Faculty of Health Sciences (Research Outputs)
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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 technologiesItem The effect of a ketogenic diet versus a high-carbohydrate, low-fat diet on sleep, cognition, thyroid function, and cardiovascular health independent of weight loss: study protocol for a randomized controlled trial(BMC, 2018-01) Iacovides, Stella; Meiring, Rebecca M.Background: Many physiological health benefits observed after following a ketogenic diet (KD) can be attributed to the associated weight loss. The KD has become more prominent as a popular health choice, not only in obese/ overweight individuals, but also in healthy adults. The study aims to determine the effects of a KD, independent of weight loss, on various aspects of physiological health including: sleep, thyroid function, cognition, and cardiometabolic health. The study will also aim to determine whether a change in basal metabolic rate may be associated with any changes observed. Methods: Twenty healthy men and women between 18 and 50 years of age will take part in this study. In a randomized controlled, cross-over design, participants will follow two isocaloric diets: a high-carbohydrate, low-fat diet (55% CHO, 20% fat, 25% protein) and a KD (15% CHO, 60% fat, 25% protein). Each dietary intervention will last for a minimum of 3 weeks, with a 1-week washout period in between. Before and after each diet, participants will be assessed for sleep quality, cognitive function, thyroid function, and basal metabolic rate. A blood sample will also be taken for the measurement of cardio-metabolic and immune markers. Discussion: The present study will help in understanding the potential effects of a KD on aspects of physiological health in healthy adults, without the confounding factor of weight loss. The study aims to fill a significant void in the academic literature with regards to the benefits and/or risks of a KD in a healthy population, but will also explore whether diet-related metabolic changes may be responsible for the changes observed in physiological health.Item The importance of morphological identification of African anopheline mosquitoes (Diptera: Culicidae) for malaria control programmes(BMC, 2018-01) Erlank, Erica; Koekemoer, Lizette L.; Coetzee, MaureenBackground: The correct identification of disease vectors is the first step towards implementing an effective control programme. Traditionally, for malaria control, this was based on the morphological differences observed in the adults and larvae between different mosquito species. However, the discovery of species complexes meant that genetic tools were needed to separate the sibling species and today there are standard molecular techniques that are used to identify the two major malaria vector groups of mosquitoes. On the assumption that species-diagnostic DNA polymerase chain reaction (PCR) assays are highly species-specific, experiments were conducted to investigate what would happen if non-vector species were randomly included in the molecular assays. Methods: Morphological keys for the Afrotropical Anophelinae were used to provide the a priori identifications. All mosquito specimens were then subjected to the standard PCR assays for members of the Anopheles gambiae complex and Anopheles funestus group. Results: One hundred and fifty mosquitoes belonging to 11 morphological species were processed. Three species (Anopheles pretoriensis, Anopheles rufipes and Anopheles rhodesiensis) amplified members of the An. funestus group and four species (An. pretoriensis, An. rufipes, Anopheles listeri and Anopheles squamosus) amplified members of the An. gambiae complex. Conclusions: Morphological identification of mosquitoes prior to PCR assays not only saves time and money in the laboratory, but also ensures that data received by malaria vector control programmes are useful for targeting the major vectors.Item The assessment and aetiology of drug-induced ischaemic priapism(Springer Nature, 2024-12) Moodley, Divyen; Badenhorst, Anja; Choonara, Yahya; Adam, AhmedIschaemic priapism is a urological emergency characterised by a prolonged, painful erection unrelated to sexual stimulation. While several aetiological factors contribute to this condition, the pharmacological causes have gained significant attention in recent years. This narrative review aims to comprehensively assess ischaemic priapism, specifically focusing on its pharmacological aetiology. We propose an approach and assessment strategy to the numerous factors associated with pharmacologically induced ischaemic priapism. By enhancing our understanding of the harmacological causes of this condition, healthcare professionals can improve patient management and reduce the long-term complications associated with ischaemic priapism.Item Mobile Technology use in clinical research examining challenges and implivations for health promotion in South Africa: mixed methods study(JMIR Publications, 2024) Norris, Shane A.; Mabetha, Khuthala; Soepnel, Larske M.; Mabena, Gugulethu; Motlhathedi, Molebogeng; Nyathi, Lukhanyo; Draper, Catherine E.Background: The use of mobile technologies in fostering health promotion and healthy behaviors is becoming an increasingly common phenomenon in global health programs. Although mobile technologies have been effective in health promotion initiatives and follow-up research in higher-income countries and concerns have been raised within clinical practice and research in low- and middle-income settings, there is a lack of literature that has qualitatively explored the challenges that participants experience in terms of being contactable through mobile technologies. Objective: This study aims to explore the challenges that participants experience in terms of being contactable through mobile technologies in a trial conducted in Soweto, South Africa. Methods: A convergent parallel mixed methods research design was used. In the quantitative phase, 363 young women in the age cohorts 18 to 28 years were contacted telephonically between August 2019 and January 2022 to have a session delivered to them or to be booked for a session. Call attempts initiated by the study team were restricted to only 1 call attempt, and participants who were reached at the first call attempt were classified as contactable (189/363, 52.1%), whereas those whom the study team failed to contact were classified as hard to reach (174/363, 47.9%). Two outcomes of interest in the quantitative phase were "contactability of the participants" and "participants' mobile number changes," and these outcomes were analyzed at a univariate and bivariate level using descriptive statistics and a 2-way contingency table. In the qualitative phase, a subsample of young women (20 who were part of the trial for ≥12 months) participated in in-depth interviews and were recruited using a convenience sampling method. A reflexive thematic analysis approach was used to analyze the data using MAXQDA software (version 20; VERBI GmbH). Results: Of the 363 trial participants, 174 (47.9%) were hard to reach telephonically, whereas approximately 189 (52.1%) were easy to reach telephonically. Most participants (133/243, 54.7%) who were contactable did not change their mobile number. The highest percentage of mobile number changes was observed among participants who were hard to reach, with three-quarters of the participants (12/16, 75%) being reported to have changed their mobile number ≥2 times. Eight themes were generated following the analysis of the transcripts, which provided an in-depth account of the reasons why some participants were hard to reach. These included mobile technical issues, coverage issues, lack of ownership of personal cell phones, and unregistered number. Conclusions: Remote data collection remains an important tool in public health research. It could, thus, serve as a hugely beneficial mechanism in connecting with participants while actively leveraging the established relationships with participants or community-based organizations to deliver health promotion and practice.Item Molecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials(Nature Research, 2023) Madhi, Shabir A.; Ahani, Bahar; Tuffy, Kevin M.; Aksyuk, Anastasia A.; Wilkins, Deidre; Abram, Michael E.; Dagan, Ron; Domachowske, Joseph B.; Guest, Johnathan D.; Ji, Hong; Kushnir, Anna; Leach, Amanda; Mankad, Vaishali S.; Simões, Eric A. F.; Sparklin, Benjamin; Speer, Scott D.; Stanley, Ann Marie; Tabor, David E.; Hamrén, Ulrika Wählby; Kelly, Elizabeth J.; Villafana, TonyaNirsevimab is a monoclonal antibody that binds to the respiratory syncytial virus (RSV) fusion protein. During the Phase 2b (NCT02878330) and MELODY (NCT03979313) clinical trials, infants received one dose of nirsevimab or placebo before their first RSV season. In this pre-specified analysis, isolates from RSV infections were subtyped, sequenced and analyzed for nirsevimab binding site substitutions; subsequently, recombinant RSVs were engineered for microneutralization susceptibility testing. Here we show that the frequency of infections caused by subtypes A and B is similar across and within the two trials. In addition, RSV A had one and RSV B had 10 fusion protein substitutions occurring at >5% frequency. Notably, RSV B binding site substitutions were rare, except for the highly prevalent I206M:Q209R, which increases nirsevimab susceptibility; RSV B isolates from two participants had binding site substitutions that reduce nirsevimab susceptibility. Overall, >99% of isolates from the Phase 2b and MELODY trials retained susceptibility to nirsevimab.Item Comparable safety and non‑inferior immunogenicity of the SARS‑CoV‑2 mRNA vaccine candidate PTX‑COVID19‑B and BNT162b2 in a phase 2 randomized, observer‑blinded study(Nature Research, 2024) Madhi, Shabir A.; Tran, Richard; Martin‑Orozco, Natalia; Panicker, Rajesh Krishnan Gopalakrishna; Pastrak, Aleksandra; Reiter, Lawrence; Grefrath, Johann; Zidel, Bian; Ostrowski, Mario; Gommerman, Jennifer; Cooper, CurtisIn the aftermath of the COVID-19 pandemic, the evolution of the SARS-CoV-2 into a seasonal pathogen along with the emergence of new variants, underscores the need for dynamic and adaptable responses, emphasizing the importance of sustained vaccination strategies. This observer-blind, double-dummy, randomized immunobridging phase 2 study (NCT05175742) aimed to compare the immunogenicity induced by two doses of 40 μg PTX-COVID19-B vaccine candidate administered 28 days apart, with the response induced by two doses of 30 µg Pfzer-BioNTech COVID-19 vaccine (BNT162b2), administered 21 days apart, in Nucleocapsid-protein seronegative adults 18–64 years of age. Both vaccines were administrated via intramuscular injection in the deltoid muscle. Two weeks after the second dose, the neutralizing antibody (NAb) geometric mean titer ratio and seroconversion rate met the non-inferiority criteria, successfully achieving the primary immunogenicity endpoints of the study. PTX-COVID19-B demonstrated similar safety and tolerability profle to BNT162b2 vaccine. The lowest NAb response was observed in subjects with low-to-undetectable NAb at baseline or no reported breakthrough infection. Conversely, participants who experienced breakthrough infections during the study exhibited higher NAb titers. This study also shows induction of cell-mediated immune (CMI) responses by PTX-COVID19-B. In conclusion, the vaccine candidate PTX-COVID19-B demonstrated favourable safety profle along with immunogenicity similar to the active comparator BNT162b2 vaccine.