School of Clinical Medicine (ETDs)
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Item Identification of (Novel) Immune Targets with Potential Roles in the Progression of Pancreatic Ductal Adenocarcinoma (PDAC)(University of the Witwatersrand, Johannesburg, 2024) Nsingwane, Zanele; Nweke, EkeneBackground: Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a growing incidence and mortality despite novel therapeutic strategies. Its aggressiveness and difficulty to treat suggest the need for a better understanding of associated molecular mechanisms which could be targeted for treatment. The complement signalling pathway may play diverse roles in PDAC by eliciting an immune response, inducing inflammatory responses, and may elevate pathways linked to chemoresistance. However, their role in the progression of PDAC is not fully understood. This study aimed to identify potential immune response-related targets in a group of patients. Methods: In this study, 30 tissue samples (tumours and corresponding normal tissues) were obtained from 15 PDAC patients, 34 plasma samples were obtained from 25 PDAC patients, 6 patients with chronic pancreatitis, and 3 healthy control participants. Targeted pathway-specific PCR analysis was conducted to determine the gene expression profiles of immune-response-related genes. The circulating levels of complement proteins C3 and C5 were further investigated. Pharmacological inhibition of the complement pathway in MIA PaCa-2 pancreatic cancer cell lines was performed and the effect on cells was assessed by cell proliferation, cell migration, and cell cycle assays. Finally, SWATH-mass spectrometry was performed to identify potential molecular mechanisms during inhibition. Results: The results identified C3 to be overly expressed in early PDAC compared to later stages in plasma (p=0.047). Pharmacological inhibition of the complement pathway led to increased cell growth (p<0.0001), proliferation (p=0.001) and migration (p=0.002) in vitro. Proteomic analysis implicated several proteins such as the mitochondrial and histone proteins, that could play a role in inducing this phenotype. Conclusion: Both Complement C3 and C5 are elevated in PDAC samples compared to healthy ones. Furthermore, the inhibition of the complement pathway was shown in vitro to result in a more aggressive phenotype by stimulating cellular growth, proliferation, and migration, indicating the involvement of complement C3 and C5 in tumour progression. This study helps to further delineate the role of the complement pathway in PDAC progression.Item An in-silico analysis of the glycosylation inhibitors Brefeldin A and Tunicamycin C in colorectal cancer; characterization of novel targets(University of the Witwatersrand, Johannesburg, 2024) Naidoo, VivashColorectal cancer (CRC), a prevalent malignancy in South Africa, is significantly influenced by posttranslational modifications such as glycosylation. This study investigates the complex interactions between genes, signalling pathways, and cellular processes involved in CRC progression and glycosylation. The glycosylation inhibitors, Tunicamycin and Brefeldin A, are known to hinder colon cancer cell proliferation, migration, and invasion, making them potential therapeutic agents. We used Swiss Target Prediction Software to identify target proteins for both compounds and revealed that Protein Kinase C Alpha (PRKCA), Peroxisome Proliferator- Activated Receptor Gamma (PPARG), and Mitogen-Activated Protein Kinase 1 (MAP2K1) are specific for Brefeldin A, and TK1 and PRKCA for Tunicamycin, respectively. These proteins were selected based on their potential role in the glycosylation process and their role in CRC-related pathways. Further, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis disclosed significantly enriched pathways, including Epstein-Barr virus infection, cellular senescence, and cancer pathways. The 3D-crystallographic structures of PrKC1 (PDB ID 6ar4), TK1 (PDB ID 1w4r), PrCK1 (PDB ID: 6ar4) and MAPK (PDB ID: 3eqc) were retrieved from RCSB Protein Data Bank. The compounds BSP and EGCG were downloaded from PubChem. All non-relevant co-crystallized molecules, including ions, crystallographic water, and others, were removed. Missing residues in the proteins were filled in using the MODELLER algorithm on the UCSF Chimera Graphic User Interface. Molecular docking of Tunicamycin C and Brefeldin A was performed with UCSF Chimera, and the docked conformations were visualised in Maestro and Chimera. The complexes with the top docking scores were selected and prepared for molecular dynamics simulation studies to offer structural and dynamic perspectives on the inhibitory potential of the compounds against the target proteins. The Origin Lab software tool was used to post- analyze the docking conformations. Molecular Dynamics simulation was conducted using Graphics Processing Units version of the Particle Mesh Ewald Molecular Dynamics engine in the AMBER18 suite. Our investigation into the dynamic events leading to the proximal binding of Tunicamycin at the pockets of TK1 and PrKC1 suggested that the binding of Tunicamycin induced a conformational perturbation of the 3D structures of these proteins, resulting in a structural deviation that inhibited their activity. Tunicamycin's time-based dynamics indicated a stable pattern, leading to optimal interaction and maximal stabilization in the hydrophobic pockets of TK1 and PrKC1. Binding energy calculations showed a high-affinity interaction of Tunicamycin with these proteins. Similarly, the structural investigation revealed that the binding of Brefeldin A to Mitogen- Activated Protein Kinase (MAPK) and Protein Kinase C (PrKC1) inhibited their activity. A detailed analysis of active site residues revealed crucial residues that contributed to the binding stabilization of Brefeldin A. It was noted that the Brefeldin A/MAPK complex produced a binding energy of -22.18±4.50Kcal/mol while the Brefeldin A/PrCK1 complex produced a binding energy of -23.90±5.36Kcal/mol. These findings provide crucial insights into designing novel inhibitors of TK1 and PrKC1, potentially blocking glycosylation progression in cancer treatment. This study underscores the potential for exploiting glycosylation inhibition as a therapeutic strategy against CRC, opening avenues to mitigate cancer progressionItem Association of genetic variants with breast cancer intrinsic subtypes and splice variants of the fibroblast growth factor receptor 2 in a South African population(University of the Witwatersrand, Johannesburg, 2023) Dix-Peek, Thérèse; Duarte, Raquel; Augustine, TanyaAfrican populations are more genetically diverse than other groups, but there is a paucity of information about breast carcinomas. South Africa uses immunohistochemistry (IHC) rather than multiparameter genomic assays, such as PAM50, to classify tumors. Genome-wide association studies have shown variants in fibroblast growth factor receptor 2 (FGFR2) are associated with breast cancer, but this has not been examined in black, African women. This thesis investigated intrinsic subtypes; the effects of four FGFR2 single nucleotide polymorphisms (SNPs), and FGFR2 mRNA expression and splice variants associated with breast cancer subtypes. In a cohort of 378 breast cancer patients, we investigated the concordance between tumor samples classified by IHC and PAM50. The SNPs rs2981582, rs35054928, rs2981578 and rs11200014 were examined in 1001 patients with, and 1005 participants without, cancer. The FGFR2 mRNA expression and IIIb and IIIc isoforms were examined using cBioPortal, TCGA Splice Seq and TSVdb databases. Statistical analyses were performed using STATA v14.2. This study was approved by the Human Research Ethics Committee of the University of the Witwatersrand (clearance certificate no M161116). IHC classified patients as estrogen receptor-positive (77.45%), progesterone receptor-positive (70.56%), and epidermal growth factor receptor 2 (HER2)-positive (32.28%). These results, together with ki67, were used as surrogates for intrinsic subtyping, and showed 7% IHC-A-clinical, 73% IHC-B-clinical, 5% IHC-HER2-clinical and 15% triple negative (TNBC). PAM50 gave 19% luminal-A, 32% luminal-B, 24% HER2-enriched and 25% basal-like. Concordance was highest between basal-like and TNBC and lowest between luminal-A and IHC-A. There was no association with the SNPS, rs2981582, rs35054928, rs2981578 and rs11200014, and breast cancer in the black, South African population. However, rs2981578 was associated with invasive lobular carcinoma (ILC) and HER2-positive breast cancer was associated with rs11200014. ILC and ER-positive cancers were associated with higher FGFR2, while TNBC or HER2-positive breast cancers were associated with lower FGFR2. The IIIb isoform was prevalent in ER- positive breast cancer and IIIc prevalent in HER2-positive breast cancer. Genetic information from the black South African population can improve understanding of breast cancer in our population. We suggest that the cutoff for Ki67 be changed to 20-25% to better reflect the luminal subtype classifications. Lobular carcinoma is associated with rs2981578, and HER2-postive carcinoma is associated with rs11200014. Increased levels of FGFR2 mRNA and IIIb isoforms are associated with ER-positive breast cancer, while lower levels of FGFR2 and higher IIIc isoforms are associated with HER2 and TNBCItem Gene expression patterns of signalling pathways in PDAC: towards inhibiting metastases(University of the Witwatersrand, Johannesburg, 2024) Xelwa, Ntombikayise Hendrietta MarciaPDAC has a poor prognosis, with its prevalence varying by geographical location. In South Africa, PDAC ranked seventh among all cancer-related deaths in 2020 for both sexes. Specifically, it was the seventh leading cause of cancer death among males and the sixth among females. In 2020, an estimated 1,982 cancer deaths in South Africa were attributed to pancreatic cancer, with 1,006 occurring in males and 976 in females. However, the annual reported number of PDAC deaths in South Africa varies. This study aimed to identify potential novel therapeutic targets for PDAC in patients from the African population. Following ethical approval, tissue from fifteen patients (15 tumour and 15 corresponding normal tissues) were obtained during Whipple procedures from PDAC patients who consented to the study. Despite the development of new treatment strategies, patient outcomes have not significantly improved underscoring the necessity for extensive research to identify novel treatment options. A discovery study was conducted to determine the gene expression profile of signalling pathway-related genes using PDAC tissue samples. Top upregulated pathways included those involved in cytokine signalling, receptor kinase signalling, and PI3/Akt signalling. SPP1 was one of the most highly expressed genes identified in PDAC patients compared to normal corresponding tissues suggesting its potential role in the progression of the disease. To investigate SPP1's role in PDAC, RNA interference was employed to knockdown SPP1 in a PDAC cell line, MIA PaCa-2. Knockdown was confirmed by a significant reduction in SPP1 expression at the mRNA level. Combining SPP1 knockdown with conventional chemotherapy used for PDAC, gemcitabine, resulted in a synergistic effect, leading to an enhanced early apoptotic response. The study also examined the migratory and invasive capabilities of MIA PaCa-2 cells, revealing a noticeable decline in these abilities upon reduction in SPP1 expression with gemcitabine treatment. Furthermore, proteomic analyses uncovered the complex network of cellular processes influenced by the downregulation of SPP1 and the synergistic effects of combination therapy. Altogether, the findings from this study demonstrate the role of SPP1 in PDAC indicating that it could serve as a promising therapeutic target. The synergistic effects observed when SPP1 knockdown was combined with gemcitabine treatment suggest a potential avenue for developing more effective treatments for PDAC while exploring tumour cell adaptation for survival.Item Evaluation of the postgraduate family medicine decentralised training programme at the university of Witwatersrand, South Africa, using the logic model(University of the Witwatersrand, Johannesburg, 2024) Erumeda, Neetha Joe; George, Ann ZetaPostgraduate family medicine decentralised training programmes were implemented in South Africa about 15 years ago, but the University of the Witwatersrand’s programme has not been comprehensively evaluated. This study evaluated the programme using a complex programme evaluation logic model based on linearity theory. This theory assumes ideal inputs and processes produce good programmatic outputs and outcomes. Resources and support were evaluated as inputs, postgraduate supervision and workplace-based learning as processes, supervisory feedback as outputs and workplace-based assessments as outcomes. A parallel convergent mixed-methods instrumental case study was conducted with purposively-sampled family physicians (n=11) and trainees (n=11) from five decentralised training sites. Semi-structured interviews were audio recorded, transcribed verbatim, and analysed inductively using MAXQDA 2020 software. Descriptive statistical analysis was conducted on components of registrars’ learning portfolios (scores, supervisory feedback, and skills competence) and examination results using Stata 14.2 software. An integrative analysis involving transforming the quantitative results to qualitative findings and drawing meta-inferences was conducted. The integrated findings were used to modify the initial logic model and identify key recommendations to optimise the programme. The integrative analysis identified the need for more material and human resources, university and district management support, and standardised resources, supervision, and learning practices. Supervisors’ knowledge, skills, and behaviours varied across sites and their feedback was insufficient regarding soft skills like clinical reasoning and patient negotiation. Workplace-based assessments did not meet the required standards across training years and districts. Interpersonal interactions with patients, peers, supervisors and other professionals, engagement in district activities, promoted learning. Registrars’ professionalism and self-learning need improvement. The key recommendations include more explicit national guidelines, sufficient support from the provincial department, university, and district management, well maintained infrastructure, sufficient skilled supervisors, more professional development training for supervisors, protected time for registrar learning, and better use of self-learning and reflection. Emulating successful contextual adaptations while addressing challenges across sites contributes to thriving decentralised training programmes in district health systems. An improved understanding of the concepts and their interrelationships in training programmes could be translated to similar decentralised training platforms across medical disciplines of sub-Saharan Africa or low-middle income countriesItem The effects of indigenous South African plant extracts (cotyledon c. orbiculata and tulbaghia. violacea) on triple negative breast cancer cells(University of the Witwatersrand, Johannesburg, 2024) Alaouna, Mohammed; Dlamini, ZodwaThis dissertation explored the potential therapeutic applications of water and methanol extracts of C. orbiculata and Tulbaghia violacea, indigenous to Southern Africa, targeting triple-negative breast cancer (TNBC). TNBC, a significant subset of breast cancer cases, is notably challenging because of the absence of key hormone receptors, often leading to less favourable patient outcomes and a high relapse rate within five years. The research approach was both thorough and meticulous, utilising two cell lines: one representing normal breast tissue and the other representing TNBC. Extensive cytotoxicity assays were conducted to determine the IC50 values for TNBC cells, which is critical for understanding how plant extracts affect cellular activities such as migration, invasion, adhesion, cell cycle regulation, and apoptosis induction. Additionally, the antioxidant properties of these extracts were examined, which showed significant effects, especially in the aqueous extract of Tulbaghia violacea, on TNBC cellular dynamics. This study employed a comprehensive array of analytical techniques, including Fourier transform infrared spectroscopy (FTIR), gas chromatography-mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR) spectroscopy, to identify the specific molecular constituents of these extracts. Computational docking studies have focused on the interactions between these molecules and the anti-apoptotic protein, COX2. Whole transcriptome sequencing of RNA from both TNBC and normal breast cells treated with T. violacea extract provided valuable insights into the affected signaling pathways. An antibody array assay further elucidated protein changes in the receptor tyrosine kinase (RTK) pathway. The half-maximal inhibitory concentration (IC50) values were determined for the aqueous and methanol extracts of T. violacea at 400 μg/mL and 820 μg/mL, respectively, and for C. orbiculata at 830 μg/mL and 700 μg/mL, respectively. Exposure to the water-soluble extract of T. violacea resulted in a marked increase in apoptosis in TNBC cells, with approximately 82% undergoing programmed cell death, compared to 32% in normal breast cells. Chemical profiling identified a range of compounds, including 36 distinct compounds identified through GC-MS and 61 identified through NMR, many of which bear structural similarities to known anti-cancer agents. Notably, five compounds demonstrated a high affinity forbinding to COX2, with d-glycero-d-galacto-heptose achieving an impressive docking score, surpassing several established COX2 inhibitors. This study highlights the therapeutic potential of T. violacea compounds and lays the groundwork for further exploration of their mechanisms of action and potential applications in cancer treatment. This emphasises the importance of investigating natural plant extracts as a source for the development of new and effective treatments for TNBC, which is an area of urgent need in oncologyItem An ethico-legal analysis of broad consent for biobank research in South Africa: Towards an enabling framework(University of the Witwatersrand, Johannesburg, 2024) Maseme, Mantombi RebeccaBiobanks preserve collections of human biological material and data for the benefit of medical research. Using and transferring human biological data and materials both inside and outside of South Africa is often a requirement of biobank research. Broad consent is allowed by the South African National Department of Health Ethics Guidelines but appears to be prohibited by section 13(1) of the Protection of Personal Information Act 4 of 2013. Additionally, the Act mandates that all personal data (including biobank sample data) be collected for legitimate, definite, and clearly stated purposes. There is room for several interpretations of the Act because of this discord between the two instruments. Given the connection between the transfer of samples and data, the long-term nature of biobanking, which makes it impractical to provide too much or adequate information because it is simply not available at the time of sample collection, and the various ways that the Protection of Personal Information Act 4 of 2013 have been interpreted, I aim to respond to the following question: How should South Africa’s current regulatory framework appropriately permit broad consent use for biobank research where the transfer of samples and their associated data are contemplated? The research question is addressed by applying ethical principles and theories, as well as analysing and evaluating relevant ethico-legal frameworks and literature. The study involves no research participants and no collection or analysis of any new data. Arguments for and against using broad consent for biobank research are discussed by demonstrating the potential for biobank research to do a great deal of good for humanity; the ambiguity in the current regulatory framework regarding whether broad consent is permissible for personal information/data; and the ethical justifiability of broad consent. In summary, the proposed regulatory framework amendments are those that would be required to allow for ethically justifiable biobank research broad consent use. These include removing regulatory ambiguity regarding broad consent use, ensuring adequate safeguards for research participants by specifying rules for data access and personal information processing, and incorporating consent form information requirements into the national Consent Template as specified in the National Department of Health Ethics GuidelinesItem Medical students’ professional identity formation during a social upheaval: a qualitative study(University of the Witwatersrand, Johannesburg, 2023) Mokhachane, MantoaThis phenomenological qualitative study, with an autoethnographic aspect, explored the University of the Witwatersrand’s medical students’ experiences of professionalism and professional identity formation amidst protests and social upheaval, namely, #FeesMustFall protests. The socio-historical autoethnographic sections emanate from my undergraduate journey in the same medical school 32 years before this study. I interviewed 13 participants. The participants’ stories echoed my own story during my undergraduate years in medical training, hence the inclusion of autoethnography. In this study, I question the under- representation of previously marginalised groups in the discourse of professionalism and professional identity formation. I also question the lack of an African influence on professionalism and professional identity formation. This study was conducted at the University of the Witwatersrand after obtaining Human Research Ethics Committee approval. I used an interpretive qualitative phenomenological enquiry in order to understand the meaning of students’ experiences. I also did not want to bracket myself, as my experiences resonated with those of the contemporary students, hence the choice of an interpretive instead of a descriptive phenomenological approach. A purposive sample was drawn from medical students. Thirteen semi-structured interviews were conducted in 2020, during the Covid-19 pandemic. Interviews were conducted with 13 participants, eight final-year medical students and five recent graduates who were in the first- or second-year internship (residency) training. The participants were five women (four Black and one White) and eight men (five Black and three White). An interview guide was used to probe the students’ journeys towards becoming doctors, their experiences during the #FeesMustall protests, experiences of professionalism and how #FeesMustFall impacted their professional identity development. Interviews were transcribed verbatim and analysed in MAXQDA 2020. I used an inductive approach, where each transcript was analysed as an individual case for the essence of its meaning and how participants’ experiences influenced their being and becoming doctors. When analysing the data through an African lens, Ubuntu, I used metaphors to allow the reorientation of professional identity formation, what professionalism means to contemporary students and how professionalism is weaponised against those who do not fit the western ideals of a medical professional. Racism was the foundation of many ills in medical education, particularly in the clinical spaces at the hospitals affiliated with the University of the Witwatersrand. This study highlights the contribution of Ubuntu-based values on professional identity formation and the influence of Ubuntu on the meaning of professionalism to contemporary medical students and recent graduates. It adds an African voice to the global western professional identity theories. This study encourages other researchers to explore their contexts to define professionalism and how professional identity is attained. I recommend reconstructing professionalism using Ubuntu as professionalism in medical education through letsema, Ubuntu, advocacy, and the acceptance of the intersectionality with which trainees enter medical educationItem Developing a framework to improve glycaemic control among patients with type 2 diabetes mellitus in Kinshasa, democratic republic of the Congo(University of the Witwatersrand, Johannesburg, 2023) Lubaki, Jean-Pierre FinaDiabetes mellitus is a significant problem globally with a higher impact in developing countries. Glycaemic control is one of the main goals of type 2 diabetes treatment, as it delays or avoids the occurrence of diabetes related complications. In sub-Saharan Africa, including the Democratic Republic of the Congo, glycaemic control rates are sub optimal. This study aimed to develop a framework to improve glycaemic control among patients with type 2 diabetes in Kinshasa, Democratic Republic of the Congo. This project comprises four sub-studies. The first sub-study was a systematic review and meta-analysis of studies published from 2012 to 2022 on the prevalence and factors driving glycaemic control in sub-Saharan Africa. Younger and older age, gender, lower income, absence of health insurance, low level of education, place of residence, family history of diabetes, longer duration of diabetes, pill burden, treatment regimen, side effects, use of statins or antihypertensives, alcohol consumption, smoking, presence of comorbidities/complications, and poor management were associated with poor glycaemic control. On the other hand, positive perceived family support, adequate coping strategies, high diabetes health literacy, dietary adherence, exercise practice, attendance at follow-up visits, and medication adherence were associated with good glycaemic control. The second sub-study was a concurrent parallel mixed methods cross-sectional analytical study among a total of 643 patients with type 2 diabetes — 23 in the qualitative phase and 620 in the quantitative phase — on factors associated with poor glycaemic control in Kinshasa. Five themes were identified as explanations for poor glycaemic control: financial constraints, limited social and relational support, difficulties with lifestyle changes, beliefs and practices about diabetes, and ability to adapt to caring for the illness. The quantitative phase showed that about two-thirds of the participants (67.8%; n=420) had poor glycaemic control and more than half were on insulin monotherapy (53.9%; n=334). No sociodemographic or lifestyle characteristics were associated with poor glycaemic control. Participants on monotherapy with insulin (AOR: 1.72 (95%CI:1.17-2.55)) had increased odds of poor glycaemic control compared to participants on oral hypoglycaemic drugs. In contrast, participants having and those having uncontrolled blood pressure (AOR: 0.60 (95%CI:0.39-0.92)) were less likely to have poor glycaemic control compared to participants having controlled blood pressure. The third sub-study was a qualitative study on the perspectives of 16 healthcare providers and 10 patients with type 2 diabetes on improving glycaemic control in Kinshasa. From the healthcare providers statements regarding improving glycaemic control, three themes were identified: strengthening the healthcare system, supporting persons with diabetes/population, and adopting supportive health policies. From the persons with diabetes perspectives three themes were also identified: need for support for caring of the illness, need for enhanced knowledge about diabetes, and the need for better communication with healthcare providers. Using the results of the first three studies, the fourth sub-study, a Delphi study, brought together 36 experts on the management of diabetes, who developed and agreed on the following strategies for improving glycaemic control in Kinshasa: strengthening the healthcare system, enhancing the awareness of diabetes, alleviating the financial burden of diabetes, enhancing the adoption of lifestyle modifications, and reducing the proportion of undiagnosed diabetes. These five strategies included a total of 39 potential interventions. Strengthening the healthcare system for better care promotes better organization and provision of services for diabetes care. Enhancing the awareness of diabetes among the population/patients stresses the need to develop and share information about diabetes through the most appreciated channels by the population. Alleviating the financial burden of diabetes targets for the long-term the need for universal health coverage, and meanwhile, encouraging the development of community-based health insurance. It also includes the search for a reduction in costs of diabetes medicines and materials through public-private partnerships. Enhancing the adoption of lifestyle modifications in our setting passes through the provision of accurate information on the content of lifestyle changes, and developing realistic exercise and dietary plans. Reducing the proportion of undiagnosed patients with diabetes needs to increase the detection of diabetes by targeting high risk groups at the level of primary care settings. This study highlighted the need to ensure that patients with type 2 diabetes benefitted from the full package required for diabetes care in a broader framework of managing non-communicable diseases in KinshasaItem Children on the streets of Ibadan, Nigeria: experiences, family dynamics and health status(University of the Witwatersrand, Johannesburg, 2023) Obimakinde, Abimbola Margaret; Moosa, ShabirBackground This research explored the phenomenon of children-on-the-streets of Ibadan, Nigeria. These children are found on the streets without any adult supervision. They constitute the majority of street children but are linked to their families and therefore they come from and return home daily. The Bronfenbrenner ecological system theory on children’s development and interactions within contextual ecosystems, underpinned this study. This research aimed to understand the phenomenon of children on the streets of Ibadan, specifically their family dynamics, lived experiences, health, and needs. Method This was mixed-method research, although largely a qualitative approach was employed to obtain the narratives of children on the streets and significant adults in the children’s exosystem. All ethical principles were observed in the conduct of the studies. In-depth interviews, street photographs, field notes and observation were employed during the data collection, between June 2021 to September 2021. Fifty-three (53) participants including street shop owners, children on the street, Oyo State’s child welfare officers and parental figures were selected from a street in each of Ibadan's five urban Local Government Areas (LGAs). These LGAs include the Ido, Northwest (NW), Southwest (SW), North(N) and Northeast (NE). Relevant quantitative data was collected from the children only. The sampling of participants was initially purposive and subsequently by snowball technique. Framework analysis supported with Atlas Ti version 22, was conducted and the data was triangulated, for a robust understanding of the lived experiences, health, family dynamics and needs of children on the streets of Ibadan. Principal component analysis and frequencies were conducted with SPSS version 21 for the descriptive quantitative data obtained from the 21 recruited children, solely for thick description. The quantitative data included the Household Hunger Scale (HHS), Wealth Index (WI), and Body Mass Index (BMI). Results The participants comprised, 12 child welfare officers, 10 street shop-owners, 10 parental figures and 21 children on the street. The children were average 15.8 years old and had spent at least 4 years on the streets. The children had structurally defective families including broken large-sized families (18 of the 21 children were from families with > 4 children) with attendant poor socioeconomic resources and poor filial interpersonal relationships. More than half of the children were from families with poor WI scores. The lived experiences of children on the street included beneficial experiences related to the monetary gains on the streets with overwhelming challenging experiences. The challenging experiences included financial crisis, school failure, initiation into prostitution and street gangs, induction into substance use, harassment on the street, risk of kidnapping and ritual killing. The physical health problems of the children on the streets included poor nutrition, poor toilet habits, allergies, infectious diseases, and physical minor and major injuries (40% of them had evident facial or limb scars) sustained on the streets. Half of the children had a BMI in the “underweight” range and a third had HHS scores which indicated moderate household hunger. The mental health problems included sexual, verbal and substance abuse, although psychological strength was found in a few children on the street, more than half of the children responded “yes” to feelings of sadness or hopelessness. The children on the streets of Ibadan had many unmet needs due to governmental shortcomings including failure of the Oyo State’s education systems, inadequate vocational training programs for uneducable children, lax State child welfare laws, difficult rehabilitation of children on the street and poor policies on family size. There were bits of interventions which catered to children on the streets including parental poverty alleviation schemes and community-based child welfare alert programmes. Discussion The family dynamics driving child streetism for family-connected children in Ibadan are devaluation of family life, parental irresponsibility, and poor filial relationship, underscored by large family size, economic constraints and socio-cultural decadence. The family setting is that of broken homes with many children from a monogamous union or blended families with poor financial and social resources. The mothers were either in a monogamous unwedded union with “absent” fathers cohabiting with another woman. There was an economic-oriented filial relationship with the parentification of the children. The lived experiences of children on the street included beneficial experiences centred around monetary gains, overshadowed by challenging experiences. Monetary gains were meagre and predominantly through the hawking of edible produce. The challenging experiences included the loss or theft of money made on the streets by these children, school failure, initiation into prostitution and street gangs, induction into substance use, street harassment, risk of kidnapping and ritual killing. The physical health problems included poor carbohydrate-based diet with consequent undernutrition, open defecation with attendant health risks, predisposition to allergies, acquisition of infections including STIs, minor physical injuries and a few deaths from Road Traffic Accidents (RTAs). Sexual, verbal and substance abuse were common mental health problems, although few children acquired mental resilience. The governmental shortcoming which feds the epidemic of children on the street included the failure of the Oyo State’s education systems, inadequate vocational training programs for uneducable children, lax State child welfare laws, difficult rehabilitation of children on the street and poor policies on family size. The parental poverty alleviation scheme was one of the state’s government interventions, however, jurisdictional failure overshadows the efforts against child streetism in Ibadan. Conclusion The continuing influx of children on the streets of Ibadan is due to the peculiar family dynamics and the prevailing governmental jurisdictional failure. The presence of children on the street is fraught with a lot of difficult lived experiences and health problems. An appreciation of these factors, and synchronized targeted multi-level interventions within the ecosystems can positively influence measures to combat the epidemic of children on the streets of Ibadan, Oyo state, South- west Nigeria