School of Health Sciences

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Comparative study of covalent & non-covalent drug inhibitory mechanism investigation: targeting HSP72 protein in cancer therapy using molecular modelling techniques.
(2021) Aljoundi, Aimen Khalefa Misbah.; Soliman, Mahmoud Elsayed Soliman.
Cancer is the most complicated and diverse disease that has been menacing human beings worldwide. Up to date, important advancement has been done to improve the existing therapeutic interventions in the treatment and management of cancer. However, the side effect of these drugs that are mostly associated with the “off-target” effects is a perpetual failure in cancer drug development. Therefore, efficient regimen with minimal toxicities and high drug target selectivity should be achieved. Covalent inhibition is an emerging field in drug discovery and a very distinct category of therapeutics that reduces adverse side effects and possible interactions that lead to drug resistance due to its attainable reactivity and high selectivity. The Heat shock proteins (HSPs) play a crucial role in the clearance of damaged proteins by encouraging proteotoxicity and proteins acclamation. This process occurs by avoiding unsuitable stress-induced protein aggregation, ensure suitable refolding of denatured proteins, and promoting their degradation; thus, the involvement of this enzyme in many human diseases, including cancer. In this study, we delve into the structural features of one of the most crucial enzymatic targets of the stress proteins, the Heat shock proteins72. In drug development, the integration of computational techniques including molecular dynamic simulations, docking and molecular modelling has allowed drug developers to screen and syntheses millions of compounds and thus screen out possible lead drugs. Computer-Aided Drug Design has been validated as a cost-effective strategy to fast trace the drug discovery process due to these in silico methods. One of the characteristics of the HSP72 is its ability to be targeted either covalently or non-covalently through small drug molecules. Therefore, the above-mentioned methods, amongst several other computational tools were employed out in this study to provide insights into conformational changes that explain potential covalent and non-covalent inhibitory mechanisms, binding sites assessment features leading to promising small molecule inhibitor candidates. These combinatorial computational studies offer an inclusive in silico perspective to fill the gap in drug design studies about targeting protein degradation, thus providing insights toward the structural characteristics of the pivotal target and describing promising drug developments.
Design of advanced multifunctional biomaterial-based biomimetic and pH-responsive hybrid nanocarriers for antibiotic delivery against bacterial infections and sepsis = Ukwakhiwa kwama-haybridiangezona izedlulisela asebenza ngezindlela ezahlukahlukene enziwe nge-biomimetic eyakhiwe ngezinto eziphilayo abe ezwana futhi ne-pH. Lawa angezona izedluliseli ahambisa izinqindimagciwane ezilwisana nokutheleleka kwegciwane kanye nokudlanga kwekhovidi-19.
(2023) Elhassan, Eman Hussain Elmubarak.; Govender, Thirumala.; Omolo, Calvin Andeve.
Despite the notable improvements in the management of bacterial infections and sepsis, the mounting threat of antibiotic resistance on a global scale is leading towards a post-antibiotic era. Nano-drug delivery systems have improved the delivery and efficacy of various antibiotics. Biomimicry and stimuli-responsiveness have recently been used to improve the targetability of these nanocarriers, and enhance their localization at infected sites, thus improving overall therapeutic outcomes and reducing toxicity. Strategies such as targeting bacterial biofilms and efflux pumps can further enhance the delivery and effectiveness of antibiotics. Developing smart biomaterials with multifunctional properties to confer biomimetic, stimuli-responsive and antivirulence properties to antibiotic nanocarriers is the focus of ongoing research. Therefore, the general aim of this study was to investigate the potential of various novel multifunctional biomaterial-based hybrid nanocarriers (HNs), including biomimetic and/or pH-responsive HNs in enhancing the targeted delivery of antibiotics and modulating the proinflammatory response against bacterial infections and sepsis. In this study, two biomaterials with multifunctional activities, hyaluronic acid-lysine conjugate (HA-Lys) and tannic acid (TA), were employed to design, formulate, and extensively characterize innovative biomimetic and pH-responsive HNs for efficient and targeted delivery of antibiotics. The novel HA-Lys was synthesized and fully characterized using proton nuclear magnetic resonance (1H NMR) spectroscopy and Fourier-transform infrared spectroscopy (FT-IR). Then it was successfully employed with tocopherol succinate (TS) and Oleylamine (OLA) to fabricate biomimetic pH-responsive vancomycin-loaded hybrid nanostructured lipid carriers (VCM-HNLCs). The prepared VCM-HNLCs were spherical and had average diameters, zeta potential, polydispersity index, drug encapsulation efficiency and loading capacity of 110.77  1.69 nm, 0.11  0.02, -2.92  0.21 mV, 76.27  1.20 % and 8.36  0.25 %, respectively. Both HA-Lys conjugate and its respective nanoformulations had excellent biosafety profiles (>70 % cell viability and ˂ 1 % hemolytic effect). Possible VCM-HNLCs competitive inhibition activity to toll-like receptors 2 and 4 (TLR2 and TLR4) was demonstrated via microscale thermophoresis (MST) analysis, which showed a 5-times and 16-times lower Kd values than their natural substrates peptidoglycan (PGN) and lipopolysaccharide (LPS), respectively. VCM-HNLCs exhibited a pH-responsive drug release profile under acidic conditions, higher bacterial killing kinetics, enhanced antibacterial, anti-biofilm, and efflux pump inhibition activities over bare VCM. Also, they showed an improved activity in neutralizing reactive oxygen species (ROS) and modulating the inflammatory response induced by LPS. On the other hand, tannic acid (TA) and Oleylamine (OLA) were successfully employed to formulate biomimetic ciprofloxacin-loaded tannic acid hybrid nanoparticles (CIP-loaded TAH-NPs) to enhance the efficacy of CIP against bacterial infections and sepsis. The prepared HNs had onion-shaped morphology, with average diameters, zeta potential, polydispersity index, drug encapsulation efficiency and loading capacity of 85.65 ± 0.89 nm, 0.126 ± 0.01, +16.3 ± 0.23 mV, 68.73 ± 0.54 % and 6.86 ± 0.09 %, respectively. The hemolysis and MTT assays confirmed the biosafety and non-hemolytic activity of CIP-loaded TAH-NPs formulations (>70 % cell viability and ˂ 1 % hemolytic effect). The results of MST investigations and in-silico simulations demonstrated that TA and its nanoformulation (CIP-loaded TAH-NPs) competitively inhibited TLR4 compared to its natural substrate LPS. CIP-loaded TAH-NPs showed a diffusion-based sustained release profile at physiological pH 7.4. Also, in comparison to bare CIP, the hybrid nanovesicles demonstrated improved antibacterial, anti-biofilm and efflux pump inhibition properties, as well as faster bacterial killing kinetics. Moreover, they showed a significant neutralization of ROS and the ability to control the inflammatory responses brought on by LPS. In summary, VCM-HNLCs and CIP-loaded TAH-NPs were successfully formulated and showed significant improvement in antibiotics efficacy and overall therapeutic outcomes. This study confirmed the potential of biomimetic stimuli-responsive antibiotic hybrid nanocarriers for enhancing antibiotic efficacy against bacterial sepsis and addressing the antimicrobial resistance crisis. The data from this study has resulted in one first-authored review article, two first-authored research publications and one co-authored review article. Iqoqa. Nakuba kubonakala ukuba ngcono ukwelashwa kokutheleleka ngamagciwane kanye nokudlanga kwekhovidi-19 ukuqina kokuphikisana nokusebenza kwezinqandimagciwane emhlabeni jikelele kuholela ekuthi kubhekwe esikhathini lapho kuzobe kungasasetshenziswa izinqandimagciwane. Izindlela zokuhanjiswa kwemithi eyizinhlayiya ezincane kakhulu ezaziwa ngama-nano-drug zenze kusheshe ukuhanjiswa kanye nokusebenza ngendlela efanele kwezinqandimagciwane ezihlukahlukene. Sekusetshenziswe indlela yokubukela emvelweni kanye nokubheka ukusebenza kwezikhuthazi ukuze kuthuthukiswe ukufinyelela lapho kufanele khona kwalawa ma-nano-carrier, futhi kuthuthukiswe nokuzinza kwawo ezingxenyeni zomzimba ezitheleleke ngegciwane okwenza kusheshe kubonakale ukuphola ngokushesha kunciphe noshevu emithini. Amasu afana nokuhlasela ungwengwezi olwemboze amagciwane kanye namaphrotheyni akhipha ubuthi kumaseli aziwa ngama-efflux pump angaphinde athuthukise ukuhanjiswa kanye nokusebenza kahle kwezinqandimagciwane. Ucwaningo oluqhubekayo lusekuthuthukiseni izinto zokusebenza ezakhiwe ngemvelo zibe zinezimo ezisebenza ngokuhlukahlukana ukuze zinikeze amandla okumelana nezikhuthazi kanye nokulwisana namagciwane kuma-nanocarrier. Ngakho-ke, inhloso yalolu cwaningo ukuhlola ukuthi ama-nanocarrier ayizinhlobo ezintsha ezisebenza ngezindlela ezihlukahlukene abe eyingxubevange enziwe ngokususelwe emvelweni (HNs) okuhlanganiswa kuwo ama-HNs akopela ekusebenzeni kwemvelo kanye/noma asebenzisana ne-pH angasebenza kangakanani noma kanjani ukuthwala izinqandimagciwane ziye ngqo lapho okumele ziye khona kanye nokulawula ukungavuvukali uma kunokutheleleka ngegciwane noma kune-sepsisi. Kulolu cwaningo kwasetshenziswa izinto zokusebenza ezakhiwe ngemvelo ezimbili ezenza imisebenzi ehlukahlukene i-hyaluronic acid-lysine conjugate (HA-Lys) kanye ne-tannic acid (TA) ukuze kwakhiwe futhi kucatshangwe kabanzi ama-HNs aphambili ngokubukela emvelweni futhi asebenzisanayo ne-pH ukuze kuthwaleke izinqandimagciwane ngendlela efanele nezifika kahle lapho kumele ziyosebenza khona. Kwahlanganiswa i-HA-Lys entsha yahlolisiswa kusetshenziswa i-spectroscopy esiyi- proton nuclear magnetic resonance (1H NMR) kanye ne- Fourier-transform infrared spectroscopy (FT-IR). Yase isetshenziswa ngempumelelo isetshenziswa ne- tocopherol succinate (TS) kanye ne- Oleylamine (OLA) ekwenzeni izithuthi ezisamafutha ezisebenza njengokwasemvelweni futhi okusebenzisanayo ne-pH kube kuyingxubevange egcwele i-vancomycin (VCM-HNLC). Ama-VCM-HNLC akhiwa ayeyimbulunga enobubanzisiyingi obuyisilinganisomaphakathi, i-zeta potential, i-polydispersity index, ukugcineka ngokufanele kobungako bomuthi ozinze lapho okumele uhlasele khona , okwaziwa nge- drug encapsulation efficiency, kanye nobungako bomuthi ongafakwa oyi- 110.77  1.69 nm, 0.11  0.02, -2.92  0.21 mV, 76.27  1.20 % and 8.36  0.25 %, ngokulandelana. Kokubili ukuhlangana kwesikhashana kwe-HA-Lys kanye nama-nanoformulation ayo alandelayo kwakhombisa isimo esihle sokuphepha (>70 % ukusebenza kwamaseli kanye nemithelela kulokho okuhlangene nokuqhuma kwemithambo yegazi ˂ 1 %). Kwavela ukuthi kungenzeka kube nokuncintisana nezithiyo ze-VCM-HNLC kuma-receptor 2 kanye no-4(TLR2 kanye ne-TLR4) asebenza njengabalindisango. Lokhu kwakhonjiswa uhlaziyo lwe-microscale thermophoresis (MST) olwakhombisa ukwehla kwama-K value ngokuphindwe ka-5 kanye naka-16 uma kuqhathaniswa nama- natural substrates peptidoglycan (PGN) kanye nama- lipopolysaccharide (LPS)awo, ngokulandelana. Ama-VCM-HNLC akhombisa ukukwazi ukukhipha umuthi osebenzisana ne-pH ngaphansi kwezimo ezine-esidi, uhlololumbanozithako oluphezulu ekubulaleni amagciwane, amandla aphezulu okulwisana namgciwane, ukulwisana nongwengwezi lokuphilayo, kanye nokusebenza kwezithibi ze-efflux pump kuma-VCM ahlezi obala. Okunye futhi, akhombisa ukusebenza kangcono ekudambiseni ama-reactive oxygen species (ROS) kanye nasekwenyuseni izinga lokulwa nokuvuvukala okudalwa yi-LPS. Ngakolunye uhlangothi, kwasetshenziswa ngempumelelo i-tannic acid (TA) kanye ne-Oleylamine (OLA) ukwakha ama- ciprofloxacin-loaded tannic acid hybrid nanoparticle (CIP-loaded TAH-NP) akhiwe njengokwemvelo ukwenyusa izinga lokusebenza ngendlela efanele kwama-CIP ekulwisaneni nokutheleleka ngegciwane kanye ne-sepsisi. Ama-HN alungiselelwe ayenesimo esifana no-anyanisi enobubanzisiyingi obuyisilinganisomaphakathi, i-zeta potential, i-polydispersity index, ukugcineka ngokufanele kobungako bomuthi ozinze lapho okumele uhlasele khona , okwaziwa nge- drug encapsulation efficiency, kanye nobungako bomuthi ongafakwa oyi-85.65 ± 0.89 nm, 0.126 ± 0.01, +16.3 ± 0.23 mV, 68.73 ± 0.54 % and 6.86 ± 0.09 %, ngokulandelana. Ama-aseyi aqondene nokuqhuma kwemithambo yegazi kanye ne-MTT akuqinisekisa ukuphepha emzimbeni kanye nokusebenza kwama-TAH-NP afakwe i-CIP angayiqhumisi imithambo yegazi ((>70 % ukusebenza kwamaseli kanye nemithelela kulokho okuhlangene nokuqhuma kwemithambo yegazi ˂ 1 %). Imiphumela yokuhlola kwe-MST kanye nokulingiswa okwenziwa yikhompyutha yaveza ukuthi i-TA kanye nokwakheka kwayo (CIP-loaded TAH-NP) kwakhombisa ukuthiba i-TLR4 ngempumelelo uma kuqhathaniswa neLPS ewuhlobo lwemvelo. Ama-TAH-NP afakwe i-CIP akhombisa ukuthi ayakwazi ukukhipha ngokusabalalisa okunganqamukiyo ezingeni le-pH 7.4. Okunye futhi, uma kuqhathaniswa ne-CIP engamboziwe izikhwanyana ezincane ezaziwa nge-hybrid nanovesicles emzimbeni zakhombisa ukulwisana namagciwane okungcono, kanjalo nasongwengwezini kanye nokuthiba i-efflux pump, kanye nhlololumbanozithako lokubulala amagciwane ngokushesha. Kanti futhi zakhombisa amandla amakhulu okunciphisa i-ROS kanye nokukwazi ukulawula ukuvuvukala okudalwa yi-LPS. Kafushane, ama-VCM-HNLC kanye namaTAH-NP afakwe i-CIP akhiwa ngempumelelo futhi akhombisa ubungcono obukhulu ekusebenzeni kwezinqandimagciwane kanye nemiphumela yokwelapha ngobubanzi. Lolu cwaningo lwaqinisekisa amandla ama-nanocarrier ayi-haybhridi athwala izinqandimagciwane abe ekwazi ukusebenzisana nezikhuthazi ekuthuthukiseni ukusebenza ngendlela efanele kwenqandamagciwane ezilwa ne-sepsisi enamagciwane kanye nokubhekana nokuphikisana kwezinto ezilwisana namamaykhrobhu. Imininingo etholakala kulolu cwaningo igcine ngokuthi kukhishwe i-athikhili eyodwa ebuyekezayo okokuqala, imibhalo yocwaningo emibili ebhalwe okokuqala, kanye ne-athikhili eyodwa ebhalwe ngokuhlanganyela ebuyekezayo.
Integrating knowledge-to-practice for occupational therapists working with high-risk infants in the KwaZulu-Natal public health sector: a qualitative explorative inquiry.
(2020) Dawood, Ayesha.; Naidoo, Pragashnie.; Ogunlana, Michael Opeoluwa.; Rencken, Gina.
Introduction: Neonates are an at-risk population due to their increased susceptibility of mortality and morbidity. Occupational therapists have an important role in Early Childhood Intervention (ECI) and implementing Neurodevelopmental Supportive Care (NDSC) for high-risk infants whilst they are admitted in the Neonatal Intensive Care Unit (NICU). To the best knowledge of the author there is a paucity of literature available within the South African context in the use of evidence-based practices (EBP), and the integration of knowledge translation (KT) amongst occupational therapists who provide therapeutic management to high-risk infants and their families. Aim: This study aims to explore the knowledge to practice gaps experienced by occupational therapists who support high-risk infants in different levels of care in the public health sector of KwaZulu-Natal South Africa. Methods: A qualitative exploratory research design was used for this study. A nonprobability sampling technique was used. Seventeen occupational therapists who have more than two years of experience and are employed on a full-time basis in the public health sector of KZN participated in this study via online focus group discussions. Data were analysed using thematic analysis with inductive deductive reasoning, guided by a combined theoretical framework using the Appreciative Inquiry (AI) approach and KT process as a methodological orientation to the study. Research Ethics: Principles of confidentiality, autonomy, informed consent, beneficence, non-maleficence, and justice were adhered to. Participants were not of a vulnerable population and therefore support was not offered upon completion of the research discussions. Results: Five themes emerged in this study, namely, occupational therapy (OT) and neonatal care in the public health sector, Knowledge Acquisition and Knowledge Synthesis, Knowledge Translation/Utilization, Contextual barriers/adaptation, and the ideal OT in the ideal neonatal setting. Therapists outlined the facilitators, inhibitors, referral pathways and their personal interests in OT neonatal care. Supportive management and multidisciplinary teams (MDT) were highlighted as facilitators in the hospital environment whilst OT staff shortages, insufficient undergraduate training in the field and a lack of funding for courses for postgraduate OT training were regarded as inhibitors to practice. OTs source and synthesise knowledge from multiple sources to integrate, utilise and translate into neonatal practice. Contextual barriers are identified in various levelled facilities with acquired neonatal knowledge being adapted by therapists for low resourced settings. Participants envision the dream of the ideal day and therapist to intervene with neonates in the public health sector of KZN. Conclusion: Findings have identified several knowledge-to-practice gaps for OTs who support neonates in low resourced settings. Therapeutic resources and funding for postgraduate training, an improvement in the undergraduate curriculum, and policy development appear to be necessary to inform a standard of care across the province.
Nanoencapsulation of novel pyrazolone-based compounds to enhance solubility and biological activity.
(2022) Igbokwe, Nkeiruka Nkeonyere.; Faya, Andile Kennedy Mbuso.; Karpoormath, Rajshekhar.
The biological activity of pyrazolone-based derivatives has been thoroughly documented; nonetheless, low stability and water solubility are their main drawbacks, preventing effective translation to clinical application. Based on this, two previously reported weakly soluble pyrazolone-based compounds, PBC-301 and PBC-302, were encapsulated using PLGA: poloxamer complex to improve their solubility and further examine the influence of solubility augmentation on their biological activities. We first developed and validated a simple, accurate RP HPLC-PDA method for detecting, measuring, and standardising the compounds in nanoformulations to achieve this wide goal. Efficient separation and quantification were carried out using Shim-pack GIST C18 (5 𝜇m 150 × 4.6 mm) column, maintained at 25 ℃ with isocratic elution using acetonitrile and acidified water (0.1% Trifluoracetic acid) (75:25 v/v) at 0.5 mL/min flow rate. The injection volume was 20 𝜇L, and eluents were detected at 333 nm at a retention time of 4.82 mins. Method validation was done following ICH guidelines. Results demonstrated that the method is specific, precise, and accurate within the recommended limits. The method showed good linearity with a 0.9994 correlation coefficient over a concentration range of 2.5-50 𝜇g/ml. The method efficiently detected and quantified the novel pyrazolone compound in the nanosuspension. The obtained nanoformulations PBC-PLGA 301 and PBC-PLGA 302 were characterised using various in vitro techniques. Size, PDI and ZP of the optimised nanoformulations were 166.6 ± 7.12 nm, 0.129 ± 0.042, -14.14 ± 2.90 mV for PBC-PLGA 301 and 192.5 ± 1.08 nm, 0.132 ± 0.025, -10.77 ± 1.515 mV for PBC-PLGA 302 with the encapsulation efficiency being 84.20 ± 0.930 and 81.5 ± 2.051, respectively. The compound release from the nanovesicles followed a sustained release pattern, with PBC-PLGA 301 and PBC-PLGA 302 attaining a cumulative release of approximately 37% and 53% in 48 hours. The biological activity assays showed a better-enhanced activity with the nanoformulations compared to the non-encapsulated PBC 301 and PBC-302. In vitro antibacterial activity revealed that the compound-loaded nanovesicles have better activity against the two gram-positive bacteria S. aureus and Methicillin-resistant S. aureus compared to the standard drug vancomycin and the non-encapsulated compound. On the other, the cell penetration assay further revealed that the compound-loaded nanovesicles achieved greater than 90% propidium iodide penetration (translating to cell death) at the reported MIC well for S. aureus while showing 86% and 89% cell penetration for Methicillin-resistant S. aureus. Also, the nanoformulations showed improved radical scavenging activity in a concentration-dependent manner, with PBC-PLGA 301 exhibiting the best antioxidant activity against DPPH, FRAP and nitric oxide compared to the standard antioxidant-gallic acid and the non-encapsulated compounds. In conclusion, the aqueous solubility of the two pyrazolone compounds, PBC-301 and PBC-302, was greatly enhanced by their encapsulation into a nanosystem, resulting in improved biological activities. Therefore, the nanoformulations of the pyrazolone-based derivatives can be exploited as potential pharmaceutical agents to fight bacterial infections and other diseases triggered by oxidative stress, cancer, and hepatic and vascular diseases. The data from this study has resulted in two first-authored research publications.
Operationalizing family quality of life: occupational therapy outcome measurement for South African forensic psychiatric rehabilitation.
(2020) dHangest dYvoy, Margaux Louise.; Fewster, Deborah Leigh.
Background: Families of forensic mental health care users (MHCUs) experience a great burden of disease. Families of forensic MHCUs in KwaZulu-Natal, South Africa, are identified as the primary community based support system. Relevant psycho-social rehabilitation and support services are required to empower the family as the primary community based support structures, for successful community reintegration and role re-acquisition of young adult forensic MHCUs to be achieved. Occupational therapists (OTs) have had a limited role in forensic “family work” in achieving family-centred health outcomes. Health outcomes have not been developed for occupational therapy practice to direct strategic family-centred rehabilitation. Family Quality of Life (FQOL) has been identified as a strengths-based family outcome which could be used in forensic mental health care. Operationalization of a unique occupation-based FQOL construct was required to inform outcome measurement tool development ensuring family-centred effective and efficient service delivery in the future. Research aim: This study aimed to identify and operationally define FQOL in the development of a FQOL outcome measurement tool that could direct family centred OT services for MHCUs and their families within a forensic psychiatric facility setting in KwaZulu-Natal, South Africa. Method: A qualitative research strategy was used to establish the meaning of FQOL, particularly, an interpretivist qualitative research design. Focus groups of experts (mental health care professionals, forensic MHCUs, and family members) attributed meaning to the existing FQOL construct. A hybrid of inductive and deductive data analysis was necessary to operationalize this construct for application to forensic mental health outcome measurement tool development. Results: An operational definition of the occupation-based FQOL construct using an occupational lens for evidence-based forensic mental health OT practice, was developed. FQOL operational definition(s) of the construct, themes, sub-themes, domains, and sub-domains were formulated and presented in a meaning map of meaning attributed by expert participants. This novel construct consists of two (2) themes (family unit factors, and individual member factors), their related sub-themes (e.g. family unit factors’ sub-themes: family characteristics, family dynamics, and external family unit support) and domains addressing pertinent areas of family life contributing to a collective FQOL experience of forensic MHCUs and their family members. Findings merged FQOL and OT frameworks for application to forensic mental health as compared to previous disability fields of inquiry. A diagrammatic presentation of the novel FQOL construct using an ecological perspective iv displays pertinent areas of family life requiring support by OTs rendering psycho-social rehabilitation. Conclusion: OTs practicing within the specialist forensic mental health facility in KwaZuluNatal, South Africa, are hereby presented with an operationalized FQOL health outcome which could direct evidence-based, family-centred, strengths-based, and support-orientated service delivery, strategically positioning the profession in community-based rehabilitation.
Zulu cultural perspectives and experiences of mental health and occupational therapy in KwaZulu Natal, South Africa.
(2022) Moonsamy, Ashira.; Lingah, Thanalutchmy.; Gurayah, Thavanesi.
Background: Healthcare systems are formulated utilising worldviews, specifically in mental health, where norms are created dictating what is normal versus abnormal. The era of coloniality promoted western dogma over collectivist cultures. Occupational therapy practice must consider the client’s context during assessment and intervention for the process to be client centred. Methods: A qualitative descriptive design was utilised. Purposive sampling was used to recruit 10 participants. Data was collected through semi-structured interviews. Analysis was guided by utilising Braun and Clark’s six phases of thematic analysis. Findings: Three themes emerged from the data, personal perceptions, cultural perceptions, and health-seeking behaviour. Sub-themes accompanied each. Personal perceptions explored how Zulu people made sense of mental illness or related behaviours through a modern or traditional lens. It also explored the importance of the strength of the Zulu individual. A dissonance occurs when faced with cultural norms and personal needs. Finally, their perspectives were altered through their experience with mental illness. Cultural perceptions were that problems were solved internally in families or communities, and progress was promoted as necessary for the Zulu individual. It also explored spiritual beliefs regarding mental illness, which could range between God, Ancestors or both and could be causal factors or healing mechanisms. Suicidality is seen as a weakness in the culture, and stigma was attached to mental illness. The final theme concerns the experience of the Zulu mental health care user dealing with their mental illness. Cognitive dissonance is prevalent in all three aspects not merely due to the difference between westernised mental health treatment and traditional healing systems but also due to the value found in each. The method of sharing vulnerability or issues with an individual outside the family contradicts cultural norms. However, participants expressed that being understood in group discussions and sharing vulnerability significantly improved their healing. Conclusion: Zulu individuals create their sense of self in an interdependent manner. The family and community are intertwined in their participation, reputation, and healing. There is an emphasis on strength and the following of norms in the Zulu culture, perpetuated by the importance of consulting elders or close family when faced with conflict. Disregarding these norms can outcast the Zulu individual who thrives on being included in the community. The study was conducted with a limited sample size and in an urban area. Further research within rural communities and diverse facilities would be beneficial. Occupational therapists working in communities such as KwaZulu Natal should understand the causal factors of mental illness for the Zulu mental health care user and their personal beliefs around healing when designing an intervention.

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