Data for this analysis were obtained as part of a cluster-randomized trial involving 56 clinics to evaluate two active TB patient-funding strategies in South Africa. We utilized GBTM to identify groups of clinics with similar trajectories of the number of TB patients. Results We identified three trajectory groups: Groups 1, comprising 57.8% of clinics; Group 2, 33.9%; and Group 3, 8.3%. These groups accounted for 30.8%, 44.4%, and 24.8% of total TB-diagnosed patients, respectively. The estimated mean number of TB-diagnosed patients was highest in trajectory group 3 followed by trajectory group 2 across the 12 months, with no overlap in the corresponding 95% confidence intervals. The estimated mean number of TB-diagnosed patients over time was fairly constant for trajectory groups 1 and 2 with exponentiated slopes of 0.979 (95% CI: 0.950, 1.004) and 1.004 (95% CI: 0.977, 1.044), respectively. In contrast, there was a statistically significant 3.8% decrease in the number of TB patients per month for trajectory group 3 with an exponentiated slope of 0.962 (95% CI: 0.901, 0.985) per month. Conclusions GBTM is a powerful tool for identifying geographic clusters of varying levels of TB notification when longitudinal data on the number of TB diagnoses are available. This analysis can inform the planning and evaluation of intervention strategies.Item Improving poor outcomes of children with Biliary Atresia in South Africa by early referral to centralized units(Wolters Kluwer., 2021) van der Schyff, Francisca; Terblanche, Alberta J.; Botha, Jean F.Objectives: Biliary atresia (BA) is a progressive fibrosing cholangiopathy of infancy, the most common cause of cholestatic jaundice in infants and the top indication for liver transplantation in children. Kasai portoenterostomy (KPE) when successful may delay the requirement for liver transplantation, which in the majority offers the only cure. Good outcomes demand early surgical intervention, appropriate management of liver cirrhosis, and in most cases, liver transplantation. These parameters were audited of children with BA treated at the Steve Biko Academic Hospital (SBAH) in Pretoria, South Africa. Methods: All children with BA who were managed at SBAH between June 2007 and July 2018 were included. Parameters measured centered on patient demographics, timing of referral and surgical intervention, immediate and long-term outcomes of surgery, and follow-up management. Results: Of 104 children treated, 94 (90%) were KPE naive. Only 23/86 (26%) of children were referred before 60 days of life and 42/86 (49%) after 120 days. Median time to surgical assessment and surgery was 4 (IQR 1–70) and 5 (IQR 1–27) days post presentation, respectively. The median age at KPE was 91 days (IQR 28–165), with only 4/41 (12%) of KPEs performed before 60 days of life. Of those with recorded outcomes, 12/33 (36%) achieved resolution of jaundice. Only a third of the cohort were referred for transplantation. Conclusion: Children with BA have poor outcomes in the public health sector in South Africa. Late referrals, delayed diagnostics, advanced age at KPE with low drainage rates, poor follow–up, and low transplant rates account for low survival. Early referral to units offering expert intervention at all stages of care, including transplantation, would offer the best outcomes.Item Unprecedented Association: bilateral UPJ obstruction with grade 3 hydronephrosis caused by Type 2 circumcaval right ureter and left lower pole crossing vessels(Elsevier, 2025-01) Salem, Mohammed Salah E. Khalifa; Abdul, Alherek; DaSilva, Daniel; Mukendi, Alain Mwamba; Jacob, VargheseBilateral ureteropelvic junction obstruction resulting from distinct vascular anomalies on each side, with a preureteric vena cava on the right and crossing vessels on the left, has not been previously documented in the literature. Even more intriguing is the association between a grade 3 hydronephrosis and a type 2 circumcaval ureter. This unprecedented report discusses this association and its management.Item Impact of witnessing abuse of their mother and childhood trauma on men’s perpetration of intimate partner violence in the cross-sectional UN multi-country study on men and violence in Asia and the Pacific(Elsevier, 2025-01) Jewkes, Rachel; Shai, Nwabisa; Chirwa, Esnat; Naved, Ruchira Tabassum; Abrahams, Naeema; Ramsoomar, Leane; Dekel, Bianca; Gibbs, Andrew; Nothling, Jani; Willan, SamanthaTrauma exposure and witnessing intimate partner violence (IPV) in childhood are recognised risk factors for IPV. Using the UN Multi-country Study on Men and Violence in Asia and the Pacific dataset, we describe the pathways through which they influence adult IPV perpetration. Methods: In nine sites, from six countries, data were collected in a two-stage, randomly-selected household survey, with one man aged 18–49 years interviewed per house. 8379 interviews were completed with ever partnered men in Bangladesh, Cambodia, China, Indonesia, Papua New Guinea (Bougainville) and Sri Lanka. We present a Structural Equation Model (SEM) to understand paths through which childhood trauma and witnessing IPV impacted perpetration of physical or sexual IPV in adulthood. Results: Among the men, 25.5% had witnessed IPV, 47.0% had perpetrated physical or sexual IPV. Both wit nessing IPV and childhood trauma elevated the likelihood of such perpetration. The SEM showed four paths from witnessing IPV and childhood trauma to the latent variable for physical/sexual IPV perpetration. One was direct and three indirect. Paths were mediated by food insecurity, depression, and a latent variable measuring gender inequitable and anti-social masculinities. The masculinity variable indicators were drug use, harmful alcohol use, bullying, gang membership, fighting with other men, having sex with a sex worker and having raped a non partner. The direct and indirect effects showed both childhood trauma and witnessing maternal IPV to be important, but childhood trauma the more so. Conclusions: Both childhood trauma and witnessing IPV were important in driving IPV perpetration, with in dependent effects, however, broader childhood trauma exposure was most strongly associated. The effects were mediated by food insecurity, depression and gender inequitable and anti-social masculinities, all recognised risk factors for IPV perpetration. Thus, gender transformative IPV prevention interventions that include mental health and economic elements can mitigate the influence of these key exposures.Item Neurodevelopmental assessment of HIV-exposed uninfected and early-treated HIV-infected children: study protocol(BioMed Central, 2018-04) Strehlau, Renate; van Aswegen, Tamryn; Potterton, JoanneObjective: Sub-Saharan Africa has the highest prevalence of children at risk of not achieving their developmental potential, attributable largely to the human immunodefciency virus (HIV) pandemic coupled with negative environmental factors. Childhood developmental stimulation programmes can mitigate adverse outcomes. Methods: Neonates testing HIV positive at birth will be initiated on antiretroviral treatment (ART) and receive an ageappropriate stimulation program, updated at 3 monthly intervals through the frst year of life. Neurodevelopment at 12 months of age will be assessed using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Outcomes will be compared with HIV-infected and HIV-exposed uninfected children (HEU) not having received the stimulatory intervention. Associations between neurodevelopmental outcomes, environmental factors, and parental stress will be investigated. The study will take place at a single site in Johannesburg, South Africa. This non-randomised controlled intervention study, with a single non-blinded comparative intervention group, aims to investigate whether an early childhood stimulation programme used in conjunction with ART initiated at birth can positively impact neurodevelopmental outcomes at 1 year of age in children infected with HIV.Item Assessing runs of Homozygosity: a comparison of SNP Array and whole genome sequence low coverage data(BMC, 2018-01) Ceballos, Francisco C.; Hazelhurst, Scott; Ramsay, MichèleBackground: Runs of Homozygosity (ROH) are genomic regions where identical haplotypes are inherited from each parent. Since their first detection due to technological advances in the late 1990s, ROHs have been shedding light on human population history and deciphering the genetic basis of monogenic and complex traits and diseases. ROH studies have predominantly exploited SNP array data, but are gradually moving to whole genome sequence (WGS) data as it becomes available. WGS data, covering more genetic variability, can add value to ROH studies, but require additional considerations during analysis. Results: Using SNP array and low coverage WGS data from 1885 individuals from 20 world populations, our aims were to compare ROH from the two datasets and to establish software conditions to get comparable results, thus providing guidelines for combining disparate datasets in joint ROH analyses. By allowing heterozygous SNPs per window, using the PLINK homozygosity function and non-parametric analysis, we were able to obtain non-significant differences in number ROH, mean ROH size and total sum of ROH between data sets using the different technologies for almost all populations. Conclusions: By allowing 3 heterozygous SNPs per ROH when dealing with WGS low coverage data, it is possible to establish meaningful comparisons between data using SNP array and WGS low coverage technologies